Applied

Homogeneous Catalysis
with Organometallic
Compounds
Volume 1: Applications

Edited by
B. Cornils and W. A. Herrmann
Further Titles of Interest

B. Cornils, W. A. Herrmann, R . Schlogl, C.-H. Wong (Eds.)

Catalysis from A to Z
A Concise Encyclopedia
2000, ISBN 3-527-29855-X

A. Liese, K. Seelbach, C. Wandrey

Industrial Biotransformations
2000, ISBN 3-527-30094-5

R . A. Sheldon, H. van Bekkum (Eds.)

Fine Chemicals Through Heterogeneous Catalysis
2001, ISBN 3-527-29951-3

D. E. D e Vos, I. F. J. Vankelecom, P. A. Jacobs (Eds.)

Chiral Catalysts Immobilization and Recycling
2001, ISBN 3-527-29952-1

K. Drauz, H. Waldmann (Eds.)

Enzyme Catalysis in Organic Synthesis
A Comprehensive Handbook in Three Volumes
Second, Completely Revised and Enlarged Edition
2002, ISBN 3-527-29949-1
Applied
Homogeneous Catalysis
with Organometallic
Compounds
A Comprehensive Handbook
in Three Volumes

Volume 1: Applications

Edited by
Boy Cornils and Wolfgang A. Herrmann

Second, Completely Revised

and Enlarged Edition

683wI LEY-VCH
Prof. Dr. Boy Cornils Prof. Dr. Dr. h.c. mult. Wolfgang A . Herrmann
Kirschgartenstrarje 6 Anorganisch-chemisches Institut
D-65719 Hofheim der Technischen Universitat Miinchen
Germany LichtenbergstraRe 4
D-85747 Garching
Germ any

This book was carefully produced. Nevertheless, editors, authors and publisher do not warrant
the information contained therein to be free of errors. Readers are advised to keep in mind that
statements, data, illustrations, procedural details or other items may inadvertently be inaccurate.

Cover picture: Homogeneous catalysis in aqueous phase: the yellow catalyst solution separates
spontaneously from the colorless phase consisting of butyraldehydes. The underlying molecular model
symbolizes the water-soluble ligand of the organometallic complex. The picture was taken at the plant
site of Celanese (formerly Ruhrchemie), Oberhausen/Germany (see Chapter 1 and Section 2.1.1).

Library of Congress Card No.: applied for

A catalogue record for this book is available from the British Library

Die Deutsche Bibliothek - CIP-Cataloguing-in-Publication-Data

A catalogue record for this book is available from
Die Deutsche Bibliothek

ISBN 3-527-30434-7

0 Wiley-VCH Verlag GmbH, D-69469 Weinheim, 2002

Printed on acid-free paper

All rights reserved (including those of translation into other languages). No part of this book may be
reproduced in any form - by photoprinting, microfilm, or any other means - nor transmitted o r
translated into a machine language without written permission from the publishers. Registered names,
trademarks, etc. used in this book, even when not specifically marked as such, are not to be considered
unprotected by law.

Composition: Hagedorn Kommunikation, Viernheim

Printing: betz-druck GmbH, Darmstadt
Binding: Buchbinderei Schaumann GmbH, Darmstadt

Printed in the Federal Republic of Germany

 This book is dedicated

to the memory of the German chemist

OTTOROELEN
(1897-1 993)

whose pioneering discovery

of hydroformylation (DE 849.548, 1938)
widened up the horizons of homogeneous
catalysis, and through whose work the
industrial impact of organometallic
chemistry became visible to the scientific
community

and
to the memory of the British chemist

SIR GEOFFREY
WILKINSON
(192 1-1996)

whose pioneering discovery

of catalytic hydrogenation under mild
conditions using the catalyst
RhC1[P(C6H5),],, nowadays named the
(‘Wilkinson catalyst”, has opened the eyes
of the scientific community to the
manifold potential of homogeneous
organometallic catalysis
Foreword to the First Edition

It is indeed an honour to be asked to write a foreword to this oustanding text

on homogeneous catalysis in which complexes with transition metal-to-carbon
bonds play the key role in the catalytic cycles even if only as short-lived inter-
mediates.
I was first made aware of organometallic compounds through reading Modern
Aspects of Inorganic Chemistry (1935) by two academics, H. J. EmelCus and
J. S. Anderson at Imperial College, London, where I was a student. However,
names such as “Zeise’s compound”, “Reihlen’s butadiene iron tricarbonyl” and
“Hein’s polyphenylchromium compounds”, none of whose structures were
known, remained latent in my memory through over seven years as a nuclear
chemist.
Although I was appointed an Assistant Professor at Harvard University because
I was a “nuclear chemist”, I took the advice of my predecessor at Imperial
College, Prof. H. V. A. Briscoe, that I had better return to inorganic chemistry
- otherwise no job in England!
So the first semester at Harvard in September 1951, I started making transition
metal olefin complexes. As I was teaching inorganic chemistry, I had also to
digest the main textbook available, N. V. Sidgwick’s The Chemical Elements
and Their Compounds. Starting at the beginning I soon reached p. 78, Vol I,
and wondered what KC5H5 there described would do with metal halides or
what cyclopentadiene itself would do to metal carbonyls. I was also intrigued
by Lucas and Winstein’s work on silver olefin complexes and particularly by a
diagram showing a side-ways bonding of >C=C< to Ag’ - long before the
similar proposal by M. J. S. Dewar. So when I saw in the issue of Nature that
Kealy and Pauson (also, Miller, Tebboth and Tremaine) had given the wrong
structure for (C5HJ2Fe [l], I was certain it was “The Iron Sandwich” [2a,3].
On that evening of 18 January 1952, I was lucky to be about 2.5 hours ahead
of Bob Woodward who saw the Nature note just before his Friday night seminar
where he expounded on the structure. Only in the following September did we
read that we had competition from Munchen in Ernst Otto Fischer! [2b, 31.
Although the renaissance of inorganic chemistry from ca. 1946 started with
complex chemistry, both solid and aqueous, and with fluorine chemistry, the
discovery of ferrocene and the development of n-bonding concepts signalled a
new era in chemistry particularly of transition metals in both academic and indus-
trial laboratories. Who, of the handful of active workers in 1952, would have
predicted the present status with a vast range of new organometallic compounds
of essentially all the elements in the Periodic Table, the metal complex initiated
stoichiometric organic syntheses and above all the use of metal complexes in
homogeneous catalysis on a vast scale in industry? Merely looking at the volumes
VIII Foreword to the First Edition

of Comprehensive Organometallic Chemistry I (1982) and 11 (1995) [4] and

perusing the organometallic and catalytic literature shows the extent of the
rapid development of the symbiotic relation between organometallic and catalytic
chemistry.
Although I would never claim to be primarily an organometallic or catalytic
chemist, I had heard quite early on in the 1950s of hydroformylation and of
homogeneous hydrogenation (although not of C=C bonds). However, it was the
synthesis of (C5H&ReH on the bench in the old Polyteknisk Laereanstalt in
Copenhagen used by the great S. M. Jgrgensen that led me into the chemistry
of other hydrido complexes and interactions of hydrogen with complexes, notably
of rhodium. From this arose the question “What happens if we add an olefin to the
system?”. Somewhat to my surprise this led to hydrogenation of the C=C bond
and in due course RhCl(PPh&. The latter is now one of the most widely used
and quoted hydrogenation catalysts:* it was shortly followed by use of
RhH(CO)(PPh,), for low-pressure hydroformylation that gave predominantly
anti-Markownikoff addition and straight-chain aldehydes.
Subsequent developments have proceeded an increasingly rapid pace and
Professors Cornils and Herrmann and their co-authors are to be congratulated
on producing this most comprehensive work on the fundamentals and applied
aspects of organometallic catalysts. The vast area is one of the most intellectually
challenging and industrially important fields of contemporary science. Yet it is a
discipline that is far from being mature, ideal for chemical entrepreneurs, and still
rapidly developing and widening in scope. Industrially it has led to milder reaction
conditions, higher activities and selectivity, not least being the development
of catalytic asymmetric syntheses. The Editors have succeeded in producing a
fascinating account of all aspects of the subject. Since I doubt if the rate of
development will decrease, they may well have to contemplate a second edition
in the not too distant future. As one with a certain amount of text book writing
experience I can only wish them and their colleagues well and a big success.

Sir Geoffrey Wilkinson F.R.S.

Imperial College of Science,
Technology and Medicine, London

* Nowadays known as the “Wilkinson catalyst”, see Sections 2.1.1 and 2.2
(note added by the editors).
 Foreword to the First Edition IX

References
[ l ] (a) S. A. Miller, J. A. Tebboth, J. F. Tremaine, J. Chem. SOC. 1952, 632 (received July 11,
1951); (b) T. J. Kealy, P. L. Pauson, Nature 1951, 168, 1039 (received August 7, 1951).
[2] (a) G. Wilkinson, M. Rosenblum, M. C. Whiting, R. B. Woodward, J. Am. Chem. SOC.
1952, 74, 2125 (received March 24, 1952); (b) E. 0. Fischer, W. Pfab, Z. Naturj4orsch.
1952, 7B, 377 (received June 20, 1952).
[3] G. Wilkinson, J. Organomet. Chem. 1975, 100, 273.
[4] E. W. Abel, G. Wilkinson, F. G. A. Stone (Eds.), Comprehensive Organometallic
Chemistry I, 1982; 11, 1995, Pergamon Press, Oxford.
Preface to the Second Edition

Convinced that “homogeneous catalysis is the success story of organometallic

chemistry”, we initiated the first edition of our two-volume handbook six years
ago. From the supportive response we received from the scientific community
and from many readers, both university students and professionals, we recognized
the demand for a second edition. The growth and potential of organometallic
chemistry has developed faster than anybody had anticipated. As a matter of
fact, another Nobel Prize was just awarded to our colleagues William Knowles,
Barry Sharpless, and Ryoji Noyori (December 10, 2001) to honour their pioneer-
ing research in stereoselective organometallic catalysis (cf. their respective Sec-
tions 2.9 and 3.3.2).
The past six years have brought about several breakthroughs in the field. For
example, aqueous-phase catalysts have become of prime interest in chemical
industry, and the catalytic potential of non-aqueous ionic liquids (“NAILS”) was
discovered (Section 3.1.1). High-throughput approaches to homogeneous catalysis
have included organometallic catalysts based on novel micro-techniques in routine
applications (Section 3.1.3). We have seen new tailored catalysts that promise
great success in the next generation of organometallics. Thus, N-heterocyclic
carbenes (Section 3.1.10) have been highlighted several times since our first edi-
tion went into print. This particular development demonstrates that old, ubiquitous
ligands such as phosphanes may have competition from alternative compounds of
simple structure.
Since 1996, micellar catalysis (Section 3.1.11) has made progress in the same
time as supercritical fluids (Section 3.1.13) have come to the fore. Suffice it to say
that biocatalysis and enzyme-analogous processes enjoy an exponential growth
that has significance both to basic science and to industry (Section 3.2.1).
As a result, the majority of contributions to the present edition have had to be
either updated or completely replaced by new articles. This applies to the sections
mentioned above, but also to the rapidly growing area of enantioselective synthesis
(Sections 3.3.1 and 3.2.6), the catalytic hydrogenation of sulfur- and nitrogen-
containing compounds in raw oils (Section 3.2.13), the Pauson-Khand reaction
(Section 3.3.7), and a number of industrially relevant topics covered under
“Applied Homogeneous Catalysis” in Part 2. New aspects of organometallic cata-
lysis have emerged from the chemistry of renewable resources (Section 3.3.9) and
the chemistry around the multi-talented catalyst methyltrioxorhenium (Section
3.3.13).
The second edition has retained the character of both a scientific textbook (for
orientation) and a handbook (for detailed information). However, the many new
contributions have literally created a new book. Areas with their own specific im-
portance are being “outsourced” into specific monographs, in order not to over-
XI1 Preface to the Second Edition

load a well-balanced concept that was praised repeatedly in book reviews. The
first example is our Aqueous-Phase Organometallic Catalysis [ 13, which takes
care of water-soluble coordination compounds and catalysts. In addition, an ency-
clopedia covering the full scope of catalysis was published just recently [2], with
the second edition to appear in the year of 2002, too.
We extend our thanks once again to the team of Wiley-VCH at Weinheim,
especially Dr. G. Walter and Mrs. C. Grossl, and also Mrs. D. Boatman, for
their cooperation in the editorial and production process. The Munich research
group is acknowledged for scientific and technical assistance in the updating of
recent literature reports as well as for the arrangement of the new Subject
Index. Last but not least, we are greatly indebted to a great number of authors,
whose reputations in the scientific community guarantee the significance of
their contributions to this book.
Given the progress in organometallic chemistry and the impetus from industrial
fine-chemical synthesis technology, we are prepared to issue the third edition in
about five years’ time. We hope, however, that the present book will serve well
and frequently until then.

Hofheiflaunus and Munchen Boy Cornils

January 2002 Wolfgang A. Henmann

References
[I] B. Cornils, W. A. Herrmann (Eds.), Aqueous-Phase Organometallic Catalysis,
Wiley-VCH, Weinheim 1998.
[2] B. Cornils, W. A. Herrmann, R. Schlogl, C.-H. Wong (Eds.), Catalysisfrom A to Z,
Wiley-VCH, Weinheim 2000; 2nd edition in 2002.
Preface to the First Edition

“. . .die Chemie der Gase ist seit einigen Jahren in eine neue
Epoche, in das Zeichen der Katalyse getreten. Mit Hilfe von
Katalysatoren gelingen die wundersamsten Umwandlungen
durch Wasserstoff, Sauerstoff, Stickstoff, Kohlenoxyd bei Tem-
peraturen, die viele hundert Grad niedriger sind als diejenigen,
bei denen man friiher diese Gase reagieren sah. Dieses Kapitel
der Katalyse ist schier unbegrenzt . . .”*
Emil Fischer
Stahl und Eisen 1912, 32, 1898

Homogeneous catalysis is the success story of organometallic chemistry, a dis-

cipline that has structured and combined inorganic and organic chemistry to an
unprecedented extent. Throughout the book, reference is frequently made to the
many monographs and original publications concerning segmental aspects of
homogeneous catalysis with organometallic catalysts which are of paramount
importance in this scientifically still growing and industrially vital domain of
catalysis. A wide variety of viewpoints, including the broad spectrum of academic
and industrial work, is presented. With the enormous breadth of homogeneous
catalysis in terms of both basic research and industrial applications, the joint
editorship of an industry researcher (BC) and a university chemist (WAH) appears
to be the ideal combination of expertise.
All branches of homogeneous catalysis with organometallic complexes are
covered in this text, including borderline cases. Our definition of homogeneous
catalysis includes catalysts which, inter alia,

are molecularly dispersed “in the same phase”,

are unequivocally characterized chemically and spectroscopically and can
be synthesized and manufactured in a simple and reproducible manner,
can be tailor-made for special purposes according to known principles
and based upon a rational design, and
permit unequivocal reaction kinetics related to each metal atom.

In borderline cases (e. g., clusters, supported catalysts, catalysts for Ziegler-
Natta polymerizations) we have defined reactions to be homogeneous when the
catalyst passes a detectable catalyst cycle or parts thereof.

* “. . , for several years the chemistry of gases has been in a new era, the era of catalysis. Cata-
lysts help to make miraculous conversions with hydrogen, oxygen, nitrogen, or carbon mon-
oxide possible at temperatures several hundred degrees lower than those conditions in which
these gases reacted earlier. This chapter of catalysis is nearly unlimited. . .”
XIV Preface to the First Edition

The term applied indicates the application-oriented objective of this work. It

was an important criterion of selection not to supply merely a collection of un-
weighted facts and various practical examples of homogeneous catalysis. In this
context “applied” means a selection of homogeneous catalyzed processes,
which on the one hand have already arrived at industrial success (e. g., carbonyla-
tion of alcohols, hydroformylation, Wacker-Hoechst process). On the other hand,
the book also includes homogeneously catalyzed reactions of which the state-of-
the-art indicates commercialization in the near future. Moreover, for scientific rea-
sons the inclusion of newer catalytic reactions or reaction principles is required,
even when commercialization is not yet in sight. Both aspects are covered by
the sections “Applied Catalysis” and “Recent Developments”.
Since, for secrecy reasons, information on new processes and the state of their
development is not always published, or only after long delays, the classification
“applied” or “recent” developments may be misleading. For example, the potential
of phase-transfer catalyzed processes may already be more important than the
present literature indicates. The same statement could apply for areas such as
amidocarbonylation, the synthesis of fine chemicals by means of metallocenes,
the reductive/oxidative carbonylation of aromatic amines or nitro derivatives,
Heck coupling using palladacycles and heterocyclic carbene complexes, catalytic
McMurry coupling, or other proposed methods. “Recent developments” must
therefore leave open the stage of development reached, perhaps signaling that
at the time of publication no commercialized, licensable “process” is yet known
to the scientific community.
On the other hand, process steps which are known in principle (and thus may be
verified industrially in due course) but have not yet been applied are referred to as
“applied” processes as well. Examples are special variants of hydroformylation or
carbonylation for the manufacture of special chemicals, modifications of oxacyla-
tions (in the context of the Wacker-Hoechst process), the copolymerization of
ethylene with carbon monoxide (Shell), and several other processes.
With the emphasis on organometallic complexes and owing to the existence of
adequate reviews on other forms of homogeneous catalysis, reactions such as gas-
phase conversions or acidbase-catalyzed reactions have had to be omitted from
our book. The term organometallic complexes covers metal coordination com-
pounds of which the metal atoms are surrounded by neutral molecules and/or
ligands. A restricted definition of the terms “organometallic complexes” and
“homogeneous catalysis” is applied to classical cases (e. g., Ziegler-Natta cataly-
sis). In cases of doubt this leads to limitations and, in specific cases. to the
omission of “classical” polyethylene and polypropylene syntheses.
Keeping our target of homogeneous catalysis in mind, we adopted a broad
definition of organometallic complexes and included compounds without metal-
carbon bonds (e. g., metal-phosphine and metal-nitrosyl complexes) as far as they
retain the structural and reactivity features of typical organometallic compounds.
Recent developments, e. g., the substitution of phosphine by carbene ligands
(cf. Section 3.1.1.1). support the validity of this view.
Being part of both academic and industrial chemistry, organic chemistry in
general and homogeneous catalysis in particular are subject to rapid and steady
 Preface to the First Edition XV

change. The reasons for this are numerous and can be traced back to changed
attitudes to the environment, structural changes in the raw material bases (chemi-
cal feedstock) and the process or reaction engineering involved, varying market
requirements, and the different relationships between the chemicals produced
and the material properties required. These changes, and the increasing number
of researchers, have led to both a vast number of publications which can only
be perused by specialists, and a quicker succession of process development and
process utilization. The pressures associated with the compilation of this work
and the need to achieve a satisfactory level of topicality were challenges to be
met by the editors and VCH Publishers. They took the opportunity to organize
a multinational team of authors, who are active in both the academic and the
industrial world. We owe our thanks to this excellent team of authors for their
loyal and constructive cooperation and for the punctual preparation of their manu-
scripts.
Critical emphasis is placed on the industrial importance of homogeneous cata-
lysis as defined above and to the discussion of possibilities and limitations of the
manufacturing processes. Because of rapid developments and a vast amount of
literature, an unbiased assessment is difficult and so misinterpretations may
arise. We hope that this does not happen, and we have endeavoured to offer the
reader a useful compilation of the manifold concepts and applications of organo-
metallic catalysis.
The conceptual and topical organization of our book is such that, hopefully, the
requirements of a broad scientific audience are met. The organic chemist will find
an updated synopsis on catalytic syntheses of fine and bulk chemicals; here, we
have not specifically focused on stereoselective reactions - although they greatly
deserve special treatment - since a number of excellent monographs has appeared
recently [ 1-41. Organometallic chemists will appreciate a comprehensive treatise
on the most important applications of their discipline. Scientists originating from
other areas are expected to receive a quick impression of the scope of homoge-
neous catalysis, its basic principles and technical/commercial applications. Our
colleagues in industv may either become acquainted with catalysis or keep up
with recent developments by consulting this book. Finally, university students
entering the field of organometallic catalysis, be it for the purpose of learning
or to prepare a doctoral research topic, will find a useful, up-to-date survey herein.
We have tried to avoid any highly specialized encyclopedia-like treatment of the
respective topics; rather, we have attempted to meet equally well the interests of
advanced university students, industrial chemists (and engineers), and our peers
in academia. For this very reason, we have abandoned extensive tables of detailed
data in favor of a general outline of the field, including leading and recent
references.
We thank the team at VCH, especially Mrs. D. Boatman, Dr. A. Eckerle
and Mrs. C. Grossl, for their cooperation during preparation, for editing the
manuscripts, and for helpful technical assistance. Dr. F. Dyckhoff and Dip].-
Chem. M. Geisberger of Technische Universitat Munchen are acknowledged
for preparing all formulae, figures, and schemes throughout the book. The Sub-
ject Index was arranged by the Munich research group; we thank particularly
XVI Preface to the First Edition

Dip1.-Chem. C. P. Reisinger and Dip1.-Chem. R. Eckl for their reliable assistance.

Finally, a great number of colleagues deserve our special acknowledgement for
their valuable advice and their criticism.

Frankfurt-Hochst and Miinchen Boy Cornils

July 1996 Wolfgang A. Henmann

References
[l] R. A. Sheldon, Chirotechnology, Marcel Dekker, New York, 1993.
[2] I. Ojima (Ed.), Catalytic Asymmetric Synthesis, VCH, Weinheim, 1993.
[3] R. Noyori, Asymmetric Catalysis in Organic Synthesis, John Wiley, New York, 1994,
[4] M. Nbgridi, Stereoselective Synthesis, VCH, Weinheim, 1995.
Contents

Volume 1: Applications

1 Introduction
(B. Cornils. W A. Herrmann) . . . . . . . . . . . . . 1
Introduction . . . . . . . . . . . . . . . . . . . . 3
Historical Glossary . . . . . . . . . . . . . . . . . 16

2 Applied Homogeneous Catalysis . . . . . . . . 29

2.1 Carbon Monoxide and Synthesis Gas Chemistry . . . . . 31
2.1.1 Hydroformylation (0x0 Synthesis. Roelen Reaction)
(C. D . Frohning. C. W Kohlpaintner; H.-W Bohnen) . . . . 31
2.1.1.1 Introduction . . . . . . . . . . . . . . . . . . . . 31
2.1.1.2 Fundamental Principles . . . . . . . . . . . . . . . . 34
2.1.1.3 Kinetics, Mechanism, and Process Parameters . . . . . . . 45
2.1.1.4 Commercial Applications . . . . . . . . . . . . . . . 61
2.1.1.5 Recent Developments . . . . . . . . . . . . . . . . 85
2.1.2 Carbonylations . . . . . . . . . . . . . . . . . . . 104
2.1.2.1 Synthesis of Acetic Acid and Acetic Acid Anhydride
from Methanol (P: Torrence) . . . . . . . . . . . . . 104
2.1.2.2 Synthesis of Propionic and Other Acids (A . Hiihn) . . . . . 136
2.1.2.3 Carbonylation of Benzyl-X and Aryl-X Compounds
(M. Beller) . . . . . . . . . . . . . . . . . . . . 145
2.1.2.4 Amidocarbonylation ( J . F: Knifton) . . . . . . . . . . . 156
2.1.2.5 Oxidative Carbonylation (A . Kluusenel; J.-D. Jentsch) . . . 164
2.1.2.6 Other Carbonylations (M. Beller; A.M. Tafesh) . . . . . . 182

2.2 Hydrogenation (H. Brunner) . . . . . . . . . . . . . 195

2.2.1 Homogeneous Hydrogenation . . . . . . . . . . . . . 195
2.2.1.1 The Hydrogen Molecule . . . . . . . . . . . . . . . 195
2.2.1.2 Classical Transition Metal Hydrides . . . . . . . . . . . 195
2.2.1.3 Nonclassical Dihydrogen Complexes . . . . . . . . . . 196
2.2.1.4 Homogeneous Hydrogenation of Organic Substrates . . . . 198
2.2.1.5 Enantioselective Hydrogenation of Prochiral Substrates . . . 200
XVIII Contents

2.2.1.6 Isolated Catalysts Versus in-situ Catalysts . . . . . . . . 203

2.2.1.7 Transfer Hydrogenation . . . . . . . . . . . . . . . . 204
2.2.1.8 Hydrogen01y sis . . . . . . . . . . . . . . . . . . . 204
2.2.1.9 Mechanisms . . . . . . . . . . . . . . . . . . . . 205
2.2.1 10a
Industrial Applications . . . . . . . . . . . . . . . . 209
2.2.2 Commercial Enantioselective Hydrogenation . . . . . . . 210

2.3 Reactions of Unsaturated Compounds . . . . . . . . . 213

2.3.1 Polymerization. Oligomerization. and Copolymerization
of Olefins . . . . . . . . . . . . . . . . . . . . . 213
2.3.1.1 Chemical Background (W Kaminsky. M . Arndt-Rosenau) . . 213
2.3.1.2 Chemical Engineering and Applications ( L. L . Biihm) . . . . 230
2.3.1.3 Oligomerization of Ethylene to Higher Linear a-Olefins
( D. Vogt) . . . . . . . . . . . . . . . . . . . . . 240
2.3.1.4 Dimerization and Codimerization
(H. Olivier-Bourbigou. L . Saussine) . . . . . . . . . . 253
2.3.1.5 Evolution of the Synthesis of Group 4 Metallocene
Catalyst Components Toward Industrial Production
(C. Fritze. F! Miillel; L . Resconi) . . . . . . . . . . . . 265
2.3.2 Reactions of Other Unsaturated Compounds . . . . . . . 274
2.3.2.1 Reactions of Alkynes
(J. Henkelmann. J.-D. Arndt. R. Kessinger) . . . . . . . 274
2.3.2.2 Stereospecific Polymerization of Butadiene or Isoprene
( R. Taube. G. Sylvester) . . . . . . . . . . . . . . . 285
2.3.2.3 A Clean Route to Methacrylates via Carbonylation of Alkynes
( E. Drent. W W Jagel; J . J . Keijspel; F: G.M. Niele) . . . . 316
2.3.3 Metathesis (J. C. Mol) . . . . . . . . . . . . . . . . 328
2.3.3.1 Introduction . . . . . . . . . . . . . . . . . . . . 328
2.3.3.2 Scope of the Reaction . . . . . . . . . . . . . . . . 329
2.3.3.3 Reaction Mechanism and Catalysts in General . . . . . . . 333
2.3.3.4 Homogeneous Catalyst Systems . . . . . . . . . . . . 335
2.3.3.5 Industrial Applications . . . . . . . . . . . . . . . . 339
2.3.3.6 Conclusions . . . . . . . . . . . . . . . . . . . . 341
2.3.4 The Alternating Copolymerization of Alkenes and
Carbon Monoxide
( E. Drent. J . A . M . van Broekhoven. F! H . M . Budzelaar) . . . 344
2.3.4.1 Introduction . . . . . . . . . . . . . . . . . . . . 344
2.3.4.2 History of Polyketones . . . . . . . . . . . . . . . . 344
2.3.4.3 Copolymerization of Ethylene and CO . . . . . . . . . . 346
2.3.4.4 Scope of Olefin/CO Copolymerization . . . . . . . . . . 356
2.3.4.5 Conclusions . . . . . . . . . . . . . . . . . . . . 358
 Contents XIX

2.3.5 Telomerization (Hydrodimerization) of Olefins

( N. Yoshimura) . . . . . . . . . . . . . . . . . . . 361
2.3.5.1 Introduction . . . . . . . . . . . . . . . . . . . . 361
2.3.5.2 Development of Technologies . . . . . . . . . . . . . 362
2.3.5.3 Process for the Manufacture of 1-Octanol . . . . . . . . 366
2.3.5.4 Development and Scope . . . . . . . . . . . . . . . 366
2.3.6 Cyclooligomerizations and Cyclo-co-oligomerizations
of 1.3.Dienes (G. Wilke. A . Eckerle) . . . . . . . . . . 368
2.3.6.1 Introduction . . . . . . . . . . . . . . . . . . . . 368
2.3.6.2 Cyclodimerization and Cyclotrimerization of Butadiene
and Substituted 1.3.Dienes . . . . . . . . . . . . . . 370
2.3.6.3 Cyclo-co-oligomerization of 1.3.Dienes with Olefins
and Alkynes . . . . . . . . . . . . . . . . . . . . 374
2.3.6.4 Mechanistic Considerations . . . . . . . . . . . . . . 377
2.3.6.5 Summary . . . . . . . . . . . . . . . . . . . . . 379
2.3.7 Catalyzed Polymerisation of Epoxy Resins (M. Dbring) . . . 383

2.4 Oxidations . . . . . . . . . . . . . . . . . . . . 386

2.4.1 Oxidation of Olefins to Carbonyl Compounds (Wacker Process)
( R. Jira) . . . . . . . . . . . . . . . . . . . . . 386
2.4.1.1 Historical and Economic Background . . . . . . . . . . 386
2.4.1.2 Chemical Background . . . . . . . . . . . . . . . . 386
2.4.1.3 Kinetics and Mechanism . . . . . . . . . . . . . . . 389
2.4.1.4 Technical Applications (Wacker-Hoechst-Processes) . . . . 397
2.4.1.5 Application of the Olefin Oxidation to Organic Syntheses . . 402
2.4.2 Homogeneous Oxidative Acetoxylation of Alkenes
( I. I . Moiseev. M . N. Vargaftik) . . . .
. . . . . . . . . 406
2.4.2.1 Introduction . . . . . . . . . . . . . . . . . . . . 406
2.4.2.2 Mechanistic Considerations . . . . . . . . . . . . . . 407
2.4.2.3 Giant Cluster Catalyzed Reaction . . . . . . . . . . . . 409
2.4.3 Synthesis of Oxiranes ( R. A . Sheldon) . . . . . . . . . . 412
2.4.3.1 Historical Development . . . . . . . . . . . . . . . . 412
2.4.3.2 Metal-Catalyzed Epoxidation with Alkyl Hydroperoxides:
Kinetics and Mechanism . . . . . . . . . . . . . . . 413
2.4.3.3 Commercial Oxirane Processes . . . . . . . . . . . . . 417
2.4.3.4 Scope and Applications in Organic Synthesis . . . . . . . 419
2.4.3.5 Recent Developments and Future Prospects . . . . . . . . 421
2.4.4 Aliphatic Carboxylic Acids via Aliphatic Aldehydes (F: Koch) . 427
2.4.4.1 General . . . . . . . . . . . . . . . . . . . . . . 427
2.4.4.2 Catalysts . . . . . . . . . . . . . . . . . . . . . 428
2.4.4.3 Kinetics and Mechanism . . . . . . . . . . . . . . . 429
2.4.4.4 Technical Process . . . . . . . . . . . . . . . . . . 430
2.4.4.5 Future Trends . . . . . . . . . . . . . . . . . . . 43 1
XX Contents

2.4.5 Oxidation of Arenes and Alkyl-Substituted Aromatic

Compounds . . . . . . . . . . . . . . . . . . 433
2.4.5.1 Oxidation of Arenes to Quinones (R. W Fischer) . . . 433
2.4.5.2 Oxidation of Alkyl-Substituted Aromatic Compounds
with Air (R. W Fischel; F: Rohrscheid) . . . . . . . 443

2.5 Reactions with Hydrogen Cyanide (Hydrocyanation)

(S. Krill) . . . . . . . . . . . . . . . . . . . . . 468
2.5.1 Introduction and Scope . . . . . . . . . . . . . . . . 468
2.5.2 Mechanistic Aspects of Hydrocyanation . . . . . . . . . 469
2.5.3 Hydrocyanation of Olefins . . . . . . . . . . . . . . 470
2.5.3.1 Hydrocyanation of Non-Activated Monoolefins . . . . . . 470
2.5.3.2 Hydrocyanation of Functionalized Olefins . . . . . . . . 476
2.5.4 Hydrocyanation of Alkynes . . . . . . . . . . . . . . 479
2.5.5 Hydrocyanation of Dienes . . . . . . . . . . . . . . . 481
2.5.5.1 Adiponitrile Synthesis via Hydrocyanation of Butadiene . . . 48 1
2.5.5.2 Hydrocyanation of Other Dienes . . . . . . . . . . . . 484
2.5.6 Hydrocyanation of AldehydeslKetones . . . . . . . 485

2.6 Hydrosilylation and Related Reactions

of Silicon Compounds ( B. Murciniec) . . . . . . . . 491
2.6.1 Hy drosily lation . . . . . . . . . . . . . . . . . . . 491
2.6.1.1 General Scope and Applications . . . . . . . . . . . . 491
2.6.1.2 Homogeneous Catalysts . . . . . . . . . . . . . . . 495
2.6.1.3 Immobilized Metal Complexes as Catalysts . . . . . . . . 500
2.6.1.4 Photo- and Peroxide-Initiated Catalysis by Metal Complexes . 501
2.6.2 Dehydrogenative Coupling Reactions . . . . . . . . . . 502
2.6.2.1 Dehydrogenative Silylation of Alkenes and Alkynes
with Hydrosilanes . . . . . . . . . . . . . . . . . . 502
2.6.2.2 Silylative Coupling of Alkenes with Vinylsilanes . . . . . . 504
2.6.2.3 Dehydrocoupling of Hydrosilanes . . . . . . . . . . . . 505
2.6.3 Silylcarbonylation . . . . . . . . . . . . . . . . . . 506

2.7 Reaction with Nitrogen Compounds: Hydroamination

(R. Taube) . . . . . . . . . . . . . . . . . . . . . 513
2.7.1 Introduction . . . . . . . . . . . . . . . . . . . . 513
2.7.2 General Mechanistic Aspects . . . . . . . . . . . . . 513
2.7.3 The Different Catalyst Systems . . . . . . . . . . . . . 516
2.7.3.1 Catalyst Systems Containing Alkali Metals . . . . . . . . 516
2.7.3.2 Catalyst Systems Containing Lanthanides . . . . . . . . . 518
 Contents XXI

2.7.3.3 Catalyst Systems Containing Iridium . . . . . . . . . . 520

2.7.3.4 Catalyst Systems Containing Iron or Ruthenium . . . . . . 522
2.7.3.5 Catalyst Systems Containing Rhodium . . . . . . . . . . 522
2.7.4 Perspectives . . . . . . . . . . . . . . . . . . . . 524

2.8 Reactions of Hydrocarbons and Other Saturated

Compounds . . . . . . . . . . . . . . . . . . . . 525
2.8.1 Oxidations . . . . . . . . . . . . . . . . . . . . . 525
2.8.1.1 Homogeneous Catalysis in the Oxidation
of Hydrocarbons to Acetic Acid (C. C. Hobbs, JK) . . . . . 525
2.8.1.2 Synthesis of Dimethyl TerephthalateITerephthalic Acid
and Poly(ethy1ene terephthalate) (D.A. Schiruldi) . . . . . 544
2.8.2 Halogenations (W A . Herrmann. M . Stoeckl) . . . . . . . 552
2.8.2.1 Introduction . . . . . . . . . . . . . . . . . . . . 552
2.8.2.2 Substitution Reactions . . . . . . . . . . . . . . . . 552
2.8.2.3 Addition Reactions . . . . . . . . . . . . . . . . . 553

2.9 Asymmetric Syntheses

( R. Noyori. S. Hashiguchi. T Yamano) . . . . . . . . . 557
2.9.1 Introduction . . . . . . . . . . . . . . . . . . . . 557
2.9.2 Preparation of Selected Structures . . . . . . . . . . . . 557
2.9.2.1 Terpenes . . . . . . . . . . . . . . . . . . . . . 557
2.9.2.2 Carboxylic Acids . . . . . . . . . . . . . . . . . . 559
2.9.2.3 Pyrethroids . . . . . . . . . . . . . . . . . . . . 563
2.9.2.4 Prostaglandins . . . . . . . . . . . . . . . . . . . 565
2.9.2.5 Simple Secondary Alcohols . . . . . . . . . . . . . . 565
2.9.2.6 Amino Alcohols and Related Compounds . . . . . . . . 568
2.9.2.7 Amino Acids . . . . . . . . . . . . . . . . . . . . 572
2.9.2.8 Alkaloids . . . . . . . . . . . . . . . . . . . . . 574
2.9.2.9 Carbapenem Antibiotics . . . . . . . . . . . . . . . 576
2.9.2.10 Sulfoxides . . . . . . . . . . . . . . . . . . . . . 577
2.9.2.11 1,2-Diols and Related Compounds . . . . . . . . . . . 578
2.9.2.12 Miscellaneous . . . . . . . . . . . . . . . . . . . 578
2.9.3 Conclusions . . . . . . . . . . . . . . . . . . . . 580

2.10 Ferrocene as a Gasoline and Fuel Additive

(W A . Herrmann) . . . . . . . . . . . . . . . . . . 586
2.10.1 Introduction . . . . . . . . . . . . . . . . . . . . 586
2.10.2 Commercial Synthesis . . . . . . . . . . . . . . . . 586
2.10.3 The Gasoline and Fuel Additive . . . . . . . . . . . . 588
2.10.4 Related Antiknocking Additives . . . . . . . . . . . . 589
XXII Contents

2.11 The Suzuki Cross-Coupling ( W A. Herrmann) . . . . . . 591

2.11.1 Introduction . . . . . . . . . . . . . . . . . . . . 591
2.11.2 Advantages and Drawbacks . . . . . . . . . . . . . . 591
2.11.3 Catalysts. Substrates. Conditions . . . . . .
592 . . . . . .
2.11.3.1 Current Status . . . . . . . . . . . . .
592 . . . . . .
2.11.3.2 Recent Catalyst Improvements . . . . . . .
592 . . . . . .
2.11.3.3 Two-Phase Catalysis . . . . . . . . . . .
595 . . . . . .
2.1 1.3.4 Suzuki-Related Coupling . . . . . . . . . . . . . . . 595
2.11.4 Mechanism . . . . . . . . . . . . . . . . . . . . 596
2.11.5 Commercial Application and Further Development . . . . . 597

Volume 2: Developments

3 Recent Developments
in Homogeneous Catalysis . . . . . . . . . . . 599

3.1 Development of Methods . . . . . . . . . . . . . . . 601

3.1.1 Homogeneous Catalysts and Their Heterogenization
or Immobilization ( B. Cornils. W A. Herrmann) . . 60 1
3.1.1.1 Immobilization by Aqueous Catalysts
( B. Cornils, W A. Herrmann) . . . . . . . . . 603
3.1.1.2 Immobilization by Other Liquids . . . . . . . . . . . . 634
3.1.1.2.1 Fluorous Phases (I. T. Horva'rh) . . . . . . . . . . . . 634
3.1.1.2.2 Non-Aqueous Ionic Liquids (VZ? W Biihm) . . . . . . . . 639
3.1.1.3 Immobilization (Z? Panstel; S. Wieland) . . . . . . . . . 646
3.1.1.4 Surface Organometallic Chemistry
(J.-M. Basset, G. Z? Niccolai) . . . . . . . . . . . . . 664
3.1.1.5 Ligand-Stabilized Clusters and Colloids (G. Schmid) . . . . 677
3.1.1.6 New Generation of Re-Immobilized Catalysts
( H. Bahrmann) . . . . . . . . . . . . . . . . . 684
3.1.1.7 New Reactions ( J . Herwig) . . . . . . . . . . . . 694
3.1.2 Molecular Modeling in Homogeneous Catalysis
( R. Schmid. W Hieringer; D . Gleich. is Strassner) . . . . . 700
3.1.2.1 Molecular Modeling Techniques (R. Schmid) . . . . . . . 700
3.1.2.2 Applications . . . . . . . . . . . . . . . . . . . . 712
3.1.2.2.1 Modeling of Homogeneous Olefin Polymerization Catalysts
(R. Schmid) . . . . . . . . . . . . . . . . . . . . 712
 Contents XXIII

3.1.2.2.2 Palladium-Catalyzed C-C Coupling Reactions:

The Heck Reaction (W Hieringer) . . . . . . . . . . . 721
3.1.2.2.3 Hydrofonnylation (D. Gleich) . . . . . . . . . . . . . 727
3.1.2.2.4 C-H Activation (I: Strassner) . . . . . . . . . . . . . 737
3.1.3 High-Throughput Approaches to Homogeneous Catalysis
(Y Murphy. H . W Turnel; I: Weskamp) . . . . . . . . . 740
3.1.3.1 Introduction . . . . . . . . . . . . . . . . . . . . 740
3.1.3.2 Principal Workflow . . . . . . . . . . . . . . . . . 741
3.1.3.3 Analysis in High-Throughput Format . . . . . . . . . . 745
3.1.3.4 Data Management and Software . . . . . . . . . . . . 746
3.1.3.5 Discovery Screening Workflow for New Polyolefin Catalysts . 747
3.1.4 Chemical Reaction Engineering Aspects of
Homogeneously Catalyzed Processes ( M. Baerns, f! Claus) . 748
3.1.4.1 Kinetics in Homogeneous Catalysis . . . . . . . . . . . 750
3.1.4.2 Aspects of Catalyst Recycling . . . . . . . . . . . . . 759
3.1.5 Introduction to Selected Multicomponent and Multifunctional
Catalysts (D. Hesse) . . . . . . . . . . . . . . . . . 762
3.1.5.1 Introduction . . . . . . . . . . . . . . . . . . . . 762
3.1.5.2 Advantages in the Use of Multicomponent or Multifunctional
Catalysts . . . . . . . . . . . . . . . . . . . . . 764
3.1.5.3 Problems in the Use of Multifunctional or Multicomponent
Catalysts . . . . . . . . . . . . . . . . . . . . . 772
3.1S.4 Conclusions . . . . . . . . . . . . . . . . . . . . 773
3.1.6 Catalytic Carbon-Carbon Coupling by Palladium Complexes:
Heck Reactions (W A. Herrmann) . . . . . .. . . . . 775
3.1.6.1 Introduction . . . . . . . . . . . . . . . .. . . . 775
3.1.6.2 History . . . . . . . . . . . . . . . . . .. . . . 775
3.1.6.3 Definition . . . . . . . . . . . . . . . . . . . . . 776
3.1.6.4 Catalysts and Reaction Conditions . . . . . . . . . . . 777
3.1.6.5 Scope and Limitations . . . . . . . . . . . . . . . . 778
3.1.6.6 Mechanism . . . . . . . . . . . . . . . .. . . . 782
3.1.6.7 Catalyst Deactivation . . . . . . . . . . .. . . . . 784
3.1.6.8 Industrial Applications and Perspectives . . . . . . . . . 786
3.1.7 Catalytic Cyclopropanation (A. I? Noels. A. Demonceau) . . 793
3.1.7.1 Introduction . . . . . . . . . . . . . . . . . . . . 793
3.1.7.2 Transition Metal Catalyzed Cyclopropanations . . . . . . . 794
3.1.7.3 Recent Developments and Applications . . . . . . . . . 798
3.1.7.4 Conclusion: In Search of New Catalysts . . . . . . . . . 805
3.1.8 The Fischer-Tropsch Synthesis - Molecular Models for
Homogeneous Catalysis? (W A. Herrmann) . . . . . . . . 808
3.1.8.1 Introduction . . . . . . . . . . . . . . . . . . . . 808
3.1.8.2 Historical and Economic Background . . . . . . . . . . 809
3.1.8.3 Technological Features . . . . . . . . . . . . . . . . 811
XXIV Contents

3.1.8.4 Mechanistic Considerations . . . . . . . . . . . . . . 811

3.1.8.5 Assessment and Perspectives . . . . . . . . . . . . . 819
3.1.9 Arene Coupling Reactions (W A. Herrmann) . . . . . . . 822
3.1.9.1 Introduction . . . . . . . . . . . . . . . . . . . . 822
3.1.9.2 Aryl-Aryl Coupling . . . . . . . . . . . . . . . . . 823
3.1.9.3 Grignard Cross-Coupling . . . . . . . . . . . . . . . 824
3.1.9.4 Phenol Coupling . . . . . . . . . . . . . . . . . . 826
3.1.9.5 Perspectives . . . . . . . . . . . . . . . . . . . . 827
3.1.10 Tailoring of Catalysts : N-Heterocyclic Carbenes as an
Example of Catalyst Design
(W A. Herrmann. K. Denk. C. W K. Gstiittmayr) . . . . . . 829
3.1.10.1 Introduction . . . . . . . . . . . . . . . . . . . . 829
3.1.10.2 Ligand Design for N-Heterocyclic Carbenes (NHC) . . . . 829
3.1.10.3 Catalytic Applications . . . . . . . . . . . . . . . . 832
3.1.11 Micellar Catalysis (G. Oehme) . . . . . . . . . . . . . 835
3.1.11.1 Introduction . . . . . . . . . . . . . . . . . . . . 835
3.1.11.2 Examples of Micellar-Promoted Reactions . . . . . . . . 837
3.1.11.3 Reactions in Reverse Micelles . . . . . . . . . . . . . 839
3.11.1.4 Limits and New Developments . . . . . . . . . . . . . 840
3.1.12 Sulfur in Homogeneous Catalysis (P: Kalck, l? Serp) . . . . 842
3.1.12.1 Introduction . . . . . . . . . . . . . . . . . . . . 842
3.1.12.2 Sulfur in Carbonylation Reactions . . . . . . . . . . . 843
3.1.12.3 Sulfur in Hydrogenation, Isomerization, and Related
Reactions . . . . . . . . . . . . . . . . . . . . . 845
3.1.12.4 Sulfur in Carbon-Carbon Coupling Reactions . . . . . . . 846
3.1.12.5 Miscellaneous Reactions . . . . . . . . . . . . . . . 847
3.1.12.6 Conclusions . . . . . . . . . . . . . . . . . . . . 848
3.1.13 Homogeneous Catalysis Using Supercritical Fluids
(W Leitner) . . . . . . . . . . . . . . . . . . . . 852
3.1.13.1 Introduction . . . . . . . . . . . . . . . . . . . . 852
3.1.13.2 Single-Phase Catalysis Using SCFs as Solvents . . . . . . 854
3.1.13.3 Multiphase Catalysis Using SCFs as Solvents . . . . . . . 862
3.1.13.4 Conclusions and Outlook . . . . . . . . . . . . . . . 867

3.2 Special Catalysts and Processes . . . . . . . . . . . . 872

3.2.1 Biocatalysis and Enzyme-Analogous Processes
(C. Schultz. H . Grogel; C. Dinkel. K. Drauz. H . Waldmann) . 872
3.2.1.1 Introduction . . . . . . . . . . . . . . . . . . . . 872
3.2.1.2 Examples of Enzymatic Conversions . . . . . . . . . . 873
3.2.1.3 Enzyme-Analogous Catalysts . . . . . . . . . . . . . 886
3.2.1.4 Commercial Applications . . . . . . . . . . . . . . . 887
3.2.1.5 Outlook . . . . . . . . . . . . . . . . . . . . . . 906
 Contents XXV

3.2.2 Template or Host/Guest Relations

(F: Vogtle. R. Hoss. M . Handel) . . . . . . . . . . . . 911
3.2.2.1 Introduction . . . . . . . . . . . . . . . . . . . . 912
3.2.2.2 Metal Cations as Templates . . . . . . . . . . . . . . 913
3.2.2.3 Neutral Molecules as (Supramolecular) Templates . . . . . 914
3.2.2.4 Covalent Molecules as Templates . . . . . . . . . . . . 922
3.2.2.5 Kinetic and Thermodynamic Template Effects . . . . . . . 926
3.2.2.6 Positive and Negative Templates . . . . . . . . . . . . 928
3.2.2.7 Self-organization . . . . . . . . . . . . . . . . . . 928
3.2.2.8 Further Developments and Applications . . . . . . . . . 935
3.2.2.9 Conclusions and Outlook . . . . . . . . . . . . . . . 937
3.2.3 Membrane Reactors in Homogeneous Catalysis
(U. Kragl, C. Dreisbach) . . . . . . . . . . . . . . . 941
3.2.3.1 Introduction . . . . . . . . . . . . . . . . . . . . 941
3.2.3.2 Classification and Examples of Membrane Reactors . . . . 942
3.2.3.3 Membrane Reactors for Homogeneously Soluble Catalysts . . 947
3.2.3.4 Summary and Outlook . . . . . . . . . . . . . . . . 950
3.2.4 Phase-Transfer Catalysis and Related Systems
(E: Goldberg, H . Alper) . . . . . . . . . . . . . . . 953
3.2.4.1 Introduction . . . . . . . . . . . . . . . . . . . . 9.53
3.2.4.2 Homogeneous Transition-Metal Catalyzed Reactions
Under Phase-Transfer Conditions . . . . . . . . . . . . 9.54
3.2.4.3 Transition-Metal Containing Phase-Transfer Agents and
Their Use in Synthesis . . . . . . . . . . . . . . . . 968
3.2.4.4 Conclusions . . . . . . . . . . . . . . . . . . . . 969
3.2.5 Rare Earth Metals in Homogeneous Catalysis
(R. Anwander) . . . . . . . . . . . . . . . . . . . 974
3.2.5.1 Introduction . . . . . . . . . . . . . . . . . . . . 974
3.2.5.2 Catalytic Potential . . . . . . . . . . . . . . . . . . 976
3.2.5.3 Precatalysts . . . . . . . . . . . . . . . . . . . . 977
3.2.5.4 Carbon-Carbon Bond-Forming Reactions . . . . . . . . 978
3.2.5.5 Carbon-Heteroelement Bond-Forming Reactions . . . . . . 997
3.2.5.6 Catalyst Structure . . . . . . . . . . . . . . . . . . 1005
3.2.5.7 Perspectives . . . . . . . . . . . . . . . . . . . . 1007
3.2.6 Recent Progress in Special Phosphorus-Containing
Auxiliaries for Homogeneous Enantioselective Catalysis
(F: Agbossou-Niedercorn) . . . . . . . . . . . . . . . 1014
3.2.6.1 Introduction . . . . . . . . . . . . . . . . . . . . 1014
3.2.6.2 Monophosphines . . . . . . . . . . . . . . . . . . 1015
3.2.6.3 Bi(di,bis)phosphines . . . . . . . . . . . . . . . . . 1020
3.2.6.4 Heterofunctionalized Multidentate P-Containing
Chiral Auxiliaries . . . . . . . . . . . . . . . . . . 1024
3.2.6.5 Immobilization and Recycling . . . . . . . . . . . . . 1025
3.2.6.6 Conclusions . . . . . . . . . . . . . . . . . . . . 1027
XXVI Contents

Volume 3: Developments (continued)

3.2.7 Homologation ( H. Bahrmann) . . . . .. . . . . . . . 1034
3.2.7.1 Historical Background . . . . . . . .. . . . . . . . 1034
3.2.7.2 Chemical Basics and Applications . . .. . . . . . . . 1035
3.2.7.3 Mechanism of Reaction . . . . . . .. . . . . . . . 1040
3.2.7.4 Technical Applications . . . . . . . .. . .. . . . . 1042
3.2.7.5 Future Prospects . . . . . . . . . .. . . . . . . . 1044
3.2.8 Homogeneous Electrocatalysis ( D. Astruc) . . . . . . . . 1046
3.2.8.1 Introduction . . . . . . . . . . . . . . . . . . . . 1046
3.2.8.2 Electron-Transfer-Chain (ETC) Catalyzed Reactions . . . . 1047
3.2.8.3 Atom-Transfer-Chain (ATC) Catalysis . . . . . . . . . . 1055
3.2.8.4 Conclusions . . . . . . . . . . . . . . . . . . . . 1057
3.2.9 Homogeneous Photocatalysis (A. Heumann, M . Chanon) . . 1060
3.2.9.1 Definitions . . . . . . . . . . . . . . . . . . . . . 1060
3.2.9.2 Synthesis and Activation - What hv Metal Catalysis
Can Do Better? . . . . . . . . . . . . . . . . . . . 1065
3.2.9.3 Conclusion: What Photochemical Techniques Can Provide
in Mechanistic Studies of Transition Metal Catalysis . . . . 1074
3.2.10 Olefins from Aldehydes (W A . Herrmann) . . . . . . . . 1078
3.2.10.1 Introduction . . . . . . . . . . . . . . . . . . . . 1078
3.2.10.2 The Catalytic Approach . . . . . . . . . . . . . . . 1079
3.2.10.3 Catalysts . . . . . . . . . . . . . . . . . . . . . 1080
3.2.10.4 Scope of Reaction. Reagents, and Side Reactions . . . . . 1081
3.2.10.5 Mechanism . . . . . . . . . . . . . . . . . . . . 1082
3.2.10.6 Perspectives . . . . . . . . . . . . . . . . . . . . 1085
3.2.11 Water-Gas Shift Reaction (W A . Herrmann. M . Muehlhofer) . 1086
3.2.11.1 Introduction . . . . . . . . . . . . . . . . . . . . 1086
3.2.11.2 Definition . . . . . . . . . . . . . . . . . . . . . 1087
3.2.11.3 Mechanism . . . . . . . . . . . . . . . . . . . . 1087
3.2.11.4 Applications . . . . . . . . . . . . . . . . . . . . 1089
3.2.11.5 The Arc0 Ethylurethane Process . . . . . . . . . . . . 1090
3.2.11.6 Catalytic Implications and Perspectives . . . . . . . . . 1091
3.2.12 Catalytic McMurry Coupling: Olefins from Keto Compounds
(W A . Herrmann. H . Schneider) . . . . . . . . . . . . 1093
3.2.12.1 Introduction . . . . . . . . . . . . . . . . . . . . 1093
3.2.12.2 Stoichiometric Titanium Compounds, Other Reagents,
and Mechanistic Aspects . . . . . . . . . . . . . . . 1094
3.2.12.3 Catalytic Deoxygenation . . . . . . . . . . . . . . . 1096
3.2.12.4 Perspectives . . . . . . . . . . . . . . . . . . . . 1097
 Contents XXVII

3.2.13 Catalytic Hydrogenation of Heterocyclic Sulfur and Nitrogen

Compounds in Raw Oils (C. Bianchini. A . Meli. F: Vizzn) . . 1099
3.2.13.1 Introduction . . . . . . . . . . . . . . . . . . . . 1099
3.2.13.2 Hydrogenation of Sulfur Heterocycles . . . . . . . . . . 1100
3.2.13.3 Hydrogenolysis of Sulfur Heterocycles . . . . . . . . . . 1106
3.2.13.4 Hydrodesulfurization in Different Phase Variation Systems . . 1109
3.2.13.5 Hydrogenation of Nitrogen Heterocycles . . . . . . . . . 1109
3.2.13.6 Hydrogenolysis of Nitrogen Heterocycles . . . . . . . . . 1116
3.2.13.7 Perspectives . . . ; . . . . . . . . . . . . . . . . 1116
3.2.14 Double-Bond Isomerization of Olefins
( W A. Herrmann. M . Prinz) . . . . . . . . . . . . . . 1119
3.2.14.1 Introduction . . . . . . . . . . . . . . . . . . . . 1119
3.2.14.2 Catalysts. Scope. and Definition . . . . . . . . . . . . 1120
3.2.14.3 Mechanistic Considerations . . . . . . . . . . . . . . 1121
3.2.14.4 Applications . . . . . . . . . . . . . . . . . . . . 1124
3.2.14.5 Asymmetric Isomerization . . . . . . . . . . . . . . 1125
3.2.14.6 Recent Developments . . . . . . . . . . . . . . . . 1126
3.2.14.7 Perspectives . . . . . . . . . . . . . . . . . . . . 1128
3.3 Special Products . . . . . . . . . . . . . . . . . . 1131
3.3.1 Enantioselective Synthesis
(H.-U. Blaser; B. Pugin. F: Spindler) . . . . . . . . . . 1131
3.3. 1. 1 Introduction and Background . . . . . . . . . . . . . 1131
3.3.1.2 Critical Factors for the Technical Application
of Homogeneous Enantioselective Catalysts . . . . . . . . 1132
3.3.1.3 State-of-the-Art and Evaluation of Catalytic Transformations . 1134
3.3.1.4 Conclusions and Prospects . . . . . . . . . . . . . . 1146
3.3.2 Diols via Catalytic Dihydroxylation
( M. Beller; K . B. Sharpless) . . . . . . . . . . . . . . 1149
3.3.2.1 Introduction . . . . . . . . . . . . . . . . . . . . 1149
3.3.2.2 History and General Features of Osmium-Catalyzed
Dihydroxylation Reactions . . . . . . . . . . . . . . 1150
3.3.2.3 Mechanism of Osmium-Catalyzed Dihydroxylations . . . . 1152
3.3.2.4 Scope and Limitation of Asymmetric Dihydroxylation . . . 1153
3.3.2.5 Selected Applications of Osmium-Catalyzed Dihydroxylations 1159
3.3.3 Hydrovinylation ( P W. Jolly. G. Wilke) . . . . . . . . . 1164
3.3.3.1 Introduction . . . . . . . . . . . . . . . . . . . . 1164
3.3.3.2 The Catalyst . . . . . . . . . . . . . . . . . . . . 1165
3.3.3.3 The Product . . . . . . . . . . . . . . . . . . . . 1169
3.3.3.4 The Mechanism . . . . . . . . . . . . . . . . . . . 1178
3.3.3.5 Outlook . . . . . . . . . . . . . . . . . . . . . . 1184
3.3.3.6 Postscript . . . . . . . . . . . . . . . . . . . . . 1185
XXVIII Contents

3.3.4 Carbon Dioxide as a C1 Building Block

( E. Dinjus. R. Fornika. S. Pittel; I: Zevaco) . . . . . . . 1189
3.3.4.1 Introduction . . . . . . . . . . . . . . . . . . . . 1189
3.3-4.2 Catalytic C-C Bond-Forming Reactions . . . . . . . . . 1191
3.3.4.3 Transition Metal Catalyzed Formation of Formic Acid
and its Derivatives from C 0 2 and H2 . . . . . . . . . . 1196
3.3.4.4 Catalyzed Formation of Organic Carbonates . . . . . . . 1205
3.3.4.5 Summary and Outlook . . . . . . . . . . . . . . . . 1208
3.3.5 Reductive Carbonylation of Nitro Compounds
( M. Dugal. D . Koch, G. Nabefeld. C. Six) . . . . . . . . 1214
3.3.5.1 Introductory Remarks . . . . . . . . . . . . . . . . 1214
3.3-5.2 Synthesis of Isocyanates . . . . . . . . . . . . . . . 1214
3.3.5.3 Thermodynamics, Kinetics, and Mechanism . . . . . . . . 1218
3.3.5.4 Outlook . . . . . . . . . . . . . . . . . . . . . . 1223
3.3.6 New Approaches in C-H Activation of Alkanes (A. Sen) . .
1226
3.3.6.1 Introduction . . . . . . . . . . . . . . . . . . . . 1226
3.3.6.2 Radical Pathways . . . . . . . . . . . . . . . . . . 1227
3.3.6.3 Oxidative Addition Pathways . . . . . . . . . . . . . 1229
3.3.6.4 Electrophilic Pathways . . . . . . . . . . . . . . . . 1231
3.3.6.5 Conclusions . . . . . . . . . . . . . . . . . . . . 1238
3.3.7 Pauson-Khand Reaction (W A . Herrmann) . . . . . . . . 1241
3.3.7.1 Introduction . . . . . . . . . . . . . . . . . . . . 1241
3.3.7.2 The Catalytic Option . . . . . . . . . . . . . . . . . 1242
3.3.7.3 Related Reactions . . . . . . . . . . . . . . . . . . 1244
3.3.7.4 Stereoselective PKRs and Hetero-Reactions . . . . . . . . 1245
3.3.7.5 Degenerate (Intermittent) and Domino PK Reactions . . . . 1246
3.3.7.6 Substitution Effects, Selectivity, and Mechanism . . . . . . 1247
3.3.7.7 Commercial Perspectives . . . . . . . . . . . . . . . 1249
3.3.7.8 Outlook . . . . . . . . . . . . . . . . . . . . . . 1250
3.3.8 Cyclooligomerization of Alkynes
(H. Bonnemann, W Brijoux) . . . . . . . . . . . . . 1252
3.3.8.1 Introduction . . . . . . . . . . . . . . . . . . . . 1252
3.3.8.2 Survey of the Catalysts . . . . . . . . . . . . . . . . 1253
3.3.8.3 Five- and Six-Membered Heterocycles . . . . . . . . . . 1254
3.3.8.4 Six- and Eight-Membered Carbocycles . . . . . . . . . . 1261
3.3.9 Chemicals from Renewable Resources ( J. Z? Zoller) . . . . 1268
3.3.9.1 Introduction and General Developments . . . . . . . . . 1268
3.3.9.2 “Oleo Chemistry” . . . . . . . . . . . . . . . . . . 1268
3.3.9.3 The Chemistry of Carbohydrates . . . . . . . . . . . . 1271
3.3.9.4 The Chemistry of Starch . . . . . . . . . . . . . . . 1271
3.3.10 Special Reactions in Homogeneous Aqueous Systems . . . . 1274
3.3.10.1 Synthesis of Polymers (B. M . Novak) . . . . . . . . . . 1274
3.3.10.2 Homogeneous Catalysis in Living Cells ( L. Vigh. E Job) . . 1283
 Contents XXIX

3.3.11 Cyclic Hydrocarbons from Diazoalkanes

(W A. Herrmann. Horst Schneider) . . . . . . . . . . . 1290
3.3.11.1 Introduction . . . . . . . . . . . . . . . . . . . . 1290
3.3.11.2 Scope and Definition . . . . . . . . . . . . . . . . 1290
3.3.11.3 Mechanistic Considerations . . . . . . . . . . . . . . 1291
3.3.11.4 Catalytic Cyclization . . . . . . . . . . . . . . . . . 1292
3.3.11.5 Enantioselective Cyclization . . . . . . . . . . . . . . 1295
3.3.11.6 Perspectives . . . . . . . . . . . . . . . . . . . . 1295
3.3.12 Acrolein and Acrylonitrile from Propene ( W A . Herrmann) . 1297
3.3.12.1 Introduction . . . . . . . . . . . . . . . . . . . . 1297
3.3.12.2 Scope and Technological Features . . . . . . . . . . . 1297
3.3.12.3 Catalyst Principles and Mechanism . . . . . . . . . . . 1298
3.3.12.4 Organometallic Models . . . . . . . . . . . . . . . . 1300
3.3.12.5 The “Amm(on)dehydrogenation” . . . . . . . . . . . . 1301
3.3.12.6 Perspectives . . . . . . . . . . . . . . . . . . . . 1303
3.3.13 Chemistry of Methyltrioxorhenium (MTO) . . . . . . . . 1304
3.3.13.1 Fine Chemicals via Methyltrioxorhenium as Catalyst
( R E. Kiihn, M . Groarke) . . . . . . . . . . . . . . . 1304
3.3.13.2 Pilot-Plant Synthesis of MTO ( W A . Herrmann) . . . . . . 1319
3.3.14 Acetoxylations and Other Palladium-Promoted or
Palladium-Catalyzed Reactions ( R. Jira) . . . . . . . . . 1323
3.3.14.1 Historical and Economic Background . . . . . . . . . . 1323
3.3.14.2 Chemical Background . . . . . . . . . . . . . . . . 1323
3.3.14.3 Kinetics and Mechanism . . . . . . . . . . . . . . . 1325
3.3.14.4 Commercial Processes . . . . . . . . . . . . . . . . 1329
3.3.14.5 Transvinylation . . . . . . . . . . . . . . . . . . . 1331
3.3.14.6 Acetoxylation in Organic Synthesis . . . . . . . . . . . 1332
3.3.14.7 Other Palladium-Promoted or Palladium-Catalyzed
Reactions . . . . . . . . . . . . . . . . . . . . . 1333
3.3.14.8 Conclusions . . . . . . . . . . . . . . . . . . . . 1336

4 Epilogue . . . . . . . . . . . . . . . . . . . . 1341

4.1 Homogeneous Catalysis .Quo vadis?

(W A . Herrmann. B. Cornils) . . . . . . . . . . . . . 1343
4.1.1 Immobilization of Homogeneous Catalysts . . . . . . . . 1345
4.1.2 Colloidal Organometallic Catalysts . . . . . . . . . . . 1347
4.1.3 Multicomponent and Multifunctional Catalysis . . . . . . 1347
4.1.4 Stereoselective Catalysis . . . . . . . . . . . . . . . 1348
4.1.5 Metals from Stoichiometric Reactivity to Catalytic Efficiency . 1351
XXX Contents

4.1.6 Mechanistic Knowledge and Theory .Keys to Catalyst

Design . . . . . . . . . . . . . . . . . . . . . . 1352
4.1.7 Catalyst PerformanceAVew Techniques to Generate and
Activate Catalysts . . . . . . . . . . . . . . . . . . 1353
4.1.8 Organometallic Electrocatalysis and Biomimetic Catalysis . . 1354
4.1.9 New Chemical Feedstocks for Homogeneous Catalysis
and Renewable Resources . . . . . . . . . . . . . . . 1356
4.1.10 Catalysis under Supercritical Conditions and Supported
by Ionic Liquids . . . . . . . . . . . . . . . . . . 1362
4.1.11 New Reactions, Improved Catalysts . . . . . . . . . . . 1365
4.1.12 A New Generation of Catalyst Ligands . . . . . . . . . 1368
4.1.13 Rare Earth Catalysts . . . . . . . . . . . . . . . . . 1369
4.1.14 Organometallic Catalysts for Polymers . . . . . . . . . . 1371
4.1.15 Catalyst Reactivation. Process. and Reactor Technology . . . 1375
4.1.16 Final Closure . . . . . . . . . . . . . . . . . . . . 1375

Index . . . . . . . . . . . . . . . . . . . . . . . . . 1383
Contributors
Dr. Francine Agbossou-Niedercom
Laboratoire de Catalyse de Lille
UPRES-A CNRS 8010
Ecole Nationale SupCrieure de Lille
C7 BP 108
F-59652 Villeneuve d’Ascq CedexFrance
Tel: +33(0)3/2043-4927
Fax: +33(0)3/2043-6585
E-mail: francine.agbossou@ensc-lille.fr
Prof. Dr. Howard Alper
Department of Chemistry
University of Ottawa
10, rue Marie Curie
Ottawa, Ontario K1N 6NYCanada
Tel: +1/613-564-2214
Fax : + 1/613-564-6703
PD Dr. Reiner Anwander
Anorganisch-chemisches Institut
der Technischen Universitat Munchen
Lichtenbergstrafle 4
D-85747 Garching/Germany
Tel: +49(0)89/289-13096
Fax: +49(0)89/289-13473
E-mail: reiner.anwander @ ch.tum.de
Dr. Jan-Dirk Arndt
BASF AG
Chemicals Research and Engineering
Abt. GCVC
D-67056 Ludwigshafen/Germany
Tel: +49(0)621/60-45345
Fax: +49(0)621/60-8607066
E-mail: jan-dirk.amdt@basf-ag.de
Dr. Michael Amdt-Rosenau
Bayer AG
Abt. KA-FuE-SE
D-5 1538 Dormagen/Germany
Tel: +49(0)2133/5 1-23352
Fax: +49(0)2 133/51-4034
E-mail:
michael.arndt-rosenau.ma@ bayer-ag.de
Prof. Dr. Didier Astruc
UniversitC de Bordeaux I
Laboratoire de Chimie Organique
et OrganomCtallique
URA CNRS No 35
351, cours de la LibCration
F-33405 Talence CCdexFrance
Tel: +33/56846271
Fax: +33/56846646
Prof. Dr. Manfred Baems
Institut fur Angewandte Chemie
Berlin-Adlershof e. V.
Rudower Chaussee 5
D- 12484 BerlidGermany
Tel: +49(0)30/6392-4444
Fax: +49(0)30/6392-4454
E-mail: baems @aca.berlin.de
Dr. Helmut Bahrmann
RohstraBe 48
D-46499 Hamminkeln/Germany
Tel: +49(0)2856-1450
Prof. Dr. Jean-Marie Basset
Laboratoire COMS
CPE-LYON
43, Boulevard du 11 Novembre 1918
F-69616 Villeurbanne Cedex/France
Tel: +33/72413- 1792
Fax: +33/72413- 1793
E-mail: basset@comsl .cpe.fr
Prof. Dr. Matthias Beller
Institut fur Organische Katalyseforschung
Universitat Rostock
Buchbinderstrarje 5-6
D-18055 RostocWGemany
Tel: +49(0)381/466-9313
Fax: +49(0)381/466-9324
E-mail: Matthias.Beller@ifok.uni-rostock.de
XXXIV Contributors
Dr. Claudio Bianchini
Istituto per lo Studio della
Stereochimica ed Energetica dei
Composti di Coordinazione - CNR
Via J. Nardi, 39
1-50132 Firenzehtaly
Tel: +3905/524-5990
Fax: +3905/524-78366
E-mail: bianchin @ fi.cnr.it
Dr. Hans-Ulrich Blaser
Solvias AG
Postfach
CH-4002 BaseVSwitzerland
Tel: +4161/686-6155
Fax : +4 161/686-6311
E-mail: hans-ulrich.blaser@SOLVIAS.com
Prof. Dr. Ludwig L. Bohm
Basell Polyolefine GmbH
Industriepark Hochst, C 660
D-65926 FrankfudGermany
Tel: +49(0)69/305-5887
Fax: +49(0)69/305-3305
E-mail: ludwig.boehm@basell.com
Dr. Volker P. W. Bohm
BASF AG
Abt. GCB/K - M313
D-67056 LudwigshafedGermany
Tel: +49(0)621/605-6721
Fax : +49(0)62 1/605-6116
E-mail: volker.boehm@basf-ag.de
Prof. Dr. Helmut Bonnemann
Max-Planck-Institut fur Kohlenforschung
Postfach 10 13 53
D-45466 Mulheim an der RuhdGermany
Tel: +49(0)208/306-2374
Fax: +49(0)208/306-2983
E-mail: boennemann@mpi-muelheim.mpg.de
Dr. Hans-Willi Bohnen
Celanese GmbHmerk Ruhrchemie
Abt. FOX
Postfach 13 01 60
D-46 128 Oberhausen/Germany
Tel : +49(0)208/693-220 1
Fax: +49(0)202/693-229 1
E-mail: HBohnen @celanese.de
Dr. Werner Brijoux
Max-Planck-Institut fur Kohlenforschung
Postfach 101353
D-45466 Mulheim an der Ruhr/Germany
Tel: +49(0)208/306-2360
Fax: +49(0)208/306-2983
E-mail: brijoux @ mpi-muelheim.mpg .de
Dr. Johannes A. M. van Broekhoven
Shell Research and Technology Centre
Amsterdam
Postbus 38000
NL-1030 BN Amsterdamhe Netherlands
Tel: +31/20-6302667
Fax: +31/20-6304035
Prof. Dr. Henri Brunner
Institut fur Anorganische Chemie
der Universitat Regensburg
UniversitatsstraBe 3 1
D-93053 RegensburgIGermany
Tel: +49(0)941/943-4441
Fax: +49(0)941/943-4439
E-mail:
henri.brunner @chemie.uni-regensburg.de
Dr. Peter H. M. Budzelaar
Shell Research and Technology Centre
Amsterdam
Postbus 38000
NL- 1030 BN A m s t e r d a d h e Netherlands
Tel: +3 1/20-6302667
Fax: +3 1/20-6304035
Prof. Dr. Michel Chanon
UniversitC d’Aix-Marseille
Av. Escadrille-Normandie-Niemen
F- 13397 Marseille Cedex 20France
Tel: +33/91-670999
Fax: +33/91-288432
Prof. Dr. Peter Claus
Institut fur Chemische Technologie
TU Darmstadt
PetersenstraSe 20
D-64287 Darmstadt/Germany
Tel: +49(0)6151/16-5369
Fax : +49(0)6 151/16-4788
E-mail: claus @ct.chemie.tu-darmstadt.de
 Contributors XXXV

Prof. Dr. Boy Comils Prof. Dr. Karlheinz Drauz

KirschgartenstraBe 6 Degussa AG
D-65719 HofheidGermany Abt. FC-FEA
Tel: +49(0)6192/23502 Rodenbacher Chaussee 4
Fax: +49(0)6192/23502 D-63457 HanadGermany
E-mail: Boy.Comils @t-online.de Tel: +49(0)618 1/59-2072
Fax : +49(0)6 18 1/5 9-3930
Prof. Dr. A. Demonceau E-mail: karlheinz.drauz@degussa.com
CERM - Institut de Chimie B6
UniversitC de Liitge Dr. Claus Dreisbach
B-4000 Sart Tilman/Belgium Bayer AG
Tel: +324/3663-495 Abt. CH-FCH-R&D-LSI
Fax: +324/3663-497 D-5 1368 LeverkusedGermany
E-mail : A.Demonceau @ulg.ac.be Tel: +49(0)214/30-7 1039

Dip1.-Chem. Karin Denk Dr. Eite Drent

Anorganisch-chemisches Institut Shell Research and Technology Centre
der Technischen Universitat Munchen Amsterdam
LichtenbergstraBe 4 Postbus 38000
D-85747 Garching/Germany NL- 1030 BN Amsterdamhe Netherlands
Tel: +49(0)89/289-13073 Tel: +3 1/20-6302667
Fax: +49(0)89/289-13473 Fax: +3 1120-6304035
E-mail: karhdenk@Ch.tum.de E-mail: Eite. E.Drent@opc.shell.com

Prof. Dr. Eckhard Dinjus Dr. Markus Dugal

Institut fur Technische Chemie
Forschungszentrum Karlsruhe GmbH
Hermann-von-Helmholtz-Platz 1
D-76344 Eggenstein-Leopoldshafen/Germany
Tel: +49(0)7247/82-2400
Fax: +49(0)7247/82-2244
E-mail: eckhard.dinjus @itc-cpv.fzk.de
Dr. Car10 Dinkel
Bioorganic Chemistry of Signalling
Molecules
EMBL
Meyerhofstrarje 1
D-69 117 Heidelberg/Germany
Tel: +49(0)622 1/387-498
Fax: +49(0)622 1/387-206
E-mail: carlo.dinkel@embl-heidelberg.de
Prof. Dr. Manfred Doring
Institut fur Technische Chemie
Forschungszentrum Karlsruhe GmbH
Postfach 36 40
D-76021 Karlsruhe/Germany
Tel: +49(0)7247/82-4385
Fax: +49(0)7247/82-2244
E-mail: manfred.doering@itc-cpv.fzk.de
Bayer AG
Abt. PU-R-PI
D-41538 Dormagen/Germany
Tel: +49(0)2133/51-5443
Fax : +49(0)2 133/51-3244
E-mail : markus.dugal.md @ bayer-ag.de
Dr. Anette Eckerle
BASF AG
Abt. ZOA/SE
Gebaude C 100
D-67056 LudwigshafedGermany
Tel: +49(0)621/60-94391
Fax: +49(0)621/60-74942
E-mail : anette.eckerle @ basf-ag .de
Dr. Richard W. Fischer
Sudchemie AG
Waldheimer StraBe 13
D-83052 BruckmuhVGermany
Tel: +01/502 634-6828
Fax: +OM02 634-7265
E-mail: discher@sud-chemieinc.com
XXXVI Contributors
Dr. Roland Fornika
Degussa AG
Stockhausen Superabsorber Acrylic
Monomers Marl
Paul-Baumann-StraBe 1
D-45764 MarUGermany
Tel: +49(0)2365/49-193 17
Fax: +49(0)2365/49-6980
E-mail: roland.fornika@degussa.com
Dr. Cornelia Fritze
Basell Polyolefins
Gebaude M214
Carl-Bosch-StraBe 38
D-67056 LudwigshafedGermany
Tel: +49(0)621/6093008
Fax: +49(0)621/605 1501
E-mail: cornelia.fritze@basell.com
Dr. Carl Dieter Frohning
RegnitstraBe 50
D-46485 WeseVGermany
Tel: +49(0)28 1/56851
Fax: +49(0)281/854-9158
E-mail : Frohning @ cityweb.de
Dr. Dieter Gleich
Physikalisch-chemisches Institut
Universitat Zurich
WinterthurstraBe 190
CH-8057 ZuricWSwitzerland
E-mail : gleich @ pci.unizh.ch
Dr. Yuri Goldberg
Apotex Inc.
Weston, Ontario M9L 1T6/Canada
Dr. Michelle Groarke
Synetix, PO Box 1
Belasis Avenue
Billingham, Cleveland TS23 1LB
Great Britain
Dr. Harald Groeger
Degussa AG
Project House Biotechnology
Rodenbacher Chaussee 4
D-63457 Hanau-Wolfgang/Germany
Tel: +49(0)6181/59-6401
Fax : +49(0)6 18 1159-2961
E-mail: harald.groeger@degussa.com
DipLChem. Christian W. K. Gstottmayr
Anorganisch-chemisches Institut
der Technischen Universitat Munchen
LichtenbergstraBe 4
D-85747 Garching/Germany
Tel: +49(0)89/289-13095
Fax: +49(0)89/289-13473
E-mail: christian.gstoettmayr@ch.tum.de
Dr. Mirko Handel
Institut fur Organische Chemie
und Biochemie der Universitat Bonn
Gerhard-Domagk-StraBe 1
D-53121 Bonn
Tel: +49(0)228/73-5673
Fax: +49(0)228/73-5662
Dr. Shohei Hashiguchi
Takeda Chemical Industries
Pharmaceutical Research Division
2-17-85, Jusohonmachi, Yodogawa-ku
Osaka 532-8686/Japan
Tel: +81(06)6300-6719
Fax: +81(06)6300-6206
E-mail: Hashiguchi-Shohei@ takeda.co.jp
Dr. Jochem Henkelmann
BASF AG
Chemicals Research and Engineering
Abt. GCI/C - M311
D-67056 Ludwigshafen/Germany
Tel: +49(0)621/60-45011
Fax: +49(0)621/60-45044
E-mail: jochem.henkelmann@basf-ag.de
Prof. Dr. Wolfgang A. Henmann
Anorganisch-chemisches Institut
der Technischen Universitat Munchen
LichtenbergstraBe 4
D-85747 Garching/Germany
Tel: +49(0)89/2891-3081
Fax: +49(0)89/2891-3473
E-mail: secretariat.ac @ch.tum.de
Dr. Jurgen Herwig
Degussa AG
B-HP-FEA 15, Bau 1324-PB 16
D-45764 MallGermany
Tel: +49(0)2365/49-86395
Fax: +49(0)2365/49-5992
E-mail : juergen.herwig @ degussa.com
 Contributors XXXVII

Prof. Dr. Diethard Hesse Dr. Ralf Hoss

Institut fur Technische Chemie Siegfried AG
der Universitat Hannover Untere BriihlstraBe 4
CallinstraBe 3 CH-4800 ZofingedSwitzerland
D-30 167 Hannover/Germany Tel : +41/62-746-1282
Tel: +49(0)5 11/762-2269 Fax : +4 1/62-746-1101
Fax: +49(0)5 11/762-3004
E-mail: hesse@mbox.uni-hannover.de Dr. Willem W. Jager
Shell Research and Technology Centre
Prof. Dr. Andreas Heumann Amsterdam
UniversitC d’Aix-Marseille Postbus 38000
Av. Escadrille-Normandie-Niemen NL- 1030 BN A m s t e r d a f l h e Netherlands
F-13397 Marseille Cedex 20Prance Tel: +3 1/20-6302667
Tel: +33/91288278 Fax: +3 1/20-6304035
Fax: +33/91027776
Dr. Jorg-Dietrich Jentsch
Dr. Wolfgang Hieringer Bayer AG Uerdingen
Theoretical ChemistryPEW Abt. OC-P UER 1
Vrije Universiteit Amsterdam Gebaude R 34
De Boelelaan 1083 RheinuferstraBe 6-9
NL- 1081 HV A m s t e r d a d h e Netherlands D-47829 Krefeld/Germany
Tel: +31(0)20/4447616 Tel: +49(0)215 1/88-7885
Fax: +31(0)20/4447629 Fax: +49(0)215 1/88-4853
E-mail : hieringr @chem.vu.nl
Dr. Reinhard Jira
Dr. Charles C. Hobbs, Jr. Formerly: Wacker-Chemie GmbH
Celanese AG Private address:
Corpus Christi Technical Center KabastastraBe 9
P. 0. Box 9077 D-8 1243 MunchenlGermany
Corpus Christi, TX 78469LJSA Tel + Fax: +49(0)89/831467
Tel: +1/512-2424000
Fax: +1/512-2424087 Prof. Dr. Peter W. Jolly
Max-Planck-Institut fur Kohlenforschung
Dr. Arthur Hohn Postfach 101353
BASF AG D-45466 Mulheim an der RuhdGermany
Abt. ZAGIK Tel: +49(0)208/306-1
Gebaude M 313 Fax: +49(0)208/306-2980
D-67056 LudwigshafedGermany
Tel: +49(0)621/60-54315 Prof. Dr. Ferenc Jo6
Fax : +49(0)62 1/60-5 6 116 Institute of Physical Chemistry
Kossuth Lajos University
Prof. Dr. Istvin T. Horvith H-4010 DebrecedHungary
Eotvos University Tel: +36/52- 16-666
Department of Organic Chemistry Fax: +36/52- 10-936
Pizminy PCter sCtiny 1/A
H-1117 Budapest/Hungary
Tel: +361/209-0590
Fax: +361/209-0607
E-mail : ithorvath @ compuserve.com
XXXVIII Contributors

Prof. Dr. Philippe Kalck Prof. Dr. John F. Knifton

Laboratoire de Catalyse Huntsman Corp.
Chimie Fine et Polymkres P. 0. Box 15 730
Ecole Nationale SupCrieure Austin, TX 78761NSA
des IngCnieurs en Arts Tel: +1/512-459-6543
Chimiques et Technologiques Fax: +1/5 12-483-0925
118, route de Narbonne
F-3 1077 Toulouse Cedex 4France Dr. Daniel Koch
Tel: +335/6288-5690 Bayer AG
Fax: +335/6288-5600 Abt. PU-R-PI
E-mail: pkalck@ensiacet.fr D-41538 DormagerdGermany
Tel: +49(0)2133/5 1-8104
Prof. Dr. Walter Kaminsky Fax: +49(0)2133/5 1-3244
Institut fur Technische und E-mail: daniel.koch.dk@bayer-ag.de
Makromolekulare Chemie
Universitat Hamburg Dr. Howard Frederick (Fred) Koch
BundesstraBe 45 Celanese Chemicals
D-20146 Hamburg/Germany 1901 Clarkwood Rd.
Tel: +49(0)40/42838-3 162 Corpus Christi, TX 78410AJSA
Fax: +49(0)40/42838-6008 Tel: +1/3612424016
E-mail : kaminsky @ chemie.uni-hamburg.de Fax: +1/361242 4087
E-mail: hfkoch@celanese.com
Dr. Jan J. Keijsper
Shell Research and Technology Centre Dr. Christian W. Kohlpaintner
Amsterdam Celanese Chemicals Americas
Postbus 38000 1601 West LBJ Freeway
NL-1030 BN A m s t e r d a d h e Netherlands Dallas, TX 75234-6034LJSA
Tel: +31/20-6302667 Tel: +1/9724434416
Fax: +31/20-6304035 Fax: +1/972 443 3070
E-mail: ckohlpaintner@celanese.com
Dr. Roland Kessinger
BASF AG Prof. Dr. Udo Kragl
Chemicals Research and Engineering Universitat Rostock
Abt. GCUC FB Chemie - Technische Chemie
D-67056 LudwigshafedGerrnany Albert-Einstein-StraBe 3A
Tel: +49(0)621/60-79863 D- 18059 RostocMGermany
Fax: +49(0)62 1/60-8607213 Fax: +49(0)381/498-6450
E-mail: roland.kessinger@basf-ag.de E-mail: udo.kragl@chemie.uni-rostock.de

Dr. Alexander Klausener Dr. Steffen Krill

Bayer AG Uerdingen Degussa AG
Abt. OC-P UER 1, Geb. R 34 Abt. FA-PT
RheinuferstraBe 6-9 Postfach 13 45
D-47829 KrefeldlGermany D-6340 3 HanadGermany
Tel: +49(0)2151/88-7885 Tel: +49(0)618 1/59-4378
Fax : +49(0)2 15 1/8 8-4853 Fax: +49(0)6181/59-4631
E-mail: steffen.krill@degussa.com

PD Dr. F.E. Kiihn
Anorganisch-chemisches Institut
der Technischen Universitat Miinchen
LichtenbergstraBe 4
D-85747 Garching/Germany
Tel: +49(0)89/289- 13174
Fax: +49(0)89/289- 13473
E-mail: fritz.kuehn @ ch.tum.de
Prof. Dr. Walter Leitner
Max-Planck-Institut fur Kohlenforschung
Postfach 10 13 53
D-45466 MiilheidGemany
Tel: +49(0)208/306-2500
Fax: +49(0)208/306-2993
E-mail: leitner@mpi-muelheim.mpg.de
Prof. Dr. Bogdan Marciniec
Department of Organometallic Chemistry
Faculty of Chemistry
Adam Mickiewicz University
Grunwaldzka 6
PL-60-780 PoznanPoland
Tel: +48/61-65-96-51
Fax: +48/61-65-95-68
E-mail: marcinb@main.amu.edu.pl
Dr. Andrea Meli
Istituto per lo Studio della
Stereochimica ed Energetica dei
Composti di Coordinazione - CNR
Via J. Nardi, 39
1-50132 Firenzehtaly
Tel: +3905/524-5990
Fax: +3905/524-78366
E-mail : meli @ fi.cnr.it
Prof. Dr. Ilya I. Moiseev
N. S. Kurnakov Institute of General
and Inorganic Chemistry
Russian Academy of Sciences
Leninski Prospect 3 1
117907 Moscow GSP-1Russia
Tel: +095/952-1203
Fax: +095/954-1279
E-mail: iimois@ionchran.rinet.ru
Contributors XXXIX
Dr. Ir. Johannes C. Mol
Institute of Molecular Chemistry
Faculty of Science
University of Amsterdam
Nieuwe Achtergracht 166
NL- 1018 WV A m s t e r d a d h e Netherlands
Tel: +31/20-525690
Fax: +31/20-525656
E-mail: jcmol@science.uva.nl
Dipl.-Chem. Michael Muehlhofer
Anorganisch-chemisches Institut
der Technische Universitat Miinchen
LichtenbergstraBe 4
D-85747 Garching/Germany
Tel: +49(0)89/2891-3080
Fax : +49(0)89/289 1-3473
Dr. Patrik Miiller
Basell Polyolefins
Usine de Lamotte BP1
F-60350 Trosly-BreuiWrance
Tel: +33344/853-853
Fax: +33344/853-801
E-mail: patrik.mueller@basell.com
Dr. Vince Murphy
Symyx Technologies
3 100 Central Expressway
Santa Clara, CA 9505 1/USA
Tel: +1/408 746 2000
Dr. Guido Naberfeld
Bayer AG
Abt. PU-R-PP
D-4 1538 Dormagen/Gemany
Tel: +49(0)2133/5 1-3718
Fax: +49(0)2133/5 1-3244
E-mail: guido.naberfeld.gn@bayer-ag.de
Dr. Gerald P. Niccolai
Laboratoire COMS
CPE - LYON
43, Boulevard du 11 Novembre 1918
F-69616 Villeurbanne Cedexprance
Tel: +33/7243-1798
Fax: +33/7243-1795
XL Contributors

Dr. Frank G. M. Niele Dr. Peter Panster

Shell Research and Technology Centre Degussa AG
Amsterdam Rodenbacher Chaussee 4
Postbus 38000 D-63457 HanadGermany
NL-1030 BN A m s t e r d a d h e Netherlands Tel: +49(0)618 1/59-3763
Tel: +3 1/20-6302667 Fax: +49(0)618 1/59-3834
Fax: +31/20-6304035 E-mail: peter.panster@degussa.com

Prof. Dr. A. F. Noels Dr. Stephan Pitter

CERM - Institut de Chimie B6 Institut fur Technische Chemie
UniversitC de Likge Forschungszentrum Karlsruhe GmbH
B-4000 Sart Tilmaaelgium Hermann-von-Helmholtz-Platz1
Tel: +324/3663-463 D-76344 Eggenstein-Leopoldshafen/Germany
Fax: +324/3663-497 Tel: +49(0)7247/82-2308
E-mail: AENoels @ulg.ac.be Fax: +49(0)7247/82-2244
E-mail: stephan.pitter@itc-cpv.fzk.de
Prof. Dr. Bruce M. Novak
Department of Polymer Science and Dr. Benoit Pugin
Engineering Solvias AG
University of Massachusetts PO Box
P. 0. Box 34530 CH-4002 BaseVSwitzerland
Amherst, MA 01003-4530RJSA Tel : +4 161/686-6335
Tel: +1/4 13-545-2160 Fax: +416 1/686-6311
Fax: + 1/413-545-0764
Dr. Luigi Resconi
Prof. Dr. Ryoji Noyori Basell Polyolefins
Department of Chemistry P.le P.to Donegani, 12
Graduate School of Science 1-44110 Ferrardtaly
Nagoya University Tel: +39(0)532/468-368
Chikusa, Nagoya 464-8602/Japan Fax: +39(0)532/467-780
Tel: +81/52-789-2956 E-mail: 1uigi.resconi@basell.com
Fax: +81/52-783-4177
E-mail: noyori@chem3.chem.nagoya-u.ac.jp Dr. Freimund Rohrscheid
Amselweg 24
Prof. Dr. Gunther Oehme D-65779 KelkheindGermany
Institut fur Organische Katalyseforschung Tel: +49(0)6195/63260
Universitat Rostock
BuchbinderstraBe 5-6 Dr. Lucien Saussine
D- 18055 RostocWGermany Institut Francais du PCtrole
Tel: +49(0)38 1/466-9330 1 et 4, Avenue de Bois PrCau
Fax: +49(0)38 1/466-9324 F-92852 Rueil-Malmaison CedexErance
E-mail: guenther.oehme@ifok.uni-rostock.de Tel: +331/4752-6596
Fax: +331/4752-6055
Dr. HClkne Olivier-Bourbigou E-mail : luciensaussine @ ifp.fr
Institut Francais du PCtrole
1 et 4 Avenue de Bois PrCau
F-92852 Rueil-Malmaison Cedex/France
Tel: +331/4752-6779
Fax: +331/4752-6055
E-mail : helene.olivier-bourbigou @ ifp. fr
 Contributors XLI

Dr. David A. Schiraldi Dr. Philippe Serp

Hoechst Celanese Corporation
P. 0. Box 32414
Charlotte, NC 28232-6085mSA
Tel: +11704-554-3348
Fax: +1/704-554-3293
E-mail: dschiral@earthlink.net
Prof. Dr. Gunter Schmid
Institut fur Anorganische Chemie
Universitat-GH Essen
UniversitatsstraBe 5-7
D-45 141 Essen/Germany
Tel: +49(0)201/183-2401
Fax: +49(0)201/183-2402
Dr. Rochus Schmid
Anorganisch-chemisches Institut
der Technischen Universitat Munchen
LichtenbergstraBe 4
D-85747 Garching/Germany
Tel: +49(0)89/2891-3174
Fax: +49(0)89/289 1-3473
E-mail : rochus. schmid @ ch.tum.de
Dr. Horst Schneider
Borealis GmbH
DanubiastraRe 21-25
A-2320 SchwechatJAustria
Tel: +43 1/70111-4591
Fax: +431/70111-4141
E-mail: horst.schneider@borealisgroup.com
Dr. Carsten Schultz
Bioorganic Chemistry of Signalling
Molecules
EMBL
MeyerhofstraBe 1
D-69 117 Heidelberg/Germany
Tel : +49(0)622 1/387-210
Fax: +49(0)6221/387-206
E-mail: carsten.schultz @embl-heidelberg.de
Prof. Dr. Ayusman Sen
Department of Chemistry
The Pennsylvania State University
152 Davey Laboratory
University Park, PA 16802-630011JSA
Tel: +1/814-863-2460
Fax: +1/814-863-8403
E-mail: asen@chem.psu.edu
Laboratoire de Catalyse
Chimie Fine et Polymkres
Ecole Nationale Suptrieure
des Ingtnieurs en Arts
Chimiques et Technologiques
118, route de Narbonne
F-31077 Toulouse Cedex 4France
Tel: +335/6288-5681
Fax: +335/6288-5600
E-mail: pserp@ensiacet.fr
Prof. Dr. K. Barry Sharpless
Department of Chemistry
The Scripps Research Institute
10666 North Torrey Pines Road
La Jolla, CA 92037KJSA
Tel: +1/6 19-554-7005
Fax: + 1/619-554-6406
Prof. Dr. Roger A. Sheldon
Laboratory for Organic Chemistry
and Catalysis
Delft University of Technology
Julianalaan 136
NL-2628 BL Delft/The Netherlands
Tel: +31/15-782675
Fax : +3 1/15-781415
E-mail: Secretariat-OCK@tnw.TUDe1ft.d
Dr. Christian Six
Bayer AG
Abt. PU-P-TDI-DOR-TDD
D-4 1538 DormagedGermany
Tel: +49(0)2 133/51-8607
Fax: +49(0)2133/5 1-4912
E-mail: christian.six.cs@bayer-ag.de
Dr. Felix Spindler
Solvias AG
Postfach
CH-4002 BaseVSwitzerland
Tel : +4 161/686-6308
Fax : +4161/686-6311
XLII Contributors
Dr. Marco Stoeckl
Anorganisch-chemisches Institut
der Technischen Universitat Miinchen
LichtenbergstraDe 4
D-85747 Garching/Germany
Tel: +49(0)89/741-60966
Dr. Thomas Strassner
Anorganisch-chemisches Institut
der Technischen Universitat Miinchen
Lichtenbergstral3e 4
D-85747 Garching/Germany
Tel: +49(0)89/289-13 174
Fax: +49(0)89/289-13473
E-mail : thomas. strassner (3ch.tum.de
Dr. Gerd Sylvester
An der Steinriitsch 5A
D-5 1375 Leverkusen/Germany
Tel : +49(0)214/54419
Dr. Rudolf Taube
Fuchsienweg 17
D-06118 Halle/Saale/Germany
Tel + Fax: +49(0)345/523-0858
Dr. Paul1 Torrence
Celanese Ltd.
PO Box 9077
Corpus Christi, TX 78469-9077LJSA
Tel: +1/3612424000
Fax: +1/3612424161
E-mail: gptonence @ celanese.com
Dr. Howard W. Turner
Symyx Technologies
3 100 Central Expressway
Santa Clara, CA 95051RJSA
Tel: +1/408 746 2000
Dr. Michael N. Vargaftik
N. S. Kurnakov Institute of General
and Inorganic Chemistry
Russian Academy of Sciences
Leninski Prospect 3 1
117907 Moscow GSP-1Russia
Tel: 095/952-1203
Fax: 095/954-1279
Prof. Dr. LBszlo Vigh
Institute of Biochemistry
Biological Research Centre
Hungarian Academy of Sciences
P. 0. Box 521
H-6701 Szeged, Temesvhri krt.62/Hungary
Tel: +36/62-432-232
Fax: +36/62-433-506
E-mail:
VIGH @ nuc1eus.SZBK.U-SZEGED.hu
Francesco Vizza
Istituto per lo Studio della
Stereochimica ed Energia dei
Composti di Coordinazione - CNR
Via J. Nardi, 39
1-50132 Firenze/Italy
Tel: +3905/524-5990
Fax: +3905/524-78366
E-mail: vizza@fi.cnr.it
Prof. Dr. Fritz Vogtle
Institut fur Organische Chemie
und Biochemie der Universitat Bonn
Gerhard-Domagk-StraBe 1
D-53 121 BondGermany
Tel: +49(0)228/733495/6
Fax: +49(0)228/735662
E-mail: voegtle@uni-bomde
Prof. Dr. Dieter Vogt
Schuit Institute of Catalysis
Eindhoven University of Technology
PO Box 513
NL-5600 MB Eindhovemhe Netherlands
Tel: +3 1(0)40/247-2483
Fax: +3 1(0)40/245-5054
E-mail: d.vogt@tue.nl
Prof. Dr. Herbert Waldmann
Max-Planck-Institut
fur Molekulare Physiologie
Abt. Chemische Biologie
Otto-Hahn-Stral3e 11
D-44227 Dortmund/Germany
Tel: +49(0)231/133-2401
Fax: +49(0)231/133-2499
E-mail:
herbert.waldmann @ mpi-dortmund .mpg.de

Dr. T. Weskamp
Thiirmchenswall 35
D-50668 Koln/Germany
Tel : +49(0)22 1/122-261
E-mail : tweskamp @ yahoo.de
Dr. Stefan Wieland
Degussa AG
Postfach 13 45
D-6340 3 HanadGermany
Tel: +49(0)6181/59-4154
Fax: +49(0)618 1/59-4691
Prof. Dr. Giinther Wilke
Max-Planck-Institut fur Kohlenforschung
Postfach 10 13 53
D-45466 Miilheim an der RuhdGermany
Tel : +49(0)208/3061
Dr. Tom Yamano
Takeda Chemical Industries
Pharmaceutical Research Division
2- 17-85, Jusohonmachi, Yodogawa-ku
Osaka 532-8686/Japan
Tel: +81(06)6300-6719
Fax: +81(06)6300-6206
E-mail: Yamano-Tooru@takeda.co.jp
Contributors XLIII
Dr. Noriaki Yoshimura
Chemical Research Laboratory
Kuraray Co., Ltd.
2045-1 Sakazu, Kurashiki
710 OkayamdJapan
Tel: +81/86-423-2271
Fax: +81/86-422-4851
Dr. Thomas Zevaco
Institut fur Technische Chemie
Forschungszentrum Karlsruhe GmbH
Hermann-von-Helmholtz-Platz1
D-76344 Eggenstein-Leopoldshafen/Germany
Tel: +49(0)7247/82-4126
Fax: +49(0)7247/82-2244
E-mail: thomas.zevaco@itc-cpv.fzk.de
Dr. Jochen P. Zoller
Vitacert GmbH
WestendstraBe 199
D-80686 MiinchenlGermany
Tel: +49(0)89/579 1-1909
Fax: +49(0)89/5791-19 15
E-mail: jochen.zoller@vitacert.de
 Applied Homogeneous Catalysis with Organometallic
Edited by Boy Cornils & Wolfgang A. Herrmann
© Wiley-VCH Verlag GmbH, 2002

1
Introduction
 Applied Homogeneous Catalysis with Organometallic
Edited by Boy Cornils & Wolfgang A. Herrmann
© Wiley-VCH Verlag GmbH, 2002

Introduction
Boy Cornils, WolfgangA. Herrmann

“Le nombre des corps capables de produire des catalyses est

trbs grand, et ne cesse de s’augmenter par suite de progrits de
la chimie.”* [4d]
Paul Sabatier (Toulouse, 1913)

Before 1938, when the landmark ‘‘0x0 synthesis” was discovered by Otto Roelen
(“hydroformylation”, “Roelen reaction”), homogeneous catalysis had received
only occasional mention [l-31. Sabatier and Mittasch [4a, 51 also made only
passing reference to homogeneous catalysis. It was probably Sabatier (the discov-
erer of nickel-catalyzed hydrogenation) who gave a first rough classification of
catalytic reactions: homogeneous systems, where all the compounds present, or at
least one of them, are miscible with the catalysts (e. g., ferments, Friedel-Crafts
catalysts); and heterogeneous systems, that are based upon a solid catalyst
which is “in contact with a reactive liquid or gaseous phase. The effect takes
place either on the surface of the catalyst if it is compact . . . or in its entire
mass if it is porous . . .” [4c]. Mittasch in his notable Kurze Geschichte der
Katalyse in Praxis und Theorie (Short History of Catalysis in Practice and
Theory) mentioned homogeneous catalysis only incidentally [5a]. At that time,
the term catalysis in its general usage was inseparably linked to large-volume
industrial chemical syntheses (ammonia synthesis, coal hydrogenation, fat harden-
ing, Fischer-Tropsch synthesis, mineral oil processing). Catalysis was thus synon-
ymous with heterogeneously catalyzed reactions. Except for “exotic” applications
(Grignard reagents, the Mond process, Frankland organozinc reactions) organo-
metallic compounds were not accorded any technical or commercial importance.
Figure 1 demonstrates this clearly: after an initial period of synthetic organo-
metallic chemistry the discoveries of Roelen, Reppe, Ziegler, and others sparked
off a second, industrially oriented period of organometallic chemistry. Only since
the 1950s has homogeneous catalysis been an established field of organometallic
chemistry and it has now become a central feature within the chemical sciences
scenario.
It is hence not surprising that Otto Roelen’s initial investigations into homoge-
neous coordination catalysts in 0x0 synthesis proved a source of much frustration
(reviewed in [3]). It was only the work of Adkins and Krsek [6], Storch et al. [7],
Berty and Mark6 [8] and Natta 191 that confirmed 0x0 catalysts to be homoge-
neous in nature. The intense activity associated with hydroformylation and 0x0

* “The number of bodies that effect catalytic interactions is very large, and is still increasing
incessantly with the progressive development of chemistry” [4b,d].
4 I Introduction

ORGANOMETALLIC CHEMISTRY ORGANOMETALLIC CATALYSIS

R. Noyori (1994): supercritical fluid (COP)in
homogeneous catalysis
W. A. Herrmann (1994): N-heterocyclic
carbenes as ligands in catalysis
J.-M. Basset (>1991): surface organometallic
chemistry
W. KaminskylH. H. Brintzinger (1985):
ansa metallocenes for isotactic
C3H,-polymerization
R. Hoffmann (> 1973): theory, isolobal analogy
E. 0 . Fischer (1973): metal-carbyne complexes
R. F. Heck, T. Mizoroki (1971172): c---)
Pd-catal. "Heck coupling"
G. Wilkinson (1965): Rh-phosphine
complexes as catalysts
E. 0. Fischer (1964): metal-carbene complexes
F. A. Cotton (1962): metal-metal multiple bonds
T. H. Cofield (1957): alkyi migration M + CO
P. L. Pauson I S. A. Miller (1951):
Fe(C5H5)2,first recognition of %-complexes
W. Hieber (1931138): HCo(C0)4, H2Fe(C0)4
hydrido metalcarbonyls
Commissioning of first plants with metallo-
cenes as catalysts for PP production (1995)
BP(1992): introduction of indium in
acetic acid
Nitto (1985): first enzymatic manufacture
of acrylamide
from C2H41C0
TENNESSEE EASTMAN (1983):
Coal + acetic anhydride
Enantioselective catalysis (> 1980,
e.g., H. Nozaki, R. Noyori, B. Sharpless)
E. G. Kuntz, 8. Cornils (1980): two-phase
catalysis (hydroformylation), RUHRCHEMIE
(1968): carbonylation of CH30H
c-)
T. Alderson I DuPONT (1961): RhCI3-
catalyzed butadienelethylene coupling
G. Wilke (1959): Ni-catalyzed trimerization
of butadiene
J. Smidt, W. Hafner, R. Jira I WACKER
(1 958): Pd-catalyzed ethylene oxidation
STANDARD OIL OF INDIANA (1957):
olefin metathesis
G. Natta (1955): isotactic polymerization of
propene
K. Ziegler (1953): catalytic low-pressure
c-) polymerization of ethylene

industrial antiknocking agent

P. Barbier, V. Grignard (1899): RMgX
L. Mond (1890): Ni(CO)4,
-
T. Midgeley, T. A. Boyd (1922): Pb(C2H5)4, *-*

*:
:
0. Roelen I RUHRCHEMIE (1938):
hydroformylation

first binary metal carbonyl

-
E. Frankland (1849): Z ~ I ( C H ~ ) ~ ,
first metal alkyl
W. C. Zeise (1827): K[(C2H4)PtC13], -,*
first metal olefin complex
Cadet de Gassicourt (1760): "liqueur fu-
mante de I'arsenique", first organometallic c-)
compound (without recognition of structure)

Figure 1. Synoptic presentation of the development of organometallic chemistry and

homogeneous catalysis.
 I Introduction 5

catalysts, with carbonylations as described by Reppe [ 101, and with Ziegler’s

“borderline case,” the low-pressure polyethylene synthesis, highlighted the recog-
nition of this new special type of catalysis (more historical information is given in
[ 11-1 31 and in the historical glossary).
Table 1, showing the strengths and weaknesses of both methods, makes it easy
to differentiate homogeneous from the older, successful, heterogeneous catalysis
[ 14-1 61.

Table 1. Homogeneous versus heterogeneous catalysis.

Homogeneous catalysis Heterogeneous catalysis
Activity (relative to metal content) High Variable
Selectivity High Variable
Reaction conditions Mild Harsh
Service life of catalysts Variable Long
Sensitivity toward catalyst poisons Low High
Diffusion problems None May be important
Catalyst recycling Expensive Not necessary
Variability of steric and electronic Possible Not possible
properties of catalysts
Mechanistic understanding Plausible under More or less
random conditions impossible

The information given in Table 1 is discussed in numerous publications: a few

typical ones are recommended for further details [17-231. Despite the fact that
heterogeneous catalysis has advantages in application (not without good reason
do the most important mineral oil processing methods involve heterogeneous
catalysis), the great challenge presented by homogeneous catalysis is the far better
mechanistic understanding of its micro “processes” (catalytic cycles), with the
possibility of influencing steric and electronic properties of these molecularly
defined catalysts. It is thus possible to tailor optimized homogeneous catalysts
to the particular problem involved, by adapting their chemical and structural
basis: this is doubtless a clear advantage over heterogeneous catalysis, which is
said to be an alchemist’s “black art” [24] even though this statement is vehemently
disputed [25].
The two “philosophies” are typically exemplified by hydrofonnylation (eq. (1))
[26] on the one hand and the Fischer-Tropsch reaction (eq. (2)) [7] on the other.
They both represent catalytic carbon monoxide chemistry: in the first case the
molecular structure of the homogeneous catalyst (Structures 1 and 2) is precisely
known to be trigonal-bipyramidal, ds-Rh’.
6 I Introduction

1 2

By way of contrast, Fischer-Tropsch chemistry requires heterogeneous cata-

lysts of structures close to 3 and 4, of which the surface structures are not precisely
known, and for which therefore there is no clear molecular mechanism known
[27]:

3 4

“Organometallic surface science” [28] seems to promise a bridge function

between the classical “antipodes”: by using well-defined molecular starting
compounds such as metal alkyls, and making them react in a defined way with
surface species (e. g., = SiOH groups), molecularly dispersed but immobile
catalyst species in a more or less well-defined chemical environment can be
produced (cf. Section 3.1. I .4). The alkylzirconium(1V) surface species 5 (which
efficiently hydrogenates olefins) is an example (eq. (3)) [28b], and the molecular

5
 I Introduction 7

model (Structure 6) derived from a so-called silsesquioxane (R = cyclopentyV

-hexyl) is related to it [28c,d].
Bearing these facts in mind it is not surprising that a compromise between het-
erogeneous and homogeneous catalysts, made by combining the advantages of the
catalytic methods, has so far been attempted only from the homogeneous catalysis
side, i. e., by heterogenizing homogeneous catalysts and not vice versa (see the
discussion of biphasic processes, Section 3.1.1.1). Most experiments with sup-
ported and therefore heterogeneous catalysts (anchored catalysts; Section
3.1.1.3) failed. In this respect Heinemann’s question, “Homogeneous and hetero-
geneous catalysis - common frontier or common territory?” remains unanswered
[29]. Taking all methods of mineral oil processing into account, the relative share
of heterogeneous to homogeneous catalysis is approx. 85: 15 [30].
Table 2 shows to what extent homogeneous catalysts are tailor-made and how
variable and adaptable they are to the problem concerned by suitable reaction and
unit processes, taking as examples the modern hydroformylation processes and
catalysts. It clearly illustrates that a variety of different solutions in terms of re-
action conditions and product separation technologies are available to meet any

Table 2. Industrially important 0x0 processes 118, 31, 321.

Catalyst metal: Cobalt Rhodium
Variant: Unmodified Modified Unmodified Modified
Ligand: None Phosphines None Phosphines
Proces sa): 1 2 3 4 5
Active catalyst HCo(C0)4 HRh(CO)L3 HRh(CO)L3
species
Temperature (“C) 150-180 160-200 100- 140 60-120 110-130
Pressure (MPa) 20-30 5-15 20-30 1-5 4-6
Catalyst concn. 0.1-1 0.6 10-~-0.01 0.01-0.1 0.001-1
rel. to olefin (%)
LHSV“ 0.5-2 0.1-0.2 0.3-0.6 0.1-0.2 > 0.2
Products Aldehydes Alcohols Aldehydes Aldehydes Aldehydes
Amount of High High Low Low Low
byproducts
di ratio 80:2Ob) 88: 12 5o:so 92:8 > 95:< 5
Sensitivity to No No No Yes No
poisons
a) Key: 1 = (e. g.) BASF, Ruhrchemie; 2 = Shell; 3 = Ruhrchemie;
4 = Union Carbide (LPO); 5 = Ruhrchemie/RhGne-Poulenc.
b, 65:35 at an early stage of development.
LHSV = Liquid Hourly Space Velocity.
8 1 Introduction

list of requirements (specifications) of a modem 0x0 process. The technology and

the homogeneous catalyst may be adapted to a mutual target, whereas with hetero-
geneous catalysis the choice of the catalyst determines the reaction conditions to a
large extent (and usually the technical solution, too) (cf. [33-371).
An early example of the variability of highly sophisticated organometallic
homogeneous catalysis is the synthesis of vitamin A, developed by Pommer et
al. at BASF AG in the late 1950s [38a]; a plant producing 600 tons per year
has been operational since 1971 [38b]. While the key synthetic feature is a Wit-
tig-type coupling between vinyl-p-ionone (C and y-formylcrotyl acetate (C,),
there is also an earlier hydroformylation step in the synthesis of a precursor com-
pound: 1-vinylethylene diacetate is hydrofonnylated under high-pressure con-
ditions yielding the brunched aldehyde with regioselectivities up to 80 %. This
intermediate is then transferred into the a$-unsaturated derivative which cou-
ples with the C1,-ylide building block to form the CZo-vitaminA according to
Scheme 1 [39a-c]. An alternative Hoffmann-La Roche procedure also includes
a hydroformylation step [39d]. Both processes share most of the vitamin A world
capacity of approx. 3000 tons per year (cf. Section 2.1).
Another important and commercially essential example proving the variability
of homogeneous catalysis is the synthesis of acetic acid via carbonylation of
methanol. Here, too, a breakthrough was achieved by employing milder reaction

1-vinylethylene OAc
diacetate branched aldehyde
(600 atm, 80 "C)

---f---
CI5-building block
I - C5-building block

v
1 wittig coupling

%
vitamin-A acetate ( C ~ O )

Scheme 1. Vitamin A synthesis.

 I Introduction 9

conditions and by increasing yield and selectivity as a result of switching from

cobalt (in the old BASF process) to rhodium catalysts (Monsanto). This land-
marking change first introduced rhodium as a catalyst metal to the chemical in-
dustry. The effect of this change is seen impressively in Figure 2 by comparing
the required metal concentrations, pressures, and temperatures of the methanol
carbonylation on the one hand, and the selectivities obtained on the other, for
both catalyst metals.

Figure 2. Catalytic breakthrough of rhodium vs. cobalt in homogeneous catalysis:

the methanol carbonylation.

Parallel to this change of catalyst in methanol carbonylation, the feedstock for

the manufacture of acetic acid was also changed at many sites, where ethylene was
replaced by methanol (Scheme 2).
This development began to reduce steadily the capacities of acetaldehyde which
previously had been made by oxidation of ethylene (Wacker-Hoechst process;
cf. Section 2.4.1) and converted to acetic acid (cf. Section 2.4.4). Moreover, the
Monsanto process, the second-generation process for methanol carbonylation is
now being followed by the third generation of highly efficient carbonylation pro-
cesses, enabling acetic anhydride as well as acetic acid to be produced (cf. Scheme
2; Tennessee-Eastman [36] and BP [37] processes). The most advanced process
(Hoechst [40]) has so far not been implemented industrially because of neglects
10 I Introduction

Scheme 2. Alternative routes to acetic acid.

of an incompetent management. It should be mentioned in passing that the

Tennessee-Eastman technology is geared (although not necessarily) to coal as
a raw material and to the synthesis gas made from it by coal gasification
[12, 411, and consequently a reference to the role of homogeneous catalysis in
coal processing is made (cf. Scheme 2).
The principle of “the better to be the enemy of the good” thus applies in special
measure to the various stages of development of homogeneous catalysis as well as
to the competition between homogeneous and heterogeneous catalysis. The syn-
thesis of acrylic acid will be taken as an example of the ongoing comparison of
the most efficient homogeneous and heterogeneous processes. Acrylic acid,
which was formerly accessible, e.g., by addition of HCN to ethylene oxide on
heterogeneous catalysts, then almost solely by homogeneously catalyzed carbonyl-
ation of acetylene, is now produced, equally well, mainly by heterogeneously
catalyzed oxidation of propylene. Whether homogeneous catalysis will experience
a renaissance in the sense of alternating life cycles (see Figure 3) will be shown by
the future of the so-called “Union Oil process” (oxycarbonylation of ethylene with
PdCu catalyst systems [42]).
The history of homogeneous catalysis is evidently a success story of the
developments in process technology accompanying it (see Section 3.1.4). This
becomes particularly clear in the tremendous advances of homogeneous catalysis
in terms of catalyst separation and recycling. Table 1 shows that catalyst recycling
is free from problems in the case of heterogeneous processes but it is usually
expensive with homogeneous processes. In other words, the catalyst metal in het-
erogeneous catalyses after reaction either remains in the solid bed of the reactor or
can be recovered readily from a catalyst suspension by filtration or centrifugation
with subsequent recycling.
In the case of homogeneous catalysis it was not until strategies and techniques
for product separation from the catalyst were successfully developed that cataly-
sis with organometallic complexes “took off ’. Metal coordination catalysts predo-
 I Introduction 11

t
x
.-
c

s
Q

c
0
3
D
2
Q
Heterogeneous catalysis HC-CH + CO + H20
CH?=CHz + CO + ’I202

HCN + -
older process, e.g., UCC
7+ ACOOH

-
I

1960 1970 1980 1990 2000

year

Figure 3. Catalytic life cycles: homogeneous versus heterogeneous catalysis, taking the bulk
chemical acrylic acid as an example.

minantly comprise transition metals, particularly precious metals, whose high and
often speculatively influenced price (see Table 3) makes separation and re-use an
urgent necessity.
It is therefore not surprising that it was only when suitable methods for catalyst
separation from the substrates and reaction products of homogeneous catalysis
were developed that the importance of this type of process grew. The successful
developments (thermal separation or chemical reaction (e. g., [26]), immobi-
lization by means of supports and thus heterogenization (e.g., [44]), phase
transfer catalysis [45], biphasic processes (e. g., [46, 471) or separation with
membrane modules [48, 491) are described in the relevant sections of this book
(cf. [50]).
Besides the central atoms of the molecular organometallic complexes and the
variation of the application phase (heterogenization, two-phase catalysis; see
below), the importance of the ligands surrounding transition metal centers should
be mentioned [5 1-53]. The unexpectedly rapid advances in homogeneous cataly-
sis were only possible by virtue of ligand modification of the “naked” transition
metal complexes. This is typically demonstrated by the development of hydro-
formylation: the first processes employing HCO(CO)~catalysts (Roelen) were
followed by ligand-modified cobalt carbonyls (Shell process with alkyl phos-
12 I Introduction

Table 3. Prices of the transition metals in US dollars per gram atom (mol) in 1991 [43].
Ti v Cr Mn Fe co Ni cu
0.13 0.82 0.26 0.04 0.13 0.90 0.29 0.10
Zr Nb MO Tc”’ Ru Rh” Pd Ag
0.64 3.30 1.70 (6000) 210 4200 480 27
Hf Ta w Re 0s Ir Pt AU
28 32 7.10 160 4300 2300 3600 2900
a) p-Emitter. b, cf. Section 2.1.1, Fig. 8.

phines) from 1966 onwards; the latter were succeeded by Union Carbide’s LPO
process with the combination RNtriphenylphosphine (by the way, the term
“LPO” (low-pressure 0x0) was coined by BP [54]). The RuhrchemieRhBne-Pou-
lenc 0x0 process using Rh catalysts and water-soluble phosphines ([26, 47, %a];
cf. Sections 2.1.1 and 3.1.1.1) landmarked yet another improvement. All process
variants have been linked with improvements, in some cases major, in selectivity
and yield (LPO versus the “classic” processes), more specific product distribution
(Shell process), milder reaction conditions, easier separation of catalyst and prod-
uct, and simplified process technology (new RuhrchemieRh6ne-Poulenc pro-
cess). The importance of ligand modification of organomentallic complexes
[55b] will increase with the growing importance of homogeneous catalysis for
the stereoselective formation of fine chemicals (see, e. g., Sections 2.2, 2.9,
3.2.1, and 3.3.1). The use of CAMD (Computer-Assisted Molecular Design), a
promising “desk technology” which is highly fruitful for ligand development in
homogeneous catalysis, is dealt with in Section 3.1.2. This is particularly relevant
for homogeneous catalysts since they are normally molecularly defined, with their
exact geometries depending on the specific bonding situations and intramolecular
ligand-ligand interactions. Quantum chemical methods are underway in catalysis
research, too. Most notably, density-functionality calculations taking care of
relativistic effects so typical for heavy metal atoms are becoming useful in the
catalysis scene.
Finally, mention should be made of the great strength of homogeneous cataly-
sis, namely the possibility of manufacturing the target products of coal chemistry
and petrochemistry by varying and adapting process stages and catalysts. This
applies firstly to the “primary educt” of homogeneous catalysis, the intermediate
and starting material synthesis gas (syngas), which permits a rapid switch from
petrochemical to coal-based production because it can be obtained chemically
identical from coal as well as from petrochemical starting compounds (and
even from the unwanted waste products of biodegradation processes, e. g., clari-
fication sludges) [56]. Syngas as a readily purified intermediate is therefore the
most convenient link with homogeneous catalysis.
Secondly, the development of the highly sophisticated 0x0 processes outlined
above arose not only from the desire for ever-increasing selectivity and yield
(i. e., better utilization of the raw materials) and moderation of the initially
 I Introduction 13

severe reaction conditions (initially 150 “C/30 MPa, now 120 “C/3 MPa) but also
from the market demand for an increasingly high proportion of straight-chain
products and thus for a shift in the product pattern. To give an example, the pro-
portion of the desired n-butanal compared with its isomer from propylene hydro-
formylation increased when the processes were optimized from an “n/i ratio” (the
ratio between normal [linear] and branched aldehydes) of 65:35 to as much as
97:3, and the total yield of straight-chain products from about 70 % in “classical”
Co processes to >94 % in the latest Rh processes. These requirements for the
regioselectivity can, incidentally, also be reversed, at least partially: with further
increasing demand for the derivatives of isobutanal (such as neopentyl glycol,
isobutyric acid, methacrylic acid and its methyl ester, or other compounds with
an isobutyl structure), modern 0x0 processes with a specific high content of
isobutanal could become of interest. There is no doubt that homogeneous catalysis
could make available such processes with a high total yield and the desired regio-
selective product distribution. In the context of the example chosen, the iso-prod-
ucts will gain importance when chiral catalysts - still to be developed - permit
stereoselective product formation [57].
Similarly, market requirements can be met with homogeneous catalysis pro-
cesses for new alternative process routes (e. g., to sarcosines via amidocarbonyla-
tion, aromatic isocyanates by reductive carbonylation, C-H activation of saturated
hydrocarbons as an alternative and less expensive raw material source, or by using
C 0 2 as a C,-feedstock), for new polymers (copolymerization of CO with olefins
and with new types of matallocenes, and direct polymer syntheses such as ROMP;
cf. Sections 2.3.1, 2.3.3, 2.3.4, and 3.3.10. l), for environment-friendlier products
(replacement of CFC by HFC; cf. Section 2.8.2), for stereoselective syntheses
(profenes and other active ingredients in the pharmaceutical, agricultural, or per-
fume sectors; cf. Sections 2.9 and 3.3. l), or for biocatalytic and enzyme-type pro-
cesses (cf. Sections 3.2.1 and 3.2.3). Products made by homogeneous catalysis,
with their adjustable regio- and stereoselectivity, add to the stock of chemically
accessible processes and thus affect such different requirements as more economic
starting products, environmentally benign auxiliaries, active ingredients with
reduced application rates, or polymers with new properties.
The many attempts to create a symbiosis between heterogeneous and homo-
geneous catalysis, apart from the two-phase processes (see Section 3.1.1. l), are
dealt with in detail by a comprehensive monograph [44a] and research reports
[44b,c]. In Section 3.1.1.3 routes for the heterogenization of homogeneous
catalysts (“supported liquid-phase catalysts” (SLPC) or “supported aqueous-
phase catalysts” (SAPC)) are given. It is still questionable whether, apart from
bio-(enzyme) catalysts, this trend of development offers prospects for supported
polymerization catalysts or some special applications. Doubts exist especially
when the bonds between catalyst and educts or products are subject to severe
stresses and modifications of the geometric configuration during a catalyst
cycle (e. g., in the change between trigonal-bipyramidal and planar core geo-
metries). By way of contrast, the fact that, following Manassen’s presentation
of his principle for catalysis in 1972 [46, 58-60], a bright future is predicted
for the two-phase catalytic processes (which to some extent also represent an
14 1 Introduction

“immobilization” or “heterogenization” of the homogeneous catalyst system on a

“mobile support”) gives further impetus to efforts to synthesize homogeneous and
heterogeneous process components. It would seem to be no accident that an indus-
trial breakthrough has been made with this type of homogeneous catalysis, with
the Shell process for higher olefins [ 161, the RuhrchemieRhBne-Poulenc process
for 12-butanal and 2-ethylhexanol [ 14, 47, 55a], Monsanto’s L-DOPA process [61]
and various small-scale processes by RhGne-Poulenc [62], Montedison [63], and
Kuraray [64].
These more sophisticated processes, such as RhBne-Poulenc’s vitamin E syn-
thesis, provide a bridge to asymmetric syntheses as one of the future guidelines
which will determine the progress of homogeneous catalysis. Based on early
work on chiral phosphines by L. Homer, W. S. Knowles of Monsanto devel-
oped a first industrial enantioselective synthesis for the Antiparkinson drug
L-DOPA [61], commercialized in 1971 (later also by Isis-Chemie in East
Germany [65]) and using inter alia the configurationally stable diphosphines
Ph-p-Glup (a phosphorylated sugar derivative) and DIPAMP (Structures 7 and 8;
cf. Sections 2.9 and 3.3.1).

CH30
/to
C6H

OP(C6H5)Z 0P(C6H5)2 d& /

DiPAMP
\

A further highlight was introduced by R. Noyori in the 1980s when an efficient

stereoselective hydrogen migration (allylamine + enamine) was found to occur
with Rh’ catalysts containing the BINAP diphosphine ligand of axial chirality
(see Scheme 3 and Section 2.9). An L-menthol synthesis with an annual produc-
tion of 2000 tons was the first commercial result of this development at Takasago
Perfumery Co. Ltd. in Japan [66].
The present book mostly deals with organic reactions rather than with iso-
merizing conversions, since the reactions synthesize new structures and normally
require mild conditions (4 200 “C) to avoid side reactions. If a subdiscipline as
classical as organic synthesis now asks itself “Quo vadis?” [67], then the obvious
answer is “Towards organometallic catalysis”. Any progress in this very special
domain of chemistry is man-made: by the pioneers of organometallic chemistry
and of homogeneous catalysis - truly “a Gentle Art” [68].
 1 Introduction 15

myrcene ...-allylamine enamine

(R) / (+)-citronella1 isopulegol L-menthol

> 94 % ee

Scheme 3. The L-menthol synthesis of Takasago Perfumery, exploiting an axially

chiral ligand to generate the first chiral environment
(cat. = [Rh'{ (-)-BINAP]COD]+).

The Historical Glossary on the following pages refers to Refs. [l-3, 9, 10, 12,
73-83]. No comprehensive description of the history of organometallic chemistry
is available as yet. A first review article was published in 1975 by Thayer [69].
16

Historical Glossary

William Christopher Zeise (1789-1847)

was a Danish apothecary and professor in Co-
pcnhagcn, Dcnmark. He synthesizcd the first
metal-olefin complex by serendipity (this term
is explained in Chapter 4), when he treated
platinum(1V) chloride with ethanol and potas-
sium chloride: K[PtCI3(q2-C2H4)], “sal kalico-
platinicus inflammabilis”, cf. [73].
n-Complexation of olefins at transition metals
nowadays comprises a key feature of homoge-
neous catalysis in terms of olefin activation,
with the Wacker-Hoechst process being a pro-
minent example (cf. Section 2.4.1).

Edward Frankland (1 825-1 899)

discovered the first transition metal alkyl com-
plexes - diethylzinc (“mobile fluid”) and ethyl-
zinc iodide (“white mass ofcrystals”) - while he
worked in Robert Bunsen’s Marburg laboratory
(1 849). Frankland was later a professor of chem-
istry in London. Alkyl-metal bonding occurs
in practically all catalytic processes involving
hydrocarbons, e. g., hydroformylation (Section
2.1. I), hydrogenation of olefins (Section 2.2),
“hydrocarbon activation” (Section 3.3.6), and
C-H-activation (Chapter 4).
 17

Ludwig Mond ( 1 839-1909)

a German chemist who had emigrated from
Kassel, discovered the first binary metal carbo-
nyl, the volatile, colorless liquid Ni(C0)4, in
his soda factory at Widnes, UK 17.51. This dis-
covery not only initiated systematic research in
this particular area but also hadgreat relevance
to the activation of carbon monoxide by transi-
tion metals. Mond’s discovery initiated Paul
Sabatier’s study of the nickel chemistry of
ethylene, in which context he found the catalytic
hydrogenation of C-C double bonds.

Victor A . F: Grignard (1871-1935)

a student of P. Barbier, discovered in 1899
the “Grignard” reagents, normally written as
RMgX [74]. This class of compounds developed
a broad chemistry as nucleophilic organyl-trans-
fer reagents (“Grignard reaction”). Grignard was
a professor of chemistry in Nancy and Lyon.
He received the Nobel prize (together with
Paul Sabatier) in 1912.
18

Walter Reppe (1 892-1 969)

was the research director of Badische Anilin- &
Sodafabrik (BASF) at Ludwigshafen, Germany.
His research included metal-catalyzed reactions
of acetylene (1938) and of carbon monoxide
(1939) (Section 2.1.2.2). High-pressure catalytic
acetylene chemistry is nowadays named after
him. He also discovered the metal carbonyl-
catalyzed cyclooligomerization of acetylene to
yield styrene, benzene, and cyclooctatetraene
(1948) [lo, 771.

Walter Hieber (1895-1 976)

was a student of Rudolf Weinland, who per-
formed early experimental work on Alfred
Werner’s theory of coordination compounds
(Hauptvalenzen, Nebenvalenzen). Hieber re-
ceived his Ph. D. in 1919 from Tubingen Uni-
versity on a topic concerning ferric complexes
of hypophosphorous acid. He then developed
metal carbonyl chemistry, mainly at Technische
Hochschule Munchen (1935-1964); he is now
considered the pioneering researcher in this
area of study. His name is associated with com-
pounds like HCo(CO), and H,Fe(CO), that are
relevant to catalytic hydrogen-transfer reactions
(hydroformylation; Section 2.1.1). Nucleophilic
addition to metal carbonyls, e. g., Fe(CO), +
OH- + [(CO),FeC(=O)OH]-, is known as the
“Hieber base reaction” (cf. [76]).
 19

Otto Roelen (1897-1993)

was a chemist at Ruhrchemie AG in Oberhau-
sen, Germany. He had received his training in
(heterogeneous!) catalysis from Franz Fischer
and Hans Tropsch at the Kaiser-Wilhelm-Institut
M i i l h e i d u h r , Germany. Roelen discovered
in 1938 the cobalt-catalyzed hydroformylation
of olefins (“0x0 synthesis”, “Roelen reaction”)
[ 1-31, which today represents the largest-vol-
ume homogeneous catalysis process employing
organometallic catalysts (see Section 2 . I . 1).

Karl Ziegler (1898-1973)

headed the Max-Planck-Institut fur Kohlen-
forschung in M i i l h e i d u h r , succeeding Franz
Fischer (1877-1947) in this position. He was
an organic chemist by training but developed
the chemistry of lithium, potassium, and alumi-
num alkyls. His most revolutionary discovery
was the alkyltitanium-catalyzed low-pressure/
high-density polymerization of ethylene in fall
1953 [78]. The first polymerization plants for
HDPE went into operation in 1955, simulta-
neously at Hoechst AG in Frankfurt, Germany,
and at Ruhrchemie AG in Oberhausen, Germany
(for ultrahigh molecular weight polyethylene,
UHMW) [79]. He received the Nobel prize for
chemistry in 1963 together with G. Natta [go].
20

Giulio Nuttu (1903-1979)

one of the early supporters of the 0x0 reaction
[9, 811, discovered in 1956 the isotacticity and
syndiotacticity of olefin polymerization (e. g.,
propylene; Section 2.3.1.1) using Ziegler’s Me-
tallorganische Mischkatalysatoren (see above).
The industrial production of isotactic polypro-
pylene started at Montecatini in Italy in 1956.
Natta was a professor at the universities of
Turin and Milan. He received the Nobel prize
for chemistry together with Karl Ziegler in 1963.

Geoffrey Wilkinson (1921-1996)

is one of the pioneers of organometallic syn-
thesis and catalysis. One of his far-reaching dis-
coveries was the low-temperatureflow-pressure
hydrogenation of olefins by a then-new genera-
tion of (homogeneous) catalysts in 1965, such as
CIRh[P(C,H,),], (“Wilkinson catalyst” [82]).
This invention greatly spurred the industrial
use of rhodium-instead of cobalt-based homoge-
neous catalysts, for example in hydrogenation,
hydroformylation, and the Monsanto acetic
acid process (cf. Section 2. I .2.2). Wilkinson
was a professor (emeritus) at Imperial College
London. He received the Nobel prize for
chemistry jointly with E. 0. Fischer (Technische
Universitat Munchen) in 1973.
 21

Gunther Wilke (born 192.5)

developed the organonickel-catalyzed cyclo-
oligomerization of butadiene (1956), e. g.,
to 1,5,9-~yclododecatriene (“Wilke reaction”),
with the latter being industrially converted into
polyamide-12. Another landmarking discovery
relevant to homogeneous catalysis was nickel-
(bis-~3-allyl) (1 96 1). 1,5,Y-cyclododecatriene-
nickel became famous as a source of “naked
nickel”. Wilke headed the Max-Planck-Institut
fur Kohlenforschung at M i i l h e i m u h r , Ger-
many, from 1967 until 1992 [83].

Richard E Heck (born 1931)

was a student of Saul Winstein (UCLA) and
Vladimir Prelog (ETH Zurich). He started
mechanistic work on homogeneous catalysis in
1956 when he entered Hercules Inc. (Wilming-
ton, Del., USA) as a research chemist. He
pioneered the elucidation of reaction mechan-
isms of organometallic processes, e. g., hydro-
formylation and Ziegler-Natta polymerization,
and published a number of key papers about
the chemical and mechanistic backgrounds of
these reactions. He was a chemistry professor
at the University of Delaware from 1971 until
his retirement in 1989. For the “Heck reaction”
the reader is referred to Section 3.1.6.
22

Peter L. Pauson (born 1925)

is among the pioneers of modem organometallic
chemistry. In 195 1, he discovered ferrocene,
(C5H5)2Fe, thus initiating the renaissance of
inorganic chemistry. In 197 1, he discovered
the (cobalt-mediated) Pauson-Khand reaction,
a triple C-C coupling leading to cyclopent-2-
en-1-ones (see Section 3.3.7). Pauson was born
in Germany, emigrated in the Nazi era with his
parents to the United States, and started his
scientific career in Pittsburgh - as a post-doc
of R. B. Woodward - and in Harvard where he
met Wilkinson and Rosenblum. He is now pro-
fessor emeritus at the University of Strathclyde
in Glasgow, UK.

Ernst Otto Fischer (born 1918)

was a student of Walter Hieber at Technische
Hochschule Miinchen where he received his
Ph.D. degree in 1948. He elucidated the mole-
cular structure of ferrocene shortly after this
compound was discovered. Further highlights in
his life’s work were the synthesis of dibenzene-
chromium (C6H&Cr in 1955, the discoveries of
the first metal carbene (1967), and the first me-
tal-carbyne complex (1971). In 1964 he suc-
ceeded Walter Hieber to the chair of inorganic
chemistry at Technische Hochschule Munchen
from which he retired in 1985. He received the
Nobel prize for chemistry jointly with Geoffrey
Wilkinson (Imperial College London) in 1973.
 23

Ryoji Noyori (born 1938)

received his PhD at Kyoto University in 1967.
Since 1972 he is Professor of Chemistry at the
Nagoya University and since 2000 Director of
the Research Center for Material Science in
Nagoya, Japan. In 1980 Noyori and his co-
workers synthesized both enantiomers of the
diphosphine ligand BINAP, a ligand for chiral
catalytic reactions with rhodium complexes. In
order to synthesize more generally applicable
catalysts, Noyori replaced Rh(1) by Ru(I1). The
reactions catalyzed by ruthenium(I1) - BINAP
complexes gave high enantiomeric excess,
high yields, and can be scaled up for industrial
use (Section 2.9), e.g., as early as in 1980
with the catalytic synthesis of the chiral fine
chemical L-menthol. Noyori received the Nobel
prize for chemistry in 2001 together with
Knowles and Sharpless.

K . Burry Sharpless (born 1941)

received his PhD in 1968 at Stanford University.
Since 1990 he is W.M.Keck Professor of
Chemistry at the Scripps Research Institute in
La Jolla, USA. Among several other important
discoveries, Sharpless developed catalysts for
asymmetric oxidations. In 1980 he achieved
the catalytic asymmetirc oxidation of allylic
alcohols to chiral epoxides by utilizing titanium
complexes with chiral ligands (e. g. Section
3.3.2). One of the many applications of chiral
epoxides is the use of the epoxide (R)-glycidol
for pharmaceutical production of beta-blockers.
Sharpless received the Nobel prize for chemistry
in 2001 together with Knowles and Noyori.
24 1 Introduction

References
[ 1 1 Chemische Verwertungsgesellschaft mbH, Oberhausen ( 0 . Roelen), DE 849.548 ( I 9381
1952).
[2] 0. Roelen, ChED Chem. Exp. Didakt. 1977, 3, 119.
[3] B. Comils, W. A. Henmann, M. Rasch, Angew. Chem. 1994,106,2219; Angew. Chem.,
Int. Ed. Engl. 1994, 33, 2144.
[4] (a) P. Sabatier, Die Katalyse in der Organischen Chemie, Akademische Verlags-
gesellschaft, Leipzig, 1927; (b) P. Sabatier, ibid., p. 8; (c) P. Sabatier, ibid. p. 229C
(d) P. Sabatier, La Catalyse en Chimie Organique, Paris, Likge, 1913.
[S] (a) A. Mittasch, Kurze Geschichte der Katalyse in Praxis und Theorie, Springer,
Berlin, 1939; (b) A. Mittasch, Uber Katalyse und Katalysatoren, Springer, Berlin,
1936.
[6] H. Adkins, G. Krsek, J. Am. Chem. Soc. 1948, 70, 383.
[7] H. H. Storch, N. Golumbic, R. B. Anderson, The Fischer-Tropsch and Related
Syntheses, Wiley, Chapman and Hall, New York, London, 1951, p. 441.
[8] J. Berty, L. Markb, Acta Chim. Acad. Sci. Hung. 1953, 3, 177.
[9] G. Natta, Brennst. Chem. 1955, 36(11/12), 176.
[lo] W. Reppe, Liebigs Ann. Chem. 1953, 582, 1; W. Reppe, H. Kroper, ibid. 1953, 582, 38;
W. Reppe, H. Kroper, N. von Kutepow, H. J. Pistor, ibid. 1953, 582, 72; W. Reppe,
H. Kroper, H. J. Pistor, 0 . Weissbarth, ibid. 1953, 582, 87; W. Reppe, H. Vetter, ibid.
1953, 582, 133.
[ I l l J. A. Moulijn et al. in Catalysis (Ed.: J. A. Moulijn, P. W. N. M. van Leeuwen, R. A. van
Santen), Elsevier, Amsterdam, 1993, p. 3.
[ 121 W. A. Henmann, Kontakte (Merck-Darmstadt) 1988, (I), 3; W. A. Henmann, ibid. 1991,
(11, 22.
[I31 A. Behr in Ullmann’s Encyclopedia of Industrial Chemistry, 5th ed., Vol. A18,
VCH, Weinheim, 1991, p. 215; Paper presented on the occasion of Professor Keim’s
60th birthday, Aachen, November 1994.
[ 141 B. Cornils, J. Falbe, 4th Int. Symp. Homogeneous Catalysis, Leningrad, 1984, Preprints,
p. 487.
[I51 W. A. Henmann, Hoechst High Chem (Frankfurt) 1992, 13, 19.
[I61 W. Keim, Chem. Ing. Tech. 1984, 56, 850; A. Behr, W. Keim, Erdol, Erdgas, Kohle,
1987, 103, 126.
[I71 W. Strohmeier, E. Hitzel, B. Kraft, J. Mol. Catal. 1977/78, 3, 61.
[I81 J. A. Godfrey, R. A. Searles, Chemie-Technik 1981, 10, 1271.
[I91 Anon., Nachr: Chem. Techn. Lab. (Weinheim)1979, 27, 257.
[20] P. Braunstein, Nachr: Chem. Tech. Lab. (Weinheim) 1984, 32, 29.
[21] S. M. Michalska, D. E. Webster, CHEMTECH 1975, 117.
[22] J. Falbe, H. Bahrmann, Chem. unserer Zeit (Weinheim) 1981, 15, 37; J. Chem. Educ.
1984, 61, 961.
[23] K.-H. Schmidt, Chem. Industrie 1985, 762.
[24] R. Schlogl, Angew. Chem. 1993, 105, 402; Angew. Chem., Int. Ed. Engl. 1993, 32, 381;
R. Schlogl, Angew. Chem. 1994, 106, 319.
[25] J. M. Thomas, K. I. Zamaraev, Angew. Chem. 1994, 106, 316; Angew. Chem., Int. Ed.
Engl. 1994, 33, 308.
[26] B. Comils in New Syntheses with Carbon Monoxide (Ed.: J. Falbe), Springer, Berlin,
1980.
[27] Review in W. A. Henmann, Angew. Chern. 1982, 94, 118; Angew. Chem., Int. Ed. Engl.
1982, 21, 117.
 References 25

[28] See, for example: (a) B. C. Gates, Catalytic Chemistry, John Wiley, New York, 1992:
(b) C. Lecuyer, F. Quignard, A. Choplin, D. Olivier, J.-M. Basset, Angew. Chem.
1991, 103, 1692; Angew. Chem., Int. Ed. Engl. 1991, 36, 1660; (c) T. A. Budzichowski,
S. T. Chacon, M. Chrisholm, F. J. Feher, W. Streib, J. Am. Chem. Soc. 1991, 113, 689;
(d) W. A. Henmann, R. Anwander, V. Dufaud, W. Scherer, Angew. Chem. 1994, 106,
1338: Angew. Chem., Int. Ed. Engl. 1994, 33, 1285.
[29] H. Heinemann, CHEMTECH 1971, 286.
[30] G. W. Parshall, R. E. Putscher, J. Chem. Educ. 1986, 63, 189.
[31J B. Cornils, L. Mark6, Methoden Org. Chem. (Houben-Weyl),4th ed. 1986, Vol. E18, Part
2, p. 759.
[32] J. Gauthier-Lafaye, R. Perron, dctualite' Chimique, Mars/Avril 1989, 49.
[33] G. Ertl, H. Knozinger, J. Weitkamp, Handbook of Heterogeneous Catalysis, VCH, Wein-
heim, 1997.
[34] M. G. White, Heterogeneous Catalysis, Prentice Hall, Englewood Cliffs, NJ, 1990.
1351 B. C. Gates, Catalytic Chemistry, Wiley, New York, 1992.
[36] E. Horton, K. Gockenbach (Tennessee-Eastman Corp.), Paper presented to the EPRI
Symp. on Synthetic Fuels for Power Generation, Sun Francisco, April 1985: J. L.
Ehrler, B. Juran, Hydrocarbon Process. 1982, 61(2), 109.
1371 British Petroleum (M. Kitson), EP 0.407.091 (1991).
[38] (a) H. Pommer, Angew. Chem. 1960, 72, 811: (b) H. Pommer, ibid. 1977, 89, 437:
Angew. Chem., Int. Ed. Engl. 1977, 16, 423: (c) W. Reif, H. Grassner, Chem.-1ng.-
Tech. 1973, 4.5, 646: (d) H. Pommer, P. C. Thieme, Top. Cum Chem. 1983, 109, 165;
(e) J. Paust, Pure Appl. Chem. 1991, 63, 45.
[39] (a) BASF AG (W. Sarnecki, H. Pommer), DE 1.060.368 (1957); (b) BASF AG (H. Pom-
mer, W. Samecki), DE 1.068.702 (1958): (c) BASF AG (W. Himmele, F. J. Muller,
W. Aquila), DE 2.039.078 (1972): (d) Hoffmann-La Roche (P. Fitton, H. Moffet),
US 4.124.619 (1978).
1401 Hoechst AG (H. Erpenbach, K. Gehrmann, E. Jagers, G. Kohl), DE 3.823.645 (1989):
EP 0.170.964 ( 1 988).
[41] B. Cornils in Chemicals from Coal: New Processes (Ed.: K. R. Payne), Wiley, New
York, 1987.
[42] (a) K. L. Olivier, D. M. Fenton, J. Biale, Hydrocarbon Process. 1972 (Nov.), 95: (b)
D. M. Fenton, K. L. Olivier, CHEMTECH 1972, 2, 220.
[43] A. Behr in UllmannS Encyclopedia of Industrial Chemistry, 5th ed., VCH, Weinheim,
1991, Vol. A18, p. 215; paper presented on the occasion of Professor Keim's 60th birth-
day, Aachen, November 1994.
[44] (a) F. R. Hartley, P. N. Vezey, Supported Transition Metal Complexes as Catalysts, Adv.
Organomet. Chem. Ser. 1977, 1.5, 189; (b) F. R. Hartley, Supported Metal Complexes,
Reidel, Dordrecht, 1985: (c) J. P. Arhancet, M. E. Davis, J. S. Merola, B. E. Hanson,
J. Catal. 1990, 121, 327.
[45] E. V. Dehmlow, S. S. Dehmlow, Phase-Transfer Catalysis, 3rd ed., VCH, Weinheim,
1993.
1461 NATO Advanced Research Workshop, Aqueous Organometallic Chemistry and Cataly-
sis, Debrecen, Hungary, Aug./Sept. 1994, Prepnnts and Kluwer Academic Publ., Dor-
drecht 1995: J. Haggin, Chem. Eng. News 1994 (Oct. lo), 28.
1471 E. Wiebus, B. Comils, Chem.-1ng.-Tech.1994, 66, 916: CHEMTECH 1995, 25, 33.
[48] E. Bayer, V. Schurig, Angew. Chem., Int. Ed. Engl. 1975, 14, 493; L. W. Grosser,
W. H. Knoth, G. W. Parshall, J. Mol. Catal. 1977, 2, 253.
[49] Ruhrchemie AG (W. Greb. J. Hibbel, J. Much, V. Schmidt), DE 3.630.587 (1986),
EP 0.263.953 (1987): Hoechst AG (H. Bahrmann et al.), DE 3.842.819 (1988),
EP 0.374.615 (1989).
26 I Introduction

ISO] A. Behr, W. Keim, Erddl, Erdgas, Kohle 1987, 103, 126.

1.511 G. W. Parshall, S. D. Ittel, Homogeneous Catalysis, 2nd ed., Wiley, New York, 1992.
1.521 L. H. Pignolet (Ed.), Homogeneous Catalysip with Metal Phosphine Complexes, Plenum
Press, New York, 1983.
1531 cf. Ref. [111, p. 199.
1541 British Petroleum Co. (M. J. Lawrenson), GB 1.197.902 (1967).
1551 (a) M. Beller, B. Cornils, C. D. Frohning, C. W. Kohlpaintner, J. Mol. Cutul. 1995, 104,
17; (b) W. A. Herrmann, C. W. Kohlpaintner, R. Manetsberger, H. Kottmann, H. Bahr-
mann, ibid. 1995, 97, 65.
1561 A. M. Viturtia, J. Mata-Alvarez, S. Sans, J. Costa, F. Cecchi, Environ. Technol. 1992,
13, 1033; W. K. Elefsiniotis, Biotech. Bioeng. 1994, 44, 7.
1571 (a) N. Sakai, S. Mano, K. Nozaki, H. Takaya, J. Am. Chem. Soc. 1993, 115, 7033;
(b) N. Sakai, K. Nozaki, H. Takaya, J. Chem. Soc., Chem. Commun. 1993, 395.
1581 (a) B. Cornils, Chem.-@.-Tech. 1994,42, 1136; (b) M. Baerns, Nachr: Chem. Tech. Lab.
1995, 43, 245; (c) B. Cornils, Angew. Chem. 1995, 107, 1709; Angew. Chem. lnt. Ed.
Engl. 1995, 34, 1575.
1591 J. Manassen in Catalysis, Progress in Research (Ed.: F. Basolo, R. L. Burwell),
Proc. NATO Science Committee Conf. on Catalysis, Santa Margharita di Pula, 1972,
Plenum Press, New York, 1973, p. 183; Y. Dror, J. Manassen, J. Mol. Catal. 1977, 2,
219.
1601 W. A. Hemnann, C. W. Kohlpaintner, Angew. Chem. 1993, 105, 1588; Angew. Chem.,
Int. Ed. Engl. 1993, 32, 1524.
1611 (a) Review: W. S. Knowles, Acc. Chem. Res. 1983, 16, 106; (b) W. S. Knowles,
M. J. Sabacky, B. C. Vineyard, D. J. Weinkauff, J. Am. Chem. Soc. 1975, 97, 2567;
(c) W. S. Knowles, M. J. Sabacky, B. D. Vineyard, Ann. N. I: Acad. Sci. 1977, 295, 274.
1621 C. Mercier, P. Chabardes, Pure Appl. Chem. 1994, 66(7), 1509.
1631 L. Cassar, Chim. lnd. (Milan) 1985, 57, 256; Montecatini Edison S. p. A. (M. Foa,
L. Cassar, G. P. Chiusoli), DE 2.035.902 (1979).
1641 N. Yoshimura, Y. Tokitoh, M. Matsumoto, M. Tamura, Nippon Kagaku Kaishi 1993, ( 2 ) ,
119; Chem. Abstr: 118, 126, 927f.
1651 R. Selke, H. Pracejus, J. Mol. Catal. 1986, 37, 213; Isis-Chemie (R. Selke et al.) DD
(DDR) 140.036 (1978); W. Vocke, R. Hanel, F. W. Flother, Chem. Techn. 1978, 39, 123.
1661 Reviews: (a) R. Noyori, Science 1990,248, 1194; (b) R. Noyori, H. Takaya, Acc. Chem.
Res. 1990, 23, 345.
1671 D. Seebach, Angew. Chem. 1990, 102, 1363; Angew. Chem., Int. Ed. Engl. 1990, 29,
1320.
[68] C. Masters, Homogeneous Transition-Metal Catalysis - A Gentle Art, Chapman and
Hall, London, 1981.
(691 J. S. Thayer, Adv. Organomet. Chem. 1975, 13, I .
1701 W. A. Hemnann, J. Organomet. Chem. 1990, 383, 21.
(7 I ] F. M. McMillan: The Chain Straighteners, The McMillan Press, London, 1979.
1721 S. Neufeldt, Chronologie Chemie 1800-1980,2nd ed., VCH, Weinheim, Germany, 1987.
[73] W. C. Zeise, Ann. Physik 1827, 9, 632; W. C. Zeise, ibid. 1832, 21, 498, 542.
[74] V. Grignard, Compt. Rend. 1900, 130, 1322; Ann. Chim. Phys. (Paris) 1901, 24, 433.
1751 L. Mond, C. Langer, F. Quincke, J. Chem. Soc. (London) 1890, 57, 749.
[76] E. 0. Fischer, Chem. Bel: 1974, 112, XXI; (b) W. A. Henmann, J. Organomet. Chem.
1990, 383, 21.
[77] W. Reppe, Chem.-Ing.-Tech. 1950, 22, 361, 437, 527; Chem.-Ztg. 1952, 76, 532.
1781 (a) K. Ziegler, E. Holzkamp, H. Breil, H. Martin, Angew. Chem. 1955, 67, 541;
(b) K. Ziegler, Adv. Organomet. Chem. 1968, 6, 1; (c) K. Ziegler, H. Breil, H. Martin,
E. Holzkamp, DE 973.626 (1953/1960); (d) K. Ziegler, Angew. Chem. 1964, 76, 545.
 References 27

[79] H. Kading, Brennst. Chem. 1968, 49, 337.

[80] A. Hermann (Ed.), Deutsche Nobelpreistrager, Moos & Partner, Munich, 1987.
[81] (a) G. Natta, Chim. Ind. (Milan), 1942, 24, 389; G. Natta, E. Beati, ibid. 1945, 27, 84;
G. Natta, P. Pino, ibid. 1949, 31, 109, 111; (b) G. Natta, P. Corradini, Atti Acad.
Nuz. Lincei Mem. Cl. Sci. Fis. Mat. Nat. Sez. II 1955, 5, 73: (c) Montecatini
(G. Natta, P. Pino, G. Mazzanti), IT 535.712 (1954/1955); (d) G. Natta, Angew. Chem.
1956, 68, 393.
J. F. Young, G. Wilkinson, Chem. Commun. 1965, 131; J. A. Osbom, F. H. Jardine,
J. F. Young, G. Wilkinson, J. Chern. SOC.(London) A 1966, 1711.
G. Wilke, J. Organomet. Chem. 1980, 200, 349.
 Applied Homogeneous Catalysis with Organometallic
Edited by Boy Cornils & Wolfgang A. Herrmann
© Wiley-VCH Verlag GmbH, 2002

2
Applied Homogeneous Catalysis
 Applied Homogeneous Catalysis with Organometallic
Edited by Boy Cornils & Wolfgang A. Herrmann
© Wiley-VCH Verlag GmbH, 2002

2.1 Carbon Monoxide and Synthesis

Gas Chemistry

2.1.1 Hydroformylation (0x0 Synthesis, Roelen Reaction)

Carl D. Frohning, Christian W Kohlpaintnec
Hans- Willi Bohnen

2.1.1.1 Introduction
When he passed a mixture of ethylene and synthesis gas over a fixed-bed cobalt-
containing catalyst at 150 “C and 10 MPa pressure, Otto Roelen was certainly not
aware that not only had he detected a new chemical reaction but he had also
established one of the key points of homogeneous organometallic catalysis.
This happened on July 26, 1938, precisely, when Roelen aimed at increasing
the chain-length of Fischer-Tropsch (FT) hydrocarbons in the laboratories of
Ruhrchemie AG at Oberhausen, Germany, by recycling the primarily generated
olefins [l]. It must be attributed to Roelen’s experimental skill that he detected,
isolated, and characterized the small amounts of propanal (and diethyl ketone)
that had formed under the unconventional FT conditions, and it was his clear
scientific awareness that enabled him to draw the right conclusions from the
unexpected experimental results. However, it took some time until the general
principles and the broad applicability of metal-carbonyl-catalyzed reactions were
fully recognized and the homogeneous nature of the catalysis was proven [2].
The reaction between olefinic double bonds and the mixture of hydrogen
and carbon monoxide (synthesis gas) leads to linear and branched aldehydes
(iso-aldehydes) as primary products (eq. (1)).

m C H O (1)
R- CO/Hp_ R + R

Due to the observation that ethylene yields not only propanal but also some
diethyl ketone, it was assumed at first that as well as aldehydes and ketones,
ergo, 0x0 compounds can be generated, and the reaction was termed 0x0 synthesis
or oxonation. The correct expression, hydroformylation, was introduced later by
Adkins [ 3 ] .Some tentative approaches to link the discoverer’s name to the reac-
tion (“Roelen Reaction”) have earned only a limited response. The ratio of linear
(n-) and branched (iso-) aldehydes is referred to as n/iso (or di)ratio.
In the first 20 years after its discovery, hydroformylation gained little impor-
tance despite the chemical versatility of aldehydes as redox-amphoteric precursors
for several classes of compounds. Starting from about the mid-l950s, two devel-
opments made the main contributions to the progress of hydroformylation, which
since then has steadily increased in importance. The first was the rapid growth of
32 2.1 Carbon Monoxide and Synthesis Gas Chemistry

the petrochemical industry, which switched the olefin raw- material basis away
from natural or FT olefins to a broad variety of cheap and pure petroleum-
based olefins, thus presenting improved feedstock availability and quality. The
second factor was the emergence of at least two markets, the PVC and the deter-
gent industries. Even today, these sectors have remained the most significant cus-
tomers for alcohols produced via hydroformylationhydrogenation. The aldehydes
formed in the 0x0 reaction serve as a turntable in the bulk and specialty chemical
business (Figure 1) [4].The situation prompted the development of a number of
hydroformylation processes.

[ alcohols] carboxy'ic
acids acroleins diols acetals

r--------
I aldols I
. - ....
23
ethers

Figure 1. Bandwidth of compounds accessible through hydroformylation.

The first generation of hydroformylation processes (e.g., by BASE ICI,

Kuhlmann, Ruhrchemie) was exclusively based on cobalt as catalyst metal. As
a consequence of the well-known stability diagram for cobalt carbonyl hydrides,
the reaction conditions had to be rather harsh: the pressure ranged between 20 and
35 MPa to avoid decomposition of the catalyst and deposition of metallic cobalt,
and the temperature was adjusted according to the pressure and the concentration
of the catalyst between 150 and 180 "C to ensure an acceptable rate of reaction. As
the reaction conditions were quite similar, the processes differed only in the
solution of the problem of how to separate product and catalyst, in order to
recover and to recycle the catalyst [4]. Various modes were developed; they
largely yielded comparable results, and enabled hydroformy lation processes to
grow rapidly in capacity and importance (see Section 2.1.1.4.3).
Nevertheless, the general need for improvement became obvious, with milder
reaction conditions, increased selectivity to linear aldehydes, and reduced by-
product formation being the main objectives. Significant progress was attributable
to Shell researchers from the beginning of the 1960s. The discovery that phos-
 2. I . 1.1 Introduction 33

phines (or arsines) were able to replace carbon monoxide as electron-donating

ligand was a fundamental step in metal-carbonyl-catalyzed reactions, which
gave access, to a certain extent, to tailor-made catalysts via the electronic and
steric properties of the ligand. Besides, the stability of metal carbonyls is markedly
enhanced by ligand modification, leading to reduced carbon monoxide pressure.
The Shell process, the only process using a cobalt-phosphine catalyst, may be
considered the final step in the development of first-generation processes.
The second-generation processes combined the advantages of ligand modifica-
tion with the transition from cobalt to rhodium as catalyst metal. Although rapid
progress was achieved in the application of rhodium-phosphine catalysts on a
laboratory scale, nearly a decade had to pass until the first commercial process
was launched in 1974. It can be ascribed to the former Celanese Corporation
(later the Hoechst Celanese Corporation), which mentioned the successful opera-
tion of a butyraldehyde plant at Bishop (Texas) in their business report the same
year [192]. The next to follow was Union Carbide Corporation in 1976, and in the
following years an aggressive license policy changed the picture of propylene
hydroformylation drastically. The so-called low-pressure 0x0 (LPO) processes
soon took the leading role in this field, a consequence of their frequently cited
advantages. Moreover, the mineral-oil supply crisis in 1983 favored the processes
with high raw material utilization, and in this respect the second-generation
processes were highly advantageous over the cobalt technology (see Section
2.1.1.4.4). It should be mentioned that the expression “LPO’ was coined by
BP, not by UCC 12661.
It may be considered ironic that as early as 1969 a nearly complete description
of the characteristic features of the subsequently presented LPO technology had
been published by Monsanto researchers [ 5 ] . The company decided at that
stage not to deal with hydroformylation any longer, but instead they concentrated
on the development of the nowadays well-known acetic acid process (using mod-
ified rhodium carbonyl as catalyst) (cf. Section 2.1.2.1) [6].
Compared with the cobalt technology, considerable advances had been estab-
lished in the second-generation processes, especially with respect to material
and energy utilization, so there was not much room left for further improvement.
Nevertheless, some progress could still be achieved, and at the beginning of the
1980s an evolution started which may be tentatively designated third-generation
with respect to reaction engineering. The basic idea consisted in applying a water-
soluble phosphine as ligand and thus transferring the hydroformylation into the
aqueous phase. The biphasic but homogeneous reaction system exhibited distinct
advantages over the conventional one-phase processes and the extension of the
principle has been intensively studied since then.
With nominal production capacities of more than six million tons/year hydro-
formylation has arrived in the society of large homogeneously catalyzed reactions.
The majority of this capacity is absorbed in the form of plasticizers by the polymer
industry, the detergent industry being the other big consumer of consecutive hy-
droformylation products. It should be borne in mind that there is a pronounced
interdependence between the hydroformylation and the polymer industries (see
Section 2.1.1.4.1).
34 2.1 Carbon Monoxide and Synthesis Gas Chemistry

The hydroformylation of special structures, which is often the aim of laboratory

research, has failed by far to reach the commercial importance of the bulk
chemicals. However, as progress in the synthesis of specialty chemicals as inter-
mediates is now perceptible, this field is expected to receive increased attention in
the near future.
A fairly large number of mostly spectroscopic investigations had led to more
detailed insight into the mechanism of hydroformylation, and the role of ligands
with respect to activity, regional and steric selectivity (induction of chirality).
Generally, the basic interpretations of a sequence of steps in a closed cycle, pro-
posed by Heck and Breslow as early as 1961, have been confirmed and success-
fully transferred to ligand-modified metal carbonyls. The mechanistic picture of
hydroformylation thus appears to be nearing completion, but many details are
still under investigation.
Surprisingly little information is available about the kinetics of hydroformyla-
tion reactions. For several decades Natta’s equation served as a basic explanation;
however, in the last few years the application of reaction models of the Lang-
muir-Hinshelwood type, even to biphasic systems, has been successfully demon-
strated. This contribution (see Section 2.1.1) puts more emphasis on this area
than has been usual in reviews on hydroformylation (see Section 2.1.1.3.2). In
addition, the fundamentals of the 0x0 synthesis are discussed, along with the
most important recent developments. The industrial processes in operation
today are described as well. Due to its importance, the hydroformylation reaction
has already been extensively reviewed elsewhere. For information beyond and in
addition to this contribution, see [4, 7-12, 2931.

2.1.1.2 Fundamental Principles

2.1.1.2.1 Catalysts
A plethora of metal complexes have been stated to catalyze the hydroformylation
reaction. 0 x 0 catalysts typically consist of a transition metal atom (M) which
enables the formation of a metal carbonyl hydride species. Optionally, these
complexes may be modified by ligands (L). A general composition is represented
by Structure 1.
H,M,(CO)ZL”
1

For y1 = 0 catalysts are called “unmodified”, whereas coordination of the metal

center by ligands other than CO or hydrogen are designated “modified”. Various
precursor compounds may form the active hydroformylation species under suit-
able conditions. Even transition metal chlorides are converted to metal carbonyl
hydrides under drastic conditions (high pressure and temperature) and in the
presence of base.
 2.1.1.2 Fundamental Principles 35

Variation of the Central Atom

Monometallic Catalysts

Modern hydroformylation research is almost exclusively focused on four transi-

tion metals: cobalt, rhodium, platinum and to considerable extent ruthenium
[ 131. The generally accepted order of hydroformylation activity for unmodified
monometallic catalysts clarifies this picture [ 141:

Rh B Co > Ir, Ru > 0 s > Pt > Pd > Fe > Ni

Co, Rh, Pt, and Ru belong to the group of six transition metals forming the most
active 0x0 catalysts. Today’s hydroformylation plants operate exclusively with
catalysts based on rhodium or cobalt, namely HCO(CO)~,HCo(CO),PBu, and
HRh(CO)(PR,), [9] (see Section 2.1.1.4).
Platinum and ruthenium catalysts are mainly subjects of academic interest,
not thoroughly investigated by industrial researchers. Platinum catalysts modified
by tin(I1) chloride (SnCI2)have gained significant importance in the field of asym-
metric hydroformylation and will be discussed there (see Sections 2.1.1.2.3, 2.9,
and 3.1 S ) . Other carbonyl-forming transition metals, including Mo [ 1.5, 17~1,
Cr [lS], Mn [16], Tc [20], Ir [19, lOSa], Fe [17] or 0 s [18], have been claimed
to be active 0x0 catalysts. However, activities and lifetimes are much lower
than those of rhodium, cobalt, platinum, or ruthenium catalysts. Comparative
results of phosphine-modified and unmodified catalysts in the hydroformy lation
of olefins can be found in [4, 211.

Polymetallic Catalysts

Bi- and polymetallic hydroformylation catalysts (cf. Section 3.1 .S on multicompo-

nent and multifunctional catalysts) have been thoroughly studied. Interesting
results in the area of bimetallic catalysts have been reported recently [243-2451
and will be discussed in Section 2.1.1 .S. In the field of polymetallic 0x0 catalysts,
research on the structure and reactivity of clusters has contributed considerable
information. Numerous publications have shown that under hydroformylation
conditions clusters are degraded to at least bimetallic species, sometimes re-
versibly [22], which perform the 0x0 reaction [23]. The species investigated in
the past cover homo- and hetero-metallic, phosphido-bridged or modified by
other ligands, monometallic and mixed-metal clusters. Very recently, Garland
[24] has shown that in hydroformylation conditions multinuclear compounds
such as Rh4(C0)12,Rh6(C0)16, Rh,(CO),CI,, CoRh(C0)7, and C O , R ~ ~ ( C O ) ~ ~
are degraded to HRh(CO),, which performs the 0x0 reaction. Synergistic effects
often claimed in cluster catalysis [25] are attributed in Garland’s view to the
rapid generation of the active catalyst species HRh(CO),. The induction period
for formation of this species is two to three orders of magnitude shorter than
that of monometallic catalyst precursors. However, at low temperature and pres-
36 2.1 Carbon Monoxide and Synthesis Gas Chemistry

sure some cluster species are more active than their monometallic counterparts
(cf. Section 3.1.1.5) [26]. For a recent comprehensive review on clusters and
hydroformylation see [27]. So far, cluster catalysis exhibits no significant advant-
ages in the 0x0 reaction.

Modification by Ligands

Phosphines

The only classes of ligands used in industrial hydroformy lation plants are phos-
phines PR3 (R = C6Hsr n-C4H,), triphenylphosphine oxide and in some special
cases phosphites, P(OR)3. Nitrogen-containing ligands such as amines, amides,
or isonitriles showed exclusively lower reaction rates in the 0x0 reaction, due
to their stronger coordination to the metal center. A comparative study of Ph3E
(E = Main Group V element) in the hydroformylation of 1-dodecene at 90 "C
(0.8 MPa Corn2)showed the following order of reactivity:

Ph3P % Ph3N > Ph3As, Ph3Sb > Ph,Bi

proving the superiority of phosphine ligands [28]. Other heteroatom-containing

ligands have been tested as well. Without exception their performance in the
0x0 reaction is poorer compared with phosphines [4].
Phosphines and their coordination chemistry have been studied in great detail
[29]. Tolman introduced the cone angle 0 and the electronic parameter x to clas-
sify phosphine ligands with respect to their steric demand and coordination ability
[30]. A comprehensive review on the bonding and energetics of phosphorus(II1)
ligands in transition metal complexes has been published recently [31]. For che-
lating diphosphines Casey developed the natural bite angle, based on molecular
mechanics calculations [32]. In some cases n/iso selectivities are now predictable
by the diphosphine structure. The concept of the natural bite angle is accepted and
used by other authors as well [33]. However, studies on the structure of
phosphines and its influence on the catalytic results remain scarce [34-361. The
empirically derived propositions on phosphines and their influence on the course
of reaction are discussed in Section 2.1.1.3.3.
About 250 papers and patent applications appear annually in the area of hydro-
formylation, most of them dealing with new phosphine structures and catalytic
results obtained therewith. Discussion of this huge number of ligands would go
far beyond the limitations of this contribution. A few selected examples will be
described later, in Section 2.1.1.5.
In 1987 Mitsubishi Kasei launched a 30 000 tons/year plant for the production
of isononanol by hydroformylation of octenes [37]. The catalyst is based on a
rhodium-triphenylphosphine oxide (TPPO) complex which is stabilized a f e r
the 0x0 reaction by addition of triphenylphosphine (TPP) to avoid decomposition
during the distillation of product. The rhodium-(TPP)complex formed together
with excess of TPPO in the high-boiling residue is oxidized to the rhodium-TPPO
 2.1.1.2 Fundumental Principles 37

catalyst and re-used. This is the only example known of an oxidized phosphine
ligand used on an industrial scale. Only recently a P-N ligand with a P = 0 moiety
has been tested successfully on a laboratory scale (see Section 2.1.1.5).
Synthesis of water-soluble phosphines is nowadays one of the most active
areas in hydroformylation research. The 0x0 synthesis in a two-phase system
with water-soluble catalysts, the RuhrchemieRh6ne-Poulenc process (RCH/
RP), will be discussed in Section 2.1.1.4. Water-soluble catalysts in general are
treated in Section 3.1.1.1. Since the last exhaustive reviews in 1993 and 1992
on water-soluble complexes [38], some progress has been made in this area,
which will be discussed in Section 2.1.1 S.3.

Phosphites

Considerable progress has been made recently by using phosphites (general for-
mula (RO),P) as ligands in rhodium-catalyzed 0x0 synthesis. Rhodium catalysts
with phosphites such as 2 and 3 showed high activities in the hydroformylation
of long-chain olefins [39, 401.
OCH3 OCH3

H3CO C9H19
3

Less reactive olefins such as 2,2-dialkyl- 1-alkenes are hydroformylated at much

higher rates than those achieved with TPP-modified rhodium catalysts. Activities
of 15 000 mol (aldehyde)/mol (Rh) . h have been reported (90 "C, 1-3 MPa) [39].
1-Alkenes are converted with even higher rates (activity = 160000 moVmol . h).
At these high rates the reaction becomes mass-transfer limited. The lack of CO
dissolved in the liquid layer leads to formation of unsaturated rhodium species
which rapidly isomerize the olefin. The n/i ratio obtained is therefore low
(20-30 % linear product). The structure of hydrido-rhodium diphosphite com-
plexes was investigated in detail by NMR spectroscopy [41]. BASF reported
the hydroformylation of methyl 3-pentenecarboxylate with Rh(CO),(acac) and
3 as a ligand. Methyl 5-formalvalerate was formed with 72 % selectivity [42].
The first step in the synthesis of nonvolatile plasticizers - which are of increas-
ing importance - is hydroformylation of a long-chain olefin, for which rhodium
phosphite catalysts have very useful properties. The current use of sterically hin-
dered phosphites as antioxidants for polyalkenes together with their much simpler
38 2.1 Carbon Monoxide and Synthesis Gas Chemistry

synthesis makes them appear more attractive than phosphines. Chiral variants of
phosphites and their impact on asymmetric hydroformylation will be briefly dis-
cussed in Section 2.1.1.2.3 (cf. Sections 2.9 and 3.3.1).

Variation of the Application Phase

Industrial hydroformylation is currently performed in two basic variants: the

homogeneous processes, where the catalyst and substrate are in the same liquid
phase (Shell, UCC, BASF, etc.), and the two-phase process with a water-soluble
catalyst (RCHRP). These processes will be discussed in detail in Section 2.1.1.4.
Gas-phase hydroformylation with heterogeneous catalysts plays no role today.
The immobilization of homogeneous catalysts will be discussed in Section
3.1.1. Special applications such as SLPC (supported liquid-phase catalysts) [43]
and SAPC (supported aqueous-phase catalysts) [44] are not considered further
here. Heterogeneous 0x0 catalysts are not within the scope of this book; they
are discussed further elsewhere [267].

2.1.1.2.2 Substrates
General Principles

The virtue of the 0x0 synthesis lies in its applicability to a broad variety of sub-
strates. On a laboratory scale most unsaturated carbon-carbon bonds and some
heteroatom-carbon double bonds can be hydroformylated. Reaction rates vary
with catalysts and reaction conditions. However, industrial importance has only
been reached for I -olefins such as propene, butene, octene/ nonene and some se-

Figure 2. Relative reactivity of nonfunctionalized olefins.

 2.1.1.2 Fundamental Principles 39

lected functionalized alkenes. The relative reactivity of unfunctionalized olefins is

depicted in Figure 2 [49]. A similar picture results for unmodified rhodium cata-
lysts [50]. The order of reactivity is:

unbranched/terminal > unbranched/internal > branchedherminal >

branchedhnternal

It has been stated that a formyl group formed during the hydroformylation re-
action of unfunctionalized olefins is unlikely to be attached to a quaternary carbon
atom (the Keulemans rule). An example of this general rule is the 0x0 reaction
with 2,3-dimethyl-2-butene, where 3,4-dimethylpentanal is formed exclusively.
For both rhodium and cobalt catalysts, isomerization of the substrate is followed
by hydroformylation (Scheme 1) [47, 481.

isomerization I hydroformylation

Scheme 1. Hydroformylation pathway of 2,3-dimethyl-2-butene.

Substrates with Economic Importance

Based on their chain length, olefins converted in commercial 0x0 plants are
divided into four groups: ethylene (C,), propene (C,), butene to dodecene (C,
to C12)and longer-chain olefins (> C,2).The factors influencing product distribu-
tion and reaction rates in the hydroformylation of olefins will be discussed in Sec-
tion 2.1.1.3.3. The economical aspects of 0x0 processes are described in Section
2.1.1.4.1. The share of various products in the overall olefin hydroformylation ca-
pacity is C2 -2%), C3 (73 %), C,-C,, (19%) and >C12 (6%).
Besides these 0x0 products, some even more extraordinary compounds are pro-
duced via 0x0 synthesis. Starting in 1963, Ajinomoto produced racemic monoso-
dium glutamate by a cobalt-catalyzed hydroformylation of acrylonitrile [49, 501.
The directing effect of the functional group ensured high linearity of the resulting
aldehyde. By a Strecker reaction (HCN/NH3) and hydrolysis of the nitrile groups
(NaOH) a mixture of R- and S-glutamate was accessible which was resolved in
following steps. An annual capacity of 12 000 tons was maintained during almost
ten years of successful operation. The availability of an economically superior mi-
crobial synthesis, and concerns about acrylonitrile as a starting material for food
additives, terminated this process in 1973.
40 2.1 Carbon Monoxide and Synthesis Gas Chemistry

According to eq. (2), ally1 alcohol is converted to 1,4-butanediol by rhodium-

catalyzed hydroformylation and hydrogenation of 2-hydroxytetrahydrofuran [5 1,
521. In 1990 ARC0 launched a production plant based on the technology devel-
oped by Kuraray with a 30 000 tons/year 1,4-butanediol capacity [S3].Presumably
the rhodium catalyst is modified by the diphosphine DPPB (1,4-bis(diphenyl-
phosphino)butane) [S4].

Structure 4 is an intermediate for manufacturing vitamin A (Scheme 2). The

annual demand for vitamin A is about 3000 tons. Major producers are BASE
Hoffmann-La Roche and RhBne-Poulenc Animal Nutrition [ S S ] . At an early
stage in the synthesis BASF and Hoffmann-La Roche are using a hydroform-
ylation step to synthesize 4 starting from 1,2-diacetoxy-3-butene ( 5 ) and 1,4-di-
acetoxy-2-butene (6), respectively [S6, 571. The selectivity toward the branched
product in the BASF process is achieved by using an unmodified rhodium
carbonyl catalyst at a high reaction temperature. The symmetry of 6 in La Roche’s
process does not lead to regioselectivity problems. Elimination of acetic acid and
isomerization of the ex0 double bond (La Roche) yields the final product 4 in both
processes.
An example of the application of a water-soluble hydroformy lation catalyst
other than in the Ruhrchemie/Rh6ne-Poulenc process is the synthesis of 1,9- non-
anediol according to Kuraray [%I. Hydrodimerization of butadiene (also cata-

I BASF I I LaRocheI

T O A c
V O A C
OAc
AcO
5 6

Scheme 2. The hydroformylation step in the synthesis of vitamin A precursor 4:

BASF (left) and LaRoche process (right).
 2.1. I .2 Fundamental Principles 41

lyzed by a water-soluble complex) yields 2,7-octadienol (cf. Section 2.3.5), which

is isomerized to 7-octenal. A rhodium (TPPMS = triphenylphosphine monosul-
fonate) catalyst is used to hydroformylate the unsaturated aldehyde to I ,9-nonane-
dial. Hydrogenation over Raney nickel yields the final product, 1,9-nonanediol.
Recent patent applications imply the use of tris[o-(t-butyl)phenyl] phosphite
((O-‘BUC,H,O)~P)instead of TPPMS as a ligand [59]. The same ligand is
also applied in the rhodium-catalyzed hydroformylation of 3-methyl-3-butenol
to 2-hydroxy-4-methyltetrahydropyran, a precursor for 3-methyl- 1,5-pentanediol
[601.

Particular Structures

The broad applicability of the 0x0 synthesis is reflected by the plethora of

substrates which are converted to aldehydes - for instance, diolefins such as
butadiene, alkynes [6 I] or unsaturated fatty acids [66]. Olefinic substrates con-
taining one or more functional groups attract much attention due to the high
synthetic value of the resulting aldehyde products. The following examples
refer to some relevant publications [63], and in particular to the comprehensive
review by Botteghi [49]. For a detailed discussion of particular structures see
[4] and [8].
One substrate of particular interest in industrial 0x0 research, which should be
discussed here, is “Raffinate-2”. The economic importance of the 0x0 synthesis is
mainly based on the hydroformylation of propene. The resulting n-butanal is con-
verted to 2-ethylhexanol (2-EH) by aldol condensation and hydrogenation (see
Section 2.1.1.4). This C8 alcohol, 2-EH, is used to produce DOP (dioctyl phtha-
late), a plasticizer with properties acceptable across a wide range of PVC (poly-
(vinyl chloride)) applications. Some concerns about this plasticizer arise from
three types of exposure and emission: plasticizer migration into food from plasti-
cized packaging; plasticizer evaporation from indoor floor tiles and wall cover-
ings; and plasticizer migration into blood plasma or medicine from plasticized
medical equipment. A political push to ban plasticizers is unlikely, but pressure
to minimize exposure to them is felt. The large manufacturers are therefore look-
ing for plasticizers with less volatility. Plasticizers based on C10alcohols are inter-
esting candidates and are currently being investigated.
One possible starting material for the production of C10alcohols is the above-
mentioned Raffinate-2, a C4 feedstock derived from mixed C4 streams of steam
crackers. After butadiene has been removed from the mixed stream, “Raffinate- 1”
is obtained. The isobutene content of Raffinate-1 is removed by conversion to
MTBE (methyl t-butyl ether), leaving behind a stream rich in mixed butenes
which do not react in the MTBE process; this is designated Raffinate-2. Accord-
ingly, in the USA and western Europe MTBE plants are the main consumers for
Raffinate-2.
Raffinate-2 as a raw material is converted to C5 aldehydes and finally to C10
alcohols by sequential hydroformylation, aldol condensation, and hydrogenation
[268]. Union Carbide and Davy Process Technology have developed a hydro-
42 2.1 Carbon Monoxide and Synthesis Gas Chemistry

formylation process based on mixed butenes and a rhodiuddiphosphite catalyst

to produce 2-propylheptanol (2-PH) as the Clo analog to 2-EH (“Unoxol@ 10”)
[64]. The ligand used for this new process is presumably 7, which has shown
superior rates and selectivities compared with similar diphosphites. The catalyst
converts Raffinate-2 with 94 % yield to n-pentanal, whereas only 5 % 2-methylbu-
tanal and 1 % 3-methylbutanal (from isobutene) are formed as isomeric products.
This mixture is further reacted to the final C l 0alcohol. This new process has not
been commercialized so far. Hoechst has recently patented a process for the
hydroformylation of Raffinate 2 using a water-soluble rhodium catalyst; a plant
is on stream [65, 2711. Other feedstocks, plasticizer alcohols, and processes are
currently being investigated as well, e.g., C9 alcohols from octene hydroformyla-
tion or isodecanol from nonenes.
OCH3 OCH3
I I

H&O
7

Closely related are the efforts to hydroformylate 1,3-butadiene. A bishydrofor-

mylation of conjugated dienes to dialdehydes is only possible with modi-
fied rhodium catalysts and with a high excess of phosphine (PRh = 30: 1) [66].
The first addition of CO/H2 to yield the unsaturated monoaldehyde is fairly
easy. However, during the second step hydroformylation and hydrogenation are
competing at the double bond. Isomerization is also occurring and is strongly
influenced by the type of phosphine used [67]. Unmodified cobalt or rhodium
catalysts yield saturated monoaldehydes or monoalcohols because of their high
hydrogenation activity [68]. The n- and iso-pentanals are formed in almost an
1: 1 mixture. However, to obtain Clo alcohols via aldol condensation of pentanal
and successive hydrogenation, high d i ratios are necessary but not achievable
with unmodified catalyst. The ideal catalyst, with high selectivity toward mono-
hydroformylation and linearity at the same time, has not been found yet. Water-
soluble catalysts have recently been applied to the hydroformylation of 1,3-buta-
diene [69]. A combined process of hydroformylation, aldol condensation, and hy-
drogenation yields n-pentanol (via pentanal hydrogenation) and 2-propylheptanol
(via aldol condensationhydrogenation) in mild conditions.
 2. I. 1.2 Fundamental Principles 43

2.1.1.2.3 Special Applications

Asymmetric Hydroformylation

Through asymmetric hydroformylation a broad variety of chiral molecules are

accessible which are valuable precursors for pharmaceuticals and agrochemicals.
The potential market for synthetic chiral products in bulk form at the beginning of
the 21st century is estimated to be more than US $ 2 billion [70]. In order to obtain
pure compounds, high regioselectivity and high enantioselectivity have to be com-
bined. The desired product is the branched compound with an asymmetric carbon
atom (eq. (3)).
CHO

branched linear
chiral achiral

The current status of asymmetric hydroformylation has been reviewed by

Botteghi and others [71]. The asymmetric variant of the 0x0 synthesis was first
applied in 1972 by researchers in Italy and Japan, and at BASF in Germany
[72]. Since those early days considerable progress has been made. For a long
time platinum was considered to be the superior metal in asymmetric hydro-
formylation. In order to achieve high activity and to improve the d i ratio,
platinum-phosphine complexes were used together with Lewis acids such as
SnC12 [73] or SnF2 [74]. Tin-free [75] or modified platinum catalysts with
CH3S03H [76] have been reported as well. The role of the SnCI2 co-catalyst
in promoting the single-step olefin insertion, CO insertion, and hydrogenolysis
of the acyl complex was studied in detail [77]. An ionic mechanism for the
Pt-diphosphine-catalyzed hydroformylation was formulated recently [78]. With
chelating chiral diphosphines, very high enantioselectivities (> 96 % ee) were
achieved (Figure 3) [79]. Despite the high ee values obtained with platinum
catalysts, extensive isomerization and hydrogenation are major drawbacks, to-
gether with a rather low regioselectivity for the branched products. Additionally,
a very strong influence of the reaction temperature on the enantioselectivity was
observed [SO].
By 1993 these disadvantages had been overcome by significant progress in
asymmetric hydroformylation with rhodium catalysts as Takaya [811 and Union
Carbide [82] announced major breakthroughs with phosphine-phosphite and
diphosphite ligands, respectively. The phosphine-phosphite ligand 8 gave enan-
tioselectivities up to 95 % in the hydroformylation of substituted styrene
derivatives. The branched/linear ratios were as high as 86: 14. Conversions were
> 99 % at substratekatalyst ratios of 300-2000: 1 [83]. Similar results were
reported by Union Carbide with diphosphite 9. At moderate conditions (25 OC,
3.5 MPa) styrene was hydroformylated with up to 90% ee. An i/n ratio of 50:1
was obtained at a ligandhhodium ratio of 4: 1, yet the reaction rates were rather
low (0.11 g m o m . h).
44 2.1 Carbon Monoxide and Synthesis Gas Chemistry

Figure 3. Enantiomeric excesses (% ee) achieved with diphosphine-modified

platinudtin catalysts.

OPPh2

8 10

Me0 -0Me
 2.1.1.3 Kinetics, Mechanism, and Process Parameters 45

Both developments opened up a new era of asymmetric hydroformylation. The

results are promising and research is now focused on the synthesis of structurally
related ligands. Other ligands, such as the P-N ligand 10, are also showing very
high selectivities. Faraone and co-workers, in the hydroformylation of vinyl-
naphthalene, reported the exclusive formation of the branched aldehyde while a
rhodiud10 catalyst was used (conversion 100 %) [84]. The enantiomeric excess
obtained was 78 % for the R-enantiomer. With methylacrylates an ee of 92 % was
observed. For further informations see Sections 2.9 and 3.3.1.

Other Applications

Reactions based on syngas, in analogy to hydroformy lation, have been performed

as well. These include aminomethylation [85], amidocarbonylation (see Section
2.1.2.4), homologation of acids [86] and alcohols, (cf. Section 3.2.7) [87] or silyl-
formylation (cf. Section 2.6) [88]. All these reactions are far beyond the scope of
this chapter and are not discussed further here.

2.1.1.3 Kinetics, Mechanism, and Process Parameters

2.1.1.3.1 Mechanism of Hydroformylation

Although the 0x0 synthesis has been applied industrially almost 50 years, its
reaction mechanism has not been clarified in every detail. Some aspects of the
proposed reaction pathway are still under investigation. Among industrial hydro-
formylation catalysts, major differences are observed between modified and
unmodified systems and therefore they will be discussed separately.

Unmodified Cobalt and Rhodium Catalysts

In the early 1960s Heck and Breslow formulated the generally accepted hydro-
formylation cycle depicted in Scheme 3 [89]. Originally formulated for cobalt
catalysts, the mechanism is valid for unmodified rhodium complexes as well.
The elemental steps (Scheme 3) are:

(1) reaction of the metal carbonyl C O ~ ( C Owith

) ~ hydrogen to form the hydrido-
metal carbonyl species HCo(CO),;
(2) dissociation of CO to generate the unsaturated 16e species HCo(CO),;
(3) coordination of the olefin RCH = CH2 (18e);
(4) formation of the alkylmetal carbonyl species (16e);
( 5 ) coordination of CO (18e);
(6) insertion of CO to form the acylmetal carbonyl RCH2CH2COCo(C0)3(16e);
(7) cleavage of the acylmetal species by hydrogen to form the aldehyde and
regeneration of the hydridometal carbonyl HCO(CO)~.
46 2.1 Carbon Monoxide and Synthesis Gas Chemistry

J
RCH~CH&O(C

Scheme 3. Catalytic cycle of hydroformylation with unmodified cobalt catalysts.

A critical stocktaking of every single step, together with detailed kinetic discus-
sions, was published in 1984 [90]. The statement made by Mark6 [90]

". . . the hydroformylation catalytic cycle is far more complex than anticipated even a few
years ago and thus still a large amount of experimental work is needed for the understand-
ing of this fascinating reaction"

is still true. For instance, the Co-CO dissociation energy of HCO(CO)~ to form
HCO(CO)~ (step 2) was determined to be 186 kJ/mol [91], which makes this equi-
librium thermally unfavorable. Therefore, other sources for the 16e species
HCO(CO)~ have been discussed, including an acylcobalt complex RCOCO(CO)~
[92]. In accordance with the mechanism, the protagonist of the reaction,
HCO(CO)~, is formed during the catalytic cycle by hydrogenolysis of the acylco-
balt tricarbonyl intermediate. The authors consider HCO(CO)~ and CO*(CO)~ to be
only the cobalt carbonyl reservoirs and not involved in the immediate generation
of HCo(C0)3.
A second example is the reaction of the acylcobalt complex with hydrogen
equivalents and the successive reductive elimination of the aldehyde (step 7).
This reaction was studied in great detail and has been controversial [93]. For
this very last step of the hydroformylation cycle several pathways may be
imagined. The two most plausible pathways are shown in eq. (4).
 2. I . 1.3 Kinetics, Mechanism, and Process Parameters 47

0
HCo(C0)4 II
*-I C02(C0)8 + R-C-H

Mirbach declared the reaction of the acylcobalt complex with HCo(CO), to be

the minor pathway, whereas the reaction with H2 dominates the catalytic cycle in
the hydroformylation of 1-octene and cyclohexene. On the other hand, Mark6
found that the hydridocobalt complex reacts 12 times faster with the acylcobalt
complex than does hydrogen. Undoubtedly, under industrially applied reaction
conditions the hydrogenolysis of the acylcobalt complex is effected exclusively
by hydrogen. Yet, the remaining hydridocobalt species is still in question: besides
HCO(CO)~, the cobalt cluster H C O ~ ( C Ois) ~discussed [94].
These few examples may show that the hydroformylation mechanism is still
under investigation, even after more than 50 years of successful operation in
industrial plants.

Selectivity

The n/i ratio of aldehydes formed by unmodified metal carbonyl catalysts is

influenced by the catalyst concentration (slightly), temperature (strongly) and par-
tial pressures p(H,) (slightly) and p(C0) (very strongly) (Figure 4). Variations of
the n/i ratio from 1.6 to 4.4 have been reported, but the determining factors are
still rather obscure [95].

3.5

3
1 - Catalyst

u
.c(

<
E
a
2.5

2
- Hydrogen partial
pressure

1.5

Increasing values - -
Figure 4. The di ratio vs. increasing reaction parameters: substrate concentration, catalyst
concentration and partial pressures of hydrogenlcarbon monoxide.
48 2.1 Carbon Monoxide and Synthesis Gas Chemistry

The possible sources of isomeric aldehyde formation include olefin iso-

merization, regioselectivity of the addition of the hydridocobalt carbonyl to the
olefin, isomerization of the alkylcobalt carbonyl, and isomerization of the acylco-
balt carbonyl species. There is no evidence for an isomerization of the alkylcobalt
carbonyl species under the conditions of industrial 0x0 synthesis (high pressure)
[96]. In contrast, the isomerization of a coordinated olefin is well known and a
plethora of studies have proven this behavior [4].
The selective reaction of the hydridocobalt carbonyl with the olefin via Mur-
kovnikov and unti-Markovnikov addition gives rise to the branched and linear al-
kylcobalt carbonyl isomers. It is believed that the sterically less demanding nature
of HCO(CO)~favors the formation of the branched isomer, whereas HCO(CO)~
generates predominantly the linear isomer. This is in accordance with the in-
creased selectivity observed at higher carbon monoxide partial pressures. As
HCO(CO)~is the less reactive catalyst, the catalytic activity drops at the same
time.
Recently, the thermodynamic data for the isomerization of the acylcobalt carbo-
nyl species were determined (eq. ( 5 ) ) [97]. With AH = 0.47 F 0.2 kcal/mol (2.0 -t
0.8 kJ/mol) and A S = 2.13 F 0.6 caVmol "C (8.91 f 2.5 kJ/mol "C), the isomer-
ization rate varies in proportion to the olefin concentration and inversely with
p ( C 0 ) . The higher the p(CO), the slower is the isomerization rate and the higher
is the n/i ratio. At p(C0) = 0.25 and 9 MPa, n/i was found to be 1.6 and 4.4,
respectively. This gives a good idea of the reaction responsible for determining
the n/i ratio at a molecular level. For a kinetic approach, see Section 2.1.1.3.2.

Phosphine-Modified 0 x 0 Catalysts

The hydroformylation mechanism for phosphine-modified rhodium catalysts fol-

lows with minor modifications the Heck-Breslow cycle. HRh(CO)(TPP), [ 111 is
believed to be the precursor of the active hydroformylation species. First synthe-
sized by Vaska in 1963 [98] and structurally characterized in the same year [99],
Wilkinson introduced this phosphine-stabilized rhodium catalyst to hydroformyla-
tion five years later [loo]. As one of life's ironies, Vaska even compared
HRh(CO)(TPP), in detail with HCO(CO)~ as an example of structurally related hy-
drido complexes [98]. Unfortunately he did not draw the conclusion that the rho-
dium complex should be used in the 0x0 reaction. According to Wilkinson, two
possible pathways are imaginable: the associative and the dissociative mechan-
isms. Preceding the catalytic cycle are several equilibria which generate the key
intermediate HRh(CO),(TPP), (Scheme 4; L = ligand).
Starting with HRh(CO),(TPP),, the associative mechanism is initiated by
the coordination of an olefin to form a sixfold-coordinated species which
 2.1.1.3 Kinetics, Mechanism, and Process Parameters 49

HRh(CO)L3

+ L 11-L

+ co -L
HRh(CO)L* & HRh(C0)ZLz HRh(C0)zL
- co +L

branched products

Scheme 4. Initial equilibria forming the active catalyst species; L = TPP.

H2 1
+ co

Scheme 5. The hydroformylation cycle for modified rhodium catalysts:

(1) dissociative and ( 2 ) associative mechanisms.

is converted in a fast irreversible reaction to the alkylrhodium complex

RRh(CO),(TPP), (1 8e), the latter being an intermediate derived through the
dissociative pathway as well (Scheme 5).
The dissociative pathway is initiated by dissociation of a carbon monoxide li-
gand from HRh(CO),(TPP), to give HRh(CO)(TPP),. Olefin coordination,
50 2.1 Carbon Monoxide and Synthesis Gas Chemistry

formation of the alkyl complex and coordination of a carbon monoxide ligand

generates the alkylrhodium complex RRh(C0)2(TPP)2. For both mechanisms
the subsequent steps are the same: CO insertion to form the acyl complex
RC(O)Rh(CO)(TPP),, and oxidative addition of hydrogen, which is generally be-
lieved to be the rate-determining step in the hydroformy lation reaction. Reductive
elimination to form the aldehyde followed by coordination of an additional CO
ligand regenerates the protagonist of the catalytic cycle, HRh(CO),(TPP),.
Today, the dissociative mechanism is considered to be the major pathway, espe-
cially under industrial operating conditions. The associative mechanism is pre-
ferred at very high concentrations of catalyst and phosphine. The number of car-
bon monoxide and phosphine ligands present in the intermediates has not been
completely clarified. Dissociation of a phosphine ligand instead of CO at the be-
ginning of the hydroformylation cycle might be correct as well, especially at high
p(C0) and low ligand concentrations. The species HRh(CO),(TPP) then gener-
ated, which is less sterically hindered, would be responsible for the formation
of the branched aldehyde (see Scheme 4).
The d i selectivity of modified 0x0 catalysts increases with lower partial pres-
sure of carbon monoxide and with high concentration of ligand. The effect of tem-
perature is less pronounced. Under such conditions the predominant catalyst spe-
cies is coordinated by more than one phosphine ligand. The metal center presents
a more sterically hindered environment to the olefin and the formation of linear
alkyl and acyl species is favored. Table 1 summarizes experimental evidence
for these effects [8].
According to the mechanism described above, phosphine-modified cobalt cat-
alysts CO,(CO),(L>~behave in the same way. It is generally accepted that the se-
lective anti-Markovnikov addition of the hydridocobalt carbonyl to the olefin
forced by steric hindrance determines the n/i ratio.

Table 1. Product distribution from the hydroformylation of I-hexene"' [8].

Excess PPh3 [moll HJCO ratio Temperature ["C] n/i ratio
1 .o 25 86:14
1.o 40 88: 12
1.o 2s 92:s
1.o 40 93:7
1.2s 25 91:9
1.25 40 95:5h'
2.0 40 97:3"
2.0 40 98.5: 1.Sd'
a' 30 mM HRh(CO)(TPP),, benzene, [1-hexene] = 1.0 m o l k , 0.1 MPa H2/C0.
h, 22 5%
hydrogenation and isomerization products.
dl 31 5%
 2.1.1.3 Kinetics, Mechanism, and Process Parameters 51

A comparative study of HRh(CO)(TPP), with commercially applied 0x0

catalysts was performed by Horvith [ 1011. The water-soluble catalyst
HRh(CO)(TPPTS), is considered to react according to the dissociative mechanism
depicted in Scheme 5. However, remarkable differences exist between the catalytic
activity and the selectivity of the organic catalyst and the water-soluble one. The
latter shows much lower activity but an increased selectivity to linear products in
the hydroformylation of propene. From an Arrhenius plot it is concluded that the
dissociation energy of TPPTS from HRh(CO)(TPPTS), is about 30 1 kcal/mol *
(126 k 4 kJ/mol). This energy is about 10 kcaVmo1 (42 kJ/mol) higher than that
necessary for dissociation of TPP from HRh(C0) (TPP)3 (19 k 1 kcaVmol (80
kJ/mol) [ 1021. The lower catalytic activity, under comparable conditions, of a
water-soluble rhodium catalyst might be due to this higher dissociation energy.
Tn contrast to its organic-soluble derivative, HRh(CO)(TPPTS), does not take
up a second molecule CO to form HRh(CO),(TPPTS),, even at syngas pressures
of 20 MPa. As has been shown, the latter compound generates by dissociation of
either carbon monoxide or TPPTS the unsaturated species HRh(CO)(TPPTS),
or HRh(CO),(TPPTS), which is responsible for the formation of linear
and branched aldehydes (Scheme 4). As HRh(CO)(TPPTS), is formed by
TPPTS dissociation from the starting compound HRh(CO)(TPPTS),, and
HRh(CO),(TPPTS) is only obtained by an equilibrium reaction from
HRh(CO),(TPPTS),, the observed increased d i selectivity for water-soluble
rhodium 0x0 catalysts becomes comprehensible.

2.1.1.3.2 Kinetics of Hydroformylation

Extensive studies have appeared in the hydroformylation literature dealing with
catalysts, ligands, substrates, and product distributions, but only a few reports
on kinetic aspects and their consequences in reaction engineering have been pub-
lished. Some knowledge has been gathered about macrokinetic influences, e.g.,
temperature, pressure, synthesis gas composition, and catalyst concentration, pre-
dominantly in the field of propene hydroformylation. Quite little information is
available on rnicrokinetics, and conclusions about the rate- determining step
have been deduced mainly from spectroscopic observations.
Table 2 shows some examples of parameters determined for triphenylphos-
phine-modified and unmodified rhodium and cobalt catalysts in the hydroformy-
lation of terminal olefins. The general reaction rate equation (eq. (6)) is used:
r = k x [substrate]" x [ c a t a l y ~ t x
] ~[p(CO)p x [p(H2)1y x [ligandp (6)

Unmodified 0 x 0 Catalysts

For the high-pressure 0x0 catalysts CO,(CO)~and Rh,(CO) the equation derived
by Natta and Ercoli is generally accepted (eq. (7)) [103, 1041:
b(H2)I
r = k x [substrate] x [catalyst] x - (7)
b(W1
52 2.1 Carbon Monoxide and Synthesis Gas Chemistry

Table 2. Parameters of the hydroformylation kinetics of terminal olefins.

V W X Y Z Ref.
C02(C0)8 1 1 -1 1 0 ~031
Cop(CO)gL2a) 1 1 Negative Positive -0 [lo51
RhdCO) 12 1 1 -1 1 0 [ 1041
HRh(C0)L:' 0.6 1 -0.1 0.05 -0.7 [lo91
HRh(CO)L3b' 1 1.2 Negative 1.5 0 [I111
L = P(n-C4H9)3.h'L = P(ChH5)3.

The rate of reaction is positively influenced by increases in the concentration of

catalyst, olefin and hydrogen, whereas carbon monoxide exerts a negative effect.
In contrast to eq. (7), at low partial pressures (p(CO)<l MPa) an increasing con-
centration of carbon monoxide enhances the overall reaction rate. This reflects the
necessity for carbon monoxide to generate hydridocobalt carbonyls, namely the
16e species HCO(CO)~.At higher CO partial pressures, the less reactive
HCO(CO)~is formed, therefore explaining the negative order of reaction at
p(CO)> 1 MPa. Unmodified rhodium catalysts behave the same way, the critical
p(C0) for the latter being slightly higher (= 3 MPa).
Under high-pressure conditions the solubilities of hydrogen and carbon monox-
ide in the reaction mixture are sufficiently high to lead to catalyst concentration
and temperature being dominating variables. The influence of the syngas pressure
on the reaction rate is zero for a broad pressure range, as the effects of hydrogen
and carbon monoxide partial pressures are relatively equal, but opposite. For low-
pressure operation the solubilities or concentrations of the gaseous participants in
the reaction medium have to be taken into account. In common organic solvents
the solubilities for hydrogen and carbon monoxide are in the range of (2-10) X
mol/L . bar (in toluene: H2 = 3.1 X and CO = 10.5 X molL bar
[ 106a]), whereas the aldehyde productivity of a catalyst solution may easily
exceed 2-3 mol/L . h. The large gap between the solubilities of gaseous reactants
and their conversion rates implies the influence of transportation phenomena on
the measured overall reaction rate which contribute to the difficulties in precisely
determining even macrokinetics. Therefore, rate expressions have frequently been
derived under restricted conditions, e.g., for temperature, pressure, and con-
version.
Detailed studies by Bourne on the hydroformylation of propene [lo61 in the
temperature range 110-150 "C and at syngas pressures of up to 10 MPa confirmed
partly the earlier results of Natta. Although they were not obtained under real
industrial (i.e. commercial) hydroformylation conditions (T = 150-1 80 "C,
p = 20-35 MPa), these data give insight into the major trends.
According to eq. (8), the rate of reaction was found to be linearly dependent on
the propene concentration and to be negative order with carbon monoxide partial
pressure at > 1 MPa. However, a fractional order was observed with respect to
 2.1.1.3 Kinetics, Mechanism, and Process Parameters 53

the catalyst concentration and the hydrogen partial pressure. The overall rate of
hydroformylation over the whole pressure range from 0 to 10 MPa was deter-
mined by a two-parameter rate model as

r = k x
x [p(CO)] x [~atalyst]'.~X [substrate]
[P(H~)]'.~
(1 + KB x [P(C0)B2

with k and KB as the rate parameters. Typical values for k and K B (T =

110-150°C) are 0.6-6.0 X ( r n , / m ~ l ) ~s-'. ~ and 7.2-9.2 X lo-, m3/mol,
respectively. The rate model of eq. (8) fits with the observed kinetic data (standard
deviation = 7 %). This is the most accurate rate expression so far obtainable for
hydroformylation of propene with unmodified cobalt catalysts in the given range
of reaction conditions. By analysis of the Arrhenius plot the activation energy was
determined to be 77 kJ/mol.
For higher olefins such as 1-hexene, solvents are necessary to perform the
hydroformylation reaction. The overall rate measured for aldehyde formation is
strongly dependent on the polarity of these solvents. Alcohols like methanol
and ethanol increase the rate up to tenfold compared with nonpolar solvents
such as n-hexane or toluene [107]. It was suggested that cationic and anionic
catalyst species such as [Co(S)(CO),]+ and [HCo,(CO),J are responsible for
this effect (S = solvent). However, this proposal is based on kinetic data only
and no spectroscopic evidence has been given.
The selectivity problem has hardly been treated by kinetic analysis. Recently
Bourne published a detailed kinetic selectivity study on the aldehyde formation
[106b]. The activation energy required for the formation of n- and isobutanal
was determined to be 54 and 82 kJ/mol, respectively. The reaction rate models
r, and cs0(eqs. (9) and (10)) explained the observed n/i ratios at different reaction
conditions within 8 % standard deviation from the experimental results.
[p(Hz)Io56 x [p(CO)] x [ c a t a l y ~ t ]x~ . ~ ~
r,, = k,, (9)
(1 + Kns x IP(CO)D~

Typical values for k,, KnB,kisoand KisoB( T = 110-150°C) are (2.0-9.1) X

((m3/m~1)7.'7s-'), (8.0-6.7) x 10-~m3/moi, 2.1-29.0 x 1 0 - ~(m3/m~1)2.17 s-',
and (13.5-17.6) X m3/mol, respectively.

Ligand-Modified 0 x 0 Catalysts

For phosphine-modified rhodium catalysts, namely HRh(CO)(TPP),, the rate is

dependent on the different parameters, as follows:

(1) first order in catalyst concentration;

(2) first order in hydrogen partial pressure;
54 2.1 Carbon Monoxide and Synthesis Gas Chemistry

(3) at low olefin concentrations, positive order, and at high olefin concentrations,
negative order (substrate inhibition);
(4) at low CO partial pressure (p(C0) < 1 MPa), positive order, and at high CO
partial pressure, negative order;
( 5 ) at low ligand concentrations, positive order, and at high ligand concentrations’
zero order.

The influence of solvents on the rate of the hydroformylation reaction is signif-

icant. Polar solvents, e.g., alcohols, lead to higher rates than nonpolar solvents
such as toluene or hexane. It was observed that in the hydroformylation of l-oc-
tene with alcohols as solvents, the reaction rate passes through a maximum at a
TPP:catalyst (L/Rh) ratio of 4: 1 (catalyst = HRh(CO)(TPP),), drops at higher ra-
tios (4: 1 < L/Rh < 12: 1) and remains constant at L R h > 12: 1 [ 1081. With ben-
zene or toluene as solvents the reaction rate is highest without excess TPP, passes
through a minimum at ratios < 4 and is not influenced by high excesses of TPP.
The negative-order dependence of the reaction rate at higher carbon monoxide
pressure is mainly due to the formation of di- and tri-carbonyl acylrhodium com-
plexes RCORh(C0)2(TPP)2and RCORh(CO)3(TPP), which are unreactive toward
oxidative addition of hydrogen. At lower carbon monoxide partial pressures, the
formation of these species is expected to be negligible. A positive-order depen-
dence of the rate is observed as the monocarbonyl species RCORh- (CO)(TPP),
is stabilized. The mechanistic aspects were discussed in Section 2.1.1.3.1.
The most detailed and generally accepted kinetic study on triphenylphosphine-
modified rhodium catalysts was published in 1980 [109]. It was concluded from
the coefficients obtained (Table 2) that the fast alkene insertion is followed by the
rate-determining step involving CO or TPP [ 1101. The apparent activation energy
for propene hydroformylation was found to be 84 kJ/mol, very similar to the value
obtained for unmodified cobalt catalysts.
Recently, the activation energy for hydroformylation of 1-decene with
HRh(CO)(TPP), was determined to be 48 kJ/mol, which is significantly lower
[111]. A rate model was developed (eq. (11)) that was similar to Bourne’s two-
parameter eq. (8). The rates predicted by the model were found to agree within
6-8 % error with the experimental data. This time the oxidative addition of hydro-
gen was recognized as the rate-determining step. However, the model is not
generally applicable as the phosphine concentration was not considered and the
reaction temperatures were fairly low ( T = 50-70 “C).

[p(H2)J’ x [p(CO)] X [catalyst]‘ x [substrate]

r = k x (11)
(1 + K B x [p(C0)D3 x (1 + K D x [substrate])

In the hydroformylation of 1-hexene with the same catalyst, at high olefin con-
centrations (>0.5 mol/L) the reaction rates decrease with increasing substrate
concentration [ 1121. In this concentration range the reaction rate is negative
order in olefin concentration. The maximum of the reaction rates varies with
the polarity of the solvent [ 1131. This inhibiting effect was explained by formation
of an olefin complex of an alkylrhodium species, which is no longer part of the
 2.1.1.3 Kinetics, Mechanism, and Process Parameters 55

ongoing catalytic cycle. The extent to which this species is formed is dependent
on the solvent structure.
The kinetics of the new commercial process of hydroformylation of allyl
alcohol was studied by Chaudhari in the temperature range from 60 to 80°C
[114]. The rate of reaction is first order in catalyst concentration and 1.5th
order in hydrogen partial pressure. The dependence on p(C0) does not differ
from that observed in the hydroformylation of nonfunctionalized olefins. The
reaction is retarded at higher substrate concentrations (> 1.25 mom). This
substrate inhibition is not fully understood on the molecular level. The appar-
ent activation energy for the 0x0 reaction of allyl alcohol was found to be
94 kJ/mol.
Only limited data are available for the kinetics of 0x0 synthesis with the water-
soluble catalyst HRh(CO)(TPPTS),. The hydroformylation of 1-octene was
studied in a two-phase system in presence of ethanol as a co-solvent to enhance
the solubility of the olefin in the aqueous phase [115]. A rate expression was
developed which was nearly identical to that of the homogeneous system, the
exception being a slight correction for low hydrogen partial pressures. The lack
of data is obvious and surprising at this time, when the Ruhrchemie/ RhBne-Pou-
lenc process has been in operation for more than ten years [116]. Other kinetic
studies on rhodium-catalyzed hydroformylation have been published, too. They
involve rhodium catalysts such as [Rh(nbd)C1I2 (nbd = norbornadiene) [ 1171 or
[R~(SBU')(CO)P(OM~),]~ [ 1181, or phosphites as ligands [ 119, 1201.

2.1.1.3.3 Process Parameters

With respect to conversion, selectivity, and operation, the 0x0 synthesis is
influenced by a plethora of parameters. By fine-tuning of the operation conditions,
a broad band of product compositions is achievable. In accordance with the
mechanistic discussion and the kinetics of the hydroformylation reaction, these
issues will be treated separately for unmodified and modified catalysts. For oper-
ating processes and their reaction parameters, see Section 2.1.1.4.

Unmodified 0 x 0 Catalysts

Temperature

As for most homogeneously catalyzed reactions, the initial rate of the 0x0
synthesis increases with higher temperatures. For a normalized reaction rate at
140°C (rI4,, = 1.00) the rate at 90°C is only about 1 % of ~ 1 4 0(rg0 = 0.01)
[ 1211. With higher temperatures the n/i ratio decreases for almost all olefins.
This tendency is inverse for a-olefins bearing a functional group which is
directing the regioselectivity toward linear products. For instance, for methyl
methacrylate the di ratio at 100°C (= 1:2) is increased to 6 : l at 150°C [122].
The formation of by-products generally increases with reaction temperatures.
56 2.1 Carbon Monoxide and Synthesis Gus Chemistry

Among side-reactions, isomerization of the starting olefin, hydrogenation of the

substrate, formation of alcohols by hydrogenation of aldehydes, and condensation
reactions of the aldol type (formation of “heavy ends”), are the most important.

Pressure

According to Natta’s law (eq. (7)) the overall reaction rate is independent of the
total pressure as long as the ratio of p(C0) to p(H2) is 1: 1 and a minimum
carbon monoxide pressure is maintained to stabilize the metal carbonyl species.
The influence of the partial pressure of carbon monoxide is depicted in Figure
5 (cf. p. 58). Low p(C0) initially increases the reaction rate whereas at higher
partial pressures the rate drops (cf. Section 2.1.1.3.2) [96e, 1231. Raising the
hydrogen partial pressure increases the reaction velocity [124] and to some
extent the d i ratio [125]. The latter effect is much less pronounced than for
p(C0). Above a p(H,) of 60-80 bar almost no improvement in the n/i ratio is
observed.
High di.ratios together with considerable reaction rates are therefore obtainable
at high total pressures [126], where the rate-retarding effect of p(C0) is compen-
sated by p(H,) and the n/i ratio is determined by p ( C 0 ) alone. As a role of thumb,
for industrial, Co based 0x0 processes the n-isomer increases by 0.5 kg/100 kg
propene per 1 MPa pressure rise (C0/H2 = 1: 1, P,,, = 30-35 MPa) [4]. At higher
total pressures (>40 MPa) the n/i ratio drops again [126]. The reasons are not
completely clear. Polynuclear species that show different n/i characteristics are
discussed in [127]. These high pressures have never been applied in commercial
processes.
The formation of hydrogenation by-products such as alcohols and hydro-
carbons is favored at low p(C0). Extensive hydrogenation was often the aim of
special cobalt process variants, in order to produce alcohols in one step - for
instance, butanols. Especially for short-chain olefins, this technique has been
replaced by two-step processes: rhodium 0x0 synthesis along with a separate
hydrogenation step.

Catalyst Concentration

Conversion and formation of by-products are controlled by the catalyst concen-

tration. Besides temperature and residence time, the catalyst feed is the third para-
meter to influence the conversion in 0x0 processes with unmodified catalysts.
According to Natta’s rate expression (eq. (7)), high conversions are achieved at
high catalyst feed [128]. Under industrial conditions the n/i ratio is only slightly
affected by the catalyst concentration [ 12, 1291. However, contradictory results
[121], even recent ones [106b], have been reported. The controversy may well
be a result of the various experimental designs applied. Phase-transfer limitations
and transport phenomena are often not taken into account. For a kinetic discus-
sion, see Section 2.1.1.3.2 [106b].
 2.1.1.3 Kinetics, Mechanism, and Process Parameters 57

Modified Catalysts

Temperature

Compared with cobalt carbonyl, the phosphine-modified cobalt catalyst intro-

duced by Shell in 1966 leads to an increase of selectivity toward linear products,
to an increase in the thermal stability and hydrogenation activity, but also to a
lower reactivity. In order to compensate for the lower activity, reaction tempera-
tures have to be kept at about 180 "C. With higher temperatures the n/i selectivity
drops [ 1301 as less coordinated cobalt species are involved in the catalytic cycle.
The reduced steric demand around the metal center leads to increased formation of
branched aldehydes. With respect to formation of by-products, modified cobalt
catalysts behave similarly to their unmodified derivatives.
The decrease of the n/i ratio at higher temperatures is even more pronounced
with modified rhodium catalysts. Modem rhodium 0x0 plants are operating at
temperatures of 120 "C to maintain a high n/i ratio (Section 2.1.1.4). The reactivity
at these temperatures is lower compared with unmodified rhodium carbonyl cat-
alysts, but still high enough to bring about the reaction at considerable rates.

Pressure

For ligand-modified catalysts (M = Rh, Co), the following general equilibrium is

formulated (eq. (12):

HM(CO), + yPR3 HM(CO),-,(PR3), + yC0 (12)

At low p(CO), equilibrium (12) is shifted to the righthand side. By coordination of

ligands the metal center becomes sterically more congested. Accordingly, the for-
mation of unbranched products is favored. With increasing p(C0) the n/i ratio
diminishes constantly. Only at higher partial pressures (p(C0) > 1.5 MPa) is
the catalytic cycle dominated by the HM(C0)4 species, thus favoring linear
products again. In Figure 5 data obtained by Piacenti for CO~(CO)~(PBU&
(Bu = n-C,H,) are summarized as an example [131]. At low p(C0) the hydro-
genation activity of phosphine-modified catalysts becomes pronounced, setting
a lower limit for a practicable p(C0) [132]. Rates and hydrogenation activity
increase with increasing partial pressures of hydrogen.

Catalyst Concentration

For modified catalysts, a general rule for the influence of the catalyst concen-
tration on the selectivity has not yet been found. In case of HCO(CO)~PBU~,
results reported by Rupilius [ 1331 and Tucci [ 1341 are ambiguous. Both authors
found increasing conversion of olefin and formaton of butanols if the catalyst con-
centration is raised. Tucci, however, found no influence on the n/i ratio, whereas
58 2.1 Carbon Monoxide and Synthesis Gas Chemistry

Figure 5. The portion of n-aldehydes [di ratio (% nl% (n + iso))] vs. carbon monoxide
partial pressure [ 1311; 150 bar = 15 MPa.

Rupilius saw improved generation of linear products by increasing the cata-

lyst concentration from 1 g catalyst per mol olefin to 20 g catalyst per mol
olefin. Wilkinson has shown that for hydroformylation of 1-hexene with
HRh(CO)(PPh,), the d i ratio is increasing in the concentration region from 5 to
50 mmol [lOOc]. The lower selectivity observed at lower catalyst concentrations is
attributed to a further dissociation of HRh(CO),(TPP), to HRh(CO),(TPP). The
loss of phosphine leads to increased formation of the branched product. As can
be deduced from Table 2, the rate and conversion of the 0x0 reaction is improved
by increasing the amount of catalyst. The effect ist not linear over the whole
range of catalyst concentration, but more pronounced at low concentrations
(<6.0 mmol) [lOOc].

Ligands

As mentioned above, most published papers and patent applications deal with li-
gands and their influence on activity and selectivity in the 0x0 synthesis. When
alkylphosphine-modified cobalt catalysts were introduced by Shell [ 1351, high
di selectivities were reported. However, coordination of phosphine ligands
makes the metal-hydrogen bond more hydridic, therefore leading to substantial
formation of hydrogenation products. Hydroformylation of 1-pentene yielded hex-
anol with 91 % linearity.
In general the n/i ratio of modified 0x0 catalysts increases with increasing
ligand/metal ratio. Coordination of ligands to the metal center enhances the steric
bulkiness and linear products are favored. Depending on the structure of the
ligand this effect is more or less pronounced. Hydrogenation and isomerization
reactions are suppressed by an excess of phosphine ligand.
 2.1.1.3 Kinetics. Mechanism, and Process Parameters 59

Ratio TPP/HRh(CO)(TPP), Ratio TPP/HRh(CO)(TPP)3

Figure 6. Dependence of the reaction rate (g (C4H80)/min) (left) and portion

of n-aldehydes (right) on the phosphinehhodium ratio [ 1381.

At constant ligand/metal ratios, closely related phosphines show lower n/i ratios
when their bulkiness is increased. For instance P(i-C3H7)3 showed 85 % linear
product in the cobalt-catalyzed hydroformylation of 1-hexene whereas with
P(n-C3H7), 89,5 % was achieved [136]. This trend, which ist surprising at first
sight, is due to formation of unsaturated HM(CO)*L species (M = Co, Rh;
L = ligand) in cases where the bulky group on the ligand is positioned close to
the metal center. The steric demand of the ligand favors formation of dicarbonyl
species which generate the branched products. This correlation is only reliable if
the ligands being compared have similar electronic structures. The electronic
structure of ligands influences the selectivity as well. Although TPP is much bulk-
ier than P(n--C4H9),, n/i selectivities of 62,4 % and 89,6 %, respectively, have been
reported in the literature [136]. It is accepted as a rule of thumb that more basic
ligands give higher n/i selectivities. However, no general law has been found
and so far “no detailed understanding of how phosphine or phosphite control
the regiochemistry has emerged” [ 1371.
As far as rates are concerned, the catalytic activity varies in a nonlinear fashion
as a function of phosphine concentration. In Figure 6 the dependence of rate and
selectivity for hydroformylation of propene with HRh(CO)(TPP), on the TPP con-
centration is depicted [138]. The selectivity of the reaction remains constant above
an L/Rh ratio of 5 : 1, at a point where the activity reaches a maximum. Further
increase in ligand concentration leads to lower rates.
Tucci reported a linear correlation of the pK, of monodentate phosphines
and the rate of reaction [136]. The more basic the phosphines (the higher the
pK,) the less active they are. Due to their strong coordination to the metal, they
literally “block” the center. Lower rates are the result. With the less basic TPP
(pK, = 2.73) rates were almost two orders of magnitude higher than with the
trialkylphosphine PEt, (pK, = 8.69). A similar trend was observed with a variety
of modified TPP ligands P Q P C ~ H ~ XThe ) ~ . electron-withdrawing group X = CF3
60 2.1 Carbon Monoxide and Synthesis Gas Chemistry

increased the rate observed in the rhodium-catalyzed hydroformy lation of 1-hex-

ene about two orders of magnitude compared with X = NMe2 [139].
At low ligand concentrations triphenyl phosphite (P(OPh),) shows similar
results to TPP. Only at higher concentration does the phosphite tend to retard
the reaction. As phosphites are fairly basic and have high x values, they
give high n/i ratios along with considerable isomerization rates. Their high
reactivity toward otherwise unreactive olefins has been discussed (see Section
2.1.1.2.1).

2.1.1.3.4 Deactivation of Rhodium-Phosphine Catalysts

One important field in industrial hydroformylation research is the deactivation of
the commercially used rhodium-phosphine catalysts. It is generally accepted now
that the loss of activity with time is due to the degradation of the phosphine ligand.
The consequences are twofold. Phosphido-bridged rhodium carbonyl clusters are
formed which are inactive in the hydroformylation [140], and a strongly donating
phosphine is generated, acting as a catalyst poison. The tendency toward deacti-
vation is more pronounced with triphenylphosphine substituted with electron-do-
nating groups such as p-CH30 or p-NMe2 [ 1411 or with TPPTS [I 191. The deac-
tivation mechanism is initiated by the oxidative insertion of the rhodium metal
into the P-C bond of the triphenylphosphine ligand (Scheme 6). It has been
clearly shown by Bryant, Garrou, and Chaudhari [ 1421 that the equally discussed
ortho-metallation plays no role. Most of the phosphorus-containing by-products
formed under continuous-operation modes are explicable by subsequent reactions
of the arylrhodium species 12. This compound is presumably a phosphido-bridged
dimer which is inactive in hydroformylation. Consecutive reaction products of 12
such as C3H7PPh2and phosphinous acid (Ph,P(O)H) have been identified. The al-
kyldiphenylphosphine C3H7PPh2coordinates to the rhodium center, keeping it

Q Q
Lx(CO)RhLPPh2 - L,(CO)Rh“LPPh2
12

T O ” ’ ” ”
L,(CO)Rh‘lLPAr2
11
-- QCHO
SOl”

Scheme 6. Deactivation of phosphine-modified rhodium catalysts in the UCC process (above)

and the RCWRP process (below). Ortho-metallation can be excluded for both
processes.
 2. I.1.4 Commercial Applications 61

from participating in the catalytic cycle. A drop in the catalytic activity is the con-
sequence.
Confirmation of this mechanism was found in the RuhrchemieRhBne-Poulenc
process, where the position of the sulfonato group is an outstanding probe for oxi-
dative addition vs. ortho-metallation. The formation of the sodium salt of m-for-
mylbenzenesulfonic acid, m-OHCC6H4S03Na,indicates that the rhodium atom is
attached temporarily to the carbon atom, where the phosphorus atom was bonded
before. CO insertion and reductive elimination generate the formylated benzene-
sulfonic acid from 11. Similarly to the homogeneous process, the alkyldiarylphos-
phine Ar2PC3H7(Ar = m-C6H4S03Na)was isolated, characterized, and identified
as a catalyst poison [38a].

2.1.1.4 Commercial Applications

2.1.1.4.1 Economic Aspects

Over recent years a steady and continuous growth in production capacity of
aldehydes by the hydroformylation reaction has taken place. Table 3 shows the
estimated capacities for aldehydes generated by hydroformylation of ethylene,
propene, and higher olefins, along with their regional distribution [ 1431.
Accounting for a share of about 73 % of total production capacity, C4 products
have firmly established their leading position in this field. Ethylene hydroformy-
lation to propanal amounts to 2-3% of the hydroformylation capacity for C4
products and is only of minor importance. The hydroformylation of olefins of
medium chain length, predominantly in the C8/C9 range (diisobutene, propene
trimer), makes up around 20% of the total production capacity. Only about 6 %
of the total production capacity is used to hydroformylate higher olefins.

Table 3. Production capacities of aldehydes by hydroformylation."'

Capacity [lo00 t]
Region c
3 Cqb' c5-c13 >c,, ,z 2-EH"'
~

Europe (West) 25 1600 535 85 2245 870

Europe (East) 785 785 450
North America 75 970 450 270 1765 300
Latin America 120 55 175 150
Far East (incl. Australia) 1040 140 30 1210 650
___ ~ - ~

Total 100 4515 1180 385 6 180d' 2420''

[%I 2 73 19 6 100
Estimate for 1993. bJ Including isobutanal. 2-EH = 2-ethylhexanol.
dl Estimate for 1998: 9180 [293]. Estimate for 1998: 3185 [293].
62 2.1 Carbon Monoxide and Synthesis Gas Chemistry

Table 4. Capacities for 2-EH by various processes."'

Process Capacity [ 1000 t] Share [%I
ucc 480 24
BASF 335 17
Mitsubishi Kasei 235 12
Huls 230 11
Hoechst AG 210 10
Oxochimie 130 6
Neste Oy 120 6
Kyowa Yuka 100 5
Texas Eastman 100 5
Shell 50 2
Chisso 50 2
Subtotal 2040 100
Unknown 380
-
Total 2420b'
a) Estimate for 1993. Estimate for 1998: 3185 [293].

The most recent data are given in [293].

Table 3 further outlines the estimated capacities for 2-ethylhexanol (2-EH) pro-
duction. In total, about 60% of the C4 capacity (or about 70% of the n-butanal
capacity) is required to produce 2-EH. However, regional deviations in C4/2-EH
capacities are obvious, indicating that n-butanal is to be considered a commodity
with worldwide availability. Bearing in mind that 2-EH and the C9/Cl0alcohols
are nearly quantitatively absorbed in plasticizer production, the enormous signifi-
cance of hydroformylation for the polymer industry, especially for PVC, is under-
lined. In contrast to repeatedly published predictions, a decrease in the application
of 2-EH as plasticizer alcohol has not been observed to date.
A variety of processes has been developed for the conversion of n-butanal into
2-EH, which in general comprise the stages aldolization, predominantly two-step
hydrogenation, and subsequent distillation to final product quality. As the condi-
tions for each step may vary widely, the different modes for operation and their
combination, including the internal recycling of product streams, have led to a
number of solutions which may be considered approximately equivalent with
respect to product and energy usage. The yield of 2-EH covers the range from
92-9676, based on n-butanal feed. Table 4 lists the production capacities for
2-EH by different processes. The production capacities for n-butanal, which are
based on rhodium or cobalt catalysts, are outlined in Table 5.
 2.1.1.4 Commercial Applications 63

Rhodium-based processes dominate in the hydroformylation of propene. On the

other hand, the production capacity of cobalt-based processes has remained at a
virtually constant level in the C4 field for years (Figure 7).
Several explanations may be taken into account for only a small decrease in im-
portance: an existing high-pressure infrastructure which is also used for the hydro-
formylation of olefins higher than propene, where cobalt-based processes are ad-
vantageous; a combined cobalt recovery and recycle system for the hydroformy-
lation of different olefins; and the use of tail gases from low-pressure hydroformy-
lation units.
The completely reverse situation is encountered in the field of hydroformyla-
tion of olefins other than propene (Table 6): cobalt dominates rhodium by far,
the 9: 1 ratio being in favor of cobalt. One reason is the low reactivity of rhodium
in the case of branched olefins with partially internal carbon double bonds; the
high boiling points of the product aldehydes is the second, as too much thermal
strain is imposed on the catalyst during product separation by distillation.
Looking at the hydroformylation of propene, the technology of the cobalt- cat-
alyzed processes has remained basically unchanged over the years, whereas the
introduction of rhodium as catalyst has founded a new generation of hydroformy-
lation processes.
The rapid ascent of rhodium-based low-pressure 0x0 processes (LPO pro-
cesses) was favored by a number of frequently cited advantages: mild reaction

Table 5. Capacities for C4 products by various processes (excluding 2-EH).”’

Process Catalyst Capacity [lo00 t] Share”’ [%]
ucc Rh 2000 I 3040b’ 45
BASF Rh 600 I 900’’ 13
Leunaeftechim co 400 /425b’ 9
Mitsubishi Kasei Rh 300 I 680” I
Hoechst AG Rh $3001- I
BASF co 2001- 5
Shell co 175/75b’ 4
Hoechst-Celanese Rh 160I 890b’ 4
Texas Eastman Rh 1301610” 2
Hoechst AG co 1101- 2
Mitsubishi Kasei co 801- 2
~

Subtotal 4455 I 6620b’ 100

Unknown 60 I 230b’
Total 451516850’)
~~

a) Estimate for 1993. b, Estimate for 1998 [293].

 64 2.1 Carbon Monoxide and Synthesis Gas Chemistry

Mio Ua

Total

I [
'
4 Rh-based ..

1
b
:/a
/sed ________-
-
O1978 1984 1988 1992 1996
Year

Figure 7. Development of C4 production capacities (estimated).

Table 6. Capacities for 0x0 products by various processes (excluding C, products

and 2-EHl")
Process Catalyst Capacity [lo00 t] Share [%I
Exxon co 850 50
Shell co 400 24
Nissan co 130 8
BASF co 100 6
UCC Rh 100 6
Hoechst-Celanese Rh 40 2
Mitsubishi Kasei Rh 30 2
BASF Rh 30 2
~

Total 1680b) 100

a) Estimate for 1993. b, Estimate for 1998: 1915 [293].

conditions; simpler and therefore cheaper equipment; high efficiency; high yield
of normal products; and easy recovery of the catalyst. However, an even more de-
cisive development was the rise in propene prices which started with the first oil
supply crisis in 1973 and led to a remarkable shift in the cost structure of butanal
manufacturing in the years that followed. The increase in the price of the raw ma-
terial was paralleled by an increase in the cost of energy. With respect to raw ma-
terial utilization and energy conservation, the LPO processes were more advanta-
geous than the cobalt technology (depending on the credit for is0 products), thus
leading to their rapid growth. Even the steep increase in the rhodium prices in the
years around 1991 (Figure 8) [147] could not seriously retard the propagation of
the LPO processes. The analysis of the cost structure for a number of production
 2.1.1.4 Commercial Applications 65

7000

6000

5000

4000

3000

2000

1000

n
"
1988 1989 1990 1991 1992 1993 1994

Figure 8. Development of rhodium prices.

Table 7. Cost structure of n-butanal Droduction Drocesses 11451.

Item Share [%I
Raw materials
- Propene 59
- Syngas 17
- Catalystkhemicals 2
Utilities 4
By-products/waste (credit) -10
Fixed costs 9
Capital costs 19
Product value 100

processes for n-butanal leads to the breakdown (average figures), given in Table 7
[145, 2931.
About 76% of the product value is contributed by the costs for propene and
synthesis gas, another 19% results from capital costs. Along with the propene
price (which may be influenced by choice of the site), the generation and
purification of synthesis gas, determined by raw material and process, exhibits
a pronounced influence on the economy of a process. Credits for by-products
result from the sales of isobutanal and from the combustion of propane and
high-boiling substances. The catalyst costs account for only 1-2 % of the product
value, thus being very low. The cost structure shown points out that marginal gain
is attainable only by process improvements, because of the high share of the raw-
66 2.1 Carbon Monoxide and Synthesis Gas Chemist0

material costs. Thus the major primary and consecutive products of hydroformy-
lation are to be classified as commodity chemicals.

2.1.1.4.2 General Remarks

The hydroformylation reaction comprises at least two gaseous reactants, carbon
monoxide and hydrogen; in the case of C2-C4 olefins, even the third reactant
may be, at least partially, in the gaseous state (T,~,(propene)= 91.9 “C). The cat-
alyst, on the other hand, is always dissolved in a liquid (with very few exceptions
reported in the literature but unproven in technical application [267]). In this
respect the overall hydroformylation reaction must be considered as a “not only
homogeneous” reaction as always two (or sometimes three) phases are involved,
leading to the well-known thinking about mass transfer from a gaseous to a liquid
phase.
The catalyst is commonly dissolved in an organic medium, the origin and na-
ture of which may vary widely. In the high-pressure processes at early stages of
development, the reaction medium consisted of the reaction products themselves,
a mode of operation which is rather convenient in a continuous technical process,
because the application of an additional solvent complicates the subsequent steps
of product and catalyst recovery. In discontinuous operation, suitable for special
and high-value products only, an inert solvent such as toluene or an alkane may
be useful, especially for the start-up phase where no aldehyde product is present.
An inert solvent is also applied in low-pressure hydroformy lation processes with a
stationary catalyst phase, consisting either of e. g. high-boiling saturated hydrocar-
bons from an external source or, more advantageously, of so-called higher conden-
sation products of the aldehydes generated in the process [5, 1461.
These condensation products are principally unwanted by-products of e. g. the
propene hydroformylation, formed by a number of different reactions (dimeriza-
tion, oligomerization, aldol addition, (Cannizzaro dismutation, esterification, de-
hydration, cyclization, etc.; for details cf. [4]). The average molecular weight of
the resulting compounds is always higher than that of the aldehyde monomer;
thus they are classified as high-boiling substances in the product recovery by
distillation as part of, in the process itself or in the downstream operation. The
use of such a more or less undefined mixture of compounds as the solvent for
the catalyst and the surplus of ligand is, on first sight, quite appropriate, as
these compounds are formed anyway and therefore are readily available. In prac-
tice this very fact contains the problem: because of the steadily increasing amount
of high-boiling substances, their level has to be kept below a maximum by inter-
mittently or continuously separating catalyst and ligand from the high-boilers in
an additional process step.
When water is used as solvent for catalyst and ligand, as in the RCHRP
process (see below), the two-phase system is extended to a three-phase system
consisting of two immiscible liquid phases and a gas phase. Surprisingly, the
expectedly complicated system produced an elegant solution of the problem
cited above: the presence of a third phase had by no means a detrimental effect
 2.1.1.4 Commercial Applications 67

and the separation of catalyst solution and reaction products, including high-boil-
ing by-products, is achieved most simply and efficiently.
The required mass transfer from the gas phase through the phase boundary into
the liquid catalyst solution necessitates intimate contact between the phases.
However, in practice the mass transfer into the liquid phase has not turned out
to be the limiting step for the achievable space-time-yield for a given process.
As a consequence, sparging the synthesis gas into the catalyst solution, backed
up by some additional mechanical mixing has mostly proved to be sufficient
for LPO processes. Therefore the engineering of hydroformy lation reactors in
this case extends to continuous stirred-tank reactor principles, the application of
which is well understood. In high-pressure operation, e.g., in the range from
25-30 MPa, mechanical stirring cannot be performed satisfactorily. Therefore
reactor designs with internal or external loops have been developed, the circu-
lation being achieved by the combined effects of flowing reactants and tempera-
ture gradients (Figure 11). In the case of a homogeneous organic phase several
appropriate solutions have been found, but problems may emerge if aqueous
catalyst solutions are fed to a reactor with an internal loop, e. g., in the BASF pro-
cess. Nevertheless, the overall characteristics of common high-pressure reactors
also correspond to the stirred-tank reactor principles with complete backmixing.
In none of the technically applied processes complete conversion of the reac-
tants is achieved in a single pass. The conversion of propene, for example, can
be as low as 25-30% per pass (LPO gas recycle process) or amount to more
than 95 % (cobalt high-pressure process) as a consequence of several process vari-
ables (temperature, pressure, catalyst, reactant concentration, and residence time
of reactants). Consequently, in every case an unconverted portion remains
which, after separation from the product, has to be recycled (or partially vented
to avoid accumulation of inerts) or used in a second stage. For LPO processes
with limited olefin conversion, especially, several solutions have been proposed
for arranging single reactors in series as a cascade [147].
The hydroformylation reaction is exothermic by about 28 kcal (1 18 kJ) per mol
of carbon double bond, as an average. For a low-molecular-weight olefin such as
propene about 667 kcal (2800 kJ) per kg converted has to be dissipated. The re-
moval of heat may become the critical point of a process, as the temperature
should be regulated within narrow limits by means of process control [148], cat-
alyst and ligand stability, and di ratio, all of which may be affected. Use of inter-
nal or external heat exchangers or cooling by evaporation of part of the products
in a gas stream are common practice. With respect to energy conservation, those
processes are advantageous which deliver the heat of reaction at a temperature
level which is suitable for generating steam which may then be utilized, e.g.,
for up-grading the products by distillation.
Liberation of heat by the hydroformylation reaction is the main reason why
several attempts aimed at gas-phase fixed-bed processes have not been brought
into technical reality: when an acceptable space-time-yield was achieved, the
formation of hot spots could not be suppressed, leading to rapid disintegration
of the active components of the catalysts and therefore to insufficient shelf life
[43, 1491.
68 2.1 Carbon Monoxide and Synthesis Gas Chemistry

Given the removal of heat, separation of products and catalyst may be the sec-
ond crucial point of a process. In general, two methods may be discerned. Ligand-
free cobalt or rhodium carbonyls in high-pressure processes are unstable at re-
duced pressure and have to be chemically converted to intermediates (metal,
oxide, hydroxide, soluble complexes), which can be separated from the reaction
products and recycled to conditions in which carbonyls are formed again to close
the cycle (cf. Figure 1 in Section 3.1.1). In low-pressure operations with rhodium
complexes and a surplus of ligands, all attempts are directed towards preservation
of the catalyst and avoiding any detrimental chemical reaction (cf. [4]).
By far the most elegant solution is the separation of two immiscible phases,
one comprising the products just generated and the other the catalyst-containing
phase, which may be aqueous. This phase separation procedure is attracting
increased interest because of is obvious advantages, and the search for suitable
liquid systems showing a miscibility gap has already brought some success
[150, 151, 264, 269, 2701. The separation of products and catalyst solution by
distilling off the aldehydes becomes troublesome with increasing molecular
weight, as even under reduced pressure the stability of the catalyst and the loss
of ligand (triphenylphosphine: b. p. 198 "C at 7 mbar) gain importance. For alde-
hydes beyond C7/C8this procedure becomes inadequate as an industrial process.
The ratio of hydrogen to carbon monoxide in the synthesis gas, as introduced
into the hydroformylation system, corresponds in most cases to the stoichiometric
demand of 1: 1 with only slight deviations in favor of the hydrogen moiety. How-
ever, all low-pressure hydroformylation processes make use of internal recycle, a
consequence of the incomplete conversion of the reactants in a single pass. The
slight surplus of hydrogen is multiplied by the recycle ratio, thus leading to a
greatly increased ratio of hydrogen to carbon monoxide which is offered to the
reaction medium. This ratio may vary widely, from > 1:1 (RCHRP process) to
> 10:l (BASF LPO process with gas recycle). In every case a gas mixture en-
riched in hydrogen is introduced into the catalyst solution. Three positive effects
are under discussion as consequences: enhancement of the reaction rate by in-
creased hydrogen partial pressure (see Section 2.1.1.3.2); a favorable influence
on the n/i ratio; and the increase in stability of the ligand as a consequence of
low carbon monoxide partial pressure.
Whereas unmodified cobalt carbonyl catalysts and to a certain extent aqueous
biphasic 0x0 systems as applied in the classical 0x0 synthesis, tolerate a certain
level of poisons (oxygen, sulfur, halides, metal compounds), ligand-modified rho-
dium catalysts, which are utilized at low concentrations, demand intensive purifi-
cation of syngas and olefin. Oxygen, hydrogen sulfide, carbon oxysulfide, halo-
gen compounds, and iron carbonyl have to be carefully removed from synthesis
gas to concentrations in the sub-ppm range to ensure the long-term stability of
Rh-TPP complexes [152]. In most cases a combination of absorptive (Rectisol,
ADIP, Benfield, Sulfinol, Selexol, ZnO) [ 1531 and adsorptive (active carbon, mo-
lecular sieve) steps is applied to achieve the necessary syngas purity. Alkynes and
conjugated dienes may affect ligand-modified rhodium catalysts by formation
of complexes, thus diminishing their activity, so only trace amounts of these com-
pounds should be present in the olefin feed.
 2.1.1.4 Commercial Applications 69

2.1.1.4.3 Cobalt-Based Processes

Cobalt catalysts have been the workhorses in industrially applied hydroformyla-
tion processes since the early 1950s, and even today they comprise an appreciable
share of the total amount of 0x0 products generated (Section 2.1.1.4.1). It will be
understood that the history of cobalt-catalyzed hydroformylation has seen a con-
siderable number of approaches aiming at convenient solutions for the accompa-
nying chemical and technical problems related to the reaction. This broad field has
been reviewed exhaustively [4].
The successful introduction of rhodium catalysts has shifted the application
of cobalt catalysts away from propene hydroformylation, with few exceptions,
but has also strenghthened their position in processing medium- to long-chain
olefins. The positive experiences gathered in the past have advantageously
been transferred to this sector. Thus the presently applied cobalt-based pro-
cesses have reached a high standard of performance. The most important dissim-
ilarities between different processes arise from the mode of separation of product
and catalyst together with the related catalyst recycle. From the processes
in operation three variants deserve attention (cf. [4] and Figure 1 in Section 3.1.1):

(1) Disintegration of HCo(CO), after hydroformylation by altering the oxidation

state of cobalt. This oxidation can be achieved by either hydrothermal treat-
ment (older Ruhrchemie process) or by oxygen treatment in acidic medium
(BASF process), followed by regeneration of HCo(CO),.
(2) Preservation of the once-formed Co(CO),- by extraction with aqueous caustic
and reformation of HCo(CO), by subsequent acidification (Kuhlmann or
Exxon process).
(3) Ligand modification and thus stabilization of cobalt carbonyl, product separa-
tion by distillation and recycling of the catalyst phase (Shell process).

The main features of these variants are outlined below.

BASF Process

The BASF technology of high-pressure cobalt-catalyzed hydroformylation of pro-

pene or higher olefins is characterized by: preforming HCo(CO), in a separate
step, decobalting by oxidation of Co- to Co2+,and recycle of the cobalt inventory
as aqueous solution (Figure 9) [154-1611. Purified syngas (1) and olefin are fed to
the reactor (3) together with HCo(CO), from the carbonyl generator (2). Off-gas
from the high-pressure separator (4) is recycled. The liquid product is decobalted
in vessel ( 5 ) by the addition of oxygen and some formic or acetic acid, leading to
an aqueous solution which contains the cobalt mainly as formate or acetate, re-
spectively. The crude 0x0 product is withdrawn in the phase separator (6). The
acidic aqueous cobalt solution is concentrated (7) and sent to the carbonyl genera-
tor (2), where cobalt losses are compensated and the aqueous catalyst solution is
formed [162].
70 2.1 Carbon Monoxide and Synthesis Gas Chemistry

Vent
A

H&O Waste water

1 - 2 *

Figure 9. Flow sheet of the BASF process.

The 0x0 reactor is designed as an internal-loop reactor equipped with an

immersed tube bundle cooling system. Specially constructed baffles are applied
to achieve thorough mixing of the olefin feed and the aqueous catalyst solution.
Due to the presence of carboxylic acids or their anions, the process suffered
initally from corrosion problems. An extraction step by which HCO(CO)~ is trans-
ferred into an organic medium (olefin or circulated high-boiling liquids) reduces
the danger of corrosion but complicates the catalyst recycling. A post-reaction
zone augments the conversion of the olefin [ 1631.
Some data, which may be considered typical for high-pressure cobalt operation,
are outlined in Table 8. Improved selectivity toward normal products is claimed
for low temperatures (1 20 "C) [ 1641.

Exxon Process

Designed and applied for the hydroformylation of olefins in the C6-C12range, the
Exxon process is representative of a cobalt catalyst recycling without a change in
the oxidation or coordination state of the catalyst metal. This is in contrast to the
processes in which the removal of the catalyst after hydroformylation is achieved
by oxidation with (for example) aidacetic acid (BASF process) or by thermal de-
gradation of the cobalt carbonyl (the older Ruhrchemie process). In the Exxon
process the so-called Kuhlmann (Produits Chimiques Ugine Kuhlmann, acquired
by Exxon) catalyst cycle technology is applied [165], involving two main process
 2.1.1.4 Commercial Applications 71

steps: the recovery of sodium cobalt carbonylate, and its regenerative conversion
into cobalt carbonyl hydride [ 166-1681. Obviously the older Kuhlmann technol-
ogy has been refined and extended in some points, especially to increase the safety
of operation, the yields of valuable products, and to reduce cobalt losses in the
catalyst recycle [169-1711. A flow scheme for the Exxon process is depicted in
Figure 10.

Table 8. BASF process: typical data [164].

Parameter Unit Range
Temperature t"C1 120-1 60
Pressure 27-30
CO/H2 ratio 1:l
Feedstock 1-0ctene
LHSV" u-7 0.1-0.4
Cobalt concentration [wt. % of feed] 0.4-0.7
Product composition [wt. %]
- n-1-Octene 8-12
- Light products 3-5
- C9 aldehydes 70-75b'
- C9 alcohols 6-10
- Heavy ends 4-6"'
a) LHSV = Liquid Hourly Space Velocity. b, 68-72 % n-nonanal. ") Including formates.

Vent
- .
*
t

r
Caustic
I 0 x 0 crude *

1
-r+-
Cobalt

Figure 10. Flow sheet of the Exxon process (Kuhlmann technology).

72 2.1 Carbon Monoxide and Synthesis Gas Chemistry

Figure 11. Loop reactor design. I

Make-up cobalt enters the process via carbonyl generator (2) and is combined
with the olefin stream from extraction column (8), which already carries the
recycled HCo(CO),. With syngas from the purification section (I), the hydro-
formylation takes place under the usual conditions (160-190 "C; 25-30 MPa;
0.1-0.5 % cobalt relative to olefin) in the reactor (3) equipped with an external
loop. No mechanical stirring is applied; circulation and mixing are provided by
the stream of liquid and gaseous reactants (mammoth pump principle) and by
the heat of reaction.
Figure 11 shows an example of a layout of such an external recycle. After
passing a separator (4), the crude hydroformylation product is treated with dilute
aqueous alkali (e.g., 9-15 wt. % of reaction product as 3-5 wt. % NaOH), still
under the same temperature and pressure, to convert HCO(CO)~to water-soluble
~ , is extracted as aqueous solution into vessel (5). A cobalt-free
N ~ C O ( C O )which
organic phase results after scrubbing with water in (6). By addition of H2S04
in the presence of syngas, HCO(CO)~ is generated in (7), extracted by the stream
of fresh olefin entering, and sent to the hydroformylation zone. Instead of the ole-
fin as extractant, other suitable compounds may be applied (e.g., hexanol).
The vent stream may be scrubbed by olefin to recover traces of HCo(CO), [172].
Reclamation of cobalt as described is not complete as some formation of Co2+
by oxidation cannot be avoided, leading to deterioration of the wastewater stream.
For the recovery of cobalt from this stream, the usual techniques of precipitation
may be applied, leading to carbonate or hydroxide [177]. The overall losses are
compensated by fresh cobalt, introduced via the carbonyl generator. In order to
convert cobalt formate into HCO(CO)~,the presence of palladium on a support
as catalyst is recommended [ 1741.
The engineering of the Exxon process is beneficial because the catalyst does
not undergo decomposition and is introduced in its most active and effective
form. However, all the stages of catalyst separation and recycling have to be car-
 2.1.1.4 Commercial Applications 73

Table 9. Exxon process: typical data [ 165-1681,

Parameter Unit Range
Temperature [“CI 175
Pressure WPaI 29-30
CO/H2 ratio 1:1.16
Feedstock Propene trimer
LHSV”’ Lh-9 0.7
Cobalt concentration [wt. % of feed] 0.3
Product composition [wt. %]
- Light products 11-13
- Clo aldehydes 72-74
- Heavy ends 13-17
a) LHSV = Liquid Hourly Space Velocity.

ried out under CO pressure, a requirement which may be considered as disadvan-

tageous.
The product data (Table 9) correspond to the usual picture for cobalt
hydroformylation. A number of proposals have been put forward to make use
of the high-boiling moiety of the raw 0x0 product. The hydrolysis of esters
(formates, butyrates) may be achieved by steam in the presence of aluminum oxide
[175] in a similar procedure to the Ruhrchemie process [176], or modified steam-
cracking is applied to break down the condensation products [177].

Shell Process

Phosphine-modified cobalt catalyst is applied commercially only in the Shell

process to hydroformylate olefins of medium chain length (C7-C 14). The resulting
alcohols are sold under the brand name “Dobanol”.
Figure 12 outlines the noteworthy steps in the process. Synthesis gas (H2/C0 2
2: 1) is highly purified in (1) to remove sulfur compounds as well as oxygen and
is fed to the reactor(s) (2) together with purified olefin [178] and the recycled
catalyst. The liquid products leaving the separator ( 3 ) enter a distillation unit
(4), designed either for distillation under CO pressure (to preserve the active
catalyst) or as a flasher (to reduce the thermal strain imposed on the catalyst).
The emerging catalyst may be recycled or it may pass a make-up section (7).
Before re-entering the reactor, the catalyst recycle is upgraded by the addition
of cobalt, ligand, and (if desired) additives (e.g., KOH, amines; see below).
Depending on the properties of the olefin, the reaction conditions may vary
over a broad range: temperature 150-190 “C; pressure 4-8 MPa; cobalt concen-
tration 0.5-1 .O % wt of olefin; molar ratio phosphine/cobalt 1-3: 1; liquid hourly
14 2.1 Carbon Monoxide and Synthesis Gas Chemistry

Vent

Crude product

*
4
Olefin 6 ;
...........................

5
I
-

Figure 12. Flow diagram of the Shell process.

space velocity (olefin) 0.2. Tri-n-butylphosphine is frequently mentioned as ligand

[ 1791, but other alkyl- or cycloalkyl-phosphines also seem to be suitable
[180-1821. The presence of small amounts of water in the reaction medium en-
hances the formation of alcohols instead of aldehydes [183] and suppresses the
generation of formates [ 1841.
The combination of cobalt with phosphine ligand causes some characteristic
changes in the catalytic properties compared with unmodified cobalt:

The specific activity drops by a factor of 4-6, leading to reduced space-time

yield in spite of increased reaction temperatures.
The hydrogenation activity of the modified catalyst is drastically enhanced: up
to 80 % of the products may show up as alcohols, accompanied, however, by a
considerable amount of alkanes.
( 3 ) The n/i ratio is influenced favorably: as much as 85-90% linearity may be
achieved.
(4) The total pressure is considerably lowered in comparison with unmodified co-
balt catalyst.

The separation of catalyst and product by distillation causes some disintegration

of the complex catalyst, leading to finely divided metal which in turn tends to in-
duce side reactions of the product and has to be recovered [185]. The addition of
high-boiling oxygen-containing compounds, such as diphenyl ether or dibenzyl
ether, is claimed to have a beneficial effect [180], as well as the presence of un-
reacted olefin (6) [181, 1861 or of a carboxylic acid [187].
 2.1.1.4 Commercial Applications 75

When the hydroformylation is carried out in an alkaline reaction medium, the

aldehydes formed as primary products undergo aldolization and, consecutively,
hydrogenation. Thus the addition of, e.g., KOH (2 moVg at Co) or a tertiary
alkylamine leads to 2-ethylhexanol with yields up to 85 %, starting from propene.
The formation of by-products like C4,4,4-acetalcan be controlled by proper choice
of the alkalinity and its source [188, 1891.
Fresh cobalt is introduced into the Shell process in the form of carboxylate, e.g.,
octanoate. In the presence of phosphine (PR,) and carbon monoxide, a complex is
formed to which the formal structure [ C O ( C O ) ~ P Ris~ascribed
]~ [189J. Under car-
bon monoxide pressure this neutral complex is converted into an ionic complex
[CO(CO)~(PR~),]+[CO(CO),~, which can be precipitated (e.g., by addition of
methanol) and separated by filtration [190J. In the case of the combined hydrofor-
mylation/aldolization the precipitation may be achieved by slight acidification
under carbon monoxide pressure (make-up section 7 in Figure 12) [ 185J.
The Shell process offers a high n/i ratio, a comparatively low reaction pressure
and the direct formation of alcohols, as advantages. On the other hand, the low
specific activity of the ligand-modified catalyst requires a large volume of reac-
tion, and hydrogenation of a considerable part of the olefin feedstock has to be
tolerated.

2.1.1.4.4 Rhodium-Based Processes

Besides their high specific activity, the pronounced thermal stability of rhodium-
phosphine complexes, even in the absence of carbon monoxide, influenced the
technology of the first generation of LPO processes. The basic idea was to retain
the catalyst in the synthesis reactor and to separate catalyst and butanals by dis-
tillation under reaction conditions [ S ] . Two requirements had to be fulfilled: a
high-boiling solvent for the catalyst and the excess of ligand had to be found
[191], and sufficient gas had to be passed through the reactor to entrain the
butanals. Condensation products of butanals, i.e., the heavy ends formed anyway
in the process, turned out to be an appropriate, cheap, and readily available solvent
[ 1461, thus covering one requirement. The solution to the other one proved unsa-
tisfactory. A huge gas recycle was necessary to remove the butanals from the re-
action zone (gas recycle process) in order to keep the level of liquid inside the
reactor constant, which is energy-consuming and markedly complicates the over-
all process.
Nevertheless, in comparison with the cobalt technology even the first genera-
tion of LPO processes (the expression “LPO” being coined by BP [266]) proved
successful and was promoted by a number of companies (e.g., Celanese, Union
Carbide, BASF, Mitsubishi), mostly in parallel. One of the first plants for butanal
production belonged to Celanese [ 1921 (later Hoechst-Celanese), closely followed
by Union Carbidernavy Powergas/Johnson Matthey [ 1931 and other companies.
Later, the efficiency of the gas recycle process was improved by a switchover to
the liquid recycle process, to which most plants have been converted in the mean-
time. Catalyst solution and aldehyde products leave the reactor as liquid and are
76 2.1 Carbon Monoxide and Synthesis Gas Chemistry

separated outside in several stages of thermal operation, which finally lead to raw
aldehyde, catalyst solution and a combined stream of gas, the latter two being
recycled to the reactor. Despite the improvement with respect to the former gas
recycle, the liquid recycle also demands a relatively complicated separation of
products from catalyst.
A far more elegant solution was the one offered by the RuhrchemieRhGne-
Poulenc (RCH/RP) process, which was established in 1984 on an industrial
scale: threefold in rneta-sulfonated triphenylphosphine (TPPTS, as sodium salt)
as the ligand yields the water-soluble catalyst HRh(CO)(TPPTS),. Because of
the mutual insolubility, the separation of the aqueous catalyst phase and the
butanals was extremely simplified, circumventing all the common difficulties
and leading to very efficient operation.

UCC Process

The Union Carbide Corporation (UCC) coordinated research work of UCC, Davy
Powergas (later Davy McKee), Johnson Matthey 2% Co., and G. Wilkinson
[193-1951 to develop a rhodium based 0 x 0 process.
In commercial applications of propene hydroformylation the process underwent
several modifications predominantly aimed at improvements in productkatalyst
separation. The very first version of the process, which was later named the “gas
recycle process”, effected the removal of the product aldehydes from the catalyst
solution by applying a large gas recycle in order to evaporate the aldehydes
[ 146, 196, 1971. The catalyst solution consisted of high-boiling aldehyde conden-
sation products (dimers, trimers, and various other aldehyde consecutive products),
in which an excess of TPP and the rhodium complex itself was dissolved
[198, 1991. In order to keep the volume of this reaction mixture constant, the re-
action conditions had to be maintained in a manner which allowed continuous
evaporation of the aldehyde products generated by the hydroformy lation reaction
[200]. These requirements led to fairly complex plant equipment (Figure 13) [201].
Propene and make-up synthesis gas are carefully purified (1, 2) and, together
with recycle gas, introduced into the stainless steel reactor (3) via a sparger.
The stirred reactor is equipped with an external heating jacket (for start-up) and
internal cooling coils. Effluent product vapor passes demisting pads (4) to prevent
carry-over of catalyst and liquid products. Part of the gaseous aldehyde is con-
densed in a cooler (5) and collected in a separator (6), from which the recycle
gas leaves via the demister (7) to the recycle compressor (8). A slipstream is
taken to vent. Part of the condensed aldehyde from separator (6) is recycled to
the reactor to keep the level of liquid constant. The main stream of crude 0x0
products is sent to the upgrading section [202].
The liquid catalyst solution contains about 35 wt. % of aldehydes (Table 10)
[201]. In order to keep the volume of liquid in the reactor constant it is necessary
to control several variables carefully: reaction and condensation temperatures,
amount and composition of recycle gas, inputs of propene and synthesis gas. Tem-
peratures around 90-95 “C and pressures between 15 and 18 bar in the hydro-
 2.1.1.4 Commercial Applications 77

Figure 13. UCC process: gas recycle.

Table 10. UCC gas recycle process: composition of product streams [201].
Product Liquid Reactor [mol %] Raw aldehyde
[wt. %I In [wt. %I
out
Isobutanal”’ 0.3 1.o 7.14
n-Butanal”’ 1.8 8.8 82.56
co2 1.2 1.2 0.39
Propane 14.3 14.6 4.40
Propene 20.5 14.9 4.82
co 9.9 4.7 0.06
Methane 3.7 3.9 0.08
Hydrogen 48.3 50.9 0.01
Rh (PPm) 275
TPP 7.5
Trimer aldehydes 50
Higher condensates 7.5
a) Total iso- plus n-butanal = 35 %.
78 2.1 Carbon Monoxide und Synthesis Gas Chemistry

formylation section are the common ranges. For stable operation, a high volume
of recycle gas has to be supplied: about 4.5 Nm3/kg of aldehydes generated, an
energy-consuming procedure. The productivity is 2-4 mol aldehyde per L of
catalyst volume and hour; the selectivity toward aldehydes is 93 %.
In order to avoid these drawbacks and following RCH/RP’s excellent ex-
periences with liquid recycles, the gas recycle was replaced by the liquid recycle
variant (Figure 14) which is used in most modem LPO plants. Combinations of
gas and liquid recycle have also been described, claiming an increased propene
conversion [203, 2041.
The synthesis section was simplified: a stainless steel reactor ( I ) is provided
with a sparger through which synthesis gas and propene are introduced via a
feed line together with recycle gas. The reactor is further equipped with an impel-
ler for mixing and an internal or external cooler to control reaction temperature.
The catalyst is dissolved in high-boiling aldehyde condensation products. A liquid
effluent stream is taken from the reactor at a rate sufficient to keep a constant level
of liquid in the reactor. Besides dissolved gases this liquid stream contains
aldehydes, the rhodium-phosphine complex catalyst, free phosphine ligand and
higher-boiling aldehyde condensation products. The splitting of this complex
mixture requires several steps.
The liquid stream passes a separator (2), then a let-down valve (3) for pressure
release, and enters a flash evaporator (4) where the major part of inerts and un-
converted reactants is taken overhead. The flashed-off gases are compressed
and returned to the reactor, whereas the liquid is heated and fed to a first distilla-
tion column (5), from which vaporized aldehydes are taken as head stream. As the
bottoms still contain aldehydes, a second distillation column (6) with sub-
atmospheric pressure is required to concentrate the catalyst solution. The gaseous
aldehydes from both units are condensed and sent to the upgrading section; the
separated gases (7) are recycled (after compression) or vented. In order to limit

T- - 1
I
I
L
25 “C 130 “ C
1-2 bar 0.15 bar

Figure 14. UCC process: liquid recycle; 1 bar = 0.1 MPa.

 2.1.1.4 Commerciul Applications 79

Table 11. UCC liquid recycle process: typical data [204].

Parameter Unit Range
Temperature ["CI 85-90
Pressure [MW 1.8
Rhodium concentration [PPml 240-270
TPP [wt. %] 11-12
CO/Hz ratio 1:1.07
Propene conversion [%I 85-89
Productivity [mol/L . h] 1S 2 . 0

a buildup of inerts in the recycled gas streams and to reduce losses by venting, a
separate treatment may be applied, e.g., an extraction of propene by aldehyde
products in the first step and a stripping by synthesis gas in the second [205,
2061. Although raw material utilisation is improved by such a procedure, it
contributes to the complexity of the catalyst and product separation section,
which is the crucial part of both UCC processes. The performance of the UCC
liquid recycle variant is shown in Table 11 [204].
In the latest version of the UCC process, the lifetime of a catalyst charge may
exceed one year, given sufficient purity of the feed and appropriate control of re-
action conditions. A number of proposals have been launched, directed at upgrad-
ing poisoned catalyst solutions and/or recovering the rhodium moiety from spent
catalyst [ 198, 207-21 I].

Ruhrchemie/Rh8ne-Poulenc (RCH/RP) Process

The idea of applying water-soluble rhodium complexes as catalysts for the

hydroformylation reaction [212, 2 131 was taken up and commercialized by
Ruhrchemie AG for the hydroformylation of propene [269]. After only two
years of development on the laboratory scale the first plant was erected in
1984, followed by rapid further increases in capacity to more than 600000
tondyear today [214]. An additional unit for the production of n-pentanal from
n-butene has been brought onstream in 1995 [271, 2941.
The RCH/RP unit (Figure 15) [116] is essentially a continuously stirred
tank reactor, followed by a phase separator and a strip column. The reactor (l),
which contains the aqueous catalyst, is fed with propene and syngas. The crude
aldehyde product passes into the decanter (2), where it is degassed and separated
into the aqueous catalyst solution and the organic aldehyde phase. The catalyst
solution moves to heat exchanger (3) and produces process steam. Water lost in
the aqueous phase can be replaced at (3) after which it returns to reactor (1).
The organic phase, containing the raw aldehyde, then passes through stripping
column (4). Here the mixture is treated with fresh syngas, which acts as the coun-
80 2. I Carbon Monoxide and Synthesis Gas Chemistry

Figure 15. RuhrchemieRhGne-Poulenc process (RCWRP): flow diagram.

Table 12. RCH/RP process: typical data 1116, 2941.

Reaction conditions Unit Range Typical value
Temperature ["CI 110-130 120
Pressure [MPaI 4-6 5
CO/H2 ratio 0.98-1.03 1.01
Aqueouslorganic phase 4-9 6
Propene conversion [%I 85-99 95
Propene purity [%I 85-99.9 95
Product composition [wt. %]
lsobutanal 4-8 4.5
n-Butanal 9 1-95 94.5
Isobutanol <o. 1 <o. 1
n-Butanol 0.5 0.5
Butyl formates Traces Traces
Heavy ends 0.2-0.8 0.4
Selectivity to C4 products >99 >99.5
Selectivity to C, aldehydes 99 99
n/i ratio 93/7-9713 9515
 2.1.1.4 Commercial Applications 81

0 20 40 60

PlRh ratio (mollmol) -80 100

Figure 16. RCHRP process: influence of the ligandhhodium ratio (P/Rh ratio).

tercurrent stripping agent to move unreacted olefin back to reactor (1). Because
there is no catalyst in the stripping column, no side reactions occur to decrease
the selectivity or yield of the aldehyde. After this, the raw aldehyde is fractionally
distilled into n- and isobutanal in a conventional aldehyde distillation unit (5). The
reboiler of this n/i-column is a falling film evaporator incorporated in reactor (1).
The heat of the 0x0 reaction is thus recovered as the reboiler heat source for the n/i
column. This is an advantage over the classical 0x0 processes, which simply
discard the 0x0 reaction heat: the RCHRP process is a net steam exporter. The
catalyst in fact remains "immobilized" in the reaction system with rhodium losses
in the range of ppbs. The use of water as solvent for the noncorrosive catalyst adds
a further advantage to the process with respect to ecotoxicity considerations.
The RCHRP catalyst is not sensitive to sulfur or other 0x0 poisons that may
enter with the feed. The withdrawal of organic and other by-products with the
organic phase and in the vent stream from decanter (2) prevents the accumulation
of activity-decreasing poisons in the catalyst solution. Typical process parameters
and product distribution are shown in Table 12.
As in most LPO processes, the active species HRh(CO)(TPPTS), and the
excess TPPTS are subject to slow decomposition which determines the lifetime
of the catalyst charge [38a]. Repeated addition of fresh ligand at short time inter-
vals extends the catalyst shelf life and stabilizes the desired P R h ratio [215] over
the time of operation. The P R h ratio is kept above 50: 1 to ensure an n/i ratio of at
least 95:5 (Figure 16). The RCHRP process faces more than a decade of success-
82 2.1 Carbon Monoxide and Synthesis Gas Chemistry

ful commercial operation and has been shown to run virtually problem-free from
start-up. An extension of the beneficial properties of the aqueous biphasic system
by the introduction of improved ligands is under development [ 1161.

BASF Process

Developed nearly in parallel with the UCC's LPO process, the BASF process also
makes use of a gas recycle to separate aldehydes and catalyst solution [216]. The
latter also consists of aldehyde condensation products [217] with TPP and the cor-
responding rhodium complex dissolved therein [218, 2191. With about 3-5 wt. %
the concentration of TPP is rather low, thus limiting the rhodium concentration to
a level below 200 ppm in order to establish a P/Rh ratio of about 100: 1 (moVg-at).
Accordingly, the d iratio is somewhere in the range of 84: 16. With a temperature
of about llO"C, the pressure is limited to about 1.5-1.7 MPa to avoid too large a
recycle.
The process scheme corresponds to the gas recycle process already described.
Propene and synthesis gas (H2/C0 = 55:45) are fed to a stainless steel tank
reactor with thorough mixing. Aldehydes are withdrawn by a recycle gas stream,
condensed by partial cooling, and freed from dissolved gases in a stabilizer
column [220]. The combined gaseous streams from these operations are re-
compressed and sent to the reactor. A vent stream is used to control the level
of propane in the gas loop. Due to the application of the recycle, the syngas
actually entering the reactor is extremely rich in H2. Typical data are shown in
Table 13 [221].

Other Processes

Despite a considerable number of publications and patent applications dealing

with hydroformylation technology, comparatively few processes have been
commercialized successfully besides those which have already been mentioned
in preceding sections. Two processes have gained commercial importance.
Back in 1974, Celanese (later Hoechst Celanese) started the production of bu-
tanals by a process [I921 which closely resembles the LPO one subsequently
(1976) established by UCC. It is an open question which of the two companies
was the really first to introduce low-pressure hydroformylation, as UCC claims
to have run an ethylene hydroformylation unit at Ponce before the start-up of
the propene unit at the same site [222]. There are only minor differences if any,
between the Celanese and the UCC process [192].
Mitsubishi also operates an LPO process for propene hydroformylation
[223-2251 which comprises several features of common technology. As outlined
in Figure 17, the liquid mixture of aldehydes and high-boiling condensation
products from reactor (1) passes a heaterkooler (2) and enters the top of the
strip column ( 3 ) . The recycle-gas together with fresh propene and syngas is
used to remove dissolved gases from the liquid effluent, which enters the
 2.1.1.4 Commercial Applications 83

Table 13. BASF process: typical data [221].

Parameter Value
Reactor volume 135 m3
Liquid volume =2/3 of reactor volume
Propene in 40004400 k g h
Butanals out 5 700-65 00 kg/h
Propene conversion 84-86 %
n/i ratio 84/16
Rhodium concentration 160-1 90 ppm
Gas recycle 18 000-26 000 Nm3h
Productivity 0.063-0.072 k g L . h
TPP concentration 3.54.5 wt. %
TPPRh -100/1 mol/g-at.
Temperature -110°C
Pressure -1.6 MPa
Propane formation -2 % of propene converted
High-boiling products -0.5 % of propene converted
Partial pressures
- Propene 0.48 MPa
- Carbon monoxide 0.06 MPa
- Hydrogen 0.8 MPa

gas-liquid separator (4) and then a distillation column (5) to separate aldehydes
and the catalyst solution. Catalyst and strip gases return to the reactor entrance.
The process can be considered as a combination of gas and liquid recycle with
a strip column. The following reaction conditions are stated to be typical: tem-
perature = 100°C; pressure 1.5-1.8 MPa; fi concentration 300-350 ppm;
TPP concentration 20-22 wt. %; and H2/C0 ratio = 1.015: 1.

Special Developments

Several attempts have been published to solve the problem of the separation of
catalyst and products by anchoring the catalytically active species on fixed sup-
ports (cf. Section 3.1.1.3) [267]. So far, none of these developments has achieved
technical realization, mainly because of insufficient long-term stability. For the
 84 2.1 Carbon Monoxide and Synthesis Gas Chemistry

4 Vent Vent Vent

t t

t -I r-+ I

.
: 1 -

syngas
1
-
, Propvlene

Figure 17. Mitsubishi process: flow diagram.

liquid-phase application, the fixation of rhodium to ion-exchange resins, to

polymers with incorporated ligands, or simply to oxidic carriers, proved to be
insufficient, and losses by leaching could not be conveniently suppressed
[226, 2271. In the gas-phase operation, where rhodium was either dissolved
in an excess of the molten phosphine ligand (SLPC, supported liquid-phase
catalysts [43]) or in an aqueous solution of the ligand (SAPC, supported aque-
ous-phase catalysts [44]), the immobilizing phase was swept out by the time
on-stream, carried by the gas flow as in chromatography, supported by the
exothermicity of the hydroformylation reaction [149]. In spite of the obvious
advantages of fixed-bed operation, until now no acceptable solution has been
presented [228].
Mitsubishi uses a modification of the rhodium-catalyzed high-pressure hydro-
formylation of long-chain olefins such as octenes or nonenes [37]. Hydroformyla-
tion is carried out in the presence of the weakly complexing triphenylphosphine
oxide (TPPO) as ligand at pressures up to 20 MPa at about 130 "C. It is claimed
that the activity of rhodium is less diminished by TPPO than by TPP, thus re-
ducing the rhodium inventory in comparison with TPP as ligand. A selectivity
of 93 % aldehydes plus 5 % alcohols together with 0.4 % high-boiling by-products
is reported. Before distillation of the nonanals or decanals, a small amount of TPP
is added to stabilize rhodium, the TPP being oxidized to TPPO before re-use of
the catalyst solution by an undisclosed oxidation procedure. Part of the catalyst
solution is purged for external upgrading [229-2331.
 2.1.1.5 Recent Developments 85

2.1.1.5 Recent Developments

Ligand development is still the major subject of publications about hydroformyla-
tion. There are some interesting recent results.

2.1.1.5.1 Phosphines
The control of regioselectivity is still the major factor of hydroformylation. Che-
lating diphosphines often show a higher selectivity and even higher activity in the
hydroformylation of terminal alkenes compared to monodentate ligands. A corre-
lation of the P-M-P bite angle and the selectivity resulted from several more recent
studies [234]. Eastman Kodak developed a series of diphosphines based on NA-
PHOS (13) [235]. The derivatives BISBI (14) and PHENAP (15) are highly active
and regioselective in the hydroformylation of 1-hexene [236]. Other diphosphine
ligands such as 2,2’-bis(dibenzophosphomethyl)-1,1’-biphenyl (16) and 2,2’-bis-
(dibenzophosphomethy1-5,5’-di-t-butyl- 1,l ’-biphenyl (17) [237] give comparable
results. In addition, the favorable natural bite angles of these ligands form equa-
torial chelates which also lead to higher n:i (l:b,linear to branched) values [238].

PPh2
\

13 14 15

16

In order to investigate the electronic effects of equatorial diphosphines, elec-

tron-withdrawing substituents on the aryl rings were synthesized and tested
[239]. The introduction of an electron-withdrawing group in the BISBI ligand
increased the linear aldehyde selectivity in the hydroformylation of I -hexene up
to an 1:b ratio of 123:l.
86 2.1 Carbon Monoxide and Synthesis Gas Chernisty

Van Leeuwen and co-workers synthesized a series of new bidentate dipho-

sphine ligands, based on xanthene-like backbones like sixantphos, thixanphos
(17), xantphos (18), or benzylnixantphos with natural bite angles of approx.
102" up to 121". Again a wider bite angle led to a higher selectivity for linear
aldehydes [240a-d]. The selectivity toward the linear aldehyde is somewhat
higher for BISBI due to the very low isomerization of 1-octene to internal olefins.
X-ray crystal structure confirmed an equatorial arrangement of the diphosphine
ligand comparable to BISBI or NAPHOS [24Oc].

17 18 19

In contrast, dibenzophospho- and phenoxaphosphino-substituted xantphos

ligands like (19) have an increasing isomerization rate of the feed olefins. There-
fore, these ligands are qualified for the hydroformylation of internal alkenes [24 11
and have a high activity and selectivity while hydroformylating 2-octene.
The calculated bite angles for these ligands are close to 120". Stanley report-
ed high activities and selectivities in the Rh-catalyzed hydroformylation of
1-hexene (n/i = 96:4) by using the phosphine ligand CH2[P(Ph)CH2CH2PEt2I2
[242]. The proposed active species 20 indicates a cooperative effect by both
Rh centers. The postulated bimetallic reaction mechanism [243, 2441 is based
on plausible single steps, for instance the well-known hydride transfer reaction
between two metal centers. Further evidence is given by the fact that other struc-
turally related tetradentate phosphines that do prevent a metal-metal interaction
for steric reasons show lower activity or none at all. The high rates achieved
with (20) under moderate reaction conditions were dramatically decreased if elec-
tronically equivalent monophosphines were used. The low rates expected for elec-
tron-rich ligands were observed in these cases. Altogether, there is strong evidence
for a real cooperative effect by the two metal centers as the results obtained with

20
 2.1.1.5 Recent Developments 87

the bimetallic system are completely different from those achieved with their
monometallic counterparts.

2.1.1S.2 Water-Soluble Phosphines

Chelating water-soluble diphosphine ligands (cf. also Section 3.1.1.1) were
the target of different researchers trying to transfer the advantages of their one-
phase catalysis analogues into a two-phase system. Among them are compounds
which are derived from biphenyl (BISBIS = sulfonated bis(dipheny1-
phosphinomethy1)biphenyl with varying grades of sulfonation) [245] or binaph-
thy1 structures (BINAS = sulfonated NAPHOS (13), sulfonation grade between
six and eight) [246]. BINAS represents the most active ligand in the Rh-catalyzed
two-phase hydroformylation. Also developed was a water-soluble bidentate di-
phosphine 2,7-bis(S03Na)-xantphos (21) based on the xantphos backbone (18).
This ligand also shows an enhanced selectivity for linear aldehydes because of
the large natural bite angle [247]. For both I-hexene and propene llb ratios higher
than 30 were observed without any isomerization of 1-hexene. The sulfonation of
xantphos gives 21 in very high yields with respect to the control of the position
and number of the sulfonated substituents.

S03Na

"03W
bPh2 PPh2

21

Chiral water-soluble secondary phosphines were developed by Stelzer by nu-

cleophilic phosphination of, e. g., FC6H4-2,4-S03Kwith RPH2. This synthetic
route offered a steric control of substitution at phosphorus by bulky substituents
R and sulfonic groups in the o-position of the aromatic ring [248]. Hanson and
co-workers synthesized surface-active phosphines 22 or 23 [249-2S 11. The in-
fluence of self-association of water-soluble ligands on the catalytic results were
studied. Some structures form aggregates in aqueous salt solutions, whereas
TPPTS shows no evidence of aggregation to a uniform size [249]. Surface-active
phosphines offer both good activity under two-phase conditions, due to the sur-
face activity of the phosphine, and excellent selectivity (97 % of 1-nonanal, at
Rh/P ratio of 1 :9) [250]. Rates and selectivity may be superior to TPPTS-modified
Rh catalysts under the same reaction conditions [25 11. Addition of salt to catalysts
with surface-active ligands improved the reaction rate, while the rate dropped
significantly when salt was added to a rhodium TPPTS catalyst [249d, 2521.
Comparable xantphos derivates have also been developed [253].
Novel water-soluble calix[4]arenes with phosphane-containing groups were
synthesized by Shimizu et al. The beneficial effect of water-soluble phospha-
88 2.1 Carbon Monoxide and Synthesis Gas Chernistty

22

23

calix[4]arenes can be attributed to an improvement in the mass transfer of the sub-

strate and products between the phases 12541.

2.1.1.5.3 Phosphites
Bulky diphosphites not only express a high selectivity toward 1-alkenes [255] but
also for less reactive internal [256] and functionalized alkenes. Recently DSM and
Du Pont reported on a ligand (24) which has a high regio- and chemoselectivity
for the hydroformylation of methyl 3-pentenoate [2531. The synthesis of mono-
phenols containing bulky substituents (25) is described in patents from Mitsubishi
[257]. High yields with 1-alkenes and llb ratios up to 20 are reported.

32; ' C02Me

24 25

Recently van Leeuwen reported the f i r - crystal structure of the diphosphite

dicarbonyl rhodium catalyst HRh(CO),(P P) 12581. Borner et al. developed a
new class of phosphonites which show promising results for the isomerization
and subsequent hydroformylation of internal olefins [259]. The number of phos-
phite ligands based on supramolecular backbones such as calix[4]arenes is grow-
ing [260]. They are attractive because of their well defined structure combined
with the ability to adopt several discrete conformations. Calix[4]arene diphos-
phites and calix[6]arene phosphites were first developed by BASF [261]. In
 2.1.1.5 Recent Developments 89

Rh hydroformylation these ligands show high llb ratios but also a high isomeri-
zation rate. Van Leeuven and co-workers have reported the conformations of
calix[4]arene monoohosphites [262].

2.1.1.5.4 P-N ligands

Recently, nitrogen-substituted phosphine ligands have attracted some interest.
Shell described phosphinoamines Ph2P(CH2),Nme2(x = 1, 2) for the Rh-cata-
lyzed hydroformylation of allyl and other unsaturated alcohols [263]. At moderate
temperatures and pressures allyl alcohol (as a basic reaction for an alternative
approach to 1,4-butanediol) was converted at high rates to 4-hydroxybutanal
and 2-methyl-3-hydroxypropanal with an overall linearity of 69 %. The selectivity
to 0x0 products is very high (>98 %), indicating only minor isomerization of allyl
alcohol to propanal. With Ph2PCH2NMe2,rates are slower but selectivity is
maintained in comparison to Ph2P(CH2)2NMe2.Addition of TPP to the catalyst
increased the regioselectivity slightly (72 % linearity). A comparative run with
TPP as ligand proved the positive influence of the P-N ligand on the reaction
velocity.
An interesting effect in the hydroformylation of styrene with Ph2PCH2NMe,-
modified Rh has been reported by Abu-Gnim and Amer [264]. The catalyst
showed 59 % conversion at 94:6 b:l ratio, whereas with the corresponding
phosphine oxide Ph2P(0)CH2NMe2conversions of 100 % and selectivities of
9 1:9 were observed under identical conditions. These surprising results were
reproduced by other authors [265]. It remains to be seen whether mixed bidentate
ligands (P-N, P-0 or P-S), with or without an oxidized phosphorus atom, will
generate a basic understanding of these results in the future. So far these ligands
have not been studied intensively in the 0x0 literature [266].

2.1.1.5.5 Other Ligands

Herrmann recently introduced carbene-based ligands for the hydroformylation
reaction (cf. Section 3.1.10) [267, 2681. The use of electron-poor phosphine-sub-
stituted cobaltocenium salts as ligands (26) for the biphasic hydroformylation has
been investigated [269]. In ionic liquids this ligand enables the hydroformylation
of 1-octene at high catalyst activity and high selectivity to the n-product without
detectable catalyst leaching (cf. Section 3.1.1.2.2) [270].

EPPh2
” ” 6

26
90 2.1 Carbon Monoxide and Synthesis Gas Chemistry

2.1.1.5.6 Conclusion and Future Trends

All of the existing commercial 0x0 processes have acquired a high degree of
maturity. With respect to propene hydroformylation, the majority of plants have
been converted to ligand-modified Rh catalysts, a fact which has led to drastic
reduction in the formation of by-products compared with the preceding cobalt-
based processes. In the second-generation processes the total yield of value
products based on propene feed has been augmented considerably, whereas the
third-generation processes have contributed additionally to the energy utilization.
With this background, the anticipated developments will concentrate on rather few
aspects: further simplification of the processes (as has already been demonstrated
by the biphasic variant RCHRP; cf. Section 3.1.1.1), an n/i ratio corresponding
to demand (about 9.55 should be reasonable), and yet higher propene conversion
(at present some tail gas has to be vented in LPO units). The last two points could
be covered by the introduction of more powerful ligands, so the research in this
wide field will continue (but without necessarily being published before realiza-
tion) [293].
The hydroformylation of alkenes of medium chain length, e. g., diisobutene or
tripropene, is still restricted to Co catalysts because of the poor ability of ligand-
modified catalysts to cope with internal carbon double bonds or with branched
structures. In spite of the refinement which cobalt technology has undergone
since the mid-I980s, there remains a potential for improvements similar to
those that have been made in propene hydroformylation. If the common reactivity
pattern of Rh catalysts can be altered by the application of newly developed
ligands, this would give access to the advantages of Rh-catalyzed hydroformy-
lation: not only to internal or branched olefins of medium chain length but also
to raffinate-2. This aim adds to the incentive to continue research for more ver-
satile ligands.
It has yet to be seen whether the principle of biphasic hydroformylation can be
further extended beyond C, olefins. Bearing in mind the advantages of biphasic
operation, two pathways may be considered: biphasic operation in the reactor
section and subsequent phase separation; or a combination of homogeneous
hydroformylation reaction with an auxiliary agent. This substance would require
a miscibility gap with the products under conditions different from the reaction
conditions. Examples of both principal methods have already been published
[271, 2721. However, a general solution is not to be expected, as each feed-
stocWproduct pair requires a specially adapted solvent. Novel developments in
the field of catalyst separation and reuse of catalyst systems are noted below.
Alcohols in the Cs-Clo range (as phthalates) are mainly consumed as plasti-
cizers. As these alcohols form by far the largest group of 0x0 products, there is
a pronounced mutual dependence between 0x0 synthesis and the polymer in-
dustry. Any extension of production capacities will be connected to the growth
in the production of polymers, especially of PVC and in Third World countries.
In this respect hydroformylation will follow the trend of other large branches of
industry to spread knowledge and experience abroad, as production follows the
markets.
 2.1.1.5 Recent Developments 91

With respect to the catalysts, future optimization will have two major goals:
improvement of the catalytic activity toward specific alkenes, and improvement
of catalytic selectivity for desired products such as chiral aldehydes. The hydro-
formylation of long-chain olefins will become a major area of interest in the
next decade as demand for long-chain plasticizers and detergent alcohols
increases. Promising progress using phosphite ligands may show which way
ligand synthesis is heading in the future. The easier synthesis and lower price
of these ligands seem to make them superior to phosphines. However, long-
term stability of these ligands is questionable as additives are necessary to main-
tain activity for longer periods of time [273, 2931.
In the area of speciality chemicals, asymmetric hydroformylation will be thor-
oughly investigated in the future. This reaction offers a convenient and waste-free
way to introduce chirality into molecules by a C-C bond formation step. The re-
cent successes in this area will replace the earlier Pt catalysts which suffer from
extensive side reactions such as hydrogenation and isomerization. The ligands
used so far are expensive (some are more highly priced than the rare catalyst me-
tals) and difficult to synthesize. Improvements in their synthesis along with new
concepts, for instance in the area of phosphomsheteroatom ligands, will make
commercial realization of the asymmetric variant of the 0x0 reaction more prob-
able.
In contrast to a number of other industrial processes, hydroformylation may be
classified as clean and environmentally friendly. The reaction itself and the
associated downstream operations are characterized by minimal product losses,
and in the case of a stationary catalyst phase (as in LPO processes) no environ-
mental impact is generated. The formation of inorganic salts is negligible, and
even in the case of Co catalysts the recycling is operated in a mode which nearly
quantitatively prevents losses of the catalyst ingredients. All of the process by-
products may serve as clean burning fuel, and with a carefully adapted design
0x0 processes can be net energy exporters. Regarding environmental aspects,
no decisive arguments against hydroformylation as a chemical process can be
raised, now or in the future [274, 293, 2941.
The development of supported aqueous-phase catalysis (SAPC) [275, 2761 is a
new and efficient way to facilitate the hydroformylation of longer olefins. Most of
the SAP catalysts described in the literature use TPPTS as ligand. Only a few
sulfonated diphosphine ligands were examined [277]. A water-soluble chelating
diphosphine ligand with a wide natural bite angle, based on a xanthene backbone,
was studied as a SAP aqueous catalyst. This ligand showed a much better selec-
tivity than the SAP catalysts known so far [278].
Current developments in combinatorial chemistry and rapid screening tech-
niques promote new systems in the field of polymer-supported catalysts (cf. Sec-
tion 3.1.3) [279]. A drawback for this technology is still the leaching tendency of
the catalyst which is clearly shown in recycling experiments (cf. Section 3.1.1.3)
[280]. Polycondensation of organo-functionalized silanes and polysiloxanes leads
to covalent support of catalyst on the surface, also known as the sol-gel process
[281-2831. Van Leeuwen and co-workers reported a phosphine ligand with a
xanthene backbone which was functionalized with a propyltrialkoxysilane
92 2.1 Carbon Monoxide and Synthesis Gas Chemistry

group prepared using the sol-gel method. Because of the wide natural bite angle
the catalyst system performed well in the hydroformylation of 1-octene with an l:b
ratio up to 40:l and quite good conversions [284].
Supercritical fluids, especially scC0, (cf. Section 3.1.13), find increasing
interest as environmentally friendly reaction media with unique properties for
chemical reactions [285]. The problem of insufficient solubility of the ligand
complexes has been solved by an approach similar to fluorous biphasic catalysis
(cf. Section 3.1.1.2.1) [286-2891.
Likewise, a thermoregulated phase transfer process within the aqueous/organic
two-phase system has been reported by Jin and co-workers (cf. Section 3.1.1.1)
[290]. A water-soluble supramolecular Rh catalyst based on functionalized
b-cyclodextrin was also described [291]. In a two-phase system this catalyst
may function as a carrier for the transfer of both the starting material and the prod-
uct between the different phases. As an alternative to polar media for biphasic
hydroformylation, Chauvin et al., used ionic liquids based on imidazolium salts
which are well known for dimerization reactions (cf. Sections 2.3.1.4 and
3.1.1.2.2) [270, 27 1, 2921. For introduction into technical processes the
currently availability and price of ionic liquids could be a drawback, especially
for bulk chemicals such as 0x0 products.

References
[ 11 a) Chemische Venvertungsgesellschaft Oberhausen m.b.H. (0.Roelen), DE 849.548
(193811952) and US 2.327.066 (1943). (b) 0. Roelen, Chem. Exp. Didakt. 1977, 3, 119.
[2] (a) B. Comils, W. A. Henmann, C. W. Kohlpaintner, Nachr: Chem. Tech. Lab. 1993,41,
544. (b) B. Comils, W. A. Henmann, M. Rasch, Angew. Chem. 1994,106,2219;Angew.
Chem., Int. Ed. Engl. 1994, 33, 2144.
[3] H. Adkins, G. Krsek, J. Am. Chem. Soc. 1948, 70, 383.
[4] B. Comils in New Syntheses with Carbon Monoxide (Ed.: J. Falbe), Springer, Berlin,
1980, Chapter 1.
[5] A. Hershman, K. K. Robinson, J. H. Craddock, J. F. Roth, Znd. Eng. Chem., Prod. Res.
Dev. 1969, 8, 372.
[6] J. F. Roth, Catal. Today 1992, 13, 1.
[7] B. Comils, L. Mark6 in Methoden Org. Chem. (Houben-Weyl), 1986, Vol. E18, p. 759.
[8] R. L. Pruett, Adv. Organomet. Chem. 1979, 17, 1.
[9] H. Bahrmann, H. Bach, Ullmannk Encycl. Ind. Chem. 5th ed. 1991, Vol. A18, p. 321.
[lo] M. Beller, B. Comils, C. D. Frohning, C. W. Kohlpaintner, J. Mol. Catal. A: 1995, 104,
17.
[11] F. H. Jardine, Polyhedron 1982, I , 569.
[12] P. Pino, F. Piacenti, M. Bianchi in Organic Syntheses via Metal Carbonyls, Vol. 2 (Eds.:
I. Wender, P. Pino), Wiley, New York, 1977, p. 43.
[13] P. Kalck, Y. Peres, J. Jenck, Adv. Organomet. Chem. 1991, 32, 121.
[ 141 F. P. Pruchnik in Organometallic Chemistry of Transition Elements, Plenum Press, New
York, 1990, p. 691.
[15] (a) G. K. I. Magomedov, L. V. Morozova, Zh. Obsch. Khim. 1981, 51, 2226; (b)
E. R. Tucci, Ind. Eng. Chem., Prod. Res. Dev. 1986, 25, 27; Chem. Abstr: 1986, 104,
111757.
 References 93

1161 T. E. Nalesnik, J. H. Freudenberger, M. Orchin, J. Organomet. Chem. 1982, 236, 95.

1171 (a) A. Fusi, E. Cesarotti, R. Ugo, J. Mol. Catal. 1981,10,213; (b) B. H. Chang, P. C. Coil,
M. J. Brown, K. W. Barnett, J. Organomet. Chem. 1984,270, C23: (c) Z. He, N. Lugan,
D. Neibecker, R. Methieu, J. J. Bonnet, J. Organomet. Chem. 1992, 426, 247.
[18] (a) Review: R. A. Sanchez-Delgado, M. Rosales, M. A. Esteruelas, L. A. Oro, J. Mol.
Catal. A : Chemical 1995, 96, 231; (b) R. A. Sanchez-Delgado, A. Andriollo,
N. Valencia, J. Chem. Soc., Chem. Commun. 1983, 444.
1191 L. A. Oro, M. T. Pinillos, M. Royo, E. Pastor, J. Chem. Res. Synop. 1984, 206; Chem.
Abstr 1984, 101, 191096.
[20] L. Kaden, B. Lorenz, M. Wahren, J. Prakt. Chem. 1986, 328, 407.
[21] L. Alvila, T. A. Pakkanen, T. T. Pakkanen, 0. Krause, J. Mol. Catal. 1992, 73, 325.
[22] D. T. Brown, T. Eguchi, B. T. Heaton, J. A. Iggo, R. Whyman, J. Chem. Soc., Dalton
Trans. 1991, 677.
[23] (a) A. D. Harley, G. J. Guskey, G. L. Geoffroy, Organometallics 1983,2,53; (b) C. Mahe,
H. Patin, J.-Y. Le Marouille, A. Benoit, Organometallics 1983, 2, 1051 ; (c) A. Ceriotti,
L. Garlaschelli, G. Longoni, M. C. Malatesta, D. Strumolo, A. Fumagalli, S. Martinengo,
J. Mol. Catal. 1984,24, 309; (d) S. Xue, Y. Luo, H. Fu, Y. Yin, Ranliao Huaxue Xuebao
1986,14,354; Chem. Abstr: 1987,107, 9264; (e) T. Hayashi, Z. H. Gu, T. Sakakura, M.
Tanaka, J. Organomet. Chem. 1988,352,373; (0W. Dai, H. Guo, R. Jiang, Q. Zhou, W.
Wei, Shiyou Huagong 1988, 17, 707; Chem. Abstr: 1989, 110, 233576; (8) J. Evans, G.
Jingxing, H. Leach, A. C. Street, J. Organomet. Chem. 1989, 372, 61; (h) A. R. El’man,
V. I. Kurkin, E. V. Slivinskii, S. M. Loktev, Nejiekhimiya 1990, 30, 46; Chem. Abstl:
1990, 112, 197383.
[24] (a) M. Garland, Organometallics 1993, 12, 535. (b) C. Fyhr, M. Garland, Organometal-
lies 1993, 12, 1753.
[25] (a) M. G. Richmond, M. Absi-Halbi, C. U. Pittman, Jr., J. Mol. Catal. 1984, 22, 367; (b)
M. Hidai, A. Fukuoka, Y. Koyasu, Y. Uchida, J. Chem. Soc., Chem. Commun. 1984,
516; (c) G. Suss-Fink, G. Henmann, J. Chem. Soc., Chem. Commun. 1985, 735; (d)
M. Hidai, A. Fukuoka, Y. Koyasu, Y. Uchida, J. Mol. Catal. 1986,35, 29; (e) D. Li,
W. Zhai, Z. Chen, Y. Sun, X. Zhao, Z. Wang, Huaxue Xuehao 1986, 14, 990; Chem.
Abstr: 1987, 107, 28819; (f) M. Hidai, H. Matsuzaka, Polyhedron 1988, 7, 2369; (8)
M. G. Richmond, J. Mol. Catal. 1989, 54, 199; (h) Y. Yin, F. Jiao, L. Qu, F. Nie, Huaxue
Xuebao 1990,18, 38; Chem. Abstr: 1990, 113, 193859; (i) M.-J. Don, M. G. Richmond,
J. Mol. Catal. 1992, 73, 181.
[26] I. T. Horvath, M. Garland, G. Bor, P. Pino, J. Organornet. Chem. 1988, 358, C17.
[27] L. N. Lewis, Chem. Rev. 1993, 93, 2693.
[28] J. T. Carlock, Tetrahedron, 1984, 40, 185.
[29] L. H. Pignolet (Ed.) Homogeneous Catalysis with Metal Phosphine Complexes, Plenum,
London, 1983.
[30] (a) C. A. Tolman, W. C. Seidel, L. W. Gosser, J. Am. Chem. Soc. 1974, 96, 53; (b) C. A.
Tolman, Chem. Rev. 1977, 77, 313.
[31] P. B. Dias, M. E. Minas de Piedade, J. A. M. Simoes, Coord. Chem. Rev. 1994, 135/136,
737.
[32] (a) C. P. Casey, G. T. Whitecker, Isr: J. Chem., 1990, 30, 299; (b) C. P. Casey,
G. T. Whiteker, C. F. Campana, D. R. Powell, Inorg. Chem. 1990, 29, 3376;
(c) C. P. Casey, G. T. Whiteker, M. G. Melville, L. M. Petrovich, J. A. Gavney, Jr.,
D. R. Powell, J. Am. Chem. Soc. 1992, 114, 5535.
[33] (a) W. A. Henmann, C. W. Kohlpaintner, E. Herdtweck, P. Kiprof, Inorg. Chem. 1991,
30, 4271; (b) K. Yamamoto, S. Momose, M. Funahashi, S. Ebata, H. Ohmura,
H. Komatsu, M. Miyazawa, Chem. Lett. 1994, 189; (c) W. A. Herrmann, R. Schmid,
C. W. Kohlpaintner, T. Priermeier, Organometallics 1995, 14, 1961.
94 2.1 Carbon Monoxide and Synthesis Gas Chemistry

[34] A. A. Oswald, D. E. Hendriksen, R. V. Kastrup, K. Irikura, E. J. Mozeleski, D. A. Young,

Phosphorus Sulfur, 1987, 30, 237.
1351 (a) A. A. Oswald, D. E. Hendriksen, R. V. Kastrup, E. J. Mozeleski, Acs. Adv. Chem. Ser:
1992, 230, 395; (b) T. V. RajanBabu, T. A. Ayers, Tetrahedron Lett. 1994, 35, 4295.
[36] (a) 0. R. Hughes, D. A. Young, J. Am. Chem. Soc. 1981, 103, 6636; (b) J. D. Unruh,
J. R. Christenson, J. Mol. Catul. 1982, 14, 19; (c) J. D. Unruh, J. R. Christenson,
0. R. Hughes, D. A. Young in Chem. Ind., Catalysis of Organic Reactions Vol. 5 ,
(Ed.: W. R. Moser) Marcel Dekker, New York, 1981, p. 309.
[37] (a) T. Onada, Chemtech 1993, 23(9), 34; (b) K. Sato, C. Miyazawa, K. Wada, T. Onoda,
Nippon Kagaku Kaishi 1994, 681; Chem. Abstr: 1994, 121, 136.524.
[38 (a) W. A. Herrmann, C. W. Kohlpaintner, Angew. Chem. 1993, 105, 1588; Angew.
Chem., Int. Ed. Engl. 1993, 32, 1524; (b) P. Kalck, F. Monteil, Adv. Organomet.
Chem. 1992, 34, 219.
[39 (a) P. W. N. M. van Leeuwen, C. F. Roobeek, J. Organomet. Chem. 1983, 258, 343;
(b) A. Polo, J. Real, C. Claver, S. Castillon, J. C. Bayon, J. Chem. SOC.,Chem. Commun.
1990,600; (c) A. van Rooy, E. N. Orij, P. C. J. Kamer, F. van den Aardweg, P. W. N. M.
van Leeuwen, J. Chem. Soc., Chem. Commun. 1991, 1096; (d) T. Jongsma, G. Challa,
P. W. N. M. van Leeuwen, J. Organomet. Chem. 1991, 421, 121.
[40] (a) D. R. Bryant, E. Billig, 4th Int. Con5 Chem. Plat. Group Met., 1990; (b) Union Car-
bide (E. Billig, A. G. Abatjoglou, D. R. Bryant), EP 213.639 (1987); Chem. Abstr: 1987,
107, 7392; (c) Union Carbide (E. Billig, A. G. Abatjoglou, D. R. Bryant), EP 214.622
(1987); Chem. Abstr: 1987, 107, 25126; (d) Union Carbide (E. Billig,
A. G. Abatjoglou, D. R. Bryant), US 4.769.498 (1988); Chem. Abstc 1989, 111,
117287; (e) Union Carbide (K. M. Maher, J. E. Babin, E. Billig, D. R. Bryant,
T. W. Leung), US 5.288.918 (1994); Chem. Abstr: 1994, 121, 56996.
[41] P. W. N. M. van Leeuwen, G. J. H. Buisman, A. van Rooy, P. C. J. Kamer, Recl. Trav.
Chim. Pays-Bas 1994, 113, 61.
[42] BASFAG (M. Roeper, P. M. Lorz, D. Koeffer), DE 4.204.808 (1993); Chem. Abstr: 1994
120, 133862.
[43] (a) L. A. Gemtsen, A. van Meerkerk, M. H. Vreugdenhill, J. J. F. Scholten, J. Mol. Catal.
1980, 9, 139; (b) L. A. Gemtsen, J. M. Herman, W. Klut, J. J. F. Scholten, J. Mol. Catal.
1980, 9, 157; (c) L. A. Gemtsen, J. M. Herman, J. J. F. Scholten, J. Mol. Catal. 1980, 9,
241; (d) L. A. Gemitsen, W. Klut, M. H. Vreugdenhill, J. J. F. Scholten, J. Mol. Catal.
1980, 9, 257; (e) L. A. Gemitsen, W. Klut, M. H. Vreugdenhill, J. J. F. Scholten, J. Mol.
Catal. 1980,9,265; (0 N. A. de Munck, J. P. A. Notenboom, J. E. de Leur, J. J. F. Schol-
ten, J. Mol. Catal. 1981, 11, 233; ( g ) H. L. Pelt, L. A. Genitsen, G. van der Lee, J. J. F.
Scholten, Stud. S u Sci.~ Catal. 1983,16, 369; (h) J. Hjortkjaer, M. S. Scurrell, P. Simon-
sen, J. Mol. Catal. 1979,6,405; (i) J. Hjortkjaer, M. S. Scurrell, P. Simonsen, H. Svend-
sen, J. Mol. Catal. 1981, 12, 179. 6 ) J. J. F. Scholten, R. van Hardeveld, Chem. Eng.
Commun. 1987, 52, 75; Chem. Abstr: 1987, 107, 98563. (k) J. M. Herman, A. P. A. F.
Rocourt, P. J. van den Berg, P. J. van Krugten, J. J. F. Scholten, Chem. Eng. J. 1987,
35, 83; Chem. Abstr: 1987, 107, 98567.
[44] M. E. Davis, Chemtech 1992, 22, 498.
[45] I. Wender, S. Metlin, S. Ergun, H. W. Stemberg, H. Greenfield, J. Am. Chem. SOC.1956,
78, 5101.
[46] B. Heil, L. Markb, Chem. Ber: 1969, 102, 2238.
[47] J. Falbe, Carbon Monoxide in Organic Synthesis, Springer, Berlin, 1970.
[48] A. J. M. Keulemans, A. Kwantes, T. van Bavel, Recl. Trav. Chim. Pays-Bas 1948, 67,
298.
[49] C. Botteghi, R. Ganzerla, M. Lenarda, G. Moretti, J. Mol. Catal. 1987, 40, 129.
[SO] T. Yoshida, Encycl. Chem. Techn. (Kirk-Othmer)3rd ed. 1978 Vol. 2, p. 410.
 References 95

[SI] N. Noujiri, M. Misono, Appl. Catal. A: General, 1993, 93, 103.

[52] (a) Kuraray Co. (M. Matsumoto, M. Tamura), US 4.215.077 (1980); (b) Kuraray Co.
(Y. Harano), US 4.465.873 (1984); (c) Kuraray Co., Daicel Chem. Ind. (M. Matsumoto,
S. Miura, K. Kikuchi, M. Tamura, H. Kojima, K. Koga, S. Yamashita), US 4.567.30s
(1986); (d) N. Yoshimura, M. Tamura, Stud. Su@ Sci. Catal. 1988, 44, 307.
[53] N. Nagato in Encycl. Chem Technol. (Kirk-Othmer), 4th ed., 1991, Vol. 2, p. 144.
[54] G. W. Parshall, S. D. Ittel, Homogeneous Catalysis, 2nd ed., Wiley, New York, 1992,
p. 126.
[ S S ] (a) C. Mercier, P. Chabardes, Pure Appl. Chem. 1994, 66, 1509; (b) C. Mercier, P. Cha-
bardes in 15th Cont Catalysis of Organic Reactions, Phoenix, Arizona, 1994, Paper 20.
[56] (a) BASF AG (W. Himmele, W. Aquila), US 3.840.589 (1974); (b) BASF AG
(W. Himmele, F. J. Muller, W. Aquila), DE 2.039.078 (1972).
[S7] Hoffmann La Roche (P. Fitton, H. Moffet), US 4.124.619 (1978).
[SS] Kuraray Co. (Y. Tokito, N. Yoshimura), JP 62.030.734 (1987).
[59] (a) Kuraray Co. (T. Omatsu, Y. Tokito, N. Yoshimura), EP 303.060 (1989); Chem. Abstr:
1989, 111, 38870; (b) Kuraray Co. (K. Adachi, N. Yoshimura), JP 02.243.681 (1990).
[60] (a) Kuraray Co. (Y. Tokito, N. Yoshimura), EP 223.103 (1987); (b) Kuraray Co.
(Y. Tokito, N. Yoshimura), JP 61.249.940 (1986).
1611 (a) B. Fell, M. Beutler, Erdol, Kohle, Erdgas, Petrochem. 1976, 29, 149; (b) C. Botteghi,
C. Salomon, Tetrahedron Lett. 1974, 15, 4285; (c) P. G. M. Wuts, A. R. Ritter, J. Org.
Chem. 1989, 54, 5180; (d) E. M. Campi, W. R. Jackson, Y. Nilsson, Tetrahedron Lett.
1991, 32, 1093; (e) J. R. Johnson, G. D. Cuny, S. L. Buchwald, Angew. Chem. 1995,
107, 1877; Angew. Chem., lnt. Ed. Engl. 1995, 34, 1760.
[62] Review: E. H. Pryde, J. Am. Oil Chem. Soc. 1984, 61, 419.
1631 (a) C. Botteghi, G. Del Ponte, M. Marchetti, S. Paganelli, J. Mol. Catal. 1994, 93, 1; (b)
G. D. Cuny, S. L. Buchwald, J. Am. Chem. SOC.1993, 115, 2066; (c) C. Botteghi, S.
Paganelli, J. Organomet. Chem. 1993, 451, C18; (d) C. Botteghi, G. Chelucci, G. Del
Ponte, M. Marchetti, S. Paganelli, J. Org. Chem. 1994, 59, 7125; (e) C. Botteghi, S. Pa-
ganelli, L. Bigini, M. Marchetti, J. Mol. Catal. 1994, 93, 279; (f) C. Botteghi, M. March-
etti, S. Paganelli, Speciality chemicals by selected carbonylation processes, in Trends in
Organometallic Chemistry (Ed.: S . B. Pandalai), in press.
1641 D. R. Bryant. Presentation at 203rd ACS National Meeting, San Francisco, 1992.
[65] (a) Hoechst AG (H. Bahrmann, G. Dambkes, C. D. Frohning, W. Greb, P. Heymanns, H.
Kalbfell, H. Kappesser, P. Lappe, H. Springer, E. von Muhlmann, J. Weber, E. Wiebus),
DE 4.333.323 (1993); (b) Hoechst AG (H. Bahrmann, W. Greb, P. Heymanns, P. Lappe,
T. Muller, J. Szameitat, E. Wiebus), DE 4.333.324 (1993) and EP 646.563 (1994).
[66] B. Fell, W. Rupilius, Tetrahedron Lett. 1969, 2721.
1671 (a) B. Fell, W. Boll, J. Hagen, Chem.-Ztg. 1975, 99, 487; (b) B. Fell, H. Bahrmann,
J. Mol. Catal. 1977, 2, 2 11.
1681 H. Adkins, J. L. R. Williams, J. Org. Chem. 1952, 17, 980.
[69] Hoechst AG (B. Fell, P. Hermanns), EP 643.031 (1994).
[70] M. Barber, Stereotechnol. Pharm. Manut lnt. 1990, 137.
1711 Recent reviews: (a) C. Botteghi, S. Paganelli, A. Schionato, M. Marchetti, Chirality
1991, 3, 355; (b) J. K. Stille in Comprehensive Organic Synthesis (Eds.: B. M. Trost,
I. Fleming, M. F. Semmelhack), Pergamon, Oxford, 1991; (c) G. Consiglio in Catal.ytic
Asymmetric Synthesis (Ed.: I. Ojima), VCH, Weinheim, 1993; (d) S. Gladiali, J. C. Bay&,
C. Claver, submitted; (e) G. Consiglio, P. Pino, Top. Curr: Chem. 1982, 105, 77.
1721 (a) BASFAG (W. Himmele, H. Siegel, W. Aquila, F. J. Muller), DE 2.132.414 (1972);
Chem. Abstr: 1973, 78, 97328; (b) C. Botteghi, C. Giambattista, P. Pino, Chimia 1972,
26, 141; (c) M. Tanaka, Y. Watanabe, T. Mitsudo, K. Yamamoto, Y. Takegami, Chem.
Lett. 1972, 483; (d) I. Ogata, Y. Ikeda, Chem. Lett. 1972, 487.
96 2.1 Carbon Monoxide and Synthesis Gas Chemistry

[73] C. Y. Hsu, M. Orchin, J. Am. Chem. SOC.1975, 97, 3553.

[74] L. Kollir, T. KCgl, J. Bakos, J. Organomet. Chem. 1993, 453, 155.
[75] P. W. N. M. van Leeuwen, C. F. Roobeek. R. L. Wife. J. H. G. Frijns. J. Chem. SOC..
Chem. Commun. 1986, 31.
[76] C. Botteghi, S. Paganelli, U. Matteoli, A. Scrivanti, R. Ciorciaro, L. M. Venanzi, Helv.
Chim. Acta 1990, 73, 284.
[77] (a) G. K. Anderson, H. C. Clark, J. A. Davies, Organometallics 1982, 1, 64; (b)
P. J. Stang, Z. Zhong, A. M. Arif, Organometallics 1992, I ] , 1017; (c) A. Scrivanti,
G. Cavinato, L. Toniolo, C. Botteghi, J. Orgartomet. Chem. 1985, 286, 115;
(d) H. J. Ruegg, P. S. Pregosin, A. Scrivanti, L. Toniolo, C. Botteghi, J. Organornet.
Chem. 1986, 316, 233; (e) E. Paumard, A. Mortreux, F. Petit, J. Chem. SOC.,Chem.
Comrnun. 1989, 1380.
[78] I. T6th, T. KCgl, C. J. Elsevier, L. Kolliir, Inorg. Chem. 1994, 33, 5708.
[79] J. K. Stille, H. Su, P. Brechot, G. Parrinello, L. S. Hegedus, Organometallics 1991, 10,
1183.
[80] I. T6th, I. Guo, B. E. Hanson, Organometallics 1993, 12, 848.
[81] (a) N. Sakai, S. Mano, K. Nozaki, H.Takaya, J. Am. Chem. Soc. 1993, 115, 7033:
(b) N. Sakai, K. Nozaki, H. Takaya, J. Chem. Soc., Chem. Commun. 1994, 395;
(c) T. Higashizima, N. Sakai, K. Nozaki, H.Takaya, Tetrahedron Lett. 1994, 35, 2023.
I821 (a) Union Carbide (J. E. Babin, G. T. Whitecker), PCT Int. Appl. WO 93103839 (1993);
(b) G. J. H. Buisman, E. J. Vos, P. C. J. Kamer, P. W. N. M. van Leeuwen, J. Chem. Soc.,
Dalton Trans. 1995, 409.
[83] (a) Mitsubishi Gas Chem. Co. and Takasago Int. Corp. (H. Takaya, N. Sakai, K. B. M.
Tamao, S. Mano, H. Kumobayashi, T. Tomita), EP 614.901 (1994): Chem. Abstr:
1994, 122. 10257; (b) Takasago Int. Corp. (K. Matsumura, T. Saito, N. Sayo, H. Kumo-
bayashi, H. Takaya), EP 614.902 (1994): Chem. Abstr: 1994, 122, 31704: (c) Takasago
Int. Corp. (T. Saito, K. Matsumura, Y. Kato, N. Sayo, H. Kumobayashi), EP 614.903
(1994).
[84] C. G. Arena, F. Nicolo, D. Drommi, G. Bruno, F. Faraone, J. Chem. Sac., Chem. Com-
mun. 1994, 255 1.
[85] (a) W. Reppe, Experientia 1949, 5, 93; (b) W. Reppe, H. Vetter, Liebigs Ann. Chem.
1953, 582, 133; (c) Texaco Co. (E. E. MacEntire, J. F. Knifton), EP 240.193 (1986);
(d) R. M. Laine, J. Org. Chem. 1980, 45, 3370; (e) K. Murata, A. Matsuda, T. Matsuda,
J. Mol. Catal. 1984,23, 121; (f) A. L. Lapidus, A. P. Rodin, L. Y. Brezhnev, I. G. Pruidze,
B. I. Ugrak, Izv. Akad. Nauk SSSR, Ser: Khim. 1990, 1448; Chem. Abstr: 1990,
113, 171812: (g) T. Baig, P. Kalck, J. Chem. SOC.,Chem. Commun. 1992, 1373;
(h) T. Baig, J. Molinier, P. Kalck, J. Organomet. Chem. 1993, 455, 219.
[86] (a) J. F. Knifton, Hydrocarbon Process. 1981, 60(12), 113; (b) J. F. Knifton, Chemtech
1981, I], 609: (c) L. Kaplan, J. Org. Chem. 1982, 47, 5422; (d) G. Jenner, Applied
Catal. A: General 1995, 121, 25; (e) G. Jenner, J. Mol. Catal. 1995, 96, 215;
(t) H. Kheradmand, A. Kiennemann, G. Jenner, J. Organomet. Chem. 1983, 251, 339;
(g) H. Bahrmann, B. Cornils, Chem.-Ztg. 1980, 104, 39.
[87] (a) K. G. Moloy, R. W. Wegman, J. Chem. Soc., Chem. Commun. 1988, 820;
(b) G. Jenner J. Organomet. Chem. 1988, 346, 237; (c) K. G. Moloy, R. W. Wegman,
Organometallics 1989, 8, 2883; (d) M. J. Chen, J. W. Rathke, Organometallics 1989,
8, 515; (e) N. Isogai, K. Tanaka, J. Organomet. Chem. 1990, 397, 101; (f) E. Lindner,
A. Bader, H. Braunling, R. Jira, J. Mol. Catal. 1990, 57, 291; (g) N. Chatani, T. Sano,
K. Ohe, Y. Kawasaki, S. Murai, J. Org. Chem. 1990, 55, 5923; (h) G. Braca, A. M.
Raspolli Gallctti, G. Sbrana, E. Trabuco, ACS Adv. Chem. Ser: 1992, 230, Chapter 21 ;
(i) Review: H. Bahrmann, B. Cornils in New Syntheses with Carbon Monoxide
(Ed.: J. Falbe), Springer, Berlin, 1980, Chapter 2.
 References 97

[88] Recent references: (a) I. Matsuda, A. Ogiso, S. Sato, Y. Isumi, J. Am. Chem. Soc. 1989,
I l l , 2332; (b) I. Matsuda, A. Ogiso, S. Sato, J. Am. Chem. SOC. 1990, 112, 6120; (c) N.
Chatani, S. Ikeda, K. Ohe, S. Murai, J. Am. Chem. SOC. 1992,114, 9710; (d) F. Monteil,
I. Matsuda, H. Alper, J. Am. Chem. SOC. 1995, 117, 4419; (e) I. Ojima, E. Vidal, M.
Tzamanoudaki, I. Matsuda, J. Am. Chem. Soc. 1995, 117, 6797.
[89] (a) D. S. Breslow, R. F. Heck, Chem. Ind. (London) 1960, 467; (b) R. F. Heck,
D. S. Breslow, J. Am. Chem. SOC. 1961, 83, 4023; (c) M. Orchin, W. Rupilius,
Catal. Rev. 1972, 6, 85.
[90] L. Markb, Fundam. Res. Homogeneous Catal. 1984, 4, 1.
[91] L. Versluis, T. Ziegler, E. J. Baerends, W. Ravenek, J. Am. Chem. Soc. 1989, I l l , 2018.
[92] M. S. Borovikov, I. Kovks, F. Ungvary, A. Sisak, L. Mark6, J. Mol. Catal. 1992, 75,
L27.
(931 (a) F. Ungviry, L. Mark6, Organometallics 1983, 2, 1608; (b) M. F. Mirbach, J. Orga-
nomet. Chem. 1984, 265, 205; (c) M. F. Mirbach, Inorg. Chim. Acta 1984, 88, 209;
(d) J. Azran, M. Orchin, Organometallics 1984, 3, 197; (e) I. Kovacs, F. Ungvary,
L. Markti, Organometallics 1986, 5, 209.
[94] (a) G. Fachinetti, L. Balocchi, F. Secco, M. Venturini, Angew. Chem. 1981, 93, 215;
Angew. Chem. Int. Ed. Engl. 1981, 20, 204; (b) P. Bradamante, A. Stefani,
G. Fachinetti, J. Organomet. Chem. 1984, 266, 303; (c) P. Pino, A. Major, F. Spindler,
R. Tannenbaum, G. Bor, I. T. Horvith. J. Organomet. Chem. 1991, 417, 65.
[95] F. Piacenti, M. Bianchi, P. Frediani, G. Menchi, U. Matteoli, J. Organomet. Chem.
1991, 417, 77.
[96] (a) J. Falbe, H. Feichtinger, P. Schneller, Chem.-Ztg. 1971, 95, 644; (b) F. Piacenti,
M. Bianchi, P. Pino, J. Org. Chem. 1968, 33, 3653; (c) F. Piacenti, M. Bianchi,
P. Frediani, U. Matteoli, J. Organomet. Chem. 1975, 87, C54; (d) M. Bianchi,
U. Matteoli, P. Frediani, P. Piacenti, J. Organomet. Chem. 1976, 120, 97;
(e) M. Bianchi, F. Piacenti, P. Frediani, U. Matteoli, J. Organomet. Chem. 1977, 135,
387.
[97] M. S. Borovikov, I. Kovacs, F. Ungviry, A. Sisak, L. Mark6, Organometallics 1992, 11,
1576.
[98] S. S. Bath, L. Vaska, J. Am. Chem. Soc. 1963, 85, 3500.
[99] S. J. LaPlaca, J. A. Ibers, J. Am. Chem. Soc. 1963, 85, 3501.
[ 1001 (a) D. Evans, J. A. Osbom, G. Wilkinson, J. Chem. Soc. ( A )1968,3133;(b) C. K. Brown,
G. Wilkinson, Tetrahedron Lett. 1969, 1725; (c) C. K. Brown, G. Wilkinson, J. Chem.
SOC. (A) 1970, 2753.
[ l o l l I. T. HorvBth, R. V. Kastrup, A. A. Oswald, E. J. Mozeleski, Catal. Lett. 1989, 2, 85.
[lo21 R. V. Kastrup, J. S. Merola, E. J. Mozeleski, R. J. Kastrup, R. V. Reisch, ACS Symp. Ser:
1982, 196, 43.
[lo31 (a) G. Natta, R. Ercoli, Chim. Ind. (Milan) 1952, 34, 503; (b) G. Natta, R. Ercoli,
S. Castellano, Chim. Ind. (Milan) 1955, 37, 6; (c) G. Natta, Brennstojf- Chem. 1955,
36, 176; (d) G. Natta, R. Ercoli, S. Castellano, F. H. Barbieri, J. Am. Chem. SOC.
1954, 76, 4049.
[lo41 B. Heil, L. Markb, Chem. Ber: 1968, 101, 2209.
[lo51 (a) F. E. Paulik, Catal. Rev. 1972, 6, 49; (b) J. D. Unruh, Internal Report JDU-43-75,
Celanese Corp. 1975.
[I061 (a) R. V. Gholap, 0. M. Kut, J. R. Bourne, Ind. Eng. Chem. Res. 1992, 31, 1579;
(b) R. V. Gholap, 0. M. Kut, J. R. Bourne, Ind. Eng. Chem. Res. 1992, 31, 2446.
[lo71 (a) 0. Gurtler, F. Schiirmann, A. Saus, Chem.-Ztg. 1989, 113, 193; (b) 0. Gurtler,
C. Silberg, W. Laarz, A. Saus, Chem.-Ing.-Tech. 1993, 65, 575.
[lo81 R. M. Deshpande, B. M. Bhanage, S. S. Divekar, R. V. Chaudhari, J. Mol. Catal. 1993,
78. L37.
98 2.1 Carbon Monoxide and Synthesis Gas Chemistry

[ 1091 (a) G. Gregorio, G. Montrasi, M. Tampieri, P. Cavalieri d’Oro, G. Pagani, A. Andreetta,

Chim. Ind. (Milan) 1980, 62, 389; (b) P. Cavalieri d’Oro, L. Raimondi, G. Pagani,
G. Montrasi, G. Gregorio, A. Andreetta, Chim. Ind. (Milan) 1980, 62, 572.
[110] P. W. N. M. van Leeuwen, G. van Koten, Studies S u f Sci. Catal. 1993, 79, 199.
[ l l l ] S. S. Divekar, R. M. Deshpande, R. V. Chaudhari, Catal. Lett. 1993, 21, 191.
[112] R. M. Deshpande, R. V. Chaudhari, Ind. Eng. Chem. Res. 1988, 27, 1996.
[113] R. M. Deshpande, S. S. Divekar, B. M. Bhanage, R. V. Chaudhari, J. Mol. Cutul. 1992,
77, L13.
[I141 R. M. Deshpande, R. V. Chaudhari, J. Catal. 1989, 115, 326.
[ I 1 51 (a) P. Purwanto, H. Delmas in Catalysis in Multiphase Reactors, Lyon 1994, Book of
Abstracts C IV-2; (b) P. Purwanto, H. Delmas, Catal. Today 1995, 24, 135.
[ I 161 (a) B. Comils, E. Wiebus, Chem.-Ing.-Techn. 1994, 66, 916 and references cited
therein; (b) E. Wiebus, B. Cornils, CHEMTECH 1995, 25, 33.
[117] M. Royo, F. Melo, A. Manrique, Transition Met. Chem. 1982, 7, 44.
[I181 T. G. Southern, J. Mol. Catal. 1985, 30, 267.
[119] J. Hjortkjaer, P. Toromanova-Petrova, J. Mol. Catal. 1989, 50, 203.
[ 1201 A. van Rooy, E. N. Orij, P. C. J. Kamer, P. W. N. M. van Leeuwen, Organometallics
1995, 14, 34.
[121] V. L. Hughes, I. Kirshenbaum, Ind. Eng. Chem. 1957, 49, 1999.
[122] J. Falbe, N. Huppes, Brennstoff Chem. 1967, 48, 46.
[123] (a) M. Bianchi, F. Piacenti, J. Organomet. Chem. 1977, 137, 361.
[124] (a) R. Martin, Chem. Ind. (London) 1954, 1536; (b) G. Natta, R. Ercoli, S. Castellano,
Chim. Ind. (Milan) 1955, 37, 6; (c) R. Iwanaga, Bull. Chem. Soc. Jpn. 1962, 35, 778.
[125] F. Piacenti, P. Pino, R. Lazzaroni, M. Bianchi, J. Chem. SOC. (C) 1966, 488.
[I261 S. Brewis, J. Chem. SOC. 1964, 5014.
[I271 (a) P. Chini, Inorg. Chem. 1969, 8, 1206; (b) P. Chini J. Chem. SOC., Chem. Commun.
1967, 440; (c) P. Chini, S. Marinengo, Inorg. Chim. Acta 1969, 3, 315.
[I281 B. Cornils in [4], p. 78.
[I291 J. Falbe, H. Tummes, J. Weber, Brennstoff Chem. 1969, 50, 46.
[I301 B. Cornils, J. Falbe, H. Tummes, Chem.-Ztg. 1973, 97, 368.
[I311 F. Piacenti, M. Bianchi, E. Benedetti, P. Frediani, J. Organomet. Chem. 1970, 23, 257.
[132] K. L. Olivier, F. B. Booth, Hydrocarbon Process. 1970, 49(4), 112.
[133] W. Rupilius, J. J. McCoy, M. Orchin, Ind. Eng. Chem., Prod. Res. Dev. 1971, 10, 142.
[134] E. R. Tucci, Ind. Eng. Chem., Prod. Res. Dev. 1968, 7, 32.
[135] (a) Shell Oil (L. H. Slaugh, R. D. Mullineaux), US 3.239.569 (1966); (b) Shell Oil (L. H.
Slaugh, R. D. Mullineaux), US 3.239.570 (1966); (c) L. H. Slaugh, R. D. Mullineaux, J.
Organomet. Chem. 1968, 13,469.
[I361 E. R. Tucci, Ind. Eng. Chem., Prod. Res. Dev. 1970, 9, 516.
[137] C. P. Casey, L. M. Petrovich, J. Am. Chem. Soc. 1995, 117, 6007.
[138] K. L. Olivier, F. B. Booth, Hydrocarbon Process. 1970, 49(4), 112.
[139] W. R. Moser, C. J. Papile, D. A. Brannon, R. A. Duwell, S. J. Weininger, J. Mol. Catal.
1987, 41, 27 1.
[140] Union Carbide (D. E. Bryant, E. Billig), US 4.277.627 (1981).
[141] W. R. Moser, C. J. Papile, S. J. Weininger, J. Mol. Catal. 1987, 41, 293.
[142] (a) R. A. Dubois, P. E. Garrou, K. Lavin, H. R. Allock, Organometallics 1984, 3,649;
(b) A. G. Abatjoglou, E. Billig, D. R. Bryant, Organometallics 1984, 3, 923;
(c) A. G. Abatjoglou, D. R. Bryant, Organometallics 1984,3,932; (d) R. M. Deshpande,
S. S. Divekar, R. V. Gholap, R. V. Chaudhari, J. Mol. Catal. 1991, 67, 333.
[ 1431 D. Kirchhof, ex Ruhrchemie AG, private communication.
[ 1441 Engelhard Corp., Chem. Catal. News 1994.
[ 1451 Anon., 0x0 Alcohol Production Costs, ChemSystems, 1991.
 References 99

[146] Union Carbide Corp. (R. L. Pruett, J. A. Smith), US 3.527.809 (1967).

[147] Union Carbide Corp. (D. L. Bunning, M. A. Blessing), EP 188.246 (1986).
[148] P. H. M. Vleeschhouwer, R. D. Carton, J. M. H. Fortuin, Chem. Eng. Sci. 1992,
47(9-11) 2547.
[149] H. L. Pelt, R. P. J. Verburg, J. J. F. Scholten, J. Mol. Catal. 1985, 32, 77.
[I501 J. Haggin, Chem. Eng. News 1995, April 17, 25.
[151] Exxon Res. Eng. Co. (J. T. Horvhth, J. Rabai), EP 633.062 (1994).
[152] Union Carbide Corp. (R. W. Halstead, J. C. Chaty), DE 2.730.527 (1977).
[153] G. Astarita, D. W. Savage, A. Bisio, Gas Treating with Chemical Solvents, Wilcy, Ncw
York, 1983.
[154] (a) BASF AG, Hydrocarbon Process. 1977, 11, 135; (b) BASF AG, Hydrocarbon
Process. 1977, 11, 172.
[155] BASF AG (H. J. Nienburg et al.) DE 2.206.252 (1973).
[156] R. Kummer, H. J. Nienburg, H. Hohenschutz, M. Strohmeyer, ACS Adv. Chem. Ser:
1974, 132, 19.
[157] BASF AG (W. Kniese et al.) DE 2.103.454 (1972).
[158] G. Dumbgen, D. Neubauer, Chem.-Zng.-Techn. 1969, 41, 974.
[159] G. Dumbgen, D. Neubauer, Erdol, Kohle 1969, 22, 664.
[ 1601 BASF AG (D. Neubauer et al.) DE 2.544.570 (1975).
[161] BASF AG (R. Kummer et al.) DE 2.244.379 (1974).
[162] BASFAG (H. Moell et al.) DE 1.272.911 (1966).
[ 1631 W. J. Scheidmeier, Chem.-Ztg. 1973, 96, 383.
[164] R. Kummer, H. J. Nienburg, H. Hohenschutz, M. Strohmeyer, New Hydroformylation
Technology with Cobalt Carbonyls, Paper presented at the Symposium on Homo-
geneous Catalysis, Chicago, August 1973.
[I651 Prod. Chim. Ugine Kuhlmann, Znfi Chim. Ed. Spec. Esport 1973, 105.
[166] Prod. Chim Ugine Kuhlmann (C. Demay, C. Bourgeois), FR 2.544.713 (1983).
[I671 Prod. Chim. Ugine Kuhlmann (H. Lemke), DE 1.443.799 (1969) and DE 1.206.419
(1968).
[168] H. Lemke, Hydrocarbon Process. 1966, 45, 148.
[169] Exxon Res. Engng. Co. (J. A. A. Hanin), EP 183.545 (1985).
[170] Exxon Res. Engng. Co. (J. A. A. Hanin), EP 183.546 (1985).
[171] Exxon Chem. Pat. Inc. (J. A. A. Hanin), EP 343.819 (1989).
[172] Exxon Chem. Pat. Inc. (W. H. Summerlin), US 5.237.104 (1992).
[173] Exxon Chem. Pat. Inc. (E. van Driessche et al.), EP 372.925 (1989).
[I741 Exxon Chem. Pat. Inc. (J. A. A. Hanin, E. van Driessche), PCT Int. WO 93/24.436
(1993).
[I751 Exxon Chem. Pat. Inc. (J. M. Vargas et a].), US 5.059.718 (1990).
[176] Ruhrchemie AG (H. Tummes, J. Falbe), DE 1.817.051 (1968).
[I771 Exxon Res. Engng. Co. (A. van Vliet), EP 183.547 (1985).
[178] Shell Oil Co. (T. H. Johnson), US 4.584.411 (1985).
[179] W. W. Spooncer, A. C. Jones, L. H. Slaugh, J. Organomet. Chem. 1969, 18, 327.
[ 1801 Shell Oil Co. (L. H. Slaugh, R. D. Mullineaux), US 3.239.569 ( 1 966).
[I811 Shell Oil Co. (L. H. Slaugh, R. D. Mullineaux), US 3.239.570 (1966).
[182] L. H. Slaugh, R. D. Mullineaux) J. Organomet. Chem. 1968, 13, 469.
[183] T. Bartik, B. Bartik, B. E. Hanson, J. Mol. Catal. 1993, 85, 121.
[I841 C. D. Wood, P. E. Garrou, Organometallics 1984, 3, 170.
[185] Shell Int. Res. (B. L. Goodall, P. A. M. Grotenhuis), GB 2.213307 (1989).
[186] Shell Oil Co. (C. R. Greene), US 3.369.050 (1964).
[I871 Shell Int. Res. (C. R. Greene, R. E. Meeker), DE 1.212.953 (1962) and US 3.274.263
(1961).
100 2.1 Carbon Monoxide and Synthesis Gas Chemistry

[188] Shell Int. Res. (C. R. Greene), DE 1.468.615 (1962).

[189] Shell Int. Res., BP 1.002.429 (1963).
[190] Shell Int. Res. (C. R. Greene, W. A. Brown), DE 1.593.368 (1966).
[191] J. H. Craddock, A. Hershman, F. E. Poulik, J. F. Roth, Ind. Eng. Chem., Prod. Res. Dev.
1969, 8, 291.
[192] Anon., Celanese Corp. Annual Business Report 1974, p. 9.
[193] Anon., Chem. Eng. 1977, 84, 110.
[194] E. A. V. Brewester, Chem. Eng. 1976, 83, 90.
[195] Johnson, Matthey & Co. (G. Wilkinson), DE 1.939.322 (1969).
[196] Union Carbide Corp. (R. L. Pruett, J. A. Smith), US 4.148.830 (1969).
[I971 Union Carbide Corp. (R. L. Pruett, J. A. Smith), DE 2.062.703 (1971).
[I981 Union Carbide Corp. (D. G. Morrell, P. D. Sherman), DE 2.802.922 (1978).
[I991 Union Carbide Corp. (W. Otte et al.), EP 017.183 (1980).
[200] Union Carbide Corp. (E. A. V. Brewester, R. L. Pruett), DE 2.715.685 (1977).
[201] Union Carbide Corp. (E. A. V. Brewester, R. L. Pruett), DE 2.715.686 (1977).
[202] Union Carbide Corp. (D. L. Bunning, D. B. Stanton), EP 097.891 (1983).
[203] Davy Powergas Ltd. (R. Fowler), GB 1.387.657 (1973).
[204] Union Carbide Corp. (D. L. Bunning, M. A. Blessing), EP 188.246 (1986).
[205] Union Carbide Corp. (K. D. Sorensen), EP 484.976 (1991).
12061 Union Carbide Corp. (D. L. Bunning), EP 404.193 (1990).
[207] Union Carbide Corp. (D. R. Bryant et al.), EP 504.814 (1992).
[208] Johnson, Matthey PLC (D. F. Booker et al.), GB 2.097.795 (1982).
[209] Union Carbide Corp. (A. G. Abatjoglou, D. R. Bryant), US 5.114.473 (1988).
[210] Davy Int. Ltd. (N. Harris, T. F. Shevels), EP 007.768 (1979).
[211] Arco Chemical Techn. L. P. (Te Chang), US 5.290.743 (1993).
[212] RhGne-Poulenc Ind. (E. Kuntz et al.), FR 2.230.654 (1983), FR 2.314.910 (1975),
FR 2.338.253 (1976), FR 2.349.562 (1976), FR 2.366.237 (1976), FR 2.473.504
(1979), FR 2.478.078 (1980), FR 2.550.202 (1983), FR 2.561.650 (1984).
[213] E. G. Kuntz, CHEMTECH 1987, 17, 570.
[214] (a) Europ. Chem. News 1995, Jan. 15, 29; (b) Europa Chemie 1995, (l), 10.
[215] Ruhrchemie AG (H. Bach, B. Cornils, W. Gick, H. D. Hahn, W. Konkol, E. Wiebus),
DE 3.640.614 (1986).
[216] BASF AG (R. Kummer, K. Schwirten), DE 3.301.591 (1983).
[217] BASF AG (R. Zehner et al.), DE 3.625.261 (1986).
[218] BASF AG (W. Richter, R. Kummer, K. Schwirten), DE 3.126.265 (1981).
[219] BASF AG (H. Elliehausen et al.), DE 3.220.858 (1982).
[220] BASFAG (K. Fischer et al.), DE 3.114.147 (1981).
[221] BASF AG (P. Zehner et al.), EP 254.180 (1987).
[222] Davy International Oil & Chemicals Ltd., LP 0x0 Process, Evaluation Data,
1979.
[223] Mitsubishi Kasei Corp. (C. Miyazawa, H. Mikami), EP 423.769 (1990).
[224] Mitsubishi Kasei Corp. (T. Mori, A. Ueda, K. Fujita), DE 4.419.898 (1994).
[225] Mitsubishi Kasei Corp. (M. Ogawa et a].), EP 0.589.463 (1994).
[226] (a) C. U. Pittman, Jr. in Polymer-Supported Reactions in Organic Synthesis (Eds.:
P. Hodge, D. C. Shenington), Wiley, New York, 1980, 249; (b) C. U. Pittman, Jr. in
Comprehensive Organometallic Chemistry (Eds. : G. Wilkinson, F. G. A. Stone,
E. W. Abel), Pergamon, Oxford, 1982, Vol. 8, 553.
[227] J. Lieto, D. Milstein, R. L. Albright, J. V. Minkiewicz, B. C. Gates, Chemtech 1983, 13,
46.
[228] M. J. Sundell, J. H. Nasman, Chemtech 1993, 23(12), 16.
[229] Mitsubishi Kasei Corp. (K. Tano, K. Sato, T. Okoshi), DE 3.338.340 (1983).
 References 101

[230] Mitsubishi Kasei Corp. (K. Sato, Y. Kawaragi), EP 429.963 (1 990).

12311 Mitsubishi Kasei Corp. (C. Miyazawa, H. Mikami), EP 423.769 (1990).
[232] Mitsubishi Kasei Corp. (C. Miyazawa, S. Orita, A. Tsuboi), EP 278.407 (1988).
[233] Mitsubishi Kasei Corp. (C. Miyazawa, H. Mikami, A. Tsuboi), EP 272.608 (1987).
[234] P. Dierkes, P.W.N.M. van Leeuwen, J. Chem. Soc., Dalton Trans. 1999, 1519;
G.J.H. Buisman, E.J. Vos, P.W.N.M. van Leeuwen, P.C.J. Kamer, C.P. Casey,
G. T. Whiteeker, M. G. Melville, L. M. Petrovich, J. A. Gavney, D. R. Powell, J. Am.
Chem. SOC.1992, 114; 5535 and 10680; K. Yamamoto, S. Momose, M. Funahashi,
S. Ebata, H. Ohmura, H. Komatusa, M. Miyazawa, Chem. Lett. 1994, 189.
[235] K. Tamao, H. Yamamoto, H. Matsumoto, N. Miyake, T. Hayashi, M. Kumada, Tetra-
hedron Lett. 1977, 16, 1389.
[236] (a) Eastman Kodak (T. J. Devon, G. W. Phillips, T. A. Puckette, J. L. Stavinoha, J. J.
Vanderbilt), WO 87/07.600 (1987); Chem. Abstr: 1988, 109, 8397; (b) Eastman
Kodak (T. J. Devon, G. W. Phillips, T. A. Puckette, J. L. Stavinoha, J. J. Vanderbilt),
US 4.694.109 (1987); Chem. Abstr: 1988, 108, 7890; (c) Eastman Kodak (T. A.
Puckette, T. J. Devon, G. W. Phillips, J. L.: Stavinoha), US 4.879.416 (1989);
Chem. Abstr: 1990, 112, 217269; (d) Eastman Kodak (J.L. Stavinoha, G.W.
Phillips, T.A. Puckette, T.J. Devon), EP 326.286 (1989); Chem. Abstr: 1990, 112,
98823.
[237] W. A. Herrmann, C. W. Kohlpaintner, R. B. Manetsberger, H. Bahrmann, H. Kottmann,
J. Mol. Catal. 1995, 97, 65.
[238] J. M. Brown, A. G. Kent; J. Chem. SOC.Perkin Trans. I f 1987, 1597.
[239] C. P. Casey, E. L. Paulsen, W. E. Beuttenmueller, R. B. Proft, L. M. Petrovich, B. A.
Matter, D.R. Powell, J. Am. Chem. Soc. 1997, 119, 11817.
[240] (a) L. A. van der Veen, P. C. J. Kamer, P. W. N. M. van Leeuwen, P. H. Keeven, G. C.
Schoemaker, J. N. H. Reek, M. Lutz, L. A. Speck, Organometallics 2000, 19, 872;
(b) P. W. N. M. van Leeuwen, M. Kranenburg, Y. E.M. van der Burgt, P.C. J. Kamer,
K. Goubitz, J. Fraaije, Organometallics 1995, 14, 3081; (c) L . A . van der Veen,
M. D. K. Boele, F. R. Bregmann, P. C. J. Kamer, P. W. N. M. van Leeuwen, K. Goubitz,
J. Fraanje, H. Schenk, C. Bo, J. Am. Chem. Soc. 1998, 120, 11616; (d) Celanese
(H. GeiBler, P. C. J. Kamer, P. W. N. M. van Leeuwen, L. van der Veen), EP 0.982.314
(1999).
[241] L. A. van der Veen, P.C. J. Kamer, P. W.N.M. van Leeuwen, Angew. Chem. 1999, 111,
349.
[242] S.A. Laneman, F.R. Fronczek, G.G. Stanley, J. Am. Chem. Soc. 1988, 110, 5585.
[243] (a) S. A. Laneman, G. G. Stanley, ACS Adv. Chem. Ser: 1992,230, 349; (b) M. E. Brous-
sard, B. Juma, S. G. Train, W.-J. Peng, S. A. Laneman, G. G. Stanley, Science 1993,
260, 1784; (c) Lousiana State University (G.G. Stanley, S.C. Laneman), US
5.200.539 (1993).
[244] G. Suss-Fink, Angew. Chem. 1994, 106,71; Angew. Chem., Int. Ed. Engl. 1994,33,67.
[245] W.A. Herrmann, C. W. Kohlpaintner, H. Bahrmann; DE 4.040.314 (1990); Chem.
Abstr: 1990, 114, 143702~;W.A. Herrmann, C.W. Kohlpaintner, H. Bahrmann,
W. Konkol, J. Mol. Catal. A: 1992, 73, 191.
[246] W. A. Herrmann, C. W. Kohlpaintner, Angew. Chem., Znt. Ed. Engl. 1993, 32, 1524;
W. A. Herrmann, C. W. Kohlpaintner, R. B. Manetsberger, H. Bahrmann, H. Kottmann,
J. Mol. Catal. A: 1995, 97, 65.
[247] M. Schreuder Goedheijt, P.C. J. Kamer, P. W.N. M. van Leeuwen, J. Mol. Cutal. A:
1998, 134, 243.
[248] F. Bitterer, 0. Herd, A. Hessler, M. Kuhnel, K. Rettig, 0. Stelzer, W.S. Sheldrick,
S. Nagel, N. Rosch, Inorganic Chem. 1996,35,4103;0.Stelzer, 0. Herd, N. Weferling,
EP 0.638.578.
102 2.1 Carbon Monoxide and Synthesis Gas Chemistry

[249] (a) T. Bartik, B. Bartik, 1. Guo, B. E. Hanson, J. Organomet. Chem. 1994, 480, 15; (b)
H. Ding, B. E. Hanson, T. Bartik, B. Bartik, Organometallics 1994, 13, 3761 ; (c) T. Bar-
tik, B. Bartik, B. E. Hanson, J. Mol. Catal. 1994, 88, 43; (d) H. Ding, B. E. Hanson, J.
Chem. SOC.,Chem. Commun. 1994, 2747; (e) T. Bartik, H. Ding, B. Bartik, B. E. Han-
son, J . Mol. Catal. A: 1995, 98, 117.
[250] H. Ding, J. Kang, B. E. Hanson, C. W. Kohlpaintner, J. Mol. Catal. A: 1997, 124, 21.
[251] H. Ding, B.E. Hanson, C.W. Kohlpaintner, Card Today 1998, 42, 421.
[252] E. Fache, C. Santini, F. Senocq, J.-M. Basset, J. Mol. Catal. 1992, 72, 337; Ruhrchemie
AG (H. W. Bach, B. Comils, E. Wiebus), DE 3.640.614 (1986).
[253] M. Schreuder Goedheijt, B. E. Hanson, J. N.H. Reek, P.C. J. Kamer, P. W.N.M. van
Leeuwen, J. Am. Chem. Soc. 2000, 122, 1650.
[254] S. Shimizu, S. Shirakawa, Y. Sasaki, C. Hirai, Angew. Chem., Int. Ed. 2000, 39, 1256.
[255] Union Carbide (E. Billig, A.G. Abatjoglou, D.R. Bryant), US 4.668.651 (1987);
EP Appl. 213.639 (1987); Chem. Abstr: 1987, 107, 7392; Union Carbide (E. Billig,
A. G. Abatjoglou, D. R. Bryant, R. E. Murray, J. M. Maher), US 4.599.206 (1986),
Chem. Abstr: 1988, 109, 233177.
[2.56] DSMDuPont (P. M. Burke, J. M. Gamer, W. Tam, K. A. Kreutzer, A. J. J. M. Teunissen),
WO 97133854 (1997); Chem. Abstr: 1997, 127, 294939.
[257] Mitsubishi (K. Sato, J. Karawagi, Y. Tanihari), JP 07.278.040; Chem. Abstr: 1996, 124,
23 1851 ; Mitsubishi (K. Sato, J. Karawagi, M Takai, T. Ookoshi), US 5.235.11 3 (1993);
and EP 518.241; Chem. Abstr: 1993, 118, 191183.
[258] A. van Rooy, P.C.J. Kramer, P.W.N.M. van Leeuwen, N. Veldman, A.L. Spek,
J. Organomet. Chem. 1995, 494, C15
[259] D. Selent, K. D. Wiese, D. Rottger, A. Bomer, Angew. Chem. 2000, 112, 1694.
[260] C. Wieser, C. B. Dielemen, D. Matt, Coord. Chem. Rev. 1997, 165, 93.
[261] BASF (R. Paciello, M. Roper, H. J. Kneuper, E. Langguth, M. Peter), DE 4.321.194
(1995); Chem. Abstr: 1995, 122, 160937; R. Paciello, L. Siggel, M. Roper, Angew.
Chem., Int. Ed. Engl. 1999, 38, 1929; R. Paciello, L. Siggel, M. Roper, N. Walker,
J. Mol. Catal. A: 1999, 143, 85.
[262] F. J. Parleviet, C. Kiener, J. Fraanje, K. Goubitz, M. Lutz, A. L. Speck, P. C. J. Kamer,
P. W. N. M. van Leeuwen, J. Chem. Soc., Dalton Trans. 2000, 1113.
[263] Shell Int. Res. (E. Drent, W. W. Jager), GB 2.282.137 (1995).
12641 C. Abu-Gnim, I. Amer, J. Chem. Soc., Chem. Commun. 1994, 115.
126.51 C. Basoli, C. Botteghi, M. A. Cabras, G. Chelucci, M. Marchetti, J. Organomet. Chem.
1995,488, C20.
[266] (a) A. Bader, E. Lindner, Coord. Chem. Rev. 1991, 108, 27; (b) C. Vaecher, A. Mor-
treux, F. Petit, J. P. Picaret, H. Sliwa, N. W. Murall, A. J. Welch, Inorg. Chem. 1985,
24, 2338; (c) S. Gladiali, L. Pinna, C.G. Arena, E. Rotondo, F. Faraone, J. Mol.
Catal. 1991, 66, 183; (d) D. Drommi, F. Nicolo, C. G. Arena, G. Bruno, F. Faraone,
R. Gobetto, Inorg. Chim. Acta 1994, 221, 109; (e) G.R. Newkome, Chem. Rev.
1993,93,2067; (0S. Naili, J.-F. Carpentier, F. Agbossou, A. Mortreux, G. Nowogrocki,
J.-P. Wignacourt, Organometallics 1995, 14, 401 ; (g) P. A. T. Hoye, R. D. W. Kemmit,
D. L. Law, Appl. Organomet. Chem. 1993, 7, 513; (h) C. Abu-Gnim, I. Amer. J. Mol.
Cutal. 1993, 85, L275; (i) A. Buhling P. C. J. Kamer, P. W. N. M. van Leeuwen, J. Mol.
Cutal. A: 1995, 98, 69.
12671 (a) W. A. Herrmann, M. Elison, J. Fischer, C Kocher, G. R. J. Georg, Chem. Eur: J.
1996, 2, 772; (b) Hoechst AG (W.A. Henmann, M. Elison, C. Kocher, J. Fischer,
K. Ofele), DE 4.447.066 (1995); (c) Hoechst AG (W.A. Herrmann, M. Elison,
C. Kocher, J. Fischer), DE 4.447.067 (1995); (d) Hoechst AG (W.A. Herrmann,
M. Elison, C. Kocher, J. Fischer), DE 4.447.068 (1995); (e) Hoechst AG (W. A. Herr-
mann), DE 4.447.070 (1995)
 References 103

[268] (a) A.J. Arduengo, R.L. Harlow, M. Kline, J. Am. Chem. Soc. 1991, 113, 361;
(b) D. A. Dixon, A. J. Arduengo, J. Phys. Chem. 1991, 95, 4180; (c) A. J. Arduengo,
H.V. Rasika-Diaz, R.L. Harlow, M. Kline, J. Am. Chem. Soc. 1992, 114, 5530.
[269] (a) Celanese (C.C. Brasse, A. Salzer, H. Bahrmann), WO 99A6.737 (1999); (b) Cela-
nese (C. C. Brasse, A. Salzer, H. Bahrmann), WO 99/16.776 (1999).
[270] C. C. Brasse, U. Englert, A. Salzer, H. Waffenschmidt, P. Wasserscheid, Organometal-
lics 2000, 19, 3818.
12711 J. Haggin, Chem. Eng. News 1995, April 17, 25.
12721 (a) I.T. HorvBth, J. Rkbai, Science 1994, 266, 72; (b) Exxon Res. (I.T. HorvAth,
J. RBbai), EP 633.062 (1994); (c) J. A. Gladysz, Science 1994, 266, 55.
[273] (a) Union Carbide Corp. (J.E. Babin, J.M. Maher, E. Billig), US 5.364.950 (1992);
(b) Union Carbide Corp. (T.W. Leung, D.R. Bryant, B.L. Shaw), US 5.731.472
(1998); (c) Union Carbide Corp. (E. Billig, D. R. Bryant, C. A. Beasley, D. L. Momson,
M. D. Warholic, K. E. Stockman), US 6.090.987 (2000).
12741 B. Cornils, E. Wiebus, Rec. Trav. Chim. Pays-Bas 1996, 115, 211.
[275] J. P. Arhancet, M. E. Davis, J. S. Merola, B. E. Hanson, Nature 1989, 339, 454.
[276] M. E. Davis, CHEMTECH 1992, 498.
[277] I. Toth, I. Guo, B.E. Hanson, J. Mol. Catal. 1997, 116, 217.
[278] A. J. Sandee, V. F. Slagt, J. N. H. Reek, P. C. J. Kamer, P. W. N. M. van Leeuwen, Chem.
Commun. 1999, 1633.
[279] (a) A. D. Pomogailo, D. Wohrle in Macromolecule-Metal Complexes (Eds.: F. Ciar-
delli, E. Tsuchida, E. Wohrle), Springer, Berlin, 1996; (b) W. Keim, B. Driessen-
Holscher in Handbook of Heterogenous Catalysis, Vol. 1 (Eds.: G. Ertl, H. Knozinger,
J. Weitkamp), Wiley-VCH, Weinheim, 1997.
[280] (a) K. Nozaki, Y. Itoi, F. Shibahara, E. Shirakawa, T. Ohta, H. Takaya, T. Hiyama, J.
Am. Chem. Soc. 1998, 120, 4051; (b) K. Nozaki, Y. Itoi, F. Shibahara, E. Shirakawa,
T. Ohta, H. Takaya, T. Hiyama, Bull. Chem. Soc. Jpn. 1999, 72, 1911.
[281] U. Deschler, P. Kleinschmidt, P. Panster, Angew. Chem., Int. Ed. Engl. 1986, 25, 236.
[282] S. J. Monaco, E.I. KO, CHEMTECH 1998, (6), 23; (b) C.M. Ingersoll, F. V. Bright,
CHEMTECH 1997, (l), 26.
[283] S. Wieland, P. Panster, Catal. Org. React. 1994, 62, 383.
[284] J. S. Albertus, L. A. van der Veen, J. N. H. Reek, P. C. J. Kamer, M. Lutz, A.L. Speck,
P.W.N.M. van Leeuwen, Angew. Chem. 1999, 111, 3428.
[285] P. G. Jessop, W. Leitner (Eds.), Chemical Synthesis Using Supercritical Fluids, Wiley-
VCH, Weinheim, 1999.
12861 S. Kainz, D. Koch, W. Baumann, W. Leitner, Angew. Chem., Int. Ed. Engl. 1997, 36,
1628.
[287] D. Koch, W. Leitner; J. Am. Chem. SOC. 1998, 120, 13398.
[288] D. R. Palo, C. Erkey, Organometallics 2000, 19, 81.
[289] (a) I.T. Horvath, J. Rabai, Science 1994, 266, 72; (b) I.T. Horvath, Acc. Chem. Res.
1998, 31, 641.
[290] J. Jinayang, Y. Wang, C. Liu, F. Han, Z. Jin, J. Mol. Catal. A: 1999, 147, 131.
[291] M.T. Reetz, S.R. Waldvogel, Angew. Chem., Int. Ed. Engl. 1997, 36, 865.
[292] (a) Y. Chauvin, L. Mussmann, H. Olivier, Angew. Chem. 1995, 107, 2941 ; (b) Y. Chau-
vin, L. Mussmann, H. Olivier, EP 0.776.880 (1996).
[293] B. Cornils, H.-W. Bohnen, Adv. Catalysis 2002, in press.
[294] B. Cornils, Org. Proc. Res. & Dev. 1998, 2, 121.
104 2.1 Carbon Monoxide and Synthesis Gas Chemistry

2.1.2 Carbonylations

2.1.2.1 Synthesis of Acetic Acid and

Acetic Acid Anhydride from Methanol
Paull Torrence"

2.1.2.1.1 Basic Catalysis

According to eq. ( I ) carbonylation of methanol by formal CO insertion into the
C-0 bond yields acetic acid:

CH30H + CO - cat.
Ap, AT
CH3COOH andlor (CH3CO)20 (1 1
The reaction is catalyzed by metal complexes, the central atoms favorably being
Co or Rh. Nowadays all other routes to acetic acid (especially via acetaldehyde, cf.
Section 2.4.1, and its oxidation, Section 2.4.4) are economically obsolete.
As far as the central atoms are concerned, in particular the Group VIII metals
Co, Ni, Ru, Rh, Pd, Ir, and Pt form effective carbonylation catalysts, each metal
demonstrating a different carbonylation activity. Rh and Lr are the most active and
preferred catalysts for carbonylation reactions to produce acetic acid or acetic
anhydride, or for co-production of acetic acid and acetic anhydride [l, 21. Co is
only of historical interest.
The key elements of these carbonylation processes is the ability of a metal com-
plex to undergo facile oxidative addition with methyl halide (especially iodide),
carbon monoxide (CO) insertion into the methyl-metal bond, and reductive
elimination of the acetyl group as the acetyl halide [3].
When Rh is the metal catalyst, a common catalytic pathway is proposed which
involves the nucleophilic attack of the active Rh' catalyst complex, [Rh(CO),I,]-,
on methyl iodide (CH31) to form a methylrhodium(II1) intermediate, [Rh(CH,)
(CO)2(I)3]-. Rapid methyl migration in this complex generates the acylrho-
dium(II1) intermediate, [Rh(CH,CO)(CO)IJ, which reacts with CO to form
[Rh(CH,CO)(CO),I,]- and subsequently reductively eliminates acetyl iodide
and regenerates the rhodium(1) anion. The final reaction of acetyl iodide with
compounds containing hydroxyl groups such as water, methanol (CH,OH), or
acetic acid (eq. (2)) leads to the formation of hydrogen iodide (HI) and the corre-
sponding acetyl derivatives.
CH3COI + HOR - CH3COOR + HI (2)
R = H, CH3, COCH3

* Basedon the contribution to thejrst edition by Michael GauJ, Andreas Seidel,

Paull Torrence, and Peter Heymanns.
 2.1.2.1 Synthesis of Acetic Acid and Acetic Acid Anhydride from Methanol 105

This final reaction step of the carbonylation mechanism is the primary dis-
tinguishing feature of each carbonylation process. A sufficient concentration of
water or acetic acid in the reactor is therefore necessary to achieve high acetic
acid or acetic anhydride formation rates respectively.
The hydrogen iodide liberated then reacts with methanol, methyl acetate (or di-
methyl ether) to regenerate methyl iodide promoter (eq. (3)):
HI + CH3OR - CH3l + HOR (3)
R = H, CH3, COCH3

For the carbonylation of methyl acetate and the co-carbonylation of methyl

acetate and methanol, the reaction of acetyl iodide with methyl acetate (or
dimethyl ether, DME) is a key reaction step also (eq. (4))[4]:
CH3COl + CHsOR - CH3l + CH3COOR (4)
R = CH3, COCH3

Credence for this general carbonylation mechanism is supported by IR model

studies in various solvents of key steps in the proposed reaction pathway
[5b, 6-8, 9c,e]. These investigations include isolation and characterization of
the acyl carbonyl complex as the dimer [lo] and most recently spectroscopic
evidence of the methyl intermediate in the presence of excess CH31 [9c, 9e].
The carbonylation rate is independent of the type of rhodium compound charged
to the reaction as long as sufficient CHJ and CO are available. This supports the
concept of the generation of a common active catalyst under reaction conditions
[11, 121.
An overview of Monsanto's catalyst system in comparison with other processes
is given in Table 1 [23, 801.

Table 1. Catalyst systems for carbonylations of methanol and methyl acetate.

Company Product Central atom Complex Co-cataly st
Monsanto AcOH Rh [Rh(CO)2IJH+ MeVHI
HCC AcOH Rh [Rh(C0)J2]-Li+ MeULiI
Eastman Ac~O Rh [Rh(CO),I,]-Li+ MeVLiI
Hoechst Ac20 Rh [Rh(CO),I2I-p(R)'l+ MeVP salts
BP Ac20/AcOH Rh [Rh(CO),I,]-N(R),' MeVN salts
(Zr compound)
BP AcOH Ir [Ir(CO),I,IH' MeViodide
salts, metal
carbon yls
(i.e., Ru iodide
carbonyls
106 2.1 Carbon Monoxide and Synthesis Gas Chemistry

2.1.2.1.2 Acetic Acid

Introduction

The manufacture of acetic acid by the rhodium-catalyzed carbonylation of metha-

nol (eq. ( 5 ) ) is one of the most important industrial processes.

CH3OH + CO - Rh, 12
150-200 “C
30-60bar
CH3COOH (5)

Acetic acid is a key commodity building block [l]. Its most important deriva-
tive, vinyl acetate monomer, is the largest and fastest growing outlet for acetic
acid. It accounts for an estimated 40 % of the total global acetic acid consumption.
The majority of the remaining worldwide acetic acid production is used to man-
ufacture other acetate esters (i.e., cellulose acetates from acetic anhydride and
ethyl, propyl, and butyl esters) and monochloroacetic acid. Acetic acid is also
used as a solvent in the manufacture of terephthalic acid [2] (cf. Section
2.8.1.2). Since Monsanto commercially introduced the rhodium- catalyzed carbo-
nylation process (“Monsanto process”) in 1970, over 90 % of all new acetic acid
capacity worldwide is produced by this process [2]. Currently, more than 50 % of
the annual world acetic acid capacity of 7 million metric tons is derived from the
methanol carbonylation process [2]. The low-pressure reaction conditions, the
high catalyst activity, and exceptional product selectivity are key factors for the
success of this process in the acetic acid industry [13].
Since 1979, numerous reviews have appeared on the kinetics, mechanisms, and
process chemistry of the metal-catalyzed methanol carbonylation reaction [ 11,
14-20], especially the Monsanto rhodium-catalyzed process. In this section, the
traditional process chemistry as patented by Monsanto is discussed, with emphasis
on some of the significant improvements that Monsanto’s licensee, Celanese
Chemicals (CC) has contributed to the technology. The iridium-based methanol
carbonylation process recently commercialized by BP Chemicals Ltd. (BP) will
be discussed also.

Process History

The low-pressure acetic acid process was developed by Monsanto in the late
1960s and proved successful with commercialization of a plant producing
140 X lo3 metric tons per year in 1970 at the Texas City (TX, USA) site [21].
The development of this technology occurred after the commercial implementa-
tion by BASF of the cobalt-catalyzed high-pressure methanol carbonylation
process [22]. Both carbonylation processes were developed to utilize carbon
monoxide and methanol as alternative raw materials, derived from synthesis
gas, to compete with the ethylene-based acetaldehyde oxidation and saturated
hydrocarbon oxidation processes (cf. Sections 2.4.1 and 2.8.1.1). Once the Mon-
santo process was commercialized, the cobalt-catalyzed process became noncom-
 2.1.2.1 Synthesis of Acetic Acid and Acetic Acid Anhydride from Methanol 107

petitive. Today over ten companies worldwide practice the methanol carbonyla-
tion technology [2].
In 1978, Celanese Chemicals (CC) was the first Monsanto licensee to operate
the Monsanto acetic acid process commercially. Soon after start-up of this unit,
Celanese implemented several process improvements to expand the unit capacity.
Later, in the early 1980s, CC developed the proprietary, low reaction water tech-
nology which improved the process significantly (known as Acid Optimization
(AO)). The low-water technology was achieved in part by increasing the rhodium
catalyst stability by addition of inorganic iodide in high concentrations to the re-
action system [23] above an iodide concentration level not usually thought to be
effective as a catalyst stabilizer and promoter [15, 241. This alteration to the cata-
lyst composition allows reactor operation at low water and high methyl acetate
reaction concentrations to increase reactor productivity, purification capacity,
and methanol and carbon monoxide efficiency [5, 231. As a result, the composi-
tion of the catalyst solution used in the low-water technology by Celanese [23] is
significantly different from the catalyst composition used in the original methanol
carbonylation process patented by Monsanto [25]. In 1986 BP Chemicals Ltd.
purchased from Monsanto the technology and licensing rights to the low-pressure
methanol carbonylation technology which did not include the proprietary technol-
ogy developed by Celanese.
In 1996 BP announced the commercialization of their version of a low-water
methanol carbonylation technology named CativaTMbased upon a promoted iri-
dium catalyst. The CativaTMprocess replaced the high-water Monsanto process
which had been used by BP.

Process Chemistry

Monsanto Technology

The reaction chemistry of the rhodium-catalyzed methanol carbonylation process

under Monsanto conditions has been investigated extensively [6-8, 10, 12, 21,
26-29] (cf. Section 2.1.2.1.1). The overall reaction kinetics are first order in
both rhodium catalyst and methyl iodide promoter. The reaction is zero order in
methanol and zero order in carbon monoxide partial pressure above 2 atm (eq.
(6)) [27]. The kinetics agree well with the basic mechanism common to the
three carbonylation reactions (see Section 2.1.2.1.1 and Tables 1 and 2).
-d [CHsOH]
= k[Rh] [CHsI]
dt

The reaction medium also plays a key role in the overall activity of the catalyst
system. The reaction rate is highly dependent on the nature of the medium;
however, the overall kinetics are unaffected by reaction solvent [Sc, 27, 30-321.
This suggests that the rate dependence of the solvent is not involved in the transi-
tion-state species of the rate-determining step [5c]. Maximum carbonylation rates
are demonstrated in polar solvents and the additions of protic solvents accelerate
108 2. I Carbon Monoxide and Synthesis Gas Chemistry

the reaction rate. In particular, water exhibits a general rate enhancement in

most reaction solvents [27, 301. Acetic acid/water is the preferred medium in
the commercial process for carbonylation reactivity [25]. The dependence on
water of the reaction rate in acetic acid has been studied [24, 30-321. The carbo-
nylation reaction rate decreases markedly with a concomitant decrease in water
concentration (below ca. 10 molar) [30]. The catalyst stability also decreases
[5c, 231.

Hoechst Celanese Low-Water Acid Optimization (AO) Technology

In the Monsanto process a substantial quantity of water in the reaction system

is required to maintain catalyst activity, to achieve economically acceptable
carbonylation rates, and to maintain good catalyst stability [23, 251. Because
of the high water concentration in the reactor, the separation of water from
acetic acid is a major energy cost and unit capacity limitation in this process.
A considerable saving in operating cost and a low cost expansion potential can
be realized by operating at a low reaction water concentration if a way can
be found to compensate for the decrease in the reaction rate and catalyst sta-
bility.
Low-water operation can be accomplished with modifications to the process
which include significant changes in the catalyst system [23]. The main catalytic
cycle for high-water methanol carbonylation is still operative in the low-water
process (see Section 2.1.2.1.1), but at low water concentration two other catalytic
cycles influence the carbonylation rate. The incorporation of an inorganic or or-
ganic iodide as a catalyst co-promoter and stabilizer allows operation at optimum
methyl acetate and water concentrations in the reactor. Carbonylation rates com-
parable with those realized previously at high water concentration (ca. 10 molar)
are demonstrated at low reaction water concentrations (less than ca. 4 molar) in
laboratory, pilot plant, and commercial units, with beneficial catalyst stability
and product selectivity [23]. With this proprietary A 0 technology, the methanol
carbonylation unit capacity at the Celanese Clear Lake (TX) facility has increased
from 270 X lo3 metric tons per year since start-up in 1978 to 1200 X lo3 metric
tons acetic acid per year in 2001 with very low capital investment [33]. This unit
capacity includes a methanol-carbonylation acetic acid expansion of 200 X 1O3
metric tons per year in 2000 [33].
Recently start-up of a new 500 X lo3 metric tons per year acetic acid unit at the
Celanese Singapore facility was successful using A 0 technology.

Promotion by Methyl Acetate

In the low-water A 0 technology [23], the major function of the iodide salts is to
stabilize the rhodium carbonyl catalyst complexes from precipitation as insoluble
rhodium triiodide (Rh13) [5c]. Lithium iodide (LiI) is the preferred salt. The iodide
salts also promote catalyst activity (see below). However, the key factor that con-
 2.1.2.1 Synthesis of Acetic Acid and Acetic Acid Anhydride from Methanol 109

tributes most significantly to carbonylation rate enhancement at low water is the

methyl acetate (CH,OAc) concentration [S, 231 (CH30H fed to the reactor exists
mainly as CH,OAc in an acetic acid catalyst solution).
Monsanto investigators demonstrated that the methanol carbonylation is zero
order in CH30H even at low CH30H concentration [21]. This is true as long as
the concentration of the active catalytic species, [Rh(CO),I,]-, does not vary
with CH30H (CH,OAc) concentration, which is probably the case under the
high water concentrations of the Monsanto process. For the low-waterhigh-
iodide-promoted catalyst system, increasing the CH30Ac concentration over a
range (ca. 0-1 molar) affords an increase of the carbonylation rate by raising
the proportion of total rhodium in the catalyst solution as [Rh(CO),I,]-, the active
catalyst species [23, Sc]. This shift in the concentration of [Rh(CO),12]presults
from the direct effect of CH,OAc concentration on the rhodium-catalyzed
water-gas shift reaction (WGSR; see Section 3.2.11) [5c]. The rhodium-catalyzed
WGSR produces carbon dioxide and hydrogen (eq. (7)), the major inefficiency of
the methanol carbonylation technology.

This reaction is inherent to the process and plays an integral role in the activity
of the carbonylation reaction. It has been well studied by two different research
groups [15, 34, 351. The WGSR consists of an oxidation and reduction process
as represented in eqs. (8) and (9) and shown in more detail in Scheme 1.

[Rh(C0)212]- + 2 HI - [Rh(C0)2lJ + H2 (8)

[Rh(C0)214]- + H20 + CO - [Rh(C0)212]- + 2 HI + CO2 (9)

The steady-state concentration of [Rh(CO),I,]- which affects the carbonylation

rate depends on whether the reduction or the oxidation process is rate-limiting in
the WGSR catalytic cycle (Scheme 1). The CH30Ac concentration determines
which reaction is the rate-determining step of the WGSR by influencing the
hydriodic acid concentration in the catalyst solution. The CH,OAc concentration
affects the equilibrium concentration of HI due to the equilibrium represented in
eq. (10) [23].
HI + CH~OAC - CH3l + HOAC (10)

In the low-waterhigh-LiI catalyst system at high CH30Ac, the HI concentra-

tion is very low (<0.004 molar limit of detection). This is also indicated by
the presence of lithium acetate (LiOAc) (ca. 0.3 molar) in the catalyst solution
from equilibrium with LiI (eqs. (11) and (12)) [23].

Lil + CH30Ac - CH31 + LiOAc (11)

HI + LiOAc - Lil + HOAc (12)

110 2.1 Carbon Monoxide and Synthesis Gas Chemistry

METHANOL

Scheme 1. Interrelated reaction paths for the rhodium-catalyzed methanol carbonylation

process [k]; Me = CH3.

At this low HI concentration, the rate-determining step of the WGSR is

probably the oxidative addition of HI to [Rh(CO),I,]- to form [HRh(CO),IJ
(Scheme 1). The rate of oxidation of [Rh(CO),I,)- is very low. The [Rh(CO),I,]-
complex is therefore the predominant species in solution which affords a maximum
methanol carbonylation rate for each level of water concentration. Increasing the
water concentration within the low-water regime, the rate-limiting step of the
WGSR remains the oxidation of [Rh(CO),IJ, so the CO, production is still
very low; but the [Rh(CO),I,]- concentration increases since the rate of reduction
of [Rh(CO),I,]- increases (Scheme 1).
Another effect of the low-waterhigh-LiI catalyst system at high CH,OAc is the
suppression of the overall WGSR (ca. 10-fold) with the reduction of HI
concentration [23]. This decrease in HI concentration leads to a marked
improvement in the CO efficiency of the process.

Promotion by Iodide and Acetate

Though the primary effect of the addition of iodide salts at low water concentra-
tion is catalyst stabilization, high iodide salt concentration and the low concentra-
 2.1.2.1 Synthesis of Acetic Acid and Acetic Acid Anhydride from Methanol 111

tion of acetate salt generated by the iodide salt under process conditions (eq. (11))
affords a moderate promotional effect on the carbonylation reaction. This promo-
tional effect has been proposed by others, however, under significantly different
reaction conditions [36-381. This rate effect has been demonstrated by room-tem-
perature IR model studies of the oxidative addition of CH31on [Rh(CO),I,]- and
kinetic studies of the reaction in batch and continuous experimental units [24].
Under process conditions the rate enhancement by these salts is lower than the
rate enhancement by CH,OAc of the carbonylation rate.
Prior to these investigations by HCC the promotional effect of iodide on the
oxidative addition of Me1 was investigated by others 19, 39, 401. Foster demon-
strated that the rate enhancement of this reaction in anhydrous medium was
attributable to increased nucleophilicity of the rhodium catalyst with added iodide.
The rationale for this observation was the generation of an anionic rhodium
carbonyl complex, [Rh(CO),I(L)]-. Generation of this species was observed
only with iodide added to certain neutral Rh’ species. No rate enhancement
occurred with iodide added to the anionic complex, [Rh(CO),IJ [39]. Similarly,
in solvents with a high water concentration, iodide salts exhibited no rate enhance-
ment in the presence of [Rh(CO),I,]- [ 1 I]. Maitlis and co-workers, in more recent
investigations, reported a promotional effect of iodide in aprotic solvents on the
oxidative addition of CH31 on [Rh(CO),I,]- [9a, 9cl.
The promotion by iodide or acetate salt of methanol carbonylation at a low
water concentration is truly unique. Based on the currently available evidence,
the overall carbonylation rate increase is presumably due in part to the formation
of a strong nucleophilic five-coordinate dianionic intermediate [RhI,(CO),(L)’-
(L = 0 or OAc)] which is more active toward oxidative addition of MeI. This re-
action pathway is described in Scheme 1, together with the traditional proposed
rate-determining step. In related nucleophilic reactions, a five-coordinate dianion
is proposed for the promotion by halide salt in anhydrous solvents of the oxidative
addition of CHJ to [Rh(CO),I,]- in the carbonylation of methyl acetate to acetic
anhydride [9a]. Also, the Rh’ dianion, [Rh(CO)&]’-, is postulated for the reaction
of HI with [Rh(CO),I,]- in the rhodium-catalyzed WGSR [35]. Though
[Rh(C0)212(L)]2-has not been detected spectroscopically under ambient condi-
tions in model studies, it cannot be ruled out at higher temperatures [5,9c].
Most likely, the more nucleophilic dianion is present in much lower concentration
relative to the monoanion catalyst, so detection is very difficult.
In low-water conditions, it is proposed that the promotional effects of iodide
and acetate involve two competitive pathways between four-coordinate and
five-coordinate nucleophilic intermediates for rate-determining reactions with
CH31 (Scheme 2).
The rate law from the steady-state derivation of the proposed reaction paths is
consistent with kinetic studies under process conditions of the overall reaction and
with room-temperature model studies for the rate-determining oxidative addition
step (eq. (13)) PI.
112 2.1 Carbon Monoxide and Synthesis Gas Chemistry

Me1 k3 Me1 k2

L- I
[Me-Rh(C0)213]2-

1 (fast)

?
[Me--C-Rh(C0)l2L]-

Scheme 2. Pathways to [AcORh(CO)I,L]

These kinetic and model studies support a promotional effect contributed

primarily by the formation of acetate salts [5]. The iodide functions as a catalyst
stabilizer to preclude the formation of insoluble rhodium iodides [5c, 231. Under
process conditions the majority of the inorganic salt is in the LiI form (eq. (1 1))
~231.
Other explanations have been proposed for the carbonylation rate enhance-
ment at low water concentration with iodide and acetate salts; e.g., contact
ion-pairing or “general salt effect” [9a, 9c] or formation of CH31 from the re-
action of iodide with CH30Ac (eq. 11) [9c, 191. Ion-pairing effects cannot be
ruled out but are highly unlikely. Model studies of the rate of oxidative addition
of CH31 on [Rh(CO),IJ with LiI and LiOAc demonstrate a very small effect
of polar solvents on the reaction rate or the IR spectra of [Rh(CO),I,]- [5b].
In comparison, poorly coordinating salts such as LiBF, and LiCF3S03 have
no effect on the rate of carbonylation or on the IR spectra of the rhodium
anion.
It is speculated also that the promotional effect observed for LiOAc in the
model studies is rather a “general salt effect” from the formation of LiI [Sc].
This is clearly not the case. In model studies, no CH30Ac is detected when
LiOAc is added to CH31 under the IR conditions. The reaction rate to LiI from
LiOAc and CH31 under these conditions is very slow relative to the oxidative
addition reaction.
Formation of additional CH31 [9c] from LiI is not sufficient in the low-water
A 0 process to affect the carbonylation rate. In model studies, the generation of
CHJ is not possible since CH30Ac is not present in any of the experiments. In
continuous carbonylation experiments under commercial reaction conditions,
the reactor operation is controlled to minimize variations in the CH31 concentra-
tion in the catalyst solution so that the CH31 is kept constant [5c].
 2. I .2.1 Synthesis of Acetic Acid and Acetic Acid Anhydride from Methanol 113

In anhydrous conditions for the carbonylation of CH30Ac to acetic anhydride,

CH31 is regenerated from LiI; this is considered an important step in the reaction
and can become rate-determining [4I]. In the low-water methanol carbonylation
process, LiI has little effect on the regeneration of CH31. Instead, the CH31 is
regenerated from a faster and irreversible hydrolysis of acetyl iodide (see
Scheme 1).
The process chemistry of the methanol carbonylation reaction is summarized
in Scheme 1. This catalytic reaction scheme depicts the balanced relationship
between the methanol carbonylation, the WGSR and the iodide cycles under
both regimes of water concentration. Within the scope of methanol carbony-
lation in an aqueous/acetic acid medium, the overall reaction rate depends
not only on the nature of the rate-determining step(s), but also on reaction con-
ditions influencing the steady-state concentration of the active Rh' species,
[Rh(CO),I,l-.

BP Low-Water Technology (CativaTM

Process)

In the 1990s, BP re-examined the iridium-catalyzed methanol carbonylation

chemistry first discovered by Paulik and Roth and later defined in more detail
by Forster [20]. The thrust of this research was to identify an improved methanol
carbonylation process using Ir as an alternative to Rh. This re-examination by BP
led to the development of a low-water iridium-catalyzed process called CativaTM
[20]. Several advantages were identified in this process over the Rh-catalyzed
high-water Monsanto technology. In particular, the Ir catalyst provides high car-
bonylation rates at low water concentrations with excellent catalyst stability
(less prone to precipitation). The catalyst system does not require high levels of
iodide salts to stabilize the catalyst. Fewer by-products are formed, such as
propionic acid and acetaldehyde condensation products which can lead to low
levels of unsaturated aldehydes and heavy alkyl iodides. Also, CO efficiency is
improved.
The Ir-catalyzed methanol carbonylation reaction has been studied extensively
by several groups 9f-h. The mechanism for the reaction is more complex than for
the Rh reaction. The reaction involves a neutral and an anionic catalytic cycle. The
extent of participation by each cycle depends on the reaction conditions. The
anionic carbonylation pathway predominates in the CativaTMprocess. The active
Ir catalyst species is the iridium carbonyl iodide complex, [Ir(CO)212]-.The carbo-
nylation reaction proceeds through a series of reaction steps similar to the Rh
catalyst process shown in Figure 1 ; however, the kinetics involve a different
rate determining step.
The proposed rate-determining step in Ir-catalyzed carbonylation is the
formation of the acyl complex, [Ir(CH3CO)(CO),13]-, via methyl migration of
the methyliridium(II1) intermediate, [Ir(CH3)(CO)2(I)3]-. This step involves the
elimination of iodide and the subsequent addition of CO. This pathway is con-
sistent with the direct dependence of CO and the inverse dependence of iodide
on the observed reaction rate.
114 2.1 Carbon Monoxide and Synthesis Gas Chemistry

BP extended this Ir carbonylation chemistry with the discovery of pro-

prietary promoters to achieve commercially viable high reaction rates at low
reaction water conditions with essentially no dependence of CO partial
pressure on the reaction rate [20]. These promoters can be categorized in two
groups: simple iodide complexes of Zn, Cd, Hg, Ga, and In or carbonyl
complexes of Re, Ru, Os, or W. It is believed these promoters participate in the
rate-determining step to abstract iodide from [Ir(CH3)(CO)2(I)3]-, thus
facilitating methyl migration to form the corresponding acyl complex,
[Ir(CH&CO)2 (1131 -.
Since the development of CativaTM,BP has converted three world-scale acetic
acid plants from the old Rh-based high-water Monsanto technology to the Ir-based
low-water process. Significant capital and operating cost savings were achieved
from the conversion of a Rh-based process to an Ir-based process. Also, the
start-up in 2000 of a 500 X lo3 metric ton per year acetic acid plant in Malaysia
uses the CativaTMprocess [20d].

Process Technology

The continuous rhodium-catalyzed methanol carbonylation process consists of

three major areas: the reaction, flasher, and purification sections, as represented
in Figure 1 [15].

reactor flasher light ends dehydration heavy ends

column column column
to vent
recovery

to vent
recovery r+

I
L
purilication column recycle
t i t
1L b product
acetic acid

mixed acid
by-products

Figure 1. Rhodium-catalyzed methanol carbonylation commercial process flow scheme [ 151.

 2.1.2.1 Synthesis of Acetic Acid and Acetic Acid Anhydride from Methanol 115

Reaction Section

Acetic acid is manufactured in a liquid-phase reaction at ca. 150-200°C and

3-6 MPa [15, 201. Carbon monoxide and methanol are introduced continuously
into a back-mixed reactor. Carbon monoxide mass transfer into the reactor liquid
phase is maximized with adequate mixing at a high carbon monoxide partial
pressure. The noncondensable by-products are vented from the reactor to maintain
an optimum carbon monoxide partial pressure in the reactor. The reactor off-gas is
treated to recover reactor condensables (i.e., CH31) before flaring. Methanol and
carbon monoxide efficiencies are greater than 98 % and 90 % respectively [ 151.
Major inefficiencies of the process are the concurrent manufacture of carbon di-
oxide and hydrogen from the WGSR, and methane from the hydrogenolysis of
methanol. Both reactions are catalyzed by the same rhodiudiodide catalyst
system as is methanol carbonylation. Propionic acid is the major liquid ineffi-
ciency [4244] ; however, higher-boiling carboxylic acids are also formed.
These heavy ends are derived from methanol homologation reactions (eq. (14);
cf. Section 3.2.7) [45].

CH30H + (n+l)CO + 2nH2 -

Rh 12
CH3C,H2,COOH + nH20 (14)

Flash Section

The product acetic acid and a majority of the light ends (methyl iodide, methyl
acetate, water) are separated from the reactor catalyst solution and forwarded
with dissolved gases to the distillation section by an adiabatic single-stage
flash. This crude separation also functions to remove the exothermal heat of
reaction. The catalyst solution is recycled to the reactor. Under the process condi-
tions of the flash, the rhodium catalyst is susceptible to deactivation at the low CO
partial pressure of the flash vessel [46].

Purification Section

The purification of acetic acid requires distillation in a three-column process

[15]. The vapor product from the flasher overhead feeds a light ends column.
Methyl iodide, methyl acetate, and a portion of the water condense overhead
in the light ends column to form two phases (organic and aqueous). Both over-
head phases return to the reaction section. The dissolved gases from the light
ends column feed vent through the distillation section. Before this vent stream
is flared, residual light ends are scrubbed and recycled to the process. The aque-
ous acetic acid side draw-off from the light ends column feeds the dehydration
column. Water and some acetic acid from this column separate and recycle to
the reaction section. The dry crude acetic acid is a residue stream from this col-
umn which feeds the heavy ends column. Product acetic acid is afforded as a
vapor side draw-off of the heavy ends column. A mixture of high-boiling
1 16 2. I Carbon Monoxide and Synthesis Gas Chemistvy

acid by-products, primarily propionic acid, are removed as bottoms from this
column.
The corresponding Ir-catalyzed process consists of the same sections as
described in Figure I for the Rh version except for a few improvements made
to the reaction and purification section. In the reaction section, an agitator is
not required to stir the reaction solution. Instead the reactor mixing is provided
by the jet mixing effect of a reaction cooling loop. In the purification, the light
ends and dehydration columns of the Rh-catalyzed process are combined in one
distillation column, the “drying column” [20d].
With continuing refinements to the rhodium-catalyzed, liquid-phase, methanol
carbonylation technology (see Section 2.1.2.13, this industrial process will
remain the most competitive route to acetic acid, well into the 21st century.

2.1.2.1.3 Acetic Anhydride

Introduction

The processes for the manufacture of acetic anhydride have included, initially, the
distillation of wood pulp, which was followed by the ketene route from acetic acid
or acetone and finally the ethylene based oxidation of acetaldehyde. The carbony-
lation of CH30Ac to acetic anhydride has in part replaced anhydride capacity
from the more expensive processes.
The intensive investigation of new metal-catalyzed processes for the manufac-
ture of acetic anhydride and acetic acid was driven by the high cost of petroleum
and raw materials in the 1970s. As a result, synthesis gas-based technologies were
introduced. The major sources of syn gas are coal and heavy petroleum residues.
Natural gas or naphtha fractions were also used as feedstocks for synthesis gas.
The broad development of homogeneously catalysed syntheses of commercial
anhydride manufacturing is directly related to the process developments of several
companies. In particular, Tennesee Eastman developed a rhodium-catalyzed
process based on syngas [47].
On the basis of the carbonylation of methyl acetate using Co, Ni or Fe catalysts
by BASF [48] in the 1950s and of the initial results from the Rh catalyzed carbo-
nylation of methanol by Monsanto [21, 491 in the early 1970s, Halcon [49, 501,
Eastman [41b, 511, Ajinamoto [52], Showa Denko [53], BP [2, 20, 54, 551, and
Hoechst [56] worked on substantial developments for the Group VIII metal-cata-
lyzed manufacture of acetic anhydride. Promising catalyst metals are Rh, Pd, Ni,
and Co; among these, Rh has an essential position due to its exceptional carbony-
lation activity [20].
The preference for rhodium was known from the investigations conducted by
Monsanto. Diversifying from these patents, the available low-cost catalyst
metals were studied which have catalytic properties comparable with those of
rhodium. In the presence of alkali metal salts and Group VIB metal carbonyls,
Ni-catalyzed carbonylation operates under mild conditions of nearly 190 “C and
40 bar [57]. Nevertheless, only limited success was found with other catalyst
 2.1.2.1 Synthesis of Acetic Acid and Acetic Acid Anhydride from Methanol 117

metals, which mostly showed decreasing selectivity, lower yields and higher
energy consumption.

Process Chemistry

Through the investigation of different carbonylation raw materials for manufac-

ture of acetic anhydride, carbonylation of methyl acetate (eq. (15)) was found
to be the method of choice.
CH3COOCH3 + CO + (CH3CO)2O (15)
Using a Monsanto catalyst system (Rh/MeI/CO) the carbonylation of methyl
acetate has a long induction period in the absence of water and a low reaction
rate in comparison with the synthesis of acetic acid under typical reaction condi-
tions.
As a result, two significant developments contributed to increased carbony-
lation rates and reduced induction periods. The first development was the
introduction of hydrogen with the carbon monoxide feed to reduce Rh"' to the ac-
tivated Rh' carbonylation complex (eq. (1 6)).

[Rh(C0)214]- + H2 + [Rh(C0)212]- + 2 HI (16)

This reduction reaction minimizes the formation of unreactive Rh"'-species that

form insoluble compounds such as rhodium triiodide (Scheme 3).

vco = 2075 cm-' vco = 2040 cm-' vco = 2060; 1990 cm '

;:11 ;:
Rhls

Scheme 3. Rh"' complexes through formal addition of iodine to the active Rh' complex

This catalyst deactivation results from the oxidation of the Rh' complex by
formal addition of iodine (eqs. (18)-(20)). This form of deactivation in particular
occurs at high temperatures under CO-deficient conditions [58]. The state of
activity of the rhodium complex system can be observed by IR spectroscopy
(Figure 2). Inactive Rh"' species are transformed to the Rh' complex by reduction
with hydrogen.
The second development was the use of promoter salts (e.g., alkali, phospho-
nium or ammonium salts) to stabilize the activated complex in the catalyst system
[41b] and the use of co-catalysts with rhodium, such as base catalyst metals Ti, Zr,
118 2. I Carbon Monoxide and Synthesis Gas Chemistry

Figure 2. IR Spectroscopy by Rh complexes: (a) active species; (b) inactive species

(in catalyst solution).

V, Nb, Ta, Cr, Mo, W, Sn, Mn, Re, Fe, Co, and Ni. Halcon patents [59] describe
catalyst systems containing Zr, Mo/Ni, or Sn/Ni as synergistic co-catalysts.
Furthermore, metals of Group VIII combined with Hf, phosphines, amines, or
arsines, as promoter additives, have been reported [60].
Alkaline salts, preferably lithium iodide, pyridines, and phosphines, stabilize
the catalytically active [Rh(CO),I,]- ion and considerably increase the reaction
rate. These promoters increase the carbonylation rates in the order [41b]:

Li+ > A13+ > Na+ > Bu,P+ - Bu,MeP+ > Mg2+ - Bu,N+
The concentration of the promoter cation and its ability to activate the equilibrium
between methyl acetate and methyl iodide greatly influence the reaction rate
(eq. (17)).
CH3COOCH3 + Lil -
CH31 + CH3COOLi (17)

The mechanism of the Limh-catalyzed carbonylation of methyl acetate was for-

mally described by a catalyst cycle by Zoeller et al. based on kinetic measure-
ments under high pressure [41b]. The organic reaction cycle is combined with
the rhodium catalyst cycle in the LiRh catalyst system (Figure 3).
An important aspect in the development of this process is the understanding of
by-product formation, as a means of implementing specific ways to minimize side
reactions. The important by-products are ethylidene diacetate, acetone, carbon di-
oxide, methane, and heavy ends.
The hydrocarbonylation of methyl acetate catalyzed by homogeneous Rh
complexes generates 1,l-diacetoxyethane (“ethylidene diacetate”) [6 11 the formal
addition product of acetic anhydride and acetaldehyde. Ethylene diacetate is the
predominant by-product of the process. The level of ethylidene diacetate pro-
duction is directly related to the hydrogen partial pressure in the reactor [62].
 2.1.2.1 Synthesis of Acetic Acid and Acetic Acid Anhydride from Methanol 119

cHq7-
CH3COOLi CH3COOCH3

CH3COOH

CH3COOCH3 + ~Rh(c0)(c0cH3~131- co

HI
Lil [Rh(C0)212]-

(CH3C0)20 %
CH3COOH C H 3 C d L [Rh(C0)2(COCH3)13]-

CH3COOLi (CH3CO)zO

Figure 3. Proposed mechanism for the carbonylation of methyl acetate to acetic

anhydride.

A side reaction related directly to the carbonylation of methyl acetate is the

formation of acetone and carbon dioxide via methylation of the acetyl rhodium
complex intermediate [63] through addition of a second molecule of methyl
iodide (eqs. (18)-(21)):

[Rh(C0)212]- + CH3l + CO - [CH3CO-Rh(C0)213]- (18)

[CH3CO-Rh(C0)213]- + CH31 - CH3COCH3 + [Rh(C0)214]- (19)

[Rh(C0)214]- + 2 CH3COOCH3 + CO - (CH3CO)2O

+
+ [Rh(C0)212]-
2CH31 + COz (20)

2CH3COOCH3 + 2CO + CH3COCH3 + COP + (CH3CO)10 (21)

Acetone steady-state concentrations are maintained at a low level through sub-

sequent side reactions involving formation of heavy ends by condensation of ace-
tone and through its removal from streams of light ends using countercurrent dis-
tillation/extraction methods [64a-c]. The formation of azeotropes of acetone,
methyl acetate and methyl iodide preclude the separation of acetone by conven-
tional distillation techniques.
Besides condensation reactions to form heavy ends, polyester ketones are
formed by the decomposition of acetyl iodide to polyester polyketones (eq. (22))
following a mechanism similar to the decomposition of acetyl chloride [64d,e].
120 2.1 Carbon Monoxide and Synthesis Gas Chemistq

The heavy end products of acetic anhydride processes are separated from
catalyst streams and distillation residues. The high affinity of the heavy ends
for rhodium components affords specified procedures to separate rhodium and re-
cycle it to the reaction stage of the process. Different methods for rhodium recov-
ery were tested during the process development, including extraction methods
[65], precipitation [66], complexing, and electrochemical methods [67].
A number of methods were also developed for removing iodide impurities from
acetic anhydride, such as syn-gas stripping [68], extraction in the presence of phe-
nyl or alkyl phosphines [69], the use of lower fatty acids in combination with rho-
dium recovery [70], the use of silver-containing ion-exchangers [7 11, or oxidation
with hydrogen peroxide [72].

Process Technology

Eastman Process

Eastman Chemical Company, together with Halcon, developed a commercial

acetic anhydride process to an industrial scale [41b, 471. This process starts
with coal to make a hydrogen-rich synthesis gas, which is purified (Figure 4).
A portion of the syn gas is separated to produce methanol from 2 : l H2/C0.
Part of the methanol is used to scrub H2S from the coal-gasification step. The re-
mainder of the methanol is combined with acetic acid to make methyl acetate. The
methyl acetate is carbonylated to give acetic anhydride. The acetic anhydride is
used to produce cellulose acetate in another process, and the resulting acetic
acid is recycled to the esterification section. The acetic anhydride step of the pro-

acetic acetic

7 oxygen

1
acid

acetic
anhydride

gasification
separation separation plant

pqslurry

t t
t
I
sulfur methanol recovered
acetic acid

Figure 4. Block flow diagram for production of acetic anhydride from coal.
 2.1.2.1 Synthesis of Acetic Acid and Acetic Acid Anhydride from Methanol 121

methyl acetate

scrubber

acetic

low boilers
I I

-1u
acetic
anhydride

vessel iodide
absorption
catalyst cycle wiped film light ends
acetic
acid heavy ends
low boilers
evaporator column column
anhydride
column co'umn

Figure 5. The Eastman acetic anhydride process (simplified).

cess is catalyzed by rhodium. Less expensive ruthenium and nickel catalysts have
also been developed, but the efficiency of the rhodium-catalyzed process is such
that it has the most favorable economics [2].
On the basis of this development afforded by Eastman and Halcon, in 1983 the
Eastman Chemical Company (Kingsport, TN) started the commercial process for
the manufacture of acetic anhydride (Figure 5). Methyl acetate, the feedstock for
the carbonylation reaction, was produced in a separate esterification step from
acetic acid and methanol. The process was designed to produce 225 000 tons of
acetic anhydride and 75 000 tons of acetic acid/year. The overall yield of acetic
anhydride based on methanol is approximately 96 % [2, 471.
The carbonylation process incorporates a rhodium salt, lithium iodide, and
methyl iodide as primary catalyst components [80]. The active catalyst form is
maintained by the lithium iodide promoter and hydrogen in the carbon monoxide
feed to the reaction system. Preferred reaction conditions are a temperature of
nearly 190 "C and a pressure of 5 MPa HJCO. The conversion of methyl acetate
to acetic anhydride per passage of reactor is between 50 and 75 %.
Small amounts of water are present in the system and some acetic acid is
produced by hydrolysis of acetic anhydride. Most of the acetic acid is derived
from addition of methanol to the reaction mixture. The reaction is conducted
under essentially anhydrous conditions.

Hoechst Process

The process developed by Hoechst in the early 1980s [73, 741 originated from
previous investigations by Monsanto and Halcon. The development was based
122 2.1 Carbon Monoxide and Synthesis Gas Chemistry

on the rhodium-catalyzed carbonylation of methyl acetate or dimethyl ether using

methyl iodide promoter and heterocyclic aromatic nitrogen compounds or phos-
phonium salts as co-promoters. Preferred co-promoters are tetraalkylphosphonium
iodides or N-methylimidazolium and picolinium iodides, which have melting
points lower than 140 O C , so the high promoter concentrations in acetic anhydride
are in a fluid phase or melted during the catalyst cyclization. The carbonylation
was carried out at a temperature below 200°C and at a pressure of approx.
5 MPa of carbon monoxide in a stirred tank reactor, to give 1200-1500 g acetic
anhydrideL catalyst solution per hour [73, 801.
Although ready for commercialization, the process has not been realized.
A description can be found in the 1st edition.

2.1.2.1.4 Coproduction
Introduction

The concept of co-carbonylation of methanoVmethy1acetate mixtures was first in-

troduced by BASF in the early 1950s, but the reaction chemistry was not fully
developed to commercial realization [75].Not until the mid- 1980s, after the devel-
opment of carbonylation processes to produce acetic acid and acetic anhydride,
were co-carbonylation processes patented using homogeneous rhodiudiodine
catalyst systems (Table 2) [2, 561. The basic process concept is to manufacture
acetic acid and acetic anhydride from methanol and carbon monoxide as the
only raw materials and to generate methyl acetate within the process. Similiarly,
the suitability of dimethyl ether as a raw material for the generation of the an-
hydride equivalent in addition to or as a substitute for methyl acetate was revealed
by Hoechst [76]. To produce a small fraction of acetic acid besides acetic anhy-
dride as the main product, the carbonylation of methyl acetate could be conducted
with small amounts of water or methanol. This variant, first demonstrated by
Hoechst [56], is practiced by Eastman Kodak [2].
BP Chemicals was the first to commercialize a combination process based on
the carbonylation of methyl acetate in the presence of water at the “AS’ plant
complex in Hull, UK, which was completed in 1988 [20]. Due to internal con-
flicts, Hoechst AG so far has not realized plans for a combination process.

Process Chemistry

The reaction course of the co-carbonylation of methanol and methyl acetate

(Figure 6) can be interpreted in three phases.

(1) At the start of the reaction sequence, manifested by CO uptake, the formation
of methyl acetate with low reaction rates dominates (eq. (23):
2CH30H + CO - CH3COOCH3 + H20 (23)
Table 2. Examples of co-carbonylation systems.
BP [81a] Kuraray [82] Daicel [84a] Hoechst [84b] UCC [SS]

Catalyst system
17 mmol/L 10 mmol/L 13 mmoVL 10 mmol/L 20 mmol/L
Rhodium
Ligand Ph*PCH*CH*P(O)Ph2
Methyl iodide concn. No data 1.2 m o m 2.1 mom 1.2 mom 3.2 m o m
Iodide promoter N,N(Me),Imidazol' 1- Me(n-Bu),P' I (n-Bu),P+ 1- Li' I-
Iodide concentration 260 mmol/L 430 mmol/l 325 mmol/L 1.1 m o m
Co-catalyst ZrO(O A C ) ~ CC0)6 Aluminum
Co-catalyst-concn. 50 mmol/L 20 mmol/L 150 m 0 v L

Charge
1 : 13.2 1 : 1.8 1 : 1.5 1 : 0.3 1 : 3.1
MeOWMeOAc (mo1:mol)
Water 12.1% in reactor feed None None None None

Reaction conditions
183 "C 180 "C 175 "C 182 "C 115 "C
Temperature
Pressure 3 MPa 3.2 MPa 5.9 MPa 5 MPa 1 MPa
Solvent Acetophenone
124 2.1 Carbon Monoxide and Synthesis Gus Chemistry

Figure 6. Reaction course of the methanoVmethy1 acetate co-carbonylation [ 1401.

(2) After water reaches its maximum concentration, all the acetic acid is generated
rapidly (eq. (24)):
CH3COOCH3 + H20 + CH30H + 2 C O -3CH3COOH
Addition of eqs. (23) and (24) leads to the already-known eq. (5).
(24)

(3) Not until the concentration of water has decreased to zero is the consumption
of methyl acetate to form acetic anhydride by carbonylation initiated at a con-
stant acetic acid concentration (eq. (25)):
CH3COOCH3 + CO -
(CH&O)20 (25)
The conversion of methyl acetate is not quantitative. In a continuous process
methyl acetate conversion is limited by the reactor residence time to 10-20 %.
The unreacted methyl acetate must be separated from the product stream and
recycled to the reactor.
Analogously to the carbonylations of methanol [77] and methyl acetate [78],
the dependence of the reaction velocity of the co-carbonylation on water-free
conditions, high promoter salt concentrations, and rhodium and methyl iodide
concentrations can be described by second-order kinetics (eq. (26)).
-d [CHBOH] -d [CH~OAC]
= kl [Rh] [CH31] > = k2 [Rh] [CH31]
dt dt
 2.1.2.1 Synthesis of Acetic Acid and Acetic Acid Anhydride from Methanol 125

As mentioned in Section 2.1.2.1.1, the catalytic cycle of the combined carbo-

nylation (Scheme 4) differs from the single-product process in the final reaction
step, as it includes the complete reactions of eqs. (2)-(4).
The organophosphonium or organoammonium iodides in this process act as
promoter salts to stabilize the rhodium complex system and also to raise the
reaction velocity of the carbonylation. The primary contribution of promoter
salts to the reaction is to accelerate the regeneration of methyl iodide through

CH31 ............________..,...
...
.... ........_________.....
CH3COl

i'
ROH CH3COOR CH3OR ROH

R = CH3; COCH3

CH3COOH
HI

Scheme 4. Catalytic cycle of the methanoVmethyl acetate co-carbonylation

126 2.1 Carbon Monoxide and Synthesis Gas Chemistry

Figure 7. Dependence of space-time yield on the ratio of methanollmethyl acetate charge at

constant residence time [140].

the reaction with methyl acetate (eq. (27)) [41b], to form possibly a more
nucleophilic rhodium iodidocarbonylate [79, 41b] and to generate a general
salt effect [78].

R4EI + C W O O C H 3

E=N,P
- CH3l + CH3COOER4 (27)

The temperature dependence follows the Arrhenius equation and the reaction is
usually carried out below 200 "C. The ratio of methanollmethyl acetate affects the
overall reaction rate. With an increasing proportion of methanol, the space-time
yield (gL.h) increases (Figure 7). Therefore, the variability of the process in
continuous operation is limited to certain acetic acidacetic anhydride production
ratios.
The carbonylation of methyl acetate is discussed as an equilibrium reaction de-
pending on pressure and temperature [41b]. This might explain the strong depen-
dence of the space-time yield on CO pressure (Figure 8) [go]. Accordingly, the
combined carbonylation, and the carbonylation of methyl acetate, demand higher
process pressures than the carbonylation of methanol.
 2.1.2.1 Synthesis of Acetic Acid and Acetic Acid Anhydride from Methanol 127

Independently of the initial rhodium compound charged, the catalyst system is

based on a rhodium compound which under reductive reaction conditions forms
the active complex [Rh(C0)212]-.Bcsidcs methyl iodide, quaternary compounds
of Group V elements such as N,N-dimethylimidazolium iodide [81] or tri-n-butyl-
methylphosphonium iodide [82, 831 may be used. The promoter salts can be
formed in situ by quarternization with methyl iodide. Their preference as promoter
salts is based on their favorable solubility behavior and low volatility, which are
important properties with respect to catalyst separation by distillation. A number
of other catalyst promoters and stabilizers are claimed in the patent literature to
prevent the precipitation of insoluble rhodium compounds or to support the halo-
lysis of methyl acetate (eq. (27)). Some of these compounds are claimed to func-
tion as ligands or co-metal catalysts [18, 81a, 82, 84a, 851. Although the ligand
concept makes sense, it is questionable whether the substituted rhodium iodocar-
bonylates are inert to quarternization by methyl iodide in a continuous process. To
stabilize the catalyst system, moreover, hydrogen is fed to the reactor together
with the carbon monoxide (up to 5 %) to reduce Rh"' complexes which have
been formed in side reactions from the active Rh' complex (see Scheme 3)
[41b, 56, 861.

reactor pressure [bar]

17 mmole Rhll 24 mmole Rhll
- _.._.._
Figure 8. Dependence of space-time yield on the process pressure [140]; 10 bar = 1 MPa.
128 2. I Carbon Monoxide and Synthesis Gas Chernistq

With the introduction of hydrogen to the process 1,l-diacetoxyethane is formed

as the main by-product of the acetic anhydride distillation residue.
Through side reactions inherent in the process, small amounts of other im-
purities are formed. Whilst the spectrum of the side products is similar to the
anhydride process, the low formation rates reflect the relationship of the com-
bined carbonylation to the Monsanto process. The removal of these impurities
compared with distillation of 1,l-diacetoxyethane requires considerable proces-
sing effort.
The formation of nondistillable polymer impurities with ester and ketone
structures is a key processing problem. A buildup of these polymers in the cata-
lyst solution, if not continuously removed, will cause considerable operational
problems.
These polymers are removed at the place of highest concentration, the catalyst
solution. The main task of suitable processes is to achieve a rhodium-free separa-
tion. This task was solved by differently conceived 1iquidAiquid extractions
[87-911. With a shift of the production ratio toward acetic acid, the formation
of polymers decreases.
Organic iodine impurities in the product streams must remain only in trace
quantities since iodine can be a severe catalyst poison in other processes that
use acetic anhydride or acetic acid as a feed, e.g., the production of vinyl acetate.
The tolerable iodine concentration limit is less than 10 ppb.
A number of methods have been investigated to remove iodine compounds
from the crude product mix. Among these methods are distillation [92], oxidation
[93] and hydrogenation [94] treatments. The oxidation treatment of the products
has the advantage of reducing oxidizable impurities, thus also improving the
permanganate product quality. These methods are only sufficient to reduce the
iodine concentration to the low-ppm range. Additional treatment with metals
or metal compounds [95], especially silver [96], is necessary to obtain low-ppb
iodine concentration levels.
The highly corrosive nature of the reaction solution requires reactor process
equipment to be manufactured of hastalloy-type steels with high nickel con-
tent.
Corrosion in the reactor area leads to the formation of metal iodides and ace-
tates which if precipitated can cause mechanical failures. The corrosion metals
can be removed from the catalyst solution through exploitation of the different
metal salt and Rh-complex solubilities in water [97].

2.1.2.1.5 Outlook
Potential Process Improvements

A number of iodide salts have been proposed as catalyst stabilizers and copro-
moters, in particular the iodide salts of Main Group IVA, VA, and VIA elements
[99-1041. At equivalent iodide catalyst concentrations, these salts appear to have
no significant stabilization or promotional benefit over the preferred alkali metal
 2.1.2. I Synthesis of Acetic Acid and Acetic Acid Anhydride ,from Methanol 129

iodide salts [5c, 231. This is consistent with previous work that demonstrates that
it is the iodide, not the respective cation of the salt, that contributes to catalyst
stabilization and rate promotion [5c, 231.
The use of heterobifunctional phosphorous-nitrogen and phosphorus-sulfur
bidentate ligands in the catalyst system is claimed to afford very high carbonyla-
tion rates under reaction conditions [ 105-1 071. These ligands presumably form
stable carbonyl complexes similar to the phosphorus-phosphorus bidendate
ligands studied by Wegman [108-1101. The long-term thermal stability and the
resistance to quaternization by CH31 of these unique heterobifunctional ligands
are questionable under reaction conditions, based on previous work [ 1101. The
apparent rate enhancement may be due simply to the formation of organic iodide
salts through quaternization with CH31.
Development of “heterogenized” homogeneous carhonylation catalysts is
being investigated also [ 1111. Since the initial investigations of “heterogenized”
rhodium catalyst systems, more thermally stable polymer backbones have
been developed, such as the crosslinked polyvinylpyridine and polyvinylpyrro-
lidone systems [ 112-1 141. High carbonylation rates with these “heterogenized”
systems are reported under reaction conditions for extended periods of contin-
uous operation [115]. For these systems to have commercial value, catalyst
leaching from the support must be negligible and polymer stability is para-
mount.
Recently, a more stable Rh catalyst for methanol carbonylation based on the
crosslinked polyvinylpyridine system has been disclosed in which the degree of
crosslinking of the resin support is as high as 60 % [ 115-el. This catalyst im-
provement is the basis for the potential development of a commercial methanol
carbonylation acetic acid process named “Acetica”. This process is being offered
for license by Chiyoda and UOP. Even with this announcement, there are still
considerable doubts whether heterogenized carbonylation catalyst systems can
compete with the low-water homogeneous Rh- and Ir-catalyzed processes
(cf. Sections 2.1.1 and 3.1.1.3).
Currently rhodium and iridium are the most effective metal catalysts for these
carbonylation processes. Some attempts have been made to substitute rhodium
and iridium in part or total by other metals: however, results are not competitive
[127, 1281.
Improvements to the basic commercial process also involve modifications to the
purification stage and implementation of chemical treatment applications within
that section, such as treatment with ozone, peroxides, or hydrogen [116-1261.
These improvements are designed specifically to remove low levels of iodides,
acetaldehyde, and acetaldehyde-derived impurities (i.e., crotonaldehyde and 2-
ethylcrotonaldehyde) to reduce the concentration of these impurities in the final
product. Removal of these impurities improves the acetic acid product quality
[116-1261.
Currently rhodium and iridium are the most effective metal catalyst for
these carbonylation processes. Some attempts have been made to substitute Rh
or Ir in part or totalby other metals; however, results are not competitive [127,
1281.
130 2.1 Carbon Monoxide and Synthesis Gas Chemistry

Acetic Acid from Synthesis Gas

The direct production of acetic acid from synthesis gas [80] instead of methanol as
feedstock has demonstrated selectivities up to 80 % using rhodium fixed-bed
catalysts with Group IIIA-VIIIA promoters and alkaline metals. Other C2 com-
pounds were also formed (acetaldehyde, ethanol, and ethyl acetate) [ 1291.
A “melt” RuCoI/Bu4PBrcatalyst system yields acetic acid from syn gas at 95 %
selectivity and 97 % carbon efficiency [130].
The competitive success of these processes is primarily dependent on the prices
of syngas and achieving a high (>95 %) selectivity to acetic acid.

Isomerization of Methyl Formate

Methyl formate can be “isomerised” to acetic acid [80] on several homogeneous

catalysts, including complexes of Co, Ni, Ru, Rh, Ir, and Pd [131]. With the R M
catalyst system methyl formate is formed via the mixed formic acetic anhydride,
which is hydrolyzed to the acids [132], and formic acid decomposes according to
eq. (28) to generate CO.

HCOOCH3 + Co -
cat.
HCOOCOCH3 -
H20
CHBCOOH + CO (28)

The proposed mechanism for this carbonylation reaction, which occurs in the
absence of water, involves basic catalytic steps similiar to the rhodium-catalysed
methanol carbonylation process (see Section 2.1.2.1.1). The mechanism leads to
the formation of acetyl iodide, which reacts with methyl formate to produce the
mixed anhydride [ 1331.
The production of methyl formate by carbonylation of methanol with basic
catalysts [134] can be used to separate carbon monoxide from by-product syn-
thesis gas streams, e.g., steel-mill off-gases [ 1351, to generate clean sources of
CO for production of acetic acid by methyl formate isomerization. Therefore
methyl formate could be produced near cheap CO sources and then transported
to an appropriate site for conversion to acetic acid. This route to acetic acid is
potentially competitive with a classic grass-roots methanol carbonylation process.
Though the process has not been commercialized, numerous companies have
patented the isomerization of methyl formate [ 1361.

Oxidative Carbonylation of Methane

The first oxidative carbonylation reactions (cf. Section 2.1.2.5) with methane used
superacid catalysts to perform the carbonylation in a Koch-type reaction which in-
volved protolytic oxidation of methane to the methyl cation (eq. (29) [137]):

CH4 + CO + HX - CH3COX + H2 -
H20
CH3COOH (29)
 References 131

Recent investigation of this reaction indicates that the C-H bond activation
necessary for the reaction with CO can also be achieved using metal catalysts
[ 1381. It is surprising that again the Rh/I system was found to be an active catalyst,
if the reaction was carried out in water with oxygen as oxidation agent [139].
Ethane has also been used as a source for acetic acid [141].

References
[ l ] H. Cheung, R. S. Tanke, G. P. Torrence, Ullmunn’s Encycl. Ind. Chem., 6th ed., Wiley-
VCH, 2000.
[2] (a) M. K. Guerra, Acetic Acid and Acetic Anhydride, SRI International, Menlo Park, CA,
1994, Report No. 37B; (b) Anonymous, Eur: Chem. News 2000, Apr., 10.
[3] S. L. Cook, Chem. Ind. 1993, 49, 145.
[4] (a) Halcon Int. Inc. (C. Hewlett) DE 2.441.502 (1974); (b) Halcon Int. Inc. (C. Hewlett)
DE 2.462.444 (1974).
[5] (a) M. A. Murphy, B. L. Smith, G. P. Torrence, A. Aguilo, Inorg. Chim. Actu 1985, I O I ,
L47; (b) M. A. Murphy, B. L. Smith, G. P. Torrence, A. Aguilo, J. Organomet. Chem.
1987,303,257; (c) B. L. Smith, M. A. Murphy, G. P. Torrence, A. Aguilo, J. Mol. Catal.
1987, 39, 115.
[6] D. Forster, Ann. N.I! Acud. Sci. 1977, 295, 79.
[7] D. Forster, J. Am. Chem. Soc. 1976, 98, 846.
[8] A. G. Kent, B. E. Mann, C. P. Manuel, J. Chem. Soc., Chem. Commun. 1985, 728.
[9] (a) C. E. Hickey, P. M. Maitlis, J. Chem. Soc. Chem. Commun. 1984, 1609; (b)
A. Fulford, P. M. Maitlis, J. Organomet. Chem. 1974, 71, C20; (c) A. Fulford,
C. E. Hickey, P. M. Maitlis, J. Orgunomet. Chem. 1990, 398, 311; (d) A. Haynes, B.
E. Mann, D. J. Gulliver, G. E. Morris, P. M. Maitlis, J. Am. Chem. Soc. 1991, 113,
8567; (e) A. Haynes, B. E. Mann, D. J . Gulliver, G. E. Moms, P. M. Maitlis, J. Am.
Chem. Soc. 1993, 115, 4093; (f) P. M. Maitlis, A. Haynes, G. J. Sunley, M. J. Howard,
J. Chem. SOC.Dalton Trans., 1996,2187; (8) J. M. Pearson, A. Haynes, G. E. Morris, G.
J. Sunley, P. M. Maitlis, J. Chem. Soc., Chem. Commun. 1995, 1045; (h) T. Ghaffar, H.
Adams, P. M. Maitlis, G. J. Sunley, M. J. Baker, A. Haynes, J. Chem. Soc., Chem. Com-
mun. 1998, 1023.
[lo] G. W. Adamson, J. J. Daly, D. Forster, J. Organomet. Chem., 1974, 71, C17.
[ l l ] D. Forster, Adv. Organomet. Chem. 1979, 17, 255.
[12] D. Brodzki, C. Leclere, B. Denise, G. Pannetier, Bull. Chim. Soc. FI: 1976, 61.
[13] F. E. Paulik, J. F. Roth, J. Chem. Soc., Chem. Commun. 1968, 1578.
[14] D. Forster, T. C. Singleton, J. Mol. Cutul. 1982, 17, 299.
[I51 R. T. Eby, T. C. Singleton, Appl. Ind. Catul. 1983, I , 275.
[16] T. W. Dekleva, D. Forster, Adv. Catal. 1986, 34, 81.
[I71 D. Forster, T. M. Dekleva, J. Chem. Ed. 1986, 63, 204.
[ 181 J. Gauthier-Lafaye, R. Perron, Methanol et Carbonylation, RhBne-Poulenc Recherches,
Courbevoie, France, 1986 [English translation: Methanol and Carbonylation, Editions
Technip, Paris, and RhBne-Poulenc Recherches, Courbevoie, France, 1987, pp. 117-1481,
[ 191 V. H. Agreda, J. R. Zoeller, (Eds.), Acetic Acid and its Derivatives, Marcel Dekker, New
York, 1993, pp. 35-51.
[20] (a) M. J. Howard, M. D. Jones, M. S. Roberts, S. A. Taylor, Cutul. Today 1993, 18, 325;
(b) G. J. Sunley, D. J. Watson, Catal. Today 2000, 58, 293; (c) D. J. Watson, Chem. Ind.
(Dekker) 1998, 75 (Catalysis of Organic Reactions), 369; (d) J. H. Jones, Platinum Met.
Rev. 2000, 44 (3), 94.
132 2.1 Carbon Monoxide and Synthesis Gas Chemistry

[21] J. F. Roth, J. H. Craddock, A. Hershman, F. E. Paulik, Chem. Technol. 1971, 600.

[22] H. Hohenschutz, N. von Kutepow, W. Himmle, Hydrocurb. Proc. 1966, 45, 141.
[23] Hoechst Celanese Corp. (B. L. Smith, G. P. Torrence, A. Aguilo. J. S. Alder),
US 5.001.259 (1991).
[24] Monsanto Chemicals (T. C. Singleton, W. H. Urry, F. E. Paulik), EP 055.618 (1981).
[25] Monsanto (F. E. Paulik, A. Hershman, W. R. Knox, J. F. Roth), US 3.769.329 (1973).
[26] J. F. Roth, Plat. Met. Rev. 1975, 19, 12.
[27] J. Hjortkjaer, V. W. Jenson, Ind. Eng. Chem., Prod. Res. Dev. 1976, 15, 46.
[28] D. Forster, The Chemist, January 1981, 7.
[29] L. Nowicki, S. Ledakowlez, R. Zarzycki, Ind. Eng. Chem. Res. 1992, 31, 2472.
[30] J. Hjortkjaer, 0. R. Jenson, Ind. Eng. Chem., Prod. Res. Dev. 1977, 16, 281.
[31] T. Matsumoto, K. Mori, T. Mizoroki, A. Ozaki, Bull. Chem. Soc. Japan 1977, 50(9),
2337.
[32] S. B. Dake, D. S. Kolhe, R. V. Chaudhari, Ind. Eng. Chem. Res. 1989, 28, 1107.
[33] (a) Anonymous, Chem. Week June 15, 1994, 9; (b) Anonymous, Petrochem. News, 26
March, 2001, 1.
[34] T. C. Singleton, L. J. Park, D. Forster, Prepr: Am. Chem. Soc. Div. Pet. Chem. 1979, 98,
846.
[35] E. C. Baker, D. E. Hendricksen, R. Eisenberg, J. Am. Chem. Soc. 1980, 102, 1020.
[36] Daicel Chem. Ind. Ltd. (H. Kojima, H. Koyama), JP 60.214.756 (1985).
[37] Union Carbide Corp. (D. J. Schreck), EP 144.935 (1985).
[38] Union Carbide Corp. (D. J. Schreck), EP 144.936 (1985).
[39] D. Forster, J. Am. Chem. Soc. 1975, 19, 951.
[40] T. Mizoroki, T. Matsumoto, A. Ozaki, Bull. Chem. Soc. Jpn. 1979, 52(2), 479.
[41] (a) V. H. Agreda, J. R. Zoeller (Eds.), Acetic Acid and Its Derivatives, Marcel Dekker,
New York, 1993, pp. 145-160; (b) J. R. Zoeller, V. H. Agreda, S. L. Cook,
N. L. Lafferty, S. W. Polichnowski, D. M. Pond, Catal. Today 1992, 13, 73.
[42] J. Hjortkjaer, J. C. Jorgensen, J. Mol. Catal. 1978, 4, 199.
[43] S . B. Dake, D. S. Kolhe, R. V. Chaudhari, J. Mol. Catal. 1984, 24, 99.
[44] T. W. Dekleva, D. Forster, J. Am. Chem. Soc. 1985, 107, 3565.
[45] H. Dumas, J. Levisalles, H. Rudler, J. Organomet. Chem. 1979, 177, 239.
[46] Monsanto (L. S. Eubank, R. T. Eby, C. M. Cruse, H. L. Epstein, H. R. Null,
F. E. Rosenberger), US 3.845.121 (1970).
[47] V. H. Agreda et al., CHEMTECH March 1992, 172.
[48] BASF (W. Reppe) US 2.729.651, US 2.730.546 (1956).
[49] N. Rizkalla, paper presented to Symposium on Chemicals from Syngas and Methanol,
ACS Div. Petroleum Chem., New York, 1986.
[50] Halcon (C. Hewlett), BE 819.455 (1975).
[51] T. H. Larkins, Jr., paper presented to Symposium on Chemicals from Syngas and Metha-
nol, ACS Div. Petroleum Chem., New York, 1986.
[52] Ajinamoto (T. Kogawa et al.), Japan Kokai 50/30.820 (1975).
[53] Showa Denko (T. Onouchi et al.), Japan Kokai 50/47.922 (1975).
[54] J. R. Aitken et al., Large Chem. Plants, 8th Int. Symp. Royal Flemish SOC.Engrs.,
Antwerp. 1992.
[55] B. von Schlotheim, Chem. Industrie 1994, 9/89, 80.
[56] Hoechst (H. Kuckerts), DE 24.50.965 (1974).
[57] Halcon (N. Rizkalla), GB 2.128.609 (1984).
[58] (a) BP Chemicals (D. J. M. Ray, A. J. Stringer), GB 8.404.136 (1984), EP 0.153.834
(1985); (b) BP Chemicals (D. J. Gulliver), GB 8.724.972 (1987), EP 0.314.352 (1989).
[59] Halcon (N. Rizkalla), US 4.335.059 (1982); Halcon (J. Pugach), US 4.284.585 (1981).
[60] Halcon (J. Pugach), US 4.284.586 (1981).
 References 133

I611 (a) Hoechst AG (H.-K. Kubbeler, H. Erpenbach, K. Gehrmann, G. Kohl), DE 2.941.232

(1979), EP 0.027.501 (1981); (b) BP Chemicals (J. Cook, D. J. Drury), GB 8.231.103
(1982), EP 0.108.539 (1984).
[62] Hoechst (H. Erpenbach et al.), DE 3.136.072 (1981), EP 0.074.506 (1982), US 4.444.624
(1984).
[63] (a) BP Chemicals (F. P. Fanizzi, P. M. Maitlis), GB 8.706.767 (1987), EP 0.284.295; (b)
See [l8], p. 173: (c) L. S. Hegedus, S. M. Lo, D. E. Bloss, J. Am. Chem. SOC.1973, 95,
3040; (d) Co complex instead of Rh complex: N. E. Schore, C. Ilenda, R. G. Bergmann,
J. Ant. Chem. Soc. 1976, 98, 7436; (e) Pd complex instead of Rh complex: T. Ito,
H. Tsuchiya, A. Yamamoto, Bull. Chem. Soc. Japan, 1977, 50, 1319; (0Ru complex
instead of' Rh complex: Saunders et al., J. Chem. Soc., Dalton Trans. 1983, 2473.
1641 (a) Hoechst AG (H. Erpenbach, K. Gehrmann, W. Lork, P. Prinz), DE 3.136.027 (1981),
EP 0.074.506 (1982); (b) BP Chemicals (D. J. Gulliver), GB 8.724.971 (1987),
EP 0.314.355 (1989); (c) BP Chemicals (J. B. Cooper, J. Dixon-Hall, S. J. Smith),
GB 9.112.623 (1991), EP 0.518.562 (1992): (d) G. A. Olah, E. Zadok, R. Edler,
D. H. Adamson, W. Kasha, G. K. Surya Prakash, J. Am. Chem. Soc. 1989, I l l , 9123;
(e) F. Wudl, K. C. Khemani, J. Am. Chem. Soc. 1989, l I I , 9124.
[65] Eastman Kodak (C. F. Fillers et al,), US 5.100.850 (1992).
[66] Halcon SD (J. Pugach), EP 210.017 (1987).
[67] BP Chemicals (R. B. A. Pardy), US 4.871.432 (1989).
[68] Eastman Kodak (N. Rizkalla), US 4.792.420 (1988).
[69] Halcon (N. Rizkalla), US 4.650.615 (1987).
[70] Eastman Kodak (J. R. Zoeller), US 4.650.649 (1987).
[71] Hoechst (H. Erpenbach et al.), DE 3.329.781 (1983), EP 0.135.085 (1984).
[72] Hoechst (H. Erpenbach et al.), DE 3.534.815 (1985), EP 0.217.191 (1986).
[73] Hoechst (H. Erpenbach et a].), DE 2.939.839 (1979), EP 0.026.280 (1981).
[74] Hoechst (H. Erpenbach et al.), DE 2.836.034 (1978), EP 8.396 (1980).
[75] BASFAG (H. Friederich), DE 921.938 (1952).
[76] Hoechst AG (H. Erpenbach, K. Gehrmann, P. Horstermann), DE 3.429.179 (1984),
EP 0.170.965 (1985).
[77] (a) I. Hjortkjaer, V. W. Jansen, Ind. Eng. Chem., Prod. Res. Dev. 1976, 15(1), 46; (b)
I. Wender, Crit. Prep. Appl. Chem. 1987, 14, 430.
[78] P. M. Maitlis et al., J. Organomet. Chem. 1990, 398, 311.
[79] (a) J. Hjortkjaer et al., J. Mol. Cutul. 1978, 4, 2454; (b) D. Foster et al., J. Am. Chem.
Soc. 1985, 107, 3565.
[80] H. Papp, M. Baerns in New Trends in CO Activation (Ed.: L. Guczi), Elsevier Science,
Amsterdam 1991, p. 430.
[81] (a) BP Chemicals (J. B. Cooper), GB 8.204.284 (1982); (b) BP Chemicals (D. J. M. Ray,
A. J. Stringer), WO 85/03703 (1985), EP 0.153.834 (1985).
[82] Kuraray KK, JP 163.034 (1982).
[83] Hoechst AG (H. Erpenbach, K. Gehrmann, E. Jagers, G. Kohl), DE 3.823.645 (1988),
EP 0.350.635 (1989).
[84] (a) Daicel (H. Kojima, M. Kagotani, H. Mimeji), JP 124.342 (1983), DE 3.424.471
(1984); (b) Hoechst AG (H. Erpenbach, K. Gehrmann, P. Horstermann, K. Schmitz),
DE 3.429.180 (1984), EP 0.170.964 (1985).
[85] Union Carbide Corp. (R. W. Wegman, D. J. Schreck), US 641.477 (1984), EP 0.173.170
(1985).
[86] Eastman Kodak (T. H. Larkins, S. W. Polichnowski, G. C. Tustin, D. A. Young),
US 209.350 (1980), EP 0.064.986 (1981).
[87] BP Chemicals (D. J. Gulliver), GB 8.618.710 (1986), EP 0.255.389 (1988).
[88] BP Chemicals (J. L. Carey), GB 9.218.346 (1992), EP 0.584.964 (1993).
134 2. I Carbon Monoxide and Synthesis Gas Chemistry

[89] Hoechst AG (H. Erpenbach, K. Gehrmann, W. Lork, P. Prim), DE 3.610.603 (1986),

EP 0.240.703 (1987).
[90] Hoechst AG (H. Erpenbach, E. Goedicke, W. Lork, H. Tetzlaff), DE 3.902.515 (1989),
EP 0.380.91 1 (1990).
[91] Hoechst AG (H. Erpenbach, W. Lork, N. Weferling, P. Pnnz) DE 3.909.445 (1990).
[92] BP Chemicals (J. B. Cooper), GB 9.120.902 (1991), EP 0.535.825 (1993).
[93] Hoechst AG (H. Erpenbach, K. Gehrmann, P. Horstermann), DE 3.534.815 (1985),
EP 0.217.191 (1986).
[94] (a) Hoechst AG (H. Erpenbach, K. Gehrmann, A. Ohorodnik, W. Lork, H. Joest),
DE 3.331.548 (1983), EP 0.143.179 (1984); (b) Hoechst AG (H. Erpenbach, K. Gehr-
mann, W. Lork, P. Prinz), DE 3.534.070 (1985), EP 0.217.182 (1986).
[95] Hoechst AG (H. Erpenbach, K. Gehrmann, W. Lork, P. Prinz), DE 3.329.781 (1983),
EP 0.135.085 (1984).
[96] (a) BP Chemicals (B. P. Gracey), GB 8.822.661 (1988), EP 0.361.785 (1990);
(b) Hoechst Celanese Corp. (C. B. Hilton), US 708.992 (1985), EP 0.196.173 (1986).
[97] Hoechst AG (H. Erpenbach, W. Lork, A. Seidel, P. Prinz), DE 3.903.909 (1989),
EP 0.381.988 (1990).
[98] Hoechst AG (H. Erpenbach, K. Gunther, G. Kohl), DE 3.908.555 (1989), EP 0.387.674
(1990).
[99] AS USSR Chem. Phys.; Zelinski Org. Chem. (L. G. Korableva, A. L. Lapidus,
I. P. Lavrentev), SU 1204251 (1986).
[IOO] Akad. Wiss. ORG. Chem (H. Dilcher, J. Freiberg, M. Knothe, W. Kuhn, H. Marschner),
DD 290.876 (1991).
[loll BP Chemicals (R. G. Bivor, D. J. Gulliver), SU 1808826 (1993).
[I021 BP Chemicals (B. R. George, G. D. Jeffrey, R. G. Beevor, D. J. Gulliver), EP 391.680
(1990).
[lo31 BP Chemicals (D. J. M. Ray, A. J. Stringer), EP 153.834 (1985).
[lo41 Daicel Chem Ind. (H. Kojima, H. Koyama), US 5.391.821 (1995).
[lo51 (a) University of Alberta (R. G. Cavell, K. V. Katti), US 5.352.813 (1994);
(b) University of Alberta (R. G. Cavell, K. V. Katti), CA 2.024.284 (1992).
[ 1061 (a) BP Chemicals (M. J. Baker, J. R. Dilworth, J. G. Glenn, N. Wheatley), EP 632.006
(1994); (b) M. J. Baker, M. F. Giles, A. G. Orpen, M. J. Taylor, R. J. Watt, J. Chem.
SOC., Chem. Commun. 1995, 197.
[lo71 M. S. Balakrishna, R. Klein, S. Uhlenbrock, A. A. Pinkerton, R. Cavell, Znorg. Chem.
1993, 32, 5676, and refs. therein.
[I081 Union Carbide Chem (D. J. Schreck, R. W. Wegman), US 5.026.907 (1991).
[lo91 R. Wegman, A. Abatjoglou, A. M. Harrison, J. Chem. SOC., Chern. Commun. 1987,
1891.
[ 1101 K. G. Moloy, R. W. Wegman, Organometallics 1989, 8, 2883.
[ l l l ] (a) G. Ritter, G. Luft, Chern.-1ng.-Tech.1987, 59(6), 485; (b) P. Trabold, F. Steinacker,
G. Luft, Chem.-1ng.-Tech. 1989, 61(7), 556; (c) Hoechst AG (G. Luft, G. Ritter),
DE 3.511.050 (1985), EP 0.203.286 (1986); (d) Hoechst AG (G. Luft, P. Trabold),
DE 3.811.343 (1988), EP 0.336.216 (1989); (e) Hoechst AG (G. Luft, P. Trabold),
DE 3.808.867 (1988), EP 0.332.969 (1989); (f) BP (D. J. Watson, B. L. Williams, R.
J. Watt), GB 9.303.770 (1993), EP 0.612.712 (1994).
[I121 J. Hjortkjaer, Y. Chen, B. Heinrich, Appl. Cutul. 1991, 67, 269, and refs. therein.
[I131 Reilly Tar & Chem Corp., Reilly Ind. Inc. (G. L. Goe, C. R. Marston), US 5.155.261
(1992).
[ 1141 (a) Hoechst Celanese Corp. (M. 0. Scates, G. P. Torrence, R. J. Warner), US 5.28 1.359
(1994); (b) BP Chemicals (J. G. Sunley, D. J. Watson, R. J. Watt, B. L. Williams),
US 5.360.929 (1994).
 References 135

[I151 (a) Chiyoda Corp. (K. Hamato, T. Minarni, K. Shimokawa, Y. Shiroto, N. Yoneda), US
5.364.963 (1994); (b) Chiyoda Corp. (S. Asaoka, K. Harnato, T. Maejima, Y. Shiroto,
N. Yoneda), US 5.334.755 (1994); (c) N. Yoneda, T. Minami, J. Weiszmann, B. Spehl-
mann, Science and Technology in Catalysis. Proc. Third Tohyo Conj On Adv. Catul.
Sci. and Technol. July 1998, 93; (d) Chiyoda Corp. (N. Yoneda, T. Minarni, Y.
Nakagawa, A. Yarnaguchi, H. Sugiyama, F. Uemura), US 6.066.762 (2000); (e)
UOP LLC (W. Leet, S. Kulprathipanja), US 6.153.792 (2000).
[I161 Daicel Chem. Ind., JP 07.025.814 (1995).
[117] Daicel Chern. Ind., JP 07.025.813 (1995).
[118] BP Chemicals (S. D. Aubigne, J. B. Cooper, B. L. Williams, D. J. Watson),
US 5.416.237 (1995).
[ 1191,Daicel Chem. Ind., JP 06.040.998 (1994).
[lY]G) Hoechst Celanese Corp. (G. A. Blay, W. D. Picard, M. 0. Scates, M. Singh),
US 5.371.286 (1994); (b) Celanese International Corp., USA (M. Singh, G. A. Blay,
M. L. Karnilaw, M. A. Meilchen, W. D. Picard, V. Santillan, M. 0. Scates, R. S.
Tanke, G. P. Torrence, R. F. Vogel, R. J. Warner), US 6.143.930 (2000).
[121] Hoechst Celanese Corp. (R. K. Gibbs, M. 0. Scates, G. P. Torrence), US 5.202.481 (1993).
[122] Hoechst Celanese Corp. (P. M. Colling, W. D. Picard, M. 0. Scates, G. P. Torrence),
EP 372.993 (1990).
[123] Hoechst Celanese Corp. (R. K. Gibbs, M. 0. Scates, G. P. Torrence), EP 322.215 (1989).
[124] Hoechst Celanese Corp. (R. K. Gibbs, M. 0. Scates, G. P. Torrence), US 5.155.266
(1992).
[I251 Hoechst Celanese Corp. (R. K. Gibbs, M. 0. Scates, G. P. Torrence), US 5.155.265
(1992).
[I261 (a) Hoechst Celanese Corp. (C. B. Hilton), US 4.615.806 (1986); (b) BP chemicals
(J. Cook, R. A. Hazel, P. J. Wilson), US 5.387.731 (1995); (c) BP Co. (M. D. Jones),
EP 482.787 (1 992).
[I271 (a) Hoechst AG (H. Erpenbach, R. Gradl, E. Jagers, A. Seidel), DE 4.034.867 (1990),
EP 0.483.536 (1991); (b) Hoechst AG (H. Erpenbach, R. Gradl, E. Jagers, A. Seidel),
DE 4.029.917 (1990), EP 0.476.333 (1991).
[128] (a) Halcon (N. Nagliari, N. Rizkalla), US 642.813 (1975); (b) Mitsubishi Gas Chern.
(T. Isshiki, Y. Kijima, Y. Miyauchi) JP 121.772-77 (1977), DE 2.844.371 (1978);
(c) Halcon (N. Rizkalla) US 219.786 (1980); (d) Halcon (N. Rizkalla) US 219.788
(1980); (e) Halcon (N. Rizkalla) US 430.094 (1982); ( f ) BP (J. Cook, R. D. Crack)
GB 8.314.137 (1983), EP 0.129.332 (1984); (8) A. A. Kelkar, R. S. Ubale, R. V. Chaud-
hari, J. Mol. Catal. 1993, 80(1), 21; (h) X. Wang, Z . Jia, Z. Wang, J. Nat. Gas Chem.
1992, I , 65; (i) S. Bischoff, K. Fujimoto, B. Liicke, Chem.-Ing.-Techn. 1994, 66(4), 516.
[129] U. Dettmeier, E. I. Leupold et al., Erdol, Kohle, Erdgas, Petrochem. 1985, 38, 59.
[130] J. F. Knifton, J. Cutal. 1985, 96, 439.
[131] J. S. Lee, J. C. Kirn, Y. G. Kirn, Appl. Catal. 1990, 57, I .
[132] D. J. Schreck, D. C. Busby, R. W. Wegman, J. Mol. Catul. 1988, 47, 117.
[133] G. Bub, H.-U. Hog, J. Mol. Catul. A, Chem. 1995, 95, 45.
[ 1341 (a) J. A. Christiansen, J. C. Gjaldboeck, Kgl. Danske Videnskab. Selskab. Medd. 1942,
20; (b) L. J. Kaplan, Chem. Eng. 1982, 89, 71.
[135] Pohang Steel, KR 9.201.987 (1989).
[136] (a) Halcon (N. Rizkall), US 268.029 (1981); (b) Halcon (N. Rizkall), US 431.450
(1982); (c) BP (D. J. Drury) GB 8.231.526 (1982), EP 0.109.212 (1984); (d) BP
(P. S. Williams), GB 8.319.184 (1983), EP 0.135.286 (1985); (e) Hiils AG (G. Bub,
H.-U. Hog), DE 3.333.317 (1983); ( f ) Union Carbide (R. W. Wegmann, D. C. Busby,
D. J. Schreck), US 557.270 (1983), EP 0.146.823 (1984); (8) Daicel (H. Kojima,
T. Fujiwa), JP 68.212-84 (1984), US 4.996.357 (1985); (h) Union Carbide (R. W. Weg-
136 2.1 Carbon Monoxide und Synthesis Gas Chemistry

mann), US 632.837 (1984), EP 0.171.651 (1985); (i) Sollac (J.-A. Cordier, F. P. Petit,
Y. Castenet, S. Melloul, A. Mortreux) FR 8.805.462 (1988), EP 0.342.084 (1989);
(i) Pohang Steel, KR 9.200.893 (1989); (k) Sollac (Y. Castanet, B. Seuillet, A. Mor-
treux, F. Petit), FR 9.105.145 (1991), EP 0.511.038 (1992).
[ 1371 (a) H. Hogeveen, J. Lukas, C. F. Robeek, Chem. Commun. 1969, 970; (b) G. A. Olah,
K. Dunne, Y. K. Mo, P. Szilagyi, J. Am. Chem. Soc. 1972, 94, 4200; (c) G. A. Olah,
A. Bagno, J. Bukala, J. Org. Chem. 1990, 55, 4284.
[138] T. Nishiguchi, K. Nakata, K. Takaki, Y. Fujiwara, Chem. Lett. 1992, 7, 1141.
[139] M. Lin, A. Sen, Nature (London) 1994, 368, 613.
[ 1401 According to unpublished results of Hoechst AG.
[141] D. Linke et al., 1. Catal. 2002, 205, 16.

2.1.2.2 Synthesis of Propionic and Other Acids

Arthur Hiihn

The synthesis of carboxylic acids by carbonylation of unsaturated hydrocarbons or

alcohols was developed mainly by Reppe and his co-workers in the laboratories of
BASF at Ludwigshafen. Many industrially important processes such as the syn-
thesis of acrylic acid, propionic acid, and acetic acid were elaborated there in
the period from the late 1930s to the mid-1950s [ l , 21. Reppe’s introduction of
metal carbonyls as catalysts for carbonylation reactions was of paramount im-
portance and many processes, which are still industrially relevant today, were
developed rapidly (eq. (l), [3]).

R+ + CO + H20 5 R\/\COOH

Metal carbonyls proved to be superior to earlier catalytically active systems,

where in particular strong acids were used [4], because the conditions, namely
pressure and temperature, that had to be applied led to skeletal isomerization of
the substrates and resulted predominantly in the formation of branched isomers
of carboxylic acids. Metal carbonyls were of great advantage over the older
catalysts in this respect. Despite the fact that it was possible to optimize the
catalyst metal, the ligands, and the promoters for nearly every carbonylation
reaction, enabling the reactions to take place under milder conditions than had
been previously used, these processes could only be realized industrially after
the development of appropriate reactor materials because of the corrosive proper-
ties of the reaction media and products.

2.1.2.2.1 Propionic Acid

Properties and Applications [5-71

Propionic acid is a monobasic fatty acid. It is a colorless liquid and has an

acidic taste and a pungent odor. Propionic acid is miscible with water and
 2.1.2.2 Synthesis of Propionic and Other Acids 137

almost all conventional organic solvents. It is an intermediate for the chemical

industry and is used, for example, in the production of plastics, plasticizers,
textile and rubber auxiliaries, dye intermediates, solvents, synthetic fragrances
and flavors, cosmetics, pharmaceuticals, crop protection agents, pesticides, and
preservatives. Because of the pronounced antimicrobial activity of propionic
acid, the acid itself and its calcium, ammonium, and sodium salts are used
for preserving feedstuffs and various foods. In fairly high dosages propionic
acid exhibits bactericidal, fungicidal, insecticidal, viricidal, and acaricidal
activity and has a powerful action on yeasts. Free propionic acid is found
in nature where fermentation takes place under the appropriate anaerobic con-
ditions, in particular in the mmen of ruminants. Propionic acid is also present
in Emmental cheese, kefir, yoghurt and many other products produced by
fermentation.

Synthesis

Various molecules can serve as a starting material for the synthesis of carboxylic
acids by carbonylation. Because of the differing chemical nature of the starting
materials, special catalysts or catalytic systems have been developed. However,
despite the fact that tremendous efforts have been made to develop large-scale pro-
cesses, few have been brought to commercial maturity.

Carbonylation of Ethylene

BASF is the only producer of propionic acid by the carbonylation of ethylene,

which is reacted exothermically (AH = -64.5 kJ/mol) with carbon monoxide
and water. Nickel chloride was patented as early as 1943 as a catalyst for the
carbonylation of ethylene [8]. For the industrial-scale process, however, a halo-
gen-free system is used [9, 101. Propionic acid is formed according to eq. (2).

H*C=CH* + CO + H20 fiCOOH

The catalyst is a nickel hydride complex that is generated under the reaction
conditions (10-30 MPa, 250-320 "C) by reduction of the nickel salt using
Ni(C0)4 as a precursor. Assuming the catalyst to be a nickel hydride complex,
the mechanism for the formation of propionic acid is straightforward. It very
likely follows the elementary steps of the catalytic cycle outlined below
(Scheme 1). Addition of ethylene to the hydride intermediate generates an
ethyl complex which, after insertion of CO and nucleophilic attack of water,
releases propionic acid with regeneration of the initial hydride intermediate.
The dependencies of reaction parameters such as temperature, pressure, and
feed composition were investigated thoroughly in order to find optimum condi-
tions [ll].
138 2.1 Carbon Monoxide and Synthesis Gas Chemistry

H'
I
Ni
L/
Ni
I
I co
co

Scheme 1. Catalytic cycle of the carbonylation of ethylene.

The catalyst is generated under reaction conditions from nickel(I1) salts. The
mechanism of this process has not been fully established: It has been suggested
that Ni(CO), which is formed in situ using one molecule of carbon monoxide
as a reducing equivalent according to eq. (3) is protonated according to eq. (4),
[ 121 yielding the active catalyst.

Nix2 + 5CO + H20 - Ni(C0)4 + C02 + 2 HX (3)

Ni(C0)4 + HX - HNi(CO)2X + 2CO (4)

The abundant chemistry of Ni(C0), under reductive reaction conditions leading

to the formation of dinuclear nickel complexes or even to nickel clusters suggests
the involvement of higher aggregates, however. An overview of the reactivity of
nickel complexes, and of Ni(C0), in particular, is given in a series of excellent
reviews by Jolly [13]. There seems to be evidence of an autocatalytic cycle for
the formation of the active catalyst [14]. Parallel to this, the water-gas shift reac-
tion (eq. ( 5 ) ) occurs, resulting in the formation of carbon dioxide and hydrogen,
which is known to form metal hydrides in the presence of metal carbonyls [15].
CO + H20 Cop + H2 ( 51
In addition, the presence of hydrogen opens up the way to various possible side
reactions such as the formation of ethane by hydrogenation of ethylene or the for-
mation of diethyl ketone from ethylene, carbon monoxide, and hydrogen. Ethanol
is formed independently by hydration of ethylene, which condenses with pro-
pionic acid to form the corresponding ester.
The industrial-scale BASF process is characterized by low raw material costs,
high conversion and yield, and a simple work-up (Figure 1).
Ethylene and carbon monoxide are compressed and continuously pumped into
the high-pressure reactor (1) together with feed solution. The crude propionic acid
 2.1.2.2 Synthesis of Propionic and Other Acids 139

formed at 10-30 MPa and 250-320°C is drawn off at the top of the reactor and
cooled in a heat exchanger (2), generating steam. Part of the cooled reaction
product is recycled to the reactor for temperature regulation ( 3 ) ;the main quantity
is allowed to expand and is separated into an off-gas and a crude acid stream (4).
Nickel is recovered from the off-gas and recycled to the reactor. The off-gas is in-
cinerated with recovery of heat. The crude acid stream is subsequently dehydrated
and worked up by distillation in several columns (5).The nickel salts thus formed
are recycled to the process. The pure propionic acid is finally obtained by distilla-
tion. The product residue is channeled out of the process.
Due to its corrosiveness, which is not only determined by the water content,
pressure, and temperature, but also by the degree of purity, ordinary steel is
totally unsuitable for handling propionic acid. Only silver has proved to be a
suitable material above the boiling point up to about 230 "C [lo].
In contrast to the carbonylation of alkynes, the advantages of nickel as the
catalyst metal are much less pronounced with alkenes. As a result, various cata-
lytic systems have been developed. They can be roughly subdivided into two
classes, i. e., halogen-containing and halogen-free. So far, none of these catalyst
systems has achieved industrial significance.
Halogen-containing systems arc characterized by higher activities at lower
reaction pressures. Rhodium carbonyl chloride dimer is reported to be an active
carbonylation catalyst in the absence of additional halogen compounds [ 161.
Parallel to investigating the carbonylation of methyl iodide (from methanol
and hydrogen iodide) to acetic acid (cf. Section 2.1.2. I), the carbonylation of
ethyl iodide (from ethanol or ethylene and hydrogen iodide) to propionic acid
was investigated inter alia by Monsanto. As in the case of the production of

t
, propionicacid ~

ethylene
'f t L
by-products

carbon
monoxide
t
water

Figure 1. BASF process for the production of propionic acid.

140 2.1 Carbon Monoxide and Synthesis Gas Chemistry

acetic acid, the most promising system seems to be rhodium iodide. The oper-
ating pressure is as low as 3 MPa; however, temperatures of around 200°C are
required. As a consequence, the system is corrosive and, in a commercial-scale
plant, materials such as Hastelloy B and C, zirconium, and stainless steel are
necessary, depending on the conditions (temperature and pressure) in the dif-
ferent areas of the unit, such as the reaction and the separation sections. Yet
another problem of the system is the toxicity of chemicals that are formed in
the process. In an operating plant large quantities of ethyl iodide are handled.
Consequently measures have to be taken to ensure that in case of an incident
no iodine is formed from ethyl iodide-containing vapors in a plume, which
would cause a serious pollution problem.
Some insight into the mechanisms of the iodine-promoted carbonylation has
been obtained by radioactive tracer techniques [ 171 and low-temperature NMR
spectroscopy [18]. The mechanism involves the formation of H1, which in a
series of reactions forms with rhodium a hydrido iodo complex which reacts
with ethylene to give an ethyl complex. Carbonylation and reductive elimination
yield propionic acid iodide. The acid itself is then obtained after hydrolysis. The
rate of carboxylation was reported to be accelerated by the addition of minor
amounts of iron, cobalt, or manganese iodide [19]. The rhodium catalyst can be
stabilized by triphenyl phosphite [20]. However, it is doubtful whether the ligand
itself would meet the requirements of an industrial-scale process.
In principle other halogens apart from iodide may also be used as a promoter.
For bromide, Monsanto reports the synthesis of propionic acid from ethylene with
selectivities of more than 99 % when a large excess of bromide in the form of hy-
drobromic acid is added to a rhodium catalyst [21]. The carbonylation is catalytic
both with respect to the rhodium and the bromide components. Nonhalogen pro-
moters in combination with rhodium as catalyst are phenols, thiophenols, thiocar-
boxylic acids, and sulfonic acids [22].
In early patents by Halcon, molybdenum carbonyls are claimed to be active cat-
alysts in the presence of nickel and iodide [23]. Iridium complexes are also re-
ported to be active in the carbonylation of olefins, in the presence of other halogen
[24] or other promoting co-catalysts such as phosphines, arsines, and stibines [25].
The formation of diethyl ketone and polyketones is frequently observed. Iridium
catalysts are in general less active than comparable rhodium systems. Since the
water-gas shift reaction becomes dominant at higher temperatures, attempts to
compensate for the lack of activity by increasing the reaction temperature have
been unsuccessful.
The use of palladium and ruthenium as halogen-free carbonylation catalysts
has been studied intensively by Shell. The catalysts were principally designed
for the carbonylation of olefins in the presence of alcohols in order to yield
carboxylic esters [26], but work also well for the synthesis of carboxylic acids
or anhydrides. The latter are formed when the reaction is conducted in an acid
as a solvent [27]. The palladium systems typically consist of palladium acetate,
tertiary phosphines, and strong acids such as mineral acids or acids with weak
or noncoordinating anions such as p-toluenesulfonic acid. Remarkable activities
are achieved when aromatic phosphines that carry pyridines as substituents are
 2.1.2.2 Synthesis of Propionic and Other Acids 141

used [27]. The reaction conditions that are required are more severe than similar
palladium systems with ruthenium as the active metal center. What is crucial to all
the systems is the stability of the organic ligand.

Homologation of Acetic Acid

The homologation of acetic acid to carboxylic acids in general and to propionic

acid in particular is not a typical carbonylation reaction, in that the substrate is
not treated with carbon monoxide gas but with synthesis gas. However, as out-
lined below, the homologation step itself is, within the sequence of consecutive
reactions, a typical carbonylation reaction and, therefore, the reaction sequence
will be dealt with here (cf. Sections 2.1.2.4 and 3.2.7).
For the generation of propionic acid from acetic acid the overall equation (13)
can be formulated [28]. Thorough investigation of the reaction in the presence of
iodide by following the formation of products with time gave insight into the pro-
cess and an evaluation of its practical limits [29]. For the Ru/iodide system Zoeller
[30] suggests that acetic acid is initially relatively rapidly hydrogenated via acet-
aldehyde to ethanol (eqs. (6)-(S)), which together with unreacted acetic acid is in
equilibrium with the corresponding ester and water (eq. (9)). The ester is then con-
verted to acetic acid and ethyl iodide (eq. (lo)), which is carbonylated (eq. (1 1))
and yields propionic acid after hydrolysis (eq. (12)).

CH3COOH + HI - CH3COl + H20 (6)

+ - +
-
CH3COl H2 CH3CHO HI (7)
CH3CHO +
+
H2
- C2H5OH
+
(8)
(9)
-
CH3COOH C2H50H CH3COOC2H5 H20

+ HI +
CH~C O O C~HS
+ - CH3COOH C2H51 (10)

-
C2H51 CO C2H5COI (11)
C2H5COI + H20 C2H5COOH + HI (12)

CH3COOH + CO
~~

+
~

2H2 - ~

C2H5COOH + H20 (13)

Suitable catalysts for this type of process must be capable of hydrogenating

both carboxylic acids and their esters to alcohols, but also of carbonylating
these compounds to their homologous acids. The best catalytic systems known
contain either Rh or Ru in the presence of iodide. Ruthenium iodide systems
are the most active ones in the hydrogenation reaction, but suffer from low activity
in the carbonylation step, whereas rhodium iodide systems are very active when
carbonylating alcohols to their acids (cf. Section 2.1.2.1).
From the commercial point of view, the industrial realization of such a process
seems to be very unlikely for various reasons: The most serious drawback is the
liberation of water in the process, which in practice limits the conversion of the
142 2.1 Carbon Monoxide and Synthesis Gas Chemistry

reaction. Additionally, drastic temperatures and pressures are necessary, iodine-

containing compounds have to be handled, and selectivities are still rather poor.
The main side reactions are hydrogenation to hydrocarbons and the formation
of higher homologous acids.

Various Routes to Propionic Acid by Curbonylation

For the purpose of completeness, the synthesis of propionic acid from its anhy-
dride by hydrolysis should be mentioned here. In principle, when the carbonyla-
tion of ethylene is conducted in propionic acid instead of water as a solvent, the
reaction product is the anhydride (eq. (14)).

Similarly, when an alcohol is present the corresponding ester forms, from which
the acid is liberated analogously (eq. (15)).

HpC=CH2 + CO + ROH -
cat' /\lfO0
\R (15)

Of more academic interest is the carbonylation of dioxane according to eq. (16):

Propionic acid is also formed as a co-product when methyl acetate is treated

with carbon monoxide in the presence of hydrogen [28]. Rhodium-based homo-
geneous catalyst systems have been described which permit the homologation
of esters according to two alternative stoichiometries. The reactions proceed
under mild conditions according to eqs. (17) and (18) [31]:
0
2 A 0 / + 2 C 0 + 2H2 5 Ao- + 2CH3COOH (17)

Ao/ + 2CO + 2H2 5 \/loH

+
0
CH3COOH (18)

The two stoichiometries, combined with esterification, form the basis for a two-
step route for the synthesis of ethyl acetate and propionic acid from methanol and
syngas as the only feedstock.
Ethanol, in combination with halides, gives in principle the same intermediates
which form when ethylene is carbonylated in the presence of hydrohalic acids, as
discussed in detail above.
 2.1.2.2 Synthesis of Propionic and Other Acids 143

2.1.2.2.2 Higher Carboxylic Acids

The production of carboxylic acids other than propionic acid by carbonylation is
of little industrial relevance today. In principle the same catalytic systems that can
be used for the carbonylation of ethylene (or any other adequate equivalent) to
propionic acid are applicable for the synthesis of the higher carboxylic acids
from olefins [32].
Higher olefins inherently show distinct chemical and physical differences from
ethylene, which result in a number of obstacles when producing carboxylic acids
from them. Additionally, the hydrocarboxylation of higher alkenes gives mixtures
of the saturated acids (eq. (19)):

Selectivities are in general lower due to the facile double-bond isomerization

by the carbonylation catalysts [15, 33, 341. Depending on the availability of the
olefins, i.e., a- or internal olefins, and the target acids, the choice of the catalyst
is of utmost importance. If terminal acids are to be produced from internal ole-
fins with more than three carbon atoms, a double-bond isomerizing catalyst such
as cobalt has to be used. The olefins are equilibrated prior to carbonylation, re-
sulting in an identical mixture of carboxylic acids, no matter what starting olefin
is used. Modification of the catalytic system with aromatic heterocycles, e.g.,
with pyridines, gives control of the ratio of the linear/terminal acids produced
[35, 361. In contrast nickel catalysts show very little isomerization activity.
Still, because of the difficulty of controlling the regioselectivity of the carbony-
lation, a- and 2-methyl branched acids are formed. Selectivities are further
diminished due to the hydrogenation of the higher olefins (hydrogen stems
from the water-gas shift reaction).
Sterically hindered olefins are substantially less reactive. Tetraalkylethylenes
are inactive under Reppe conditions.
Despite the fact that hydrocarboxylation is a one-step synthesis to alkanoic
acids and that with specific catalysts and under certain reaction conditions the
straight-chainhranched-chain isomer (di) ratio can be rather high, this route to
carboxylic acids is not used commercially today. It will be up to future R&D
workers to design catalysts that are active and stable enough to replace today’s
commercial two-step synthesis for the preparation of alkanoic acids from their al-
dehydes by oxidation.
144 2.1 Carbon Monoxide and Synthesis Gas Chemistp

References
[ l ] W. Reppe, Ann. Chim. (Paris) 1953,582, 1; W. Reppe, H. Kroper, ibid. 1953, 582, 3 8 ;
W. Reppe, H. Kroper, N. v. Kutepov, H. Pistor, ibid. 1953,582, 72; W. Reppe, H. Kroper,
H. Pistor, 0. Weissbarth, ibid. 1953, 582, 87.
[2] J. Falbe, J. Organomet. Chem. 1975, 94, 213.
131 W. Reppe et al., Ann. Chem. (Paris) 1953, 582, 116; W. Reppe, H. Vetter, ibid. 1953,
582, 133.
[4] K. Weissermel, H.-J. Arpe, Industrielle Organische Chemie, 4th ed., VCH, Weinheim,
1994, p. 154.
[5] U. Samel, W. Kohler, A. Gamer, U. Keuser, Ullmann’s Encycl. Ind. Chem., 5th ed. 1993,
Vol. A22, p. 223.
[6] Anon., Propionic Acid, BASF data sheet, BASF AG Intermediates Operating Division,
Ludwigshafen, Germany, 1991.
[7] Anon., Compound Feed Preservation with Luprosil, BASF leaflet, BASF AG Fine
Chemicals Operating Division, Ludwigshafen, Germany 1991.
[S] BASF (W. Reppe, H. Kroper), DE 862.748 (1952); BASF (W. Reppe, H. Kroper), DE
863.194 (1952).
[ 91 K. Weissermel, H.-J. Arpe, Industrielle Organische Chemie, 4th ed., VCH, Weinheim,
1994, p. 152.
[lo] BASFAG (H. Hohenschutz, D. Franz, H. Bulow, G. Dinkhauser), DE 2.133.349 (1973).
[ I l l R. Brooks, W. Gresham, J. Hardy, J. Lupton, Ind. Eng. Chem. 1957, 49, 2004.
[12] R. Heck, J. Am. Chem. Soc. 1963, 85, 2013.
[I31 P. Jolly, Comprehensive Organometallic Chemistry (Eds.: G. Wilkinson, F. G. A. Stone,
E. W. Abel), Pergamon, Oxford, 1982, Vol. 6, pp. 3, 15, 37, 101.
[ 141 BASF AG, 1995, unpublished results.
[15] M. Roper in New Trends in CO Activation (Ed.: L. Guczi), Elsevier, Amsterdam, 1991,
Chapter 9.
[16] BP Chemicals Ltd. (G. E. Foster, J. R. E. Bethell), DE 2.101.909 (1972).
[17] D. E. Moms, G. V. Johnston, Proc. Symp. Rhodium Homogeneous Catalysis, 1978,
VeszprCm Vegyip. Egy. Kozp. Konyvtara, Veszprkm, Hungary, 1978, p. 113.
[18] D. C. Roe, R. E. Sheridan, E. E. Bunel, J. Am. Chem. SOC.1994, 116, 1163.
[I91 Monsanto Company (T. C. Singleton), US 4.327.345 (1976).
[20] BP Chemicals International Ltd. (M. J. Wriglesworth, D. J. Westlake), GB 1.363.961
(1972).
[21] Monsanto Company (J. H. Craddock, J. F. Roth, A. Hershman, F. E. Paulik), US
3.989.747 (1974).
[22] Monsanto Company (D. Foster, D. E. Moms), US 3.816.490 (1971).
[23] Halcon Research and Development Corp. (R. Nabil), US 4.335.058 (1981).
[24] Monsanto Company (F. E. Paulik, A. Hershman, J. F. Roth, J. H. Craddock), US
3.989.748 (1974).
[25] Monsanto Co. (D. E. Moms, H. B. Tinker), US 3.948.962 (1974).
[26] Shell (E. Drent), EP 55.875 (1981).
[27] Shell (E. Drent, L. Petrus, S. A. J. Van Langen) EP 282.142 (1988).
[28] G. Braca, A. M. Raspolli Galletti, G. Sbrana in Oxygenates by Homologation or CO Hy-
drogenation with Metal Complexes (Ed. : G. Braca), Kluwer Academic Publishers, Dor-
drecht, 1994.
[29] J. F. Knifton, Hydrocarbon Process., Int. Ed. 1981, 60, 113.
[30] J. R. Zoeller, J. Mol. Catal. 1986, 37, 7.
[31] E. Drent, J. Mol. Catal. 1986, 37, 93.
[32] P. Escaffre, A. Thorez, P. Kalck, J. Mol. Catal. 1985, 33, 87.
 2.1.2.3 Carbonylation of Benzyl-X and Aryl-X Compounds 145

[33] P. Pino, F. Piacenti, M. Bianchini in Organic Synthesis via Metal Carbonyls Vol. 2,
(Eds.: I. Wender, P. Pino), John Wiley, New York, 1977.
[341 W. Bertleff, UllrnannS Encycl. Ind. Chern. 5th ed. 1993, Vol. A5, p. 217.
[35] D. R. Levering, A. R. Glasebrook, J. Org. Chern. 1958, 23, 1836.
[36] N. S. Imyanitov, D. M. Rudkovskii, J. Appl. Chern. USSR 1968,41, 157.

2.1.2.3 Carbonylation of Benzyl-X and Aryl-X Compounds

Matthias Beller

2.1.2.3.1 Introduction
New functionalizing reactions with carbon monoxide to give carbonyl com-
pounds, in addition to hydroformylation, have been developing rapidly during the
past ten years, but mainly for laboratory-scale synthesis. Industrial applications of
carbon monoxide in the synthesis of fine chemicals have been until now rare. In
this section, applications of the carbonylation of benzyl-, aryl-, and related vinyl-
and allyl-X compounds are discussed [ I]. Emphasis is given especially to a fun-
damental understanding and to technically interesting developments.

2.1.2.3.2 General Considerations and Mechanism

The carbonylation of C-X derivatives represents a large family of related homo-
geneous metal-catalyzed organic reactions (eq. ( 1)). Prominent members include
hydroxy, alkoxy, and amido carbonylations, and double carbonylations.

R-X + n CO + NU-H -
catalyst
R-(CO),-NU + HX (1)
From formal retrosynthetic considerations and a mechanistic point of view
these carbonylations are closely related. The reactions are thought to proceed as
shown in Scheme 1. The salient points of the mechanism include: ligand dissocia-
tion to the active catalyst (eq. (2)), oxidative addition (eq. (3)) of the organic com-
pound to a metal(0) complex (e. g., M = Pd, Co, Ni, Pt; L = PR3), CO insertion
forming a metal(I1) acyl complex (eq. (4)), either reductive elimination (eq. ( 5 ) )
or reaction of this complex with nucleophiles yielding the carbonylated product
and an X(hydrido)metal(II) complex (eq. (6)) and elimination of HX to regenerate
the original catalyst (eq. (7)).
Clearly, the first step in the carbonylation of allylic and benzylic derivatives to
3,4-unsaturated carboxylic acid derivatives and arylacetic acid derivatives,
respectively, requires activation of a C-X bond at an sp3-hybridized carbon
atom. Such activation could proceed either via nucleophilic attack with anionic,
18-electron metal complexes, which has been described, e. g., with cobalt [2]
146 2.1 Carbon Monoxide and Synthesis Gas Chemistry

and iron catalysts [3], or via oxidative addition with electronically unsaturated
catalysts, e. g., nickel [4], rhodium [5], platinum [5a], and mainly palladium
compounds [6].
MOLx + 2 - MOL~ + 2 L (2)
MoLx + R-X . (3)
-
RMIIXL~

co
RMIIXL~

RCO-M~~XL~
+

+
-
-
RCO-M~~XL~
MOL~ + RCO-x
RCO-NU + Hm"XLx
(4)
(5)
or RCO-M"XLx NuH (6)
HMIIXL~ - HX + MoLx (7)
Scheme 1. General mechanism of the carbonylation of C-X.

In contrast, nucleophilic attack at an sp2-carbon center with anionic 18-electron

species like [Co(CO)J and [Fe(C0),l2- usually fails to activate aromatic or vinylic
halides. Thus, catalytic carbonylations of aryl halides are initiated by oxidative
addition of a C-X bond to an electronically unsaturated metal complex, normally
a palladium [7], cobalt [8] or nickel complex [9]. The rate of this oxidative
addition decreases along the sequence

C-I > C-OTf 3 C-Br >> C-CI >> C-F

which is in agreement with the magnitudes of the C-X bond energies. The
presence of electron-withdrawing groups or an additional coordination site
(e.g., the o-acetamido group) on the aryl ring accelerates the reaction. For the
carbonylation of iodo- and activated bromo-aromatics the rate-determining step
of the reaction is the nucleophilic attack on an acylmetal intermediate. Thus, ami-
dation proceeds more rapidly than esterification under similar conditions. Stereo-
specifity in carbonylations of cis or trans vinylic halides is also greater for amida-
tions (100 % retention) compared with esterifications (90-95 % retention).
As an example, the mechanism of the palladium-catalyzed methoxycarbon-
ylation of bromobenzene has been investigated in detail by cylindrical internal re-
flectance-Fourier transform infrared spectroscopy (CIR-FTIR) [ lo]. Infrared
spectra of the active reaction at high alcohol concentration show that the
dominant palladium complex does not contain a carbonyl group, which is con-
sistent with a rate-limiting step involving oxidative addition of bromobenzene
to a palladium-phosphine complex. At low methanol concentrations the palla-
dium-acyl complex predominates and the rate strongly depends on the basicity
of the base. The acyl complex is quite stable unless both alcohol and base are pre-
sent, suggesting that the active species for nucleophilic attack is an alkoxide ion.
Beside alkoxide itself, alcoholate complexes of various elements, such as boron,
aluminum, and titanium, can act as alkoxide source. Kudo and coworkers [ 111 re-
ported for alkoxycarbonylations the following order of reactivity:

ally1 > benzyl > phenyl = methyl > vinyl > propyl > ethyl
 2.1.2.3 Curbonylution of Benzyl-X and Aryl-X Compounds 147

This again correlates with the dissociation energy of the R-X bond.
Most work reported on carbonylations of C-X used corresponding halides as
starting materials. Moreover, diazonium compounds [ 121, triflates [ 131, alkyl-,
aryl- or fluorosulfonates [ 141, or iodoxyarenes [ 151 (although technically not
very important), were used as starting materials because of the ease of C-X
activation.
After insertion of CO, the resulting metal acyl complex could undergo a
reductive elimination of RCOX. Alternatively, it may react with a variety of
nucleophilic counterparts, which is what makes this chemistry so valuable in
organic synthesis. Depending on the reaction media and the conditions, it is
possible to synthesize acids, esters, amides, or acid fluorides from the same start-
ing material, as shown in Scheme 2 for aryl-X compounds [16].
Moreover, aryl-oxazoles, -imidazoles [ 171, or -thiazoles [ 181, anhydrides [ 191,
and imides [20] are accessible via intramolecular Heck-type carbonylations. In
addition to typical acid derivatives, aldehydes [2 11, ketones [22], aroyl cyanides,
aroyl acetylenes, and their derivatives [23] could be synthesized via nucleophilic
attack of the acyl metal complex with the corresponding hydrogen or carbon
nucleophiles. Even anionic metal complexes like [Co(CO)J can act as nucleo-
philes and lead to aroylcobalt complexes as products [24].
Depending on the catalyst system and the reaction conditions, especially at ele-
vated CO pressure it is possible to obtain selectively double carbonylation
reactions to 1-keto carboxylic derivatives [25]. Recent mechanistic investigations
have shown that double CO insertion into the palladium-carbon bond does not
occur directly; instead, the terminal step of double carbonylation is generally a
coupling reaction between metal-bonded acyl, alkoxycarbonyl or amidocarbonyl
groups and CO.
Halides are the dominating starting materials for carbonylation of aryl-X
derivatives. This is not true for benzyl-X and allyl-X compounds. Here, alcohol
derivatives [26] such as acetates, carbonates, ethers, and phosphates, and the
alcohols themselves, are more important today. According to Murahashi et al.
[27] the reactivity of the leaving group of allylic substrates decreases in the order

Br > OP(O)OEt), > C1 > OCOCF3 > OC0,Et > OCOPh > OCOMe

cat. = Pd, Co, Ni

X = I, Br, CI, NzX, OSOzR, 102; M = SnR3, SIRS, BR3

Nu’ = H, alkyl, aryl, CN; Nu2 = OH, OR, NR2, F, CI

Scheme 2. Carbonylation of aromatic compounds.

148 2.1 Carbon Monoxide and Synthesis Gas Chemistry

No reactivity was found for OPh, NEt,, and OH as leaving group. For allylic acet-
ates the carbonylation has been a problem for some time. It has been shown that
for the intermediate allylpalladium acetate complex, the back reaction to form
ally1 acetates proceeds faster than the insertion of CO into the complex [28]. In-
troduction of bromide ions as co-catalyst lead to a fast ligand exchange of the
acetate with bromide. Therefore the resulting bromide complexes could be carbo-
nylated in moderate to good yields [27]. A similar co-catalysis of chloride ions
was observed in the carbonylation of 4-hydroxybenzyl alcohol to 4-hydroxyphe-
nylacetic acid with palladium-hydrogen chloride systems.

2.1.2.3.3 Industrial Applications

From a commercial point of view, organic halides are in principle a less attractive
feedstock for the synthesis of alkanoic or benzoic acid derivatives compared with
alkenes or toluenes, which can lead to the corresponding acids via hydroformyla-
tion and oxidation, hydrocarboxylation, or direct air oxidation, respectively. Thus,
apart from methanol, an economically viable carbonylation of C-X compounds is
restricted to the synthesis of higher-value fine chemicals in cases where alternative
starting materials are not easily accessible, e. g., phenylacetic acid derivatives
(cf. Section 2.1.2.1).
The catalytic carbonylation of benzylic halides to arylacetic acids has been im-
proved by using two-phase systems under phase-transfer conditions [29]. Usually
the reactions were performed with an excess of base in a biphasic system with a
metal catalyst in the organic phase. As phase transfer catalysts surfactants are
used, which appear to play an important transport function to move the cobalt car-
bony1 salt from the aqueous phase to the organic droplets (cf. Section 3.2.4).
While the structure of the phase transfer co-catalyst was being studied it was ob-
served that benzyltrialkylammonium salts were easily carbonylated. In some cases
the yields of arylacetic acids are higher compared with the carbonylation of the
corresponding benzyl halides [30].
It is reported that the two-phase carbonylation methodology has been used on a
pilot plant scale by Montedison [ 3 11 for the conversion of benzyl chloride to phe-
nylacetic acid for use in perfume constituents and pesticides (eq. (8)). The carbo-
nylation is run in a biphasic medium employing diphenyl ether and aqueous 40 %
sodium hydroxide as solvents. The catalyst system consists of a cobalt carbonyl
complex and a benzyltrialkylammonium surfactant. The reaction takes place at
low temperature and CO pressure, while benzyl chloride is added continuously
to the reaction mixture.

6'. 6 co
c%E)8
H20,PhOPh
40 % NaOH
~

/
C02Na

H20, HCI,
-NaCI
&02H (8)

In 1992 the world market for arylpropionic acids (profenes) which are used
as nonsteroidal antiinflammatory agents was > $ 2.5 billion ($ 2500 million).
 2.1.2.3 Carbonylation of Benzyl-X and Atyl-X Compounds 149

Because of an increasing demand for these products in the pharmaceutical indus-

try, a number of companies have paid special interest to the synthesis of profenes
[32] such as ibuprofen, naproxen, ketoprofen and others from 1-arylethanol
derivatives. Catalysts used for this transformation are palladium-phosphine com-
plexes in concentrated hydrochloric acid, and to a lesser extent nickel-phosphine
complexes in the presence of alkyl iodides or rhodium salts (cf. Section 2.9).
Based on the palladium-catalyzed carbonylation of 1-(4-isobutylphenyl)etha-
nol, which is produced via salt-free acylation of isobutylbenzene to 4-isobutyl-
acetophenone and subsequent hydrogenation, the former Hoechst Celanese Cor-
poration [33] developed an ecologically superior process to produce ibuprofen
in a plant operating since 1992 on a 3500-ton scale (eq. (9); 1 bar = 0.1 MPa) [34].

$ / 30 "C
MeOH + $ o /
5 barHP,
PdK, H m 50
~ ~bar
H20, ~HCI
~ CO,~130
~ "C $co2H
? ~ t o n/~ (9)

The carbonylation step is performed in a mixture of an organic solvent and

hydrochloric acid. As catalyst, PdC12(PPh3)2is used. The economic feasibility
of the overall process is to a large extent determined by the ability to recycle
the palladium catalyst. Careful reaction design makes possible total catalyst turn-
over numbers (TONS)high above 10000.
Relatively limited work on profene synthesis via carbonylation of benzyl-X
derivatives has been reported from university groups. One exception is the stero-
selective carbonylation of racemic benzylic bromides. The asymmetric reaction
toward enantiomerically pure profenes could a priori proceed either by a kinetic
resolution or by true asymmetric induction via the intermediacy of a trigonal
substrate. Results from Arzoumanian et al. [35] strongly suggest that the
carbonylation of 1-methylbenzyl bromide with oxazaphospholene-palladium
complexes is a kinetic resolution process with a discriminative slow oxidative
addition step. Best enantiomeric excess is about 64 % ee at 9 % chemical yield.
Another possible way to synthesize enantiomerically pure profenes is to start
from optically pure benzyl derivatives. Baird et al. investigated the carboxylation
of optically active benzyl carbonates with palladium catalysts. The enantiomeric
excess was only modest [36]. Thus, the development of an efficient catalytic
asymmetric carbonylation of C-X derivatives is still an existing challenge.
Very recently another reaction, which involves a palladium-catalyzed benzyl
halide carbonylation step, has been commercialized by Clariant AG. Here, the car-
bonylation of 1,2-xylyl dichloride in the presence of a palladium-phosphine
catalyst yields isochromanone (eq. (10)) [54].
150 2.1 Carbon Monoxide and Synthesis Gas Chemistry

Apart from carbonylation reactions of benzyl halides, similar reactions using

aryl halides have attracted industrial interest. Among the carbonylation reactions
of aryl halides, those of heteroaryl halides were of special interest to industrial re-
search groups. The attachment of carbonyl functionalities onto heterocyclic frame-
works by replacing a halide substituent provides an easy access to valuable inter-
mediates for the manufacture of herbicides and pharmaceuticals (e. g., Diflufeni-
can, Imazapyr, Nicosulfuron, Isoniazid, Etofibrat, Nifluminacid [55]).
Hence, it is not surprising that this type of carbonylation reaction has found ap-
plication in industry. The pilot plant production of Lazabemide, a monoamine oxi-
dase B inhibitor, by Hofmann-La Roche started from simple 2,5-dichloropyridine.
The original eight-step laboratory synthesis of Lazabemide was replaced by a one-
step protocol (eq. (11)) [56]. The product is isolated in 65 % yield. As only small
amounts of catalyst have to be used (TON = 3000), traces of palladium in the
product could be removed by appropriate work-up.

. N
co

2.1.2.3.4 New Developments

Based on the pioneering work of Heck and coworkers [7b,c] during the mid-
1970s aryl-, vinyl-, benzyl- and allyl-X carbonylations (Heck carbonylations)
have been used extensively on the laboratory scale (cf. Section 3.1.6). Compared
with the reaction conditions originally described by Heck et al., improvements
have been claimed using different solvents, bases, and special ligands. For alk-
oxycarbonylations, solid-liquid phase transfer conditions have been described to
lead to improved yields of butylbenzoic acid ester [37]. For the synthesis of
model compounds for polyesters, the effect of added base for palladium-catalyzed
aryloxycarbonylation has been studied [38]. Interestingly, conventionally used
bases such as sodium acetate and tertiary amines lead only to low yields of desired
product, while cyclic amidines drastically increase the rate of reaction and the
yield. Despite all generalizations, it seems clear that every reaction needs its
own optimization study.
In this respect it is interesting to note that statistical reaction design has been
shown to be a valuable tool for the optimization of aryl chloride alkoxycar-
bonylations [57].
Much effort has been devoted to the extension of this chemistry by the use of
new starting materials and by combining the carbonylation step with new modes
of trapping reactions of the intermediate acylmetal complex. The combination of
metal-catalyzed C-C coupling reactions with carbonylation chemistry to develop
regio- and stereoselective atom-economic cascade reactions has been a major sub-
ject of interest. This resulted in a number of new inter- and intramolecular meth-
ods for the synthesis of complex organic intermediates, mainly heterocycles.
 2.1.2.3 Curbonylation of Benzyl-X and A r y - X Compounds 151

Some typical examples [39] include the carbonylation of 2-halophenols or 2-ha-

loanilines to 0-or N-heterocycles, and intramolecular enolate or enamine trapping
to isocoumarins or quinolinones. In this respect, the carbonylative cyclization to
indanones and tetralones with different late transition-metal complexes (Pd, Co,
Ni) has been studied (eq. (12)) [40].

o & t
COzEt

+ co
cat.
NEt3, THF
MeCN,lOo"C- Wc:::: 0

85-92 Yo
(12)
cat. = Pd, Ni, Co

It deserves mention that related palladium-catalyzed C-C coupling cascades

have been combined with a carbonylation terminating step [41]. In such cases
vinyl-, alkyl- or allylpalladium(I1) intermediates were generated in situ and
trapped by carbonylation reactions, mainly carboxylations. As an example pelar-
gonic (nonanoic) acid, an industrially interesting synthetic fatty acid, has been pre-
pared via butadiene telomerization in the presence of methanol, subsequent carbo-
nylation of the resulting allylic ethers and hydrogenation (eqs. (13) and (14)) [42].

-
-
OMe

MeOH, 80 "C 90 Yo (97:3)

\
'
OMe
Pd cat.
+ OMe +- C02Me (14)
I 30 bar CO
/ toluene, 100 "C 80 Yo

The main product of the carbonylation of either 1- or 3-methoxyoctadiene is the

linear ester. While the reaction is retarded by halide ligands, the use of a strong
Bronsted or Lewis acid lead to improved yields. Screening of different catalysts
for the carbonylation step showed that [(methyl-2-allyl)PdC1], with [Bu,N]BF,
as co-catalyst is superior to conventional palladium catalysts.
Allylic halogenides containing an additional internal functional group in a
suitable position, e.g., an alkene moiety or a hydroxy group, produce the
corresponding cyclopentenone derivatives or lactones, respectively, via palla-
dium-catalyzed carbonylation [43]. Related cyclocarbonylations of cinnamyl
halides or acetates to form polycyclic aromatics such as naphthol derivatives
have been reported (eq. (15)). Moreover, the synthetic utility of the method was
demonstrated by the synthesis of acetoxybenzofurans, acetoxyindoles, and
acetoxycarbazoles [44].

PdCIz(PPh3)2
" r CH3
0 / X + co 160 "C, 60 bar
CsHs, Ace0
OAc
(15)
X = OAc, Br 76 %
152 2.1 Carbon Monoxide and Synthesis Gas Chemistry

Because of the relatively high cost of palladium it is significant that cobaltcar-

bony1 complexes catalyze carbonylation of aryl and vinyl halides to acids at low
CO pressure under conditions of photostimulation [45]. Photolysis to a coordina-
tively unsaturated 16-electron cobalt species seems to be the key reaction step.
Foa et al. discovered a more practical solution because photochemical regenera-
tion of the catalyst could be avoided if an alkylating agent, e.g., chloroacetate,
is added [46]. The resulting alkylcobalt complex CH302CCH2Co(C0)4-promotes
carbonylation of aryl and vinyl halides under mild conditions in good to excellent
yields (eq. (16)). The mode of action of the electron-withdrawing group is be-
lieved to be that it inhibits CO insertion into the alkyl-cobalt bond, but full details
of the mechanism are yet to be established.

6
R'
Br

+ CO + ROH
(CO)4CoCH,CO,Et
25-35 "C, 1 bar
MeOH R'
C02R

12-86 Yo
R' = H, CI, CH30, CH3

With regard to the importance of substituted benzoic acid derivatives, it is

surprising that the efficient carbonylation of economically attractive aryl chlo-
rides is still a challenging problem. Clearly, the carbonylation of aryl chlorides
is more difficult than other C-C coupling reactions due to the presence of a
large excess of the z-accepting carbon monoxide ligand. CO bound to the
metal center reduces the activity of the Pd complex toward oxidative addition.
Moreover, clustering and agglomeration of Pd atoms is facile in the presence
of CO [47] , leading to non-active Pd species. Until very recently only the im-
portant discovery by Milstein and co-workers [48], who introduced Pd com-
plexes containing the highly basic 1,3-bis(di-iso-propylphosphino)propane li-
gand, provided a more general solution to the carbonylation of aryl chlorides.
The drawbacks of this catalyst system, however, are the difficult synthesis
and the high sensitivity of this pyrophoric phosphine along with the compara-
tively low turnover numbers of the catalyst (1 mol% of Pd). Other catalyst sys-
tems known in the literature for the carbonylation of aryl chlorides suffer from
additional disadvantages. Tricyclohexylphosphine (PCy,) has been frequently
employed as a ligand for the Pd-catalyzed hydroxy- or methoxycarbonylation
of chloroarenes. Unfortunately the reported yields of the carbonylation products
were always below 30 % [49, 50aI. Aminocarbonylation employing a Pd cata-
lyst based on 1,2-bis(diphenylphosphino)ethane in the presence of sodium
iodide proceeds under mild conditions with high yields. In general the scope
of aryl chloride substrates was restricted to electron-deficient (i. e., activated)
derivatives [50b].
Very recently in a joint effort from industry and academia an improved Pd cat-
alyst system based on bidentate ferrocenyl phosphine ligands was developed that
enables the carbonylation of electron-deficient, electronically neutral, and elec-
tron-rich aryl chlorides in good to excellent yield [58]. The new catalyst
represents a substantial improvement in efficiency, utility and practicability for
 References 153

the alkoxy carbonylation of aryl chlorides. Critical to the success of this method is
the use of cyclohexyl-substituted bidentate ferrocenyl phosphines, along with so-
dium carbonate as a basc.
It is important to notice that certain N-heteroaromatic chlorides are much more
readily carbonylated, due to the reduction of electron density in the aromatic ring
and stronger polarization of the C-CI bond. An overview of the alkoxycarbonyl-
ation of N-heteroaryl chloride has been published recently [Sob].
Despite its potential, none of the methods described so far has been used for
commercial production. This is partly due to the low catalyst activities. Turnover
frequencies (TOF) remain usually below 20 h-'. For any of the methods to be
of practical value, more research is clearly needed in future, taking technical
questions such as catalyst activity (TON, TOF), catalyst lifetime, and recycling
into consideration. The concept of two-phase catalysis using water-soluble
organometallic catalysts [Sl] might lead to new oppurtunities here. New ap-
proaches for the carbonylation of bromobenzene [S2] and substituted benzylic
chlorides [S3] using water-soluble palladium catalysts with triphenylphosphine
trisulfonate (TPPTS, cf. Section 3.1.1.1) as ligand offer efficient product separa-
tion together with more active catalyst systems. As an example, the carbony-
lation of benzyl chloride proceeds in a biphasic medium with a TON of more
than 1500, a significant improvement compared with the homogeneous organic
system [S3].

References
[ l ] Reviews: (a) M. Beller, B. Cornils, C. D. Frohning, C. W. Kohlpaintner, J. Mol. Catal.
1995, 104, 17; (b) H. M. Colquhoun, D. J. Thompson, M. V. Twigg, Carbonylation,
Direct Synthesis of Carbonyl Compounds, Plenum Press, New York, 1991; (c)
R. F. Heck, Palladium Reagents in Organic Syntheses, Academic Press, New York,
1985; (d) Y. V. Gulevich, N. A. Bumagin, I. P. Beletskaya, Russ. Chem. Rev. 1988,
57, 299; (e) M. Roper, Stud. Surf Sci. Catal. 1991,64, 381 ; (f) D. J. Thompson in Com-
prehensive Orgunic Synthesis, (Eds.: B. M. Trost, I. Fleming) Pergamon Press, Oxford,
1991, Vol. 3, p. 1015; (8) M. Beller, C. Bolm, Transition Metals for Organic Synthesis,
Wiley-VCH, Weinheim, 1998.
[2] (a) Y. Hu, J.-X. Wang, W. Cui, Synth. Commun. 1991, 24, 1743; (b) S. C. Shim,
C. H. Doh, W. H. Park, Y. G. Kwon, H. S. Lee, J. Organomet. Chem. 1990, 382,
419; (c) M. Foa, F. Francalanci, E. Bencini, A. Gardano, J . Organomet. Chem. 1985,
285, 293; (d) V. Galamb, G. Palyi, F. Ungvary, L. Marko, R. Boese, G. Schmid, J.
Am. Chem. Soc. 1986, 108, 3344.
[3] (a) G. Tanguy, B. Weinberger, H. Des Abbayes, Tetrahedron Lett. 1983, 24, 4005; (b) S.
G. Davies, A. J. Smallridge, A. Ibbotson, J. Organomet. Chem. 1990, 386, 195.
[4] (a) 1. Amer, H. Alper, J. Am. Chem. Soc. 1989, 111, 927; (b) S. R. Adapa, C. S. N. Pra-
sad, J. Chem. Soc., Perkin Trans. 1989, I , 1706.
[5] (a) J. F. Knifton, J. Organomet. Chem. 1980, 188, 220; (b) S.-I. Murahashi, Y. Imada,
Chem. Lett. 1985, 1477.
[6] (a) S. Zhang, S. Xiao, M. Ran, H. Dai, J. Mol. Catal. 1987, 115, 1; (b) H. Alper,
K. Hashem, J. Heveling, Organornetallics 1982, I , 775; (c) K. Yamamoto, R. Deguchi,
J. Tsuji, Bull. Chem. SOC.Jpn. 1985, 58, 3397; (d) T. Kobayashi, M. Tanaka, J. Mol.
154 2.1 Carbon Monoxide and Synthesis Gas Chemistry

Catal. 1988,47,41; (e) T. Kobayashi, F. Abe, M. Tanaka, J. Mol. Catal. 1988,45,91; (f)
T. Okano, N. Okabe, J. Kijii, Bull. Chem. Soc. Jpn. 1992, 65, 2589.
[7] Some examples: (a) D. Valentine, J. W. Tilley, R. A. LeMathieu, J. Org. Chem. 1981,46,
4614; (b) A. Schoenberg, I. Batoletti, R. F. Heck, J. Org. Chem. 1974, 39, 3318; (c) A.
Schoenberg, R. F. Heck, J. Org. Chem. 1974, 39, 3327; (d) P. P. Nicholas, J. Org. Chem.
1987, 52, 5266; (e) J. K. Stille, P. K. Wong, J. Org. Chem. 1975, 40, 532.
[S] K. Kudo, T. Shibata, T. Kashimura, S . Mori, N. Sugita, Chem. Lett. 1987, 577.
[9] I. Amer, H. Alper, J. Org. Chem. 1988, 53, 5147.
[lo] (a) W. R. Moser, A. W. Wang, N. K. Kildahl, J. Am. Chem. Soc. 1988, 110, 2816; (b) W.
R. Moser, A. W. Wang, N. K. Kildahl, Chem. Znd. (Dekker), 1990, 40, 137.
[ I l l K. Kudo, M. Sato, M. Hidai, Y. Uchida, Bull. Chem. Soc. Jpn. 1973, 46, 2820.
[12] (a) K. Kikukawa, K. Kono, K. Nagira, F. Wada, T. Matsuda, J. Org. Chem. 1981, 46,
4413; (b) K. Kikukawa, T. Totoki, F. Wada, T. Matsuda, J. Organomet. Chem. 1984,
270, 283.
[I31 (a) Review: K. Ritter, Synthesis 1993, 735; (b) G. T. Crisp, A. G. Meyer, J. Org. Chem.
1992, 57, 6972; (c) J. Wrobel, A. Dietrich, Tetrahedron Lett. 1993, 34, 3543; (d) Y. Uo-
zumi, N. Suzuki, A. Ogiwara, T. Hayashi, Tetrahedron, 1994, 50, 4293; (e) M. Ishikura,
M. Terashima, J. Org. Chem. 1994,59, 2634; (f) C. Haffner, Tetrahedron Lett. 1994,35,
1349.
[14] (a) G. Cometti, A. Du Vosel, F. Francalanci, R . Santi, W. Cabri, M. Foa, J. Organo-
met. Chem. 1993, 451, C13; (b) G. P. Roth, J. A. Thomas, Tetrahedron Lett. 1992,
33, 1959.
[I51 V. V. Grushin, H. Alper, J. Org. Chem. 1993, 58, 4794.
[16] (a) N. A. Bumagin, K. V. Nikitin, I. P. Beletskaya, J. Organomet. Chem. 1988, 358, 563;
(b) J. T. Lee, H. Alper, Organometallics 1990, 9, 3064; (c) M. Foa, F. Francalani, A. Gar-
dano, G. Cainelli, A. Umani-Ronchi, J. Organomet. Chem. 1983, 248, 225; (d) D. E.
Bergbreiter, B. Chen, D. Weatherford, J. Mol. Catal. 1992, 74, 409; (e) R. Vanderesse,
J. Marchal, P. Caubere, Synth. Commun. 1993, 23, 1361; (0 K. Maeda, H. Yagita, K.
Omata, K. Fujimoto, J. Mol. Catal. 1992, 71, 347; (g) T. Kobayashi, M. Tanaka, J. Or-
ganomet. Chem. 1982,233, C64; (h) T. Okano, N. Harada, J. Kijii, Bull. Chem. Soc. Jpn.
1992, 65, 1741.
[ 171 (a) R. J. Perry, B. D. Wilson, J. Org. Chem. 1992,57,6351; (b) R. J. Perry, B. D. Wilson,
J. Org. Chem. 1993, 58, 7016.
[18] R. J. Perry, B. D. Wilson, Organometallics 1994, 13, 3346.
[19] 1. Pri-Bar, H. Alper, J. Org. Chem. 1989, 54, 36.
[20] R. J. Perry, S. R. Turner, J. Org. Chem. 1991, 56, 6573.
[21] (a) T. Okano, N. Harada, J. Kijii, Bull. Chem. Soc. Jpn. 1994,67,2329; (b) Y. Misumi, Y.
Ishii, M. Hidai, J. Mol. Catal. 1993, 78, 1 ; (c) Y. Ben-David, M. Portnoy, D. Milstein, J .
Chem. Soc., Chem. Commun. 1989, 1816; (d) V. P. Baillargeon, J. K. Stille, J. Am.
Chem. Soc. 1986, 108, 452.
[22] (a) M. Ishikura, M. Terashima, J. Org. Chem. 1994, 59, 2634; (b) J. J. Brunet,
M. Taillefer, 1. Organomet. Chem. 1990, 384, 190; (c) A. C. Gyorkos, J. K. Stille, S.
L. Hegedus, J. Am. Chem. SOC. 1990, 112, 8465; (d) Y. Hatanaka, S. Fukushima, T.
Hiyama, Tetrahedron 1992, 48, 2113; (e) R. Grigg, J. Redpath, V. Sridharan,
D. Wilson, Tetrahedron Lett. 1994, 35, 4429.
1231 (a) M. Tanaka, Bull. Chem. Soc. Jpn. 1981, 54, 637; (b) L. Delaude, A. M. Masdeu,
H. Alper, Synthesis 1994, 1149; (c) K. Nozaki, N. Sato, H. Takaya, J. Org. Chem.
1994, 59, 2679.
[24] Y. Misumi, Y. Ishii, M. Hidai, Chem. Lett. 1994, 695.
[25] (a) F. Ozawa, H. Soyama, H. Yanagihara, I. Aoyama, H. Takino, K. Izawa, T. Yamamoto,
A. Yamamoto, J. Am. Chem. Soc. 1985, 107, 3235; (b) H. Yamashitd, T. Sakakura, T.
 References 155

Kobayashi, M. Tanaka, J. Mol. Catal. 1988, 48, 69; (c) L. Huang, F. Ozawa, A. Yama-
moto, Orgunometullics 1990, 9, 2603.
[26] (a) S.-I. Murahashi, Y. Imada, Y. Taniguchi, S . Shinya, .I. Org. Chem. 1993,58, 1538; (b)
J. Tsuji, Tetrahedron 1986, 42, 4361; (c) D. Neibecker, J. Oirier, I. Tkatchenko, J. Org.
Chem. 1989, 54, 2459; (d) Y. Imada, 0. Shibata, S.4. Murahashi, J . Organomet. Chem.
1993, 451, 183; (e) G. Cavinato, L. Toniolo, J. Mol. Catal. 1993, 78, 131.
[27] Murahashi, Y. Imada, Y. Taniguchi, S. Higashiura, Tetrahedron Lett. 1988,29,4945.
1281 T. Yamamoto, M. Akimoto, 0. Saito, A. Yamamoto, Organometallics 1986, 5, 1559.
[29] (a) H. Alper, Adv. Organomet. Cherrr. 1981, 19, 183; (b) F. Haasz, T. Bartik, V. Galamb,
G. Palyi, Organometallics 1990, 9, 2773.
[30] J.-J. Brunet, C. Sidot, P. Caubere, J. Org. Chem. 1983, 48, 1919.
1311 (a) L. Cassar, Chem. Znd. (Milan) 1985, 67, 256; (b) G. W. Parshall, W. A. Nugent,
ChemTech 1988, 314.
1321 (a) Ethyl Corp. (B. C. Stahly, R. W. Lin, E. E. Atkinson), US 04.990.658 (1989); Chem.
Abstr: 1991,114,246962; (b) Daicel Chem. Ind. (M. Kawabe, H. Kojima), JP 63.162.044
(1986); Chem. Abstr: 1988, 109, 238149; (c) Daicel Chem. Ind. (Y. Tanaka, H. Kojima,
Y. Tsuji, GB 02.199.030 (1986); Chem. Abstr: 1988, 109, 212807n; (d) Nippon Petro-
chem. (i. Shimizu, Y. Matsumura, Y. Inomata, K. Uchida), JP 02.101.041 (1990);
Chem. Abstr: 1990, 113, 97202e; (e) Mitsubishi Gas Chemical Co. (K. Tanaka, Y.
Shima), EP 00.361.021 (1990); Chem. Ahstr: 1990, 113, 114825e.
[33] (a) Hoechst Celanese Corporation (V. Elango, M. A. Murphy, G. L. Moss, B. L. Smith,
K. G. Davenport, G. N. Mott), EP 00.284.310 (1988); Chem. Abstc 1989, 110, 153916t;
(b) Hoechst AG (S. Rittner, A. Schmidt, L. 0. Wheeler, G. L. Moss, E. G. Zey), EP
00.326.027 (1989); Chem. Abstc 1990, 112, 35448k.
1341 J. N. Armor, Appl. Catal. 1991, 78, 141.
1351 H. Arzournanian, G. Buono, M. B. Choukrad, J.-F. Petrignani, Organometallics 1988, 7,
59.
1361 J. M. Baird, J. R. Kern, G. R. Lee, D. J. Morgans, M. L. Sparacino, J. Org. Chem. 1991,
56, 1928.
[37] B. M. Choudary, N. P. Reddy, B. Ashok, Appl. Catal. 1987, 32, 357.
1381 Y. Kubota, T. Hanaoka, K. Takeuchi, Y. Sugi, Synlett 1994, 515.
[39] (a) S. D. Knight, L. E. Overman, G. Pairaudeau, J. Am. Chem. Soc. 1993, 115, 9293; (b)
E.-I. Negishi, Y. Zhang, I. Shimoyama, G. Wu, Tetrahedron Lett. 1990, 31, 2841; (c) S.
Torii, H. Okumoto, L. H. Xu, Tetrahedron Lett. 1990, 31, 7175.
[40] E.-I. Negishi, Y. Zhang, I. Shimoyama, G. Wu, J. Am. Chem. Soc. 1989, 111, 8018.
[41] (a) T. Sugihara, C. Coperet, Z. Owczarczyk, L. S. Haning, E.-I. Negishi, J. Am. Chem.
Soc. 1994,116, 7923; (b) R. Grigg, P. Kennewell, A. J. Teasdale, Tetrahedron Lett. 1994,
33, 7789; (c) E.-I. Negishi, Pure Appl. Chem. 1992, 64, 323.
[42] (a) M. C. Bonnet, J. Coombes, B. Manzano, D. Neibecker, I. Tkatchenko, J. Mol.
Catal. 1989, 52, 263; (b) D. Neibecker, J. Poirier, I. Tkatchenko, J. Org. Chem. 1989,
54, 2459.
[43] (a) E.-I. Negishi, G. Wu, J. M. Tour, Tetrahedron Lett. 1988, 29, 6745; (b) A. Cowell, J.
K. Stille, J. Am. Chem. Soc. 1980, 107, 4193; (c) Y. Tamaru, T. Bando, M. Hojo,
Z. Yoshida, Tetrahedron Lett. 1987, 28, 3497.
[44] (a) Y. Koyasu, M. Matsukaza, Y. Hiroe, Y. Uchida, M. Hidai, J. Chem. Soc., Chem. Com-
mun. 1987, 575; (b) H. Matsuzaka, Y. Hiroe, M. Iwasaki, Y. Ishii, Y. Koyasu, M. Hidai,
J. Org. Chem. 1988, 53, 3832; (c) M. Iwasaki, Y. Kobayashi, J.-P. Li, H. Matsuzaka, Y.
Ishii, M. Hidai, J. Org. Chem. 1991, 56, 1922.
[45] (a) J.-J. Brunet, C. Sidot, P. Caubere, Tetrahedron Lett. 1981, 22, 1013; (b) K. Kudo, T.
Shibata, T. Kashimura, S. Mori, N. Sugita, Chem. Lett. 1987, 577.
1461 M. Foa, F. Francalanci, J. Mol. Catal. 1987, 41, 89.
 2. I Carbon Monoxide and Synthesis Gas Chemistry

(a) For a recent review of palladium carbonyl complexes see: T. A. Stromnova,

I. I. Moiseev, Russ. Chem. Rev. 1998, 67, 485; (b) K. Kudo, M. Hidai, Y. Uchida, J.
Organomet. Chem. 1971, 33, 393; (c) M. Hidai, M. Kokura, Y.Uchida, J. Organomet.
Chem. 1973, 52, 431.
(a) Y. Ben-David, M. Portnoy, D. Milstein, J. Am. Chem. Soc. 1989, 111, 8742; (b)
Y. Ben-David, M. Portnoy, D. Milstein, J. Chem. Soc., Chem. Commun. 1989, 1816;
(c) M. Portnoy, D. Milstein, Organometallics 1993, 12, 1655; (d) M. Portnoy, D. Mil-
stein, Organometallics 1993, 12, 1665.
(a) M. Huscr, M.-T. Youinou, J. A. Osborn, Angew. Chem., Int. Ed. Engl. 1989, 28,
1386; (b) V. V. Grushin, H. Alper, J. Chem. SOC., Chem. Commun. 1992, 611; (c) T.
Miyawaki, K. Nomura, M. Hazama, G. Suzukamo, J. Mol. Catal. 1997, 120, L9-Lll.
[50a] (a) V. Dufaud, J. Thivolle-Cazat, J.-M. Basset, J. Chem. SOC., Chem. Commun. 1990,
426; (b) R. J. Perry, B. D. Wilson, .I.Org. Chem. 1996, 61, 7482.
[Sob] M. Beller, W. Magerlein, A. F. Indolese, C. Fischer, Synthesis 2001, 1098.
[51] (a) W. A. Herrmann, C. W. Kohlpaintner, Angew. Chem., Int. Ed. Engl. 1993,32, 1524;
(b) B. Cornils, E. Wiebus, CHEMTECH, 1995, 33; (c) P. Kalck, F. Monteil, Adv. Orga-
nomet. Chem. 1992,34,219;(d) T. Okano, I. Uchida, T. Nakagaki, H. Konishi, J. Kishi,
J. Mol. Catal. 1989, 54, 65; (e) T. Okano, N. Okabe, J. Kishi, Bull. Chem. Soc. Jpn.
1992, 65, 2589.
1521 F. Monteil, P. Kalck, J. Organomet. Chem. 1994, 482, 45.
1531 Hoechst AG (C. W. Kohlpaintner, M. Beller), DE 4.415.681 and DE 4.415.682
(1994).
1541 (a) Clariant (H. Geissler, R. Pfirmann), DE 19.815.323 (1998); (b) Clariant (H. Geissler,
R. Pfirmann), EP 1.086.949 (2000).
[55] J. Stetter, F. Lieb, Angew. Chem. 2000, 112, 1793; Angew. Chem., Int. Ed., 2000, 39,
1724.
[56] (a) R. Schmid, Chimia, 1996, 50, 110; (b) Hoffmann-La Roche (M. Scalone, P, Vogt),
EP 385.210 (1990).
[57] W. Magerlein, A. F. Indolese, M. Beller, J. Organomet. Chem. 2001, in press.
[58] W. Magerlein, A. F. Indolese, M. Beller, Angew. Chem., Int. Ed. 2001, 40, 2856.

2.1.2.4 Amidocarbonylation
John F: Knifton

2.1.2.4.1 Introduction
Amidocarbonylation is a recently developed, organometallic-catalyzed route to
amino acid generation - particularly N-acyl a-amino acids - using either alde-
hydes or alkenes as starting materials and synthesis gas as an integral building
block. The two principal classes of reaction are illustrated in eqs. (1) and (2).
Both syntheses offer the opportunity to introduce two functionalities, amido and
carboxylate, simultaneously where an amide is the co-reactant. Homogeneous
amidocarbonylation catalysts are typically cobalt carbonyl-based, or utilize
transition-metal binary systems, e. g. cobalt-rhodium, cobalt-palladium, and
cobalt-iron.
 2.1.2.4 Amidocarbonylation 157

The amidocarbonylation reaction was discovered by Wakamatsu [ 11, who

demonstrated the synthesis of a range of N-acyl amino acids through the cobalt
carbonyl-catalyzed reactions of various combinations of aldehyde plus amide,
with carbon monoxide (eq. (1)). Some aspects of the mechanism of aliphatic
aldehyde amidocarbonylation have been examined by both Pino and co-workers
[2] and by Getman [3]. Magnus and Slater [4] subsequently investigated the
scope of this synthesis for variety of N-substituted amide co-reactants and C-sub-
stituted aldehydes. Further mechanistic revisions were proposed involving acyl-
iminium species.
Ojima and co-workers have undertaken extensive research into the formation of
N-acyl-a-amino acids via amidocarbonylation chemistry [5]. Their focus includes
the generation of N-acyl-a-amino acids directly from ally1 alcohols, oxiranes, or
olefins using homogeneous binary catalyst systems, particularly cobalt octacarbo-
nyl - Group VIII transition-metal complex combinations. New catalytic processes
feature:

(1) the isomerization-amidocarbonylation of allylic alcohols (eq. ( 3 ) ) [6] ;

(2) the isomerization-amidocarbonylation of oxiranes (eq. (4)) [6], such as sty-
rene oxide;
( 3 ) the hydroformylation-amidocarbonylation of fluoroolefins, including 3,3,3-
trifluoropropene (eq. (5)) [7] and pentafluorostyrene.
158 2.1 Carbon Monoxide and Synthesis Gas Chemistry

An efficient, highly regioselective, synthesis of fluoro amino acids could have

particular significance in medicinal chemistry and pharmacology, because of the
increasing interest in the incorporation of fluoro amino acids into physiologically
active peptides.
Emphasizing industrial applications, Lin et al. have extended amidocarbon-
ylation technology to make a variety of specialty chemicals using synthesis gas
as a primary building block [8]. By tailoring the individual homogeneous cobalt
or cobalt-rhodium catalysts, they have demonstrated that the amidocarbonylation
reactions can be used to make numerous commercially important specialty
products [9], including:

(1) surface-active agents, such as the CI4-Cl6 alkyl amido acids;

(2) specialty surfactants, as in the use of sarcosinates;
( 3 ) intermediates for sweeteners such as @aspartame;
(4) food additives, e. g., glutamic acid;
( 5 ) chelating agents such as the polyamido acids.

Currently, most amino acids are obtained from natural resources and/or by fer-
mentation. Amidocarbonylation is a viable alternative to the conventional Strecker
reaction, which utilizes toxic hydrogen cyanide and ammonia to make aliphatic
amino acids from aldehydes.

2.1.2.4.2 Scope of Amidocarbonylation Reaction

Monoolefins

Long-chain alkyl N-acetyl amino acids, which have applications as detergents and
thickeners, may be prepared from monoolefins, acetamide, and synthesis gas [ 10,
111 in the presence of cobalt-rhodium or cobalt catalysts. Both hydroformylation
and amidocarbonylation occur in a single step (eq. (6)). Starting with typically
available, CI2-Cl4, straight-chain, a-olefin feedstocks, amido acids with up to
95 % linearity can be generated using the cobalt-rhodium bimetallic catalyst
[8]. Advantages of this bimetallic catalyst system include excellent reproducibil-
ity, high product yields and linearity, as well as the need for only moderate syn
gas pressures. Purification procedures by recrystallization have been worked
out [ 121.

P R + H&CONH* Co’H2, R d:A H

(6)

Cobalt calatysts in combination with certain bidentate phosphines, such

as 1,3-bis(diphenylphosphino)propane, are also very effective for amidocarbon-
ylations. Their advantage is that reactions can be conducted at lower pressures
~31.
 2.1.2.4 Amidocarbonylatiorz 159

Terminal, internal, and vinylic olefins may also be amidocarbonylated in good

yields. Applications for these acid derivatives include surface-active and chelating
agents.

Diolefins

Certain N-acetyl-a-amino acids may also be prepared from diolefins, including

dicyclopentadiene, 4-vinyl- 1-cyclohexene, 1,3-butadiene and 1,7-0ctadiene
(Table 1). Monoamido acids are the predominant products obtained from unsym-
metrical dienes, such as dicylopentadiene and 4-vinyl- 1-cyclohexene; diamido
acids are formed from symmetrical dienes. A number of these polyamido acids
have potential as chelating agents.

Functionalized Olefins

Amidocarbonylation of functionalized olefins provides routes to a number of

interesting and valuable amido acids. N-Acetylglutamic acid ester, a precursor
for monosodium glutamate, can be synthesized from acrylate, acetamide, and
syn gas in 85 % yield (eq. (7)) [ 141. This in-situ hydroformylatiodamidocarbonyl-
ation route affords the linear amido acids as the major product. By comparison,

rhodium-catalyzed hydroformylation of acrylate gives dimethyl 2-formyl-

2-methylglutarate in 75 % selectivity and 60 % conversion. This product was
derived from hydroformylation of acrylate at the a-position and subsequent
Michael addition of a second equivalent of methyl acrylate (eq. (8)) [15].

U
2. H30+

Amidocarbonylation of allyl acetate, 2-pentenenitrile and allyl alcohol eth-

oxylates realizes the corresponding amido acids in good yields (Table 2). Potential
applications for these products also include surfactants and polyamide-polyesters.
160 2.1 Carbon Monoxide and Synthesis Gas Chemistry

Table 1. The amidocarbonylation of various diolefins.

~~

Starting material cw2

CH,CONH; Major producta’ Yield [%I

78
2

0“’

1 2n34 47

a) Formation of the new C-C bond may occur at positions 1 or 2, 3 or 4, 7 or 8 of the olefinic
double bond.

Table 2. The amidocarbonylation of functionalized olefins.

Starting olefin ,-.ZgH;Major producta’ Application

Polyamide-
ester

Pol yamide

-85 %

-80 %

a) Formation of the new C-C bond may occur at positions 1 or 2 of the olefinic double bond.
 2.1.2.4 Amidocarbonylation 161

Aldehyde Amidocarbonylation

N-Acetylglycine, the simplest amido acid, has been generated from paraformal-
dehyde in good yields (eq. (9)) [16]. Improved catalyst recovery can be achieved
by combining cobalt carbonyl with weakly coordinating ligands [I71 such as
diphenyl sulfoxide and succinonitrile. The use of stronger bases, such as tri(n-bu-
tyl)phosphine, allows reaction to proceed at lower pressures. By comparison,
chelating agents, including TMEDA (N,N,N',N'-tetramethylethylenediamine)
adversely affect the reaction rate.
COIH2 H
(CH20)x + CH3CONHz H02C-N (9)
Y
0

P-Phenylalanine, a key intermediate in the preparation of the sweetener

8
aspartame (the methyl ester of L-phenylalaninell-aspartic acid dipeptide)
[ 18, 191 may be prepared similarly according to eq. (10). Amidocarbonylation
of phenylacetaldehyde, obtainable from styrene, affords N-acetyl-P-phenylalanine
in 72 mol % yield and with > 98 % cobalt recovery [20].
H

Alkyl Sarcosinates

Sarcosinate specialty surfactants are currently made by acylation of naturally

occurring amino acids with an acyl chloride. The use of a secondary amide for
amidocarbonylation has been reported to give poor yields of amido acid since
the corresponding oxazolone intermediate cannot be formed. Lin has demon-
strated, however, that the amidocarbonylation of N-methylamine gives excellent
yields of N-acyl sarcosinates (eq. (11)) when conducted in the presence of dicobalt
octacarbonyl at 120 "C with CO/H2 = 3 : 1. Sarcosinate selectivity is typically
95 %, at 92 % N-methylamine conversion.
0
P 0 II
162 2.1 Carbon Monoxide and Synthesis Gas Chemistry

This simple synthesis, which avoids the use of chloride, allows the introduction
of both the carboxylic acid and the secondary amide moieties in a single step [21,
25-27].

Other Amido Acids

Other amido acids may be prepared via formaldehyde amidocarbonylation using

dicobalt octacarbonyl in the presence of N-substituted acyclic amides or cyclic
amides. Amidocarbonylation of 2-pyrrolidone and e-caprolactam [22] affords N-
(2-pyrrolidone)-2-acetic acid and N-(e-caprolactam)-2-acetic acid, respectively
(eqs. (12) and (13)). The side products shown can be recycled and eventually con-
verted to the desired amido acetic acids.

2.1.2.4.3 Mechanism
Detailed mechanisms for the amidocarbonylation reaction have been proposed by
both Pino [2] and Magnus [4], wherein the first step is the formation of a hemi-
amidal, followed by the nucleophilic substitution of a hydroxyl group by cobalt
tetracarbonyl hydride and carbonyl insertion to an (a-amidoalkanoyl) cobalt inter-
mediate. This intermediate then provides the desired N-acyl-a-amino acid by di-
rect hydrolysis, or via an lactame intermediate, followed by hydrolysis.
In a very elegant mechanistic study by Ojima et al., involving the amidocarbo-
nylation of three structurally related cyclic amides having methallyl side chains
(utilizing cobalt carbonyl catalysis) they have demonstrated [23] that coordination
of the amide carbonyl to the cobalt metal is essential for amidocarbonylation,
whereas lactame formation is not. A general mechanism of amidocarbonylation,
featuring the very unique hydrolysis (alcoholysis) of the acyl-cobalt bond by
water (or alcohol) generated in situ, is reproduced in Scheme 1 [23].
 2.1.2.4 Amidocurbonylution 163

Scheme 1. Mechanism for amidocarbonylation.

(Reproduced by permission from the American Chemical Society).

Ojima notes that the cobalt catalyst is particular to amidocarbonylation, i. e., no

other metals have been found to catalyze this reaction so well. The fact that cobalt
can form stable aquo-complexes may account for this uniqueness [lo].

2.1.2.4.4 Conclusions
In conclusion, the development of amidocarbonylation technology over the past
20 years has led to a gamut of exciting new amino acid chemistry. Potential
advantages to the novel cobalt-based catalysis include the following [24].

(1) The ability has been demonstrated to make a host of useful amido acid
products, with applications as surface-active agents, specialty surfactants,
food additives, chelating agents, and intermediates for sweeteners, etc.
(2) Less hazardous reagents are required than in the Strecker process.
(3) Specialty chemicals are being produced from inexpensive aldehyde/olefin
feedstocks, independently of natural products.
(4) There is the opportunity to prepare specialty chemicals using synthesis gas as
a basic building block.

In its new expanded form, regioselective amidocarbonylation to make fun-

damental biochemicals, i. e., N-acyl-a-amino acids and fluoro amino acids [ 101,
is a particularly versatile and potentially very valuable chemical technique.
164 2.1 Carbon Monoxide and Synthesis Gas Chemistry

References
[ l ] H. Wakamatsu, J. Uda, N. Yamakami, J. Chem. SOC.,Chem. Commun. 1971, 1540.
[2] J.-J. Parnaud, G. Campari, P. Pino, J. Mol. Card. 1979, 6, 341.
[3] D. P. Getman, 187th ACS Div. Ind. Eng. Chem. Meeting, St. Louis, Mo. 1984, Paper 109.
[4] P. Magnus, M. Slater, Tetrahedron Lett. 1987, 28, 2829.
[S] I. Ojima, J. Mol. Catal. 1986, 37, 2.5.
[6] I. Ojima, K. Hirai, M. Fujita, T. Fuchikawa, J. Organomet. Chem. 1985, 279, 203.
[7] 1. Ojima, M. Okabe, K. Kato, H. B. Kwon, I. T. Horvath, J. Am. Chem. Soc. 1988, 110,
150.
[8] J. J. Lin, J. F. Knifton, Homogeneous Transition Metal Catalyzed Reactions (Eds.: W. R.
Moser, D. W. Slocum), Adv. Chem. Sel: 1992, 230, 235.
[9] J. J. Lin, J. F. Knifton, CHEMTECH, 1992, 248.
[lo] I. Ojima, Chem. Rev. 1988, 88, 1011.
[ I l l Institute FranGais du Petrole (R. Stern, A. Hirschauer, D. Commereuc, Y. Chauvin), US
4.264.515 (1981).
[12] Texaco Inc. (J. J. Lin), US 4.676.933 (1987).
[I31 Texaco Inc. (J. J. Lin), US 4.892.687 (1990).
[14] Texaco Inc. (J. J. Lin), US 4.720.573 (1988).
[15] Texaco Inc. (J. J. Lin), US 4.849.543 (1989).
[16] Ajinomoto Co., Inc. (H. Wakamatsu, J. Uda, N. Yamagami), US 3.766.266 (1973).
[17] Texaco Inc. (J. J. Lin, J. F. Knifton, E. L. Yeakey), US 4.918.222 (1990).
[18] W. S. Fong, Sweeteners, Stanford Research Institute Report No. 170, 1984.
[I91 M. Hatada, J. Jancarik, B. Graves, S.-H. Kim, J. Am. Chem. SOC. 1985, 107, 4279.
[20] Texaco Inc. (J. J. Lin, J. F. Knifton), US 4.891.442 (1990).
[21] J. J. Lin, US Patent Application.
[22] Texaco Inc. (J. J. Lin), US 4.620.949 (1986).
[23] J. Ojima, Z. Zhang, Organometallics 1990, 9, 3122.
[24] J. F. Knifton, J. J. Lin, D. A. Storm, S. F. Wong, Catal. Today 1993, 18, 355.
[25] Hoechst AG (M. Beller, H. Fischer, P. GroB, T. Gerdau), DE 4.415.712 (1994).
[26] Hoechst AG (S. Bogdanovic, H. GeiBler, M. Beller, H. Fischer, K. Raab), DE application
19,545,641.6 (1995).
[27] M. Beller, B. Cornils, C. D. Frohning, C. W. Kohlpaintner, J. Mol. Catal. A: 1995,104, 17.

2.1.2.5 Oxidative Carbonylation

Alexander Klausenel; Jorg-Dietrich Jentsch

2.1.2.5.1 Introduction
Carbonylations which are accompanied by oxidation reactions, are frequently
called “oxidative carbonylations”. Reactions of this type are usually carried out
in the presence of a catalyst and an oxidant, for example air. In principle, similar
starting materials to those in classical Reppe carbonylations may be used, but as a
result of the additional oxidation step different reaction products are obtained. To
some extent, this method represents an extension of the Reppe carbonylation. For
 2.1.2.5 Oxidative Curbonylution 165

example, in the presence of suitable catalysts and oxygen, CO is added to alkenes

under retention of the double bond [l, 21, leading to unsaturated carboxylic acids.
The palladium-catalyzed reaction of alcohols with carbon monoxide, using alkyl
nitrites as oxidants, giving dialkyl carbonates and dialkyl oxalates is another ex-
ample. Both reactions are discussed in detail later. For the economically important
conversion of lower aliphatic alcohols to dialkyl carbonates and oxalates the reac-
tion follows eq. (1):

4ROH + 3CO + 02 -
cat.
R-0-COOR + ROOC-COOR + 2H20 (1)

Nearly all catalyst systems which are used for oxidative carbonylations are
based on Pd2+salts and complexes formed from them. They are modified by li-
gands, such as phosphines and amines, and promoters (for example, halogen, hy-
drochloric or hydrobromic acid) as well as different types of co-catalysts. In ad-
dition, there is a strong dependence on the chosen solvent, which has a great in-
fluence on the course of an oxidative carbonylation. The following conditions
have to be considered.

(1) Pure carbonyl compounds of palladium are not known; complexes of palla-
dium and CO have to contain further ligands to stabilize the whole complex.
(2) The oxidation of a substrate by any Pd2+ species in principle is a stoichio-
metric reaction, consuming first of all molar amounts of the Pd2+ present,
thus forming equivalent quantities of Pdo. If catalytic oxidative carbonylations
are required with respect to the palladium compound, appropriate conditions
for the reoxidation of Pdo have to be found. This may be achieved by the pre-
sence of suitable co-catalysts, for example of certain transition metal salts,
which are capable of changing their oxidation state.
( 3 ) As a strongly oxidizing agent Pd2+is readily reduced even by CO, giving Pdo
especially in the presence of acids. Reoxidants such as Cu2+,Fe3+, or others,
stabilize the Pd2' species.

For example, if the co-catalyst system Cu2+/Cu+is used for the regeneration
of Pd2+ from Pd' formed during the course of the reaction, the simultaneously
arising Cu+ has to be regenerated itself by another oxidant, for example oxygen.
In this case water arises as a side product. In Scheme 1 this is shown in a sim-
plified form.

educt oxidant

product reduction
product

Scheme 1. Pd2+catalyzed oxidative carbonylation under participation of co-catalysts

of the Cu2'/Cu+ type.
166 2.1 Carbon Monoxide and Synthesis Gas Chemistry

The exact tuning of each single step of the reaction is usually not easy and
leaves a wide field for optimization by variation of catalysts, co-catalysts, promot-
ing compounds, and solvents. Therefore, and because of the numerous chances
and challenges oxidative carbonylations offer to synthetic chemistry, it is easy
understandable that research activities have been increasing during the last two
decades. Homogeneous oxidative carbonylations in some cases already have
industrial importance, for example in the manufacture of dimethyl carbonate
and dibutyl oxalate. In a number of other cases intensive efforts can be observed
to develop new processes based on this reaction type, thus providing attractive
alternatives to current procedures. The recent literature shows many patent appli-
cations directed to the manufacture of organic carbonates, acrylicacid, or adipic
acid precursors by oxidative carbonylation. Nevertheless, attempts are made to
substitute even well-developed homogeneously catalyzed procedures by heteroge-
neously catalyzed reactions, the latter having the advantage of easier handling and
separation of catalysts.

2.1.2.5.2 Oxidative Carbonylation

Oxidative Carbonylation of Unsaturated Compounds

Oxidative Carbonylation of Simple Alkenes

The very first observed oxidative carbonylation was the stoichiometric reaction of
CO with a complex prepared from ethylene and PdC12, which was found in 1963.
In benzene as solvent 3-chloropropionyl chloride was obtained. Higher alkenes
having terminal double bonds under analogous conditions predominantly yielded
terminal carboxylic acid chlorides with a chlorine as substituent in the 2-position
[3-51. In the presence of alcohols the corresponding esters were obtained.
Depending on the nature of the substrate and on the chosen reaction parameters
twofold carbonylations were also observed (Scheme 2). For example, under com-
parable reaction conditions the styrene-PdC12 complex gave a mixture of methyl
cinnamate and dimethyl 2-phenylsuccinate [ 5 ] . Using PdC12, MgC12, and sodium

CI
COCl
R1&

CI
J\/COOR2

R1
&COOR2
R1 = H, alkyl, phenyl; R2 = alkyl
- Pd', - 2 HCI R200C

Scheme 2
 2.1.2.5 Oxidative Carbonylation 167

acetate as the catalyst system, methyl cinnamate was obtained in yields up to

40%, if a carbon monoxide partial pressure of not more than 0.02 MPa was
applied [27].
Summarizing the different results from the literature, under the conditions of
oxidative carbonylation in the presence of alcohols and catalytic amounts of
PdCI2, esters of a$-unsaturated carboxylic acids, P-alkoxy-esters and 2-sub-
stituted dialkyl succinates are generally obtained, or mixtures of all of these
compounds. Preferably CuC12, but also other transition metal salts, can be used
as co-catalysts (eq. (2)).
PdCI2/ co-cat.
R
’1/ + co + R~OH *

R’
R 2C
0,O
,)OR2 + R 2 0 0 CL C O O R ’

R’, R2 = alkyl

The reaction of ethylene with CO and oxygen using alcohols as solvents and
PdCI2/FeCl3as the catalyst system may serve as another well-developed example.
Dialkyl succinates are obtained in fair yields, while alkyl P-alkoxypropionates
occur as side products [6, 681. Simultaneously generated water is removed by
the addition of orthoformates to the reaction mixture, supressing the undesirable
formation of carbon dioxide. Increased yields are found if the concentration of
chloride ions is reduced by adding sodium acetate as a buffer.
The oxidative carbonylation of cis-2-butene in the presence of methanol, cata-
lytic amounts of PdC12, and stoichiometric quantities of CuC12 under a reaction
pressure of about 3 bar yields a racemic mixture of threo- and erythro- methyl
3-methoxy-2-methylbutyrate (ratio of the isomers, 87 : 13). Under comparable
conditions, but in the presence of sodium acetate, twofold carbonylation is
observed, giving meso-dimethyl 2,3-dimethylsuccinate as the only reaction
product. Starting from truns-2-butene, in an analogous manner threo- and
erythro-methyl3-methoxy-2-methylbutyrates are again obtained, but in a different
ratio of the isomers (40:60). If sodium acetate is added, racemic dimethyl (R,S)-
2,3-dimethylsuccinate is the sole product [7-91.
Cyclic olefins preferably undergo twofold carbonylation, even without the
presence of buffer compounds such as sodium acetate. With methanol serving
as the solvent and under comparable reaction conditions to those mentioned
above, cycloalkenes give product mixtures consisting of methyl trans-2-methoxy-
cycloalkanecarboxylates, dimethyl cis-cycloalkane- 1,2-dicarboxylates and di-
methyl cis-cycloalkane- 1,3-dicarboxylates (eq. (3) and Table 1). The formation
of 1,3-diesters may be explained by an intermediate reaction sequence which
involves an oxidative elimination and a subsequent readdition of the Pd2+species,
thus giving rise to an isomerization [9].
Intramolecular oxidative carbonylations are also known. If an olefinic double
bond and a hydroxyl group are in appropriate positions relative to each other,
168 2.1 Carbon Monoxide and Synthesis Gas Chemistry

Aa- A3coocH3 + ApJc00cH3 + COOCH3

a
'""OCHs

b
COOCH3 AT
H3COOC
C
(3)

Table 1. Carbonylation of cyclic olefins.

A Ratio of isomers (racemic)
a b C

CH2 4 68 27
CH2CH2 95 3.5 0.5
CH2CH2CH2 2 24 63
CH2CHZCH2CH2 4 10 85

cyclizations may occur leading preferably to substituted pyran ring systems

[28-301. The key step is the intramolecular attack of the nucleophilic hydroxyl
group on the coordinated complex formed from the double bond and the Pd2+spe-
cies (eq. (4)).

ROH, CO, 0 2 COOR

(4)
- H20

The oxidative carbonylation of alkenes leading to a,/?-unsaturated acids may

be of growing importance as an alternative procedure to related current industrial
processes, e. g., acetylene carbonylation or the oxidation of propene. For example,
until now technical-grade crotonic acid has been obtained by aldol condensation
of acetaldehyde and subsequent oxidation. Oxidative carbonylation of propene
yields the same product in a single-step reaction. A process developed by
Union Oil gives mixtures of acrylic acid and a-acetoxypropionic acid by palla-
dium-catalyzed liquid-phase reaction of ethylene with carbon monoxide and
oxygen. a-Acetoxypropionic acid is easily decomposed to acrylic acid and acetic
acid (eqs. ( 5 ) and (6)). The catalyst system consists of PdC12, lithium chloride,
lithium acetate, and CuC12. If the reaction is carried out on a technical scale, tita-
nium vessels should be used because of corrosion phenomena. The selectivities
observed for acrylic acid and /?-acetoxypropionic acid basing on ethylene
consumption are up to 85 %. CO, small amounts of propionic acid, vinyl acetate,
acetaldehyde, and some higher-boiling compounds have been identified as side
products. From a theoretical point of view, essentially no water leaves the ligand
sphere of the catalyst complex during the actual procedure of oxidative car-
bonylation. Nevertheless, formation of some water is always observed and may
 2.1.2.5 Oxidative Carbonylation 169

cause undesirable side reactions: therefore it has to be removed carefully. This

may be achieved by adding 10-20% acetic anhydride to the reaction mixture.
Numerous patent applications have been published that cover special catalyst
systems, procedures for catalyst regeneration, and other experimental details
[lo-231.

w C O O H A + AcOH
AcO F C O O H

Equation ( 5 ) can be divided into three reaction steps:

(1) Oxidative carbonylation of ethylene in the presence of Pd2+(eq. (7)).

During this first step PdC1, reacts in a stoichiometric reaction with ethylene,
water, and carbon monoxide forming acrylic acid, hydrogen chloride and Pd'.

PdC12 + CH2=CH2 + H20 + CO - @COOH + Pdo + 2HCI (7)

(2) Reoxidation of the resulting Pdo species by Cu2+, which acts as a co-catalyst
(eq. (8)).
This second step represents the regeneration of PdC12 under the influence of
CuCl,, by which Cu' is formed.
Pdo + 2CuC12 - PdC12 + 2CuCl (8)

(3) Regeneration of Cu2+(eq. (9)).

In the presence of oxygen and hydrochloric acid Cu' is reoxidized to CuC12.
Water which is generated in this reaction step may again act as hydroxylating
agent as depicted in (7), thus completing the reaction cycle.
2CuCl + 2HCI + '/202 -+ 2CuC12 + H20 (9)

A detailed discussion of the influence of pressure, temperature, catalyst

variations, and the removal of water from the reaction mixture, as well as the
influence of different solvents on selectivity and reaction rates, may be found in
[12]. For more details about the reaction mechanism and the chemistry of
palladium-alkene-CO complexes cf. [ 13, 14, 171.

Oxidative Curbonylution of 1,3-Dienes

The oxidative carbonylation of conjugated dienes has frequently been reported to

yield product mixtures as represented in Scheme 3.
In some cases reaction conditions have been successfully optimized in such
a way that certain products are obtained with good selectivities [123]. For ex-
170 2.1 Carbon Monoxide and Synthesis Gas Chemistry

W C O O M e
r+ Meo
’ COOMe

-COOMe
MeOOC

Scheme 3

ample, the reaction of butadiene with benzyl alcohol and carbon monoxide in the
presence of PdCI2 and CuC12 gives dibenzyl 3-hexene-l,6-dicarboxylatein about
90 9% yield [24].
Intensive work on the oxidative carbonylation of butadiene, mainly directed
toward finding a feasible manufacturing method for adipic acid and sebacinic
acid, was done by Stille et al. and by research groups from Atlantic Richfield
(ARCO) [ 1231. In early publications stoichiometric amounts of CuC12 were
used for the reoxidation of the PdCI, catalyst [24, 125, 1261. The process elabo-
rated later by Atlantic Richfield starts from methanol as the alcohol component
and uses 1,l-dimethoxycyclohexanone as water-binding agent. Adipic acid is
produced in a reaction sequence starting from butadiene involving a hydrogena-
tion (100°C/12.5 MPa) and a hydrolysis step [25, 26, 127-1291. Butadiene con-
version is about 30 % and selectivity to adipic ester precursors about 79 %. Using
catalyst systems consisting of PdC12, CuI, lithium iodide, and ferric chloride,
under a somethat lower pressure of about 7 MPa methyl 2,4-pentadiene-l-carbox-
ylate is obtained [26, 1241.

Oxidative Carbonylation of Arenes

Only in a very few cases direct oxidative carbonylations of arenes have been
described. For example, if naphthalene is reacted with CO and oxygen in the
presence of Pd(OAc)*, naphthalene- 1- and -2-carboxylic acids are obtained [69].

Oxidative Carbonylation of Alcohols

Depending on the catalyst system and the chosen reaction conditions, aliphatic
and aromatic alcohols can in general act as substrates for oxidative carbonylations.
In principle this reaction type can occur in the presence of metal ions which are
able to oxidize CO in the presence of an alcohol function. As already mentioned
above, it is also here necessary to carry out the reaction in the presence of a
suitable reoxidant in order to establish a catalytic cycle process. Preferably that
may be another metal salt, for example CuC12.Typical products and side products
which are observed in the oxidative carbonylation of alcohols are alkyl and
aryl carbonates, oxalates, formates, haloformates, acetals, and carbon dioxide.
 2.1.2.5 Oxidative Carbonylation 171

The observed selectivity strongly depends on the catalyst system, on promoters

which are added to the reaction mixture, and on the choice of the reaction condi-
tions.
By far the most important industrial process based on oxidative carbonylation
of alcohols is the manufacture of dialkyl carbonates and dialkyl oxalates [38, 39,
5 1, 52, 671. For these products especially, dimethyl carbonate is of growing inter-
est as a potential substitute for phosgene and dimethyl sulfate, both highly toxic
and corrosive key chemical intermediates. As a versatile and environmentally
harmless C, building block, as an alternative methylating agent and as a nontoxic,
nonpolluting solvent, dimethyl carbonate could come to represent a new philoso-
phy in industrial chemistry. Most work on the development of suitable procedures
allowing the large-scale preparation of this compound has been done by industrial
research groups and is well documented in the patent literature. Since 1970, it is
mainly Enichem (Italy), Bayer (Germany), Texaco, Dow, and General Electric (all
USA), Ube and Daicel (both Japan) who have elaborated attractive procedures
which are or nearly are competitive with classical methods even in their economic
aspects.

Oxidative Carbonylation of Aliphatic Alcohols Giving Dialkyl Carbonates

By oxidative carbonylation of lower aliphatic alcohols in the presence of oxygen

or other suitable oxidants dialkyl carbonates and dialkyl oxalates are obtained,
depending on the catalyst and the chosen reaction conditions (eqs. (10) and (1 1)).

2ROH + CO + '/202 5 RO-CO-OR + H20 (10)

The oxidative carbonylation of alcohols in the presence of oxygen catalyzed

by copper salts currently represents the most important industrial procedure for
the preparation of dimethyl carbonate. It was developed by Enichem Synthesis
(formerly ANIC, resp. Snamprogetti) and it is carried out in two plants in
which 8000 t/a (Enichem Synthesis, Ravenna, Italy) and 12 000 t/a (General Elec-
tric Plastics Japan, Chiba, Japan) of this compound are manufactured. In numer-
ous patent applications [31-371 as well as in a few scientific publications [38, 39,
65, 661, many details of this process have been documented. In Scheme 4 the
presumed reaction mechanism is shown in a simplified form. CuCI, which is pre-
sent in the reaction mixture in high concentrations (about 15-20 w. %) is oxidized
in the presence of oxygen and methanol to give Cu(OCH3)C1 as the primary
reaction product. This intermediate, which optionally may be isolated, reacts in
a second step with CO to yield dimethyl carbonate and CuCl again, which enters
the next catalytic cycle. It is of great importance to control carefully the level of
water generated continously during the first reaction step, because it causes the
undesirable formation of carbondioxide. The optimized reaction conditions are
pressures between 2.5 and 3.5 MPa and temperatures between 120 and 160°C.
172 2.1 Carbon Monoxide and Synthesis Gas Chemistry

Obviously only dimethyl carbonate is obtained in acceptable selectivities and

space-time yields according to this method, although the analogous preparation
of higher dialkyl carbonates and simple cyclic carbonates has also been
described. Phenols do not give diary1 carbonates by CuC1-catalyzed oxidative
carbonylation.

2CH30H +
H20

'1202 1 1c;< 2 Cu(OCH3)CI

2 CuCl

OCH3

Scheme 4. Dimethylcarbonate formation according to Enichem proposed reaction

mechanism.

The solubility of both CuCl and Cu(OCH,)Cl in the reaction system is quite
low, but it has been proven that the formation of dimethyl carbonate takes
place in the homogeneous phase and is mediated by soluble Cu" species [52].
For example, according to recent patent applications this can be achieved by
passing a constant flow of feed gas through the liquid reaction mixture, consisting
of a large excess of CO and a small amount of oxygen, which is completelycon-
sumed. Only a small part of the CO is converted to dimethyl carbonate, while the
rest acts as a carrier gas. By this method a steady state is reached and methanol,
dimethyl carbonate, and water are removed in a ratio which corresponds to their
partial vapor pressures under the given conditions [35,37, 641. After condensation
of methanol and dimethyl carbonate and removal of C 0 2 and low boiling com-
pounds, excess CO is recycled to the reaction, while dimethyl carbonate itself
can be isolated from its low-boiling azeotrope with methanol for example by
extractive or azeotropic distillation or by pervaporation. In Figure I a simplified
block flow diagram shows the Enichem process as a summary of several descrip-
tions published mainly in the patent literature.
Different variations of the Enichem process have been described that may show
some improvements in selectivity and efficiency of the catalyst system, but they
generally seem to be less attractive from the economic point of view and none
of them has been realized until now. For example, since 1986 the Japanese
company Daicel especially has applied for numerous patents on modifications
of the Enichem process, in which dimethyl carbonate is prepared in the presence
of catalyst systems that contain copper and palladium salts and additional modi-
fiers, e. g., quinoid compounds and quaternery phosphonium halides [40-48].
Although Daicel has announced several times the construction of an industrial
plant for the production of dimethyl carbonate, all investment plans now seem
to be put aside. The separation of the reaction product from the complicated
catalyst system as well as the complete recycling of the palladium compounds,
which is a necessary requirement for any economic process design, seem not to
be solved sufficiently.
 2.1.2.5 Oxidative Carbonylation 173

- wastegas

excess CO co-
* purification

DMC, MeOH
*
co-
separation
- light ends
H,O, CO

MeOH H@-.
A - DMC- DMC, MeOH, H2O * separat,on
reaction
CuCl
.__.___..... ~

25-35 bar
120-160 "C * waste water
DMC,
MeOH
co T t 1

02 I MeOH-
separation

recycle MeOH I DMC

Figure 1. Block flow diagram dimethyl carbonate according to Enichem.

Extensive efforts to achieve the oxidative carbonylation of methanol in the gas

phase using CuCl or Cu(OCH3)C1complexes supported on active carbon have
been undertaken to Dow Chemicals [49, 501. Because of the rapid catalyst de-
activation this method has not become an alternative to the Enichem process.
The oxidative carbonylation of aliphatic alcohols in the presence of homoge-
neous catalysts using alkyl nitrites instead of air or oxygen as oxidants has
been described by Ube and Toa Nenryo [53-561. Best yields have been found
using catalyst systems containing PdC12 and different co-catalysts, especially
CuC12. Alkyl nitrites act as reoxidants of the Pdo species generated during the
course of the reaction. This effect will be discussed below. The method is not
suitable for the preparation of aryl carbonates, because phenol derivatives are
readily nitrosated in the presence of organic nitrites. Because of low space-time
yields, unsatisfactory selectivities, and problems concerning the separation and
recycling of the catalysts, this early work has not been continued.
Since 1989, Ube (Japan), Bayer (Germany), and a Chinese group independently
of each other have taken up these results again and developed improved processes
for preparing dimethyl carbonate by the nitrite route [57-631. In contrast to the
results already described in the early Ube and Toa Nenryo patent applications,
174 2.1 Carbon Monoxide and Synthesis Gas Chemistry

the new process design is based on heterogeneous catalysis. PdC12 and optionally
in addition other metal salts or complexes supported on active carbon or y-A1203
are used as catalysts, and CO and methyl nitrite are reacted in the gas phase.
Losses of chlorine during the process cause a rapid decrease in catalyst activity,
which has to be restored by the addition of chlorine, hydrogen chloride, or methyl
chloroformate to the feed gas mixture or by regeneration cycles of the catalyst.
Since 1993 Ube has run a plant in which about 3000 t/a dimethyl carbonate is
produced. While in the case of the Enichem process it has to be acknowledged
that so far it has not been possible to substitute this process based on homogeneous
catalysis by a heterogeneously catalyzed one, the methyl nitrite process for
dimethyl carbonate is an example of the opposite case.

Oxidative Carbonylation of Aliphatic Alcohols Giving Dialkyl Oxalates

Dialkyl oxalates are of great interest as solvents, as C2 building blocks in fine

chemicals synthesis and as intermediates in the manufacture of oxamide, which
serves as a fertilizer mainly in the cultivation of rice. Hydrogenation of dimethyl
oxalate was extensively studied at the beginning of the 1980s, when Ube
(Japan) and Union Carbide searched jointly for an alternative route to the
base chemical ethylene glycol, independent of natural mineral-oil resources
[51, 70, 711.
The preparation of dialkyl oxalates by oxidative carbonylation of alcohols was
first described by Fenton et al. in the early 1970s [72-741. For example, the
reaction can be carried out at a temperature around 125°C and a pressure of
about 70 bar in the presence of PdC12 and iron or copper salts. Water is formed
as a by-product and has to be removed from the reaction mixture by the addition
of water-binding agents such as trialkyl orthoformates. Instead of oxygen benzo-
quinone can also be used for the reoxidation of the catalyst system. Ammonia or
amines seem to have a positive influence on selectivity and efficiency of the reac-
tion. For some more examples, cf. [77-80, 1171. Mechanistic studies give some
indication that alkoxycarbonylpalladium species occur as intermediates [52, 75,
761 (eq. (12)).
"\

CI/
/"
Pd
\co
-
2CH30- CI,

CI
/COOCH3
/Pd\
COOCH3
- (COOCH3)2 + Pdo + 2 CI- (12)

Based on their alkyl nitrite technology, Ube developed their own new process
for the manufacture of dialkyl oxalates by oxidative carbonylation of alcohols.
This process is a two-step reaction, in which alkyl nitrite acts as an reoxidant
for the palladium catalyst system, similarly to the situation in the preparation of
dialkyl carbonates mentioned above. The published patent literature does not
make it possible to give exact details about the Ube industrial plant in
Yamaguchi, Japan, which has produced several thousands tons of dibutyl oxalate
annually since 1978. The first step of the manufacturing process for dialkyl
oxalates is the preparation of the gaseous alkyl nitrite from NO, oxygen, and
 2.1.2.5 Oxidative Carbonylation 175

alcohol, whereby water is formed as a side product and is separated. After

purification the alkyl nitrite is fed, together with carbon monoxide, into an
autoclave or a column containing an alcoholic solution of a platinum metal salt,
preferably a palladium salt, for example Pd(CN)2 or the PdC12/CuC12 couple
[84, 85, 1161. The reaction is carried out under CO pressure at higher temperatures
in the presence of basic promoters such as inorganic carbonates or trialkylamines.
If the CO pressure is too low, selectivity for dialkyl oxalates decreases. Dialkyl
oxalate and 2 mol of NO are formed simultaneously. The reaction product is
isolated according to conventional techniques, while NO is recycled to the alkyl
nitrite generator. Typical side products of the liquid-phase dialkyl oxalate process
according to Ube are dialkyl carbonates and alkyl esters of the conjugated car-
boxylic acids (eq. (13)).

R = H, alkyl

In Figure 2 a simplified block flow diagram shows some principles of this pro-
cess. One of the main advantages is that water is formed and removed in another
part of the plant than the one where the carbonylation takes place. Therefore it
does not give rise to the undesirable formation of carbon dioxide.
Similarly to the case of dimethyl carbonate, much work has been done to make
dialkyl oxalates accessible by a heterogeneously catalyzed gas-phase process [77,

co

+ i.
alkyl nitrite synthesis
2 RONO
1
dialkyl oxalate synthesis

2RONO + 2CO Pd/Pdzt ROOC-COOR + NO

2 NO
L ROOC-COOR

- Hz0

Figure 2. Dialkyl oxalate process according to Ube.

176 2.1 Carbon Monoxide and Synthesis Gas Chemistry

811. The most promising process is also an oxidative carbonylation based on alkyl
nitrites and was developed for dimethyl oxalate mainly by Ube. It uses supported
palladium catalysts, modified with Fe, Ni, or Mo on y-A1203 [82, 83, 1361.

Oxidative Carbonylation of Phenols

The oxidative carbonylation of aromatic alcohols leads to diary1 carbonates.

Among these diphenyl carbonate especially is of great interest for several applica-
tions in industrial chemistry. As a versatile C, building block, which can be used
for an easy transfer of the C = 0 unit, it shows a much higher reactivity than, e. g.,
dimethyl carbonate. It plays a role of growing importance in polymer chemistry,
in the manufacture of organic intermediates, and in fine chemicals synthesis. In
many processes diphenyl carbonate can or could serve as an alternative to phos-
gene, although it has a lower reactivity and still higher manufacturing costs. While
phosgene is produced from chlorine and carbon monoxide, diphenyl carbonate
can be manufactured according to chlorine-independent, and thus environmentally
benign, routes: by transesterification of dimethyl carbonate or, alternatively, by
direct oxidative carbonylation of phenol. The latter method has not been devel-
oped as an industrial process so far, although currently many chemical companies
are doing intensive research on it. A very promising example is the new 25 000 t/a
polycarbonate plant of General Electric Plastics Japan (Chiba, Japan) that was
started up in early 1993. In contrast to all other current manufacturing procedures
for polycarbonate, this plant uses dimethyl carbonate, which is prepared according
to the Enichem process (see above). In a second step dimethyl carbonate is trans-
esterified with phenol to give diphenyl carbonate, which itself is again transester-
ified with bisphenol A to give a so-called "melt polycarbonate". Phenol which is
formed during the latter reaction step, can be recycled to the synthesis of diphenyl
carbonate or bisphenol A. The present situation involving the manufacture of
polycarbonate or other bulk products of the phosgene downstream as well as
some future options concerning the use of organic carbonates are shown in
Scheme 5.

DMC = dimethyl carbonate bisphenol A HO- C~ H~ - C ( C H ~) Z - C ~H ~- O H

DPC = diphenyl carbonate polycarbonate [-O-C~H~-C(CH~)Z-C~H~-O-CO.]~

Scheme 5. Use of organic carbonates as substituents for phosgene in the manufacture

of polycarbonate.
 2.1.2.5 Oxidative Carbonylation 177

In respect to its growing technical importance, the oxidative carbonylation of

phenol has been widely studied. The first systematic research on this subject
was done by Hallgren et al. from General Electric. Between 1976 and 1982 a
number of fundamental scientific publications [86-881 and patent applications
[89-961 by this group appeared in literature, but because of low conversion
rates and space-time yields this basic work was not continued. Some years
later, stimulated by broad efforts in developing new processes for the manufacture
of polycarbonate and a therefore increased interest in diphenyl carbonate, inten-
sive research activities were resumed in order to find reaction conditions that
would allow an industrial realization of the oxidative carbonylation of phenol.
Since 1987 a continuous growth of the number of patent applications concerning
this subject can be observed [97-1151. Meanwhile nearly all big producers of
polycarbonate have joined this very promising field of research.
Important characteristics of the reaction are the use of Pd2+ compounds as
catalysts as well as the presence of a base, an ammonium salt, and a suitable
co-catalyst. Water which is formed in course of the reaction has to be removed
as efficiently as possible. This is usually effected by the addition of a water-bind-
ing agent such as zeolites, acetals or orthoformates. Due to eqs. (1 4) and (15) Pdo
species are formed within the catalytic cycle that are reoxidized under the action
of the co-catalyst to give Pd2+again. Transition metal compounds, especially com-
plexes of such metals, that are soluble in the reaction system and capable of a
reversible change of their oxidation state, showing an oxidation potential suffi-
cient for the reoxidation of Pdo to Pd2+,are in principle the co-catalysts of choice.
In recent patent applications, for example, cobalt and manganese complexes are
used for such purposes. The main differences concern the proposed catalyst-co-
catalyst systems, solvents, basic additives, ammonium salts, and further modifiers
such as quinones and aryl ketones. The optimized reaction conditions seem to be a
pressure between 3 and 12 MPa, a temperature between 100 and 130°C, and the
use of excess phenol as solvent. The best space-time yields are about 20-120 g/L
h, and selectivities reach values up to 99%. Although good progress has been
made, the unacceptable high consumption of Pd2+,incomplete recovery of the ex-
pensive compounds comprising the catalyst-co-catalyst system, and comparatively
rapid decreases of catalytic properties due to deactivation phenomena are still
unsolved problems. Successful industrial production of diphenyl carbonate or
other aryl carbonates by oxidative carbonylation of phenol(s) still does not
seem to be foreseeable.

PdX2 + CO + 2PhOH 3 PhO-CO-OPh + 2HX + Pdo (14)

co-cat.
Pdo + 2HX + '1202 PdX2 + H20

Oxidative Carbonylation of Amines

Oxidative carbonylation of aliphatic and aromatic amines in the presence of sup-

ported platinum metals or platinum metal salts as catalysts and iodide ions gives
carbamates [118, 1191. Iodide is presumed to promote the partial redox reactions
178 2.1 Carbon Monoxide and Synthesis Gas Chemistry

of the metal or to serve as an activator for oxygen or CO (eq. (16)). Carbamoyl-

metal species are believed to occur as intermediates, and ureas are obtained as side
products.

R1-NH2 + CO + l/2 0 2 + R20H R1-NH-COOR2 + Rl-NH-CO-NH-Rl

(16)
R' = alkyl, aryl; R2 = alkyl, M = supported platinum metal or metal salt

This process was elaborated as a heterogeneously catalyzed variation by Asahi

Chemicals (Japan) in order to open a new route to diisocyanates, not depending on
the use of phosgene [120, 1341. Ethyl phenylcarbamate, which in a first step is
obtained by catalytic oxidative carbonylation of aniline, CO, oxygen, and ethanol
(eq. (17)), is condensed with aqueous formaldehyde to yield methylene diphenyl
diurethane. Thermal decomposition leads to methylene diphenyl diisocyanate
(MDI), which is one of the most important intermediates for the industrial manu-
facture of polyurethanes (eq. (18)). The yields and selectivities of the last reaction
step seem to be the main reasons why this process is still inferior to the existing
ones.

-
H

ON"'+
+ CO '/202 + C2HsOH
Pd, I-
170 "C
+ H 20 (17)
90 bar

If primary aliphatic or aromatic amines and aliphatic alcohols are reacted with
CO and oxygen in the presence of a catalyst system containing hydrochloric acid,
Pd2+salts or complexes, and CuCI, or FeC13, then carbamates are obtained in fair
yields even at ambient temperature and atmospheric pressure. In the absence of
alcohols N,N'-disubstituted ureas are obtained [121, 122, 130-132, 1351. Long
reaction times and problems arising from CO, generation due to the water formed
in the course of the reaction can be overcome by the use of di-t-butyl peroxide
instead of oxygen as an oxidant. If the reaction is extended to secondary amines,
depending on the nature of the substrate oxamate esters may also be observed as
side products.
The preparation of urethanes from primary aliphatic and aromatic amines by
oxidative carbonylation has been described in which - instead of Pd2+ salts or
complexes - lanthanide compounds, particularly of cerium, and promoters com-
prising alkali metal salts or quaternary ammonium salts, are used [133].
 References 179

References
[1] W. Bertleff in Ullmann’s Encycl. Ind. Chem. 5th ed. 1986, Vol. A5, p. 217.
[2] W. Keim, Grundlagen der Industriellen Chemie. Technische Produkte und Prozesse,
Salle und Sauerllnder, Frankfurt, 1986.
[3] J. Tsuji, M. Morikawa, J. Kiji, Tetrahedron Lett. 1963, 1061.
[4] J. Tsuji, M. Morikawa, J. Kiji, J. Am. Chem. Soc. 1964, 86, 4851.
[5] T. Yukawa, S. Tsutsumi, J. Org. Chem. 1969, 34, 738.
[6] D. M. Fenton, P. J. Steinwand, J. Org. Chem. 1972, 37, 2034.
[7] J. K. Stille, D. E. James, L. F. Hines, J. Am. Chem. Soc. 1973, 95, 5062.
181 D. E. James, L. F. Hines, J. K. Stille, J. Am. Chem. Soc. 1976, 98, 1806.
[9] D. E. James, J. K. Stille, J. Am. Chem. Soc. 1976, 98, 1810.
[lo] Union Oil (K. L. Oliver), US 3.505.394 (1970).
[ I ll Shell (D. Medema, C. F. Kohll, R. van Helden) DE 1.468.987, BE 650.980 (1969).
[12] K. L. Olivier, D. M. Fenton, J. Biale, Hydrocarbon Process. 1972, 51, 95.
[13] Universal Oil Products (G. Biale, D. M. Fenton, K. L. Olivier, W. D. Schaeffer),
DE 1.493.375, NL 6.506.951 (1969).
[I41 Union Oil (K. L. Olivier), US 3.415.871 (1968).
[15] Union Oil (K. L. Olivier, W. D. Schaeffer), US 3.461.157 (1969).
[16] Hercules Powder (R. Heck, D. Henry), BE 685.626 (1966).
[17] Union Oil (K. L. Olivier), US 3.420.873 (1969).
1181 Rohm (W. Ganzler, K. Kabs, G. Schroder), DE 2.232.088 (1974).
[19] Rohm (W. Ganzler, K. Kabs, G. Schroder), DE 2.237.837 (1972).
[20] Rohm (W. Ganzler, K. Kabs, G. Schroder), DE 2.237.590 (1974).
[21] Rohm (W. Ganzler, K. Kabs, G. Schroder), DE 2.238.837 (1974).
[22] Rohm (W. Ganzler, K. Kabs, G. Schroder), DE 2.247.312 (1974).
[23] D. M. Fenton, K. L. Olivier, G. Biale, Prepr: Div. Petrol. Chem., Am. Chem. Soc. 1969,
14, C77.
1241 J. K. Stille, R. Divakaruni, J. Org. Chem. 1979, 44, 3474.
[25] Atlantic Richfield (H. S. Kesling, L. R. Zehner), US 4.189.599 (1980).
[26] Atlantic Richfield (H. S. Kesling, L. R. Zehner), US 4.236.023 (1980).
[27] G. Cometti, G. P. Chiusoli, J. Organomet. Chem. 1979, 181, C14.
[28] M. F. Semmelhack, A. Zask, J. Am. Chem. Soc. 1983, 105, 2034.
[29] M. F. Semmelhack, C. Bodurow, J. Am. Chem. Soc. 1984, 106, 1469.
[30] M. McCormick, R. Monahan 111, J. Soria, D. Goldsmith, D. Liotta, J. Org. Chem. 1989,
54, 4485.
[31] Anic (U. Romano, R. Tesei, G. Cipriani), DE 2.743.690 (1976).
1321 Anic (U. Romano, F. Rivetti, F. Schio, N. di Muzio), DE 3.045.767 (1979).
1331 Enichem Synthesis (U. Romano, F. Rivetti), EP 366.177 (1988).
1341 Enichem Synthesis (U. Romano, F. Rivetti), EP 365.083 (1988).
[35] Enichem Synthesis (N. Di Muzio, C. Fusi, F. Rivetti), EP 460.732 (1991).
[36] Enichem Synthesis (G. Paret, G. Donati, M. Ghirardini), EP 460.735 (1991).
[37] Enichem Synthesis (F. Rivetti, U. Romano), EP 534.545 (1992).
[38] U. Romano, R. Tesei, M. M. Mauri, P. Rebora, Ind. Eng. Chem., Prod. Res. Dev., 1980,
19, 396.
[39] M. M. Mauri, U. Romano, F. Rivetti, Quad. Ing. Chim. Ital. 1985, 21, 6.
[40] Daicel (S. Yokota, H. Kojima), JP 62.212.350 (1987).
[41] Daicel (S. Yokota, H. Kojima), JP 63.057.552 (1988).
[42] Daicel (S. Yokota, H. Koyoma, H. Kojima), EP 452.997 (1991).
[43] Daicel (S. Yokota, H. Kojima), JP 64.013.058 (1989).
[44] Daicel (S. Yokota, Y. Tanaka, H. Miyake), EP 354.970 (1990).
180 2.1 Carbon Monoxide and Synthesis Gas Chemistry

[45] Daicel (K. Koga, H. Tatsumi), JP 01.279.859 (1989).

[46] Daicel (S. Oda), JP 01.311.054 (1989).
[47] Daicel (H. Suzuki, H. Kojima), JP 02.004.737 (1990).
[48] Daicel (S. Yokota, H. Suzuki), JP 02.006.438 (1990).
[49] Dow (G. L. Curnutt), US 4.625.044 (1986).
[SO] Dow (G. L. Curnutt), US 5.004.827 (1991).
[Sl] H. Itatani, Chem. Econ. Eng. Rev. 1984, 16, 21.
[52] U. Romano, Chim. Ind. (Milan) 1993, 75, 303.
[53] Ube (H. Itaya), JP 54.106.429 (1979).
[54] Ube (S. Utsumi), JP 56.164.145 (1981).[55]Toa Nenryo (Y. Okumura), JP 60.011.443
(1985).
[56]Toa Nenryo (T. Sakakibara), JP 60.094.943 (1985).
[57] X.-Z. Jiang, Y.-B. Zhu, S.-Y. Xu, Cuihuu Xuebao 1989, 10(1), 75.
[ 5 8 ] X.-Y. Jiang, Platinum Metals Rev. 1990, 34(4), 178.
[59] Ube (K. Nishihira, M. Mizutare), EP 425.197 (1991).
[60] Ube (K. Nishihira, S. Yashida, S. Tanaka), EP 523.728 (1993).
[61] Ube (T. Matsuzaki, T. Shimamura, Y. Toriyahara, Y. Yamasaki), EP 565.076 (1993).
[62] Bayer (H. Landscheidt, A. Klausener, E. Wolters, H.-U. Blank, U. Birkenstock),
EP 523.508 (1991).
[63] Bayer (H. Landscheidt, E. Wolters. P. Wagner, A. Klausener), EP 634.386 (1994).
[64] BASF (K. Joerg, F.-J. Muller, W. Harder, R. Kummer), EP 413.215 (1991).
[6S] P. Koch, G. Cipriani, E. Perotti, Guzz. Chim. Itul. 1974, 104, 599.
[66] F. Rivetti, U. Romano, J. Organomet. Chem. 1979, 174, 221.
[67] A. Niiyama, Fine Chem. 1992, 21, 5.
[68] L. F. Hatch, Hydrocarbon Process 1970, 49, 101.
[69] Teijin (Y. Ichikawa, T. Yamaji), DE 2.340.592 (1974).
[70] K. Weissermel, H.-J. Arpe, Industrielle Organische Chemie, VCH, Weinheim, 1988,
p. 164.
[71] K.-H. Keim, J. Korff, W. Keim, M. Roper, Erdol, Kohle, Erdgas, Petrochem. 1982, 35,
297.
[72] D. M. Fenton, K. L. Olivier, Chem. Technol. 1972, 220.
[73] Union Oil (D. M. Fenton, P. J. Steinwand), US 3.393.136 (1972).
1741 D. M. Fenton, P. J. Steinwand, J. Org. Chem. 1974, 39, 701.
[75] F. Rivetti, U. Romano, J. Organomet. Chem. 1978, 154, 323.
[76] M. Roper in Industrial Applications of Homogeneous Catalysis (Eds.: A. Mortreux,
F. Petit), D. Reidel, Dordrecht, 1988, p. 14.
[77] G.-S. Chen, H.-D. Chen, H.-M. Yan, B. Xue, J . Nut. Gas Chem. 1993, 2, 321.
[78] Atlantic Richfield (L. R. Zehner, R. W. Sauer, J. J. Heffron), US 4.005.128 (1977).
[79] Atlantic Richfield (L. R. Zehner), US 4.005.129 (1977).
[80] Atlantic Richfield (L. R. Zehner), US 4.005.130 (1977).
1811 A. M. Gaffney, J. J. Leonard, J. A. Sofranko, H.-N. Sun, J. Catal. 1984, 90, 261.
[82] Ube (H. Miyazaki et al.), US 4.384.133 (1983).
[83] Toa Nenryo (Y. Okumura, H. Takai, T. Sakakibara, K. Kaneko), JP 60.181.051
(1985).
[84] Ube (K. Nishimura, S. Uchiumi, K. Fujii, K. Nishihira, M. Yamashita, H. Itatani,
M. Matsuda), DE 2.838.856 (1979).
[85]K. Nishimura, S. Uchiumi, K. Fujii, K. Nishihira, H. Itatani, P r e p Div. Pet. Chem., Am.
Chem. Soc. 1979, 24(1),355.
[86] J. E. Hallgren, R. 0. Matthews, J. Organomet. Chem. 1979, 175, 135.
[87] J. E. Hallgren, G. M. Lucas, R. 0. Matthews, J. Organomet. Chem. 1981, 204, 135.
[88] J. E. Hallgren, G. M. Lucas, J. Organomet. Chem. 1981, 212, 135.
 References 18 1

[89] General Electric (J. E. Hallgren), DE 2.738.437 (1978).

[90] General Electric (A. J. Chalk), DE 2.738.487 (1978).
[91] General Electric (J. E. Hallgren), DE 2.738.488 (1978).
[92] General Electric (A. J. Chalk), DE 2.738.520 (1978).
[93] General Electric (A. J. Chalk), DE 2.815.501 (1979).
[94] General Electric (J. E. Hallgren), DE 2.815.512 (1979).
[95] General Electric (J. E. Hallgren), DE 2.949.936 (1980).
[96] General Electric (J. E. Hallgren), US 4.349.485 (1982).
[97] Asahi Chemicals (N. Fukuoka, H. Kogawa, T. Watanabe), JP 01.165.551 (1987).
[98] General Electric (T. C.-T. Chang), EP 350.697 (1990).
[99] General Electric (T. C.-T. Chang), EP 350.700 (1990).
[ 1001 General Electric (J. A. King), EP 450.442 (1991).
[I011 Asahi Chemicals (S. Fukuoka), JP 04.257.546 (1992).
[lo21 Asahi Chemicals (S. Fukuoka), JP 04.261.142 (1992).
[103] Idfemitsu Kosan (H. Kezuka, F. Okuda), EP 503.581 (1992).
[lo41 General Electric (J. A. King, G. R. Faler, T. E. Krafft), EP 507.546 (1992).
[lo51 Idemitsu Kosan (H. Kezuka, F. Okuda), EP 508.340 (1992).
[lo61 Mitsui Petrochemicals (A. Fujita, Y. Kiso, T. Nagata, H. Iwasaki), JP 05.025.095
(1993).
[lo71 General Electric (J. A. King, P. D. McKenzie, E. J. Pressman), WO 93/03.000,
EP 550.743 ( I 993).
[lo81 Mitsui Petrochemicals (Y. Kiso, T. Nagata, A. Fujita, H. Iwasaki), JP 05.058.961
(1993).
[lo91 Mitsubishi Gas (M. Mizukami, K. Hayashi, K. Iura, T. Kawaki), EP 572.980 (1993).
[110] Mitsubishi Petrochemicals (H. Iwane, H. Miyagi, S. Imada, S. Senoo), JP 06.009.595
(1 994).
[ l l l ] General Electric (R. P. Joyce, J. A. King, E. J. Pressman), EP 583.935 (1994).
[112] General Electric (S. J. Shafer), EP 583.936 (1994).
[113] General Electric (E. J. Pressman, J. A. King), EP 583.937 (1994).
[114] General Electric (E. J. Pressman, S. J. Shafer), EP 583.938 (1994).
[ 1 151 Idernitsu Kosan (F. Okuda), JP 06.211.750 (1994).
[116] Ube (T. Yamazaki, M. Eguchi, S. Ushiumi, A. Iwayama, M. Takahashi, M. Kurahashi),
DE 2.514.685 (1975).
[ 1 171 Montedison (L. Cassar, A. Gardano), DE 2.601.139 (1976).
[ 1181 S. Fukuoka, M. Choro, M. Kohno, J. Chem. SOC., Chem. Commun. 1984, 399.
[119] S. Fukuoka, M. Chono, M. Kohno, J. Org. Chem. 1984, 49, 1460.
[120] S. Fukuoka, M. Chono, M. Kohno, CHEMTECH 1984, 670.
[121] H. Alper, F. W. Hartstock, J. Chem. SOC., Chem. Commun. 1985, 1141.
[122] H. Alper, G. Vasapollo, W. Hartstock, M. Mlekuz, D. J. H. Smith, G. E. Moms,
Organometallics 1987, 6, 2391.
[123] H. S. Kesling in Industrial Chemicals via CI Processes, ACS Symp. Ser: 1987,
328, 77.
[124] Atlantic Richfield (H. S. Kesling, L. R. Zehner), US 4.195.184 (1980).
[125] J. K. Stille, D. E. James, J. Am. Chem. SOC. 1976, 98, 1810.
[126] Polymer Sciences Corp. (J. K. Stille), US 4.259.519 (1991).
[127] Atlantic Richfield (H. S. Kesling, L. R. Zehner), US 4.171.450 (1979).
[128] Atlantic Richfield (H. S. Kesling, L. R. Zehner), US 4.166.913 (1979).
[I291 Atlantic Richfield (H. S. Kesling, L. R. Zehner), US 4.281.173 (1981).
[I301 P. Giannoccaro, J. Organomet. Chem. 1987, 336, 271.
[ 13I ] P. Giannoccaro, Znorg. Chim. Acta 1988, 142, 8 1.
[132] P. Giannoccaro, J. Organomet. Chem. 1994, 470, 249.
182 2.1 Carbon Monoxide and Synthesis Gas Chemistry

[133] Industrial Technology Research Institute (P. K.-L. Loh, P. Shieh, J.-L. Chen,
T.-K. Chuang), US 5.101.063 (1992).
[134] Asahi Chemicals (S. Fukuoka, M. Chono), EP 83.096 (1983).
[135] Bayer AG (R. Becker, J. Grolig, C. Rasp), DE 2.908.251 (1980).
[136] Ube (Y. Shiomi, T. Matsuzaki, K. Masunaga), EP 108.359 (1984).

2.1.2.6 Other Carbonylations

Matthias Bellel; Ahmed M. Tafesh

2.1.2.6.1 Hydrocarboxylations and Related Reactions

Catalytic hydrocarboxylations and related esterifications as well as amidations of
alkenes belong to a family of carbonylation reactions which has attracted con-
siderable industrial interest. Minor changes in the catalyst system as well as in
reaction conditions can lead to simple carboxylic acids, diacids, polyketones, or
unsaturated acids as products (Scheme 1). Most importantly, these methods
provide routes to monocarboxylic acids, e.g., ethylene to propanoic acid (see Sec-
tion 2.1.2.2), or 1-olefins (readily available from the oligomerization of ethylene
discussed in Section 2.3.1.3) to higher carboxylic acids.
For technical purposes standard carbonylation catalysts such as Co2(C0)*and
Ni(C0)4 have been used to prepare fatty-acid esters [l]. More recently, other
catalysts based on Pd, Pt, Rh, and Ru found widespread use because of their better
performance under milder reaction conditions [2]. As seen in eq. (1) and Table 1,
hydrocarboxylation of simple olefins with palladium catalysts occurs at tempera-
tures of 70-120°C and 0.1-20 MPa, while cobalt catalysts needed 150-200°C
and 15-20 MPa.

m- M cat. R-
M cat.
t =R q
oxidant "OH

+ co
NuOH
H

CONu
+ R F C O N U

H
M cat.
oxidant
I
C02R'
* I3'OH

/\/COzR'
R

Scheme 1. Hydrocarboxylations and related reactions.

 2.1.2.6 Other Curbonylutions 183

Table 1. Comparison of hydrocarboxylations with different catalyst systems.

R- CO R'OH Rm C O 2 R ' (1)

Catalyst C O ~ ( C O ) ~Ni(C0)4 PdX2L2 PtX,LZ + SnX2 RhX3

Temperature ("C) 150-200 200-320 70-120 80-100 100-130
Pressure (bar) 130-200 150-300 1-150 1-200 1-100

Platinum catalysts are superior concerning the regioselectivity of ester forma-

tion, especially with tin compounds as co-catalysts. However, the rates remain
quite low even under high pressure.
Two possible mechanisms have been envisaged for the hydrocarboxylation of
olefins to monocarboxylic acid derivatives (Scheme 2), one involving olefin
insertion into a metal hydride followed by CO insertion, and the other starting
with a metal alkoxycarbonyl complex [3]. It is commonly assumed for cobalt- cat-
alyzed carbonylations that C O ~ ( C Oreacts
) ~ with adventitious hydrogen or with an
alcohol to form the actual catalytically active intermediate HCO(CO)~. After repla-
cement of CO by the olefin, which could occur by either an associative or a
dissociative mechanism, olefin insertion into the Co-H bond takes place. Sub-
sequent coordination and insertion of CO into the metal-alkyl bond leads to a
labile acyl complex. Finally, hydrolysis of the acyl complex with water or alcohol
gives the corresponding carboxylic acid derivative and completes the catalytic
cycle. Presumably the acyl cleavage takes place by a nucleophilic attack on the
carbonyl carbon of the acyl group [4].

HCO(CO), RCH2CH2CO-Co(C0)4

RCH&H&O&H3 CH3OH

Scheme 2. Mechanism of cobalt-catalyzed alkoxycarbonylation of alkenes.

184 2.1 Carbon Monoxide and Synthesis Gas Chemistry

I
L2Pd(CI)CH2CHRC02R LzPdCI(0R)
t I

Scheme 3. Palladium-catalyzed alkoxycarbonylation of olefins.

Support for the involvement of HPdC1(PPh3)2as the active species in palla-

dium-catalyzed hydroesterifications comes from the isolation of trans-Pd-
(COPr)C1(PPh3)2 from propene hydroformylation [ 5 ] , while Pd(CO)(PPh,), is
inactive as a catalyst in the absence of HC1 [6]. In the case of PdX2L2/SnX2
catalyst systems olefins seem to be the hydrogen source for the formation of
the active Pd-H species [7].
Under neutral or basic conditions with palladium catalysts, another mechanism
involving a carbalkoxy complex may operate (Scheme 3) [3]. It is proposed that
reaction of an alcohol with a Pd" species forms a labile alkoxy complex. Coordi-
nation and insertion of CO into the Pd-0 bond yields the carbalkoxy complex.
Insertion of an olefin into the Pd-C02R bond gives an alkyl complex which reacts
with HX to yield predominantly the branched carboxylic acid as product, and to
regenerate the Pd".
In hydrocarboxylations, as in the 0x0 process, selectivity of linear versus
branched products is an important issue, because (in general) mixtures of isomeric
carboxylic acids are obtained, owing not only the occurrence of both Markovni-
kov and anti-Markovnikov addition of the alkene to the metal hydride, but also to
metal-catalyzed alkene isomerization (eq. (2)). In the case of higher olefins,
C O ~ ( C Oas
) ~catalyst leads to a number of different carboxylic acid isomers due
to the isomerization activity of the catalyst.

+ CO + H20 145 "C, 180 bar* AC02H

COZ(C0)8 17 %
(2)
 2.1.2.6 Other Carbonylations 185

In the presence of 3-8 mol equiv. of pyridine as ligand (compared with Co) the
phenomenon of ligand-accelerated catalysis [ 81 is observed with higher activity
and improved selectivity of the catalyst system [9]. The cobaltcarbonyl/ pyridine
catalyst system is applied industrially for the synthesis of higher alkanoic acids,
e.g., the hydrocarboxylation of isomers of undecene yields dodecanoic acid
with approximately 80 % selectivity [ 101.
As mentioned earlier, palladium, rhodium, and platinum catalysts lead to supe-
rior regioselectivities because they work under milder reaction conditions
(20-80 "C, 0.1-1 MPa CO) [ 111, e.g., bimetallic catalysts based on tin(I1) chloride
and either platinum or palladium complexes afford linear esters in up to 98 %
selectivity [ 121. In addition, catalyst systems with preference for branched isomers
are known. A recent example employed palladium acetate immobilized on
montmorillonite in the presence of triphenylphosphine and an acid promoter for
the hydroesterification of aryl olefins (eq. (3)). The reaction is totally regiospecific
for the branched isomer of aromatic olefins, while aliphatic olefins afford
branched chain esters only regioselectively with d i = 1: 3 [ 131.

R+ + CO + CH3OH - "'(
M cat.

COpCH3
+ R*C02CH3
(3)

R = C5Hll; M = Pt[P(OPh)3]2C12,SnCI2 <2:98

R = Ph; M = Pd-clay, HCI, PPh3 100 : 0

R = C8H1,; M = Pd-clay, HCI, PPh3 72 : 2a

R = CO2CH3; M = PdC12(PPh3)2 >97:3

R = COzCH3; M = PdC12(DIOP) 40 : 60

The regioselectivity of hydroesterification of alkyl acrylates or aromatic olefins

catalyzed by [PdCI,L,] complexes (L = phosphine ligand) could be largely
controlled by variation of the ligands. Triphenylphosphine promotes preferential
carboxylation to the branched isomer, whereas with bidentate bisphosphines the
linear product is produced overwhelmingly [ 141.
In combination with the incremental advances concerning reaction conditions
in recent years, especially for low-pressure carbonylations, there is a trend toward
increasing use of this chemistry to synthesize advanced building blocks. In this
respect carboxylation of alkenes with an appropriate alcohol or amine function
leads to the formation of lactones or lactams. Thus, cobalt, rhodium, or palladium
chloridekopper chloride catalysts convert ally1 and homoallyl alcohols or amines
to the corresponding butyrolactones or butyrolactams, respectively [ 151.
Moreover, hydrocarboxylation reactions have been expanded to include func-
tionalized olefins as substrates, leading to arylpropionic acids [ 161, fluorinated
acids [17], silylated esters [18], and b-amino acids [19] as products (Structures
1-6).
While progress in controlling the regiochemistry of hydrocarboxylations has
been made, stereoselective carboxylations which are of interest for intermediates
186 2.1 Carbon Monoxide and Synthesis Gas Chemistry

"Lo
O 1
y-~actones"~]
R

t2 2 0
6-lactones" 51
Me0
d C
/

3
0
/ 2

arylpropionic acids['6]
R

C02R SiMe3 SiMe3

L C 0 2 R
RF4C02RP-4 A
RF a-4 a-5
RAC02R R P-5
a-or p-perfluorinated acids["] a-or p-silyl esters[l81

NHR'

p-arnino

for pharmaceuticals and agrochemicals are still underdeveloped. Valuable repre-

sentatives of higher-value acids are the commercially important 2-arylpropionic
acids. Despite reasonable research efforts which led to progress in this area
[16], better catalyst systems which fulfill technical needs have yet to be devel-
oped. Best optical yields so far were reported by Alper et al., who claim enantios-
electivities of 84% with a turnover number (TON) of 7-8 for the synthesis of
ibuprofen with PdC12/CuC12as catalysts and 1,l '-binaphthyl-2,2'-diyl hydrogen
phosphate (BNPPA) as ligand in mixtures of hydrochloric acid and tetrahy-
drofuran [20]. The same reaction conditions have been applied to the asymmetric
cyclocarbonylation of 2-butenol- 1 to yield 1-methylbutyrolactone [2 11. Best
enantioselectivities up to 61 % (49 % yield) afforded poly-l-leucine as ligand.
As an example of the trend toward using homogeneous catalysts to assemble
complex organic intermediates as building blocks via sequential insertions,
Sisak, Ungvary, and Mark6 developed an efficient one-pot hydroesterification-
Michael addition [22]. Thus, hydroalkoxycarbonylation of acrylonitrile with
alcohols proceeds in the presence of catalytic amounts of C O ~ ( C Oand) ~ pyridine
bases to yield 2,4-dicyano-2-methylbutanoic acid esters.

2.1.2.6.2 Hydrocarboxylation of Butadiene

Butadiene is a very inexpensive and attractive molecule for the industrial chemist.
Several products can be made from butadiene and carbon monoxide under specific
conditions. Subtle effects control the outcome of palladium-catalyzed carboxyla-
tion of conjugated dienes such as butadiene. Depending on the reaction condi-
tions, monocarboxylate, dicarboxylate, or telomerized products could be obtained
(Scheme 4, cf. Section 2.3.5).
 2.1.2.6 Other Carbonylations 187

-C02H
pelargonic acid

Scheme 4. Hydrocarboxylations of butadiene.

Telomerization of butadiene occurs in the presence of methanol and CO using

halide-free Pd as catalyst to give telomerization product 3,s-nonadienoate ester
[23]. Hydrogenation of the telomerization product provides pelargonic acid in
good yield. Halide ions seem to inhibit dimerization because they occupy the
coordination site on palladium and thus block the coordination of a second
diene group required for the dimerization. Thus, palladium acetate solubilized
by tert-amines gives the best yield of dimerization products [24]. In contrast,
oxidative carbonylation of butadiene in methanol catalyzed by PdC1, gives di-
methyl-2-butene- 1,4-dicarboxylate [25],while palladium chloride under nonoxi-
dative conditions catalyzes the hydrocarboxylation to yield primarily 3-penteno-
ates [26]. Likewise, the palladium-catalyzed hydrocarboxylation of substituted
1,3-dienes affords unsaturated mono acids in the presence of phosphine ligands
and formic acid [27].
A most important application of butadiene carbonylations is BASF's devel-
opment of a three-stage process for the synthesis of adipic acid from the buta-
diene-containing C4 cut [ 11 (eqs. (4) and (5)). Cobalt is the catalyst metal of choice
for this process. The reaction takes place in two steps; the first stage, which
involves a lower temperature (100-140 "C), uses a fairly high concentration of
HCO(CO)~ and pyridine as catalyst system to ensure rapid carbonylation of buta-
diene to give methyl pent-3-enoate in 90 % selectivity, thus avoiding typical side
reactions such as dimerization and oligomerization.

300-1000 bar 90-95 %

-C02CH3 + CO + CH3OH HCo(C0)4, PY, 7 C O 2 C H 3 (5)

150-170 "C CO2CH3
150-200 bar
80 %
188 2.1 Carbon Monoxide and Synthesis Gas Chemistry

In the second step, the concentration of pyridine as ligand must be low because
it has an inhibitory effect on the hydroalkoxycarbonylation. In situ isomerization
to the 4-pentenoic acid ester is a prerequisite for the subsequent carbonylation
which provides dimethyl adipate. To ensure internal double-bond rearrangement,
the temperature of the reaction is increased to 160-200°C to give dimethyl adi-
pate with 80% selectivity. After hydrolysis of the ester, adipic acid is obtained
with an overall selectivity of about 70% [l]. So far, this process has been
performed on pilot-plant scale.

2.1.2.6.3 Dicarboxylations and Other Oxidative

Carbonylations of Olefins
Dicarboxylation of alkenes to 1,2-dicarboxylic acid derivatives takes place under
mild conditions (It; 0.3 MPa, 25 "C) in alcohol with stoichiometric amounts of
metal complexes.
Palladium chemistry dominates this area and the main problems are related to
the way of reoxidizing Pdo efficiently. In general the reaction could be made
catalytic in palladium by the use of an additional oxidant capable of reoxidizing
the Pd" to Pd". Typically, stoichiometric copper chloride, or catalytic amounts
of copper chloride in the presence of air, have been used [28]. Other catalyst
systems which have been described for bisalkoxycarbonylation of olefins to suc-
cinate derivatives are PdC12 and butyl nitrite [29], Pd(OAch, O2 and benzoqui-
) ~ di-t-butyl peroxide [3 I]. So far, low TONS have de-
none [30], and P d ( a ~ a c and
layed industrial applications. Because the reoxidation process is generating water,
which causes side reactions, it is also necessary to add a water scavenger such as
triethyl orthoformate in order to obtain good conversions and selectivities.
The first stereoselective version of this reaction was developed by Consiglio
and co-workers [32], who described the bisalkoxycarbonylation of styrene
using chiral PdL2X2 complexes and benzoquinone with enantioselectivities up
to 93 % in the presence of chiral biphenylphosphines, although the chemoselectiv-
ity of the reaction was lower (eq. (6)).
C02CH3

0". CO + CH30H
PdL2X2
50 "C
benzoquinone,

50-350 bar
@co2cH3 (6)

Reminiscent of the succinate formation are intramolecular dialkoxycarbonyla-

tions [33], e.g., of 3-butenols [34], and 4-pentenols [35] leading to the cor-
responding lactones.
Depending on the oxidative reaction conditions, besides dicarboxylated
products, unsaturated carboxylic acid derivatives or in the case of hydroesteri-
fication P-alkoxy esters could be formed [32]. Thus, linear 1-alkenes afford in
principle P-alkoxy esters under neutral oxidative conditions, but under more
basic conditions, e.g., sodium butyrate buffer, 1,2-diesters predominate [36].
 2.1.2.6 Other Carbonylations 189

Considerable interest in industry has been paid to the oxidative carbonylation of

styrene as a promising method for producing cinnamic acid derivatives (eq. (7)).
As catalyst systems, ordinary Pd complexes in the presence of Cu salts as well as
other metals as co-catalysts have been used [37].

A detailed study of the most active catalyst system, consisting of PdC12,CuC12,

Cu(OAc),, and M ~ ( O A C )showed
~, that the introduction of Mn(OAch as additive
substantially increased the activity [38].

2.1.2.6.4 Carbonylation of Alkanes

An interesting but rather unusual reaction involves the direct carbonylation
of carbocations to carboxylic acid derivatives. Carbenium ions can be generated
from alkenes or alkanes in strong acidic media. Thus, tertiary carboxylic acids
can be produced from C4 or higher alkenes (Koch-Haaf reaction) [39]
(e.g., eq. (8)). Interestingly, Koch carbonylations are known to be catalyzed by
copper or silver cations [40].

Since the early 1960s, superacids have been known to react with saturated
hydrocarbons to yield carbocations, even at low temperature [41]. This discovery
initiated extensive studies devoted to electrophilic reactions and conversions of sat-
urated hydrocarbons. Thus, the use of superacidic activation of alkanes to their
related carbocations allowed the preparation of alkanecarboxylic acids from al-
kanes themselves with CO. In this respect, Yoneda et al. have found that alkanes
can be directly carboxylated with CO in an HF-SbF5 superacid system [42]. Ter-
tiary carbenium ions formed by protolysis of C-H bonds of branched alkanes in
HF-SbFS undergo skeletal isomerization and disproportionation prior to reacting
with CO in the same acid system to form carboxylic acids after hydrolysis (eq. (9)).

SbFS, CO*
HF, 30°C \ O I ( V X C 0 2 C H 3
(9)

When using tertiary C5 or C6 alkanes, considerable amounts of secondary car-

boxylic acids are produced by the reaction of CO with secondary alkylcarbenium
ions. Such cations are formed as transient intermediates by skeletal isomerization
of the initially formed tertiary cations (eq. (10)) [43].

-1.R+,CO_ - RH
2. H20 VXc02H
190 2.1 Carbon Monoxide and Synthesis Gas Chemistry

Besides carbonylation of cations, C-H activation and subsequent carbonylation

of aromatic and aliphatic groups via organometallic complexes have experienced
growing interest in the scientific community. In 1982 Janowicz and Bergman re-
ported the first well-characterized example of oxidative addition of an unactivated
alkane to a homogeneous permethylcyclopentadienyl-iridium complex [44].
With respect to carbonylation chemistry Sakakura and Tanaka have shown that
irridiation of rhodium complex RhCl(CO)(PMe3)2in pentane as solvent under a
CO atmosphere (1 bar) at ambient temperature gives rise to carbonylated products.
Selectivity for linear aldehyde is > 98 % (eq. (11)) [45]. This insertion reaction is
photochemically driven, since it is known that aldehyde decarbonylation is a ther-
modynamically favorable process. Other photochemial C-H activation reactions
have been investigated [46]. When toluene is reacted in the presence of CO
and the same Rh complex, phenyl acetaldehyde is obtained as the major product
(eq. (12)) WI.
-CHO
RhCI(CO)(PMe&
w CO, hv
* +
I

Direct C-H activation of hydrocarbon by means of transition metals has also

been explored. Cyclohexane reacted with Pd(OAc), in the presence of potassium
persulfate-trifluoroacetic acid under CO pressure and produced the desired cyclo-
hexanecarboxylic acid in low yields and TON (eq. (1 3)). The electrophilic carbox-
ylation is explained by the change of Pd(OAc), to Pd(OCOCF3), in trifluoroacetic
acid as solvent. Electrophilic attack on a C-H bond should give an alkyl Pd"
complex. CO insertion followed by reductive elimination affords a reactive
mixed anhydride which was detected before workup.

In a similar example, propane was reacted with CO in the presence of a Pd" and
Cu" mixture, and was found to give low yields of isobutyric acid and n-butyric
acid. The yield is much lower when only one of the metals is used [48,49]. More-
over, C-H activation on aromatic aldehydes can take place in the presence of
PdC12- and secondary amines to give a-ketoamides [50].
An impressive example of functionalizing aromatics was presented by Moore
and co-workers. Thus, pyridine can be regioselectively acylated with carbon
monoxide and olefins (eq. (14)). In the presence of a rhodium carbonyl cluster,
first-order rate dependence on the Ru3(CO)1 2 concentration led to the belief that
the cluster framework remains intact during the course of the acylation reaction.
 2.1.2.6 Other Curbonylutions 191

Turnover frequencies of ca. 160h and 65 % yields were obtained in this reaction
with 1-hexene as the olefin [51].

13:l

2.1.2.6.5 Radical Carbonylations

The role of free-radical intermediates in one-electron reactions has been studied
over many decades and characterized in a large number of chemical transforma-
tions. It has only been since the mid-1980s that interest in free- radical reactions
has increased in the context of functionalization of organic molecules. The incor-
poration of CO in organic molecules via free-radical reactions was another clever
method for the formation of lactones, acids, and aldehydes starting from alkanes
(Scheme 5 ) .
As a mechanistically interesting example the reaction of an unsaturated di-
methyl malonate derivative with Mn(OAc), resulted in the formation of sub-
stituted cyclopentanes. The primary radical can either be trapped by CO or cyclize
to an unstable radical intermediate, which in turn reacts with CO. Because the
trapping of the first-generated radical is reversible, the cyclized acyl intermediate
gives the desired product after oxidation [52].

dE% AnLE2%dE
Mn2+ + H+

- co co

I
H + + Mn2+

H20 + Mn3+

co
Scheme 5. Radical carbonylations to give cyclopentanes. E is, for example, -COOR.
192 2.1 Carbon Monoxide and Synthesis Gas Chemistry

Scheme 6. Remote carbonylation of alcohols.

Concerning the coupling of CO with an unactivated hydrocarbon, the

synthesis of lactones from saturated alcohols and CO is unique. It involves
the generation of an oxygen-centered radical from n-octanol by Pb(OAc),,
a well-established one-electron oxidant. Abstraction of a hydrogen atom
gives a more stable carbon-centered radical which in turn reacts with CO
to give an acyl radical. Finally, oxidation of the acyl radical gives an acyl
cation which cyclizes to give the desired lactone in 51 % yield (Scheme 6)
[53]. This type of remote carbonylation was proven very recently to be
quite general.
Another type of free-radical reaction was explored starting from a long-chain
alkyl iodide for the synthesis of a macrolactone (eq. (15)). The reaction utilized
(Me3Si),SiH as a hydrogen transfer agent [54, 551. 2,2’-Azoisobutyronitrile
(AIBN) was used as a radical initiator. Furthermore, a CO pressure of 30 bar
was required for the alkyl radical to trap CO. The resultant acyl radical reacted
with the activated double bond to give desired product.

(Me3Si)3SiH
q0-fp1iiixx
0 CO, 30 bar
- (Me3Si)3S~I

70 Yo
 References 193

References
[ I ] (a) W. Bertleff, Ullmann’s Encycl. lnd. Chem. 5th ed., VCH, Weinheim 1986, Vol. AS,
p. 217; (b) J. Falbe (Ed.), New Syntheses with Carbon Monoxide, Springer, Berlin, 1980.
[2] Reviews: (a) M. Beller, B. Cornils, C. D. Frohning, C. W. Kohlpainter, J. Mol. Catal.
1995, 104, 17; (b) H. M. Colquhoun, D. J. Thompson, M. V. Twigg, Carbonylation,
Direct Synthesis of Carbonyl Compounds, Plenum Press, New York, 1991;
(c) R. F. Heck, Palladium Reagents in Organic Syntheses, Academic Press, New
York, 1985; (d) M. Roper, Stud. Su@ Sci. Catal. 1991, 64, 381.
[3] Review: D. Milstein, Acc. Chem. Res. 1988, 21, 428.
[4] R. W. Johnson, R. G. Pearson, Inorg. Chem. 1971, 10, 2091.
[ 5 ] R. Bardi, A. del Pra, A. M. Piazzesi, L. Toniolo, Inorg. Chim. Acta 1979, 35, L345.
[6] F. Morandini, G. Consiglio, F. Wenzinger, Helv. Chim. Acta 1979, 62, 59.
171 T. Chenal, R. Naigre, I. Cipres, P. Kalck, J.-C. Daran, J. Vaissermann, J. Chem. SOC.,
Chem. Commun. 1993, 747.
[8] D. J. Bemsford, C. Bolm, K. B. Sharpless, Angew. Chem., Int. Ed. Engl. 1995, 34,
1059.
[9] B. Fell, Methoden Org. Chem. (Houben-Weyl)4th ed. 1986, Vol. E18, p. 779.
[lo] P. Hofmann, K. Kosswig, W. Schafer, Ind. Eng. Chem., Prod. Res. Dev. 1980, 19, 330.
[ I l l (a) T. Chenal, I. Cipres, J. Jenck, P. Kalck, Y. Peres, J. Mol. Catal. 1993, 78, 351; (b) L.
Garlaschelli, M. Marchionna, M. C. Iapalucci, G. Longoni, J. Organomet. Chem. 1989,
378, 457; (c) M. Miekuz, F. Joo, H. Alper, Organometallics 1987, 6, 1591; (d) G.
Cavinato, L. Toniolo, C. Botteghi, J. Mol. Catal. 1985, 32, 211; (e) H. Alper, J. B.
Woell, B. Despeyroux, D. J. H. Smith, J. Chem. Soc., Chem. Commun. 1983, 1270;
(f) G. Consiglio, L. Kollar, R. Kolliker, J. Orgunomet. Chem. 1990, 396, 375.
[I21 (a) J. F. Knifton, J. Org. Chem. 1976, 41, 793; (b) J. F. Knifton, J. Org. Chem. 1976, 41,
2885.
[13] C. W. Lee, H. Alper, J. Org. Chem. 1995, 60, 250.
[14] G. Consiglio, S. C. A. Nefkens, C. Pisano, F. Wenzinger, Helv. Chim. Acta 1991, 74,323.
[15] Review: J. K. Stille in Comprehensive Organic Synthesis, Vol. 4, B. M. Trost, I. Fleming
(Eds.), Vol. 4, Pergamon Press, Oxford, 1991, p. 913.
[16] (a) G. Chelucci, M. A. Cabras, C. Botteghi, M. Marchetti, Tetrahedron Asymm. 1994,
5, 299; (b) G. Consiglio, L. Roncetti, Chirality 1991, 3, 341; (c) T. Hiyama,
N. Wakasa, T. Kusumoto, Synlett 1991, 569.
[ 171 Review: C. Botteghi, G. D. Ponte, M. Marchetti, S. Paganelli, J. Mol. Catal. 1994, 93, 1.
[I81 (a) R. Takeuchi, N. Ishii, M. Sugiura, N. Sato, J. Org. Chem. 1992, 57, 4189; (b)
M. M. Doyle, W. R. Jackson, P. Perlmutter, Tetrahedron Lett. 1989, 30, 233.
[19] G. M. Wieber, L. S. Hegedus, B. Akermark, E. T. Michalson, J. Org. Chem. 1989, 54,
4649.
[20] H. Alper, N. Hamel, J. Am. Chem. Soc. 1990, 112, 2803.
[21] H. Alper, N. Hamel, J. Chem. Soc., Chem. Cornmun. 1990, 1356.
[22] A. Sisak, F. Ungvary, L. Marko, J. Org. Chem. 1990, 55, 2508.
[23] D. Neibecker, B. Stitou, I. Tkatcher, J. Org. Chem. 1989, 54, 2459.
[24] J. F. Knifton, J. Catal. 1979, 60, 27.
[25] Idemitsu Petrochemical Co. (M. Kanzawa, T. Ishibashi, T. Kumazawa) JP 03.255.054
(199 1); Chem. Abstr: 1992, 116, I5 I I64w.
[26] S. Hosaka, J. Tsuji, Tetrahedron 1971, 27, 3821.
[27] G. Vasapollo, A. Somasunderam, B. El Ali, H. Alper, Tetrahedron Lett. 1994, 34, 6203.
[28] D. E. James, J. K. Stille, J. Am. Chem. Soc. 1976, 98, 1810.
[29] P. Brechot, Y. Chauvin, D. Commereux, L. Saussine, Organometallics, 1990, 9, 26.
[30] Shell AG (E. Drent), EP 00.231.044 (1986); Chem. Ahstr 1988, 108, 166984.
194 2. I Carbon Monoxide and Synthesis Gas Chemistry

[31] G. E. Morris, D. Oakley, D. A. Pippard, D. J. H. Smith, J. Chem. SOC.,Chem. Commun.

1987, 4 10.
1321 S . C. A. Nefkens, M. Sperrle, G. Consiglio, Angew. Chem. 1993, 105. 1837.
[33] M. F. Semmelhack, C. Kim, N. Zhang, C. Bodurow, M. Sanner, W. Dobler, M. Meier,
Pure Appl. Chem. 1990, 62, 2035.
[34] (a) Y. Tamam, M. Hojo, Z. Yoshida, Tetrahedron Lett. 1987, 28, 325; (b) S. Toda,
M. Miyamoto, H. Kinoshita, K. Inomata, Bull. Chem. SOC.Jpn. 1991, 64, 3600.
[35] M. F. Semmelhack, C. Bodurow, J. Am. Chem. SOC.1984, 106, 1496.
[36] J. K. Stille, R. Divakaruni, J. Org. Chem. 1979, 44, 3474.
[37] G. Cometti, G. P. Chiusoli, J. Organomet. Chem. 1979, 181, C14.
[38] A. R. El’Man, 0. V. Boldyreva, E. V. Slivinskii, S. M. Loktev, Izv. Akad. Nauk, Ser:
Khim. 1992, 3, 552.
[39] (a) G. A. Olah, J. A. Olah, Friedel-Crafts and Related Reactions, Vol. 3, Part 2, Wiley-
Interscience, New York, 1964, p. 1972; (b) H. Bahrmann, Koch Reactions, in New
Syntheses with Carbon Monoxide, J. Falbe (Ed.), Springer, Berlin, 1980, p. 372.
[40] Y. Souma, H. Sano, Bull. Chem. SOC. Jpn. 1974, 47, 1717.
[41] (a) G. A. Olah, Angew. Chem., Znt. Ed. Engl. 1973, 12, 173; (b) G. A. Olah,
G. K. Prakash, J. Sommer, Superacids, Wiley-Interscience, New York, 1985;
(c) G. A. Olah, J. Sommer, La Recherche, 1979, 10, 624.
1421 N. Yoneda, H. Sato, T. Fukuhara, A. Suzuki, Chem. Lett. 1983. 19.
[43] N. Yoneda, T. Fukuhara, A. Suzuki, Bull. Chem. SOC.Jpn. 1986, 59, 2819.
[44] A. H. Janowicz, R. G. Bergman, J. Am. Chem. Soc. 1982, 104, 352.
[45] T. Sakakura, M. Tanaka, J. Chem. SOC.,Chem. Commun. 1987, 758.
[46] (a) A. J. Kunin and R. Eisenberg, Organometallics 1988, 7, 2124; (b) T. Sakakura,
K. Sasaki, Y. Tokunaga, M. Tanaka, Chem. Lett. 1988, 155.
[47] M. Tanaka, T. Sakakura, H. Wada and Y. Sasaki, Jpn Kokai, Tokyo Koho JP 01.249,
1989, p. 741; Chem. Abstr: 1990, 12, 98197.
1481 K. Nakata. T. Miyata, T. Jintoku, A. Kitani, Y. Taniguchi, K. Takaki, Y. Fujiwara, Bull.
Chem. SOC.Jpn. 1993, 66, 3755.
[49] Reviews: (a) C. C. Hill, New J. Chem. 1989, 13 (10-1 1); (b) R. H. Crabtree, Chem. Rev.
1985, 85, 245.
[50] F. Ozawa, I. Yamagami, M. Nakano, F. Fujisawa, A. Yamamoto, Chem. Lett. 1989, 125.
[Sl] E. J. Moore, W. R. Pretzer, T. J. O’Connel, J. Hams, L. Labounty, L. Chou, S. Grimmer,
J. Am. Chem. SOC.1992, 114, 5888.
[52] I. Ryu, H. Alper, J. Am. Chem. SOC.1993, 115, 7543.
[53] S . Tsunoi, I. Ryu, N. Sonoda, J. Am. Chem. SOC. 1994, 116, 5473.
[54] I. Ryu, K. Nagahara, H. Yamazaki, S. Tsunoi, N. Sonoda, Synlett 1994, 643.
[55] I. Ryu, N. Sonoda, Angew. Chem. Int. Ed., 1996, 35, 1050.
 Applied Homogeneous Catalysis with Organometallic
Edited by Boy Cornils & Wolfgang A. Herrmann
© Wiley-VCH Verlag GmbH, 2002

2.2.1.2 Classical Transition Metal Hydrides 195

2.2 Hydrogenation
Henri Brunner

2.2.1 Homogeneous Hydrogenation

2.2.1.1 The Hydrogen Molecule

In the hydrogen molecule, the two hydrogen atoms are connected by a strong
covalent bond, which has a bond dissociation energy of 103 kcaVmol [I]. The
molecular orbital (MO) scheme of the H, molecule is one of the simplest possible.
It is characterized by a strongly bonding MO which contains the two electrons of
the covalent bond, and the corresponding antibonding MO which is empty. In the
bonding MO, the electron density is concentrated between the two hydrogen
atoms (see Figure 1, below). The orientation of the two empty lobes of the anti-
bonding MO of the H2 molecule (see Figure 1) was actually of only little interest
before the advent of the nonclassical q2-H2 complexes.
The hydrogen molecule readily undergoes radical chain reactions, e. g., with
oxygen or chlorine. Other reactions, such as hydrogenation of unsaturated sub-
strates, are usually slow and require high temperatures and/or the use of catalysts.
These catalysts may be heterogeneous or homogeneous. In heterogeneous systems
the hydrogen molecule is activated on the surface of the catalysts, whereas in
homogeneous catalysts activation occurs by different mechanisms. All of them
include the uptake of hydrogen as a ligand in specific complexes. The present
review focuses on the homogeneous activation of hydrogen.

2.2.1.2 Classical Transition Metal Hydrides

Until recently, it was assumed that hydrogen can be present as a ligand in co-
ordination compounds only in the form of classical hydride ligands. Prominent
examples are the compounds HMn(CO)s [2], H2Fe(CO), [3], and HCO(CO)~[4],
which are prepared by acidification of the corresponding carbonyl metallates [5].
Carbonyl hydrides may be weak to strong acids. Thus, the first dissociation step of
H,Fe(CO), has a pK, value of 5 [6], whilst HCO(CO)~is a strong acid, fully
dissociated in water [6]. However, not all of the transition metal hydrides are
acids. Thus, ($-CSH&ReH [7] is a weak base due to the lone electron pairs avail-
able on the metal atom. It has a pK, value of 5 [8].
In low-temperature X-ray analysis and in neutron diffraction studies the struc-
ture of solid HMn(CO)S was elucidated [9]. The arrangement of the ligands around
the Mn atom is octahedral with the four equatorial carbonyl groups somewhat bent
toward the axial hydrogen atom. This proves that hydrogen is a small but stereo-
chemically active ligand, a fact which had been questioned previously [ 101.
Among the classical hydride complexes there are not only monohydrides and
dihydrides, but also polyhydrides. Well-known trihydrides are ($-CsHs),NbH3
196 2.2 Hydrogenation

[ I l l and ($-CSHS),TaH3 [12]. They contain three M-H bonds in the opening
formed by the bent $-C5HS rings [13].
The family of transition metal phosphine hydrides contributes a variety of ex-
amples of polyhydrides, e. g., ReHS(PR3),,ReH7(PR3),,MoH4(PR& WH6(PR3)3,
R u H ~ ( P R ~OsH4(PR&.
)~, Some of these phosphine hydndes had to be reformu-
lated after the discovery of the nonclassical q2-H2complexes [14] (vide infra).
Nine hydride ligands are bound to one metal atom in the ion [ReHgI2-,which is
synthesized by reduction of Re04- with sodium in ethanol [15]. It has the structure
of a trigonal prism capped by another three hydrogen ligands on the three rec-
tangular faces.
In 1962 it was discovered that the Vaska complex, the square planar trans-
IrCl(CO)(PPh,), reacts with molecular hydrogen to give the dihydride IrH2C1-
(CO)(PPh,), [16]. This reaction occurs under mild conditions and it is reversible
(eq. (1)). The reaction from left to right in eq. (1) is called an oxidative addition in
which both the coordination number and the oxidation number of the metal atom
are increased by two, e.g., the square planar I? complex is converted into an
octahedral Ir"' dihydride. The reverse reaction is a reductive elimination. In the
mechanistic understanding of catalytic hydrogenation reactions, oxidative
addition and reductive elimination processes became most important elementary
steps.
H

CI

In 1965 the compound RhC1(PPh3)3, coined the "Wilkinson catalyst", was

shown to be an excellent hydrogenation catalyst [ 17-19]. Although there had
been scattered reports on hydrogenation catalysts before [20], it was this discovery
which started a worldwide activity in the field of hydrogenation reactions (vide
infra).

2.2.1.3 Nonclassical Dihydrogen Complexes

It was a scientific sensation when Kubas in 1984 found the nonclassical co-
ordination mode of molecular hydrogen in transition metal complexes [ 1, 2 11.
His starting materials were the complexes Mo(CO),(PPr',), and W(CO)3(PP?3)2
which contain the bulky phosphine ligand trisisopropylphosphine. To attain
noble gas configuration at the metal atom, agostic M-CH interactions form
between the metal atoms and one of the isopropyl substituents. These complexes
react with molecular hydrogen to give what are now called nonclassical v2-H2
complexes. In these reactions the agostic CH groups are displaced by the hydro-
gen molecule and the complexes Mo(CO),(PPr',),(H,) and W(CO)3(PPr'3)2(H2)
are obtained [21].
 2.2.1.3 Nonclassical Dihydrogen Complexes 197

The structure of W(CO),(PP?,),(H,) has been established by a variety of meth-

ods, including a neutron diffraction study. The hydrogen molecule is present as a
ligand with the H-H axis collinear to the P-M-P vector (eq. (2)).

The complex W(CO),(PPr',),(H,) is a true a-complex, because its H, ligand is

bound by way of the electron pair forming the H-H bond. Consequently, it is the
midpoint of the H2 ligand which occupies one of the octahedral coor{ination sites
at the tungsten atom. The H-H distance in the complex is 0.82 A. It is only
slightly longer than the H-H distance in the hydrogen molecule with 0.74 A,
whereas for a classical dihydride an H-H distance of about 1.8 A would be
expected.
The nonclassical dihydrogen complex W(CO),(PPr',),(H,) is in a slow and
reversible equilibrium with the classical dihydride complex W(CO),(PPr',),(H),
(eq. (2)) which is seven-coordinate and stereochemically nonrigid. The activation
energy for this oxidative addition is 16 kcaVmol [ l , 22-24].
After the advent of the nonclassical q2-H2complexes, polyhydrides had to be
reinterpreted [ 141. Thus, RuH4(PPh3), is not a classical tetrahydride of coordina-
tion number seven at the ruthenium atom but a dihydride-dihydrogen complex
Ru(H,)(H),(PPh,), of octahedral geometry [25].
The number of recognized q2-H2 complexes increased rapidly [ 11. Interest-
ingly, however, there are also q2-H2 complexes with elongated H-H bonds
[24]. An example is ReH7[P(p-tolyl),I2, for which a distance of 1.35 A for
one of the H-H pairs has been documented [26]. Such a stretched a-complex
truly is an intermediate between a classical dihydride and a nonclassical q2-H2
complex.
In a-complexes of the hydrogen molecule the pK, value of the q2-H2ligand is
dramatically increased compared with free H2 [24]. Whereas in free H2 the pK, is
35, the pK, values of o-complexes are in the range 10 to -2 [27, 281, facilitating
the heteiolytic cleavage of the H2 ligand to form a metal hydride and a proton
1241.
~ The metal-dihydrogen bonding is similar to the Dewar-Chatt-Duncanson
model for metal-olefin bonding [29-311. There is a donor bond from the electron
pair in the bonding orbital of the H2 ligand into an empty metal orbital (Figure 1,
left-hand side).
In addition, there is n-back-bonding in which electron density is delocalized
from a filled metal d-orbital into the empty antibonding orbital of the H2 system
(Figure 1, right-hand side). The donor bond is supposed to be more important than
the back-donation. According to this model an increase in the electron density at
the metal center strengthens the metal to ligand back-bond, inducing cleavage of
the H-H bond in the sense of an oxidative addition [l].
198 2.2 Hydrogenation

Figure 1. Metal-dihydrogen bonding in r2-H2 complexes. Donor bond from the filled
bonding orbital of the H2 ligand into an empty metal orbital (left-hand side);
n-back-donation from a filled metal d-orbital into the empty antibonding
orbital of the H2 ligand (right-hand side).

Hydrogen complexes form by reaction of transition metal compounds with

molecular hydrogen or by protonation. The hydrogen in a transition metal
complex may be bonded in the classical or nonclassical way. The complexes
may interconvert, may be deprotonated, or may lose molecular hydrogen, gener-
ating vacant coordination sites. Thus, the picture of transition metal hydrogen
complexes to-day is one of considerable complexity [1, 20, 24, 32, 331.

2.2.1.4 Homogeneous Hydrogenation of Organic Substrates

Hydrogenation reactions of unsaturated organic compounds are clean reactions.
Frequently, they proceed quantitatively without formation of side products and
there is no waste except the trace amount of catalyst. Thus, in terms of ecology
and atom economy [34], they are ideal reactions.
There are standard techniques to hydrogenate unsaturated organic substrates
with heterogeneous transition metal catalysts such as Raney nickel, palladium
on carbon, platinum on alumina, etc. [35-39, 891. The scope of this methodology
is well known. It is easy to separate the product from the heterogeneous catalyst,
which may be re-used. In homogeneous catalysis it is difficult to separate product
and catalyst. Therefore, to hydrogenate a normal organic substrate with a homo-
geneous catalyst only pays if there are other advantages, e.g., with respect to
selectivity.
Hydrogenations with the Wilkinson catalyst RhC1(PPh3)3 are operationally
simple. They are usually carried out at ambient temperatures. In many cases a
blanket of hydrogen (1 bar or 0.1 MPa) is sufficient and no hydrogen pressure
is necessary. Solvents are usually methanol, ethanol, acetone, THF or benzene
[20]. Chloroform and carbon tetrachloride should be avoided because they may
undergo WCl exchange [40].
As far as olefinic double bonds are concerned, there is a clear trend along the
series of compound types shown in Figure 2 [20].
Terminal olefins are easily hydrogenated. Their hydrogenation is much faster
than the hydrogenation of double bonds in cyclic systems or internal double
bonds. cis-Olefins are hydrogenated faster than trans-olefins. Conjugated diole-
 2.2.1.4 Homogeneous Hydrogenation of Organic Substrates 199

R\ /H R\ R\ /R
c=c: > ,C=C, >
H H R/ H H H

R\ /R R\ /R
,C=C, > /C =C\
H R R H R R

Figure 2. Reactivity sequence of different types of olefins toward hydrogenation with the
Wilkinson catalyst RhCl(PPh&

fins react more slowly than terminal olefins. Generally, the higher the degree of
substitution at the double bond, the lower the reactivity toward hydrogenation
with Wilkinson-type catalysts. Carbonyl compounds are not compatible with
Wilkinson-type catalysts. Aldehydes are decarbonylated during hydrogenation
reactions [41] and the hydrogenation of ketones is slow compared with olefins.
Functional groups, such as arene, carboxylic acid, ester, amide, nitrile, ether,
chloro, hydroxy, and even nitro groups, are tolerated during hydrogenations
with Wilkinson-type catalysts. These reactivity differences can be utilized for
selective reactions in the synthesis of natural products containing a variety of
unsaturated functionalities. Another advantage of Wilkinson-type hydrogenation
catalysts is their stability toward sulfur compounds which tend to poison hetero-
geneous catalysts [42].
The catalyst RuHCI(PPh3)3is extremely fast in the hydrogenation of terminal
olefins and suitable for the reduction of dienes and trienes to monoenes [20].
However, systems with RuHCI(PPh& are usually very air-sensitive and there is
extensive isomerization and hydrogen exchange. For the selective hydrogenation
of conjugated dienes to monoenes the (arene)Cr(C0)3 family is a promising cat-
alytic system [36, 431.
The catalyst [COH(CN),]~~ is soluble in water. It is selective for the reduction of
olefinic double bonds in a$-unsaturated systems. Reduction of NO2 groups only
occurs at elevated pressures. Hydrogenolysis of C-Hal bonds is observed [20].
Progress as far as water-soluble hydrogenation catalysts is concerned has also
been made with Wilkinson-type catalysts by using phosphine ligands with sulfo-
nic acid substituents [44].
In cluster catalysis there is always the possibility that the cluster breaks down
and fragments or monomers are the actual catalysts. O S ~ H ~ ( C O[45] ) , ~ in the
hydrogenation of alkenes, and R U ~ H ~ ( C O[46] ) ~ * and its phosphine derivatives
in the hydrogenation of alkynes, alkenes, and even ketones, seem to catalyze as
clusters. The dimer R ~ , ( O A C )[47]
~ is an active hydrogenation calatyst for
alkenes.
The hydrogenation of alkynes with homogeneous transition metal catalysts
proceeds by &-addition to give the corresponding alkenes, which subsequently
are reduced to the alkanes. A selective reduction from the alkyne to alkene
stage requires a careful control of the reaction conditions and choice of the catalyst
and its ancillary ligands [20]. A side reaction is the polymerization of the alkyne.
200 2.2 Hydrogenation

As alkynes usually bond strongly to transition metals, the number of suitable

catalysts for selective alkyne hydrogenation is limited.
The hydrogenation of arenes with heterogeneous transition metal catalysts is
no problem. However, there are only a few homogeneous systems capable of
hydrogenating arenes under ambient conditions [48]. In this context, it should
be recalled that aryl substituents are tolerated in the hydrogenation of alkenes
with Wilkinson-type catalysts. An example of a homogeneous catalyst which
hydrogenates benzene is the allylcobalt(1) system (v3-C3H5)CoL3,where L = ter-
tiary phosphine and phosphite [49, SO]. As no competing hydrogen exchange
takes place and neither cyclohexadiene nor cyclohexene can be detected during
the hydrogenation of benzene, mechanisms were discussed in which the
substrate remains attached to the metal atom until the ultimate hydrogenation
product (cyclohexane) is eliminated. Nitrogen-containing heterocycles, such as
pyridine and quinoline derivatives, can be hydrogenated with the catalysts
[($-CSMe,)Rh(acetonitrile)3]2+ [ S I] and [Rh(cod)(PPh,)J (cod = 1,S-cycloocta-
diene) [ S 2 ] , Benzene is selectively hydrogenated to cyclohexene with bis(hexa-
methylbenzene)ruthenium(O) [53]. For a new technical process to hydrogenate
benzene to cyclohexane with Ziegler-type catalysts, see Section 2.2.1.10.

2.2.1.5 Enantioselective Hydrogenation

of Prochiral Substrates
The limited success of heterogeneous catalysts in enantioselective reactions is
due to the fact that on the surface of a heterogeneous catalyst there are many
different catalytically active centers. Each of these centers has its own selectiv-
ity and the total selectivity is usually low. It is different for a homogeneous cat-
alyst. In the ideal case a homogeneous catalyst consists of a single catalytically
active species which can be tailored by ligand variation and adjusted to the
problem to be solved. In fact, there are only two heterogeneous catalysts
which reliably give high enantioselectivities of 90% ee or above: the Raney
nickel system modified with tartaric acid and sodium bromide in the hydro-
genation of B-keto esters [S4], and the platinum-on-charcoal or platinum-on-alu-
mina system modified with cinchona alkaloids in the hydrogenation of a-keto
esters [55, 561.
Heterogenization of a homogeneous catalyst is an approach to combining the
advantages of heterogeneous and homogeneous catalysis (cf. Section 3.1.1.3).
A homogeneous catalyst is bonded to a surface such as silica or a resin directly
or via a spacer. In such a heterogenized system the catalytically active species
resembles its homogeneous counterpart in solution, whereas the catalyst can be
separated from the product by filtration similarly to a truly heterogeneous system.
Nevertheless, heterogenized catalysts have drawbacks compared with homo-
geneous catalysts, e. g., reduced reaction rates and selectivities as well as leaching
of the catalytically active species, mostly a noble metal compound, from the
support. Thus, homogeneous catalysis remains the domain of stereoselectivity,
 2.2.1.5 Enantioselective Hydrogenation of Prochiral Substrates 201

in particular enantioselectivity, and the story of homogeneous hydrogenation is

actually the story of enantioselective hydrogenation.
In the pioneering studies of Horner et al. [57] and Knowles and Sabacky [58],
chirally modified Wilkinson catalysts were introduced in the homogeneous
enantioselective hydrogenation of prochiral olefins. To this end, in Wilkinson-
type catalysts the triphenylphosphine ligand was replaced by the optically active
phosphine ligands (+)-PMePr"Ph and (-)-PMePr'Ph, chiral at the phosphorus
atom.
In these 1968 papers, the substrates to be hydrogenated were a-ethylstyrene,
a-methoxystyrene, a-phenylacrylic acid, itaconic acid, etc. The hydrogenation
of dehydroamino acid derivatives entered the literature with the papers of
Kagan and co-workers [59, 601 and Knowles et al. [61]. Actually, the hydrogena-
tion of (2)-a-acetamidocinnamic acid to give N-acetylphenylalanine (eq. (3))
became the most frequently studied test system for the evaluation of new catalysts.

(3)
H2

L D
acetylphenylalanine

In the 1970s and early 1980s the development of new catalysts was mainly
based on new optically active chelating phosphines used in Wilkinson-type cata-
lysts. This era of design and synthesis of optically active bidentate phosphines
started in 1971 with Kagan's tartaric acid derived ligand DIOP [59, 601. Success-
ful and well-known examples followed, namely DIPAMP [62], prophos [63],
chiraphos [64], BPPM [65], BPPFA [66], norphos [67], and BINAP [68]. A selec-
tion is depicted in Figure 3.
Up to the mid- 1980s the field of enantioselective hydrogenation had been
dominated by the Rh-based Wilkinson-type catalysts. Then, Noyori et al. intro-
duced a new family of Ru-based catalysts, which showed a wider applicability
than the Rh catalysts. a$-Unsaturated acids other than dehydroamino acids
became substrates which could be hydrogenated with high enantioselectivity
[69]. In these reactions, catalysts of the type [Ru(BINAP)(OAC)~],[Ru2-
(BINAP),Cl,NEt,] and ((arene)Ru(BINAP)I] I were used (cf. Sections 2.9 and
3.3.1). These catalysts also proved effective in the enantioselective hydrogenation
of carbonyl compounds, and specifically in the hydrogenation of p-keto esters
1701.
- -
In the enantioselective hydrogenation of p-keto esters optically active 3-hydro-
xyalkanoic esters, important compounds in the synthesis of natural products, are
202 2.2 Hydrogenation

DlOP

chiraphos prophos

p(c6H5)2
BPPM norphos

BPPFA

Figure 3. Representative optically active chelating phosphines used in enantioselective

hydrogenation reactions.

formed. Until recently, heterogeneous catalysts of the Raney nickel/tartaric acid/

NaBr type were used for this reduction, the enantioselectivities being around
90 % ee [54]. Recently, however, homogeneous isolated Ru-(BINAP) catalysts
took over, with enantioselectivities approaching 100 % ee [70].
Enantioselective hydrogenation of prochiral carbonyl compounds with Wilkin-
son-type catalysts is less successful than the hydrogenation of prochiral olefins.
Both rates and enantioselectivities are greatly diminished in the hydrogenation
of ketones, compared with olefins. Enantioselectivities only occasionally reach
80 % ee, e. g., in the hydrogenation of acetophenone with the in-situ catalyst
[Rh(nbd)CI],/DIOP, where nbd = norbornadiene [7I]. The Ru-based BINAP
catalysts improved this situation, by allowing the hydrogenation of a variety of
functionalized ketones in enantioselectivities close to 100 % ee [72].
 2.2.1.6 Isolated Catalysts Versus in-situ Catalysts 203

An interesting recent extension of the palette of substrates was the enantioselec-

tive hydrogenation of hydrazones [73]. Subsequent cleavage of the N-N bond
permitted conversion of prochiral ketones via their hydrazones into optically
active primary amines. Wilkinson-type catalysts containing the new optically
active ligand DUPHOS proved especially efficient [74]. Another recent
approach is the hydrogenation of C = N systems with chiral titanocene catalysts.
With these catalysts it is possible to hydrogenate imines [75, 761, enamines
[77], and olefins [78] with high enantioselectivities.

2.2.1.6 Isolated Catalysts Versus in-situ Catalysts

Usually, a catalyst has to be synthesized or conditioned prior to its use in a
catalytic reaction. However, there is an alternative to such an isolated or pre-
formed catalyst, the so-called in-situ catalyst. The in-situ catalyst is prepared
by mixing the transition metal compound (the procatalyst) and the ligand (the
cocatalyst) in the solvent in which the reaction is to be carried out [79]. The
use of in-situ catalysts is most appropriate in enantioselective hydrogenation
reactions with Wilkinson-type catalysts. The optically active phosphines needed
for optical induction have to be synthesized in multi-step syntheses [80, 811. It
is most convenient to combine them directly with the Rh-containing procatalysts.
A typical in-situ catalyst for the enantioselective hydrogenation of (3-a-acet-
amidocinnamic acid is the system [Rh(cod)Cl],/DIOP (1).

1
The procatalyst [Rh(cod)C1I2 is an orange, air-stable solid which is commer-
cially available, accessible in one step from RhC13 and 1,5-~yclooctadiene[82].
The cocatalyst DIOP (Figure 3 ) , the most frequently used optically active
phosphine, is also commercially available. A survey of the literature shows that
more than half of the numerous studies on the hydrogenation of (3-a-acetamido-
cinnamic acid have been carried out with in-situ catalysts [79, 811.
Commonly applied procatalysts are chloroolefin complexes of rhodium, in
which the olefin is 1,5-~yclooctadiene(cod), norbornadiene (nbd), 1,5-hexadiene,
cyclooctene, or ethylene, e. g., [Rh(cod)C1I2, [Rh(nbd)Cl],, and [Rh(C2H4)2C1]2.
They give rise to so-called “neutral catalysts,” whereas complexes such as
[Rh(nbd)*]X and [Rh(cod),]X (X = BF,, PF6, C104, etc.) are examples of so-called
“cationic catalysts.”
Procatalyst and cocatalyst combine in solution to give the actual catalyst, a
procedure most suitable for routine application. There are no synthetic steps
necessary to prepare the catalyst prior to the catalytic reaction to be performed.
204 2.2 Hydrogenation

Thus, in-situ catalysts can be conveniently prepared within minutes before a

reaction is carried out. Normally, there is no decrease in selectivity compared
with isolated catalysts. Moreover, contrary to the case of an isolated catalyst,
the metal-to-ligand ratio may be varied in an in-situ catalyst. Usually, a 10%
phosphine excess is used in Wilkinson-type in-situ catalysts [79]. This small
ligand excess compensates for partial ligand oxidation by traces of air in the
hydrogenation system. Furthermore, it ensures that all the metal atoms present
will be coordinated, avoiding an achiral reaction channel which would be open
if the metal component were in excess. For mechanistic studies in-situ catalysts
are inappropriate; for this purpose well-defined catalysts are required.

2.2.1.7 Transfer Hydrogenation

In the large-scale production processes of the chemical industry the use of gaseous
hydrogen is operationally simple and advantageous. Application of molecular
hydrogen in a research laboratory requires the availability of high-pressure
equipment and is considered to be expeditious and time-consuming. In addition,
in small-scale experiments under conditions changing from run to run there is
always the danger of an explosion of hydrogedair mixtures. Therefore, hydro-
genation procedures have been developed which avoid gaseous hydrogen and
allow the use of standard reflux techniques. In these transfer hydrogenation
reactions, manifold hydrogen donors can be used. Well-known hydrogen sources
are primary and secondary alcohols, e. g., isopropanol, benzyl alcohol, and 1-phe-
nylethanol, which are converted into the corresponding aldehydes and ketones, or
formic acid, which is converted into COz. A convenient hydrogen source is the
5 :2 azeotrope of formic acid and triethylamine, which is commercially available.
Also, carbon monoxide in combination with water, giving carbon dioxide and
hydrogen, can be used as a source of molecular hydrogen in the so-called
“water-gas shift reaction” [48, 831 (cf. Section 3.2.11).
A example, typically enantioselective, is the transfer hydrogenation of itaconic
acid, which is reduced to methylsuccinic acid with the formic acid/triethylamine
azeotrope (Scheme 1).
Successful in-situ catalysts for this transfer hydrogenation used BPPM
(Figure 3) as a cocatalyst together with either [Rh(cod)C1I2, Rh,(OAc), or
RhC13 as a procatalyst [84]. The enantioselectivities matched those of the hydro-
genation with molecular hydrogen. Replacing triethylamine by (S)- l-phenylethyl-
amine, the stereoselectivity (>97 % ee) was even better [85].

2.2.1.8 Hydrogenolysis
The term “hydrogenolysis” is used to describe the cleavage of a bond by the
reaction with molecular hydrogen. Although used for bonds such as transition
metal alkyls, the term mainly refers to organic substrates. A well-known reaction
of this type is the cleavage of heteroatom-benzylic bonds. This debenzylation,
 2.2.1.9 Mechanisms 205

NR3 [Rh(cod)CI]2 Rhp(OAc)4 RhC13

NEt3 84.9 92.2 82.2 o/o ee
ph2p&PPh2
I (R)-PhMeCHNH2 74.6 87.0 80.1 Oh ee
(S)-PhMeCHNH2 90.5 98.7 99.5 % ee
o”c, 0-t-BU

Scheme 1. Transfer hydrogenation of itaconic acid to give methylsuccinic acid with the
formic acid/amine system using different rhodium-containing procatalysts and the
cocatalyst BPPM.

usually catalyzed by heterogeneous palladium catalysts, is part of a well-estab-

lished protecting group technique, used in the removal of benzylic substituents
in carbohydrate chemistry. It is easier to remove allyl groups with transition
metal catalysts. A homogeneous variant using Pd(PPh&, has recently been applied
to remove protecting allyl substituents in DNA synthesis using an n-butylaminel
formic acid hydrogenation system [86].

2.2.1.9 Mechanisms
The addition of hydrogen to olefinic or acetylenic bonds is symmetry-forbidden
[87, 881. However, the participation of a catalyst subdivides the addition of
H2 to an unsaturated system into a series of successive steps which do not suffer
from these symmetry restrictions. These successive steps are oxidative addition of
hydrogen, insertion of the coordinated unsaturated system into a metal-hydrogen
bond, and reductive elimination of the hydrogenation product. Irrespective of the
individual mechanism there is overwhelming evidence from D2 addition
experiments that the catalytic addition of H2 to carbon-carbon double and triple
bonds is a cis-addition [20].
In heterogeneous catalysis, there are many methods of investigating the
processes occuring on the surface of the catalysts. However, the results obtained
are usually difficult to interpret [89]. Therefore, the elucidation of reaction me-
chanisms in heterogeneous catalysis continues to be a problem. Homogeneous
catalysis mostly takes place in solution and normally only a limited number of
catalytically active species are involved. These species are directly susceptible
to investigation by well-established spectroscopic and kinetic measurements.
Nevertheless, many of the mechanisms in homogeneous catalysis are only partly
known or still unknown. This is different for the hydrogenation reactions, particu-
larly as far as Wilkinson-type catalysts are concerned, which have been intensely
206 2.2 Hydrogenation

studied since the 1970s [90]. Thus, many of the mechanisms operating in hydro-
genation reactions are well understood. The famous mechanism of the enantio-
selective hydrogenation of dehydroamino acids and their esters is an important
example.
The species starting the catalytic cycle of the hydrogenation of dehydroamino
acid derivatives is a square planar Rh’ complex containing a chelating phosphine
P*P, such as chiraphos, and two solvent molecules S, e. g., methanol, ethanol, or
acetone. This species reacts with the substrate, methyl (2)-a-acetamidocinnamate
(Scheme 2, line 1). The substrate displaces the solvent molecules, giving the
square planar species in line 2 of Scheme 2. The substrate acts as a bidentate
ligand bonded via the olefinic double bond and the oxygen atom of the acetyl
group.
The two square planar species of line 2 are diastereomers. They contain the
same optically active chelating phosphine chiraphos, but the rhodium atom is
coordinated to different sides of the prochiral olefin (rehi sides). The two diaster-
eomers of line 2 are rapidly interconverting. In this equilibrium the isomer shown
on the left-hand side (si-coordination of the olefin) is the minor isomer and the
isomer shown on the right-hand side (re-coordination of the olefin) is the major
isomer [91, 921.
The next step is the oxidative addition of hydrogen, converting the square
planar diastereomers of line 2 into the octahedral dihydrides of line 3 [93].
In the present system this reaction is the rate-determining step. The fast step
following is the insertion of the coordinated olefin into one of the Rh-H
bonds, giving rise to the two diastereomeric a-alkyl complexes of line 4. By
reductive elimination they generate the enantiomeric forms of the product,
regenerating the catalytically active square planar species, which reenters the
catalytic cycle.
Assuming intramolecular hydrogen transfer via cis-addition within the catalyst,
the minor diastereomer (left-hand side) of the preequilibrium in line 2 of Scheme 2
will give rise to the (R) product (bottom left), whereas the major diastereomer
(right-hand side) will lead to the (S) product (bottom right). Experiment shows
that the (R) product predominates by more than 95 % ee [64]. Thus, it must be
concluded that the final product is not formed from the major diastereomer dom-
inating the equilibrium of line 2 by more than 95 %, but from the minor diaster-
eomer present in the equilibrium mixture to the extent of less than 5 % according
to NMR measurements. This is only possible if the rates of reaction of the two
diastereomers with hydrogen in the rate-determining step are strikingly different.
Obviously the reactivity of the minor diastereomer is so much higher than that of
the major diastereomer that it overrides the inverse influence of their disparing
equilibrium concentrations. Thus, the minor isomer becomes product-determining
~901.
This celebrated mechanism follows what is called the “unsaturated route”. This
means that in the catalytic cycle the substrate is bonded first, before the oxidative
addition of hydrogen occurs. However, this order may be reversed. If the oxidative
addition of hydrogen precedes the coordination of the olefin, the reaction is said to
occur by the “hydride route”. Actually, the hydride route is the mechanism of the
 2.2.1.9 Mechanisms 207

line

1 HZ 1 HZ

H J

I - [Rh(P
0
P)Sz]+
0
- [Rh(P P)SJ

Scheme 2. Mechanism of the hydrogenation of methyl (3-a-acetamidocinnamate

with Wilkinson-type catalysts.
208 2.2 Hydrogenation

hydrogenation of cyclohexene in benzene at 25 “C with the Wilkinson catalyst

(Scheme 3) [94, 951.
By dissociation of a triphenylphosphine ligand from the Wilkinson catalyst,
the 14e species RhC1(PPh3)*of coordination number 3, which is the catalytically
active species in the catalytic cycle, is formed (Scheme 3). It reacts with mole-
cular hydrogen in an oxidative addition. Afterwards cyclohexene is coordinated
to give the species containing the activated hydrogen and the coordinated olefin.
In this system, the insertion of the olefin into one of the rhodium hydrogen
bonds is the rate-determining step. The resulting c-alkyl-hydride species elimi-
nates the product cyclohexane and regenerates the 14e species RhC1(PPh3)>
(Scheme 3).
The mechanisms of the hydrogenation of cyclohexene and dehydroamino acid
derivatives differ by a couple of key features. In addition to the different routes
(“hydride” versus “unsaturated”), there are differences in the stereochemistry of
the catalytically active species. In the hydrogenation of dehydroamino acid
derivatives, the optically active chelating phosphines, e. g., chiraphos, bind to
cis positions (Scheme 2), whereas the two monodentate triphenylphosphine
ligands in the cyclohexene hydrogenation occupy trans positions within the
catalyst (Scheme 3). Furthermore, the rate-determining step in the cyclohexene
hydrogenation is no longer the oxidative addition of hydrogen as in the dehydro-

/c=c
\

Scheme 3. Mechanism of the hydrogenation of cyclohexene with the Wilkinson catalyst

RhCI(PPh3)1.
 2.2.1.10 Industrial Applications 209

amino acid hydrogenation, but the insertion of the coordinated olefin into the
Rh-H bond to give the a-alkyl complex. Thus, a hydrogenation mechanism
cannot be transferred from one unfunctionalized olefin to another. Going from
cyclohexene to styrene, different species are observed during catalytic hydro-
genation. In the styrene system there are species which contain two olefins bonded
to one Rh atom [96] not present in the cyclohexene system. Thus, depending on
the ligands within the catalyst, the substrates, and even factors such as solvent or
hydrogen pressure, etc., there are characteristic changes in the mechanism
observed.

2.2.1.10 Industrial Applications

Millions of tons of benzene are hydrogenated each year to give cyclohexane,
which is converted to nylon via adipic acid. Whereas this process has been carried
out with heterogeneous Raney nickel catalysts until now, a homogeneous process
using Ziegler-type catalysts is about to take over. Catalysts based on nickel and
cobalt salts in combination with triethylaluminum hydrogenate benzene under
relatively mild conditions (1 55 O C , 1 MPa). This process is called the IFP process
(Institut Franpis du Petrole) [97] (cf. Section 2.3.1.4).
In the early 1970s, the Monsanto amino acid process was the first to use
homogeneous transition metal-catalyzed hydrogenation on an industrial scale.
In this process L-dopa, a drug needed in quantities of ca. 200 tons a year
[98] for the treatment of Parkinson's disease, is formed by enantioselective
hydrogenation of the corresponding dehydroamino acids [99-10 I]. In this
hydrogenation a Wilkinson-type Rh catalyst containing the ligand DIPAMP
(Figure 3) is used which gives L-dopa in 94% ee [loll. A similar process
was established by VEB Isis-Chemie based on a glucose-derived phosphine
ligand, but this was later abandoned (cf. Introduction, Section 1 [102]). Another
enantioselective commercial hydrogenation of a dehydroamino acid is the Eni-
chem process for the synthesis of (S)-phenylalanine, needed for the sweetener
aspartame [99].
A variety of important drugs contain the chiral substituent 2-propanoic acid,
e.g., naproxen, for which the patent has now expired. Using the methodology
of enantioselective hydrogenation, the corresponding a-substituted acrylic acids
give high optical inductions [69]. However, in most cases the tedious synthesis
of the acrylic acid precursor is the obstacle to industrial application (cf. Sections
2.9 and 3.3.1).
Hydrogenation reactions are involved in other technically important processes
for which there are homogeneous and heterogeneous variants: hydroformylation
of olefins with CO,(CO)~/HCO(CO)~ as a constituent part and a side reaction
(see Section 2.1.1) ; hydrogenation of unsaturated fats obtained from soybean,
linseed, and cotton seed [20] ; liquefaction of coal (arene hydrogenation) [20] ;
hydrogenation of butadiene rubbers [ 1031; and hydrodesulfurization of crude
oil to remove sulfur from thiophene and other sulfur-containing compounds by
hydrogenolysis [ 1041.
2 10 2.2 Hydrogenation

2.2.2 Commercial Enantioselective Hydrogenation

Since the commercial applications of enantiomer-selective hydrogenations are at
only the beginning of their career, the state-of-the-art, industrial realizations and
most recent development work are complied in Section 3.3.1 (H.-U. Blaser,
B. Pugin, F. Spindler).

References
[ l ] G. J. Kubas, Ace. Chem. Res. 1988, 21, 120.
[2] A. Davidson, J. W. Faller, Inorg. Chem. 1967, 6, 845.
131 L. Vancea, W. A. G. Graham, J. Organomet. Chem. 1977, 134, 219.
[4] H. W. Sternberg, I. Wender, M. Orchin, Inorg. Synth. 1957, 5, 192.
151 H. Sternberg, I. Wender, M. Orchin, Inorg. Synth. 1957, 5, 192.
[6] W. Hieber, W. Hiibel, Z. Elektrochem. 1953, 57, 235.
[7] R. B. King, Organomet. Synth. Vol. I , Academic Press, New York, 1965, p. 80.
[8] M. L. H. Green, L. Pratt, G. Wilkinson, J. Chem. Soc. 1958, 3916.
[9] S. J. La Placa, W. C. Hamilton, J. A. Ibers, A. Davidson, Inorg. Chem. 1969, 8, 1928.
[lo] J. A. Ibers, Annu. Rev. Phys. Chem. 1965, 16, 375.
[ I l l J. A. Labinger, K. S. Wong, J. Organomet. Chem. 1979, 170, 373.
[12] M. L. H. Green, J. A. McCleverty, L. Pratt, G. Wilkinson, J. Chem. Soc. 1961, 4854.
1131 R. D. Wilson, T. F. Koetzle, D. W. Hart, A. Kvick, D. L. Tipton, R. Bau, J. Am. Chem.
Soc. 1977, 99, 1775.
[14] Zhenyang Lin, M. B. Hall, Inorg. Chem. 1992, 31, 4262.
[15] A. P. Ginsberg, C. R. Sprinkle, Inorg. Chem. 1969, 8, 2212.
[I61 L. Vaska, J. W. Diluzio, J. Am. Chem. Soc. 1963, 84, 679.
1171 J. F. Young, J. A. Osborn, F. H. Jardine, G. Wilkinson, Chem. Commun. 1965, 131.
[18] D. Evans, J. A. Osborn, F. H. Jardine, G. Wilkinson, Nature (London) 1965, 208, 1203.
[19] J. A. Osborn, F. H. Jardine, J. F. Young, G. Wilkinson, J. Chem. Soc. (A) 1966, 1711.
[20] B. R. James in Comprehensive Organometallic Chemistry (Eds.: G. Wilkinson, F. G. A.
Stone, E. W. Abel), Pergamon, Oxford, 1982.
[21] G. J. Kubas, R. R. Ryan, B. I. Swanson, P. J. Vergamini, H. J. Wasserman, J. Am. Chem.
Soc. 1984, 106, 451.
[22] G. J. Kubas, C. J. Unkefer, B. I. Swanson, E. Fukushima, J. Am. Chem. Soc. 1986, 108,
7000.
[23] G. J. Kubas, R. R. Ryan, D. Wroblewski, J. Am. Chem. Soc. 1986, 108, 1339.
[24] R. H. Crabtree, Angew. Chem. 1993, 105, 828; Angew. Chem., Int. Ed. Engl. 1993,
32, 789.
[25] R. H. Crabtree, D. G. Hamilton, J. Am. Chem. SOC.1986, 108, 3124.
[26] L. Brammer, J. A. K. Howard, 0. Johnson, T. F. Koetzle, J. L. Spencer, A. M. Stringer,
J. Chem. Soc., Chern. Cornmun. 1991, 241.
[27] M. S. Chinn, D. M. Heinekey, J. Am. Chem. SOC.1987, 109, 5865.
[28] G. Jia, R. H. Moms, Inorg. Chem. 1990, 29, 581.
[29] P. J. Hay, Chem. Phys. Lett. 1984, 103, 466.
[30] J.-Y. Saillard, R. Hoffmann, J. Am. Chem. Soc. 1984, 106, 2006.
[31] H. Rabaa, J.-Y. Saillard, R. Hoffmann, J. Am. Chem. SOC. 1986, 106, 4327.
[32] R. H. Crabtree, Ace. Chem. Res. 1990, 23, 95.
[33] R. P. Jessop, R. H. Morris, Coord. Chem. Rev. 1992, 121, 155.
[34] M. Trost, Angew. Chem. 1995, 107, 285; Angew. Chem., Int. Ed. Engl. 1995, 34, 259.
 References 2 11

13.51 F. J. McQuillin, Homogeneous Hydrogenation in Organic Chemistry (Ed.: R. Ugo)

Vol. 1, D. Reidel, Dordrecht, Holland, 1968.
[36] B. R. James, Homogeneous Hydrogenation, John Wiley, New York, 1973.
[37] M. Freifelder, Catalytic Hydrogenation in Organic Synthesis, John Wiley, New York,
1978.
[38] P. N. Rylander, Catalytic Hydrogenation in Organic Syntheses, Academic Press, New
York, 1979.
[39] P. N. Rylander, Hydrogenation Methods, Academic Press, London, 1985.
1401 H. D. Kaesz, R. B. Saillant, Chem. Rev. 1972, 72, 231.
[41] K. Ohno, J. Tsuji, J. Am. Chem. Soc. 1968, 90, 99.
[42] [36], p. 228.
[43] M. Cais, Chim. Ind. (Milan) 1979, 61, 395.
[44] W. A. Herrmann, C. W. Kohlpaintner, Angew. Chem. 1993, 105, 1588; Angew. Chem.,
Int. Ed. Engl. 1993, 32, 1524.
[45] J. B. Keister, J. R. Shapley, J. Am. Chem. SOC.1976, 98, 1956.
[46] M. P. Lausarot, G. A. Vaglio, M. Vallee, Inorg. Chim. Acta 1979, 36, 213.
1471 B. C. Y. Hui, W. K. Teo, G. L. Rempel, Inorg. Chem. 1973, 12, 757.
[48] B. R. James, Adv. Organomet. Chem. 1979, 17, 319.
[49] L. S. Stuhl, M. Rakowski Du Bois, F. J. Hirsekorn, J. R. Bleeke, A. E. Stevens,
E. L. Muetterties, J. Am. Chem. SOC. 1978, 100, 2405.
[SO] E. L. Muetterties, Acc. Chem. Res. 1979, 12, 324.
[51] R. H. Fish, E. Baralt, S. J. Smith, Organometallics 1991, 10, 54.
1521 R. A. Sanchez-Delgado, D. Rondbn, A. Andriollo, V. Herrera, G. Martin, B. Chaudret,
Organometallics 1993, 12, 429 1.
1531 J. W. Johnson, E. L. Muetterties, J. Am. Chem. SOC.1977, 99, 7395.
[54] Y. Izumi, Adv. Catal. 1983, 82, 215.
[SS]H. U. Blaser, Chem. Rev. 1992, 92, 935.
1.561 H. U. Blaser, Tetrahedron: Asymmetry 1991, 2, 843.
1571 L. Horner, H. Siegel, H. Biithe, Angew. Chem. 1968, 80, 1034; Angew. Chem., Znt. Ed.
Engl. 1968, 7, 942.
[58] W. S. Knowles, M. J. Sabacky, Chem. Commun. 1968, 481.
[59] T. P. Dang, H. B. Kagan, Chem. Commun. 1971, 481.
[60] H. B. Kagan, T. P. Dang, J. Am. Chem. Soc. 1972, 94, 6429.
[61] W. S. Knowles, M. J. Sabacky, B. D. Vineyard, J. Chem. Soc., Chem. Commun. 1972, 10.
[62] W. S. Knowles, M. J. Sabacky, B. D. Vineyard, D. J. Weinkauff, J. Am. Chem. Soc. 1975,
97, 2567.
[63] M. D. Fryzuk, B. Bosnich, J. Am. Chem. Soc. 1977, 99, 6262.
[64] M. D. Fryzuk, B. Bosnich, J. Am. Chem. SOC.1978, 100, 5491.
[65] K. Achiwa, J. Am. Chem. Soc. 1976, 98, 8265.
[66] T. Hayashi, K. Yamamoto, M. Kumada, Tetrahedron Lett. 1974, 4405.
[67] H. Brunner, W. Pieronczyk, Angew. Chem. 1979,91, 655; Angew. Chem., Int. Ed. Engl.
1979, 18, 620.
[68] H. Takaya, K. Mashima, K. Koyano, M. Yagi, H. Kumobayashi, T. Taketomi,
S. Akutagawa, R. Noyori, J. Org. Chem. 1986, 51, 629.
[69] T. Ohta, H. Takaya, M. Kitamura, K. Nagai, R. Noyori, J. Org. Chem. 1987, 52, 3174.
[70] R. Noyori, T. Ohkuma, M. Kitamura, H. Takaya, N. Sayo, H. Kumobayashi,
S. Akutagawa, J. Am. Chem. SOC.1987, 109, 5856.
[71] S. Toriis, B. Heil, L. KollBr, L. Marko, J. Organomet. Chem. 1980, 197, 85.
[72] M. Kitamura, T. Ohkuma, S. Inoue, N. Sayo, H. Kumobayashi, S. Akutagawa, T. Ohta,
H. Takaya, R. Noyori, J. Am. Chem. Soc. 1988, 110, 629.
[73] J. M. Burk, J. Feaster, J. Am. Chem. Soc. 1992, 114, 6266.
2 12 2.2 Hydrogenation

[74] J. M. Burk, J. Am. Chem. SOC.1991, 113, 8518.

[75] C. A. Willoughby, S. L. Buchwald, J. Am. Chem. Soc. 1992, 114, 7562.
[76] A. Viso, N. E. Lee, S. L. Buchwald, J. Am. Chem. Soc. 1994, 116, 9373.
[77] N. E. Lee, S. L. Buchwald, J. Am. Chem. Soc. 1994, 116, 5985.
[78] R. D. Broene, S. L. Buchwald, J. Am. Chem. SOC. 1993, 115, 12569.
[79] H. Brunner, W. Zettlmeier in Advances in Catalytic Processes, Vol. 1 (Ed.: M. P. Doyle),
Jay Press, Greenwich, CT, 1995, p. 1.
[80] H. B. Kagan in Asymmetric Synthesis, Vol. 5 (Ed.: J. D. Morrison), Academic Press,
Orlando, FL, 1985, p. 1 .
[811 H. Brunner, W. Zettlmeier, Handbook of Enantioselective catalysis, VCH, Weinheim,
1993.
[82] G. Giordano, R. H. Crabtree, Inorg. Synth. 1979, 19, 218.
[83] C. Masters, Adv. Organomet. Chem. 1979, 17, 61.
[84] H. Brunner, W. Leitner, Angew. Chem. 1988, 100, 1231 ; Angew. Chem., Int. Ed. Engl.
1988, 27, 1180.
[ 8 5 ] H. Brunner, E. Graf, W. Leitner, K. Wutz, Synthesis, 1989, 743.
[86] R. Noyori, M. Uchiyama, H. Kato, S. Wakabayashi, Y. Hayakawa, Pure Appl. Chem.
1990, 62, 613.
[87] R. G. Pearson, Acc. Chem. Res., 1871, 4, 152.
[88] R. G. Pearson, Trans. Am. Crystallogr: Assoc. 1978, 14, 89.
[89] G. Ertl, H. Knozinger, J. Weitkamp (Eds.), Handbook of Heterogeneous Catalysis,
VCH, Weinheim, 1997.
[90] J. Halpern in Asymmetric Synthesis, Vol. 5 (Ed.: J. D. Momson), Academic Press,
Orlando, FL, 1985, p. 41.
[91] A. S. C. Chan, J. J. Pluth, J. Halpern, J. Am. Chem. Soc. 1980, 102, 5952.
[92] P. S. Chua, N. K. Robert, B. Bosnich, S. J. Okrasinski, J. Halpern, J. Chem. Soc., Chem.
Commun. 1980, 344.
[93] A. S . C. Chan, J. Halpern, J. Am. Chem. Soc. 1980, 102, 838.
[94] J. Halpern in Organotransition Metal Chemistry (Eds.: Y. Ishida, M. Tsutsui), Plenum
Press, New York, 1975, p. 109.
[95] J. Halpern, T. Okamoto, A. Zakhariev, J. Mol. Catal. 1977, 2, 65.
[96] J. Halpern, Trans. Am. Crystallogl: Assoc. 1978, 14, 59.
[97] G. W. Parshall, S. D. Ittel, Homogeneous Catalysis, 2nd ed., John Wiley, New York,
1992, p. 180.
[98] Y. Izumi, Angew. Chem. 1971, 83, 956; Angew. Chem., Int. Ed. Engl. 1971, 10, 871.
[99] H. N. Collins, G. N. Sheldrake, J. Crosby, Chirality in Industry, Wiley, Chichester,
1992, p. 37.
[I001 [97], p. 33.
[I011 W. A. Knowles, Acc. Chem. Res. 1983, 16, 106.
[lo21 W. Vocke, R. Hanel, F.-U. Flather, CHEMTECH 1987, 39, 123.
[lo31 A. J. Birch, K. Walker, Aust. J . Chem. 1971, 24, 513.
[lo41 R. Prins, V. H. J. de Beer, G. A. Somorjai, Catal. Rev.-Sci. Eng. 1989, 31, 1.
 Applied Homogeneous Catalysis with Organometallic
Edited by Boy Cornils & Wolfgang A. Herrmann
© Wiley-VCH Verlag GmbH, 2002

2.3. I . I Chemical Background 2 13

2.3 Reactions of Unsaturated Compounds

2.3.1 Polymerization, Oligomerization, and
Copolymerization of Olefins

2.3.1.1 Chemical Background

Walter Kaminsky, Michael Arndt-Rosenau

2.3.1.1.1 Introduction
The main industrial use for organometallic catalysts - not necessarily homoge-
neous catalysis - is the polymerization and oligomerization of olefins. About
75 million tons of polyolefins are produced worldwide every year, 60% of
those with (heterogeneous) Ziegler-Natta catalysts [ 11. Polyolefins show a rapidly
growing potential because they contain only carbon and hydrogen atoms, are inert,
are stable to water, and can be easily recycled or used as a source of energy for
incineration. The classical Ziegler-Natta catalysts are heterogeneous materials
formed by titanium(II1)chloride and aluminum alkyls, or by magnesium chlor-
idekitanium tetrachloride and triethylaluminum [2,3].
Among the great number of Ziegler-Natta catalysts, homogeneous systems
have been studied preferentially in the past in order to understand the elementary
steps of polymerization [4-61. In the most recent years there have been many
rapid advances in the academic and industrial homogeneous catalysis of olefin
polymerization by metallocene, late metal and other single-site catalysts [7-91.
The homogeneous catalysts are totally different from heterogeneous systems.
Their homogeneous nature leads to lower polydispersities and more uniform
incorporation of a-olefin comonomers forming new types of polymers, different
from those obtained with Ziegler-Natta catalysts. Only soluble vanadium-based
systems have been used as catalysts for the production of elastomers for more
than 30 years.

2.3.1.1.2 Vanadium Catalysts

Homogeneous vanadium-based catalysts formed by the reaction of vanadium
compounds and reducing agents such as organoaluminum compounds [ 10-121
are used industrially for the production of elastomers by ethylene/propene
copolymerization (EP rubber) and ethylene/propene/diene terpolymerization
(EPDM rubber). The dienes are usually derivatives of cyclopentadiene such
as ethylidene norbornene or dicyclopentadiene. Examples of catalysts are Struc-
tures 1-4. Third components such as anisole or halocarbons are used to prevent
a decrease in catalyst activity with time which is observed in the simple systems.
214 2.3 Reactions of Unsaturated Compounds

/
acac / (C,H,)
o=v, I CIA1 (activator)
acac '(C*H,)
1

/ jBU

VCI,/Al - 'Bu
\
\.
'Bu
2

'B u
/
VO(OR), / Al - CI

3
' 'Bu

VOCI, / AICI,, R,
4

The oxidation state of the active vanadium species is under discussion [13];
some authors propose the trivalent V(II1) state and describe the deactivation to
occur by reduction to V"; others favor V" to be the active form. Nevertheless it
is generally assumed that the active site contains alkylvanadium halide entities
such as VC12R.Chain initiation is believed to arise from the sequence of reactions
shown in eq. (1).

In contrast to the heterogeneous catalysts which produce polymers with a broad

molecular weight distribution (Mw/Mn)of 5-30, the compounds containing vana-
dium produce polymers with a narrow Mw/Mnof 2-4.

2.3.1.1.3 Group IV Catalysts

Homogeneous catalysts for the ethylene polymerization based on bis(cyc1openta-
dienyl)titanium(IV) compounds [4], tetrabenzyltitanium [ 141, tetraallylzirconium
and hafnium are formed with diethylaluminum chloride, dimethylaluminum chlor-
ide or triethylaluminum as co-catalysts. Their activities are poor (less than 200 kg
PE/mol catalyst per h), so no industrial application resulted.
 2.3.1.1 Chemical Background 215

This situation changed when a new breed of homogeneous catalysts, based

on metallocenes and methylalumoxane (MAO) as co-catalyst, which are
10-1 00 times more active than common heterogeneous ones, found great
industrial and scientific interest [15,16]. The metallocene and the MAO, as
well as the active complex, are soluble in hydrocarbons. Using these catalysts it
became possible to tailor the microstructures of the polymers by tuning the
ligands. Table 1 reviews the efficiency of the zirconocene/methylalumoxane
catalysts.
Not only polyethylene can be synthesized, but also many kinds of copolymers
and elastomers, new structures of polypropylenes, polymers and copolymers of
cyclic olefins. In addition, polymerization can be performed in the presence of
fillers and oligomerization to optically active hydrocarbons is possible. For
recent reviews and books see [ 17-20].

Table 1. Features of metalloceneMA0 catalysts.

Process, products Remarks
~

Ethylene homopolymerization High activity, highly linear, M J M , = 2

Ethylene copolymerization Random comonomer distribution,
LLDPE comonomers: propene, higher
a-olefins, cycloolefins (COC), dienes
EPDM elastomers Low transition metal concentration in the
polymer, M J M , = 2
Propene (a-olefin) polymerization to
polymers of various microstructures
Syndiotactic polystyrene
Cycloolefin polymerization to polymers
with high melting points
Polymerization in the presence of fillers
Oligomerization of propene to optically
active hydrocarbons
Cyclopolymerization of a,w-dienes

Mechanism

Kinetic studies and the application of various analytical methods have helped
to define the nature of the active center, to explain the aging effects of Ziegler
catalysts, to establish the mechanism of interaction with olefins, and to obtain,
evidence of elementary steps [21].
216 2.3 Reactions of Unsaturated Compounds

Methylalumoxane formed by controlled reaction of trimethylaluminum with

water, under elimination of methane, is a mixture of oligomers [22]. The basic oli-
gomer (Structure 5) forms associates and cage structures complexing additional
trimethylaluminum [23,24].
Me Me Me Me
I I I I
Al Al Al
/ \ / \ / \ /Al\
Me 0 0 0 Me

Cryoscopic measurements in benzene show M A 0 to have a molecular mass

between 1000 and 1500 g/mol. Usually an excess of M A 0 is needed, covering
an AUmetallocene ratio of 50-100 for supported systems and 400-20 000 in solu-
tion. The optimum AVmetallocene ratio depends on the metallocene used and the
experimental conditions [25].
The alumoxane cocatalysts have at least two functions: alkylation of the metal-
locene component, which takes place within seconds even at -60°C (eq. (2));
and formation of the active species by abstraction of Me- (eq. (3)).The resulting
active species is discussed as being a 14e (= 14 valence electron) cationic
alkylmetallocenium ion formed by dissociation of the metallocene alumoxane
complex [26,27]. The [alumoxane-Me]- anion is regarded as weakly or non-co-
ordinating. Nearly every zirconocene atom is active, forming a single-site catalyst
[28, 291.

CPZM
\Cl
M A 0 or TMA ~

CP2M
/Me

\a
- MA0 /Me
CP2M\
Me (2)

Evolution of methane is observed simultaneously with the mixing of metallo-

cene and methylalumoxane. This is caused by the formation of species containing
Zr-CH,-Al bonds. The process is repeatable, as shown by the fact that up to
60 mol methane are formed per mol metallocene. Aluminoxane probably reac-
tivates the centers by alkyl transfer [30].
The methylalumoxane may be replaced by a mixture of trialkylaluminum as an
alkylating agent and dimethylaluminum difluoride as Lewis acid [311. Dialkyl or
dibenzyl metallocenes form active species when combined with the Lewis acidic
tris(pentafluoropheny1)borane or organic salts of the noncoordinating tetrakis
(pentafluorophenyl)borate, generating alkylmetallocenium ions [32-351. With
these co-catalysts a metalloceneko-catalysts ratio of 1: 1 is used. Usually trial-
kylaluminum is added as a scavenger to prevent decomposition by impurities of
the alkylmetallocenium ions generated in situ.
 2.3.1.1 Chemical Background 217

Polyethylene

Using bis(cyclopentadieny1)zirconium dichloride (Cp,ZrCl,; Structure 6) and

MAO, up to 40 000 000 g polyethylene/g Zr per h are obtained. Every zirconium
atom forms an active complex and produces about 46000 polymer chains per h.
The time of insertion of one ethylene unit is only 3 X s. Table 2 shows the
polymerization behavior of different metallocene/alumoxane catalysts.

Table 2. Ethylene polymerization”)with metallocene/methylaluminoxane catalysts.

Metalloceneb) Structure Activity Molecular weight
[kg PE/(mol Zr . h cmOn)] [g/mol]
CP2ZrCl2 6 60 900 62 000
[MezC(Ind)(Q)lZKlz 8 3 330 18 000
[En(IndH4),]ZrC1, 9 22 200 1 000 000
[En(Ind),]ZrCI, 11 12 000 350 000
[En(Ind),]HfCl, 12 2 900 480 000
[Me2Si(Ind)2]ZrClz 13 36 900 260 000
[Me2Si(2,4,7-Me31nd)2]ZK12 15 111 900 250 000
[Me2C(Flu)(Cp)lZrClz 18 2 000 500 000
a) Ethylene pressure = 0.25 MPa, temp. = 30 “C, [metallocene] = 6.25 X M,
metallocene/MAO = 250, solvent = toluene.
b, Cp = cyclopentadienyl; Ind = indenyl; En = C2H4; Flu = fluorenyl.

Generally zirconium catalysts are more active than the hafnium or titanium sys-
tems. Especially, substituted bisindenyl systems (14, 15) and bridged bis(fluore-
ny1)zirconocenes (23, 24) [36] show very high activities, exceeding those of steri-
cally less hindered Cp2ZrC12(6). Among the different aluminoxane co-catalysts,
methylalumoxane is much more effective than the ethyl- or isobutylalumoxane.
The catalyst shows a long-lasting activity; even after more than 100 h polymeri-
zation time they are still active.
Polyethylenes produced by metallocene catalysts feature a molecular weight
distribution of M J M , = 2; 0.9-1.2 methyl groups per 1000 C atoms, 1.1-1.8
vinyl and 0.2 trans-vinyl groups per 100 C atoms. The molecular weight is easily
lowered by increasing the temperature, raising the metallocene/ethylene ratio, or
adding small amounts of hydrogen (0.1-2 mol %) [37].
It is also possible to copolymerize ethylene with a-olefins such as propene,
1-butene, 1-pentene, 1-hexene, and I -octene, forming linear low-density polyethyl-
ene (LLDPE). The product of copolymerization parameters rl . r2 obtained by
using ethylenebis( 1-indenyl)zirconium dichloride (11) indicates random incor-
poration of the comonomer [38].
218 2.3 Reactions of Unsaturated Compounds

9 X=C2H4
10 X=MepSi

4yH3
-

R’

11 M = Z r , X=C2H4 14 X = C2H4, R’ = R2 = Me 18 M = Zr, X = Me& R = H

1 2 M = H f , X=C2H4 15 X = Me2Si, R’ = R2 = Me 19 M = Hf, X = Me2C, R = H
13 M = Zr, X = MeZSi 16 X = Me2Si, R’ = Ph, R2 = H 20 M = Zr, X = PhzC, R = H
21 M = Zr, X = Me2C, R = Me
17 X = Mepsi,R’ = Naph, R2 = H
22 M = Zr, X = Me2C, R = Me$

23 X=Me2Si
24 X=CpH4

A half-sandwich structure (25) [39, 401 in conjunction with tetrakis(pentafluor-

opheny1)borate is used by Dow and Exxon for commercial production of ethylene/
1-octene copolymers. These “constrained geometry catalysts” allow the incorpora-
tion of long-chain a-olefins (C4-C2,,), styrene, and 1,4-hexadiene, as well as the
incorporation of vinyl-terminated oligomers produced during polymerization to
 2.3.1.1 Chemical Background 219

form long-chain branched ultralow-density polyethylenes. Copolymers containing

more than 25 wt % of octene are elastomeric.

25

Polypropylenes

Achiral metallocenes such as Cp,ZrC12 (6) or [Me2Si(Flu)2]ZrC12(23) produce

atactic polypropylenes (Figure 1). The polymerization is not stereo- but regiose-
lective, due to the bent structure of the tetrahedral active complex favoring 1,2411-
sertions (2,l -misinsertions are barely detectable). The molecular weight of these

stereo block

J - l ~ l - l - l + J l ~ l
syndiotactic

atactic

117-11-11-11-11-1
hemiisotactic

Figure 1. Microstructures of polypropylene.

220 2.3 Reactions of Unsaturated Compounds

Figure 2. Origin of the stereospecificity of C2-symmetnc bis(indeny1)zirconocene catalysts.

The orientation shown on the right is favored over the one shown on the left due to
nonbonding interaction of the approaching monomer and the ligand.

polymers is temperature-dependent, ranging from oligomers to high-molecular-

weight polymers at low polymerization temperatures [4 11.
For stereospecific polymerization of a-olefins such as propene, a chiral active
center is needed, giving rise to diastereotopic transition states when combined
with the prochiral monomer and thereby different activation energies for the inser-
tion (see Figure 2). Stereospecificity may arise form the chiral P-carbon atom at
the terminal monomer unit of the growing chain - “chain end control” - or
from a chiral catalyst site - “enantiomorphic site control”. The microstructure
of the polymer produced depends on the mechanism of stereocontrol as well as
on the metallocene used [42-44].
The first chiral bridged zirconocene synthesized in 1984 by Brintzinger and
used as an isospecific polymerization catalyst was racemic ethylenebis-(4,5,6,7-
tetrahydro- 1-indenyl)zirconium dichloride (see Structure 9) [45]. Ewen showed
that the analogous ethylenebis( 1-indenyl)titanium dichloride (a mixture of the
meso form and the racemate) produces a mixture of isotactic and atactic polypro-
pylene [46]. The chiral titanocene as well as the zirconocene were shown to work
by enantiomorphic site control; in the case of the titanocene, the achiral meso
structure causes the formation of atactic polymer.
Due to the fact that the polymer chain migrates during insertion, the symmetry
of the metallocene is of fundamental importance to the tacticity of the polymer
produced. C,-symmetric metallocenes such as the bridged bis(indeny1) com-
pounds mentioned above have homotopic coordination sites and thereby always
favor the same orientation of the prochiral monomer during the approach. This
leads to the formation of an isotactic polymer (Figure 3).
The heptane-insoluble portion of polypropylene prepared with the ethylene-
bis( l-indeny1)zirconium dichloride (11) catalyst at 0 “C was found to crystallize
in the y (70 %) and a modifications (30 %). The formation of the y modification
is attributed to a small portion of 2,l-regioerrors and the quite unusual 1,3-misin-
sertions [47, 481.
The misinsertions are responsible for the low melting points of the polymers
produced at high temperatures. Also, the low molecular weights obtained at
industrially favored temperatures (60-70 “C) caused the need for catalyst
improvement. Since the mid- 1980s about a hundred C,-symmetric metallocenes
 2.3.1.1 Chemical Background 22 1

F.9-
-'?r-cH2

Figure 3. Mechanism of the isotactic polymerization of propene using an alkylzirconocenium

ion generated from a C,-symmetric bis(indeny1)zirconocene.

have been synthesized, aiming for catalysts producing high-molecular-weight,

high-melting-point polypropylene at a reasonable activity (see Section 2.3.1.5
by Fritze et al.) [49].
Table 3 compares some of these metallocenes. Replacing the CH2CH2
bridge (11) by the more rigid dimethylsilylene bridge (13) slightly increases
the activity but barely influences the molecular weight and melting point.
Great progress was made by introducing a methyl or ethyl group in position
2 of the indenyl rings, thus preventing bimolecular a-hydrogen transfer as a
chain termination reaction (Structures 14-17, 26). Spaleck et al. showed that
an isopropyl, or even better a phenyl or naphthyl group (16, 17), enhances
the regioselectivity as well as the stereospecificity, the activity, and the mo-
lecular weight [50].

26
Table 3. ProDene Dolvmerization"' with metallocene/methvlaluminoxane catalvsts.
Metallocene" Structure Activity Molecular weight Isotacticity Melting point
[kg PP/(mol Zr . h)] [g/mol] mmmm [%I ["Cl
CPZZrC12 6 140 2 000 15
(NmCp),ZrCl2 7 170 3 000 59 118
[MeK(W(Cp)lZrCb 8 180 3 000 49 125
[En(IndH4)2]ZrC12 9 1200 24 000 98 140
[En(Ind)z]ZrC12 11 1 700 32 000 95 136
[MezSi(Ind)z]ZrC1z 13 1900 79 000 97 148
[En(2,4,7-Me31nd)z]ZrClz 14 750 420 000 >99 162
[Me2Si(2-Me-4,5-BenzInd)2]ZrC12 26 14 000 680 000 98 157
[MezC(Flu)(Cp)lZrC12 18 1500 160000 0.6"' 138
[Ph2C(Flu)(Cp)lZrCls 20 2 000 730 000 0.4" 141
[Me2C(Flu)(Cp)]HfCI2 19 130 750 000 0.7'' 138
a) Propylene pressure = 0.2 MPa, temp. = 30 "C, [metallocene] = 6.25 X M, metallocene/MAO = 250, solvent = toluene.
Cp = cyclopentadienyl; Nm = neomenthyl; Ind = indenyl; En = C,H,; Benz = benzyl; Flu = fluorenyl.
') Syndiotactic.
 2.3.1.1 Chemical Background 223

Miya and co-workers [S 11 simulated bridged bis(indeny1) compounds using

bridged 1,2-dimethylcyclopentadienyl ligands featuring C2 symmetry. Their
zirconocenes are highly active and produce highly isotactic polypropylenes with
melting points of 162 "C.
Ewen and Razavi [52] have shown that stereoselective C,-symmetric
metallocenes (18-20) with their enantiotopic vacancies form syndiotactic poly-
mers. The rrrr stereosequences indicate enantiomorphic site control with chain
migratory insertion; errors arise from site isomerization without insertion and
occasional reversal in diastereoface selectivity.
Metallocenes with diastereotopic sites for monomer coordination show quite
an interesting polymerization behavior: introduction of a methyl group in position
3 of the cyclopentadienyl ring in (21) disturbs the stereospecificity at this site,
giving rise to hemiisotactic polypropylene [53], while a r-butyl group at the
same position inverts the preferred mode of coordination (22); thus an isotactic
polymer is generated [54]. Metallocene (8) has one nonspecific and one stereo-
specific site, too; at low temperature, hemiisotactic polypropylene is produced
while at high temperatures site isomerization without insertion facilitates the
formation of isoblock polypropylene.
Stereoblock polypropylene is synthesized by unbridged metallocenes such
as bis(neomenthy1)zirconium dichloride (7) with cyclopentadienyl or phenyl
substituted indenyl ligands [55, 561. The stereoblock length increases at
lower polymerization temperatures. Products containing isotactic and atactic
blocks are elastomeric if the isotactic block length is short. Rieger [57] obtained
similar polypropylenes by bridged fluorenyl-substituted indenyl zirconium com-
plexes.
For technical purposes, the metallocenes are heterogenized by supporting on
silica or alumina which is pretreated with M A 0 [58, 591.

Polycycloalkenes and Copolymers

While it is very difficult to polymerize cyclic olefins such as cyclopentene

or norbornene using heterogeneous catalysts without ring opening, a metallo-
cene/alumoxane catalyst polymerizes them exclusively by double-bond opening
[601.
Table 4 shows polymerization conditions and properties of crystalline polymers
of cyclobutene, cyclopentene, norbornene, and tetracyclododecene produced by
zirconocenes. The activities for the polymerization of cycloalkenes are signifi-
cantly lower than for ethylene. The melting points are surprisingly high: they
were found to be 395 "C for polycyclopentene and over 400 "C for the others;
the decomposition temperatures lie in the same range.
In the case of poly(cyclopentene), the configurational base units are cis-
and trans- 1,3-enchained (27) while poly(norbornene) shows cis-ex0 insertion
[61, 621.
While the homopolymers cannot be processed because of their high melting
points there is much interest in the copolymers of norbornene or tetracyclodode-
224 2.3 Reactions of Unsaturated Compounds

27

Table 4. Polymerization of cycloolefins using metallocene catalysts.

Monomer Metallocene Temp. Activity Melting point
structure ["C] [kg PP/(mol Zr . h)] ["Cl
Cy clobutene 11 -10 50 485
11 0 149 485
Cyclopentene 11 0 32 395
11 22 195 395
Norbornene 11 20 40 >500
18 23 45 8 >500

cene with ethylene or propene, respectively. These cycloolefin copolymers (COC)

are amorphous if more than 12 wt.% of the cyclic monomer is incorporated
[63, 641. They are highly resistant to chemicals and heat, have high glass transi-
tion temperatures, desirable elastic modules, transparency and low density
(1.02 gkm'), and show low absorption of water (< 0.05 %). Therefore these
new polymers are predestined for optoelectronic applications (e. g. compact
discs, polymer optical fibers).
The bulky cycloolefin is incorporated into the growing polymer chain only two
to three times more slowly than ethylene. By varying the metallocene and the
reaction conditions, the molecular weight, the molecular distribution, and the
microstructure of the COC are tailored.
Metallocene and other homogeneous single-site catalysts offer significant
advantages over heterogeneous catalysts for the polymerization of functional
olefins. They are not electrophilic in the same way and poisoned by Lewis-base
containing monomers [65]. In contrast, they offer the potential for steric
protection of the active site through careful ligand design. Monomers such as
5-(N,N-diisopropylamino)-l-pentene,allyltrimethylsilane, vinyl alcohols and
methyl methacrylate have been converted to the isotactic polymers or to copoly-
mers [66].
Polymers with ring structures, interspaced with CH2 groups, can be obtained
by polymerization of 1,5-dienes. 1,2-Insertion of the terminal double bond
into the zirconium-carbon bond is followed by an intramolecular cyclization
forming a ring. Waymouth describes the cyclopolymerization of 1,Shexadiene
to poly (methylene- 1,3-cyclopentane) [67]. Of the four possible microstructures,
the optically active trans-, isotactic structure (Figure 4) is predominant (68 %)
when using a chiral pure enantiomer of [En(IndH4)2Zr](BINAP)2and MAO.
 2.3.1.1 Chemical Background 225

cis isotactic cis syndiotactic

trans isotactic trans syndiotactic

Figure 4. Microstructures of poly(methylenecyc1opentane).

Cyclopolymerizations of functionalized 1,6-dienes such as 4-trimethylsilyloxy-

1,6-heptadiene are also possible, using B(C6F& as co-catalyst. After hydrolysis
with HC1 poly(methylene-l,3-5-hydroxycyclohexane)(eq. (4)) is formed [68].

OSiMeB OSiMe3 OSiMe3

I HCI (4)

OH OH OH

Asymmetric Oligomerization

A separation of the racemic mixture of chiral zirconocene compounds into the

optically active pure enantiomers is performed using O-acetyl-(R)-mandelic acid
as chiral auxillary (Structure 28). Using this enantiomerically pure metallocene
in oligomerization experiments confirms the mechanistic hypothesis of stereospe-
cificity predicting the topicity of insertion [69].
While polymers of a-olefins are only pseudochiral trimers, tetramers and higher
oligomers are optically active. Oligomerization can be achieved by adding hydro-
gen to the reaction mixture [70] or by decreasing the monomer/ metallocene ratio
[71]. While the first technique ends up with saturated hydrocarbons, the latter
leads to the formation of alkenes. In the case of propene it is possible to obtain
oligomers from trimers up to hexamers at low monomer concentrations. The
226 2.3 Reactions of Unsaturated Compounds

trimer (2,4-dimethyl- 1-heptene) has one chiral carbon and shows optical rotation.
Using a chiral cyclodextrin stationary phase, the trimer may be resolved into its
enantiomers by capillary gas chromatography. With decreasing oligomerization
temperature, the expected enantiomer is favored up to an enantiomeric excess
(ee) of 95 % at 20°C [72].

Aco)r,
Ph 'li

28

2.3.1.1.4 Late Metal Catalysts

The lower oxophilicity and the greater functional group tolerance of late transition
metals relative to early metals such as Ti, Zr, and Hf make them likely targets for
the development of catalysts for the homo- and copolymerization of ethylene with
polar comonomers under mild conditions.
Homogeneous nickel catalysts are formed when well-known oligomerization
catalysts (29) of the Shell Higher Olefin Process (SHOP; cf. Section 2.3.1.3)
[73] are modified by the addition of strong phosphine acceptors as second com-
ponent or if the phosphine ligand is replaced by a weaker donor such as pyridine
[74]. Ethylene polymerization is also achieved by some bis(y1ide)nickel catalysts
(30) with remarkably high activity. The ylide is synthesized by the reaction of
Ni(0) complexes with phosphines [75-781. Using these single-component cata-
lysts, polymerization is possible in solvents of various polarities. The best solvents
are methylene chloride or hexane, but even in polar solvents like THF, acetone, or
water the catalysts are quite active. The main interest in these compounds arises
from the possibility of polymerizing olefins bearing polar groups. By tuning the
ligands it is possible to obtain oligomers as well as high-molecular-weight poly-
mers. Using 30, the activity reaches 50 000 mol of ethylene consumed per mol of
nickel at 1 MPa ethylene pressure and 100"; the molecular weight ranges up to
lo6. Branching is more favored than with metallocene catalysts (about 50 methyl
groups per 1000 C atoms were found in oligomers).
Brookhart and co-workers [79-8 11 introduced catalysts based largely on chelat-
ing, nitrogen-based ligands that are active for the homopolymerization of ethylene
and the copolymerization of ethylene with 1-olefins and polar comonomers (31).
Ni, Co, Fe or Pd are used as late transition metals. The diimine ligands have big
substituents to prevent b-hydride elimination. Ni(I1) or Pd(I1) complexes form
cations by combination with M A 0 and polymerize ethylene to highly branched
polymers with molecular weights up to one million. The activities reach TON
 References 227

Ph3P,
Ni
,Ph

0‘ ‘PPhP
Ph\ x
Ni. PMe3

Ph
XH obpph2 M = Ni, Pd
R’ = Me, H, 0.5 Naphthalene-l,&diyl
R = iPr, Me
29
30 L = OEt2, R2CN
Y- = BArF4-,SbF6-

31
R

M = Fe, Co
R = iPr, Me

32 33

values of 4 million in one hour. The branching happens by “chain-running”; the

nickel or palladium runs along the carbon atoms of the polymer chain before a
new insertion happens [79]. The copolymerization of ethylene with acrylates is
possible with palladium catalysts [82].
In 1998, Grubbs and co-workers [83, 841 reported on a new type of neutral
Ni(I1) complexes with salicylaldimin ligands (32).With these catalysts low-
branched polyethylenes were obtained with a narrow molecular weight distribu-
tion. The copolymerization of ethylene and norbornene is possible. Fe and Co
catalysts were used for the linear polymerization of ethylene by Gibson [85]
and Brookhart [86] independently (33). Activities of lo7 TONS were reported.
The polyethylenes obtained are highly crystalline with a broad molecular weight
distribution.
The late transition metal complexes have widened the possibilities of synthesiz-
ing new polymers with special microstructures and polar monomers.

References
[l] S. Mecking, Angew. Chem. 2001, 113, 550.
[2] K. Ziegler, Angew. Chem. 1964, 76, 545.
[3] Metalorganic Catalysts for Synthesis and Polymerization (Ed.: W. Kaminsky), Springer,
Berlin, 1999.
[4] D. S. Breslow, N. R. Newburg, J. Am. Chem. SOC.1957, 79, 5072.
[5] T. Keii, Kinetics of Ziegler-Natta Polymerization, Kodansha, Tokyo, and Chapman and
Hall, London 1972.
228 2.3 Reactions of Unsaturated Compounds

[6] A. Andresen, H.-G. Cordes, J. Herwig, W. Kaminsky, A. Merck, R. Mottweiler, J. Pein,

H. Sinn, H.-J. Vollmer, Angew. Chem. 1976, 88, 689; Angew. Chem., Znt. Ed. Engl. 1976,
15, 630.
[7] W. Kaminsky, Macromol. Chem. Phys. 1996, 197, 3907.
[8] H. H. Brintzinger, D. Fischer, R. Miilhaupt, B. Rieger, R. Waymouth, Angew. Chem.
1995, 107, 1255.
[9] S. D. Ittel, L. K. Johnson, M. Brookhart, Chem. Rev. 2000, ZOO, 1169.
[ 101 H. Emde, Angew. Makromol. Chem. 1977, 60, 1.
[ l l ] N. Kashiwa, T. Tsutsui, Makromol. Chem. Rapid Commun. 1983, 4, 491.
[12] T. Nozaki, J. C. W. Chien, J. Polym. Sci., Polym. Chem. Ed., 1991, 29, 1807.
1131 F. J. Karol, K. J. Cann, B. E. Wagner in Transition Metals and Organometallics as
Catalysts for Olefin Polymerization (Eds.: W. Kaminsky, H. Sinn), Springer, Berlin,
1988.
[14] D. G. Ballard, Adv. Catal. 1973, 23, 263.
[15] H. Sinn, W. Karninsky, Adv. Organomet. Chem. 1980, 18, 99.
[16] H. Sinn, W. Kaminsky, H.-J. Vollmer, R. Woldt, Angew. Chem., Znt. Ed. Engl. 1980, 19,
390.
[17] W. Kaminsky, J. Chem. Soc., Dalton Trans., 1998, 1413.
[18] M. Bochmann, Top. Catal., 1999, 7, 9.
[ 191 Organometallic Catalysts and Olefin Polymerization (Eds.: R. Blom, A. Follestad,
E. Rytter, M. Tilset, M. Ystenes), Springer, Berlin, 2001.
[20] Metallocene-Based Polyolefins, Vols. 1 and 2 (Eds.: J. Scheirs, W. Kaminsky, Wiley,
Chichester, 2000.
[21] I. Tritto, M. C. Sacchi, P. Locatelli, F. Fortini, in ref. [19], p. 253.
[22] J. Bliemeister, W. Hagendorf, A. Harder, B. Heitrnann, I. Schimmel, E. Schmedt,
W. Schnuchel, H. Sinn, L. Tikwe, N. v. Thienen, K. Urlass, H. Winter, 0. Zarncke,
in: Ziegler Catalysts (Eds.: G. Fink, R. Miilhaupt, H. H. Brintzinger), Springer, Berlin,
1994, p. 57.
[23] M. Ystenes, J. L. Eilertsen, J. Liu, M. Ott, E. Rytter, J. A. Stovneng, J. Polym. Sci., Part
A: Polym. Chem. 2000, 38, 3106.
[24] Y. Koide, S. G. Bott, A. R. Barron, Organometallics 1996, 15, 2213.
[25] N. Herfert, G. Fink, Makromol. Chem. 1992, 193, 1359.
[26] R. F. Jordan, Adv. Organomet. Chem. 1991, 32, 325.
[27] M. Bochmann, Angew. Chem. 1992, 104, 1206.
[28] P. Tait in Transition Metals and Organometallics as Catalysts for Olefin Polymerization
(Eds.: W. Kaminsky, H. Sinn), Springer, Berlin, 1988, p. 309.
1291 J. C. W. Chien, B. P. Wang, J. Polym. Sci., Part A 1989, 27, 1539.
[30] W. Kaminsky, A. Bark, R. Steiger, J. Mol. Catal. 1992, 74, 109.
[31] A. Zambelli, P. Longo, A. Grassi, Macromolecules 1989, 22, 2186.
[32] G. G. Hlatky, H. W. Turner, R. R. Eckmann, J. Am. Chem. Soc. 1989, 111, 2728.
[33] J. C. W. Chien, W. M. Tsai, M. D. Rausch, J. Am. Chem. Soc. 1991, 113, 8570.
[34] C. Sishta, R. M. Hathorn, T. J. Marks, J. Am. Chem. Soc. 1992, 114, 1112.
[35] M. Bochmann, S. J. Lancaster, Organometallics 1993, 12, 633.
[36] H. G. Alt, W. Milius, S. J. Palackal, J. Organomet. Chem. 1994, 472, 113.
[37] W. Kaminsky, H. Liiker, Makromol. Chem., Rapid Commun. 1989, 5, 225.
[38] W. Kaminsky, U. Weingarten, Polym. Bulletin, 2001, 45, 451.
[39] J. Stevens, Proc. MetCon 93, Catalyst Consultant Inc., Houston, TX, 1993, p. 157.
[40] K. Swogger in Catalyst Design for Tailor Made Polyolefins (Eds.: K. Soga, M. Terano),
Kodansha Elsevier, Tokyo, 1994, p. 285.
[41] W. Karninsky, M. Miri, Homogeneous and Heterogeneous Catalysis (Eds.: Y. Yermakov,
W. Likholobor), VNU-Science Press, Utrecht, 1986, p. 327.
 Rejerences 229

[42] A. Zambelli, C. Pellecchia, L. Oliva, Makromol. Chem., Macromol. Symp. 1991, 48/49,
297.
1431 L. Resconi. L. Cavallo, A. Fait, F. Piemontesi, Chem. Rev. 2000, 100, 1253.
1441 P. Corradini, G. Guerra, L. Cavallo, G. Moscardi, M. Vacatello in Ziegler Catalysts
(Eds.: G. Fink, R. Miilhaupt, H. H. Brintzinger), Springer, Berlin, 1994, p. 237.
[45] W. Kaminsky, K. Kiilper, H. H. Brintzinger, F. R. W. P. Wild, Angew. Chem., Int. Ed.
Engl. 1985, 24, 507.
[46] J. A. Ewen, J. Am. Chern. SOC.1984, 106, 6355.
[47] B. Rieger, X. Mu, D. T. Mallin, M. D. Rausch, J. C. W. Chien, Macromolecules 1990,23,
3559.
[48] K. Soga, T. Shiono, S. Tdkemura, W. Kaminsky, Mukromol. Chem., Rapid Commun.
1987, 8, 305.
1491 W. Spaleck, M. Antberg, M. Aulbach, B. Bachmann, V. Dolle, S. Haftka, F. Kiiber,
J. Rohrmann, A. Winter in Ziegler Catalysts (Eds.: G. Fink, R. Miilhaupt, H. H. Brint-
zinger), Springer, Berlin, 1994, p. 83.
[SO] W. Spaleck, F. Kuber, A. Winter, J. Rohrmann, B. Bachmann, P. Kiprof, J. Behn, W. A.
Henmann, Organometallics 1994, 13, 954.
[51] T. Mise, S. Miya, H. Yamazaki, Chem. Lett. 1989, 1853.
[52] J. A. Ewen, R. L. Jones, A. Razavi, J. D. Ferrara, J. Am. Chern. SOC. 1988, 110, 6255.
[53] J. A. Ewen, M. J. Elder, R. L. Jones, L. Haspeslagh, J. L. Atwood, S. G. Bott, K. Robin-
son, Mukromol. Chem. Mucromol. Symp. 1991, 48/49, 253.
[54] J. A. Ewen, Macromol. Chem. Phys. Macromol. Symp. 1995, 89, 181.
[55] W. Kaminsky, M. Buschemohle in Recent Advances in Mechanistic and Synthetic
Aspects of Polymerization (Eds.: M. Fontanille, A. Guyot), D. Reidel, Dordrecht,
1987, p. 503.
[56] R. M. Waymouth, G. W. Coates, E. M. Hauptmann, US 5.594.080 (1997).
[57] U. Dietrich, M. Hackmann, B. Rieger, M. Klinga, M. Leskela, J. Am. Chem. SOC.1999,
121, 4348.
[58] K. Soga, M. Kaminaka, Makromol. Chem. 1993, 194, 1745.
[59] W. Kaminsky, F. Renner, Makromol. Chem., Rapid Commun. 1993, 14, 239.
[60] W. Kaminsky, R. Spiehl, Makromol. Chem. 1989, 190, 515.
[61] S. Collins, W. M. Kelly, Mucrornolecules 1992, 25, 233.
[62] W. Kaminsky, A. Bark, M. Amdt, Makromol. Chem. Macromol. Symp. 1991, 47, 83.
1631 H. Cherdron, M.-J. Brekner, F. Osan, Angew. Mukromol. Chem. 1994, 223, 121.
[64] M. Amdt, 1. Beulich, Macromol. Chem. Phys. 1998, 199, 1221.
[65] A. Guyot, Polym. Adv. Tech. 1996, 7, 61.
[66] S. Habane, H. Baraki, Y. Okamoto, Macromol. Chem. Phys. 1998, 199, 2211.
[67] G. W. Coates, R. M. Waymouth, J. Am. Chem. Soc. 1993, 115, 91.
[68] M. R. Kesti, G. W. Coates, R. M. Waymouth, J. Am. Chem. SOC. 1992, 114, 9679.
[69] P. Pino, P. Cioni, J. Wei, J. Am. Chem. Soc. 1987, 109, 6189.
[70] P. Pino, M. Galimberti, J. Organomet. Chem. 1989, 370, 1.
[71] W. Kaminsky, A. Ahlers, N. Moller-Lindenhof, Angew. Chem. 1989, 101, 1304.
[72] W. Kaminsky, A. Ahlers, 0. Rabe, W. Konig in Organic Synthesis via Organometallics
(Eds.: D. Enderes, H. J. Gais, W. Keim), Vieweg, Braunschweig, 1993, p. 151.
[73] W. Keim, F. H. Kowaldt, Erdol, Erdgus, Kohle, 1978, 78-79, 594.
1741 U. Klabunde, R. Miilhaupt, J. Polym. Sci., Polym. Chern. Ed. 1987, 25, 1989.
[75] W. Keim in Catalytic Polymerization of OleBns (Eds.: T. Keii, K. Soga), Kodansha,
Tokyo, 1986, p. 201.
[76] W. Keim, Chem. Ing. Tech. 1984, 56, 850.
[77] K. A. Ostoja-Starzewski, J. Witte, Angew. Chem. 1987, 99, 76.
[78] K. A. Ostoja-Starzewski, J. Witte, Angew. Chem. 1985, 97, 610.
230 2.3 Reactions of Unsaturated Compounds

[79] L. K. Johnson, C. M. Killian, M. Brookhart, J. Am. Chem. Soc. 1995, 117, 6414.
1801 C. M. Killian, L. K. Johnson, M. Brookhart, Organometallics 1997, 16, 2005.
[81] D. P. Gates, S. A. Svejda, E. Onate, C. M. Killian, L. K. Johnson, P. S. White, M. Brook-
hart, Macromolecules 2000, 33, 2320.
[82] S. Mecking, L. K. Johnson, L. Wang, M. Brookhart, J. Am. Chem. Soc. 1998, 120,
888.
1831 C. Wang, S. Friedrich, T. R. Younkin, R. T. Li, R. H. Grubbs, T. R. Bansleben, M. W.
Day, Organometallics 1998, 17, 3149.
[84] T. R. Younkin, E. F. Connor, J. I. Henderson, S. K. Friedrich, R. H. Grubbs, D. A.
Bansleben, Science 2000, 287, 460.
1851 G. J. P. Britovsek, M. I. Bruce, Y. C. Gibson, B. S. Kimberley, P. J. Maddox,
S. Mastroianni, S. J. McTavish, C. Redshaw, G. A. Solan, S. Stromberg, A. J. P. White,
D. J. Williams, J. Am. Chem. Soc. 1999, 121, 8728.
[86] B. L. Small, M. Brookhart, A. M. A. Bennett, J. Am. Chem. SOC. 1998, 120, 4049.

2.3.1.2 Chemical Engineering and Applications

Ludwig L. Bohm

2.3.1.2.1 Introduction
Alkenes such as 1-olefins but also cycloolefins (e. g., cyclopentene, norbornene)
can be polymerized to homo- or copolymers with different chain lengths, copoly-
mer compositions and molecular mass distributions. A broad variety of polyole-
fins is accessible, such as homo- or copolymers for injection molding, rotamold-
ing, blow molding, extrusion, film blowing, and fiber spinning [l]; elastomers [2];
waxes [3]; or ultrahigh molecular mass polyethylenes [4]; and for special applica-
tions, such as lubricant oils or lubricant oil additives (viscosity index improvers)
[5]; oil additives (e. g., drag reducers) [6, 71; and ultrahigh modulus polyethylene
fibers [8, 91. Also, various grades of polymers can be synthesized to enter into
new applications [lo-141.
There are various routes for the oligomerization and polymerization of olefins.
Ethylene can be polymerized under high pressure and at high temperature,
initiated by radicals [ 151. Isobutene (1,l-dimethylethylene) is easily polymerizable
at low temperature, initiated with Lewis acids (cationic polymerization) [ 161. Oli-
gomers can be synthesized using various “Aufbau” reactions [ 171. However, only
the catalytic polymerization process offers a general route to polymerize 1-olefins
and cycloolefins. Catalysts are transition metal compounds, mainly of Group 4-6
elements either with co-catalysts (Ziegler-Natta catalysts [ 18, 191, metallocenes
[20]) or without (Phillips catalysts [21]).
The catalytic polymerization process is carried out in hydrocarbon diluents
(diesel oil, hexane, isobutane) or the bulk monomers (ethylene, propylene, nor-
bornene, styrene). The transition metal catalysts are usually insoluble and thus
act heterogeneously, except for some homogeneously active vanadium com-
pounds [2] and the metallocenes [20] (cf. Section 2.3.1.1). Over a wide tempera-
 2.3.1.2 Chemical Engineering and Applications 23 1

ture range the polymers can also be insoluble and precipitate during polymeriza-
tion (slurry polymerization process). Such heterogeneous processes are state-
of-the-art for industrial polyolefin production [22, 231. Homogeneous catalysis
especially requires the solubility of the catalyst or catalystko-catalyst system in
hydrocarbon diluents, irrespective of whether the polymer or oligomer is also
soluble or not.

2.3.1.2.2 Features of Catalytic Olefin Oligomerization

and Polymerization Processes
The catalyst or catalystko-catalyst system always plays the key role in olefin
oligomerization and polymerization processes. It was the discovery of transition
metal catalysts by Hogan and Banks [24] and Ziegler and co-workers [18, 251,
and their application to the polymerization of propylene by Natta and co- workers
[ 19,261 which have provided the opportunity to synthesize new types of polymers
such as high-density polyethylene (PE-HD) and isotactic polypropylene (PP) [27].
This shows that new types of polyolefins become accessible by progress in
catalyst development, sometimes in combination with the development of new
technologies. The discovery of high-mileage homogeneous metallocene/methyl-
alumoxane (MAO) catalyst systems by Sinn, Kaminsky and co-workers [28,
291 can be regarded as an important milestone toward making new types of
polyolefins. Because such catalysts are single-site ones they produce polyolefins
with a molecular mass distribution similar to the Schulz-Flory most probable mo-
lecular mass distribution [30]. Together with a uniform comonomer distribution in
the copolymers [311. Both points are of importance because state-of-the-art multi-
site catalysts lead to polyolefins with broader molecular mass distributions and for
the most part to nonuniform comonomer distributions [32].
A further breakthrough was the synthesis of enantiomeric sterorigid ansa-
metallocenes by Brintzinger and co-workers [33] and the discovery by Ewen
[34] that such racemic metallocene/methylalumoxane systems generate isotactic
polypropylene. It was further found that the metallocene structure determines
the polymer structure [35-371. Again, with these compounds polyolefins such
as syndiotactic polypropylene become available on a large scale [38]. Indeed,
metallocene/methylalumoxane catalysts offer new prospects for olefin oligomers
and polymers [39-42].
Although the catalyst - homogeneous or heterogeneous - mainly determines
the oligomerization or polymerization process and hence the polymer properties,
the technical process also plays an important role. The oligomers or polymers may
or may not precipitate during the synthesis, depending on several factors. Hydro-
carbons with six or more carbon atoms (n-hexane, n-heptane, decalin, toluene,
xylene, and others) are solvents for polyolefins, but semicrystalline polyolefins
are not soluble at room temperature. Only amorphous polyolefins can be
dissolved.
232 2.3 Reactions of Unsaturated Compounds

300
I octane
I
250
t e!
eg
200 +.
z
W
ii E
L
I!
$ 150

!
d
4
100

50

0
0 20 40 so 80 100
composition [X b.w.1

Figure 1. Phase diagram for high-density polyethylenehydrocarbon systems.

The phase diagram of polyolefins and hydrocarbon diluents is exemplified for

high-density polyethylene in Figure 1. When the polymer-diluent mixture is
heated, dissolution of the semicrystalline polymer takes place along the borderline
1 (turbidity curve) [43, 441. This line depends on the polymer (e. g., polyethylene,
isotactic polypropylene), average chain length, and copolymer composition.
Figure 1 further shows phase separation along a lower critical solution tempera-
ture 2 (LCST) [43, 451. It is characteristic for this phase borderline 2 that it
depends mainly on the molecular mass or chain length of the diluent.
This phase diagram shows that for semicrystalline polymers with high melting
points such as high-density polyethylene or polypropylene the temperature to
dissolve these polymers must be higher than approximately 120°C (area I). If
the melting points decrease [44], the range of polymer solubility extends to
lower temperatures, and amorphous polymers are soluble at room temperature
and even lower temperatures. For diluents with less than five carbon atoms
such as isobutane, propane or propylene, the LCST is below curve 1, which
means that all polymers - either semicrystalline or amorphous - precipitate in
these diluents along the borderline 2 (area 11).
 2.3.1.2 Chemical Engineering and Applications 233

2.3.1.2.3 Technical Processes

Homogeneous catalysis takes place at transition metal complexes dissolved in
the reaction medium. For the oligomerization or polymerization of olefins, such
transition metal complexes are provided by some vanadium compounds and the
metallocenes, both activated with soluble organoaluminum compounds. The poly-
mers can be dissolved (solution process) or precipitated (slurry process).
The phase diagram (see Figure 1) shows that there are two solution processes: a
low-temperature process (below 100 "C) for the production of amorphous copoly-
mers like ethylene/propylene elastomers (EPR or EPM) [2], and a high-tempera-
ture process (far beyond 100 "C) for the production of semicrystalline homo- and
copolymers like high-density polyethylenes (PE-HD), linear low-density poly-
ethylenes (PE-LLD) and ethylene waxes [ I , 31. Polypropylenes (PP) cannot be
made in high-temperature solution processes, except for propylene waxes.
Low-temperature solution processes are state-of-the-art for the production of
ethylene/propylene or ethylene/propylene/diene elastomers (EPDR or EPDM).
A continuous stirred-tank reactor (CSTR) or a series of two or even more such
reactors is used [2]. n-Hexane, n-heptane, or Chr C, fractions are the solvents.
Catalyst, co-catalyst and other compounds are introduced with the solvent into
the reactor. The monomers (ethylene, propylene) are injected as gases; other
olefins are introduced in liquid form. The polymerization process runs around
50°C and at pressures up to 2 MPa. Downstream the catalystko-catalyst system
is deactivated and their residues are dissolved in dilute acid or aqueous NaOH.
The copolymer is stabilized with an antioxidant. Steam treatment removes the
rest of the solvent and monomers, and agglomerates the product to crumbs.
These crumbs are then dried and finished to bales or pellets.
Such copolymers made by homogeneous catalysis have an ethylene content
ranging from SO to 85 mol %, and contain up to 10 mol % of a diene compound.
The average molecular mass (by viscometry) is in the range between SO000 and
300000 g/mol. The copolymer must be random with no block structures of the
minor monomer, the termonomer (diene) must be evenly distributed along the
polymer chain, and the copolymer composition must be as constant as possible,
independently of chain length. These recommendations are best fulfilled by a
series of soluble vanadium catalysts with organoaluminum co-catalysts. For
these homogeneous catalystko-catalyst systems the product of the Mayo, Lewis
parameters rl, r2 is mostly lower than but close to 1, as required [2, 321. However,
this does not mean compositional homogeneity at all [32].
Nowadays homogeneous metallocene catalysts activated with oligomeric
methylalumoxanes or other co-catalysts [ 16, 20, 46-54] open new prospects.
These systems have an excellent activity, they have the ability to form random
copolymers in combination with a narrow molecular mass and comonomer distri-
bution. Further important advantages are that a broad variety of structures can be
synthesized to obtain tailor-made catalysts [49, 531, and that zirconium com-
pounds are scarcely reduced with the co-catalyst [S4]. It is further reported that
metallocenes have been used in combination with methylalumoxanes for EPDM
production at temperatures below 100 "C in liquid propylene [55].
234 2.3 Reactions of Unsaturated Compounds

Ethylene and/or propylene waxes are produced by the high-temperature solu-

tion process using Ziegler-Natta catalysts and organoaluminum compounds as
co-catalysts [3]. To reach the required low average molecular mass (see Figure
2), large amounts of hydrogen must be added. Because hydrogen considerably
reduces the catalytic activity, large amounts of catalyst and co-catalyst have to
be used and their residues must be removed after deactivation [3].
Metallocenes in combination with methylalumoxanes are able to synthesize
these waxes at temperatures below 100°C [56]. The technical process is again
performed in a CSTR at approx. 70°C in liquid propane at 3 MPa. The waxes
precipitate during polymerization, as previously discussed (see Figure 1). Metal-
locenes can be used because the average molecular mass can easily be regulated
by small amounts of hydrogen without reducing catalytic activity. Therefore all
catalyst residues can remain in the product without disadvantage to the quality.
A broad spectrum of unbridged and bridged metallocenes can be used. The fasci-
nation is the challenge to tailor the polymer by employing the proper metallocene
[571.
It is further possible to use metallocenes for the oligomerization of 1-olefins to
obtain lubricant oils or viscosity index improvers [58, 591. The oligomerization
process can be performed at temperatures below 100"C, with or without hydro-
gen. If there is no hydrogen, each oligomer can contain a vinyl end group [58].
These telechelics offer the opportunity to make further chemical modifications
[60]. Homogeneous catalytic systems open new prospects for the synthesis of oli-
gomers and telechelics for interesting applications.
Metallocenes as homogeneous catalysts, in combination with methylalumox-
anes, can be used to copolymerize 1-olefins (e. g., ethylene) and cycloolefins to
obtain thermoplastic materials called cycloolefin copolymers [ 10-1 31. The poly-
merization is again performed in a CSTR at temperatures in the range 50 to
100°C and pressures below 5 MPa, either in bulk norbornene or in a mixture
of norbornene and hydrocarbons such as decalin. A broad variety of amorphous
copolymers (see Figure 2) can be synthesized with a wide range of glass transition
temperatures. It is further known that the metallocene influences the copolymer
structure. The amorphous copolymers are soluble in excess norbornene or the
hydrocarbon diluent. Polymerization in bulk styrene using metallocene catalysts
activated with methylalumoxane [61] at temperatures between 50 and 75 "C gen-
erates syndiotactic polystyrene. This polymer precipitates during polymerization
because a semicrystalline, solid products is formed which is insoluble in styrene
within the applied temperature range [62].
The high-temperature solution process is state-of-the-art for the production of
ethylene homopolymers as well as ethylene/l -olefin copolymers with a wide
range of average molecular mass and copolymer composition [15]. This process
is performed in a CSTR or in a cascade of two reactors, like the low-temperature
process. Only the downstream equipment is different. The diluent is an aliphatic
hydrocarbon such as cyclohexane, n-hexane, or a C6-Cl0 alkane fraction. Homo-
geneous catalyst and co-catalyst are fed into the polymerization reactor mixed
with solvent. Ethylene, hydrogen to regulate average molecular mass, and the
comonomer are injected either as a gas or as a liquid. Temperature can be con-
 2.3.1.2 Chemical Engineering and Applications 235

trolled by dosing cold solvent (adiabatic process) or by external cooling. If cata-

lyst residues must be removed downstream, this is done by filtration after
decomposition. Then the solvent, together with residual monomers, is flashed
to obtain the polymer as a melt. This melt can be pelletized after addition of
stabilizers, or otherwise transferred to finished products. For process parameters,
see [3, 151. A broad product portfolio of ethylene homo- and copolymers and
ethylene and propylene waxes [3] is accessible. Ethylene/l -octene copolymers
(PE-LLD, PE-VLD) are also produced.
For the production of ethylene/l -octene copolymers, metallocenes in com-
bination with oligomeric methylalumoxanes or other compounds are now used
[3 1, 631. Half-sandwich transition metal complexes such as [(tetramethyl-y5-
cyclopentadienyl) (N-t-butylamido)dimethylsilyl]titanium dichloride are applied
to synthesize linear low-density copolymers and plastomers, called “constrained
geometry catalysts” [3 11. Ethylene and styrene can be copolymerized to products
ranging from semicrystalline rubber-like elastomers to highly amorphous rigid
materials at room temperature [64].
PE-LLD and even PE-VLD can further be synthesized with metallocenes and
methylalumoxanes in the bulk ethylene (high-pressure) process. The polymeriza-
tion is performed in a stirred tank reactor at temperatures above 120°C and
pressures of at least 50 MPa [65, 661. The copolymer continuously leaves the
reactor with excess ethylene, then the ethylene is vented and recycled into the
polymerization reactor. The polymer melt is transferred into pellets. In this case
the comonomers are propylene, 1 -butene, and 1-hexene.

2.3.1.2.4 Products and Applications

By homogeneous catalysis a wide spectrum of polyolefin products for a broad
variety of applications can be produced [l-lo]. Figure 2 shows the product port-
folio in a map of copolymer composition vs. average molecular mass.
1-Olefin, isobutene and ethylene/propylene oligomers with an average molecu-
lar mass in the range between 300 and 2000 g/mol are employed for lubricants
(oil, grease) [5]. Such oligomers are accessible by cationic processes with
Lewis acids or Friedel-Crafts compounds as catalysts [16, 171. With metallo-
cene/methylalumoxane catalysts, oligomers can now be produced under reason-
able conditions for a technical process, as described elsewhere [58, 591. If there
is no hydrogen to regulate chain length, telechelics can be produced with a
vinyl end group. These reactive oligomers can be modified to produce functiona-
lized products for applications like viscosity index improvers [63] or compatibili-
zers in polymer blends [67].
Ethylene/propylene homo- and copolymer waxes are manufactured by the high-
temperature solution process [3] using high-mileage Ziegler-Natta catalysts [68].
Again, metallocenes in combination with methylalumoxane offer the opportunity
to build up a new technology, as described elsewhere [56], with the further
prospect of tailoring the products by tailoring the metallocenes.
236 2.3 Reactions of Unsaturated Compounds

n poly-loletins

P
105
OD

potyhobutylenes
a d other
pol y-Ioleflnr

I I I I
0 20 40 60 80 100
polyethylenes homopolymem
copolymer compositlon [mol%]

Figure 2. Product map (average molecular mass vs. copolymer composition) and applications.
EPR = ethylene/propylene rubber; PE = polyethylene; HD = high-density;
LLD = linear, low-density; VLD = very low-density; PP = polypropylene;
i = isotactic; s = syndiotactic; PS = polystyrene.

With the high-temperature solution polymerization processes, various ethylene

homo- and copolymers with different average molecular mass and copolymer
compositions are produced. The product portfolio comprises PE-HD, PE-LLD,
PE-VLD, and the ethylene/propylene elastomers (EPM, EPDM) (see Figure 2).
The thermoplastic products have a wide range of applications [l]. The elastomeric
ethylene/propylene copolymers can also be applied widely in the automotive in-
dustry, for plastics modification, in industrial applications such as seals, in electri-
cal cables, and in tires [2]. Uncured ethylene/propylene copolymers are applicable
as viscosity index improvers for lubricant oils [5].
With metallocenes and methylalumoxane or other compounds, ethylenel
1-octene copolymers can be synthesized under solution polymerization process
conditions [3 13. A wide spectrum of high-performance products are available,
as described elsewhere [69]. These tailor-made products are used for sealant
applications (blown film), injection molding and flexible insulation (wire and
cable).
Introduction of metallocenes in state-of-the-art technologies gives access to
new copolymers of ethylene and 1-olefins such as propylene, 1-butene, 1-hexene,
4-methyl- 1-pentene, and 1-octene with narrow molecular mass distributions and
uniform copolymer compositions. On this basis it is possible to synthesize
polyolefins with well-balanced properties. These metallocene/methylalumoxane
 References 237

catalyst systems further open new prospects in the field of ethylene/propylene

elastomer (EPM, EPDM) production because in this field compositional homo-
geneity is of high importance [32, 49, 501.
Metallocenes and methylalumoxanes can further be used to synthesize isotactic
polypropylene [70, 7 11, syndiotactic polypropylene [38], other propylene poly-
mers or oligomers [72], ethylenekycloolefin copolymers [ 10-1 31, syndiotactic
polystyrene [ 14, 6 I], and ethylenehtyrene copolymers [64]. Cycloolefin copoly-
mers are amorphous, with high glass transition temperatures [ 10-131. The syndio-
tactic polystyrenes are semicrystalline polymers with a glass transition tempera-
ture around 100 "C and a melting point of 270 "C [14].
All these new polymers and copolymers are based on wellknown monomers.
By tailoring the polymer structure using catalysts or catalyst systems new combi-
nations of properties can be achieved which open the door for new applications.
The catalytic polymerization processes show new possibilities in the polyolefin
field to broaden the field of applications for these products [73].
Metallocenes can be used not only in homogeneous catalysis. To introduce
metallocenes in existing bulk or gas-phase processes they have to be immobilized
on supports (cf. Section 3.1.1.3). In general, if there is a particle-forming process
during polymerization, as described elsewhere [74], the metallocenes must be sup-
ported before being applied as heterogeneous catalysts.

References
[ l ] G. Burkhardt, U. Hiisgen, M. Kalwa, G. Potsch, C. Schwenzer. Ullmann's Encyclopedia
of Industrial Chemistry (Eds.: B. Elvers, S. Hawkins, G. Schulz), VCH, Weinheim,
Vol. 20, 1992, p. 663.
[2] G. Ver Strate, Encyclopedia of Polymer Science and Engineering (Eds.: H. F. Mark,
N. N. Bikales, C. G. Overberger, G. Menges, J. I. Kroschwitz), J. Wiley & Sons, New
York, Vol. 6, 1986, p. 552.
[3] G. Illmann, H. Schmidt, W. Brotz, G. Michalczyk, W. Payer, C. D. Frohning, W. Dietsche,
G. Hohner, J. Wildgruber, Ullmanns Encyklopadie der Technischen Chemie, VCH,
Weinheim, Vol. 24, 1983, p. 1.
[4] W. Payer, Kunststoffe 1993, 83, 775.
[S] H. G. Muller, Angew. Mukromol. Chem. 1978, 67, 61.
[6] Hoechst AG (G. Hohner, W. Interthal, D. Ohlendorf), DE 3.323.729 (1985).
[7] F. Durst, R. Haas, W. Interthal, T. Keck, Chem. Ing. Techn. 1982, 54, 213.
[8] Stamicarbon BV (P. S. Smith, P. J. Lemstra, A. J. Pennings), DE 3.004.699 (1980).
[9] Allied Corporation (G. A. Harpell, S. Kavesh, I. Palley, D. C. Prevorsek), US 4.455.273
(1984).
[lo] H. Cherdron, M.-J. Brekner, F. Osan, Angew. Makromol. Chem. 1994, 223, 121.
[ 1 1 ] T. Weller, D. B. Schulz, Kunststoffe 1998, 88, 1748.
[I21 E. Beer, W. Hatke, Plastic Special 6/1999.
[ 131 P. Thomas-Hasenzahl, Kunsfstoffe2000, 90, 11.
[14] U. Koch-ReuB, Kunststoffe, 1998, 88, 1139.
[IS] K. S. Whiteley, T. G. Heggs, H. Koch, R. L. Mawer, W. Immel, Ullmann's Encyclopedia
of Industrial Chemistry, Vol. 21, 1992, p. 487.
238 2.3 Reactions of Unsaturated Compounds

[16] BASFAG (H. Hoffmann, H. Mach, H. P. Rath, P. Reuter), EP 116.913 (1990); BASFAG
(P. Rath), EP 628.575 (1994).
[ 171 K. Weissermel, H.-J. Arpe, Industrielle Organische Chemie, VCH, Weinheim, 1978,
p. 69; B. Comils, W. A. Herrmann, R. Schlogl, H.-C. Wong (Eds.), Catalysis from
A to Z, Wiley-VCH, Weinheim, 2000.
[18] K. Ziegler, Angew. Chem. 1964, 76, 545.
[19] G . Natta, Angew. Chem. 1964, 76, 553.
[20] H. Sinn, W. Kaminsky, Adv. Organomet. Chem. 1980, 18, 99.
[21] J. P. Hogan, Applied Industrial Catalysis, Vol. 1 (Eds.: B. E. Lcach), Academic Press,
Orlando, 1983, p. 149.
[22] L. Bohm, Chem. Ing. Techn. 1984, 56, 674.
[23] P. C. BarbC, G. Cecchin, L. Noristi, Adv. Polym. Sci., 1987, 81, 1.
[24] Phillips Petroleum Co. (J. P. Hogan, R. L. Banks), BE 530.617 (1953).
[25] K. Ziegler, E. Holzkamp, H. Breil, Angew. Chem. 1955, 67, 426, 541.
[26] G. Natta, P. Pino, P. Corradini, F. Danusso, E. Mantica, G. Mazzanti, G. Moraglio, J. Am.
Chem. Soc. 1955, 77, 1708.
[27] H. Domininghaus, Die Kunststoffe und ihre Eigenschafen, VDI Verlag, Diisseldorf,
1986.
[28] W. Kaminsky, J. Kopf, H. Sinn, H.-J. Vollmer, Angew. Chem. 1976, 88, 688.
[29] A. Andresen, H.-G. Cordes, J. Herwig, W. Kaminqky, A. Merck, R. Mottweiler, J. Pein,
H. Sinn, H.-J. Vollmer, Angew. Chem. 1976, 88, 689.
[30] L. L. Bohm, J. Berthold, R. Franke, W. Strobel, U. Wolfmeier, Studies in SurJace Science
and Catalysis, Vol. 25 (Eds.: T. Keii, K. Soga), Elsevier, Amsterdam, 1986, p. 29.
[31] J. C. Stevens, Catalyst Design for Tailor-Made Polyolefns (Eds.: K. Soga, M. Terano),
Kodansha, Tokyo, 1994, p. 277.
[32] C. Cozewith, G. Ver Strate, Macromolecules 1971, 4, 482.
[33] F. R. W. P. Wild, L. Zsolnai, G. Huttner, H. H. Brintzinger, J. Organomet. Chem. 1982,
232, 233.
[34] J. A. Ewen, J. Am. Chem. Soc. 1984, 106, 6355.
[35] W. Spaleck, M. Antberg, V. Dolle, R. Klein, J. Rohrmann, A. Winter, New J. Chem.
1990, 14, 499.
[36] J. A. Ewen, M. J. Elder, R. L. Jones, L. Haspeslagh, J. L. Arwood, S. G. Bott, K. Ro-
binson, Makromol. Chem., Macromol. Symp. 1991, 48/48, 253.
[37] H. H. Brintzinger, D. Fischer, R. Miilhaupt, B. Bieger, R. M. Waymouth, Angew. Chem.
1995, 107, 1255.
[38] T. Shiomura, M. Kohno, N. Inoue, Y. Yokote, M. Akiyama, T. Asanuma, R. Sugimoto,
S. Kimura, M. Abe, Catalyst Design for Tailor-Made Polyolefns (Eds.: K. Soga,
M. Terano), Kodanska, Tokyo, 1994, p. 327.
[39] T. Sasaki, T. Ebara, H. Johoji, Polym. Adv. Tech. 1993, 4, 406.
[40] M. Aulbach, F. Kiiber, Chem. uns. Zeit 1994, 28, 197.
[41] M. Farina, Trends Polym. Sci. 1994, 2, 80.
[42] R.-D. Maier, Kunststofle 1999, 89, 120.
[43] H. Horacek, Makromol. Chem. Suppl. 1975, 1, 415.
[44] L. Mandelkem, Comprehensive Polymer Science (Eds.: G. Allen, J. C. Bevington),
Vol. 2, Pergamon Press, Oxford, 1989, p. 363.
[45] F. Hamada, K. Fujisawa, A. Nakajima, Polym. J. 1973, 4, 316.
[46] M. Bochmann, Nachl: Chem. Techn. Lab. 1993, 41, 1220.
[47] H. Sinn, I. Schimmel, M. Ott, N. von Thiemen, A. Harder, W. Hagendorf, B. Heitmann,
E. Haupt, Metalorganic Catalysts for Synthesis and Polymerization (Ed.: W. Kaminsky),
Springer Verlag, Berlin, 1999, p. 105.
[48] E. Zurek, T. K. Woo, T. K. Firman, T. Ziegler, Inorg. Chem. 2001, 40, 361.
 References 239

[49] M. Galimberti, E. Martini, F. Sartori, F. Piemontesi, E. Albizzati, Proc. MetCon ‘94,

Catalyst Consultant Inc., 1994.
[SO] M. Galimberti, E. Martini, F. Piemontesi, F. Sartori, I. Camurati, L. Resconi, E. Albizzati,
Macromol. Symp. 1995, 89, 259.
[Sl] W. Kaminsky, Cutal. Today, 1994, 20, 257.
[52] W. Kaminsky, Angew. Makromol. Chem. 1994, 223, 101.
[53]J. Scheirs, W. Kaminsky, Metallocene-Based Polyolefins, Vols. I, 11, John Wiley and
Sons, New York, 1999.
[54] D. Cam, F. Sartori, Macromol. Chem. Phys. 1994, 2817.
[55]Exxon Chemical Patents Inc. (S. Floyd, E. L. Hoel), EP 347.129 (1989).
[56] Hoechst AG (H.-F. Henmann, L. Bohm, H. Voigt, W. Spaleck, G. Hohner), EP 602.509
(1 994).
[57] R. Hess, Siiddeutsches Kunststoff-Zentrum Wiirzburg, Technologien und Murkte fur
Metallocen-Kunststoffe 2000, G.
[58] Fina Research SA (W. Vermeiren, P. Bruns, H. Hinnekens), EP 586.777 (1994).
[59] Shell International Research Maatschappij BV (A. von Zon, E. J. M. de Boer, H. J. R. de
Boer), EP 613.873 (1994).
[60] Exxon Research and Engineering Co. (R. D. Lundberg, R. R. Phillips), EP 630.917
(1994).
[61] N. Ishihara, M. Kuramoto, Catalyst Design for Trrilor-Made Polyolefins (Eds.: K. Soga,
M. Terano), Kodansha, Tokyo, 1994, p. 339.
[62] R. Po, N. Cardi, Progr: Polym. Sci. 1996, 21, 47.
[63] The Dow Chemical Co. (J. C. Stevens, F. J. Timmers, D. R. Wilson, G. F. Schmidt, P. N.
Nickias, R. K. Rosen, G. W. Knight, S. Lai), EP 416.815 (1991).
[64] C. Rickett, B. Walter, Siiddeutsches Kunststoff-Zentrum Wiirzburg, Technologien und
Markte fur Metallocen-Kunststoffe 2000, cf. [57], p. 7.
[65] Exxon Chemical Patents Inc. (H. C. Welbom, C. S. Speed), EP 260.999 (1988).
[66] J. L. Hemmer, The 1990s and Beyond, The Plastics and Rubber Institute, 1992, p. S2A/3/1.
[67] R. Miihlhaupt, T. Duschek, D. Fischer, S. Setz, Polyrn. Adv. Technol. 1992, 4 , 439.
[68] B. Diedrich, Appl. Polym. Symp. 1975, 26, 1.
[69] K. W. Swogger, G. M. Lancaster, Catalyst Design for Tailor-Made Polyolefns (Eds.:
K. Soga, M. Terano), Kodansha, Tokyo, 1994, p. 285.
[70] W. Spaleck, M. Antberg, M. Aulbach, B. Bachmann, V. Dolle, S. Haftka, F. Kiiber,
J. Rohrmann, A. Winter, Ziegler Catalysts, Springer, Berlin, 1995, p. 83.
[71] J. R. Grasmeder, D. Ozdemir, Kunststoffe 1998, 88, 1126.
[72] K.-D. Hungenberg, J. Kerth, F. Landhauser, H.-J. Miiller, P. Miiller, Angew. Makromol.
Chem. 1995, 227, 159.
[73] R. Miilhaupt, Plastverarbeiter 1999, 50, 68.
[74] L. L. Bohm, R. Franke, G. Thum, Transition Metals and Organometallics as Catalysts
for Olefn Polymerization (Eds.: W. Kaminsky, H. Sinn), Springer, Berlin, 1988, p. 391.
240 2.3 Reactions of Unsaturated Compounds

2.3.1.3 Oligomerization of Ethylene to Higher

Linear a-Olefins
Dieter Vogt

2.3.1.3.1 Introduction
The development of polymers has seen a great impact from organometallic chem-
istry over recent decades. In the early 1950s Ziegler discovered the so-called Auf-
baureaktion during his studies on organoaluminium chemistry [I]. On this basis
Gulf Oil [2] and Ethyl Corporation [ 3 ] developed commercial processes (cf.
eq. (1)).
( n + 2 ) CH2=CH2 -P p y
cat.

The most important discovery, made at Miilheim in 1952, is based on the ob-
servation that in the presence of nickel salts the alkylaluminium-catalyzed Auf
baureaktion is directed to yield mainly butenes. In the literature this phenomenon
is referred to as the “nickel effect” [4, 51. This led to low-pressure olefin polymer-
ization. These findings initiated an intensive investigation of organonickel chem-
istry. Wilke and co-workers observed for the first time that ligands control the
selectivity in nickel-catalyzed reactions. Ligand variations extended to bidentate
P n O chelates was applied by Keim at Shell Development Co. to oligomerize
ethylene, leading to the Shell higher olefin process (SHOP), today producing
about one-half of the linear a-olefins made by oligomerization.
Today linear a-olefins are produced mainly by ethylene oligomerization be-
cause of the high product quality and the good availability of ethylene. Other
routes to a-olefins with decreasing importance are paraffin wax-cracking, paraffin
dehydrogenation, and alcohol dehydration. The wide application and increasing
need for short-chain a-olefins as comonomers for polymers cause the linear olefin
market still to grow.

2.3.1.3.2 Applications and Commercial Aspects of a-Olefins

Linear a-olefins are very versatile intermediates and building blocks for the che-
mical industry. The main applications are comonomers for polyethylene (C,-C,)
and feedstocks for surfactants (C,2-C20) and plasticizers (C6-C Today the
predominant route to a-olefins is oligomerization of ethylene, which is readily
available from pyrolysis of light naphtha, gas-oil, or wet natural gases. In addition,
the high product quality compared with that from classical routes via wax-crack-
ing makes oligomerization the preferred process. It is anticipated that nearly all
wax-cracking sites will be shut down in the near future [6, 71. As shown in
Table 1 the overall installed capacity for ethylene oligomerization to linear a-ole-
fins in 1992 was about 2 million metric tons per year. Worldwide production in
 2.3.1.3 Oligomerization of Ethylene to Higher Linear a-Olefns 241

Table 1. Linear a-olefin capacities by ethylene oligomerization.

Technology Company and location Capacity 110’ t/a]
Initial [year] Expansion [year] Present total”’
Ziegler Chevron 125 (1966) 125 (1990) 249
type (Cedar Bayou, USA)
Ethyl (Pasadena, USA) 400 (1971) 55 (1989) 472
Ethyl (Feluy, Belgium) 200 (1992) 200
Chemopetrol 120 (1992) 120
(Czech Republic)
Mitsubishi Kasei Corp. 50 50
(Kurashiki, Okayama
Pref., Japan)
SHOP Shell (Geismar, USA) 200 (1 977) 390 (1989) 590
Shell (Stanlow, UK) 170 (1982) 100 (1989) 278
Zr Idemitsu Petrochemicals 50 (1989) 50
(Ichihara, Chiba Pref.,
Japan)
a) In 1992.

1992 was approximately 1.5 million tons, from which the major part (70 %) was
made in the USA; 25 % was made in Europe and 4 % in Japan. The remainder was
produced at a site in the Czech Republic starting operation in the second half of
1992 and based on Ziegler technology [7].
The lower C4-Cs a-olefins are mainly used as comonomers [S]. Small amounts
of up to 3 % a-olefins are used to produce high-density polyethylene (HDPE) with
a higher stresdcrack resistance [9] and a slightly reduced density (0.959-0.938
g/cm3) compared with the homopolymer (0.965-0.955 g/cm’). Higher quantities
of 4-12 % a-olefins are added to produce linear low-density polyethylene
(LLDPE) with considerably reduced density (0.935-0.9 15 g/cm3), for which
1-butene and 1-hexene are preferred in the gas-phase process and 1-octene in
the liquid phase [ 101.
Hydrocarboxylation of the C6-C8 a-olefins with cobaltcarbonyllpyridine cata-
lysts at 200°C and 20 MPa gives predominantly the linear carboxylic acids.
The acids and their esters are used as additives for lubricants. The C6-Cl,,
a-olefins are hydroformylated to odd-numbered linear primary alcohols, which
are converted to polyvinylchloride (PVC) plasticizers with phthalic anhydride.
Oligomerization of (preferably) 1-decene, applying BF3 catalysts, gives oligomers
used as synthetic lubricants known as poly-a-olefins (PAO) or synthetic hydrocar-
bons (SHC) [ l l , 121. The Clo-C,2a-olefins can be epoxidized by peracids; this
opens up a route to bifunctional derivatives or ethoxylates as nonionic surfactants
~131.
242 2.3 Reactions of Unsaturated Compounds

The main applications of the middle-range a-olefins are biodegradable deter-

gents. Hydroformylation leads to the primary detergent alcohols. Alkylation of
benzene, followed by sulfonation of the aromatic ring, gives the linear alkylben-
zene sulfonates (LAS or LABS). Linear alkyl sulfates are obtained on conversion
with sulfuric acid. Direct sulfonation followed by hydrolysis with sodium hydro-
xide yields the a-olefin sulfonates (AOS) as a mixture of the alkene sulfonates and
the hydroxyalkane sulfonates. Alkylphenols derived from alkylation of phenol
with CI4-Cl6a-olefins are utilized as surfactants and lubricant oil additives. Dif-
ferent amines in the CI4-Cl8range can be obtained by hydrobromination, addition
of amines, or conversion with acetonitrile. The CI6and CISa-olefins are converted
with maleic anhydride to alkenylsuccinic anhydrides which are used as paper si-
zers. Detergents, copolymers, and plasticizers are the main applications of a-ole-
fins, making up about 75 % of the whole market as is indicated in Table 2 [14].
The uses of some of the products from linear a-olefins in the USA and in Europe
are given in Table 3 [ 151.

Table 2. a-Olefin markets 171.

Application
.. Market share [%I a-Olefin cut
USA Western Europe Japan

Detergents 32 56 35 cIo-c2”+
Copolymers 26 13 37 c4-C8
Plasticizers 12 8 22 c6-c I0
Poly-a-ole fins 9 12
Others 21 11
a) Included in “Others”.

Table 3. Uses of higher linear a-olefins in 1992 (Stanford Research Institute).

Final products Olefin consumption [ lo3 t]
USA Western Europe
Detergent alcohols 215 150
Plasticizer alcohols 91 34
Amines and derivatives 25 a)
a-Olefin sulfonates (AOS) 10 3
Linear alkylbenzenes (LAB) 11 40
Copolymers (HDPE, LLDPE) 208 60
Synthetic lubricants (SHC) 70 50
Lubricant additives 25 40
Total 787 385
a) Unknown.
 2.3.1.3 Oligomerization of Ethylene to Higher Linear a-Olefns 243

2.3.1.3.3 Commercial Oligomerization Processes

The first process which allowed the industrial oligomerization of ethylene was
developed by Ziegler in the early 1950s [l]. In the two-step Alfen process, the
chain-growth reaction is first accomplished at about 100 "C and 10 MPa ethylene
pressure (eq. (2)).

AIEt3 + 3n CH2=CH2 -
In a following high temperature elimination step the a-olefins are displaced by
ethylene at about 300°C and 1 MPa (eq. (3)).
In this stoichiometric reaction sequence, a Poisson distribution of a-olefin
products is obtained. The main disadvantage of this process is the large amount
of aluminium alkyls needed in an industrial plant. To overcome this drawback,
improvements of the process were developed by several companies. Only the
two most important examples, the Gulf process and the Ethyl process, will be
described in more detail. Shell developed a different route based on a nickel com-
plex catalyst. Though other processes based on different transition metal catalysts
have been developed, only the three processes mentioned above became important
H61.
r 1

Gulf Oil Process (Chevron)

In 1966 the first commercial plant producing linear a-olefins by ethylene oli-
gomerization was built by the Gulf Oil company (since 1983, Chevron) at
Cedar Bayou, TX [2, 171. The Gulf process uses a one-step catalytic proce-
dure, where chain growth and elimination occur simultaneously in the same
reactor [2]. About 0.4% wt. of AlEt, (with respect to the ethylene reacted)
are needed. As solvent heptane is used, at about 200°C and 25 MPa ethylene
pressure [18]. After the reaction, the catalyst is destroyed by hydrolysis. In this
catalytic reaction a Schulz-Flory distribution of a-olefins is obtained. Due to
the reaction of the product a-olefins with aluminium alkyls, increasing amounts
of branched olefins are obtained with increasing chain length. Nevertheless, the
a-olefins obtained have a considerably higher purity than those produced by
wax-cracking (cf. Table 4). The selectivity to a-olefins reaches 94-98 % at
an ethylene conversion of 40-80 % [ 191. Currently Chevron's overall capacity
is approx. 250000 t/a. The Chevron technology is used also by Mitsubishi
Chemical Industries in Japan and Chemopetrol in the Czech Republic (see
Table 1).
 244 2.3 Reuctions of Unsaturated Compounds

Table 4. Comparison of product qualities of technical C6-CI8 a-olefins [16].

Quality [wt. % a-olefin]
Wax-cracking Chevron Ethyl SHOP
a-Olefins 83-89 91-97 63-98 96-98
Branched olefins 3-12 2-8 2-29 1-3
Paraffins 1-2 1.4 0.1-0.8 0.1
Dienes 3-6 - - -

Monoole fins 92-95 99 >99 99.9

Ethyl Process

The Ethyl Corporation developed a process based on a combination of stoichio-

metric and catalytic chain-growth reactions. Unifying these two parts with a trans-
alkylation step allows very efficient control of the a-olefin chain length, in order
to meet the market needs [3,20]. A typical flow diagram of the process is given in
Figure 1.
The first oligomerization step uses a catalytic one-step process similar to
Chevron's process. This is operated at 160-275°C and 13-27 MPa of ethylene
pressure. After the reaction, the catalyst is destroyed by hydrolysis. The product
mixture, consisting mainly of C4-Clo a-olefins, is distilled and separated into
the c4-clO and CI2-Cl8fractions. The latter can be used directly. The lower
a-olefins are subjected to transalkylation with higher aluminium alkyls, liberating
the higher a-olefins. The higher aluminium alkyls are produced in the stoichio-

catalytic reactor transalkylation stoichiometric reactor

r AIR',

AIEt3

ethylene

I
m
Figure 1. Flow scheme of the Ethyl process.
AIR$

c1z - C18
 2.3.1.3 Oligomerization of Ethylene to Higher Linear a-Olefins 245

metric part of the reaction, operating at about 100 "C and 20 MPa. Transalkylation
is carried out at about 300°C and 10 MPa. In a second distillation, the liberated
olefins are separated from the aluminium alkyls. These alkyls are fed into a chain-
growth reactor, where they are grown with ethylene to long-chain aluminium
alkyls, which are recycled to the transalkylation stage. Because of the recycle,
co-oligomerization of product a-olefins with ethylene yields considerable amounts
of branched olefins. The higher-molecular-weight C 16-C fraction, especially,
consists of only 63 % linear a-olefins (cf. Table 4). Ethyl's total capacity for
ethylene oligomerization is now about 670000 t/a.

Shell Higher Olefin Process (SHOP)

The Shell higher olefin process is not only a process for ethylene oligomerization,
but a very efficient and flexible combination of three reactions: oligomerization,
isomerization, and metathesis. It was designed to meet the market needs for linear
a-olefins for detergents [21]. Basic research for the oligomerization stage was car-
ried out at the laboratories of the Shell Research Company at Emeryville by Keim
from the late 1960s to the early 1970s 122-311. The whole process was developed
in a colaboration between Shell Development USA and the Royal Shell Labora-
tories at Amsterdam in the Netherlands 132-411. The first commercial plant was
built at Geismar, LA, in 1977. The development of this plant and that at Stanlow
(UK) is summarized in Table 1. Though there was some speculation about other
plants to be built in Canada and Japan, these two sites are currently the only
operational ones, having a total capacity of nearly 1 million tons of a-olefins
per year.

Process Description

The oligomerization reaction is carried out in a polar solvent in which the nickel
catalyst is dissolved but the nonpolar products, the a-olefins, are nearly insoluble.
Preferred solvents are alkanediols, especially 1,4-butanediol. This was one of
the first examples of a biphasic liquid/liquid system to be used in catalysis and
is one of the key features of the process. The nickel catalyst is prepared in situ
from a nickel salt, e.g., nickel chloride, and a chelating P n O ligand like
o-diphenylphosphinobenzoic acid (Structure 1) by reduction with sodium boro-
hydride 130, 391. Suitable ligands are the general type of diorganophosphino
acid derivatives (2).

aPPh2
1
COOH
RR'P
n
2
COOR"
246 2.3 Reactions of Unsaturated Compounds

-- I

0.4 0.5 0.6 0.65 0.7 0.75 0.8 0.85 1 9

Growth factor, K

Figure 2. Schulz-Flory product distribution dependence on the chain growth factor K .

The nickel concentration in the catalyst system is in the range 0.001-0.005

mol%. The oligomerization is carried out in a series of reactors at temperatures
of 80-140°C and pressures of 7-14 MPa. The rate of the reaction is controlled
by the rate of catalyst addition [38]. A high partial pressure of ethylene is required
to obtain good reaction rates and high product linearity [30]. The linear a-olefins
produced are obtained in a Schulz-Flory type of distribution with up to 99%
linearity and 96-98% terminal olefins over the whole range from C4 to C30+
(cf. Table 4) [21].
The shape of the Schulz-Flory distribution and the chain length of the a-olefins
are controlled by the geometric chain-growth factor K, defined as K = n(C,+,)/
n(C,) (see Figure 2). For the economy of the whole process it is very important
that the K-factor can easily be adjusted by varying the catalyst composition.
Usually the value is between 0.75 and 0.80.
The heat of the reaction is removed by water-cooled heat exchangers between
the reactors (see Figure 3). In a high pressure separator the insoluble products and
the catalyst solution as well as unreacted ethylene are separated. The catalyst
solution is fed back into the oligomerization reactor. Washing of the oligomers
by fresh solvent in a second separation step removes traces of the catalyst. In a
series of distillation columns the a-olefins are separated into the desired product
fractions.
First the lower C4-Clo a-olefins are stripped off. In a heavy ends column the
C20+a-olefins are removed from the desired C12-C20a-olefins. Finally the mid-
dle-range products meeting the market needs are separated into the desired cuts
and blends. The very high flexibility of the "SHOP" results from the following
steps. The C4-Clo and the C20+-fractionsare combined to be isomerized to internal
linear olefins (eq. (4)) and then subjected to a metathesis reaction (eq. (5)). Both
steps require about 80-140 "C and 0.3-2 MPa. Isomerization is accomplished by a
typical isomerization catalyst such as N d K on AI2O3 or a MgO catalyst in the
liquid phase [42], where about 90% of the a-olefins are converted to internal
 2.3.1.3 Oligomerization of Ethylene to Higher Linear a-Olefns 247

Figure 3. Flow scheme of the Shell higher olefin process (SHOP).

A 0 = a-olefin; C.W.= cooling water.

olefins. Metathesis of the lower and higher internal olefins gives a mixture of
olefins with odd and even carbon chain lengths. The mixture comprises about
11-15 % of the desired CII-C14linear internal olefins, which are separated by
distillation. The undesired fractions can be recycled, feeding the light olefins
directly back to metathesis while the higher-boiling fractions are again subjected
to isomerization. Because of the high proportion of short-chain olefins in the
metathesis feed, the double bonds in the end product are shifted toward the
chain ends.
Altogether the different possibilities of shifting products to the desired chain
length and double-bond position make the “SHOP” the most elegant and flexible
process operating today. It is furthermore one of the larger applications of homo-
geneous catalysis.

L/ Co / Mo or Re
+ *
/-==\
ClO c18
248 2.3 Reactions of Unsaturated Compounds

Mechanistical Aspects

The mechanism of the nickel-chelate complex-catalyzed oligomerization has been

investigated by Keim and co-workers. For this purpose a large number of nickel-
chelate complexes (e.g. 3-7) have been prepared and tested as one-component
catalyst precursors [43-45].
It turned out that the function of the different parts of the precursor complex can
be rationalized by the generalized structure as shown in Figure 4. The chelate part
of the complex controls the selectivity of the reaction while the organo part serves
only to stabilize the complex [46, 471.

chelate part organo part

Figure 4. Generalized catalyst precursor complex.

Ph Ph Ph Ph
\ /

0 ko:iyy Ph
f,:Np
i" PPh3

Ph
x > N i < h PPh3

3 4 5

Ph Ph
\ /

x > N i< PPh3

Ph
6

An interesting feature in the formation of complex 4 from bis(cyclooctadieny1)-

nickel and the phosphorane is the shift of one phenyl group from phosphorus to
the nickel (eq. (6)) [48].
 2.3.1.3 Oligornerization of Ethylene to Higher Linear a-Olefins 249

Complexes 3-7 oligomerize ethylene in toluene at 80 "C and 5 MPa to 99 %

linear olefins with 98% a-olefins. Complex 4 reaches an activity of 6000 mol
ethylene per mol of catalyst [43]. Applying the reaction in suspension in n-hex-
ane, high-molecular-weight linear polyethylene is obtained.
It is largely accepted that the active species in ethylene oligomerization is a
nickel hydride species like 8. The mechanism for the hydride formation is sup-
ported by the reactions depicted in eqs. (7)-(9). Complex 9 eliminates butadiene
at low temperatures and becomes active at 40 "C.Insertion of ethylene and elim-
ination of styrene from structure 4 at 70 "C causes the complex to become active,
while the more strongly bound cyclopentadienyl ligand in structure 10 needs
130°C [49]. The elimination products of these reactions could be detected by
GLC.
Ph, ,Ph Ph, ,Ph

9 8

Ph
x>NiT 0"
Ph\ / Ph

PPh3
CH;!

-
=CH2 / 70 "C

Ph
Ph\

x > N i - H
/
Ph

4 8

In the case of complex 3, in-situ NMR studies gave hints of the existence of a
nickel hydride [50].The stable nickel hydride (Structure 11) could be isolated and
characterized by X-ray diffraction analysis [5 11. Complex 11 inserts ethylene to
give an ethylnickel complex which reverts to the hydride on warming up.
Based on these results the mechanism shown in Scheme 1 was postulated. If an
excess of triphenylphosphine is added, chain termination is preferred. Using 10
equivalents of triphenylphosphine, mainly 1-butene is observed. A variety of
substitutions in the chelate ligand have been described in order to gain a better
understanding of the factors controlling selectivity [45, 521. Other groups became
interested. For example, Kissin [53] and Beach [54-561 introduced sulfonated
ylides. Compound 12 is an active one-component oligomerization catalyst
which can be activated by a factor of 20-200 by the addition of aluminium alk-
oxides such as Et,AlOEt [56]. The sulfonate group brings about a better solubility
in polar solvents and therefore improves catalyst separation.
250 2.3 Reactions of Unsaturated Compounds

Ph\ / Ph
Na03sx'P<Ni<h
Ph Ph

0 PCY3 '
0 PPh3
Ph
F3c 11 12

Scheme 1. Postulated mechanism for ethylene oligomerization via a P n0-stabilized nickel

hydride species: p I , p2 . . . pn = propagation steps; e , , e2 . . . e,, = elimination steps.

2.3.1.3.4 Recent Developments

Triggered by the developments in late transition metal catalyzed polymerization,
new catalyst systems were described very recently for the oligomerization of
ethene. Nickel and palladium complexes based on a-diimine ligands 13 and imi-
nophosphines 14 were reported to be very active and selective oligomerization
catalysts [57, 581. Activation of the Ni(I1) diimine halides with a large excess
of M A 0 (210 equiv.) leads to oligomerization catalysts with activities of between
 References 25 1

20 000 to 116 000 TON within an hour. The Pd complexes are activated by an acid
containing a weakly coordinating anion.
Extremely active and highly selective iron-based catalysts are derived with
bis(imino)pyridine ligands 15 [59-621. Turnover frequencies of up to an amazing
1.8 X 108hand a-olefin selectivity of > 99 % can be obtained. The K value can
be controlled and adjusted to the requested range between 0.70 and 0.85.
Increasing the temperature lowers K , while increasing the bulk of R at the aryl
substituent results in the formation of a larger amount of higher a-olefins.
These new findings can be regarded as a considerable spur to technology, stimu-
lating new developments in a process that was already in its mature phase.

References
[I] K. Ziegler, H. Gellert, H. Kuhlhorn, H. Martin, K. Meyer, K. Nagel, H. Sauer, K. Zoser,
Angew. Chem. 1952, 64, 323; K. Ziegler, Angew. Chem. 1955, 67, 541.
[2] Gulf Res. Dev. Co. (H. B. Fernald, B. H. Gwynn, A. N. Kresge), DE 1.443.927
(1961).
[3] Ethyl Corp. (C. W. Lanier), US 3.906.053 (1975).
[4] G. Wilke, Angew. Chem. 1988, 100, 189; Angew. Chem., Int. Ed. Engl. 1988, 27,
185.
[S] G. Wilke in Fundamental Research in Homogeneous Catalysis (Ed.: M. Tsutsui), Vol. 3,
Plenum, New York, 1979, pp. 1-24.
[6] Anon., Eur: Chem. News Jan. 19, 1987, 8.
[7] C. S. Read, R. Willhalm, Y. Yoshida in Linear Alpha-Olejins, The Chemical Economics
Handbook Marketing Research Report, SRI International, Oct. 1993, 68 1S030A.
[8] Anon., Neodene Alpha and Internal Olejins, Shell Technical Bulletin, Shell Chemicals,
1989.
[9] M. Sherwood, Chem. Ind. (London) 1982, 994.
[lo] F. J. Karol, CHEMTECH 1983, 222.
[ I l l J. A. Brennan, lnd. Eng. Chem., Prod. Res. Dev. 1980, 19, 2.
[I21 R. L. Shubkin, M. S. Bayerlan, A. R. Maler, Ind. Eng. Chem., Prod. Res. Dev. 1980,
19, 15.
1131 B. W. Werdelmann, Fette, Seifen, Anstrichm. 1974, 76, 1.
1141 P. Layman, Chem. Eng. News 1988 (22), 9.
[IS] A. Behr, Ullmann’s Encycl. Ind. Chem. 5th ed. 1992 Vol. A13, p. 251.
[I61 A. M. Al-Jarallah, J. A. Anabtawi, M. A. B. Siddique, A. M. Aitani, A. W. Al-Sa’doun,
Catal. Today 1992, 14, I .
252 2.3 Reactions of Unsaturated Compounds

[ 171 Anon., Guljene Olefins, Chevron Technical Bulletin, Chevron Chemical Co., 1988.
[18] Chevron/Gulf, GB 186.610 (1970).
[19] A. Hennico, J. Leonard, A. Forestiere, Y. Glaize, Hydrocarbon Process, 1990, 69, 73.
[20] Anon., Alpha Olefns, Ethyl Technical Bulletin, Ethyl Chemicals Group, 1981.
[21] A. H. Turner, J. Am. Oil Chem. Soc. 1983, 60, 594.
[22] Shell Dev. Co. (S. R. Baur, H. Chung, P. W. Glockner, W. Keim, H. van Zwet),
US 3.635.937 (1972).
[23] Shell Dev. Co. (R. Baur, H. Chung, D. Camel, W. Keim, H. van Zwet), US 3.637.636
(1972).
[24] Shell Dev. Co. (R. Baur, P. W. Glockner, W. Keim, H. van Zwet, H. Chung),
US 3.644.563 (1972).
[25] Shell Dev. Co. (H. van Zwet, R. Baur, W. Keim), US 3.644.564 (1972).
[26] Shell Dev. Co. (P. W. Glockner, W. Keim, R. F. Mason), US 3.647.914 (1972).
[27] Shell Dev. Co. (R. Baur, P. W. Glockner, W. Keim, R. F. Mason), US 3.647.915
(1972).
[28] Shell Dev. Co. (R. Baur, H. Chung, W. Keim, H. van Zwet), US 3.661.803 (1972).
[29] Shell Dev. Co. (R. Baur, H. Chung, Amett, P. W. Glockner, W. Keim), US 3.686.159
(1972).
[30] E. R. Freitas, C. R. Gum, Chem. Eng. Prog. 1979, 75, 73.
[31] E. L. T. M. Spitzer, Seifen ole Fette Wachse 1981, 107, 141.
[32] Shell Oil (R. F. Mason), US 3.676.523 (1972).
[33] Shell Oil (R. F. Mason), US 3.686.351 (1972).
[34] Shell Oil (A. J. Berger), US 3.726.938 (1973).
[35] Shell Oil (R. F. Mason), US 3.737.475 (1973).
[36] Shell (R. F. Mason, G. R. Wicker), DE 2.264.088 (1 973).
[37] Shell Oil (E. F. Lutz), US 3.825.615 (1974).
[38] Shell Oil (E. F. Lutz), US 4.528.416 (1985).
[39] Shell (E. F. Lutz, P. A. Gautier), EP 177.999 (1986).
[40] W. Keim in Fundamental Research in Homogeneous Catalysis (Eds.: M. Graziani et al.),
Vol. 4, Plenum, New York, 1984, p. 131.
[41] E. F. Lutz, J. Chem. Educ. 1986, 63, 202.
[42] Shell Oil (F. F. Farley), US 3.647.906 (1972).
[43] W. Keim, F. H. Kowaldt, R. Goddard, C. Kriiger, Angew. Chem. 1978, 90,493; Angew.
Chem., Int. Ed. Engl. 1978, 17, 466.
[44] W. Keim, A. Behr, B. Limbacker, C. Kriiger, Angew. Chem. 1983, 95, 505; Angew.
Chem., lnt. Ed. Engl. 1983, 22, 503.
[45] W. Keim, A. Behr, B. Gruber, B. Hoffmann, F. H. Kowaldt, U. Kiirschner, B. Limbacker,
F. P. Sistig, Organometallics 1986, 5, 2356.
[46] W. Keim, New J. Chem. 1987, 11, 531.
[47] W. Keim, J. Mol. Catal. 1989, 52, 19.
[48] A. Behr, W. Keim, Arab. J. Sci. Eng. 1985, 10, 377.
[49] W. Keim, Angew. Chem. 1990, 102, 251; Angew. Chem., lnt. Ed. Engl. 1990,
29, 235.
[50] W. Keim, Ann. N.Y Acad. Sci. 1983, 415, 191.
[51] U. Miiller, W. Keim, C. Kriiger, P. Betz, Angew. Chem. 1989, 101, 1066; Angew. Chem.,
lnt. Ed. Engl. 1989, 28, 1011.
[52] W. Keim, R. P. Schulz, J. Mol. Catal. 1994, 92, 21.
[53] Y. V. Kissin, J. Polym. Sci., Polym. Chem. Ed. 1989, 27, 147.
[54] ChevrodGulf Co. (D. L. Beach, J. J. Harrison), EP 46.330 (1982).
[55] ChevrodGulf Co. (D. L. Beach, J. J. Hamson), US 4.529.554 (1985).
[56] ChevrodGulf Co. (D. L. Beach, Y. V. Kissin), US 4.686.315 (1987).
 2.3.1.4 Dimerization and Codimerization 253

[57] S. A. Svejda, M. Brookhart, Organometallics 1999, 18, 65-74.

[58] E. K. van den Beuken, W. J. J. Smeets, A. L. Spek, B. L. Feringa, Chem. Commun. 1998,
223-224.
[59] B. L. Small, M. Brookhart, J. Am. Chem. SOC.1998, 120, 7143-7144.
[60] G. J. P. Britovsek, S. Mastroianni, G. A. Solan, S. P. D. Baugh, C. Redshaw, V. C.
Gibson, A. J. P. White, D. J. Wiliams, M. R. J. Elsegood, Chem. Eul: J. 2000,
2221-223 1.
[61] E. I. Du Pont De Nemours Co. (M. S. Brookhart, B. L. Small), WO 99.02.472
(1999).
[62] E. I. Du Pont De Nemours Co. (S. A. Svejda), WO 00.10.945 (2000).

2.3.1.4 Dimerization and Codimerization

He'l2ne Olivier-Bourbigou, Lucien Saussine

2.3.1.4.1 Introduction
Dimerization and codimerization reactions are widely used on an industrial scale
either to provide chemicals of high added value or to upgrade by-product olefinic
streams coming from various hydrocarbon cracking processes (steam or catalytic
cracking) or hydrocarbon forming processes (Fischer-Tropsch synthesis or metha-
nol condensation) (e. g., according to eq. (1)).

n=x+y+z

Several years ago dimerization was essentially achieved (and is still currently
performed) by means of acidic catalysts, sometimes as liquids but mainly as
solids. However, in spite of its economic interest owing to its low price and
low sensitivity to impurities, cationic oligomerization is limited in scope, the
main drawbacks being its poor selectivity and low activity toward linear olefins.
Organometallics of highly electropositive metals (aluminum, potassium) afford
better selectivities but their specificity and their poor activity restrict their use
to some specialized syntheses, e. g., dimerization of propene into 2-methyl-1-pen-
tene (Al(i-Pr)3) or 4-methyl- 1-pentene (K). Coordination catalysts offer a broader
spectrum of activity (which is often the opposite of that observed in cationic
reactions) and more diversified selectivities: their practical use can be expected
to grow.
Dimerization reactions have been the subject of recent reviews [1,2]. For
applications of homogeneous catalysis, see [ 3 ] .
254 2.3 Reactions of Unsaturated Compounds

2.3.1.4.2 Dimerization and Codimerization

of Ethylene, Propene and rz-Butenes Catalyzed
by “Cationic” Nickel Complexes
The dimerization reaction catalyzed by a nickel compound and an alkylaluminum
chloride derivative was first described in a patent in 1955 [4]. In 1966 Wilke et al.
[5] gave crucial impetus to this reaction starting from a well-defined cationic
y3-allylnickel complex (Structure 1).

They confirmed the reaction mechanism and underlined the effect of tertiary
phosphanes on the regioselectivity of the linking of propene molecules. This
complex is soluble only in chlorinated hydrocarbons. Many other systems
based on nickel catalyze the dimerization reaction and have been described in
many publications and patents.
The dimerization mechanism can be visualized as a polyaddition reaction to
Ni-H and Ni-C bonds. The Ni-H species is formed by p-hydrogen abstraction.
The reaction pathway for the formation of various propene dimer structures is
given in Scheme 1.

first insertion second insertion primary products isomerized products

- 2,3-dtmethyl-l -butene -2,3-dimethyl-Z-butene

Scheme 1. Propene dimerization by “cationic nickel” complexes. Reaction pathways of dimer

formation.
 2.3.1.4 Dimerization and Codimerization 255

Sterically demanding phosphanes such as P(i-Pr)3 and P(cyclohexyl), favor the

formation of 2,3-dimethylbutene (tail-to-tail dimer). This selectivity is tempera-
ture-dependent.
The position of the double bond inside each structure depends on the catalyst
composition. Formation of 2-methyl-2-pentene and 2,3-dimethyl-2-butene results
from a consecutive isomerization reaction and thus depends not only on the
catalyst composition but also on propene conversion. The relative reactivities of
isomeric dimers for a double-bond shift are given in [6].
Olefin dimers predominate in the reaction products due to a high rate of p-hy-
drogen abstraction. Trimers and tetramers form both by a parallel growing-chain
reaction and by consecutive reactions of dimers with monomer (see Scheme 2).
Thus at high conversion (e. g., > 80 %) dimer selectivity strongly depends on
the type of reactor used, i. e., batch and plug-flow open systems, or semi-batch
and one-stage well-mixed open systems. The type of reactor has no effect on
the parallel-growing chain reaction but has a strong influence on the consecutive
reaction. This is illustrated in diagrams in Figure 1. The reaction rate is second
order in monomer concentration and first order in catalyst concentration. The
olefin reactivities decrease in the following order:

ethylene > propene > n-butenes

Nonregioselective olejin dimerization (in the absence of any phosphine ligand)
affords an average isomer composition which hardly depends on the temperature.

Main reaction:

Parallel growing-chain reaction:

Ni ‘ud - NiH+ + trimers

I
Ni - NiH+ + tetramers

Consecutive reactions:

NiH+ + A/j
/ - N i U - Ni

NiH+ + & NiH+ + trimers

Scheme 2. Olefin oligomerization by “cationic nickel” complexes. General scheme for the
formation of various oligomers.
256 2.3 Reactions of Unsaturated Compounds

100% B

LI
E
.-
U
I
0
I!
._
W
%

A”
I E
conversion 100% conversion 100%

Batch reactors and plug flow open systems Semi-batch and continuous well-mixed
one stage reactor

Figure 1. Olefin oligomerization by “cationic nickel” complexes. Yields of dimers vs.

conversion for various types of reactors. AB: hypothetical 100 % selective
dimerization. AC: hypothetical oligomerization without any consecutive reaction
(BC: percentage of trimers, tetramers). ADE: the actual curve (DE: zone of
prevailing consecutive reaction).

Thus propene dimers, e. g., at 50 “C, have a composition of 22 % n-hexenes, 72 %

2-methylpentenes, and 6 % 2,3-dimethylbutenes. Under the same conditions,
isomer structures of n-butene dimers are 6 % n-octenes, 59 % 3-methylheptenes,
and 34 % 3,4-dimethylhexenes; propene-butene codimerization yields the follow-
ing isomer distribution: 12 % n-heptenes, 12 % 2-methylhexenes, 40 % 3-methyl-
hexenes and 35 % 2,3-dimethylpentenes. The relative rate constants for codimer-
ization are

k33 = 50; k34 = 1; k 4 4 = 0.02

(where subscript “3” represents propene; “4” represents n-butenes). When diluted
in n-butenes, isobutene (10-15 %) codimerizes with n-butenes. Codimers consist
of 80 % of dibranched octenes (2,4-dimethylhexenes).
Nonregioselective dimerization is widely used on an industrial scale for pro-
pene, n-butenes and ethylene (Institut FranCais du Pitrole’s Dimersol@process).
The catalyst results from the interaction of a nickel organic salt, soluble in a
paraffinic hydrocarbon solvent, and an ethylaluminum chloro compound; the
active species is formed in situ inside the dimerization reactor.
A process flow diagram of Dimersol@is depicted in Figure 2. The reaction
takes place at 50°C, without any solvent, in two (or more, up to four) well-
mixed reactors in series. The pressure is sufficient to maintain the reactants in
the liquid phase (no gas phase). Mixing and heat removal are ensured by external
circulation. The residence time could be between 5 and 10 h. To increase the
conversion while maintaining an acceptable dimer selectivity, a plug-flow reactor
 2.3.1.4 Dimerization and Codimerization 257

(a pipe or “snake”) can be added as a finishing reactor (see Figures 1 and 3). By
using a feedstock containing substantial amounts of alkane, this makes it possible
to comply with US specifications concerning the level of olefins in liquefied
petroleum gas (LPG) used as fuel ( 5 % max. propene in propane). The catalyst
is deactivated by anhydrous ammonia to prevent the formation of chlorinated
hydrocarbons. Washing with aqueous caustic soda and water eliminates inorganic
compounds. A stabilizing distillation column removes unconverted olefins and
saturated hydrocarbons which can be used as such (LPG) or sent back to the
cracker. Additional columns can separate each oligomer family. Typical selectiv-
ities in dimers are 85 %. To compensate for the great difference in reaction rates
between propene and butene, the codimerization reaction requires a low ratio of
propene to butene to be maintained. Thus, in several reactors connected in series,
propene has to be injected into each reactor to ensure the highest selectivity to
heptenes.
Regioselective dimerization of propene to 2,3-dimethylbutenes (DMBs) is
currently operated by Sumitomo and BP Chemicals. Both use P(cyclohexyl), as
the bulky ligand. In the Sumitomo process [7] very high selectivities in DMBs
(up to 85 %) are obtained at 20-50 OC, thanks to a sophisticated, highly efficient,
Ziegler-type catalyst system (ten times more efficient than those of conventional
catalysts) and by using toluene as a solvent. Isomerization of 2,3-dimethyl-1-
butene (DMB- 1) into 2,3-dimethyl-2-butene (DMB-2) takes place directly in

n (well-stirred) reactors plug-flow reactor

AICI,R3.,

Ni”

LPG

caustic wash water wash

dimates

Figure 2. General scheme for the Dimersol@process.

258 2.3 Reactions of Unsaturated Compounds

Figure 3. Plug-flow reactor for the Dimersol@process. The finishing reactor (“the snake”) to
comply with LPG specifications in the USA (less than 5 % olefins).

the dimerization reactor owing to the presence of an acidic component (a chlori-

nated phenol) in the catalyst formula. DMB-2 can easily be extracted from the
mixture by distillation. The flow diagram of the process shows two series-con-
nected well-mixed reactors. The residence time in each reactor is about 5 h.
The catalyst removal section is similar to that of Dimersol@.The only drawback
arises from toluene recycling, which needs an efficient distillation column. The
BP Chemicals process [8] operates without any solvent, at lower temperature,
and the catalyst composition is simpler but gives DMB-1 as the main product.
DMB-2 is obtained by subsequent isomerization on an acidic resin catalyst.
The DMBs selectivity of the BP Chemicals process is not very high.
Ethylene dimerization and oligomerization (Dimersol’ and Phillips process)
is much less developed, because of the economic situation. Even in the most
favorable conditions, nickel catalysts unavoidably produce a mixture of 1- and
2-butenes and ethylene is generally more expensive than 2-butene and l-bu-
tene/2-butene mixtures. Feedstocks are either polymerization-grade ethylene
or a 50:50 mixture with ethane. In this latter case a gas phase is inevitably
present in the reactor. The product composition is strongly dependent on ethyl-
ene conversion. The Phillips process probably uses NiCI2 . 2 PBu3 as catalyst.
Due to the very high reactivity of ethylene, catalyst consumption is remarkably
low.
 2.3.1.4 Dimerization and Codirnerization 259

Use and Economic Situation

One of the applications of the Dimersol@process is to yield products which can be

used as gasoline additives (Dimates@).Generally speaking, the Research Octane
Numbers (RONs) of olefins are much less sensitive to branching than those of
the corresponding alkanes. For instance, the RON values for n-hexane and 2-hex-
ene are respectively 25 and 93. Thus, mixed isohexenes obtained with nonregio-
selective catalysts, and in some special situations mixed isooctenes, can be used
as such, as components for gasoline, with neither hydrogenation nor separation
of higher oligomers (RON = clear 97; blending value with a conventional gasoline
= 103).
Mixed butenes obtained by ethylene dimerization are used for paraffinic
alkylation (isobutane + n-butene + trimethylpentanes) or to make propene by a
subsequent metathesis reaction (ethylene + 2-butene + 1 propene; cf. Section
2.3.3). Higher ethylene oligomers are also used as high-octane-number gasoline
components.
Isooctenes (butene dimers) and isoheptenes (propene-butene codimers) are used
as feedstocks for 0x0 synthesis, giving respectively isononanols and isooctanols to
produce valuable phthalates. By-product trimers such as isononenes (propene) and
isododecenes (butenes) are also hydroformylated to the corresponding alcohols
(cf. Section 2.1.1).
DMBs are used for the synthesis of fine chemicals for agrochemicals and
fragrances. Each of the two plants has a capacity of about 2000 t per year.
Feedstocks typically used for a Dimersol plant are C3 and C, cuts from catalytic
cracking and steam cracking units. They contain from 70 to 90 % of olefins, with
the remaining part being paraffins. These cuts must first be selectively hydro-
genated to eliminate diolefins and acetylenes. Thus the dimerization reaction is
a way of increasing the yield of high-RON gasoline from a cracker. On the
other hand the butene dimerization route to isononanols is very competitive
with the propene hydroformylation route to 2-ethylhexanol.
More than 25 plants are in operation, mainly for propene dimerization: their
total output is 3.4 Mt per year. Plant investments are comparatively low.

2.3.1.4.3 Dimerization of Ethylene to 1-Butene Catalyzed

by Titanium Complexes
This selective dimerization reaction was first described in 1954 by Ziegler [9],
who used a mixture of titanium tetrabutyl ester and a trialkylaluminum. Later,
the selectivity of the reaction was improved by modification of the catalyst and
optimization of the reaction conditions [lo].
The catalytic cycle presumably involves the oxidative addition with coupling of
two molecules of ethylene to a Ti" species, generating a titanacyclopentane. A
1,3-hydrogen shift across the ring generates 1-butene. Because it does not involve
a hydride intermediate that might catalyze a double-bond shift, 1-butene is stable
260 2.3 Reactions of Unsaturated Compounds

Main reaction:
\
/Ti\
,
\
//
- /

Consecutive reaction:
\ ,- - \
/Ti +

Non-observed reaction:
\ *
Ti +
Scheme 3. Reaction pathways for ethylene dimerization catalyzed by titanium.

60 ! ! I
t
I

70 80 90 '0
% conversion

Figure 4. Ethylene dimerization catalyzed by titanium: selectivity vs. conversion.

in the reaction mixture. The only important side reaction results from the co-reac-
tion of 1-butene with ethylene giving isohexenes (see Scheme 3), namely l-hex-
ene (9 %), 2-ethyl-1-butene (65 %), and 3-methyl-1-pentene (26 %). Coupling of
two 1-butene molecules is not observed. Thus, the selectivity depends essentially
on the ratio of 1-butene to ethylene in the liquid phase (Figure 4). The reaction
rate is first order in ethylene concentration.
This reaction has been developed commercially by IFP (Alphabutol' process).
The flow diagram for this process is given in Figure 5.
To control the consecutive trimerization reaction at an economic level, the
liquid phase is equilibrated with an ethylene vapor phase at a constant pressure
(e. g., 2 MPa at 50 "C) to ensure a constant ethylene/l-butene ratio in the liquid
phase. As a consequence there is only one well-mixed reactor. Each of the two
 2.3.1.4 Dimerization and Codimerization 26 1

ethylene Li’, recycle column

7 ’-butene

Ti’” 4
AIR, .f

T
catalyst removal
k isohexenes

Figure 5. General scheme for the AlphabutolO process.

components of the catalyst (a complex of titanium tetrabutoxide and triethylalumi-

num) is injected into the external recirculating loop. The process does not use any
solvent. At the reactor output, the catalyst is deactivated by a high-boiling amine
to prevent isomerization of the product during the separation step. Then, uncon-
verted ethylene, butene, and isohexenes are flash-distilled and ethylene is recycled
to the reactor. Catalyst residues and heavy hydrocarbons containing a small
amount of polyethylene are incinerated.

Use and Economic Situation

The main use of 1-butene is as a comonomer for linear low-density polyethylene

(LLDPE), for which there is a fast growing demand; it is used to a lesser extent for
the production of isotactic polybutene.
1-butene is generally obtained by distillation of C, cuts from a naphtha steam
cracker after removal of butadiene (extraction and/or selective hydrogenation) and
isobutene (etherification with methanol). However, when ethane or propane is
used as steam cracker feed, the Alphabutol process is the only way to obtain 1-
butene, considering the cost of transportation and storage of “imported” 1-butene.
On the other hand, the synthetic process provides a better-quality 1-butene for
LLDPE production. It contains no traces of isobutene or butadiene, thus ensuring
the smooth running of the polymer plant. The only impurities are small amounts
of butane and 2-butenes.
262 2.3 Reactions of Unsaturated Compounds

Today, 20 Alphabutol units have been licensed, having a combined 1-butene

capacity of 330000 t per year, the LLDPE 1-butene content is generally on the
order of 8-12 wt. %. Nearly 50 % of the world’s 1-butene incorporated as como-
nomer in LLDPE is produced using Alphabutol technology.

2.3.1.4.4 Trimerization of Ethylene into 1-Hexene Catalyzed

by Chromium Complexes
The formation of 1-hexene from ethylene has been known for a long time. At the
beginning, 1-hexene was detected as an oligomeric by-product in the ethylene
polymerization with a homogeneous chromium-based system [ 111. Later, the
reaction was studied by different industrial and academic researchers to figure
out the reaction steps and to improve the catalyst selectivity. In a similar way
to the selective formation of 1-butene (Alphabutol@process), it has been sug-
gested that the exclusive formation of 1-hexene resulted from the formation of
a seven-membered metallacyclic Cr intermediate [ 121. This seven-membered
metallacyclic species can possibly be formed from a five-membered Cr species,
by the ring expansion reaction with one additional ethylene molecule, as described
in the Scheme 4. The key of the reaction pathway lies in the relative stability
toward intramolecular p-H transfer of the metallacyclopentane ring compared to
the metallacycloheptane ring.

Scheme 4. Trimerization of ethylene.

Phillips Petroleum discloses a process for the trimerization of ethylene to 1-

hexene [ 131. According to patents, the process employs a complex catalyst system
comprising 2,5-dimethylpyrrole, triethylaluminum, and diethylaluminum chloride
in combination with a chromium(II1) salt in the presence of a solvent. The purity
of 1-hexene in the hexene fraction is reported higher than 99 %. The main by-
products are decenes and polymer.
This technology should be used in a 50 000 tJyear plant in construction in Qatar
and a second 90 000 vyear plant has been under consideration in Pasadena, Texas.
1-Hexene is mainly used as a comonomer for LLDPE manufacture.
 2.3.1.4 Dimerization and Codirnerization 263

2.3.1.4.5 Butadiene-Ethylene Codimerization

Many Ziegler-type catalysts based on nickel, cobalt, and iron salts are very effec-
tive for this codimerization. But only rhodium selectively gives the sought-after
trans isomer. The reaction was first described by Alderson et al. [14] and the me-
chanism was discussed by Cramer [15]. The starting complex is "RhCl3 . 3H20"
which is reduced to Rh' by olefin, then oxidized by protonation to Rh"'. The in-
termediate species is suspected to be an Rh'" hydride ("HRhCl,'') which reacts
with butadiene to give a dimeric $-crotyl complex. Insertion of ethylene into
the q'-crotyl-Rh bond results in the formation of a hexenyl complex. A b-elimi-
nation regenerates the hydride species and 1,4-hexadiene. The preferential forma-
tion of 1:l adduct is a consequence of the favored stability of the y3-crotyl-Rh
complex compared to an ethyl-Rh complex.
To prevent isomerization of 1,4-hexadiene to 2,4-hexadiene, overwhelming
excesses of butadiene and ethylene are used.
The catalyst does not maintain its activity indefinitely and part of the active
Rh"' species is decomposed to an inactive Rh' complex. This latter can be re-
oxidized in situ or ex situ by organic chlorides.
The reaction rate is first order in ethylene and rhodium concentrations, and
depends on the butadiene concentration [ 161.
This reaction has been developed industrially by Du Pont in the USA.

Use

1,4-truns-hexadiene is used as the third monomer in the ethylene-propylene-

diene monomer (EPDM), which is an elastomer with outstanding properties.
However several other nonconjugated dienes compete with hexadiene for
EPDM - for example, ethylidenenorbornene, which is easily made by the
Diels-Alder reaction of cyclopentadiene with butadiene, then isomerization.
The annual capacity is probably 2500 t per year.

2.3.1.4.6 Recent Developments

Whatever metal is used, homogeneous processes suffer from high cost resulting
from the consumption of the catalyst, whether recycled or not. This is why
two-phase catalytic processes have been developed such as hydroformylation cat-
alyzed by rhodium complexes, which are dissolved in water thanks to hydrophilic
phosphines (cf. Section 3.1.1.1) [ 171. Due to the sensitivity of most dimerization
catalysts to proton-active or coordinating solvents, the use of non-aqueous ionic
liquids (NAILS) as catalyst solvents has been proposed. These media are typically
mixtures of quaternary ammonium or phosphonium salts, such as 1,3-dialkylimi-
dazolium chloride, with aluminum trichloride (cf. Section 3.1.1.2.2). They prove
to be superb solvents for cationic active species such as the cationic nickel com-
plexes which are the active species of olefin dimerization [18, 191. The dimers,
264 2.3 Reactions of Unsuturated Compounds

which form a second phase, can be separated by simple decantation. The sol-
vent-catalyst complex can be recycled and reused.
Regioselective dimerization of propene to 2,3-dimethylbutenes can be per-
formed in a biphasic system using liquid acidic chloroaluminates as the solvent
for the nickel-phosphine catalytic system [ 191.
Nonregioselective biphasic olefin dimerization and codimerization have been
developed on a continuous pilot plant at IFP and are now being offered for com-
mercialization. Compared to the Dimersol@ process, the biphasic technology
(named Difasol@)affords a more economical use of the catalyst, thus reducing
catalyst disposal and cost [20]: the nickel productivity is more than ten times
higher. The Difasol@promotes olefin dimerization, with very high dimer selectiv-
ity (90-95 %), even in poorly concentrated feed. This is an advantage over the
homogeneous system, in which the conversion level is highly dependent on the
initial concentration of the olefin in the feedstock. It also extends the field of
application of the Dimersol@process to less reactive C5 olefins, allowing for
the production of nonenes and decene by codimerization of C4 and C5 olefins.

2.3.1.4.7 Future Trends

Much work is still dedicated to reducing catalyst consumption and waste. Im-
mobilization (or the heterogenization of homogeneous catalysts) is one of the
approaches but may result in a loss of activity and/or selectivity and a high
sensitivity to impurities.
On the other hand, organometallic catalysis in liquid-liquid biphasic media is
of growing importance. The development of this approach should probably paral-
lel that of alternative solvents.

References
[ l ] S. Muthukurnaru Pillai, M. Ravindranathan, S. Sivararn, Chem. Rev. 1986, 86, 353.
[2] J. Skupinska, Chem. Rev. 1991, 91, 613; A. W. Al-Sa’doun, Catal. Today 1992, 14, 1 ;
A. W. Al-Sa’doun, Appl. Catal. A: General 1993, 105, 1.
[3] (a) G. W. Parshall, S. D. Ittel, Homogeneous Catalysis, 2nd ed., John Wiley and Sons
1992, p. 72; (b) Y. Chauvin, H. Olivier, in Applied Homogeneous Catalysis with Orga-
nometallic Compounds (Eds.: B. Comils, W. A. Henmann), Wiley-VCH, 2000, p. 258.
141 Phillips Petroleum (G. Nowlin, G. Bumie, H. D. Lyons), US 2.969.408 (1955).
1.51 G. Wilke, B. Bogdanovic, P. Hardt, 0. Heirnbach, W. Kroner, W. Oberkirch, K. Tanaka,
E. Steinrucke, D. Walter, H. Aimmerman, Angew. Chem., Int. Ed. Engl. 1966, 5, 151.
161 G. Lefevre, Y. Chauvin, in Aspects of Homogeneous Catalysis (Ed.: R. Ugo), Carlo
Manfredi, Milano, 1970, Chapter 3, p. 142.
[7] (a) K. Nomura, M. Itagaki, M. Ishino, M. Yamamoto, G. Suzukamo, Catal. Lett. 1997,
47, 47; (b) K. Nornura, , M. Ishino, G. Suzukamo, Bull. Chem. Soc. Jpn. 1997, 70, 2671 ;
(c) G. Suzukamo, K. Nomura, M. Ishino, M. Hazama, J. Mol. Catal. 1997, 126, L93;
(d) M. Itagaki, G. Suzukarno, K. Nomura, Bull. Chem. SOC.Jpn. 1998, 71, 79; (e) H.
Sato, H. Tojima, K. Ikimi, J. Mol. Catul. 1999, 144, 285.
 2.3.1.5 Evolution of the Synthesis of Group 4 265

[8] Anonymous, Chem. Britain 1990, 26, 400.

[9] K. Ziegler, H. Martin, US 2.943.125 (1954).
[lo] A. M. Al-Jarallah, J. A. Anabtawi, M. A. B. Siddiqui, A. M. Aitani, Catal. Today 1992,
14, 1.
[ l l ] R. M. Manyik, W. E. Walker, T. P. Wilson, J. Catal. 1977, 47, 197.
[12] (a) J. R. Briggs, J. Chem. Soc., Chem. Commun. 1989, 674; (b) R. Emrich, 0. Heine-
mann, P. W. Jolly, C. Kriiger, G. P. J. Verhovnik, Organometallics, 1997, 16, 8, 1511;
(c) Y. Yang, H. Kim, J. Lee, H. Paik, H. G. Jang, Appl. Catal. A: General 2000, 193, 29.
[ 131 (a) W. K. Reagen, Am. Chem. Soc. Symp., Division o j Petroleum Chemistry 1989, 34,
583, 3 ; (b) Phillips Petroleum (W. K. Reagen, B. K. Conroy), US 5.288.823, (1994);
(c) Eur: Chem. News 2000, 2-8 October, 29.
1141 T. Alderson, E. L. Jenner, R. V. Lindsey, J. Am. Chem. Soc. 1965, 87, 5638.
[15] R. Cramer, J. Am. Chem. Soc. 1967, 89, 1639.
[16] A. C. L. Su, Adv. Organomet. Chem. 1979, 17, 269.
1171 (a) B. Cornils, E. Wiebus, CHEMTECH 1995, January, 33; (b) B. Cornils, E. G. Kuntz,
in Aqueous-Phase Organometallic Catalysis, Concepts and Applications (Eds.: B. Cor-
nils, W. A. Herrmann), 1998, Wiley-VCH, p. 271.
[ 181 Y. Chauvin, H. Olivier-Bourbigou, CHEMTECH 1995, 25 September, 26.
[19] Y. Chauvin, S. Einloft, H. Olivier, Ind. Eng. Chem. Res. 1994, 34, 1149.
[20] (a) H. Olivier-Bourbigou, J. A. Chodorge, P. Travers, Petrol. Technol. Quart. 1999, Au-
tumn, 141; (b) M. Freemantle, Chem. Eng. News 1998, March, 30; (c) D. Adams, Nature
2000, 407, 26 October, 938.

2.3.1.5 Evolution of the Synthesis of Group 4

Metallocene Catalyst Components Toward
Industrial Production
Cornelia Fritze, Patrik Mullec Luigi Resconi

2.3.1.5.1 Introduction
Within the past five years, commercial interest in metallocene catalyst components
for the polymerization of olefins has increased enormously. Commercial produc-
tion of a rising number of polyolefin types from different companies is creating a
burgeoning and highly diversified demand for metallocenes. New brand names
(e. g., Metocene (Basell), Elite (Dow Chemical), Engage (DuPont), Exact (Exxon-
Mobil), Luflexen (Basell), Ape1 (Mitsui Chemicals), Borecene (Borealis),
Finathene (TotalFinaElf), Topas (Ticona), just to name a few) characterize poly-
olefins such as PE, elastomers, PP, cycloolefin copolymers (COCs) and PS
from metallocene-type catalysts [ 1-31.
This increasing demand for metallocenes as key components of polymerization
catalysts has been recognized as a business opportunity for many companies. Not
only the established suppliers of catalysts and other intermediates for the polyole-
fin industries (e. g., Albemarle, Crompton/Witco, Akzo-Nobel) but also typical
fine chemicals producers (e. g. Boulder, Catalytica, Norquay, etc.) and polyolefin
266 2.3 Reactions of Unsuturuted Compounds

producers (e. g., Basell in cooperation with Clariant) seek a market share in this
promising business field. The economic factors and the scientific achievements
that have made possible the industrial production of the latest generation of highly
selective metallocene catalysts will be explained below.

2.3.1.5.2 Economic and Operational Factors

The synthesis of metallocenes may in a very general way be subdivided into var-
ious process steps. First the ligand precursor has to be synthesized by a more or
less complicated multistep reaction, or in some rare cases it must be directly pur-
chased as a basic chemical. Due to the number of the subsequent process steps,
and often to the inconvenience of the purification of the final product, the ligand
precursor has to be used with a very high purity.
The second process step is optional and comprises bridging of the ligand. Most
common are SIR2 or CR2 bridges, but the classic ethylene bridge, or other more
exotic variations, also play a certain role. Transmetallation is the key term to char-
acterize the third process step where the metallatedhimetallated ligand reacts with
a transition metal source to form the corresponding transition metal complex. A
rac/meso separation as the fourth process step has to be taken into account for
some metallocene complexes based on bridged ligands with reduced symmetry.
Depending on the final use and especially on the demand for purity, the fifth
and last production step may be a purification of the crude product obtained.
There are examples where two or more of these process steps can be carried
out as a one-pot synthesis without isolating the intermediates [4, 51.
It is clear that a large number of economic factors are influencing the total man-
ufacturing costs of such “fine chemicals”. Very important ones are the cost of the
ligand precursor, the number of process steps, the overall yields, the purification
requirements, and the air and moisture sensitivity of the final product. Less impor-
tant to nearly negligible are the costs of standard raw materials such as solvents
and basic chemicals, production scale and analytics [6].
Looking at the most relevant cost-determining factors, one could easily deduce
that an on-going process development is enormously important for driving a suc-
cessful business in the field of metallocene chemicals. This is the reason why we
set the focus of this article on recent examples of successful process development
which is necessary not only for the formation of the metallocene itself but also in
the field of ligand precursors.

2.3.1.5.3 Ligand Synthesis

In the field of isospecific propylene polymerization, systematic structure-activity
relationship studies of metallocenes have shown that the combination of 2-alkyl
and 4-aryl substitution is crucial for a technically suitable catalyst performance
(high catalytic activity, excellent stereoselectivity, high melting point of the poly-
mer, certain copolymer properties, etc.) [7, 81. Consequently, there is a consider-
 2.3.1.5 Evolution of the Synthesis of Group 4 267

able need for sophisticated synthetic methodology in order to achieve structural

variety quickly and efficiently.

Synthetic Approaches Toward 2-Alkyl-4-Aryl-Substitutedansa Metallocenes

Indanones are very useful and versatile intermediates in the synthesis of metallo-
cene catalysts. Scheme 1 has the synthetic scheme originally used for the prepara-
tion of 2-alkyl-4-aryl-substituted ansa metallocenes [9-111. In the first part of this
sequence, the biaryl unit is assembled and the missing carbon atoms are intro-
duced as a side chain. The reaction of 2-phenylbenzyl bromide with malonic
acid ethyl ester under basic conditions, followed by a decarboxylation, affords
the 2-(2-phenylbenzyl)propionic acid. Chlorination and Friedel-Crafts acylation
yields the 2-methyl-4-phenylindanone in 93 % yield. From here, only a few stan-
dard transformations are required to complete the synthesis, finally yielding the
desired metallocene.

1. Mg

b” 2. NiCIz(PPh3)2
3. Bromobenzene
m

1. SOCI2
Ph 2. AICI,

-1 . 2 BuLi
2.ZrCl.1
I 1. BuLi
Me -
Q
1. NaBH4
2. H*

Scheme 1. Synthesis of r~c-Me~Si(2-Me-4-Ph-Ind)~ZrCl~.

This route works well for certain metallocenes on the laboratory scale. It is
characterized by its linear sequence, thus affecting the economic efficiency and,
furthermore, limiting the structural flexibility, especially since various
functional groups are not compatible with the reactions involved. The multistep
nature of the sequence is not particularly attractive from a practical point of
view. Finally, some reactions give rise to the formation of side products, which
in certain cases are very difficult to separate from the desired product.
An alternative concept, which provides a convergent approach and a shorter
reaction sequence, and would be structurally flexible with respect to the substitu-
ent in the final metallocene, is based on a palladium-mediated coupling reaction
268 2.3 Reactions of Unsaturated Compounds

of a 2-alkylindanone bearing a replaceable group (a halogen, for instance) in the 4-

position and an aryl metal species, such as a boronic acid. For example, 2-methyl-
4-naphthylindanone is obtained by a Suzuki-type reaction of 7-chloro-2-methyl- 1-
indanone with naphthylboronic acid (Scheme 2) [ 121 (cf. Section 2.11).

00
Me + Me

Scheme 2. Synthesis of ra~-Me~Si(2-Me-4-Naphth-Ind)~ZCl~.

The key intermediate of this novel convergent approach is a haloindanone,

which is readily available from cheap starting materials and provides access to
structurally diverse aryl- and heteroarylindanones. Yields are typically in the
range from 85 % to 95 %. The facile isolation of the pure products sufficiently
high TONS, excellent yields, and the choice of solvents employed in the reaction
render this process technically feasible and very attractive.
A wide variety of 4-aryl substituents can be introduced, ranging from aromatic
residues bearing functionality to heteroaryl groups. Numerous functional groups
are compatible with the reagents and conditions employed, as illustrated in
Scheme 3.

Synthetic Approach Toward 4,7-Alkyl-Substituted Metallocenes

The original synthesis of indenes alkylated on the benzene ring required multistep
sequences, often with low regioselectivity and low overall yield. More efficiently,
4,7-alkyl-substituted indenes can be prepared in a one-step synthesis by cyclocon-
densation of alkanediones with cyclopentadienes (eq. (1)) [ 13, 141.
 2.3.1.5 Evolution of the Synthesis of Group 4 269

Scheme 3. Examples of the scope of the convergent approach.

For example, the cyclocondensation of cyclopentadiene with 2,s-hexanedione

in the presence of sodium affords 4,7-dimethylindene in 65 % yield. Subsequent
standard transformations yield the desired bridged-metallocene structures.

Regioselectivity in the Bridging Step of ansa-Ligand Synthesis

Full regioselectivity has been achieved in the bridging step of 3-substituted in-
denes, when the bridging unit is CH2: although not yet commercially exploited,
these reactions have all the prerequisites for successful development: atom effi-
ciency, high yield, mild reaction conditions, cheap and readily available starting
materials [ 15-1 71 (Scheme 4).
270 2.3 Reactions of Unsuturated Compounds

- -
R
CH20, OH- CH20, H+
I DMSO toluene, A
y 2 CH*
I

R b
Scheme 4. Regioselectivity in the bridging step with CH20.

2.3.1.5.4 The One-Pot Synthesis of Dimethylmetallocenes

Dialkyl metallocenes and other dialkyl Group 4 transition metal complexes are
useful as precatalysts in combination with co-catalysts such as tris(perfluoro-
ary1)boranes or tetrakis(perfluoroary1)borate salts [ 181. Recently, an expedient
procedure for the production of dimethyl metallocenes and Cp-amido dimethyl
metal complexes in high yields and purity has been reported. The “direct” syn-
thesis of Group 4 dimethylmetallocenes [19] consists of the one-pot reaction be-
tween the n-ligand, a 2-fold excess of MeLi, and MtC1,. This simple method
produces the dimethylated complexes in higher overall yield, and saves on re-
action time and solvents, compared to the classic two-step route, which consists
in the synthesis of the metallocene dichloride followed by its methylation with
2 equiv. MeLi.
Reaction of the n-ligand precursor with a 2-fold excess of MeLi in Et,O gen-
erates the ligand anion without detectable side reactions (potentially arising from
the excess MeLi). Subsequent addition of ZrC14 as a slurry in hydrocarbons gives
the dimethylzirconocenes directly (exemplified for the simplest, Ind,ZrMe,, in
Scheme 5). The reaction is most conveniently carried out at room temperature.
Evaporation of the ether followed by extraction with a suitable hydrocarbon (de-
pending on the solubility of the dimethyl metallocene) gives fully soluble, analy-
tically pure complexes in high yields.
In the case of Ind2ZrMe2,yields as high as 85 % have been obtained. This has to
be compared with the best literature result reported for the preparation of
Ind,ZrCI2 yield (58%) [20] and the following methylation of Ind2ZrCl2 with 2
equiv. MeLi that gives Ind,ZrMe, in 57 % yield [21]; hence the combined yields
of the two-step synthesis of Ind2ZrMe2is substantially lower than that obtained
with the “direct” synthesis. This protocol has been successfully applied to several

Scheme 5
2 Indene --
4MeLi
Et20
ZrCb
pentane
IndzZrMe2 + 4 LiCl
 2.3.1.5 Evolution of the Synthesis of Group 4 271

different indenyl ligands, both unbridged and bridged, and in some cases good
diastereoselectivity has been observed. For example, CH2(3-tBuInd)2ZrMe2[22]
and C,H4(4,7-Me2Ind),ZrMe2 [23] were obtained in 90: 10 and 20: 80 rucmeso
ratios respectively. The meso isomer of the latter was then obtained in 54 % iso-
lated yield and 99 % diastereoisomeric purity by washing with pentane to remove
the more soluble racemic isomer, followed by toluene extraction.
Another class of commercially important olefin polymerization catalysts is that
of the cyclopentadienyl amido “Constrained Geometry” complexes (CGCs) of Ti.
Different versions of the titanium-based CGC catalysts [24] [25] are now being
used commercially. The most successful ligand has been Bercaw’s Me,Si
(Me,Cp)(tBuNH) [26]; the polymerization performance of [Me2Si(Me,Cp)
(tBuN)]TiCl, (CGC-TiCl,) has been extensively investigated [24-271. The syn-
thesis of CGC-TiC1, requires the use of TiC13(THF)3followed by oxidation, be-
cause TiC14 leads to metal reduction [26]. Alternatively, CGC-TiC12 can be pre-
pared in quantitative yield by reaction of the ligand dimagnesium salt (obtained
in 79% yield) with Ti(O-iPr)4, followed by reaction with SiC14 in an overall
yield of about 77 % from the ligand [28]. CGC-TiMe, was obtained in 100 %
yield from [Me2Si(Me4Cp)(tBuN)]Ti(O-iPr),by reaction of the latter with excess
A1Me3 [28].
Analogously to the dimethylmetallocenes, CGC-TiMe2 and other Cp-amido
dimethyl metal complexes were also obtained in 70-90 % yield, at room tempera-
ture, from the ligand, a 2-fold excess of MeLi, and TiC14, without noticeable Ti
reduction [29].

2.3.1.5.5 Racemo-Selective Synthesis

For some applications of metallocenes, especially for making i-PP, only the race-
mic isomers formed in the transmetallation step are of interest. In some cases the
meso isomer formed with the ruc isomer in a 50:50 mixture is not active in
propene polymerization, while in other cases it produces undesired a-PP causing
unacceptably high soluble polymer fractions.
There are different techniques to obtain pure racemic metallocene from a crude
50:50 ruclmeso mixture [4, 5, 30-331.
Unfortunately the meso isomer of the metallocene mixture is in most cases use-
less or decomposes during the separation, so the yield in such a synthesis is by
definition limited to 50 % maximum. To overcome this principal disadvantage
of unselective synthesis there have been many efforts to develop “racemo-selec-
tive synthesis”.
In the case of unsubstituted or poorly substituted bisindenyl systems, several
methods have been devised 134-401 but only recently was a general way identi-
fied that makes the much more interesting highly substituted bisindenyl systems
available by a racemo-selective synthesis [4 11.
This method is based on modified zirconium sources which subsequently are
reacted with bimetallated ligands to obtain the corresponding bridged bisindenyl
systems racemo-selectively. With zirconium biphenolate dichlorides highly sub-
272 2.3 Reactions of Unsaturated Compounds

stituted bisindenyl ligands give initially kinetically controlled mixtures of the rac-
and meso-zirconocene biphenolate derivatives which can be transformed to the
thermodynamically favored rac derivative by heating [42]. Unexpectedly, there
is no difference in the polymerization activity and behavior between these biphe-
nolate derivatives and the corresponding dichlorides.

+ [Me2Si(2-R'4-R2-5-R3-lnd)2]Li2

'R
R3

k3

2.3.1.5.6 Conclusions
We have here described only a few recent, selected examples of different syn-
thetic advances in the synthesis of highly substituted metallocenes, which are
or are likely to be used commercially as components of metallocene-based indus-
trial olefin polymerization catalysts. The commercial interest in these new sys-
tems is a strong incentive for the evolution of organic and organometallic syn-
thetic methods. The diastereoselective synthesis of racemic zirconocenes and
the convergent approach to 2,4-disubstituted indenes are notable examples of
this evolution. New and more selective approaches will continuously be devel-
oped, to the benefit not only of polymerization catalysis, but also of synthetic
chemistry in general. Full integration between organic chemistry, organometallic
chemistry, and catalysis is making this development enormously efficient and
economically viable.

References
[l] S. K. Moore, A. Scott, Chem. Week 2000 (February 9), 35.
[2] R. D. Maier, KU Kunststoffe 1999, 89, 120.
[3] A. H. Tullo, Chem. Eng. News 2000, (Aug. 7), 35.
[4] Hoechst AG (M. Aulbach, F. Kiiber), EP Appl. 704.454.
[5] Hoechst AG (T. Rink, T. Wisser, R. Zenk, I. Cabrera, M. Riedel, J. Streb, W. Kaufmann
et al.), EP Appl. 780.396.
[6] J. M. Birmingham, J. M. Sullivan, Economics of Metallocene Catalyst Production, in
Proc. Metallocenes '95.
 References 273

[7] W. Spaleck et al., Organometallics 1994, 13, 954.

[8] U. Stehling et al., Organometallics 1994, 13, 964.
[91 Hoechst AG (B. Bachmann, J. Rohrmann, W. Spaleck, A. Winter, F. Kiiber), EP Appl.
576.970.
[lo] Hoechst AG (A. Winter, F. Kuber., M. Aulbach, B. Bachmann, R. Klein, K. Kuehlein,
W. Spaleck, C. Kohlpaintner), EP Appl. 659.757.
[ I l l Hoechst AG (J. Rohrmann, F. Kuber), EP Appl. 545.304.
[12] Targor GmbH (C. Bingel, M. Gores, V. Fraaije, A. Winter), WO 9W40.331.
[I31 Hoechst AG (A. Weiss, D. Reuschling, G. Erkcr, M. Aulbach, R. Noltc, J. Rohrmann),
EP Appl. 500.005.
[14] Hoechst AG (A. Winter, M. Antberg, V. Dolle, J. Rohrmann, W. Spaleck), EP Appl.
537.686.
[15] Targor GmbH (F. Kuber, M. Riedel, B. Schiemenz), EP Appl. 832.866.
[16] Montell (V. A. Dang, L.-C. Yu, L. Resconi), WO 9W43.931 (1998).
[17] Montell (L. Resconi), WO 00/29.415 (2000).
[18] E. Chen, T. J. Marks, Chem. Rev. 2000, 100, 1391.
[19] Montell (L. Resconi, D. Balboni, G. Prini), WO 99/36.427 (1999).
[20] A. R. Siedle, R. A. Newmark, W. M. Lamanna, J. N. Schroepfer, Polyhedron 1990,
9, 301.
[21] E. Samuel, an M. D. Rausch, J. Am. Chem. Soc. 1973, 95, 6263.
[22] L. Resconi, D. Balboni, G. Baruzzi, C. Fiori, S. Guidotti, Organometallics 2000, 19, 420.
[231 D. Balboni, I. Camurati, G. Prini, L. Resconi, Inorg. Chem. 2001, in press.
[24] Dow (J. C. Stevens, F. J. Timmers, D. R. Wilson, G. F. Schmidt, P. N. Nickias, R. K.
Rosen, G. W. Knight, S. Y. Lai), EP Appl. 416.8 15.
[25] A. L. McKnight, R. M. Waymouth, Chern. Rev. 1998, 98, 2587.
[26] J. Okuda, T. Eberle, in Metallocenes: Synthesis, Reactivity, Applications (Eds.: A. Togni,
R. Halterman), Wiley-VCH, Weinheim, 1998, p. 415.
[27] A. L. McKnight, M. A. Masood, R. M. Waymouth, Organometallics 1997, 16, 2879.
[28] Dow (R. K. Rosen, B. W. Kolthammer), WO 9Y19.984 (1995).
[29] Basell Polyolefins (L. Resconi), WO 00/75.151 (2000).
[30] Montell (L. Resconi, D. Balboni), EP Appl. 819.695.
[31] Ethyl Corp. (S. Diefenbach, M.-S. Ao, J. Power, J. Strickler), US 5.302.733.
[32] Albemarle Corp. (R. Lin, T. DeSoto, J. Balhoff), WO 9W20.014 (1998).
[33] Albemarle Corp. (J. Strickler, J. Power), WO 97/21.717 (1997).
[34] Wirtco GmbH (R. Lisowsky), US 5.612.462.
[35] University of Iowa Res. Found. (R. F. Jordan, G. Diamond), WO 95/32.979 (1995).
[36] Montell (I. E. Nifant’ev, P. V. Ivchenko, L. Resconi), EP Appl. 722.950.
[37] Kanto Kagaku Kabushiki Kaisha (K. Murata, J. Hori, M. Yoshida), EP Appl.
834.5 14.
[38] Boulder Science Company (D. Gately), WO 98h6.794 (1998).
[39] BASF AG (C. Suhling, M. Huettenhofer, H.-H. Brintzinger, F. Schaper), EP Appl.
891.980.
[40] Albemarle Corp. (J. Strickler, J. Power, R. Lin, T. DeSoto, J. Balhoff), US 5.883.278.
[41] Targor GmbH (H. Gregorius, C. Siiling, W. Bidell, H.-H. Brintzinger, H.-R.-H. Damrau,
A. Weber), WO 99A5.538 (1999).
[42] H.-R.-H. Damrau, E. Royo, S. Obert, F. Schaper, A. Weeber, H.-H. Brintzinger,
Organometallics 2001, 20 (25), 5258.
214 2.3 Reactions of Unsuturuted Compounds

2.3.2 Reactions of Other Unsaturated Compounds

2.3.2.1 Reactions of Alkynes

Jochem Henkelmann, Jan-Dirk Arndt, Roland Kessinger

2.3.2.1.1 General Properties of Alkynes

Alkynes are highly reactive building blocks in synthesis which, despite the fact
that their positive enthalpy of formation (acetylene: HF = +229.4 kJ/mol) [l]
makes them metastable at room temperature, react only at elevated tempera-
ture, under increased pressure, and in the presence of suitable catalysts.
Under these conditions they are able to take part in a large number of reac-
tions, which are subdivided below into two main groups: reactions with reten-
tion of or with transformation of the triple bond. For clarity there is further
division, in accordance with conventional practice, into the basic reactions
of vinylation, ethynylation, carbonylation, and cyclization, although these do
not reflect the variety of reaction paths and mechanisms. The cyclization reac-
tions are excluded from the following review since they are dealt with in detail
in Section 3.3.8.
The alkyne used most widely in industry to date has been acetylene - the sim-
plest of the homologs -which had first to clear the twin hurdles of industrial avail-
ability and control of the safety problems encountered in the course of its indus-
trial use. Acetylene [ 11 was first made available in the quantities necessary for use
in industry by the hydrolysis of calcium carbide. Nowadays this process has been
largely superseded by petrochemical production techniques. Acetylene was first
used as a raw material in chemistry at the beginning of the 20th century and ex-
perienced a boom period from about 1928, after the safety problems associated
with its use at increased pressure and temperature had been successfully over-
come. This success was owed largely to the fundamental work of W. Reppe of
BASF [2], who, together with his colleagues, carried out systematic investigations
into the decomposition of acetylene [2-4] under increased pressure and tempera-
ture and thus laid the foundation for its widespread industrial utilization.
Only some of the syntheses with acetylene which are practiced industrially are
carried out with homogeneous metal catalysis; initially it was predominantly the
late transition metals Fe, Co, Ni, Cu, Zn, Cd, Hg, and Pd which were employed. In
recent times the use of the noble metals Rh, Ru, Pd, and Pt has opened up a multi-
plicity of new reaction possibilities for alkynes. These methods have quickly
found their way into the toolkit of the synthetic organic chemist.
 2.3.2.1 Reactions of Alkynes 275

2.3.2.1.2 Reactions with Retention of the Triple Bond

Ethynylation of Carbonyl Compounds

Reactions of acetylene with retention of the triple bond lead to valuable building
blocks for synthesis, which can be made to undergo further functionalization. In
industry, the most important examples of ethynylation are C-C linkages by addi-
tion of acetylene to carbonyl compounds.
In volume terms, the most important ethynylation product is butynediol. It
is prepared with copper acetylide catalysis [5] from aqueous formaldehyde and
acetylene (eq. (1)). Heterogeneous copper catalysts, on support materials, are
most commonly used for this reaction.

By hydrogenation of the acetylenic triple bond, butynediol can be converted

into butenediol and into the particularly important butanediol. Partial hydrogena-
tion is effected with noble metal catalysts under mild conditions, whereas total
hydrogenation is usually carried out over heterogeneous Co and Ni catalysts.
In the presence of copper acetylide complexes, the reaction of aldehydes
with acetylene and secondary amines (eq. ( 2 ) ) leads to propargylamines [6]. In
contrast to the synthesis of butynediol, this reaction is catalyzed homogeneously.

The ethynylation of ketones (eq. (3)) produces substituted propargyl alcohols.

In comparison with the aldehydes, however, the ketones are less reactive, so
that no reaction occurs when the above-mentioned copper acetylide complexes
are used. For this reason the reaction is carried out in the presence of bases
such as alkali metal alcoholates or basic ion exchangers [7, 81. The substituted
propargyl alcohols which are made accessible by this reaction are, inter a h ,
important precursors in the synthesis of the carbon structures of vitamins A and
E [9, 101. In the course of these syntheses the propargyl alcohols are partially
hydrogenated over noble metal catalysts to give the allyl alcohols. Pd complexes
and Pt complexes are particularly suitable for this purpose [ 111. Subsequently, the
allyl alcohols are extended by three carbon atoms to form new ketones which can
again be ethynylated and subjected to partial hydrogenation and further reactions.
216 2.3 Reactions of Unsaturated Compounds

Whereas transition metal-catalyzed 1,2-additions of alkynes to ketones pro-

ceed with only poor conversions, the 1,4-addition to a,P-unsaturated ketones
(eq. (4)) in the presence of Rh'-phosphine complexes produces high yields
WI.
- RhCI(PMe3)3 -
-
*
acetone, 20 oc
0
95% 0

A similar reaction (eq. ( 5 ) )has been described with an activated butadiene sys-
tem using ruthenium catalysis [ 131.
0
+ --
Me0

Under the same conditions even free alkynyl aldehydes undergo a 1,4-addition
to propargylic acid esters (eq. (6)) [14].

0
(BU3P)4RUHZ, MeO
benzene
60 - 100 "C
\\
H
84 %

Ethynylation of Aromatic Compounds and Olefins

An elegant method for linking terminal alkynes with aromatic compounds and
olefins is the Sonogashira reaction [ 151. The palladium-catalyzed reaction en-
ables the simultaneous introduction of two or even more alkyne units and thereby
makes it possible to synthesize acetylene derivatives, for example hexaalkynyl-
benzenes [16], (eq. (7)), which can be obtained only with difficulty by other
methods. It has been shown by Herrmann, Beller, and co-workers that the
copper reagent is not necessary as a co-catalyst for the coupling of terminal
alkynes with sp2-carbon halides. By using phosphapalladacyclic catalysts 1 the
 2.3.2.1 Reactions of Alkynes 277

Sonogashira coupling can be elegantly and efficiently carried out copper-free [ 171.
Similarly to sp2-carbon halides, activated olefins can be linked with terminal
alkynes [ 181.
SiMe3

SiMe3

Br
'r)$Br Br + 6 - s ~ M ~ ~CUl,PPH3 Me3Si$
PdC12(PPh&,
NEt3 ~ 4 / + SiMe3 (7)
Br MeBSi

SiMe3

In the reaction with nonactivated olefins in the presence of Pd catalysts, self-

dimerization of the alkynes is predominant [ 141 (eq. (8)).

2 ,
,/ pdo_ / (8)

2.3.2.1.3 Reactions with Transformation of the Triple Bond

Carbonylation Reactions

Acrylic acid is by far the most important product prepared by carbonylation of

acetylene. The processes employed industrially since the mid- 1950s for the homo-
geneously catalyzed carbonylation of acetylene (eq. (9)) have enabled the broad
use of acrylic acid derivatives as mass products. This reaction was first discovered
in 1939 by Reppe [19] and was investigated intensively in the subsequent period
POI.
- NiBr&u I
- + CO + H20
80 bar; 200 "C (9)

Suitable catalysts are both simple halides and complex metal compounds
which, under the reaction conditions, form catalytically active metal carbonyl
complexes. Particularly active in this context are nickel compounds, which
278 2.3 Reactions of Unsaturated Compounds

are activated by the addition of metals such as Cu which do not form carbonyls.
A particularly favorable reaction is the synthesis of acrylic acid at 180-205 "C
under a pressure of 4-9 MPa in the presence of a catalyst system consisting of
NiBr, and Cul. The solvent employed is tetrahydrofuran, which is of infinite
miscibility with water and possesses good solubility for acetylene. The reaction
described is carried out industrially in a BASF plant in Ludwigshafen (Figure 1)
[211.
As already mentioned, the processes for the homogeneously catalyzed carbony-
lation of acetylene have opened up the way for acrylic acid to become a mass
product for which worldwide production capacities are currently two million
tonnes per annum. Acrylic acid and its esters are important monomers for polymer
dispersions, whose use is widespread. Since the mid- 1960s, however, the avail-
ability of propene, a less expensive feedstock than acetylene, has led to the devel-
opment of an even more advantageous production process: the heterogeneously
catalyzed gas-phase oxidation of propene [21, 221. Nowadays, acrylic acid is
produced almost exclusively by this process (cf. Chapter 1). The Reppe acrylic
acid plant at BASF is now the only one left in the world which still uses acetylene
as feedstock.
A further development of the Reppe acrylic acid synthesis is the reaction, de-
scribed in recent literature, of the noble metal-catalyzed carbonylation of higher
acetylenes to give the corresponding acrylic acid derivatives. Thus, for example,
the Pd-catalyzed carbonylation of propyne (eq. (10)) in the presence of methanol
leads directly to methyl methacrylate [23]. Based on this work, Shell has devel-
oped a new production process for methyl methacrylate [24]. The propyne
required can be isolated from the product streams from crackers, (cf. Section
2.3.2.3).

fresh THF
carbon monoxide recycling of unreacted gases
t
fi
-r:
residual C2H2 gas

water

nickel cat. 4<

t
0
in THF

t
acrylic acid in THF
I
1
waste water
'I!rt
acrylic acid
to distillation

tetrahydrofuran (THF)

Figure 1. Manufacture of acrylic acid from acetylene, CO and H 2 0 [ 2 2 ] .

(a, c) saturator, (b) reactor, (d, e) columns, ( f ) distillation.
 2.3.2.1 Reactions of Alkynes 279

- Pd(OAc)$2-PyPPh*
- + CO + MeOH
NMP. 20 - 60 bar * +OM, (10)
45-115°C 0
90 %

Under comparable reaction conditions, the carbonylation of alkynes can be

steered in another direction by varying the catalyst metals. For instance, using
iron pentacarbonyl [25] or ruthenium carbonyl [26] as catalysts, the principal
product is hydroquinone (eq. (1 1)).
Fe(CO)s/dioxane
2 + 3 CO + H20
170 "C, 700 bar

32 % I
OH

In the presence of dicobalt octacarbonyl [27], a mixture of cis- and truns-bis-

furandione becomes the main product (eq. (12)).

Co2(CO)$acrylonitrile
+ 4co * +
65 "C, 27 bar

40 Yo

Finally, with rhodium catalysts 5H-furan-2-ones and dihydrofuran-2-ones can

be obtained in high yields (eq. (13)) [28].

(ly
Rh,(CO),$dioxane
-
- + 3C0 + H$
NEt,, Nal, collidine, * (13)
100 bar, 80 OC
- co, 86%

2.3.2.1.4 Vinylation Reactions

Vinyl Esters

Whereas the carbonylation of acetylene lies firmly within the domain of homo-
geneous transition metal catalysis, in the case of vinylation the methods are as
280 2.3 Reactions of Unsaturated Compounds

numerous as the products. The synthesis of vinyl esters makes this particularly
clear. The basic reaction (eq. (14)) is homogeneously catalyzed by mercury
salts and zinc salts.
A) HgS04' , 6 0 "C
__ B) Zn(OAc)e/C*', 160 "C
A O H ' = * A O ' (14)
* liquid phase 98%
** gaseous phase

The first vinyl ester prepared was vinyl acetate, in 1912, by homogeneous
mercury sulfate catalysis [29]. For the vinyl esters of lower carboxylic acids,
the reaction was soon carried out in the gas phase over, for example, zinc salts
of the corresponding carboxylic acids (such as zinc acetate) heterogenized on
active charcoal [30]. By 1965, vinyl acetate was prepared almost exclusively by
this method. Since then, this synthesis has been largely superseded by the ace-
toxylation of ethylene, the petrochemical preparation of which is highly eco-
nomic (Section 2.1.4.1).
For the synthesis of higher vinyl esters, the gas-phase reaction with acetylene
becomes less favorable as the length of the carbon chain grows. In fact, the re-
action of higher carboxylic acids takes place in the gas phase only if they boil
at temperatures low enough to be evaporated below the reaction temperature in
a stream of acetylene. For this reason they are reacted - with the exception of
propionic acid at BASF [31] (cf. Section 2.1.2.2) - in the liquid phase. In these
methods acetylene is passed at 200-220°C into a melt consisting of the zinc
salts of the corresponding acids and of the acid itself. The vinyl ester formed is
discharged along with the excess acetylene and is worked up [32-351.
Recent literature describes the synthesis of vinyl esters in the presence of
platinum metal complexes. Complexes which have proven particularly suitable
in this context are those of ruthenium (eq. (15)), such as, for example, cyclooc-
tadienylruthenium halides [36], ruthenium carbonyl complexes, and ruthenium
acetate complexes [37]. A characteristic feature of these is their high selectivity
with regard to acetylene, so that the production of acetylene polymers is
reduced.
0 0
145°C
R

In the presence of Ru complexes, terminal alkynes react with C 0 2 and second-

ary amines in good yields to give vinyl esters of carbamic acid (eq. (16)) [38]
(cf. Section 3.3.4).

-0 + COP + HNEt2 Ru(C6Me6)C12PMe3

125 "C, 5 MPa
LOANEt2 (16)
67 Yo
 2.3.2.1 Reactions of Alkynes 281

Acetaldehyde

The addition reaction of water with alkynes leads to enols which isomerize to give
the corresponding aldehydes. Using acetylene, it is possible in this way to obtain
good yields of acetaldehyde (eq. (17)).

The reaction is very effectively catalyzed by Hg,'+ and Hg2+ salts. However,
Hg2+ partially oxidizes the acetaldehyde formed to acetic acid, and is itself
reduced to metallic Hg. In a process carried out at Wacker-Chemie until 1962
[39, 401, the metallic mercury was reoxidized to Hg2+by iron(II1) sulfate. In a se-
parate step, the iron(I1) sulfate formed was oxidized back to Fe"'using nitric acid
and was returned to the initial reaction. This process, carried out on a large indus-
trial scale, has also been superseded in the intervening period by a process based
on ethylene (Section 2.4.1).

Vinyl Ethers

In contrast to the addition of water, the addition of alcohols to alkynes leads to

stable enol ethers. Those of economic importance are almost exclusively the
vinyl ethers prepared from acetylene. This preparation is carried out under base
catalysis [4 I] (KOH, alcoholates, and the like). The noble metal-catalyzed alcohol
addition does in fact likewise lead, in an intermediate stage, to vinyl ethers, but
these react under the prevailing conditions, generally in a quantitative reaction,
to give to corresponding acetaldehyde dialkyl acetals [42]. This is illustrated in
(eq. (18)), which takes as its example the addition of n-butanol to acetylene in
the presence of Na,PtCl,.
OBu

> 95 Yo

Only in exceptional cases is it possible to isolate the enol ether, as with the
addition of methanol to acetylenedicarboxylic esters [43], in good yields (eq.
(19)). Catalysts which have been used in this reaction are palladium chlorides
and platinum chlorides with bidentate phosphine ligands.

Me02C-C02Me + MeOH
MClp(diphos)
AgPF6
*
CH2CIp, 20 "C
HxoMe
Me02C' C02Me
(19)

M = Pd, Pt 100 %
diphos = n
PhzP PPh2
282 2.3 Reactions of Unsaturated Compounds

C-Vinyl Compounds

Whereas there is a multiplicity of examples for the above-mentioned reactions of

acetylene with nucleophiles to give heterovinyl compounds, it is comparatively
rare to find industrially relevant additions of C-H-acidic compounds to ace-
tylenes.
The addition [44] of hydrocyanic acid to acetylene (eq. (20)) in a solution
of copper chloride in aqueous hydrochloric acid gives good yields and, prior
to the time when the synthesis of acrylonitrile by ammonoxidation [45] from
propene became technically feasible, was the major preparation process. This syn-
thesis, too, has nowadays completely lost its importance.
cuc12
+ HCN ---+

A C N
H20

A further example is the zinc stearate-catalyzed addition of malonic ester

derivatives to acetylene. The reaction also takes place with monosubstituted
malonic esters [46]. C-vinyl malonic esters have found an application, for
example, in the synthesis of barbiturates.
One example of C-vinylation of an aromatic compound is the reaction of
p-tert-butyl-phenol and acetylene [47] to give ethylidene-bridged oligomers
(eq. (21)), which are formed by dual attack of the aromatic compound on
acetylene. The catalyst employed is zinc naphthenate. These products are used,
inter alia, as vulcanizing auxiliaries in the tire industry.

n=0-2

For C-vinylation reactions as well, recent literature has described a large

number of examples of new, transition metal-catalyzed reactions [ 141 which go
beyond the conventional reactions. For instance, the linking of aldehydes with
internal alkynes [48] is accompanied by good yields (eq. (22)).

Similarly, ally1 halides can be made to undergo addition with alkynes [49].
 References 283

Isomerization Reactions

Under catalysis by phosphines (e. g., triphenylphosphine), alkynones can be

isomerized into dienones [50] (eq. (23)).

cat. PPh,

PhMe, 80 OC
0 0
83%
(23)

With ally1 alcohols, terminal alkynes react with C-C linking to give the
corresponding ketones (eq. (24)). This method makes possible a range of new
possibilities for synthesis [5 I].

2.3.2.1.4 Outlook
Those syntheses with alkynes which take place under homogeneous transition
metal catalysis are competing, both chemically and economically, with alternative
catalysts and raw materials. This has brought about a state of affairs where some
previously important syntheses have since been driven out by such alternatives. In
addition to this, however, there are also fields, as demonstrated by the example of
the propargyl alcohols and the higher vinyl esters, where the alkyne-based syn-
theses continue to be the methods of choice.
Whether the new developments which have been presented will attain the same
position as their important predecessors, only the future can tell. Ultimately, the
technical realization of these developments, following the original discovery,
has likewise taken some time to come about.

References
[ l ] P. Passler, W. Hefner, H.-J. Wemicke, G. Ebersberg, R. Muller, J. Bassler, D. Mayer,
Ullmannk Encycl. Ind. Chem. 5th ed. 1985, Vol. A l , p. 91.
[2] W. Reppe, Chemie und Technik der Acetylen-Druck-Reaktionen, Verlag Chemie, Wein-
heim, 1952.
[3] H. B. Sargent, Chem. Eng. 1957, 64, 250.
[4] D. Lietze, H. Pinofsky, T. Schendler, H.-P. Schulze, Chern.-1ng.-Tech. 1989, 61, 736.
[5] W. Fliege, D. Voges, G. Steffan, UllrnannS Encycl. Ind. Chem. 4th ed. 1975, Vol. 9, p. 19.
[6] W. Reppe, Neue Entwicklungen auf dem Gebiet der Chemie des Acetylens und des
Kohlenoxids, Springer, Berlin, 1949, p. 24.
284 2.3 Reactions of Unsaturated Compounds

[7] BASF AG (H. Pasedach, W. Hoffmann), DE 1316.042 (1970).

[8] Snam Progetti S.p.A. (G. Fusina, S. Neo) DE 2.113.354 (1971).
191 0. Isler, F. Kienzle, Kirk-Othmer Encycl. Chem. Technol. 1984, Vol. 24, p. 140.
[lo] D. C. Herting, Kirk-Othmer Encycl. Chem. Technol. 1984, Vol. 24, p. 214.
[ I l l E. N. Marvell, T. Li, Synthesis 1973, 8, 457.
[ 121 G. I. Nikishin, I. P. Kovalev, Tetrahedron Lett. 1990, 31, 7063.
[13] T. Mitsudo, Y. Nakagawa, K. Watanabe, Y. Hori, H. Misawa, H. Watanabe, Y. Watanabe,
J. Org. Chem. 1985, 50, 565.
1141 B. M. Trost, Angew. Chem. 1995, 107, 285.
11.51 (a) K. Sonogashira in Metal-Catalyzed Cross-Coupling Reactions (Eds.: F. Diederich,
P. J. Stang), Wiley-VCH, Weinheim, 1997, Chapter 5 , p. 203; (b) K. Sonogashira, in
Comprehensive Organic Synthesis (Eds.: B. M. Trost, I. Fleming), Pergamon Press, Ox-
ford, 1991, Volume 3, Chapter 2.4, p. 521; (c) S. Thorand, N. Krause, J. Org. Chem.
1998, 63, 8551; (d) A. Mori, J. Kawashima, T. Shimada, M. Suguro, K. Hirabayashi,
Y. Nishihara, Org. Lett. 2000, 2, 2935.
1161 R. Diercks, J. C. Amstrong, R. Boese, K. P. C. Vollhardt, Angew. Chem., Int. Ed. Engl.
1986, 25, 268.
[17] W. A. Herrmann, C. P. Reisinger, C. Brossmer, K. Ofele, M. Beller, H. Fischer, J. Mol.
Catal. A: 1996, 108, 5 1.
[18] R. C. Larock, S. Babu, Tetrahedron, 1987, 43, 2013.
[19] W. Reppe, Liebigs Ann. Chem. 1953, 582, 1.
1201 A. Muller in New Syntheses with Carbon Monoxide (Ed.: J. Falbe), Springer, New York,
1980, Chapter 3.
[21] B. Blumenberg, Nachl: Chem. Tech. Lab. 1984, 480.
[22] N. v. Kutepow, Ullmann’s Encycl. Ind. Chem. 4th ed. 1973, Vol. 7, p. 84.
[23] E. Drent, P. Arnoldy, P. H. M. Budzelaar, J. Organomet. Chem. 1984, 475, 57.
[24] Shell (M. I. Doyle, I. van Gogh, I. C. van Ravenswaag Classen), EP 441.447 (1991).
[25] W. Reppe, N. von Kutepow, A. Magin, Angew. Chem. 1969, 81, 717.
[26] Lonza AG (P. Pino, G. Braca, G. Sbrana), DE 1.251.329 (1964).
(271 BASF AG (W. Reppe, A. Magin), DE 1.07 1.077 (1 965).
[28] (a) BASF AG (M. Heider, T. Riihl, J. Henkelmann, S. Stutz, T. Preiss, H. Rutter,
M. Schafer, A. Hohn), WO 97/07111 (1997); (b) T. Joh. K. Doyama, K. Onitsuka,
T. Shiohara, S. Takahashi, Organometallics 1991, 10, 2493; (c) T. Joh, H. Nagata,
S. Takahashi, Inorg. Chim. Acta 1994. 220, 45.
[29] Chemische Fabrik Griesheim (W. Klatte), DE 25 1.381 (1912).
[30] Consortium fur elektrochemische Industrie GmbH (E. Baum, H. Deutsch, W. Herrmann,
M. Mugadan), DE 403.784 (1921).
[31] G. Roscher, Ullmann’s Encycl. Ind. Chem. 4th. ed. 1983, Vol. 23, p. 605.
[32] Shell (W. F. Engel, G. E. Rumscheidt), DE 1.237.557 (1963).
[33] Shell (W. F. Engel, G. E. Rumscheidt), DE 1.238.322 (1963).
[34] Wacker-Chemie (G. Huber, H. Kainzmaier), DE 1.210.810 (1963).
[35] Wacker-Chemie (G. Huber, H. Kainzmaier), DE 1.238.010 (1964).
[36] T. Mitsudo, J. Org. Chem. 1987, 52, 2230.
[37] M. Rotem, Y. Shvo, Organometallics 1983, 2, 1689.
[38] R. MahC, Y. Sasaki, C. Brumann, P. H. Dixneuf, J. Org. Chem. 1989 54, 1518.
[39] R. Jira, R. J. Laib, H. M. Bolt, Ullmann’s Encycl. Ind. Chem. 5th ed. 1985, Vol. A l , p. 31.
[40] D. F. Othmer, K. Kon, T. Igarashi, Ind. Eng. Chem. 1956, 48, 1258.
[41] W. Reppe, Justus Liebigs Ann. Chem. 1956, 601, 84.
[42] D. Steinborn, T. Rosenstock, H. Mosinski, R. Nuenthel, Proc. Con$ Coord. Chem. 1991,
13, 265.
[43] Y. Kataoka, 0. Matsumoto, M. Ohashi, T. Yamagata, Chem. Lett. 1994, 1283.
 2.3.2.2 Stereospecific Polymerization of Butudiene or Isoprene 285

[44] P. W. Langvardt, UllmannS Encycl. Ind. Chem. 5th ed. 1985, Vol. A l , p. 177.
[45] D. J. Hadley, E. G. Hancock (Eds.), Propylene and its Industrial Derivatives 1973,
Halsted Press, New York, Chapter 11.
1461 M. Seefelder, Liebigs Ann. Chem. 1962, 652, 107.
1471 W. Reppe, Liebigs Ann. Chem. 1956, 601, 88.
[48] T. Tsuda, T. Kujor, T. Saegusa, J. Org. Chem. 1990, 55, 2554.
[49] K. Kaneda, T. Uchiyama, Y. Fujiwara, T. Imanaka, S. Teranishi, J. Ovg. Chem. 1979,
44, 55.
1501 (a) B. M. Trost, U. Katzmaier, J. Am. Chem. Soc. 1992, 114 7933; (b) B. M. Trost,
C.-J. Li, J. Am. Chem. Soc. 1994, 116, 3167; (c) B. M. Trost, C.-J. Li, J. Am. Chem.
Soc. 1994, 116, 10819.
[51]B. M. Trost, G. Dyker, R. J. Kulawiec, J. Am. Chem. Soc., 1990, 112, 7809.

2.3.2.2 Stereospecific Polymerization of Butadiene

or Isoprene
Rudolf Taube, Gerd Sylvester

2.3.2.2.1 Introduction
The catalysis of the stereospecific polymerization of conjugated dienes is of con-
siderable interest from both the scientific and the industrial points of view [I, 21.
From butadiene and isoprene, as the industrially most important 1,3-dienes, in
comparison with the polymerization of olefins many more structurally different
stereoregular polymers can be derived; cf. the structures of the stereoregular
polybutadienes and polyisoprenes given in Scheme 1 [ 1061.
By 1,4-polymerization of each of these dienes, a cis or a trans isomer can be
obtained. If the dienes are 1,2-polymerized, a chiral carbon atom with a vinyl
group arises; by introducing a sequence of the asymmetric configurations in the
same or alternating orientations, an isotactic or a syndiotactic I ,2-polydiene is
formed. In the case of isoprene, a 3,4-polymerization can additionally take
place, which also leads to a chiral carbon atom but with an isopropenyl group.
Thus, the formation of an isotactic or syndiotactic structure is possible in this
case too.
To synthesize the different stereoregular dienes the appropriate combination
of regio- and stereoselectivity must be realized in the course of the catalytic
polymerization. Among the different isomeric polybutadienes, 1,4-cis-polybuta-
diene has gained much industrial importance, especially for tire production, due
to its natural-rubberlike properties. The large-scale technical synthesis is carried
out as solution polymerization with organometallic complex catalysts of the
Ziegler-Natta type containing titanium, cobalt, nickel, or neodymium in aro-
matic or aliphatic hydrocarbons as solvents at 50-70°C. In each case a ternary
catalytic system of high activity and selectivity is used, whose composition is
given in Table 1.
286 2.3 Reactions of Unsaturated Compounds

-1 nCH2=CH-C~=~~2 I

cis-l,4-polybutadiene trans-l,4-polybutadiene iso- and syndie

1,2-polybutadiene

u Isoprene

CH3
7 I
nH2C=C-CH=CH2 1-

l:E=C(H2/: [iE=C{H2)n -f.Hz;f$ f H 2 - i j

‘CH2 cH/3 c
‘nH2
cis-l,4-polyisoprene franc1 ,4-polyisoprene iso- and syndie iso- and syndie
1,2-poIyisoprene 3,4-polyisoprene

Scheme 1. The structurally different stereoregular polybutadienes and polyisoprenes

obtainable from the monomers by 1,4-, 1,2- or 3,4-C-C bond linking,
respectively.

Table 1. Ziegler-Natta catalysts applied technically for the 1,4-cis polymerization of buta-
diene 111“’
Catalytic system (composition [in moll) M [mg/L] PBD [kg/g MI cis [%]
TiC1,/12/Al(i-Bu), (1 : 1.5:8) 50 4-10 93
~ 10:200)
C O ( O ~ C R ) ~ / H ~ O / A(1: E~~C~ 1-2 40-1 60 96
Ni(02CR)2/13F3. OEtJAlEt, (1:7.5:8) 5 30-90 97
N ~ ( O ~ C R ) & ~ ~ A ~ ~ C I ~ / A(1~ (118)
~-BU)~H 10 7-15 98
a) M = transition metal; PBD = polybutadiene.
 2.3.2.2 Stereospecific Polymerizution of Butadiene or Isoprene 287

Furthermore, lithium alkyls are applied to produce 1,4-cis-polybutadiene in

aliphatic hydrocarbons by anionic polymerization. The total world production
capacity of 1,4-cis-polybutadienes already exceeds 2.2 million tons per year,
with a trend to increase further. In a much smaller quantity syndiotactic 1,2-
polybutadiene is produced by cobalt complex catalysis. This is a thermoplastic
polymer of high tensile strength which is used as a high-permeability film in
food packaging and can be transformed also into strings and fibers. Among
the different polyisoprenes the 1,4-cis isomer is practically identical to natural
rubber, while the 1,4-?runs polymer is identical to natural balata or gutta-percha.
Technically 1,4-cis-polyisoprene can be generated with titanium-containing
complex catalysts or by anionic polymerization with lithium alkyls. Unfortu-
nately, the availability and cost of isoprene have remained a problem. Since
isoprene synthesis is more difficult than that of butadiene, and its purification
is also more complicated, until now synthetic 1,4-cis-polyisoprene cannot
compete economically with natural rubber in the field of tyre production.
Only in Eastern European countries is 1,4-cis-polyisoprene produced with a
high capacity.

2.3.2.2.2 Historical Development

The development of the complex-catalyzed stereospecific diene polymerization,
whereby Nature lost a monopoly [3], started immediately after the low-pressure
polymerization of ethylene has been published by Ziegler and co-workers in
19.53 [4, 51. With the same titanium-containing catalyst system of the TiCI4/
AIR3 type in 1954 Home succeeded in synthesizing 1,4-cis- and 1,4-?runs-
polyisoprene and demonstrated by IR spectroscopy their identity with natural
rubber and gutta-percha, respectively [6,7]; in 1955 Natta and his co-workers
were able to prove the formation of 1,4-?rans- and syndiotactic 1,2-polybuta-
diene by X-ray structure analysis [8-lo]. Very quickly thereafter, the complex
catalysts containing titanium [ll], cobalt [12], and nickel [13] for the 1,4-cis
polymerization of butadiene were found, and at the beginning of the 1960s
this polymer was already being produced industrially on a large scale with
these typical Ziegler-Natta catalysts. The neodymium-containing catalyst was
introduced at the beginning of the 1980s [14,15]. It can be used in aliphatic
hydrocarbons for the homopolymerization of butadiene and isoprene to the
1,4-cis isomers, but is also suited to the copolymerization of both monomers

Development of the elucidation of the catalytic reaction mechanism and the

structure-reactivity relationships proceeded much more slowly. By the mid-
1960s Wilke [17], Porri [18], and Dolgoplosk [19] had already shown that
allyl-transition metal complexes can catalyze the butadiene polymerization
stereoselectively and quite probably represent the real catalysts. In particular
the allylnickel(I1) complexes [Ni(C,H,)X], (X = I [20], CF,CO, [21]) and
more recently the cationic complexes [Ni(C3H5)L2]PF6,with L = P(OPh)3, etc.
[22, 231, were also used to explore the catalytic reaction mechanism.
288 2.3 Reactions of Unsaturated Compounds

With [Ni(C,H,)I], as a trans catalyst and [Ni(C3H5)O2CF3I2as a cis catalyst the

“allyl insertion mechanism” has been proven directly by ‘H- and I3C-NMR spec-
troscopic measurements as the principle catalytic reaction for chain growth in
diene polymerization [24, 251 (cf. Scheme 2).

Scheme 2. Schematic representation of the “allyl insertion mechanism” as the catalytic

principle of chain growth in the complex-catalyzed diene polymerization.
M = metal; all other anions or ligands in the catalyst complex are omitted for
clarity.

The mechanism of stereoregulation, however, remained unclear for many years.

Only more recently has an experimentally well-founded comprehensive reaction
model been derived for the allylnickel complex-catalyzed 1,4-polymerization of
butadiene, which convincingly explains the catalytic reaction mechanisms and
the structure-reactivity relationships also involving the industrial nickel catalyst
[26-281.

2.3.2.2.3 General Mechanistic Principles

To derive the reaction mechanisms of the complex-catalyzed stereospecific diene
polymerization the following stereochemical and mechanistic aspects, which are
considered as well established today, must be taken into account.

The Mode of Butadiene Coordination and the Structure

of the Butenyl Anion at the Metal

It is well known that butadiene can coordinate by one or both of its double bonds
in the single trans or in the single cis form [29, 301. Thus, an y2-truns, y2-cis, y4-
cis, and y4-trans coordination of butadiene in the catalyst complex is possible.
Since the two hydrogen atoms of the methylene group in butadiene are structurally
unequivalent, a prochiral configuration is given at the terminal carbon atom.
Therefore, additionally, in the case of y2-coordination a right or left, and in the
case of y4-coordination a prone or supine, arrangement of the butadiene has to
be taken into account, leading to eight structurally different butadiene complexes
[106].
 2.3.2.2 Stereospecific Polymerization of Butadiene or Isoprene 289

On the other hand the y3-coordinated butenyl anion can exist in two different
configurations, which are customarily named as the anti and the syn forms
depending on the trans or the cis position of any substituent R bonded to the
C(3) atom, relative to the hydrogen atom at the C(2) atom in the ally1 group.
If no further substituents are present, in the strongly bonded butenyl anion
the syn form is thermodynamically more stable, while in the highly polar alkali
metal crotyls the anti form shows the higher stability [31]. The anti-syn
isomerization in the $-coordinated butenyl anion proceeds via the formation
of the @-C(3) structure and by rotation of the C(l)-C(2) vinyl group around
the C(2)-C(3) single bond [32]. Furthermore the butenyl anion can be trans-
formed from the r3 into the a-C(l) structure, which is energetically favored
over the a-C(3) structure by 1-3 kcaVmol (4-13 kJ/mol) [33]. In this case
both hydrogen atoms on the final methylene group can change their positions.
However, by free rotation of the growing chain around the C( 1)-C(2) bond the
configuration of the butenyl group is not altered.

The Course of C-C Bond Formation Between Butadiene

and the Butenyl Anion in the Coordination Sphere of the Metal

For the insertion reaction, two different mechanistic possibilities exist. As was
first suggested by Cossee and Arlman [34, 351, the r2- or y4-coordinated buta-
diene, acting as an electrophile in each case, can undergo a nucleophilic attack
by the butenyl anion in its @-bonded structure. Simultaneously with the C-C
bond formation from the butadiene an y3-coordinatedbutenyl anion is regenerated
as the chain end, while the polybutadienyl chain has been elongated by a further
C4 unit with one new double bond (cf. Scheme 3).
In contrast to this @-ally1insertion mechanism, the butenyl group can also react
with the butadiene from the q3 coordination. This n-ally1 insertion mechanism,
which is also described in Scheme 3, was introduced more recently [36] to relate
the cis-trans selectivity to the reactivity of the butenyl group in its anti or syn
configuration [23, 261 and has been established by quantum chemical calculations
using the density functional theory [37].
In agreement with earlier quantum-chemical considerations [38] the nucleo-
philic attack of butadiene always proceeds terminally, whereas the butenyl group
can react either with the primary C(l) or the secondary C(3) atom. In this way a
1,4- or a 1,2-bonded C4 unit is generated in the growing chain. From the principle
of least structure variation, one can conclude that in the 1,4-polymerization the
insertion reaction with the q4- or y*-coordinated butadiene in the single cis con-
figuration must lead to an anti structure of the new butenyl end group (anti
insertion), while the butadiene coordinated in the single trans configuration
gives always a syn structure (syn insertion). On the other hand, the anti or syn
configuration of the butenyl chain end group determines the cis or trans con-
figuration of the double bond in the new C4 unit. In [ 1061 the corresponding routes
of C-C bond formation for the structurally different butenyl butadiene complexes
are outlined.
290 2.3 Reactions of Unsaturated Compounds

o-C(l)+ C(1) 1 ,4-C4

unit rr-C(l)+ C(1)

-
O-C(3) + C(1) 1 ,2-C4
unit x-C(3)+ C(1)

Scheme 3. C-C bond formation between butadiene and the C(3)-substituted ally1 anion in the
coordination sphere of the metal to describe the 1,4- and the 1,2-polymerization,
according to the 6-and the n-ally1 insertion mechanisms.

This anti-cis and syn-trans correlation is now generally accepted as a funda-

mental aspect of the mechanism, related to the cis-trans selectivity in the com-
plex-catalyzed 1,4-polyrnerization of 1,3-dienes [I].

The Role of anti-syn Isomerization in the Mechanism of Stereoregulation

To explain the cis-trans selectivity on the basis of the anti-cis and syn-trans
correlation it is necessary to take into account not only the influence of the rate
of anti-syn isomerization relative to the rate of the insertion reaction in connection
with the different conditions of formation for the anti and the syn structures of
the butenyl end group, but also the possible dependence of the cis-trans selec-
tivity on the difference in stability and reactivity of the anti and the syn butenyl
groups.
If the rate of anti-syn isomerization is relatively low, then the cis-trans selec-
tivity can be determined by the formation of the anti- or the syn-butenyl structure,
for example from the v4-cis or the v2-trans coordinated butadiene, in the catalyst
complex. This is the mechanism of stereoregulation which was suggested in
the mid-1960s by Cossee and Arlman [34, 351 for titanium-catalyzed butadiene
polymerization, and which was reconsidered more recently for the allylne-
odymium complex catalysts to explain their cis-trans selectivity [39]. But it
is also possible that the difference in reactivity between the anti and the syn struc-
ture of the catalytically active butenyl complex can determine the cis-trans selec-
 2.3.2.2 Stereospecific Polymerization of Butadiene o r Isoprene 29 1

tivity, independently of the rate of anti-syn isomerization. For more details see
[40,106].

2.3.2.2.4 Catalytic Reaction Mechanisms

and Structure-Reactivity Relationships
The allyl-metal catalysts for stereospecific diene polymerization can be classified
chemically according to the different electronic and bonding properties of
the metals. Thus, for the hard, d-electron free, metal ions Li', Nd"' and Ti'" as a
consequence of their relatively low electronegativity and their inability to back-
bond a high polarity of the allyl-metal bond with a high carbanion activity and
a low tendency toward n-complex formation is to be expected corresponding-
ly. On the other hand, in the case of the more electronegative, d-electron con-
taining, ions of cobalt and nickel, a stronger n-coordination of the ally1 group
as well as the diene will be realized. With these constitutional differences
in mind, the course of catalytic polymerization will be discussed for those
allyl-metal catalysts where structure and reactivity have been investigated in
some detail.

Allyllithium-Catalyzed Diene Polymerization

Alkyllithium compounds LiR react stoichiometrically with butadiene and isoprene

in hydrocarbons to form the corresponding alkyl-substituted butenyllithium
compounds. If the diene is applied in excess, the polymerization can be catalyzed
by further diene insertion into the allyl-lithium bond. Both steps have been proved
directly but the mechanism of the selectivity remains an open question [41, 421.
In hydrocarbons, a polybutadiene is obtained containing about 35 % 1,4-cis,
54 % 1,4-truns and 11 % 1,2 units, while isoprene is polymerized under the
same conditions with a cis selectivity of more than 90%. By addition of polar
ligands, such as tetrahydrofuran, dimethylglycol ether, tetramethylethylendiamine,
or dipiperidylethane in the butadiene polymerization, the 1,2-selectivity can be
enhanced by up to 100%. The effect increases with the coordination power and
probably also with the space-filling ability of the ligand, and decreases with a
rise in temperature.
To explain these changes in selectivity, a reaction scheme for allyllithium-
catalyzed butadiene polymerization is formulated (Scheme 4), which is derived
tentatively on the basis of experimental and theoretical investigations of the struc-
ture and reactivity of the allyllithium compounds.
It has been shown by "C-NMR spectroscopy that the reaction of alkyl lithium
species with butadiene to form the substituted butenyl compounds gives a mixture
of the anti and the syn isomers, with the latter being the more stable one [43];
for the polybutadienyl- and polyisoprenyllithium compounds in hydrocarbons a
dimeric association has been proved [41, 441.
292 2.3 Reuctions of Unsaturated Compounds

I
'I, (LiR)" Z ? l LiR
n=4,6 I
R = Me, n-Bu, f-Bu)
f-

C(3) + C(1) + C(1) R' CH2-CH$H=CHR

1,2-polyrnerization by donor ligand addition! 1,4-polymerization in hydrocarbons!

Scheme 4. Reaction scheme for the allyllithium-catalyzed 1,4- and 1,2-polymerization

of butadiene in a weakly or noncoordinating solvent. L, donor ligand;
for the butadiene only the n-coordination in the single cis form is shown.

Quite recently, by very thorough ab-initio quantum calculations [3 1, 451 for the
allyl- and the crotyllithium compound, a highly polar "side-on'' coordination of
the lithium ion has been established. In the crotyl compound the lithium ion inter-
acts preferentially with the C( 1) atom, which bears the highest negative partial
charge, and the dimeric complex is obtained by bridge formation from this carbon
atom to the lithium ion of another crotyllithium fragment, and vice versa. Thereby
the carbanion reactivity is diminished; it seems plausible to assume that the in-
sertion reaction can take place only if the butadiene becomes n-coordinated to
the lithium ion. In that case the formation of a 6-bonded butenyl group may be
assumed, and by the stronger interaction with the n-coordinated butadiene C-C
bond formation is possible according to the 6-ally1 insertion mechanism (cf.
Scheme 3).
Depending on the butadiene coordination in the single cis or the single trans
form, by anti or syn insertion a cis- or a trans-C4 unit can be generated. Further-
more, a certain probability exists for a reaction between the C(3) atom of the
butenyl group and uncoordinated butadiene, which might be the reaction channel
for the low 1,2-selectivity, which is also observed in hydrocarbon solution.
If a stronger donor ligand is added during the complex formation with the
lithium ion, the n-coordination of butadiene can be more or less suppressed and
the bonding of the butenyl anion becomes practically completely ionic. In that
case a more symmetrical charge delocalization is possible and the partial negative
charge at the C(3) atom will increase. Since the C(l) atom remains more screened
 2.3.2.2 Stereospecific Polymerization of Butudiene or Isoprene 293

by the lithium ion, butadiene from the solution can only react with the C(3) atom
under formation of a 1,2 unit. In agreement with this mechanistic interpretation,
the extremely polar alkyls of the heavier alkali metals also show a high 1,2-selec-
tivity in butadiene polymerization [46].
Finally, the high cis selectivity in the polymerization of isoprene in hydrocar-
bon solution is a consequence of its higher basicity. Thus isoprene can be more
strongly n-coordinated to the lithium ion in the single cis form and therefore reacts
preferentially by 1,4-cisinsertion.

Allylneodymium-Catalyzed Butadiene Polymerization

As the first catalytically active allyl-lanthanide compounds, the tetrakis(ally1)

complexes Li[Ln(C3H5)4]. dioxane, with Ln = Ce, Nd, Sm, Gd, and Dy, have
been described [47]. More recently the field of allyl-lanthanide chemistry was ex-
tended considerably by the synthesis of the neutral tris(ally1) compounds of
lanthanum and neodymium, Ln(C3HJ3 . n dioxane (Ln = La, n = 1.5; Ln = Nd,
n = 1 ) from the tetrakis(ally1) complexes by abstraction of allyllithium with
tri(ethy1)boron according to eqs. (1) and (2) [48]. For the catalytic properties of
the allylneodymium(II1) complexes, see [1061.

DME
LnCI3 + 4 LiC3H5*dioxane Li[Ln(C3H5)4*1.5 dioxane
(1)
Ln = La, Nd

Li[Ln(C3H&* 1.5 dioxane + BEt3

dioxane
-
- Li[BEt3(C3H5)]
Ln(C3H5)3 n dioxane
(2)
Ln = La (n = 1.5), Nd (n = 1)

Furthermore, a chlorobis(ally1)- and a dichloromono(ally1)neodymium complex

could be prepared by the comproportionation reactions formulated in eqs. (3) and
(4) [391.

Under standard conditions the tetrakis(ally1)neodymium complex, like the

tris(ally1)neodymium complex, shows only moderate catalytic activity with a
high trans selectivity, but in combination with appropriate Lewis acids such as
alkylaluminum chlorides or methylalumoxane the activity can be increased con-
siderably and the selectivity changes mainly to cis. Extremely active catalysts
of very high cis selectivity are obtained with the chloro(al1yl)neodymium
compounds in combination with methylalumoxane in heptane. For more details
see [39, 49, 1061.
294 2.3 Reactions of Unsaturated Compounds

If the 1,4-polymerization is realized by the a-ally1 insertion mechanism, then

the butenyl group in the anti and in the syn structure should be practically equally
reactive and the cis-trans selectivity can be determined by the different mode of
the butadiene coordination in the butenyl-lanthanide complex.
In accordance with the anti-cis and syn-trans correlation and under the as-
sumption that the insertion step is more rapid than the anti-syn isomerization,
the trans units are obtained from y2-coordinated butadiene in its stable single
trans configuration by syn insertion and the y4-cis-coordinated butadiene pro-
vides the cis units via anti insertion.
Thus, the trans selectivity of the tris(allyl)neodymium(III) complex can arise
from the steric constraints in the corresponding tris(polybutadieny1) complex,
which is initially formed as the real catalyst and could sterically allow only the
y2-coordination of the butadiene. To explain the influence of the Lewis acid
addition, the formation of a cationic allylneodymium complex is assumed by
ally1 anionic transfer to the Lewis acid [48]. The cationic bis(ally1)- or mono-
(ally1)neodymium fragment, which is stabilized by coordinative interaction with
the donor atoms of the counter-anion from the Lewis acid, can react with the
butadiene under y4-cis coordination. By the high acceptor strength of the neo-
dymium(II1) the butadiene becomes strongly activated for the reaction with the
butenyl anion according to the a-ally1 insertion mechanism, giving rise to a
rapid 1,4-cis polymerization. The highest activity is reached with the chloro(ally1)
complexes in heptane because the chloride transfer to the Lewis acid is much
more favored and in the aliphatic hydrocarbon the solvent molecules do not inter-
fere with the n-coordination of butadiene [49].

Allyltitanium-Catalyzed Butadiene Polymerization

The only work on the catalysis of diene polymerization by structurally defined

organotitanium compounds that can be mentioned is that of Dolgoplosk and co-
workers [50].As these authors have found, tetrabenzyltitanium and the tribenzyl-
titanium halides can catalyze the stereospecific diene polymerization without any
co-catalyst.
In butadiene polymerization with Ti(CH,Ph), a microstructure of the chain
with 20 % l,4-cis, 20 % 1,4-trans and 60 % 1,2 units was obtained, and with
Ti(CH,Ph)31 a very high l,4-cis selectivity of 97 % was realized.
The polyisoprene generated with Ti(CH2Ph), contained 75 % 1,4-trans, 7 %
1,2 and 18 % 3,4 units, and with isoprene the iodide gave a chain composition
of 87 % 1,4-cis and 13 % 3,4 units.
In each case the titanium remains in the tetravalent state throughout the whole
polymerization, indicating the adequate stability of the organometallic compound
to 50 "C. Furthermore, only one benzyl anion is transformed by butadiene inser-
tion into the butenyl end group of the growing chain.
 2.3.2.2 Stereospecijic Polymerization of Butadiene or Isoprene 295

Allylcobalt Complex-Catalyzed Butadiene Polymerization

Ally1 complexes of cobalt in the oxidation states I11 and I have been identified as
structurally defined catalysts for stereospecific butadiene polymerization.
The ability of bis(y3-ally1)cobalt iodide to catalyze the polymerization of
butadiene without addition of any further reagent was discovered by Wilke
et al. [17]. Mainly cis-1,4-polybutadiene was obtained as well as some
1,2 units. In combination with AIBr3 the activity increases considerably and
almost pure cis- 1,4-polybutadiene is formed. Unfortunately, no further details
are reported. However, it seems plausible to conclude that the cationic
bis(y3-butenyl)cobalt(III) fragment, which can react with butadiene by y4-cis
coordination, should be considered as the real catalyst of the 1,4-cis polymer-
ization.
On the other hand, the well-known 5-methylheptatrienyl-butadiene-cobalt(I)
complex [Co(q3,y2-CH3C7Hlo)(y4-C4H6)] has been proved recently to be a very
highly active catalyst for the formation of syndiotactic 1,2-polybutadiene [5 11.
The activity increases strongly with the acceptor properties of the solvent in the
order heptane < toluene < dichloromethane < carbon disulfide, and can be
extremely enhanced by the addition of alumoxane.
Thus, under standard conditions in heptane, by addition of AlEt,/H,O (1 :0.7) in
the ratio Co/Al = 1: 10 at 0 "C a turnover number of more than 80 000 mol buta-
diene/(mol Co . h) is reached. The 1,2-selectivity increases from 75 % in toluene to
more than 95 % in dichloromethane at 0 "C and decreases in toluene at 70°C
below 50%; the remaining C4 units are mainly 1,4-cis. Nevertheless, all the
polymers, independently of the percentage of 1,2 units, were found to be crystal-
line by X-ray and IR spectroscopy, which indicates that they contain stereoregular
sequences with a 1,2-syndiotactic structure.
The catalyst system [Co(q',q2-CH3C7Hlo)(y4-C4H6)]/CS2 has been investigated
in some detail [52, 531 and is considered as the structurally defined model catalyst
for the more easily accessible Ziegler-Natta systems from Co(acac), or Co(octo-
ate), by combination with AlR, and CS, (acac = acetylacetonate). Although
apparent heterogeneity due to the insolubility of the polymer distorted the kinetic
analysis, it was found that polymerization proceeds by a rapidly initiated chain
growth mechanism with first-order rate dependence with respect to the monomer
_ _of self-deactivation and chain transfer to
and cobalt, and first-order dependence
the monomer. The polydispersity M,/M, was found to be 1.4-2.4 in agreement
with the reaction model.
By IH- and I3C-NMR spectroscopic measurements in dichlorobenzene at
150"C, the microstructure of the polymers was analyzed [53].Both the 1,2-selec-
tivity and the syndiotacticity exceed 99%. There is only a small proportion of
1,4-cis units (<1 %), which increases with temperature. Simultaneously the
molecular weight, the syndiotacticity, and also the crystallinity decrease, and at
higher temperatures a small 1,4-truns content becomes detectable. The free energy
differences of activation have been estimated.
To explain the 1,2-selectivity and the syndiotacticity a plausible reaction
mechanism is shown in Scheme 5.
296 2.3 Reuctions of Unsaturated Compounds

The structure of the starting complex [ C O ( ~ ~ , ~ ; ~ ~ - C H ~ C ~ His, known

~)(~~-C~H~)]
from X-ray structure analysis [54]. The anti configuration of the n-bonded butenyl
group is stabilized by the ?t-coordination of the terminal C-C double bond, and
the butadiene is d4-cis-coordinated in the supine arrangement. Above 70 "C the
complex catalyzes the linear dimerization of butadiene, mainly to 5-methyl-
1,3,6-heptatriene [SS]. The reason is a rapid P-hydride elimination from the
C(4) atom, which can take place very easily after the decomplexation of the termi-
nal double bond and formation of the 6-C(3) structure of the butenyl anion in the
resultant 14-electron Co' complex. If the a-hydride elimination is suppressed,
either by decreasing the temperature and stabilizing the n-coordination of the
terminal double bond and of the butenyl anion or by introduction of another pos-
sibly stronger acceptor ligand such as CS2 or alumoxane, then, according to the
n-ally1 insertion mechanism, by C(3)-C( 1) bond formation the syndiotactic 1,2-
polymerization can be catalyzed, as formulated in Scheme 5. The question of
why the C(3)-C( 1) bond formation is strongly favored over the C( 1)-C( 1) linking,
which leads to the 1,4-cis polymerization, can be answered exactly only by high-

16 e
A
18 e

Scheme 5. Tentative reaction mechanism for the allylcobalt(1) complex-catalyzed syndiotactic

I ,2-polymerization of butadiene.
 2.3.2.2 Stereospecijk Polymerization of Butadiene or Isoprene 297

level ab-initio quantum-chemical calculations of the different transition states, if

the structure of the catalyst complexes [LCo(RCH2C7HIo)(C4H6)] has been eluci-
dated unequivocally.
The chain growth is terminated by B-hydride elimination, giving rise to the
formation of a 1,3-diene group at the chain end; this has been identified by
NMR spectroscopy, together with the methyl group at the other chain end [53].
By butadiene insertion into the hydrido-cobalt(1) bond a crotyl complex is rapidly
formed again and, by further reaction with butadiene involving C(3)-C( 1) bond
formation, a new growing 1,2-poIybutadiene chain is generated.
By addition of stronger Lewis acids, such as Et3AI2Cl3or Et2A1C1/H20(2: l),
the 1,4-cis selectivity can be increased to more than 95 %. One possible explana-
tion of this change in selectivity is to assume the formation of a bis(buteny1)co-
balt(II1) complex, which can be generated from the butenyl-butadienexobalt(1)
complex by an electrophilic attack of the Lewis acid on the coordinated butadiene
and oxidation of the cobalt(1) to cobalt(II1) by the corresponding shift of one
electron pair to the butadiene. Since this transformation represents a redox equili-
brium, it is understandable that a continuous change from 1,2- to 1,4-cis selec-
tivity and vice versa can be initiated, depending on the Lewis-acid activity of
the system.

Allylnickel Complex-Catalyzed Butadiene Polymerization

Besides the dimeric allylnickel halides and halogenoacetates [Ni(v3-C3H5)XI2

(X = C1, Br, I, CF3C02, CCI,CO,) [l], cationic ally1 bis(ligand), monoligand
and ligand-free complexes [Ni($-C3H5)L2]X (L = P(OAr), [56], cyclooctadiene,
SbPh3, etc. [57], X = PF6, BF4 [58], [Ni(y3,v2-C8HI3)L]X (X = PF6, BF4 [59]) and
2 2 2
“ i ( ~ ,V ,V - Cd 1 9 )1 X (X = PF6, SbF6 1601, BF4, B(02C6&)2. CF3S03, AlBr4
[61], B(C6H3(CF3)2)4[62], B(C6FJ3F [63]) have been introduced more recently
as novel, structurally well-defined types of “single site” catalysts for stereospecific
butadiene polymerization.
The cationic allylnickel complexes can best be synthesized by partial protolysis
of the corresponding bis(ally1) compounds 1641 with one equivalent of the
Brgnsted acid in ether solution, where necessary after addition of the appropriate
ligand, according to eqs. (5), (6), and (7), respectively.
298 2.3 Reactions of Unsaturated Compounds

L = PCY3, PPh3, ~ ( O - O - T O IP) ~

( o, - T h ~ r n )P(O-OC&l4-t-BU)3
~,
X- = [PFs]., [BF4]‘

All of the complexes are well characterized. For each type the planar
coordination of the nickel(I1) is established by X-ray crystal structure analysis
~331.
Ref. [lo61 provides a survey of the catalytic properties of the different ally1
nickel complexes.
The general reaction model for the allylnickel complex-catalyzed 1,4-polymer-
ization of butadiene is outlined in [26]. From the starting y3-allylnickel(II)
complex, which has a quasi-planar structure, two structurally different
butadiene complexes are formed as the actual catalysts by successive ligand or
anion substitution: a monoligand allylnickel(I1) complex, which may also contain
the anion X instead of the neutral ligand L, with an q2 coordinated butadiene, and
a ligand-free complex with an q4-cis coordinated butadiene. The concentration of
these complexes, which is also limited by the double- bond coordination from the
growing chain, and their reactivity determine the catalytic activity.
Both modes of butadiene coordination are exemplified by appropriate
model complexes: [NiCp(CH,)(q2-C,H,)] [65] and [Ni( 1,3-(CH&C3H3)(y4-1,4-
(CHd,C,H,)IBF4 [281.
For each of the butenylnickel(I1) complexes, and for the butadiene complexes
as well, an anti-syn equilibrium has to be assumed, with the syn configuration
having the thermodynamically more stable structure (Kds = 101-102) [36, 601.
The rate of anti-syn isomerization has proved to be strongly dependent on
structure. In the bis(1igand)-butenylnickel(I1) complexes the isomerization rate
is very low (kds = s-l) [66], but in the ligand-free Cl,-allylnickel(II) com-
plexes the anti-syn isomerization is accelerated considerably by the coordination
of the next double bond, so that it is completed instantaneously even at -70°C
1601.
The insertion of butadiene into the allyl-nickel bond always proceeds with for-
mation of the new butenyl group in the anti configuration. The anti insertion has
been established experimentally for the allyl-, the aryl-, and the hydrido-nickel
 2.3.2.2 Stereospecijic Polymerization of Butadiene or Isoprene 299

bond [36, 65, 671 and can be attributed to the fact that the insertion reaction starts
solely from the single cis configuration of the butadiene, irrespective of the mode
of its coordination.
Therefore the cis-trans selectivity can be determined neither solely by the
mode of butadiene coordination nor by the rate of anti-syn isomerization as
has been suggested in the literature [50, 68-70]; rather, it is regulated kinetically
by the different reactivity of the anti- and the syn-butenylnickel(I1) complex, de-
pending on the mode of butadiene coordination, and thermodynamically by the
concentration of the structurally different butadiene complexes.
Assuming the n-ally1 insertion mechanism for the two catalyst complexes with
r2- and y4-coordinated butadiene, three structurally different transition states
can be distinguished, as shown in Scheme 6, to describe the course of the
C( 1)-C( 1) bond formation reaction in agreement with the observed cis-trans
selectivity of the different allylnickel(I1) complexes. Thus, in the monoligand-
butenylnickel(I1) complex with y2-coordinated butadiene, theC( 1)-C( 1) bond
formation can take place most easily with the butadiene in the single cis form
and it is sterically less hindered if the growing chain is arranged in the syn position
(Structure 1). Therefore, the formation of trans units is catalyzed via the reaction
channel kit.

1 2 3

Scheme 6. The three different structures of the allylnickel complex catalyst 1, 2 and 3,
presenting the energetically most favorable routes to the transition states
of C( 1)-C( 1) bond formation according to the n-ally1 insertion mechanism
in the reaction channels k,,, kZc,and kZclk2t,respectively. The interacting 2p
orbitals are shaded.
300 2.3 Reactions of Unsaturated Compounds

trans-1,4Polymerization

The course of trans- 1,4 polymerization via the monoligand butadiene complex
has been established for the bis(tripheny1phosphite) complex [Ni(r3-C3H5)
(P(OPh),),]PF,, as a typical trans catalyst, by kinetic measurements [23], giving
a first-order rate dependence of the monomer and the nickel and an inverse first-
order dependence of the ligand concentration. Furthermore, all the essential steps
of the catalytic cycle, which is shown explicitly in Scheme 7, have been elucidated
by "P-NMR spectroscopic measurements [36]. Using the crotyl bis(tripheny1-
phosphite) complex as the starting material, the existence of the anti and the
syn forms could be established by their characteristic AB spectra. In equilibrium
( K , ) the ratio of the two isomers was found to be 1 :9. With addition of butadiene
the syn form disappears immediately, while the concentration of the anti form
consequently increases. This presents evidence for the higher reactivity of the
thermodynamically more stable syn form corresponding with the trans selectivity
of the complex and for the formation of the new butenyl group in the anti con-
figuration via the reaction channel kit. Although in the butadiene-containing
reaction solution only the anti form can be seen, practically no cis units are
formed. Obviously the anti butenyl complex is not reactive, and the polymeriza-
tion can proceed only after the formation of the reactive syn form by anti-syn iso-

r l+

/ R anti 1 1 ' h A

+ k, = 2.9x 10-6S1(50 "C)

I L
L
SYn

Scheme 7. The catalytic reaction mechanism of trans-1,4polymerization of butadiene with

the bis(tripheny1phosphite) complex [N~(V~-RC~H~)(P(OP~~)~]PF~ as the catalyst.
 2.3.2.2 Stereospecijic Polymerization of Butudiene or Isoprene 30 1

merization of the butadiene complex (kds), which therefore must be considered

as the rate-determining step in the catalytic cycle. Consequently, after all the bu-
tadiene has been consumed, the syn form slowly appears again in the 31P-NMR
spectrum of the solution.
Quite analogously, the trans selectivity of the allylnickel iodide [Ni(q3-
C3H5)II2can be explained, but with the butadiene insertion as the rate-determining
step in the catalytic cycle [71-731.

cis-1,4 Polymerization

To catalyze the formation of cis units, according to the general reaction model
in [26] the second reaction channel k2c, via the extremely reactive ligand-free
cationic v4-cis-butadiene complex [Ni($-RC,Hs)(r4-C4H,)1+ as catalyst, must
be opened. This can be realized by weakening the nickel(I1)-ligand bond steri-
cally (cf. P(OPh)3 < P(O-o-Tol)3 < P(OThym), < P(O-o-Biph)3) or electroni-
cally (cf. P(OPh), < MeCN < AsPh, < COD < SbPh3) in the bis(1igand)
ally1 complexes to favor butadiene coordination by ligand substitution. Since
the cationic y4-cis-butadiene complex is highly reactive, as a rule the increase
of cis selectivity is connected with an increase in activity. The limit is reached
in the ligand-free cationic C I 2-allylnickel(II) complexes with the noncoordinat-
ing anions PF6-, SbF6-, and B(C6H3(CF3)&, where the butadiene has to com-
Pete coordinatively only with the C-C double bonds from the growing chain at
the nickel. These are indeed the most active nickel catalysts for butadiene
polymerization which are known. In the ligand-free cationic butenyl-buta-
diene-nickel(I1) complex C( 1)-C( 1) bond formation can take place only
according to the n-ally1 insertion mechanism if the next double bond from
the growing chain interacts coordinatively with the nickel center in the fifth
position, as shown by Structure 2 in Scheme 6, in order to stabilize the transi-
tion state in agreement with Tolman's 18-16-electron rule [74]. One important
consequence of the necessary double bond coordination is the higher reactivity
of the butenyl group in the anti configuration, giving rise to the formation of
cis units via the reaction channel k2c. Furthermore, the y4-cis coordinated bu-
tadiene can react more easily from the prone arrangement, as has been estab-
lished experimentally for the Ziegler-Natta catalyst Ni(02CR)2/BF3 . OEt2/
AlEt, by Porri et al. [l, 371. Both aspects have been confirmed conclusively
by quantum-chemical calculations of the corresponding transition states using
the density functional theory [75].
Since the rate of anti-syn isomerization has been proven to be very rapid in
the ligand-free C12-allylnickel(II)cation [Ni(r',112,112-C,2H,9)1+,in this case the
cis-trans selectivity depends solely on the difference in the free enthalpies of
the transition states for the insertion reaction via the anti- or the syn-butenyl com-
plex, independently of the concentrations of the two complexes in the anti-syn
equilibrium, according to the Curtin-Hammett principle [26, 6 11.
In Scheme 8 the reaction mechanism for the cis-1,4 polymerization of
butadiene with the polybutadienylnickel(I1) cation as the catalyst is shown.
302 2.3 Reactions of Unsaturated Compounds

e
4
1K5
+

i k2t f
r t

Scheme 8. The catalytic reaction mechanism of cis-1,4 polymerization of butadiene with the
polybutadienylnickel(I1) cation [Ni($,r2,q2-RC ,2H,8)]+as the catalyst.

During a very short initiation period the cation [Ni(C,,H,,)]+, which is present
mainly in the thermodynamically more stable syn form b, reacts via the less
stable but more reactive anti form a with insertion of butadiene into the anti-
-polybutadienyl complex c. As a result of the very rapid anti-syn isomerization
this complex also exists in equilibrium (cf. K3) with the more stable syn com-
plex d, which must be regarded as the stable storage complex under the condi-
tions of polymerization. With butadiene the polybutadienyl-butadiene com-
plexes e and f are formed as the actual catalysts. By the much higher reactivity
of the less stable anti complex e, the formation of cis units is catalyzed. Since
all the equilibria can be assumed to be rapid, the insertion reaction of butadiene
(/I2,) has to be taken as the rate-determining step in the catalytic cycle. Thus,
the catalytic activity is dertermined thermodynamically by the concentration
of the v4-cis-butadiene complex in the anti form e and kinetically by its reac-
tivity kZc.
 2.3.2.2 Stereospecijic Polymerization of Butudiene or Isoprene 303

For the cis-trans selectivity, which is defined as the ratio of the rates of forma-
tion for the cis and the trans units rc/rt,eq. (8) can be derived [26, 611:

ScIt = rJrt = k2Jk2[. K5 = exp[-(AGz+ - AGp+)/Rr] (8)

This means that the cis-trans selectivity depends solely on the difference
between the free standard enthalpies AG$ - AGF+ of the transition states for
the insertion reaction with the anti and the syn form of the polybutadienyl v4-
cis-butadiene complex e and f, respectively, independently of their concentration
ratio in the anti-syn equilibrium K5. To explain the cis-trans selectivity of 93 %
cis and 4 % trans attributed to the ligand-free allylnickel(I1) cation, a stability dif-
ference between the transition states of about 1.9 kcal mol-’ (8 kJ mol-’) must be
assumed, which can easily arise from the different steric conditions for the neces-
sary coordination of the next double bond in the anti and the syn forms e and f of
the catalyst complex.

Equibinary cis-trans-1,4 Polymerization

Instead of the coordination of the next double bond in the growing chain, one
hard ligand or anion can coordinate to the nickel, in the axial position either
above or below the plane of the complex, and give the necessary energetic support
for the insertion reaction with the y4-cis-coordinated butadiene; see Structure 3 in
Scheme 6.
In this case the stability difference between the transition states of the insertion
step for the anti and the syn forms of the catalyst complexes e and f, which arises
from the different steric conditions for double-bond coordination, is practically
lost and, according to S,,t = k2c/k2t. K5 = 1, an equibinary polybutadiene may
be formed. Furthermore, the formation of an alternating equibinary polybutadiene
can be explained by the assumption that the anti-syn isomerization, which is
accelerated essentially by the coordination of the next double bond, will be
more favored if this double bond is in the cis configuration. In this way the
equibinary selectivity of [Ni(q3-C3HS)CF3CO2l2 in aromatic or chlorinated hydro-
carbons can be explained. In aliphatic hydrocarbons, however, owing to the
stronger tendency toward double-bond coordination from the growing chain,
the polybutadienylnickel(I1) cation could be formed reversibly in a small con-
centration by asymmetric splitting of the dimer, giving rise to the observed cis
selectivity [26].

Molecular Weight Regulation

Besides activity and selectivity, molecular weight regulation is an important

functional property of any polymerization catalyst. For allylnickel trifluoro-
acetate in the presence of a small amount of ligands, e.g., P(OPh)3 or
chloranil, a “living” 1,4-polymerization of butadiene has been proven [76].
304 2.3 Reactions of Unsaturated Compounds

In this case the degree of polymerization Z increases linearly with the conver-
sion C of the monomer and can be calculated from the general eq. (9) since
every metal atom M of the catalyst initiates the formation of only one growing
chain.
- [Monomer], . C
n= (9)
[MI
Additionally, if the initiation reaction is more rapid
_ _ than the chain propaga-
tion, a very narrow molecular weight distribution, M,/M, = 1 (Poisson distri-
bution), is obtained. Typically living character is shown by the anionic poly-
merization of butadiene and isoprene with the lithium alkyls [77, 781, but
it has been found also in butadiene polymerization with allylneodymium
compounds [49] and Ziegler-Natta catalysts containing titanium iodide [77].
On the other hand, the chain growth can be terminated by a chain transfer
reaction with the monomer via b-hydride elimination, as has already been
mentioned above for the allylcobalt complex-catalyzed 1,2-polyrnerization of
butadiene.
The same mechanism of molecular weight regulation has been proven explicitly
for the allylnickel complex-catalyzed 1,4-cis polymerization of butadiene with the
C,,-allylnickel(I1) complex [Ni(C12Hi9)]B(C6H3(CF3)2)4 as the catalyst [28]. The
B-hydride elimination has been established by trapping the generated diene
chain end in a Diels-Alder reaction and must be considered as the rate-determin-
ing step in the chain transfer reaction with the monomer, whereby the formation of
a new chain is initiated.
From the analysis of conversion as a function of the nickel concentration and
the reaction time, the propagation constant kp = 3 1 mol-' s-' and from the
relationship between the theoretical chain length and the degree of polymerization
-
n the transfer constant k, = 6 X 10-3 s-' could be determined at room temperature.
With the given ratio kplk, as a specific parameter of the catalyst, which proved
to be practically independent of the temperature, the degree of polymerization
rt can be regulated quantitatively according to eq. (10) in the frame of the
usable experimental conditions between rt = 400 and Z = 2500 (M,, =
20 000-135 000 g mol-I), proving the adopted reaction model.

-
n= [C4H61U. c
[Nil + k/k;[2.3 log(l/l(l-C)]

Furthermore, with [Ni(C12H19)]PF6 as catalyst it has been found that, if the

cation-anion interaction is enhanced by addition of NEt4PF6 to the reaction
solution in dichloroethane, the degree of polymerization Z can be increased
[79]. Presumably the electrophilicity of the nickel(I1) and thence the tendency
toward b-hydride elimination can be decreased in this way, opening an additional
possibility for molecular weight regulation which is of practical importance in the
case of the technical nickel catalyst.
 2.3.2.2 Stereospecific Polymerization of Butadiene or Isoprene 305

The Technical Nickel Catalyst

Apart from the Ziegler-Natta catalysts used industrially for the cis--1,4 polymer-
ization of butadiene (see Table 1), until now only the nickel catalyst Ni(02CR)2/
BF3 . OEt2/A1Et3has had its structure elucidated [27]. By practically proving com-
plete identity in all essential catalytic properties (e. g., activity, selectivity, average
molecular weight, and molecular weight distribution) with the structurally defined
model catalyst [Ni(C12H19)]03SCF3/10-20 A1F3 . x toluene, in agreement with the
general reaction model outlined above, for the technical nickel catalyst an analo-
gous structure of a polybutadienylnickel(I1) cation coordinated to a polymeric
fluoroaluminate anion has been derived (Figure 1) [27].

I I
Figure 1. Fixation of the C12-allylcomplex [Ni(C12H19)]03SCF3 on amorphous AlF3 . x
toluene in the model catalyst [Ni(CIZHI9)]O3SCF3/lO-20 AlF3 . x toluene. By
electrophilic splitting of one A1-F-A1 bond the [Ni(C 12H19)]+cation is coordinated
to the polymeric fluoroaluminate anion, which is generated by bonding the counter-
anion CF3S03-.

The formation of amorphous AlF3 from AIEt, and BF3 . OEt, is well known
[80], and via a reaction route which is quite familiar from organo nickel chemistry
including the reduction of the nickel carboxylate to nickel (0) with AlEt, [64], the
reoxidation with butadiene [81] and an exchange reaction with the aluminum
halide [82] the catalytic active polybutadienyl nickel(l1) polyfluoroaluminate
can be generated.

2.3.2.2.5 Polymer Manufacturing Processes

General Process Description

The manufacture of polybutadiene rubber (BR), which is carried out mainly in so-
lution processes using butyllithium or the Ziegler-Natta-type catalysts mentioned
in Table 1, has some general features in common, despite the different catalyst
systems [83]. The feed requirements for polymerization using Ziegler-Natta or
306 2.3 Reactions of Unsaturated Compounds

other organometallic catalysts are very stringent because various materials are
known to be destructive to these catalysts. These materials include water, oxygen,
carbon dioxide, and most polar compounds [84].
Most processes are best carried out in aromatic solvents. Due to its low boiling
point, benzene is the most economical solvent. Temperatures from 0 "C to 150 "C,
depending on the catalyst system used, are employed to produce the polymer. In
general, at higher temperatures the polymerization rate increases and the viscosity
of the polymer solution decreases, resulting in better heat transfer in these exother-
mic reactions. On the other hand, higher temperature causes a loss of stereo-
specificity and a faster decomposition of the catalyst. The polymerization is
carried out at pressures sufficient to maintain butadiene substantially in the liquid
phase.
The storage of the raw materials requires exclusion of air and moisture by inert-
gas blanketing. Butadiene peroxides, if formed, are broken down by an aqueous
solution of sodium carbonate. A flow diagram for the general process is shown
in Figure 2.
Dried monomer and solvent are premixed on their way from the storage tanks
to the reactor train. Alkylaluminum catalyst component, which acts as a scaven-
ger, is pumped or transferred by nitrogen pressure into the pipe before the first
reactor. The resulting mixture of solvent, butadiene, and alkylaluminum
compound is cooled and passed into reactor R1. The solutions of other catalyst
components are introduced separately, either into the pipe or directly into R1.
Carbon steel or stainless steel is used as the main construction material. The

polymerization
storage
tanks short stop

I I 1

drying
column
Y

-_I
--I steam
- ,steam
L
vibratory

1 water
screw

stripping unit

Figure 2. Manufacturing process for cis-l,4-polybutadiene.

 2.3.2.2 Stereospecific Polymerization of Butadiene or Isoprene 307

continous reaction train comprises a number of reactors [85], usually one to five,
with the earlier ones overflowing into the later reactors; alternatively, the levels in
the reactors are controlled, with the transfer of material from one reactor to an-
other achieved by a pump. These reactors and their agitators must be suitable
for a progressive viscosity rise, and there must be sufficient heat transfer between
the solution and the cooling medium wall to keep the temperature controlled to
give a peak rate of heat evolution. Carboxylic acid or water, mainly used to
quench the reaction, is introduced after the polymer solution leaves the last
reactor. Antioxidants can be added simultaneously. The polymer solution is sent
by pump through a filter to one of several blend tanks, each of which holds the
contents of a number of reactors. Separation of the polymer is performed either
by evaporating the solvent on drum dryers or most frequently by steam-stripping.
In the first stripper the polymer solution is exposed to steam and water. The
solvent is stripped off and a slurry of small rubber particles suspended in water
is formed. Further contact with steam in the following strippers reduces the con-
tent of solvent, monomer, and other low-boiling substances. Evaporated solvent is
condensed, separated from water and then dried by distillation. The rubber is
separated from the hot water by vibratory screens and dewatered in a screw
press. The final drying of the polymer is accomplished in a tunnel dryer or in
an extruder and then in vibratory equipment. Then the butadiene rubber [BR] is
baled and packaged.

Process Variants

Lithium-Polybutadiene

Medium-cis lithium-polybutadiene was first developed by Firestone Tire and

Rubber Company in 1955 [86]. Solution polymerization using anionic catalysts
is usually based on butyllithium. Alkyllithium initiation does not have the high
stereospecificity of the coordination catalysts based on titanium, cobalt, nickel,
or neodymium compounds. Polymerization in aliphatic hydrocarbon solvents
such as hexane or cyclohexane yields a polymer of about 40% cis, 50% trans
structure with 10 % 1,2-addition. However, there is no need for higher cis content
because a completely amorphous structure is desired for rubber applications; the
glass transition temperature is determined by the vinyl content. The vinyl content
of the polybutadiene can be increased up to 90 % by addition of small amounts of
polar substances such as ethers.
Alkyllithium initiators offer some peculiarities in contrast to the coordination
catalysts [4 11. Alkyllithium initiation can tolerate very high temperatures. As
expensive cooling facilities are not needed, the polymerization can proceed at
high reaction rates with low investment and operating costs. Since the
polymerization runs without termination or other side reactions under formation
of “living polymers”, the preparation of block polymers by sequential addition
of monomers is possible. It also permits the introduction of functional groups
on the end of each chain. Because the initiation step is fast relative to the pro-
308 2.3 Reactions of Unsaturated Compounds

pagation step, a narrow molecular weight distribution results. The molecular

weight is directly proportional to the molar ratio of butadiene to BuLi (cf.
eq. (9)).
By means of a coupling agent, i.e., SiCI4, it is possible to produce a poly-
butadiene with a branched, starlike configuration, which leads to excellent pro-
cessability [87]. Whereas these coupled polymers are used in tire production,
those with narrow molecular weight distributions occupy a large market as impact
modifiers in plastics.
With barium-containing anionic initiators [88] polybutadiene with a high trans
content [89] and less then 5 % of vinyl double bonds can be synthesized. This
rubber does not crystallize at room temperature but can undergo crystallization
upon stretching. The properties of rubber, e. g., green strength, tackiness of the
compound, as well as tensile strength of the vulcanizate, are much improved by
strain-induced crystallization.

Titanium-Polybutadiene

The first technical use of a titanium catalyst, made from titanium tetraiodide
and trialkylaluminum compounds, was developed by Phillips [ 111. The preferred
alkylaluminum used was either A1(C2Hs), or Al(i-C4H& The optimal ratio of
AlR3/Ti14 is between 2:6 and 6:1, depending on the purity of the solvent and
the monomers. If the optimal conditions are not met, the activity is only affected
slightly. The stereospecificity of the reaction does not depend on the AI/Ti ratio.
The polymerization speed increases with increasing amounts of catalyst, while the
molecular weight and content of the cis-l,4 double bonds decreases. The catalyst
has been measured to carry 2-5 mmol Ti14/kg BR. At a reaction temperature
of 5-35 "C and a reaction time of 2 4 h over 90 % conversion is achieved, corre-
sponding to a turnover number of about (2-5) X lo3 mol C4H6/(mo1Ti . h).
Because of the insolubility of Ti14 in hydrocarbons, the exact amount of catalyst
used is difficult to determine and the catalyst is subject to breakdown; therefore
more soluble catalyst systems were developed. Technically important examples
are TiC14/12/AIR3[90], TiCl4/R,A1I3,/A1R3 [91], and Ti(OEt)I,/TiCl,/AlEt, [92].
With this last system, at higher activities, there is only a very slight influence of
the AVTi relationship on the molecular weight of the polymer. There is often
a slight fluctuation in the concentration of active alkylaluminum bonds, due to
solvent impurities. The third system is therefore technically desired because this
fluctuation does not influence the product quality. The molecular weight is regu-
lated through the molar ratio of Ti(OC2Hs)13to Tic&. All titanium iodide systems
exhibit a high activity only in hydrocarbons such as benzene and toluene.
Polymerization in aliphatic and cycloaliphatic solvents can be achieved with a
catalyst system consisting of Ti(OR),I, Ti(OR),CI and A1R3 [93]. The lower activ-
ity in aliphatic solvents is compensated by the higher polymerization temperature
without a loss of stereospecificity.
 2.3.2.2 Stereospecijic Polymerization of Butudiene or Isoprene 309

Cobalt-Polybutadiene

The use of cobalt catalysts in the production of cis-polybutadiene has been known
since the 1955 Goodrich work [12]. Halides make suitable cobalt compounds, as
well as acetylacetonates and the salts of the carboxylic acids from Co" and Co"'.
Only the soluble compounds such as cobalt octanoate or cobalt naphthenate have
practical use, because they build homogeneous catalysts and because they develop
a much higher activity. As co-catalysts, alkylaluminum halides such as diethyl-
aluminum chloride or ethylaluminum sesquichloride are used. These catalysts
attain their highest activity only in the presence of a small amount of water or
other donors [94]. The amount of cobalt required, 0.1-0.4 mmoVkg butadiene,
is very low at polymerization temperatures of 5-50°C. In contrast, a high
Et,AlCl/Co ratio of 50-5OO:l is necessary in order to obtain a high conversion.
While increasing the cobalt concentration leads to a lower cis content, a higher
Et2AlC1concentration results in increasing stereospecifity [95].
The H20/Et,A1CI relationship affects the conversion as well as the molecular
weight of the polymers. In the area of high activities at H,O/Et,AlCl ratios
from 0.1 : 1 to 1: 1, the molecular weight and the yield increase with a (comparable)
increase in the amount of H 2 0 [94].
The influence of temperature on the conversion and the cis content is slight.
The molecular weight decreases with increasing temperatures.
Changes in monomer concentration also have an effect on product quality. High
butadiene content causes the formation of gel that can coat the walls of the re-
action vessel and the pipeline; consequently the path of operation is disrupted.
In practice, up to 15 % butadiene is loaded in the solvent. Aromatic compounds
(especially benzene) are used as the solvent, as in Ti-BR production. By adding
small amounts of R3Al (R = C8-C1,) the polymerization can also be carried out
in aliphatic and cycloaliphatic solvents without any gel formation.
The molecular weight can be controlled by addition of ethylene, propene or
1,2-butadiene, without adversely affecting the stereospecificity or the activity of
the catalyst.
In the course of polymerization, branching grows with increasing conversion.
The rubber's properties are strongly influenced by the final monomer conversion
WI.

Nickel-Polybutadiene

This process was developed by Bridgestone Tire Co. [13], starting in 1959, using
catalyst systems that were made from three components: nickel carboxylate, boron
trifluoride-diethyl ether complex and a trialkylaluminum. With a combination
nickel naphthenate/BF3 . O(C2Hs)2/A1(C2Hs)3catalyst, BR is produced on a
large scale. BF3 . O(C2Hs)2increases the activity of the catalyst and leads to poly-
mers with the highest molecular weights. The optimum catalyst activity and
stereospecifity were attained from the molar ratio, AVNi = 0.7-2O:l and AVB =
0.7-1.5:l. The nickel added lies between 0.2 and 0.6 mmol/kg butadiene. By
3 10 2.3 Reactions of Unsaturated Compounds

changing the temperature at which the catalyst is made, the catalytic activity can
be influenced. At a higher reaction temperature, the catalytic activity is dimin-
ished, and the gel content of the polymerate increases. The catalyst formation re-
action could therefore have a temperature of between -5 and 40 "C. Aromatic hy-
drocarbons are used as solvents. In the course of the polymerization, the molecular
weight increases very fast at first, then it equilibrates at 50% yield [96]. The re-
action is strongly accelerated, without interfering with the cis content of the poly-
mer, which lies in general between 96 and 98 %, by raising the temperature from
20 to 60 "C. Slight amounts of 1,2-butadiene, acetylene or vinylcyclohexane act to
lower the molecular weight; however, these compounds are also associated with a
drastic decline in monomer conversion [97].

Neodymium-Polybutadiene

The f-transition metal catalysts were first described by von Dohlen [98] in 1963,
Tse-chuan [99] in 1964 and later by Throckmorton [loo]. In the 1980s Bayer 1141
and Enichem [ l o l l developed manufacturing processes based on neodymium cat-
alysts. The catalyst system consists of three components 11021: a carboxylate of a
rare earth metal, an alkylaluminum and a Lewis acid containing a halide. A typical
catalyst system is of the form: neodymium(II1) neodecanoate/diisobutylaluminum
hydridehutyl chloride [ 1031. Neodymium(II1) neodecanoate has the advantage of
very high solubility in the nonpolar solvents used for polymerization. The molar
ratio AVNdKl = 20: 1: 3 . Per 100 g of butadiene, 0.13 mmol neodymium(II1) neo-
decanoate is used. With respect to the monomer concentration, the kinetics are
those of a first-order reaction.
The advantages that neodymium catalysts have over other catalyst systems lie
in the solvents that can be used with them, the temperature of polymerization, and
the resulting polybutadiene product properties. In contrast to titanium, cobalt, and
nickel systems, the neodymium-based systems operate in aliphatic polymerization
solvent. The aliphatic solvents are cheaper, less toxic, and easier to remove in the
solvent-stripping process. The neodymium catalysts are stable to higher tempera-
tures than the other catalysts mentioned, with the cis content of the resulting poly-
mer remaining relatively unaffected. Higher polymerization temperature results in
less expensive cooling facilities and energy savings.
Neodymium-based systems allow independent control of the main structural
parameters, which are molecular weight, molecular weight distribution and
content of cis-1,4 double bonds. The molecular weight can be controlled via
the polymerization temperature, catalyst concentration, or ratio of alkylaluminum
to neodymium compound. The molecular weight distribution is influenced by the
reaction conditions for the preparation of the catalyst, such as time, temperature,
and the order of component addition to form the catalyst. Catalysts that are not
preformed give a narrow molecular weight distribution. The factor which influ-
ences the cis content of the polybutadiene most strongly is the nature of the alkyl-
aluminum. Triisobutylaluminum or diisobutylaluminum hydride always gives
products with a very high cis content of 98-99 %. If triisobutylaluminum is pro-
 2.3.2.2 Stereospecifc Polymerization of Butadiene or Isoprene 3 11

gressively replaced by triethylaluminum, the cis content falls accordingly. This

enables the production of polybutadiene with a cis content between 90 and 99 %.

Properties of the Rubber, Compounds, and Vulcanizates

The key properties of high-cis BR vulcanizates are outstanding low-temperature

properties, high elasticity, even at low temperatures, and better wear resistance
than all other elastomers.
These properties are affected by structural parameters [102], e. g., molecular
weight, molecular weight distribution, long chain branching, microstructure,
and crystallization behaviour, which are mainly determined by the catalyst system
used (see Table 2).
The glass transition temperature depends on the vinyl content (V) and can be
calculated from: Tg= 71 (V- 106) ["C] [104].
BR is used in nearly all parts of the tire with the exception of the inner liner;
it is always blended with natural rubber (NR) or styrene-butadiene rubber (SBR).
Apart from the extrudability, in NR blends the Nd-BR polymers exhibit advan-
tages in all important compound and vulcanizate properties. Also, in SBR blends
Nd-BR leads to the best vulcanizate properties in comparison with all other types
of BR.
Table 2. Properties of different types of BR.
Li-BR Ti-BR Co-BR Ni-BR Nd-BR
Microstructure
cis- 1,4 content[%I 35 93 97 97 98
trans-l,4 content [%I 53 3 1.5 2 1.5
Vinyl content [%I 12 4 1.5 1 0.5

Mooney viscosity
ML [ l + 4 ' , IOO'C] 55 47 47 43 52

Economic Aspects

As an example of manufacturing costs, Table 3 presents estimated production

costs for Co-BR and Li-BR. These costs are based on new construction, operating
at full capacity, and are higher than actual costs in existing commercial facilities.
Since the beginning of production in 1960 polybutadiene rubber has gained an
ever-increasing importance as a tire polymer. World consumption of BR in 1992
was 1250 thousand tons [lo51 (excluding the former centrally planned economy
(CPE) countries). Future growth is estimated at 2.2 % per year, bringing estimated
1997 world consumption to about 1395 thousand tons. Tires and tire products re-
main the largest end use for BR, accounting for 65-70 % of worldwide consump-
3 12 2.3 Reactions of Unsaturated Compounds

Table 3. Major production cost components for BR.

Cost [cents per pound]
Li-BR CO-BR
Raw materials 21.38 24.16
Utilities 4.49 4.88
Labor 2.79 3.17
Othera) 22.62 26.24

Total 5 1.28 58.45

a) Sales, general, administrative, and research costs are included.

tion. However, non-tire uses, especially impact modification of styrenic plastics,

are of steadily increasing importance. High-impact polystyrene is the largest
non-tire end use. Projections to 1997 indicate that plastics modification will be
30% of total BR consumption by that time.

2.3.2.2.6 Perspectives
Further progress in understanding catalytic reaction mechanisms and structure-
reactivity relationships in the field of stereospecific diene polymerization is to
be expected by applying the synthetic approach. By the synthesis of new cataly-
tically active ally1 metal compounds, as structurally defined single-site catalysts, it
should be possible to derive appropriate reaction models for the practically impor-
tant Ziegler-Natta catalysts in order to elucidate the structure and efficiency of
these catalysts. Additionally, the catalytic potential could also be made more
fully accessible of those transition metals, such as iron, ruthenium, rhodium,
and others, which have not been so thoroughly investigated until now. In connec-
tion with the better mechanistic understanding, new types of stereoregular poly-
mers should become available, especially by extending the capability for con-
trolled copolymerization of different dienes. Finally, technological extensions
and improvements, e. g., to stereospecific emulsion polymerization in aqueous
media or gas-phase polymerization without any solvent, are important aims of
future development.

References
[ 11 L. Porri, A. Giamsso, Conjugated diene polymerization, in Comprehensive Polymer
Science, Vol. 4, Part I1 (Eds.: G. C. Eastmond, A Ledwith, S. Russo, B. Sigwalt),
Pergamon, Oxford, 1989, pp. 53-108.
[2] R. T. La Flair, U. U. Wolf, Ullmann's Encycl. Ind. Chem.; 5th ed., 1993, Vol. A23,
pp. 273-282.
 References 3 13

[3] G. Wilke, in Structural Order of Polymers (Eds.: F. Ciardelly, P. Giusti), IUPAC,

Pergamon, Oxford, 1981, pp. 11-23.
[4] K. Ziegler, H. Breil, E. Holzkamp, H. Martin, DE 973.626 (1953).
[5] K. Ziegler, E. Holzkamp, H. Breil, H. Martin, Angew. Chem. 1955, 67, 541.
[6] Goodrich-Gulf Chemicals, Inc. (S. E. Home, Jr.), US 3.117.743 (1963); Goodrich-Gulf
Chemicals, Inc. (F. Gibbs, E. J. Carlson), GB 827.365 (1954).
[7] S. E. Home, Jr., J. P. Kichl, J. J. Shipman, V. L. Folt, C. T. Gibbs, Ind. Eng. Chem. 1956,
48, 784.
181 G. Natta, L. Porri, G. Mazzanti, IT 536.631 (1955); Chem. Abstr: 1959, 53, 3756.
[9] G. Natta, L. Porri, IT 538.453 (1956); Chem. Abstr: 1958, 52, 5032.
[lo] (a) G. Natta, Angew. Chem. 1956, 68, 393; (b) G. Natta, Angew. Chem. 1964, 76, 553.
[ I l l Phillips Petroleum Co. (R. Zelinski, D. Smith), GB 848.065 (1956); Chem. Abstl: 1961,
55, 15982.
[12] Goodrich-Gulf Chemicals, Inc. (C. E. Brockway, A. F. Ecker), US 2.977.349 (1955);
Chem. Abstr 1961, 55, 16012.
[ 131 Bridgestone Tire Co. (K. Ueda, A. Onishi, T. Yoshimoto, J. Hosono, K. Maeda), DE-AS
1.213.120 (1959).
[14] Bayer AG (G. Sylvester, J. Witte, G. Marwede) EP 0.007.027 (1978); Chem. Abstr: 1980,
92, 130.367; EP 0.011.184 (1978); Chem. Abstr: 1980, 93, 96555.
[I51 J. Witte, Angew. Makromol. Chem. 1981, 94, 119.
1161 Z. Shen, X. Song, S. Xiao, J. Yang, X. Kan, J. Appl. Polym. Sci. 1983, 28,
1585.
[ 171 G. Wilke, B. Bogdanovic, P. Hardt, P. Heimbach, W. Keim, M. Kroner, W. Oberkirch, K.
Tanaka, E. Steinrucke, D. Walter, H. Zimmermann, Angew. Chem. 1966, 78, 157; Angew.
Chem., Int. Ed. Engl. 1966, 5, 151.
[18] L. Porri, G. Natta, M. C. Gallazzi, Chim. Ind. 1964, 46, 428; J. Polym. Sci. C, 1967,
16, 2525.
[I91 B. D. Babitskii, B. A. Dolgoplosk, V. A. Kormer, M. I. Lobach, E. I. Tinyakova, V. A.
Yakolev, Izv. Akad. Nauk SSSR, Ser Chem. 1965, 1507.
[20] N. N. Drus, A. Zak, M. I. Lobach, V. A. Vasiliev, V. A. Kormer, Eur Polym. J. 1978,
14, 21.
[21] R. Warin, M. Julemont, P. TeyssiC, J. Organomet. Chem. 1980, 185, 413.
[22] R. Taube, U. Schmidt, Z. Chem. 1977, 17, 349.
[23] R. Taube, U. Schmidt, J.-P. Gehrke, P. Bohme, J. Langlotz, S. Wache, Makromol. Chem.,
Makromol. Symp. 1993, 66, 245.
[24] M. I. Lobach, V. A. Kormer, I. Yu. Tsereteli, G. P. Kondoratenkov, B. D. Babitskii, V. I.
Klepikova, J. Polym. Sci., Polym. Lett. 1971, 9, 71.
[25] R. Warin, Ph. TeyssiC, P. Bourdaudurq, F. Dawans, J. Polym. Sci., Polyrn. Lett. 1973,
11, 177.
[26] R. Taube, J.-P. Gehrke, P. Bohme, Wiss. Zeitschrift THLM, 1987, 29, 310.
[27] R. Taube, J. Langlotz, G. Miiller, J. Muller, Makromol. Chem. 1993, 194, 1273.
[28] R. Taube, S. Wache, H. Kehlen, J. Mol. Cutal. A: Chem. 1995, 97, 21.
1291 R. Benn, P. W. Jolly, Th. Joswig, R. Mynott, K. P. Schick, Z. Natu$orsch., Teil B 1986,
41, 680.
[30] H. Yasuda, A. Nakamura, Angew. Chem. 1987, 99, 745; Angew. Chem., Int. Ed. Engl.
1987, 26, 723.
1311 P. v. R. Schleyer, J. Kaneti, Y.-D. Wu, J. Chandrasekhar, J. Organomet. Chem. 1992,
426, 143.
[32] K. Vrieze, Fluxional ally1 complexes, in Dynamic Nuclear Magnetic Resonance
Spectroscopy (Eds.: L. M. Jackman, F. A. Cotton), Academic Press, New York,
1975.
3 14 2.3 Reactions of Unsaturated Compounds

[33] J. W. Faller, M. E. Thomson, M. V. Mattina, J. Am. Chem. Soc. 1971, 93, 2842.
[34] P. Cossee, in Stereochemistry of Macromolecules (Ed.: A. D. Ketley), Vol. 1 Marcel
Dekker, New York, 1967, p. 145.
[35] E. J. Arlman, J. Catal. 1966, 5, 178.
[36] R. Taube, J.-P. Gehrke, R. Radeglia, J. Organomet. Chem. 1985, 291, 101.
[37] S. Tobisch, R. Taube, Chem. Eur: J. 2001, 7, 3681.
[38] S. G. Davies, M. L. H. Green, D. M. P. Mingos, Tetrahedron 1978, 34, 3047.
[39] R. Taube, H. Windisch, S. Maiwald, Macromol. Symp. 1995, 89, 393.
[40] S. Tobisch, R. Taube, Organometallics 1999, 18, 3045.
[41] A. F. Halasa, D. N. Schulz, D. P. Tate, V. D. Mochel, Adv. Organomet. Chem. 1980,18,55.
[42] A. F. Halasa, V. D. Mochel, G. Fraenkel, ACS Symp. Ser: 1981, 166, 367.
[43] S. Bywater, D. J. Worsfold, J. Organomet. Chem. 1978, 159, 229.
[44] M. Morton, L. J. Fetters, R. A. Pett, J. F. Meier, Macromolecules 1970, 3, 327.
[45] N. J. R. v. Eikerna Hommes, M. Buhl, P. v. RaguC Schleyer, Y.-D. Wu, J. Organomet.
Chem. 1991, 409, 307.
[46] A. V. Tobolsky, C. E. Rogers, J. Polym. Sci. 1959, 40, 73.
[47] A. Mazzei, Makromol. Chem. 1981, Suppl. 4, 61.
[48] R. Taube, H. Windisch, S. Maiwald, H. Hemling, H. Schurnann J. Organomet. Chem.
1996, 513, 49.
[49] S. Maiwald, R. Taube, H. Hemling, H. Schumann, J. Organomet. Chem. 1998,552, 195.
[50] B. Dolgoplosk, Sov. Sci. Rev.,Sect. B2 1980, 203.
[51] G. Ricci, S. Italia, L. Pom, Polym. Commun. 1988, 29, 305.
[52] H. Ashitaka, K. Jinda, H. Ueno, J. Polym. Sci., Polym. Chem. Ed. 1983, 21, 1951, 1989.
[53] H. Ashitaka, K. Inaishi, H. Ueno. J. Polym. Sci., Polym. Chem. Ed. 1983, 21, 1973.
[54] G. Allegra, F. Lo Gindice, G. Natta, U. Giannini, G. Fagherazzi, P. Pino, Chem.
Commun. 1967, 1263.
[55] H. Bonnemann, Angew. Chem. 1973, 85, 1024; Angew. Chem., Int. Ed. Engl. 1973,
12, 964.
[56] R. Taube, U. Schmidt, J.-P. Gehrke, U. Anacker, J. Prakt. Chem. 1984, 326, 1.
[57] R. Taube, J.-P. Gehrke, U. Schmidt, J. Organomet. Chem. 1985, 292, 287.
[58] R. Taube, J.-P. Gehrke, J. Organomet. Chem. 1987, 328, 393.
[59] R. Taube, J.-P. Gehrke, P. Bohme, J. Kottnitz, J. Organomet. Chem. 1990, 395, 341.
[60] R. Taube, P. Bohme, J.-P. Gehrke, J. Organomet. Chem. 1990, 399, 327.
[61] R. Taube, J.-P. Gehrke, P. Bohme, K. Scherzer, J. Organomet. Chem. 1991, 410, 403.
[62] R. Taube, S. Wache, J. Organornet. Chem. 1992, 428, 431.
[63] R. Taube, S. Wache, J. Sieler, J. Organomet. Chem. 1993, 459, 335, and literature cited
therein.
[64] P. W. Jolly, G. Wilke, The Organic Chemistry of Nickel, Vol. 1, Organonickel Com-
plexes, Academic Press, New York, 1974.
[65] H. Lehmkuhl, T. Keil, R. Benn, A. Rufinska, C. Kriiger, J. Poplawska, M. Bellenbaum,
Chem. Ber: 1988, 121, 1931.
[66] J.-P. Gehrke, R. Taube, M. Jahn, R. Radeglia, Z. Chem. 1988, 28, 262.
[67] C. A. Tolrnan, J. Am. Chem. Soc. 1970, 92, 6777.
[68] P. W. Jolly, G. Wilke, The Organic Chemistry of Nickel, Vol. 2, Organic Synthesis,
Academic Press, New York, 1975, p. 255.
[69] P. TeyssiC, M. JulCmont, J. M. Thomassin, E. Walckiers, R. Warin, in Coordination Poly-
merization (Ed.: J. C. W. Chien), Academic Press, New York, 1975, p. 327.
[70] P. TeyssiC, F. Dawans, in The Stereo Rubbers (Ed.: W. M. Saltman), Wiley, New York,
1977, p. 79.
[71] J. F. Harrod, L. R. Wallace, Macromolecules 1969, 2, 449.
[72] T. Matsumoto, J. Furukawa, J. Macromol. Sci., Chem. 1972, A6, 281.
 References 3 15

[73] V. I. Klepikova, G. P. Kondratenkov, V. Kormer, M. I. Lobach, L. A. Churlyaeva,

. I Polym.
. Sci., Polym. Lett. 1973, 11, 193.
[74] C. A. Tolman, Chem. Soc. Rev. 1972, 1, 337.
[75] S. Tobisch, R. Taube, Organometallics 1999, 18, 5204.
[76] P. Hadjiandreou, M. JulCmont, P. Teyssie, Macromolecules 1984, 17, 2455.
[77] G. Sylvester, P. Miiller, Methoden Org. Chem. (Houben-Weyl)4th ed. 1987, Vol. E20,
Part 2, p. 801.
1781 J. Witte, Methoden Org. Chem. (Houben-Weyl)4th ed. 1987, Vol. E20, Part 2, p. 829.
1791 R. Taube, S. Wache, J. Langlotz in Catalyst Design for Tailor-made Polyolejins (Eds.:
K. Soga, M. Terano) Kodansha, Tokyo, 1994, p. 315.
[80] R. Koster, Liebigs Ann. Chern. 1958, 31, 618.
[81] K. Fischer, K. Jonas, P. Misbach, R. Stabba, G. Wilke, Angew. Chem. 1973, 85, 1002;
Angew. Chem., Int. Ed. Engl. 1973, 12, 943.
[82] A. C. L. Su, Adv. Organomet. Chem. 1979, 17, 269.
[83] A. L. Black, Chem. Eng. (London) Aug. 1, 1966, 65.
[84] H. J. Miiller, Ullrnann’s Encycl. Ind. Chem. 5th ed. 1985, Vol. A4, pp. 431, 440.
[85] Anon., Hydrocarbon Proc. 1965, 44/11, 260.
[86] Firestone Tire and Rubber Co. (F. C. Foster), US 3.317.918 (1967); Chem. Abstr. 1967,
67, 22713V.
1871 H. Fries, B. StollfuR, ACS Rubber Division Meeting, Cincinatti, October 1988, Paper
No. 8.
[88] Michelin et Cie (Comp. Gener. Etabl. Michelin) DE 2.115.462 (1971); Chem. Abstr:
1972, 76, 60722r.
[89] General Tire and Rubber Co. (I. G. Hagis, R. A. Livigni), US 3.903.019 (1975); Chem.
Abstr: 1975, 83, 207374j.
[90] Firestone Tire and Rubber Co., DE 1.112.834 (1961); Chem. Abstr. 1962, 56, 103.51~.
[91] Polymer Corp. Ltd. (A. Stewart, J. Darcy, L. A. McLeod), US 3.409.604 (1968); Chem.
Abstr: 1969, 70, 38665d.
[92] Bayer AG (N. Schon, G. Pampus, J. Witte), DE 1.165.864 (1964); Chem. Abstr: 1964,
60, 16085b.
1931 Bayer AG (N. Schon, G. Pampus, J. Witte), DE 1.190.441 (1965); Chem. Abstr. 1965,
63, 1974d.
[94] W. M. Saltman, L. J. Kuzuma, Rubber Chem. Technol. 1973, 46, 1055.
[95] M. Gippin, Ind. Eng. Chem., Prod. Res. Dev. 1962, I , 32.
[96] T. Yoshimoto, K. Komatsu, R. Sakata, K. Yamamoto, Y. Takenchi, A. Onishi, K. Ueda,
Makromol. Chem. 1970, 139, 61.
[97] R. Sakata, J. Honoso, A. Onishi, K. Ueda, Makromol. Chem. 1970, 139, 73.
[98] Union Carbide Corp. (W. C. von Dohlen, T. P. Wilson, E. G. Caflisch), BE 644.291
(1 964); Chem. Abstr: 1965, 63, 5874.
[99] S. Tse-chuan, G. Chung-yuan, C. Chung-chi, Ouyang-chiiin, Sci. Sinica 1964, 8, 1339.
[loo] M. C. Throckmorton, Kautsch., Gummi, Kunst. 1969, 22, 293.
[ l o l l Anic S.p.A. (U. Pedretti, G. Lugli, S. Poggio, A. Mazzei), DE 2.833.721 (1979); Chem.
Abstr: 1979, YO, 169316b.
[ 1021 G. Sylvester, B. StollfuB, ACS Rubber Division Meeting, Dallas, April 1988, Paper No. 32.
[I031 D. J. Wilson, Makromol. Chem., Makromol. Symp. 1993, 66, 273.
[lo41 W. S. Bahary, D. J. Sapper, J. H. Lane, Rubber Chem. Technol. 1967, 40, 1529.
11051 Chemical Economics Handbook, CEH Accession No. 525.300 D, Product Review
Polybutadiene Elastomers (1993; Update 1995).
[106] R. Taube, G. Sylvester, in B. Cornils, W. A. Henmann (Eds.), Applied Homoge-
neous Catalysis with Organometallic Compounds, 1st ed., VCH, Weinheim, 1996,
pp. 280ff.
3 16 2.3 Reactions of Unsaturated Compounds

2.3.2.3 A Clean Route to Methacrylates

via Carbonylation of Alkynes
Eite Drent, Willem W Jagel; Jan J. Keijspel;
Frank G. M. Niele

2.3.2.3.1 Introduction
(Meth)acrylic acid and esters are large-volume industrial chemical intermediates
for the production of co- and homopolymers. Acrylic acid (AA), with a worldwide
production of approx. 1.5 X lo6 t/a, finds its main use in the manufacture of
superabsorbent polymers and various acrylate esters. The most important
production process for AA involves the two-stage oxidation of propene (via
acrolein) in the presence of a large excess of steam by heterogeneous catalysts.
Selectivities to AA for the overall process reach 85-90% based on propene
(cf. Chapter 1, Introduction).
Of the methacrylics, methyl methacrylate (MMA) is by far the most important
intermediate, with a production of approx. 2 X lo6 t/a (1.6 X lo6 t/a for Europe
and USA [la]). It finds its main application in polymers as “Plexiglass” or
“Perspex,” a crystal-clear artificial glass with high hardness, resistance to fracture,
and chemical stability. About 80 % of the MMA is produced on the basis of the
Acetone-CyanoHydrin (ACH) process [ 1b]. This process involves stoichiometric
chemistry and is characterized by an overall yield of MMA of about 80 % (based
on acetone) with the stoichiometric production of about 2.4 t of ammonium bisul-
fatekulfuric acid waste per ton of MMA. This process is therefore faced with in-
creasing environmental costs. As a consequence, several alternative catalytic pro-
cesses for MMA production are - and have been - under development.
Mitsubishi Rayon in Japan has commercialized a three-step process on the basis
of a two-step catalytic oxidation of isobutene, preferentially through t-butanol as
primary intermediate. This process suffers not only from a relatively moderate
overall MMA yield (-80 %), but also from increasing isobutene cost due to its
alternative use for MTBE (methyl tert.-butyl ether) production as a gasoline
additive.
A third homogeneously catalyzed process, on the basis of formaldehyde
condensation with propanal to give methacrolein and subsequent oxidation to
methacrylic acid, was commercialized in 1990 by BASE Application of this
process is limited by the availability of cheap propanal, produced by large-scale
ethylene hydroformylation (cf. Section 2.1.1).
The development of both ecologically sound and economically attractive new
products and processes poses a major challenge for the modern chemical industry
in general. Taking MMA as an example, there is clearly a strong incentive for the
development of a low-cost, high-yield, clean, catalytic process for its production.
The development of a new, highly efficient class of homogeneous catalysts for the
carbonylation of alkynes, which makes possible an economically competitive and
environmentally benign process for MMA, is reported.
 2.3.2.3 A Clean Route to Methaciylates via Carbonylation of Alkynes 3 17

2.3.2.3.2 History of the Carbonylation of Alkynes

The carbonylation of alkynes has been known since the pioneering work of Reppe
in the late 1930s [2] and has attracted considerable interest from industry and
academia [3].
Interestingly, carbonylation of acetylene to give AA (eq. (1)) was among the
first large-scale industrial applications of homogeneous catalysis by organometal-
lic complexes (cf. Section 2.3.2.1).
H-CGC-H + CO + H20 H*C=CH-COOH (1)
The applied nickel catalyst, promoted by copper halides, required rather severe
reaction conditions (T = 220 "C, P = 10 MPa), but gave good AA yields up to
90 9% based on acetylene. This so-called catalytic Reppe process was commer-
cially operated in Germany, the USA, and Japan. Due to the limited availability
of cheap acetylene as feedstock and the severe reaction conditions involved in
the carbonylation process, this process has lost the competition with (heteroge-
neously catalyzed) oxidation of readily available propene, even though a perfect
selectivity to AA is not achieved in the latter process.
Although propyne can be made available from naphtha crackers as chemical
feedstock (in amounts varying between 0.2 and 1.O 9% on total intake of hydro-
carbon feedstock), until recently there existed no prospect of a feasible propyne
carbonylation process to provide a route to MMA via the reaction represented
in eq. (2) - i.e., a reaction similar to eq. (1):

H3C-CSC-H + CO + CH3OH - CH3

I
HpC=C-COOCH3
MMA
(2)

This has been predominantly due to the lack of an efficient catalyst of

sufficiently high activity and selectivity for the carbonylation of higher alkynes
such as propyne [4]. Besides a high catalyst activity, not only is a high chemos-
electivity of the carbonylation to unsaturated esters required, but a high regioselec-
tivity of the carbonylation to the desired branched isomer (MMA) is, obviously,
also essential.
In recent years, attention has been focused on alkyne carbonylation catalysts
based on the metals nickel, palladium, and platinum, modified with a variety of
tertiary (bi)phosphines [ 5 ] .The main goal has been to develop chemo- and regio-
selective carbonylation catalysts for application to higher alkyne substrates for the
synthesis of certain fine chemicals. Many of these catalysts do allow the carbon-
ylation to proceed under milder conditions than those applied in the catalytic
Reppe process, and some of these catalysts do provide the branched regioisomer
product from higher alkynes with good selectivity. However, in all cases reaction
rates are very low, i.e., below 100 (and in most cases even below 10) mol/mol
metal per h, as are the product yields in moVmol metal (< 100). These catalyst
productivities are far too low for large-scale industrial application in the produc-
tion of commodity-type products, such as (meth)acrylates.
3 18 2.3 Reactions of Unsaturuted Compounds

An interesting new class of highly efficient homogeneous palladium catalysts

for the carbonylation of alkynes was developed at Shell [6]. These catalysts not
only allow the selective and rapid carbonylation of acetylene, but also of higher
alkynes such as propyne, and do so with spectacularly high activity and selectivity
to the branched unsaturated products (e. g., acids or esters). For the first time, they
allow the development of a cost-effective MMA process on the basis of carbon-
ylation technology [7]. Due to the high selectivities achieved in the carbonylation
process, such a process has the extra benefit of being friendly to the environment,
producing minimal amounts of waste, thus competing favorably with the tradi-
tional ACH process.
The essential feature of the catalyst systems is that they are formed by the com-
bination of a palladium(I1) species with a ligand containing a 2-pyridylphosphine
moiety and a proton source containing anions weakly coordinating to palladium
[8]. These catalysts are very efficient for the conversion of propyne (for example)
as the alkyne and methanol as the nucleophilic co-reagent.

2.3.2.3.3 Carbonylation of Propyne

The discovery of the above-mentioned class of highly efficient alkyne carbon-
ylation catalysts originated from a general study of reactions homogeneously
catalyzed by cationic metal complexes [6, 8, 91, e. g., the methoxycarbonylation
of propyne (eq. (2)). The catalysts applied were cationic palladium phosphine
systems prepared in situ from three components: (1) palladium acetate, (2) an
excess (10-40-fold on Pd) of a (mono)phosphine ligand(L) and (3) an acid
(HX) [8]. Methanol was used as both reactant and solvent, but many other sol-
vents can also be used, such as N-methyl-2-pyrrolidone (NMP) or product
MMA.

The Effects of Ligand Structure

A dramatic increase in catalyst activity and selectivity was surprisingly ob-

served when PPh3 was replaced by 2-pyridyldiphenylphosphine (2-PyPPh2).
Even under much milder conditions (45 "C instead of 115 "C), the use of
this ligand resulted in a spectacular increase in activity by some three orders
of magnitude, whereas selectivity increased to 99 %! The only significant by-
product was methyl crotonate, the linear isomer of MMA. Typical MMA
formation rates of approx. 20-50 kmol/mol Pd per h are observed under
mild conditions (T = 45-60 "C, P = 1-6 MPa). These high rates are observed
both in batch autoclave and in continuously fed stirred-tank reactor experiments
[8]. Highest rates are observed at a ligand-to-palladium ratio of about 20.
Around and above this value, the reaction order is close to zero with respect
to ligand.
Rates are strongly dependent on the amount and type of acid used. For high
activity it is necessary to have an excess of an acid, containing weakly coordi-
 2.3.2.3 A Clean Route to Methacrylates via Carbonylation of Alkynes 319

50000

E 40000
2-
f 30000
1

2
E 20000
.-
.
I-

.->
.I-

3 10000

sd = 89.0 % sel= 98.9 oh sel= 99.2 oh sel = 90.0 %

T=115"C T=45"C T=70"C T=90"C

Figure 1. Effect of ligand structure; sel = selectivity.

nating anions, such as sulfonates, over and above the stoichiometric quantity of
2 moVmol Pd required for displacement of the acetate anions as acetic acid.
Kinetic measurements, in continuously fed stirred-tank reactor experiments
under steady-state conditions with 2-PyPPh2/Pd = 20 and methanesulfonic
acid/Pd 2 10, indicate a zero order in acid and first order in palladium, propyne,
and methanol.
Figure 1 shows the effect of ligand variation on rate and regioselectivity of
MMA formation. High catalyst activities and selectivities to MMA are only
observed when the (dipheny1)phosphine ligand contains a 2-pyridyl group sub-
stituent connected to phosphorus.
Figure 2 shows the effects of subtle modifications of the 2-PyPPh2 ligand
structure. It is seen that variation of the position of a methyl group substituent
in the pyridyl group can result in significant changes in the regiospecificity of
the catalyst. Whereas substitution at the 4-position of the 2-pyridyl group has
virtually no effects, it is remarkable that introduction of the methyl substituent
at the 6-position of the 2-pyridyl group raises the regioselectivity to MMA to
99.95 % (at 45 "C). This implies that formation of methyl crotonate is sup-
pressed by a factor of 20 compared with that observed with the unsubstituted
ligand. Remarkably, the high rate of MMA formation is unaffected by the
presence of the 6-methyl substituent of the pyridyl group.
Similar effects can be observed with other substituents at the 6-position of the
2-pyridyl group.
320 2.3 Reactions of Unsaturated Compounds

c3 activity
selectivity
50000 -

p 40000-
\
U
h
-
2
1
30000-
0
E
y 20000-
.-c
.->
4-

3 10000

0-

Figure 2. Effect of pyridyl substituents.

Mechanistic Aspects

The catalytically relevant palladium species in propyne carbonylation is thought to

be a d8 square-planar cationic palladium(I1) complex of Structure 1 [8], which is
symbolized by [L2PdX]X, where L stands for the 2-pyridylphosphine ligand and
X for the anion; it is thought that complexes of the type 1 are assembled in situ
from the three components added in the catalytic experiments (eq. (3)) [9, 101.

nL + Pd(OAc)? + rn HX - [L2PdX]X
1
+ (n-2) L + (rn-2) HX + 2 HOAc
(3)

The two 2-PyPPh2 ligand molecules in the coordination sphere around palla-
dium(I1) in 1 are differently bonded in the square-planar configuration. One of
the ligands is coordinated in bidentate manner to palladium(I1) through both
the phosphorus and nitrogen atoms, thus creating a four-membered ring struc-
ture. The second ligand is monocoordinated via the phosphorus atom only.
The chelating 2-pyridylphosphine moiety is suggested to play a crucial role
in the determination of the high selectivity of the carbonylation, whereas the
monocoordinated ligand, being only weakly bound to the palladium center and
rapidly displaceable by reactant molecules, may play a co-catalytic role as a
“proton messenger” during the protonolysis step of the catalytic cycle.
 2.3.2.3 A Clean Route to Methaciylates via Carbonylation of Allcynes 32 1

In the Structure 1 reported in the literature [lo], the anions (X-) are ha-
lides, relatively strongly coordinating to palladium(I1). One of the anions is
directly bound to palladium, whereas the other is present outside the immedi-
ate coordination sphere. However, in the catalytic complexes which we are
discussing, the anions need to be weakly or noncoordinating to the palladium
center. Such anions will be easily displaced by a reactant molecule and even
by a solvent molecule. The easy dissociation of the anions from the palla-
dium center also contributes to the genesis of a strongly electrophilic palla-
dium cation, which can bind reversibly the nucleophilic substrate molecules
(alcohol, carbon monoxide, and alkyne). Thus, carbon monoxide and the
alkyne can displace each other at the palladium center and become electro-
philically activated in each other’s presence, to be attacked by the respective
nucleophilic anionic organic moiety at palladium, such as a methoxy or car-
bomethoxy group (vide infra).

The Selectivity-Determining Step of the Catalytic Cycle

Methyl methacrylate can be formed via two different possible catalytic cycles.
One starts with a Pd-hydride species, undergoing propyne insertion in the 2,1
regio-mode, followed by carbon monoxide insertion in the Pd-alkenyl bond
and subsequent termination by alcoholysis to give MMA and a regenerated
Pd-hydride species (Scheme 1A). Likewise, methyl crotonate is formed via inser-
tion in the 1,2 regio-mode.
The other cycle starts from the other end of the MMA molecule by carbon
monoxide insertion in a Pd-methoxy species, followed by propyne insertion in
the 1,2 regio-mode in a Pd-carbomethoxy bond and subsequent termination by
protonolysis of the Pd-alkenyl bond to give MMA and a regenerated Pd-methoxy
species (Scheme 1B). In this cycle, methyl crotonate is formed by insertion in the
2,1 regio-mode.
There is no a priori argument to decide which cycle is actually responsible for
MMA formation, but it is important to note that the two cycles must enforce a
322 2.3 Reactions of Unsaturated Compounds

mutually reversed regio-mode of propyne insertion to form MMA. Therefore, the

effect of added steric congestion at the palladium center is expected to affect
regioselectivity in a different direction in the two possible cycles, and this gives
a clue to help determine which cycle is actually operating.
The experimental observations (Figure 2) thus strongly indicate that carbonyla-
tion of propyne with the present group of catalysts actually proceeds via the
Pd-methoxy cycle (B) in Scheme 1 [ll].
Although desirable, it is generally difficult to obtain direct experimental evi-
dence on the transition states and detailed pathways of individual elementary
steps in a catalytic cycle. It may then be useful to apply the technique of compu-
ter-assisted molecular modeling as the next-best alternative, to obtain relevant
information on proposed elementary reactions of a catalytic cycle (cf. Section
3.1.2). The results of molecular modeling studies, which we undertook to obtain
a more detailed, though qualitative, understanding of some elementary steps in the
above mentioned Pd-methoxy cycle for propyne carbonylation, are summarized
below.
The most probable mode of coordination of propyne to the electrophilic palla-
dium-carbomethoxy center, before the actual migratory insertion takes place, is
perpendicular to the square-plane of ligand coordination and cis with respect to
the carbomethoxy group. Molecular modeling suggests that the subsequent
migratory insertion step must involve a combined initial low barrier “slippage”
of the propyne molecule along a coordinate perpendicular to the coordination
plane, together with a rotation of the propyne molecule toward the coordination
plane and subsequent nucleophilic attack by the carbomethoxy moiety. A sche-
matic picture of the steric control of propyne insertion in this elementary step is
given in Scheme 2.
It can be seen that there is a clear steric disadvantage for an insertion pathway
leading to methyl crotonate relative to that leading to MMA.
Remarkably, the rate of propyne insertion via the MMA pathway in absolute
terms is not significantly affected by the presence of medium-sized substituents,
such as a methyl group (Figure 2) at the 6-position of the pyridyl group, whereas
the insertion rate to methyl crotonate is very seriously suppressed (e. g., by a factor
20, with a methyl group substituent).
The above-mentioned low-barrier slipping movement of the propyne molecule
on the pathway to MMA minimizes the steric hindrance between propyne’s
H-atom and (medium-sized) 6-pyridyl substituents on subsequent rotation and
nucleophilic attack (which is rate-determining; vide infra) by the carbomethoxy
group.
For the corresponding insertion pathway to methyl crotonate, however, the
same slipping of propyne must extend so far, to avoid the steric hindrance
between the 6-pyridyl substituent and propyne’s methyl group, that the weakly
bound propyne molecule will easily leave the palladium coordination sphere be-
fore rotatiodnucleophilic attack by the carbomethoxy group can occur. Phrased
differently, the transition state toward a rotation with the methyl group of
propyne pointing toward palladium is sterically strongly destabilized by the
presence of a substituent group at the 6-position of the pyridyl group.
 2.3.2.3 A Clean Route to Methacrylates via Carbonylation of Alkynes 323

w co
H&-CEC-H (1.2)

A 0

Scheme 1. The two possible cycles for the formation of methyl methacrylate.

STOP - methyl crotonate

Scheme 2

The Rate-Determining Step of the Catalytic Cycle

The data in Figure 1 show that introduction of a nitrogen atom in the ligand not
only has an effect on selectivity, but also on the carbonylation rate. For a high rate,
it is apparently also required that the nitrogen and phosphorus atoms of the ligand
should be positioned as in 2-PyPPh2. At the same time, sufficient “free” ligand
and acid are required for high rates. The first-order reaction rate in propyne,
324 2.3 Reactions of Unsaturated Compounds

which is observed under these conditions, indicates that propyne insertion in the
Pd-carbomethoxy bond is not only the selectivity-determining step as argued
above, but it determines the overall rate as well (making the likely assumption
that this step is irreversible).
This implies that the other elementary steps in cycle B (Scheme l), i.e., Pd-car-
bomethoxy formation and protonolysis of the palladium-alkenyl species, must
even be considerably faster than the observed overall high reaction rate. A high
rate of Pd-carbomethoxy formation (at equilibrium) could be expected for the
strongly electrophilic metal center. However, the latter step, protonolysis of the
Pd-alkenyl bond in 1-palladium-2-carbomethoxypropene and 2-palladium- 1-car-
bomethoxypropene, respectively, is expected to be a slow reaction, because the
proton has to overcome a relatively high barrier of (electrostatic) repulsion by
the cationic palladium center on its way to the palladium-carbon bond.
It is suggested that the applied excess of 2-pyridylphosphine ligand plays a
crucial role as a co-catalyst in the protonolysis step, by facilitating the transfer
of the proton to the palladium-alkenyl bond. In the absence of a (basic) nitrogen
atom or if the nitrogen atom is wrongly positioned in the ligand (Figure l),
protonolysis is slow and rate-determining. By using 2-PyPPh2 and analogous
ligands, however, rapid protonolysis is achieved.
At low acid concentrations, the carbonylation rate is also affected, pointing
again to protonolysis as rate-determining. But, once sufficient acid (acid/
Pd > 10) and phosphine (phosphine/Pd = 20), is present, a zero-order rate in
acid is found, irrespective of the acid/phosphine ratio. This indicates that protono-
lysis proceeds by a protonated phosphine and not by a “free” proton.
It is assumed that a ligand protonated at the pyridyl group (P-NH’), and mono-
coordinated via phosphorus to the palladium center, fulfills a key role as a “proton
messenger”, by bringing the proton into very close proximity with the coordina-
tion sphere at the palladium-alkenyl bond (Scheme 3).
Molecular modeling of the P-NH’ coordinated complex indeed suggests that the
proton can point into the n-electron cloud of the Pd-alkenyl moiety, bringing the
proton right to the spot for protonolysis of the palladium-alkenyl bond. This can
be seen as lowering the entropy barrier of activation in the protonolysis step. The

?!c - OCH3
H\ /
,c = c,
H CH3
 2.3.2.3 A Clean Route to Methacrylutes via Carbonylation of Alkynes 325

protonated ligand bound to the palladium center provides a way, according to

Scheme 3, to minimize the entropy loss in the transition state for protonolysis.
Under conditions of insufficient P-NH+, protonolysis becomes too slow and
therefore rate-determining. Such a situation can exist at low acid and/or low
free ligand concentration, but also in a basic solvent when the protons preferen-
tially reside on the basic solvent molecules. This explains why 2-pyridylphos-
phines with electron-withdrawing pyridyl substituents, (e. g., halides) in particular,
lead to low catalyst activities in solvents like NMP.
To be an effective proton messenger, several properties of the 2-pyridylphos-
phine moiety are thought to be essential. These are:

(1) The phosphine moiety is required to function as an anchor for efficient binding
of P-NH+ to the electrophilic palladium center.
(2) The basicity of the ligand should be within certain limits; too low a basicity
might lead to insufficient protonation, whereas too high basicity might hamper
transfer of the proton from the ligand.
(3) The distance between the phosphorus and protonated nitrogen atom should not
be too large, as is the case with ligands containing a 3-pyridyl or 4-pyridyl
group (see Figure 1).
(4)Binding of the (monocoordinated) ligand at palladium should be such that
reactant molecules, e. g., carbon monoxide and propyne, can rapidly displace
the (protonated) ligand, and vice versa.

co

P-NH+

Scheme 4. Proposed catalytic cycle for carbonylation of propyne with cationic

palladiud2-pyridylphosphine systems.
326 2.3 Reactions of Unsaturated Compounds

Obviously, ligands containing the 2-pyridylphosphine moiety combine all the

necessary properties to function not only as a selectivity-determining bidentate
ligand, but also as an ideal proton transfer catalyst. This leads to the proposed
catalytic Pd-methoxy cycle for carbonylation of propyne by cationic palladium/
2-pyridylphosphine catalyst systems as shown in Scheme 4.

2.3.2.3.4 Scope of the New Catalyst System

Very similar results to those described with propyne can be obtained with a wide
variety of other alkynes, e. g., acetylene, higher aliphatic and aromatic alkynes as
well as other nucleophilic reagents, such as water, aliphatic (primary, secondary,
and tertiary) and aromatic alcohols, thiols, and amines.
This class of catalysts thus gives easy access to a variety of unsaturated car-
boxylic acids, (thio)esters and amides. The general catalyzed reaction can thus
be represented by eq. (4).
R
I
H- CrC- R + CO + HNu H~C=C-CONU (4)

In addition to simple aliphatic or aromatic alkynes (R = alkyl, aryl), the R group

may contain a wide variety of heteroatom functionalities, including HNu (Nu =
nucleophile). This latter instance opens the possibility of intramolecular or inter-
molecular carbonylation to generate either unsaturated cyclic structures or linear
polymeric structures, respectively, depending on the distance between alkyne
and HNu functionality. An interesting further application comprises the use of
ene-yne substrates, in which R contains an alkene functionality, nonconjugated
or conjugated with the alkyne functionality. The catalysts allow the selective
carbonylation of the alkyne moiety without interfering with the alkene function-
ality. Thus, it is possible to convert but-1-en-3-yne in high selectivity to 3-carbo-
methoxybuta- 1,3-diene.

2.3.2.3.5 Conclusions
A new class of cationic palladium catalysts for the carbonylation of alkynes is
described which, under mild conditions, shows unprecedented high activity and
selectivity for the carbonylation of (higher) alkynes. As a particularly interesting
application, the catalysts allow the development of a commercially attractive and
environmentally friendly process for the carbonylation of propyne to methyl
methacrylate.
This catalysis nicely displays the way in which the electronic and steric prop-
erties of the organometallic catalytic complexes contain the three-dimensional
prescription code for the precise assembly of product molecules from substrate
molecules. The results are another demonstration of the importance of ligand
choice in homogeneous catalysis. In this particular instance, the choice of neutral
 References 327

ligands containing a 2-pyridylphosphine moiety, combined with weakly coordi-

nating anions as the anionic ligands around cationic palladium(II), has been par-
ticularly fortunate.
The enzyme-like activity and precision of the catalysis displayed by the palla-
dium complex systems described are attributed to the unique ability of the 2-pyr-
idylphosphine ligands to function as a bidentate P-N ligand, playing a crucial role
in the selectivity-determining step involving the migratory insertion of the alkyne,
and to function as a monocoordinated protonated ligand, bringing a proton in very
close proximity to the palladium coordination sphere, thus facilitating proton
transfer as a co-catalyst in the protonolysis step of the catalytic cycle.
These results are indeed reminiscent of enzyme-catalyzed reactions where basic
organic groups, being part of the enzyme, assist in proton delivery, e. g., in hydro-
lysis reactions.
The proposed mechanism makes most of the catalytic phenomena plausible, but
it is also clear that a direct observation of elementary steps of the catalytic cycle
would be highly desirable to obtain a full insight into factors that control these
highly selective and fast reactions. A detailed understanding of underlying phe-
nomena can be instrumental in designing, rather than finding by trial and error,
efficient homogeneous catalysts for other chemical transformations also.
The process is now ready for licensing.

References
[ l ] (a) ECN 2001, 8-14 Jan., 18; (b) K. Weissermel, H.-J. Arpe, Industrial Organic Chem-
istry, 2nd ed., VCH, Weinheim, 1993, Chapter 17.
[ 2 ] W. Reppe, Liebigs Ann. Chem. 1953, 582, 1.
[3] For an extensive earlier review on alkyne carbonylation until 1980, see: A. Mullen, in
New Syntheses with Carbon Monoxide (Ed.: J. Falbe), Springer, Berlin, 1980, Chapter 3.
[4] (a) J. Happel, S. Umemura, Y. Sakakibara, J. H. Blanck, S. Kunichika, Znd. Eng. Chem.,
Proc. Design Dev. 1975, 14, 44; (b) I. A. Orlova, N. F. Alekseeva, A. D. Troitskaya,
0. N. Temkin, Zh. Obshch. Khirn. 1979, 49, 1601.
[ 5 ] (a) I. Amer, H. Alper, J. Organomet. Chem. 1990, 383, 573; (b) B. E. Ali, H. Alper,
J. Mol. Cutul. 1991, 67, 29; (c) A. Scrivanti, R. Chinellato, U. Matteoli, J. Mol.
Catal. 1993, 84, L141; (d) Y. Kushino, K. Itoh, M. Miura, M. Nomura, J. Mol. Catal.
1994, 89, 151.
[6] (a) Shell Research BV (E. Drent), EP 271.145 A2, 1988; Chem. Abstl: 1989, 110, 38623;
(b) Shell Research BV (E. Drent, P. H. M. Budzelaar, W. W. Jager), EP 386.833 A l ,
1990; Chem. Abstr: 1991,114, 142679; (c) Shell Research BV (E. Drent, P. H. M. Bud-
zelaar), EP 386.834 A l , 1990; Chem. Abstl: 1991, 114, 142680; (d) Shell Research BV
(E. Drent, P. H. M. Budzelaar, W. W. Jager, J. Stapersma), EP441.447 A l , 1991; Chem.
Abstl: 1992, 116, 129842.
[7] (a) Shell Research BV (M. J. Doyle, J. Van Gogh, J. C. Van Ravenswaay Claasen),
EP 392.601, 1990; Chern. Abstl: 1991, 114, 102997; US 5.081.286 (1992); (b) R. H.
Schwaar, Methacrylic Acid and Esters, Report No. 11D, SRI International, 1994.
(81 E. Drent, P. Arnoldy, P. H. M. Budzelaar, J. Organomet. Chem. 1994, 475, 57.
191 (a) E. Drent, Pure Appl. Chem. 1990, 62, 661; (b) E. Drent, J. A. M. Van Broekhoven,
M. J. Doyle, J. Organomet. Chem. 1991, 417, 235.
328 2.3 Reactions of Unsaturated Compounds

[lo] See: (a) J. P. Farr, M. M. Olmstead, A. L. Balch, Znorg. Chem., 1983, 22, 1229; (b) V. M.
Jain, V. S. Jakkal, R. Bohra, J. Organomet. Chem. 1990,389,417; (c) T. Suzuki, M. Kita,
K. Kashiwabara, J. Fujita, Bull. Chem. SOC. Jpn. 1990,63,3434; (d) Y. Xie, B. R. James,
J. Organomet. Chem. 1991, 41 7, 277.
[ 111 There is a possibility that, whereas MMA would be produced via exclusive 1,2 insertion
in Pdxarbomethoxy species (cycle B), the small quantity of methyl crotonate formed
could arise from propyne 1,2 insertion also, but in Pd-hydride species (cycle A), possibly
concurrently being present in minor quantities. However, we consider the observed
subtle, but precise, correlation of the MMA sclectivity with the size of substituents at
the 6-position of the pyridyl group (H < F < C1 < Br, CH3) together with the absence
of any effect of substituents at the 4-position of the pyridyl group, as strong indications
against this possibility. In our opinion, there is no conceivable good reason why the
amount and/or the efficiency in catalysis of Pd-hydride species (possibly generated via
water-gas shift) should correlate with the observed ligand dependence. Although, we
cannot exclude the presence of Pd-hydride species, it is highly unlikely that these are
playing a measurable role in the underlying carbonylation catalysis and we conclude
that carbonylation of propyne with the present catalysts proceeds exclusively via the
Pd-methoxy catalytic cycle (B).

2.3.3 Metathesis
Johannes C. Mol

2.3.3.1 Introduction
Olefin metathesis is a catalytic reaction in which alkenes are converted into
new products via the rupture and reformation of carbon-carbon double bonds.
A simple example is the metathesis of propene into ethylene and 2-butene (cis
and trans); eq. (1).
2 f i ==== H1C=CH2 + H3C&CH3 (1)

The reacting alkenes need not be identical: when two different alkene mole-
cules react which each other, e. g., in the reverse of the above reaction, the term
cross-metathesis is used.
The catalytic metathesis of olefins was first reported in the open literature by
Banks and Bailey [ 11. They observed that in the presence of a supported molybde-
num catalyst linear olefins are transformed into homologs of shorter and longer car-
bon chain, and called their reaction olefin disproportionation. A few years later
Calderon et al. [2] found that the same reaction, viz. the selective disproportiona-
tion of 2-pentene into 2-butene and 3-hexene, could be performed homogeneously
using the catalyst system WCl&tAlCl,/EtOH (1 :4 : 1). This demonstrated that
olefin disproportionation can take place in the presence of heterogeneous as well
as homogeneous catalysts. Subsequent studies using labeled olefins as substrate
showed that product formation results from the breakage of double bonds, rather
than from alkyl group transfer, leading to an exchange of alkylidene moieties [2,3].
 2.3.3.2 Scope of the Reaction 329

In the course of time it appeared that many olefinic substrates could undergo
this reaction in the presence of a transition metal compound, such as substituted
alkenes, dienes, polyenes, and cyclic alkenes, and even alkynes. Calderon et al.
were the first to realize that the ring-opening polymerization of cycloalkenes,
which they observed with their tungsten-based catalyst system [4], and the
disproportionation of acyclic olefins are, in fact, the same type of reaction.
They introduced the more general name metathesis [2]. The metathesis reaction
has now become a common tool for the conversion of unsaturated compounds.
In view of the limited space this intriguing reaction is reviewed only briefly;
more information can be found in a detailed and extensive monograph [5].

2.3.3.2 Scope of the Reaction

2.3.3.2.1 Acyclic Alkenes

Both terminal and internal alkenes can undergo metathesis. As the metathesis
reaction of acyclic olefins is essentially thermoneutral, a statistical distribution
of reactants and products eventually results. In the metathesis of a symmetrical
olefin, the product molecule is the geometrical isomer of the reactant. Thus, for
example, starting with either cis- or trans-2-butene, a thermodynamic equilibrium
mixture of cis- and trans-2-butenes is obtained. Metathetical cis-trans isomeriza-
tion (i.e., “isomerization” via an exchange of alkylidene fragments, and not an
isomerization via a rearrangement of atoms within a single molecule) also accom-
panies productive metathesis of internal olefins, such as 2-pentene. Metathesis of
a-olefins yields ethylene and a symmetrical internal olefin. In these cases the
reaction can generally be driven to completion by removal of the volatile co-
product ethylene. The reverse reaction, cross-methathesis with ethylene, called
ethenolysis, makes it possible to prepare linear a-olefins from internal olefins.
The metathesis of acyclic alkadienes and polyenes may follow an inter- or
intramolecular pathway. The intramolecular metathesis of an a,w-diene yields
ethylene and a cyclic alkene, while the intermolecular reaction results primar-
ily in the formation of ethylene and a symmetric triene (eq. (2)). The loss of
a small molecule like ethylene serves to drive the equilibrium to the product
side,
, intermolecular metathesis ~

Whether the inter- or intramolecular pathway dominates depends on the relative

stability of the cyclic vs. the linear products and to some extent on the dilution of
330 2.3 Reactions of Unsaturated Compounds

the reaction mixture. For instance, intramolecular ring-closing metathesis (RCM)

takes place if one of the possible products is cyclohexene, e. g., metathesis of 1,7-
octadiene will give cyclohexene and ethylene.
The intermolecular metathesis of acyclic dienes has led to interesting appli-
cations in the field of polymer chemistry. As will be clear, the triene produced
in eq. (2) can react further via intermolecular metathesis reactions with the starting
diene to form a tetraene, a pentaene, etc. In this manner, when the appropriate
catalyst system is chosen, high-molecular-weight unsaturated polymers can
be formed. This step-growth condensation polymerization in which ethylene
is evolved is known as ADMET (Acyclic Diene METathesis) polymerization
[6] (eq. (3)). Hetero-atom-containing dienes with the general structure
CH2=CH-(CH2),-X-(CH2),-CH=CH=CH2 (X=O, C(O)O, SiMe2) are also interesting
monomers for ADMET.

Polymers with carbon-carbon double bonds in their backbone can undergo two
types of metathesis, both leading to degradation. In an intramolecular reaction
cyclic oligomers are formed, while many unsaturated polymers can be degraded
by intermolecular cross-metathesis with low-molecular-weight olefins. Identifica-
tion of the degradation products provides valuable information on the microstruc-
ture of the polymer [7] (cf. Section 3.3.10.1).

2.3.3.2.2 Cyclic Alkenes

The metathesis of monocyclic and polycyclic alkenes yields unsaturated poly-
mers, the so-called polyalkenamers, eq. (4), via a chain growth process. This
Ring-Opening Metathesis Polymerization is usually abbreviated to ROMP, and
is driven by the release of ring strain in the starting cycloalkene. If the cyclic
olefin is highly strained (e. g., norbornene), then the reaction is essentially
irreversible. Compared with other types of polymerization, ROMP has the re-
markable feature that all the carbon-carbon double bonds of the monomer are
retained in the polymer. Furthermore, the reaction may be modified to proceed
in a stereospecific way, i.e., the double bonds of the resulting polymer can be
essentially of the cis or the trans type, depending on the catalyst system and
the reaction conditions. Initiation by metal carbene complexes is sometimes
sufficiently fast relative to propagation to yield “living” polymers with a
narrow molecular weight distribution (polydispersity close to 1) and a linear
relation between conversion and molar mass [8]. Many interesting polymeric
materials can be synthesized via the ROMP of different types of unsaturated cyc-
lic monomers, such as cyclic monoenes, dienes, and polyenes, bicyclic and poly-
cyclic alkenes, and certain substituted monomers [ 5 , 9, 80, 811 (cf. Section
3.3.10.1). One interesting development is the synthesis of conducting polymers
of the polyacetylene type (eq. ( 5 ) ) [lo]; this can also be achieved by ROMP
 2.3.3.2 Scope of the Reaction 331

of cyclooctatetraene and its derivatives [ll], or via ROMP of benzvalene [12].

These routes form alternatives to the direct metathesis polymerization of acety-
lenes (see Section 2.3.3.2.5).
n

2.3.3.2.3 Cross-Metathesis Between a Cyclic

and an Acyclic Alkene
The cross-metathesis between an acyclic and a cyclic alkene, nowadays called
ring-opening metathesis (ROM), provides a convenient route to certain poly-
unsaturated compounds. For example, ethenolysis of cycloalkenes yields a,w-
dienes (eq. (6)), which may be useful, e.g., as crosslinking agents in polymers
and as precursors for a,w-difunctional compounds [ 131.

When during ROMP a small amount of an acyclic olefin is added, it acts as a

chain-transfer agent, i.e., it imparts control of the chain length, depending on the
ratio of the acyclic and cyclic alkenes.

2.3.3.2.4 Functionally Substituted Olefins

A promising synthetic application for the metathesis reaction concerns unsaturated
compounds containing heteroatom functional groups. Metathesis of functionalized
acyclic olefins would allow single-step syntheses of various mono- and difunc-
tional derivatives of hydrocarbons with well-defined structures (eq. (7)); X = func-
tional group.
332 2.3 Reactions of Unsaturated Compounds

Despite the fact that polar entities are catalyst poisons, a variety of acyclic
olefins containing a heteroatom functional group can undergo metathesis in the
presence of a suitable catalyst, although at a high catalyst level. These include
unsaturated esters, ethers, ketones, amines, nitriles, halogens, etc. [ 141. In particu-
lar metathesis reactions - including ethenolysis - of unsaturated fatty esters and
fatty oils are of interest, as they have perspectives for the oleochemical industry
~151.
The ring-closing metathesis of functionalized linear dienes, diene-ethers, diene-
amines, etc., leads to a variety of cyclic alkenes and heterocycles [16] (eq. (8)).

Since the recent discovery of new, well-defined transition metal carbene

catalysts with a high tolerance to functional groups (such as the very effective
Mo and Ru carbene complexes; see Section 2.3.3.4), tremendous progress has
been made in the area of organic synthesis via RCM [17-241. Unprecedented
RCM reactions to give synthetic routes to extremely large rings have been realized
with new Ru catalysts and, moreover, can be achieved with a high degree of
stereoselectivity.
In recent years the metathesis of cyclic alkenes containing a functional group
has also attracted a great deal of attention because of the availability of new
catalysts that are more tolerant of functional groups, and the various functionally
substituted polymers which could be produced.

2.3.3.2.5 Alkynes
The olefin metathesis reaction is also suitable for alkynes. In the presence of a
metathesis catalyst alkynes can undergo one of the three following reactions:
(1) cyclo-trimerization (e. g., trimerization of propyne into 1,3,5- and 1,2,4-
trimethylbenzene); (2) polymerization, e. g., of phenylalkynes (eq. (9)); and (3)
metathesis (rupture and reformation of carbon-carbon triple bonds), e. g., eq. (10).

In general, metathesis occurs only with disubstituted alkynes. Monosubstituted

alkynes do not undergo metathesis; instead they form cyclic products or polymer-
ize. In the latter reaction two out of three bonds are broken and a new double bond
 2.3.3.3 Reaction Mechanism and Catalysts in General 333

is formed between adjacent monomer units. Polymerization of acetylene and sub-

stituted acetylenes gives polyenes having a conjugated backbone. These have at-
tracted much attention in view of their potential utility as conductive materials,
membranes for selective gas permeation and side-chain liquid-crystalline poly-
mers. Here also, living polymerization can be achieved [5, 811.
Diynes, such as dipropargyl derivatives, are amenable to cyclopolymerization
giving high-molecular-weight polymers; (eq. (1 l), where X = 0, S, R,Si,
C(CO,Et),, etc). In the presence of an olefin metathesis catalyst, acetylenes
copolymerize with each other and with cyclic alkenes.

2.3.3.3 Reaction Mechanism and Catalysts in General

The understanding of the reaction mechanism is directly related to the role of the
catalyst, i.e., the transition metal. It is universally accepted that olefin metathesis
proceeds via the so-called metal carbene chain mechanism, first proposed by
HCrisson and Chauvin in 1971 [25]. The propagation reaction involves a transition
metal carbene as the active species with a vacant coordination site at the transition
metal. The olefin coordinates at this vacant site and subsequently a metalla-
cyclobutane intermediate is formed. The metallacycle is unstable and cleaves in
the opposite fashion to afford a new metal carbene complex and a new olefin.
If this process is repeated often enough, eventually an equilibrium mixture of
alkenes will be obtained.

M=CHR
+
R'HC =CHR
- R'HCM-CHR
I I
-CHR
- M
II
R'HC
+ II
CHR
CHR

M CHR M-CHR M=CHR

II+II ===== I I ===== +
Scheme 1 RHC CHR' R'HC -CHR' R'HC ==CHR'

For cyclic alkenes this mechanism results in unsaturated polymer chains

(eq. (12)).
n
M =CHR
+
HC=CH
- HC
11 11
CH
-
CHR HC=CH
M
(12)
U i/
334 2.3 Reactions of Unsaturated Compounds

In the ROMP of cycloalkenes the product generally consists, however, of

two distinct parts : a high-molecular-weight fraction, often having a molecular
weight >lo’, and a low-molecular-weight fraction consisting of a series of
cyclic oligomers. The simultaneous production of high polymer and cyclic oli-
gomers is readily explained in terms of competition between a propagation
reaction (eq. (12)) and an intramolecular reaction in which a double bond in
the polymer chain comes close enough to the metal center to undergo a back-
biting reaction.
Metal carbenes are also initiators for the metathetical polymerization of alkynes
by, e.g., catalysts such as MoC15 and WC16. Reaction of the metal carbene with
an alkyne gives a metallacyclobutene intermediate, followed by opening of this
intermediate metallacycle into a new metal carbene that in its turn can interact
with another alkyne molecule, and so on eq. (13). Metathesis of acetylenes
proceeds through reactions between an alkylidyne complex and an alkyne via a
metallacyclobutadiene intermediate (eq. (14)).

I
J

An obvious question for the olefin metathesis reaction is how the initiating
metal carbene is formed. In the case of the catalystko-catalyst combination of a
transition metal compound and an organometallic co-catalyst, e. g., the combina-
tion WCl,/Me,Sn (cf. Section 2.3.3.4), a transition metal alkyl species could be
readily formed by alkylation of the transition metal. a-Hydrogen abstraction
from the methyltungsten species would give the metal carbene species (eq.
(15)). Methane evolution is indeed observed when the catalyst components are
brought together. The presence of an 0x0 ligand is favorable for tungsten catalysts
and may be generated by the addition of an alcohol, traces of oxygen, etc., or by
the use of W0Cl4 instead of WC16 (eq. (16)). A “spectator” 0x0 group increases
significantly the driving force for formation of the metallacyclic intermediate.
Other routes to the initial metal carbene have also been conceived [5]. When
using metal carbene complexes as catalysts, a metal carbene forming step is, of
course, not necessary. In fact, the demonstration that discrete metal carbene
complexes could serve as highly active catalysts for olehn metathesis supported
the proposal of HCrisson and Chauvin that the reaction proceeds via metal carbene
intermediates.
 2.3.3.4 Homogeneous Catalyst Systems 335

WC16 + 2 Me4Sn
- 2 Me3SnCI
* C14W
,CH3

\
CH3
- C14W=CH2 + CH4 (15)

In any chain reaction, apart from initiation steps, the termination steps are also
important. In metathesis there are many possibilities for termination reactions.
Besides the reverse of the initiation step, the reaction between two carbene species
is also a possibility (eq. (17)). The observation that, when using the Me4Sn/WCI6
system, as well as methane traces of ethylene are also observed [26] is in agree-
ment with this reaction. Further reactions which lead to loss of catalytic activity
are (1) the destruction of the metallacyclobutane intermediate resulting in the
formation of cyclopropanes or alkenes, and (2) the reaction of the metallacycle
or metal carbene with impurities in the system or with the functional group in
the case of a functionally substituted alkene (e. g., Wittig-type reactions of the
metal carbene with carbonyl groups).
2 M=CH? T=== 2 M + HpC=CHp (17)

2.3.3.4 Homogeneous Catalyst Systems

Considering the extensive possibilities offered by the metathesis of unsaturated
hydrocarbons within chemical synthesis, it is not surprising that so much research
takes place into the development of active and selective catalysts. The metathesis
reaction can be catalyzed by both heterogeneous and homogeneous catalysts.
A wide range of transition metal compounds will catalyze the reaction, the most
important ones being based on tungsten, molybdenum, ruthenium, and rhenium,
while others, e. g., catalysts based on osmium, iridium, tantalum, and titanium,
may also be used. These include catalysts containing the transition metal in
high as well as low oxidation states. Heterogeneous catalysts generally consist
of a transition metal oxide or an organometallic precursor deposited on a high-
surface-area support. Homogeneous catalysts mainly consist of ( 1) a combination
of a transition metal halide or 0x0-halide with an alkylating co-catalyst, and
sometimes a third compound (promoter), or (2) a well-characterized carbene
(alkylidene) complex of a transition metal. Moreover, active metathesis catalysts
can also be generated by photolysis of Mo(CO)~and W(CO)6 in a halogenated
solvent (CC14). Homogeneous catalysts have generated the most interest for the
metathesis polymerization of cyclic alkenes, acyclic dienes, and alkynes as well
as for small-scale chemical syntheses.
336 2.3 Reactions of Unsaturated Compounds

Table 1 gives some representative examples of the first category of homoge-

neous catalysts - the so-called classical catalysts - with the metathesis of 2-pen-
tene as test reaction. More examples can be found elsewhere [5].
Calderon's catalyst combination WCl&tAlCl,/EtOH is already very active at
room temperature for the metathesis of 2-pentene into 2-butene and 3-hexene,
resulting in a thermodynamic equilibrium conversion of 50 % (25 % of each
product alkene) within a few minutes at a molar ratio of alkene to tungsten of
104:1, with a selectivity of 99.6%. A few of these catalyst systems, such as
WCl&le4Sn, WOC14/Me4Sn,WCl,#h2SiH2, and WC14(0C6H3-Br2-2,6)/u4Pb,
bring about the metathesis of acyclic functionalized olefins. In that case, however,
they are several orders of magnitude less active than for normal olefins. These
catalysts are in practice only attractive for ROMP of unfunctionalized monomers
(see Section 2.3.3.5).
In view of the fact that the propagation center in metathesis closely resembles
metal carbene complexes, it is not surprising that preformed carbene complexes
show catalytic activity for metathesis. Table 2 gives examples of carbene com-
plexes that are effective as metathesis catalyst.
Well-defined, relatively stable, Lewis acid-free catalysts, such as
Mt(=CHCHMe3)(=NC6H3-i-Pr2)[OCMe(CF3)2]2 (Mt = Mo, W), can provide
living polymers with very narrow molecular weight distributions. Certain carbene
complexes are active catalysts for the metathesis of internal alkynes [59]. W and

Table 1. Some examples of classical catalyst systems for the homogeneous metathesis of
2-pentene.
Catalyst system T["C] Ref. Catalyst system T["C] Ref.
Tungsten-based catalysts Molybdenum-based catalysts
WCl&tAIClJEtOH 20 [2] MoCl,/Ph,Sn 20 [34]
WCldBuLi 20 [27] MOC13(NO)/EtAICl~ 20 [35]
WCl&'hzSiHz 20 [28] MoC13(0PPh3)2N/EtAIClz 20 [36]
WCIJMe,Sn 20 [29] MoCIZ(NO)~(CSH~N)~/ 0 [371
WCI,(OC6H3-BrZ-2,6)/ 85 [30] EtAICI,
BuPb4 MoC13(NO)(OPPh3)2/ 20 [38]
WC12(CO)3(PPh3)2/ZTC& 20 [3 11 EtAICI,
Mo(N0)2(02CPh)JEtAlCI2 20 [39]
[Mo(NO)~(OM~),(E~OH)~,/
25 [401
EtAlClZ
Rhenium-based catalysts
ReClS/Bu4Sn 20 [32]
ReOCI3(PPh3)/EtA1Cl2 20 [33]
 2.3.3.4 Homogeneous Catalyst Systems 337

Ar = C6H3Ph2-2,6

1 2

Table 2. Examples of metal carbene complexes as initiators of olefin metathesis.

Complex Substrate Ref.
W(=CHCMe3)Rr2(OCH2CMe3),/GaBr, 2-Pentene [41]
Norbornene [42]
W(=CHCMe3)(=NC6H3-i-Pr2-2,6)(OR)2 2-Pentene [43]
[OR = OC6H3-i-Pr2-2,6,OCMe2CF3,OCMe(CF,),]
W(=CHCMe3)(CH2CMe3)C1(OC6H3Ph2-2,6)2(OEt2) 2-Pentene [44]
1 I
W(=CHCMe3)TOC6H3-Ph(2-C~H~)-2,6]C1(OC6H~Ph*-2,6)OEt*
(1) 2-Pentene [45]
MO(=CHCM~~)(=NCM~~)[OCH(CF~)~I~ 2-Pentene [461
Mo(=CHCM~~R)(=NC,H&-P~~-~,~)(OCM~~)~ Norbomadiene [47,48]
[R = Me, Ph] derivatives
M O ( = C H C M ~ ~ ) ( = N C ~ H ~ - ~ - P ~ ~ - ~ , ~ ) I O C M ~ (2-Pentene
CF~)~~~
Mo(=CHCMe,Ph)(=NAr)(OR)* 2-Pentene
[Ar = C6H3Me2-2,6,C6H3-i-Pr2-2,6,C6H4-i-Pr-2, 1-Hexene
C6Hd-t-Bu-2, c6HdCF3-2; R = CMe3, CMe2CF3,
; 2
CMe(CF3I2,C(CF313,C ( C S F ~ Ie.g.,
Ta(=CHCMe3)(0C6H3-i-Pr2-2,6),(THF) 2-Pentene
Norbomene
Re(=CHCMe3)(ECCMe3)[OCMe(CF3)2]2 2-Pentene
Re(=CHCH=CPh2)(0)[OCMe(CF3)2]3(THF)/GaBr3 2-Pentene
Ru(=CHCH=CPh2)Cl*(PPh3)2 Norbornene
Ru(=CHCH=CPh2)C12(PR3)2 2-Pentene
[R = Cy, i-Pr]
Ru(=CHPh)C12(PR3)2 Norbomene
[R = Ph, Cy]
338 2.3 Reactions of Unsaturated Compounds

Mo catalysts like 1 and 2 are also active in the metathesis of functionalized

alkenes, such as unsaturated carboxylic esters.
Much progress has been made in the development of very effective Mo and
Ru carbene complex catalysts, some of which are now commercially available.
For a summary of new well-defined Mo-alkylidene complexes, see f601. In
recent years Ru-carbene complexes have attracted much attention. One of the
first very active Ru-carbene catalysts was the benzylidene ruthenium complex
Ru (=CHPh)C12 (PCy,),, the so-called Grubbs catalyst. Although complex 2 is
more reactive toward a broad range of substrates than the Grubbs catalyst, it suf-
fers from high sensitivity to air and moisture. Next, a wide variety of ligands
have been used for the preparation of derivatives of the Grubbs catalyst, including
dinuclear complexes (see for example [61-671). Thus, replacing at least one of
the phosphine ligands with a more electron-donating N-heterocyclic carbene
ligand (e. g., 3-5) produces a more versatile metathesis catalyst.
-

n
Y pM‘:es
CI /Q

‘Tc>Ph C y - N dI
N
R = i-Pr. Cy. -CH(CH,)Ar Mes = Mesityl

3 4 5

Much work is still in progress to improve the Ru-carbene complexes. Consid-

erable attention has recently also been directed at efforts to immobilize a Ru-based
metathesis catalyst on solid supports, which could make the metathesis reaction
even more attractive for industrial applications.
In addition to those listed in Tables 1 and 2, many more active catalyst systems
have been reported, including W-carbyne complexes [68], and metallacycles such
as Ti or Ta cyclobutanes [8, 691, which are initiators for ROMP. The ROMP
of functionalized monomers such as 7-oxanorbomene derivatives can also be
performed successfully using certain Ru initiators, affording polymers with a
high molecular weight (eq. (18)) [70]. Moreover, in water alone, polymerization
proceeds very rapidly in nearly quantitative yields in the presence of Ru catalysts
under an atmosphere of air [71] (cf. Section 3.3.10.1).
 2.3.3.5 Industrial Applications 339

2.3.3.5 Industrial Applications

Several possible commercial applications involving heterogeneous catalysts have
been developed on a pilot-plant scale and some of them are, or have been,
operating in industrial practice to produce particular acyclic olefins. An example
is the production of neohexene via ethenolysis of diisobutene [72].A large-
scale industrial process incorporating olefin metathesis is the Shell Higher
Olefins Process (SHOP) in which ethylene is converted to detergent-range
alkenes (cf. Section 2.3.1.3).The reaction mixture is passed, inter alia, over
a solid metathesis catalyst which results in a statistical distribution of linear in-
ternal alkenes with both odd and even numbers of carbon atoms. The desired
detergent-range internal alkenes (C, ,-C14) (10-15 % per pass) are subsequently
separated via normal distillation; the remaining lower and higher alkenes are
recycled [73].
In the polymer field ROMP is an attractive process for making polyalkenamers
when based on cheap monomers or possessing special properties compensating
for a high price. Several industrial processes involving homogeneously catalyzed
ROMP have been developed and brought into practice.
The first commercial metathesis polymer was polynorbornene, which was put
on the market in 1976 by CdF-Chimie under the trade name @Norsorex.The poly-
mer is obtained by ROMP of norbornene (bicyclo[2.2.l]heptene-2)(eq. (19)) and
gives a 90 % trans polymer with a very high molecular weight (>3 X lo6 g/mol)
and a glass transition temperature (T,) of 37 "C.

The process uses a RuC1, catalyst in butanol, operates in air and produces a use-
ful elastomer, to be used, for instance, for oil spill recovery, as a sound barrier, or
for damping. 8Norsorex is produced by Elf Atochem in Carling (France) in a plant
with a capacity of 5000 t/a [74].
Since 1991, Nippon Zeon Co. has been producing the polymer @Zeonex,ob-
tained by ROMP of norbornene and related (multi-ring) monomers, followed
by hydrogenation. The product is an amorphous, colorless, transparent polymer
with a high T, (140"C) and low moisture absorption. These properties make it
very suitable for optical applications (e. g., disks, lenses, and prisms).
Since 1980, Degussa-Hiils A G has been producing 8Vestenamer 8012, the
metathetical polymer of cyclooctene. This polymer also goes under the name
TOR (truns-polyoctenamer). The polymerization is performed in hexane as
solvent in the presence of a WCl,-based catalyst, giving almost 100% yield.
The polymer contains both linear and cyclic (> 25 wt. %) macromolecules and
has a purity of 99.5 %. The cisltruns ratio, which determines the degree of crystal-
linity, is controlled by the polymerization conditions. The trans double bond con-
tent of 'Vestenamer 8012 is 80 %, the crystallinity 30 %, and the molecular weight
75 000. Used as a blending material, 'Vestenamer 8012 offers possibilities for the
340 2.3 Reactions of Unsaturated Compounds

improvement of the properties of other rubber compounds and for use in rubber-
ized asphalt. An additional type, 8Vestenamer 6213 (molecular weight 95 000),
with a lower trans content (60 %) and therefore lower crystallinity (10 %), has
been developed to provide for low-temperature applications where the admixture
of the standard type would lead to excessive stiffening [75-771.
Bayer has developed a process for the ROMP of cyclopentene, giving an all-
purpose elastomer, on pilot-plant scale. Raw materials were cheap and the product
had properties akin to those of natural rubber. Therefore, it was evaluated for the
fabrication of tires. However, because of technical difficulties (the properties of
the tires were less satisfactory under driving conditions) this process has never
been put into operation.
Much interest has been shown in the ROMP of endo-dicyclopentadiene
(DCPD), obtained as a by-product from naphtha crackers. If only the highly
strained norbornene ring opened, a linear polymer should be formed (eq. (20)).

However, under certain conditions the double bond in the disubstituted

cyclopentene ring may also undergo metathesis, thereby giving rise to cross-
linking (eq. (21)).

The product is a tough, rigid, thermoset polymer of excellent impact strength.

Quite large objects can be produced via a reaction injection molding (RIM) pro-
cess. The commercial production of molded objects from DCPD-based feed using
 2.3.3.6 Conclusions 341

RIM technology has been developed mainly by the BFGoodrich Co., under the
trade name @Telene,and by Hercules Inc., under the trade name @Metton.The
latter is now produced by Metton America, Inc. in Houston, USA, who have
also licensed their process to the Teijin-Metton Co. in Japan.
In the RIM technique, two monomer streams are used. In the Metton liquid
molding resin (LMR) system developed by Hercules, one stream contains
DCPD monomer, catalyst (WC1, + W0Cl4), nonylphenol (to solubilize the tung-
sten compounds in the monomer), additives (such as antioxidants), and fillers. The
other stream contains DCPD monomer, co-catalyst (EtAlCl,), retarder, additives,
and fillers. The two streams pass first into a mixing chamber and then into the
mold, where an exothermic polymerization takes place at a high rate after
a short induction period. The solutions of the individual catalyst components
in the monomer are stable, and the length of the induction period can be con-
trolled [9].
In the @Telene process the procatalyst is a tetrakis(tridodecy1ammonium)-
octamolybdate, activated with a mixture of Et2A1C1, propanol and SiC14. Up to
10 96 trimer of cyclopentadiene is added to the monomer to increase crosslinking
in the polymer, while the trimer also lowers the melting point of DCPD. The T, of
the product is typically 150°C. BFGoodrich has licenced their process to the
8
er
Japanese company Nip on Zeon Co., which produces it under the trade name
Pentem. In the USA elene RIM polymers are presently produced by APT,
LLC, a joint venture of BFGoodrich and Advanced Polymer Technologies, LLC,
recently renamed Cymetech, LLC.
Shell has developed a catalyst system for the RIM polymerization of DCPD
which is the reaction product of 2 mol of 2,6-diisopropylphenol and 1 mol of
WC1,; the co-catalyst is a trialkyltin hydride. Both components are soluble in
DCPD and inherently storage-stable. In addition, this catalyst system has the
advantage of being able to polymerize DCPD of technical quality. In a very
fast exothermic reaction a complete conversion of the DCPD monomer takes
place into the crosslinked polymer [78].
Poly(DCPD) has won several marine, recreational vehicle, and off-road utility
vehicle applications around the world [79].

2.3.3.6 Conclusions
In the field of homogeneous catalysis the metathesis of unsaturated hydrocarbons
offers many intriguing possibilities for producing important intermediates and end
products from alkenes and alkynes. Through major advances in catalyst design in
recent years, metathesis has become an important synthetic route to be considered
in chemical laboratories whenever a special organic product has to be obtained. In
fine chemistry metathesis is a very valuable reaction for the synthesis of natural
compounds. Metathetical polymerization has been accepted by the industry as a
viable means for producing polymers.
342 2.3 Reactions of Unsaturated Compounds

References
[I] R. L. Banks, G. C. Bailey, Ind. Eng. Chem., Prod. Res. Dev. 1964, 3, 170.
[2] N. Calderon, H. Y. Chen, K. W. Scott, Tetrahedron Lett. 1967, 3327.
[3] J. C. Mol, J. A. Moulijn, C. Boelhouwer, J. Chem. Soc., Chem. Commun. 1968, 633.
[4] N. Calderon, E. A. Ofstead, W. A. Judy, J. Polyrn. Sci. A , 1967, 5, 2209.
[5] K. J. Ivin, J. C. Mol, Olefn Metathesis and Metathesis Polymerization, Academic Press,
London, 1997.
[6] K. B. Wagener, J. M. Boncella, J. G. Nel, Macromolecules 1991, 24, 2649.
[7] K. Hummel, Pure Appl. Chem. 1993, A30, 62 1,
[8] R. H. Grubbs, W. Tumas, Science 1989, 243, 907.
[9] D. S. Breslow, Prog. Polym. Sci. 1993, 18, 1141.
[lo] J. H. Edwards, W. J. Feast, Polymer 1980, 21, 595.
[11] F. L. Klavetter, R. H. Grubbs, J. Am. Chem. Soc. 1988, 110, 7807.
[I21 T. M. Swager, D. A. Dougherty, R. H. Grubbs, J. Am. Chem. Soc. 1988, 110, 2973.
[I31 R. L. Banks, D. S. Banasiak, P. S. Hudson, J. R. Norell, J. Mol. Catal. 1982, 15, 21.
[14] J. C. Mol, J. Mol. Catal. 1991, 65, 145.
[ 151 J. C. Mol, J. Mol. Catal. 1994, 90, 185.
1161 G. C. Fu, S. T. Nguyen, R. H. Grubbs, J. Am. Chem. Soc. 1993, 115, 9856.
[17] M. Schuster, S. Blechert, Angew. Chem., Int. Ed. Engl. 1997, 36, 2037.
[ 181 A. Furstner (Ed.), Topics Organomet. Chem. 1998, 1.
[19] S. K. Armstrong, J. Chem. Soc., Perkiiz Trans 1 1998, 371.
[20] K. J. Ivin, J. Mol. Catal. A: Chemical, 1998, 133, 1 ; M. L. Randall, M. Snapper, ibid.
1998, 133, 29.
[21] C. Pariya, K.N. Jayaprakash, A. Sarkar, Coord. Chem. Rev. 1998, 168, 1.
[22] R.H. Grubbs, S. Chang, Tetrahedron 1998, 54, 4413.
[23] D.L. Wright, Curx Org. Chem. 1999, 3, 211.
[24] A. Furstner, Angew. Chem., Int. Ed. 2000, 39, 3012.
(251 J. L. Herisson, Y. Chauvin, Makromol. Chem. 1971, 141, 161.
[26] R. H. Grubbs, C. R. Hoppin, J. Chem. Soc., Chem. Commun. 1977, 634.
[27] P. B. van Dam, M. C. Mittelmeijer, C. Boelhouwer, React. Kinet. Catal. Lett. 1974, I , 48 1.
[28] J. Levisalles, H. Rudler, D. Villemin, J. Organomet. Chem. 1980, 193, 235.
[29] E. Thorn-Csanyi, Angew. Makromol. Chem. 1981, 94, 18 1.
(301 F. Quignard, M. Leconte, J. M. Basset, J. Mol. Catal. 1986, 36, 13.
[31] T. Szymanska-Buzar, J. Mol. Catal. 1991, 68, 177.
[32] J. A. Moulijn, C. Boelhouwer. J. Chem. Soc., Chem. Commun. 1971, 1170.
[33] W. K. Rybak, J. J. Ziolkowski, J. Mol. Catal. 1987, 42, 347.
[34] P. B. van Dam, C. Boelhouwer, React. Kinet. Cutul. Lett. 1974, I , 165.
[35] R. Taube, K. Seyferth, Z. anorg. ullg. Chem. 1977, 437, 213.
[36] K. Seyferth, R. Taube, J. Organomet. Chem. 1982, 229, C19.
[37] W. B. Hughes, J. Am. Chem. Soc. 1970, 92, 532.
[38] K. Seyferth, R. Taube, J. Orgunomet. Chem. 1984, 262, 191.
[39] A. Keller, L. Szterenberg, Z. Naturforsch. 1992, 476, 1469.
[40] A. Keller, J. Mol. Catal. 1991, 64, 171.
[41] J. Kress, M. Wesolek, J. A. Osborn. J. Chem. SOC., Chem. Commun. 1982, 514.
[42] J. Kress, J. A. Osborn, R. M. E. Greene, K. J. Ivin, J. J. Rooney, J. Am. Chem. Soc. 1987,
109, 899.
[43] C. J. Schaverien, J. C. Dewan, R. R. Schrock, J. Am. Chem. SOC. 1986, 108, 2771.
[44] F. Quignard, M. Leconte, J. M. Basset, J. Chem. Soc., Chem. Commun. 1985, 1816.
[45] J. L. Couturier, C. Paillet, M. Leconte, J. M. Basset, K. Weiss, Angew. Chenz., Int. Ed.
Engl. 1992, 31, 628.
 References 343

[46] G. Schoettel, J. Kress, J. A. Osborn, J. Chem. SOC.,Chem. Commun. 1989, 1062.

[47] G. C. Bazan, E. Khosravi, R. R. Schrock, W. J. Feast, V. C. Gibson, Polym. Commun.
1989. 9, 258.
[48] G. C. Bazan, J. H. Oskam, H. N. Cho, L. Y. Park, R. R. Schrock, J. Am. Chem. SOC.
1991, 113, 6899.
[49] J. S. Murdzek, R. R. Schrock, Organometallics 1987, 6, 1373.
[50] H. H. Fox, R. R. Schrock, R. O’Dell, Organometallics 1994, 13, 635.
[51] K. C. Wallace, J. C. Dewan, R. R. Schrock, Organometallics 1986, 5, 2162.
[52] K. C. Wallace, R. R. Schrock, Macromolecules 1987, 20, 448.
1531 R. Toreki, G. A. Vaughan, R. R. Schrock, W. M. Davis, J. Am. Chem. Soc. 1993,
115, 127.
1541 B. T. Flatt, R. H. Grubbs, R. L. Blanski, J. C. Calabrese, J. Feldman, Organornetallics
1994. 13. 2728.
[55] S. T.’Nguyen, L. K. Johnson, R. H. Grubbs, J. W. Ziller, J. Am. Chem. SOC.1992, 114,
3974.
[56] S. T. Nguyen, R. H. Grubbs, J. W. Ziller, J. Am. Chem. SOC.1993, 115, 9858.
[57] P. Schwab, M. B. France, J. W. Ziller, R. H. Grubbs, Angew. Chem., Int. Ed. Engl. 1995,
34, 2039.
[58] P. Schwab, R.H. Grubbs, J. W. Ziller, J. Am. Chem. SOC.1996, 118, 100.
[59] J . H. Wengrovius, J. Sancho, R. R. Schrock, J. Am. Chem. SOC.1981, 103, 3932.
[60] R.R. Schrock, Tetrahedron 1999, 55, 8141.
[61] T. Weskamp, W. C. Schattenmann, M. Spiegler, W. A. Hemnann, Angew. Chem., Int. Ed.
1998, 37, 2490; corrigendum: Angew. Chem., Int. Ed. 1999, 38, 262.
1621 M. Scholl, T. M. Tmka, J. P. Morgan, R. H. Grubbs, Tetrahedron Lett. 1999, 40, 2247.
[63] J. Huang, E. D. Stevens, S. P. Nolan, J. L. Petersen, J. Am. Chem. SOC. 1999, 121, 2674.
[64] M. Scholl, S. Ding, C. Lee, R.H. Grubbs, Org. Lett. 1999, 1, 953.
[65] T. Weskamp, F. J. Kohl, W. Hieringer, D. Gleich, W. A. Hemnann, Angew. Chem., Int.
Ed. 1999, 38, 2416.
[66] J. Huang, H.-J. Schanz, E. D. Stevens, S. P. Nolan, Organornetallics 1999, 18, 537.5.
[67] L. Jafarpour, E. D. Stevens, S. P. Nolan, J. Organomet. Chem. 2000, 606, 49.
[68] K. Weiss, Angew. Chem., Int. Ed. Engl. 1986, 25, 359.
[69] K. C. Wallace, A. H. Liu, J. C. Dewan, R. R. Schrock, J. Am. Chem. SOC. 1988,
110, 4964.
[70] B. M. Novak, R. H. Grubbs, J. Am. Chem. SOC.1988, 110, 960.
[71] B. M. Novak, R. H. Grubbs, J. Am. Chem. Soc. 1988, 110, 7542.
[72] R. L. Banks, D. S. Banasiak, P. S. Hudson, J. R. Norell, J. Mol. Catal. 1982, 15, 21.
1731 M. Sherwood, Chem. Ind. (London) 1982, 994.
[74] A. Marbach, R. Hupp, Rubber World 1989 (June), 30.
[75] R. Streck in Olefin Metathesis and Polymerization Catalysts (Eds.: Y. Imamoglu,
B. Zumreoglu-Karan, A. J. Amass), Kluwer Academic, Dordrecht, 1990, p. 489.
1761 K. M. Diedrich, Kautsch. Gummi, Kunsrst. 1989, 42, 1130.
1771 K. M. Diedrich in Ullmann’s Encyclopedia of Industrial Chemistry, 5th ed., Vol. A 23,
VCH, Weinheim, 1993, Rubber, 3. Synthetic, Section 4.4, p. 302.
[78] J. H. van Deursen, W. Sjardijn, Chem. Mag. 1989, 669.
[79] C. Kirkland, Plastic World, 1990 (September), SO.
[SO] V. Dragutan, R. Streck, Catalytic Polymerization of Cycloolefins, Elsevier, Amsterdam,
2000.
1811 M.R. Buchmeiser, Chem. Rev. 2000, 100, 1565.
344 2.3 Reactions of Unsaturated Compounds

2.3.4 The Alternating Copolymerization

of Alkenes and Carbon Monoxide
Eite Drent, Johannes A. M. van Broekhoven,
Peter H. M. Budzelaar

2.3.4.1 Introduction
The copolymerization of ethylene and carbon monoxide to give alternating
copolymers has attracted considerable interest in both academia and industry
over recent decades [I]. Attention was focused on aliphatic polyketones such as
poly(3-oxotrimethylene), (Structure 1) because of the low cost and plentiful avail-
ability of the simple monomers, ethylene and carbon monoxide.
0 0

0 0

1
polyketone

Also, the carbonyl group can be derivatized to a variety of interesting new

materials. Significant advances in technological synthesis and processing made
by Shell over the past decade have now moved aliphatic polyketones to commer-
cial reality [2].
The new family of thermoplastic, perfectly alternating olefin/carbon monoxide
polymers provides a superior balance of performance properties not found in
other commercial materials. The first commercial polymer will be an ethyl-
ene/propene/CO terpolymer which will be marketed by Shell under the trade-
name Carilon@.

2.3.4.2 History of Polyketones

The formation of non-alternating polyketones through the copolymerization of
ethylene and carbon monoxide has been known since the late 1940s [3]. Using
free-radical initiation, Brubaker at DuPont showed that these polymers could be
produced under extreme pressures (50-1 50 MPa). The polymers were generally
of a low molecular weight with branched molecular structures and irregular car-
bon monoxide incorporation. As a result, they had poor physical properties and
high solubility in ordinary organic solvents.
The first metal-catalyzed copolymerization of ethylene and carbon monoxide
to give alternating ethylene-carbon monoxide structures was reported by Reppe
and Magin in 1951 [4]. Using a nickel complex, K2Ni(CN)4,in water as solvent,
low-melting oligomers along with diethyl ketone and propionic acid were pro-
 2.3.4.2 History of Polyketones 345

duced. Shryne and Holler [5] succeeded in improving nickel cyanide catalysts by
adding strong acids in solvents such as hexafluorisopropanol (HFIPA). Klabunde
et al. 161 have reported a new nickel catalyst for the ethylene/CO copolymeriza-
tion, based on a bidentate anionic phosphorus-oxygen ligand. With these cata-
lysts, the copolymerization has to be starred with pure ethylene even for poly-
ketone formation. Similar catalysts are used in the Shell process for the oligomer-
ization of ethylene (SHOP). The use of SHOP-type catalysts for polyketone for-
mation has also been claimed by Keim and co-workers [7] (cf. Section 2.3.1.3).
The yields of polymer per gram of catalyst were still low.
The first palladium complex-catalyzed alternating copolymerization of ethyl-
ene and carbon monoxide was disclosed by Gough at ICI [8] in 1967. The poly-
mer was produced at relatively low rates in severe reaction conditions (25OoC,
200 MPa).
During the following 15 years, only small advances were achieved in increas-
ing catalyst efficiencies. Independently, Fenton [9a] at Union Oil and Nozaki
[9b] at Shell Development Company (USA) discovered several related palla-
dium chlorides, palladium cyanides, and zero-valent palladium complexes as
catalysts. Sen and co-workers [ 101 reported that cationic bis(tripheny1-
phosphine)-palladium tetrafluoroborate complexes in aprotic solvents such as
dichloromethane, produced ethylene/carbon monoxide copolymers under
very mild conditions. The reaction rates were, however, very low, as were the
molecular weights.
Rhodium carbonyls have also been reported as catalysts for the alternating
copolymerization of ethylene and carbon monoxide [ 111, but activities and yields
as well as molecular weights were again very low.
In addition to the synthesis problems mentioned above, unsurmountable
processing problems were encountered for the resulting polymers. Extensive
crosslinking under melt processing conditions led to a lack of significant thermo-
plastic properties of the resulting materials, and this also presented a major
developmental hurdle. At the end of the 1970s, it was therefore concluded that
the polymer backbone of polyketone was inherently unstable and that polyketones
could not be efficiently produced. Both conclusions proved to be invalid.
In the early 1980s, workers at Shell could demonstrate melt processability of
polyketone produced by palladium cyanide catalysts, after extensive extraction
of catalyst residues from the polymers and blending these with other polymers
such as styrene/acrylonitrile copolymer. From these studies, it was suggested
that thermoplastic properties were possible in principle, and that the polyketone
backbone was not inherently unstable in the melt as previously concluded. How-
ever, catalyst extraction did not offer a viable production option from a technical
and economic viewpoint.
During this period, at Shell Research in Amsterdam, cationic palladium-tertiary
phosphine complexes containing weakly coordinating anions, similar to those stu-
died by Sen, were used (in methanol) as catalysts for the alkoxycarbonylation of
ethylene to give methyl propionate. A surprising and remarkable change in selec-
tivity was observed upon replacement of triphenylphosphine ligands by bidentate
phosphine ligands. Under the same conditions, no methyl propionate product was
346 2.3 Reactions of Unsaturated Compounds

found; instead, high-molecular-weight polyketone was formed at very high rates

(-6000 g g-’ h-’) under economically attractive, mild, reaction conditions (85 OC,
4.5 MPa) [12, 131. These catalysts are very powerful, and turnovers above lo6 can
be achieved. Also, the catalysts are easy to prepare either separately or in situ and
can be handled easily.
This discovery of the combined importance for high catalyst activity of biden-
tate ligands and weakly coordinating anions around a cationic palladium(I1) cen-
ter has, for the first time, given access to efficient synthesis of polyketones.
These new catalysts opened the way to economically attractive production
and, equally important, provided much more stable polymers with catalyst resi-
dues now measured in parts per million rather than percentages. Polyketone
thermoplastics have been developed to be easily melt-processable, and could
therefore be shown to exhibit a unique set of desirable engineering thermoplastic
properties [2].
Moreover, the new family of catalysts is active for copolymerization or terpo-
lymerization with alkenes - both simple aliphatic and heteroatom-functionalized
ones - other than ethylene, thus providing access to a complete family of new
polymers.

2.3.4.3 Copolymerization of Ethylene and CO

The present review focuses on some of the key points of scientific interest
in “polyketone catalysis” with the above-mentioned highly active palladium
catalysts and on the various essential catalytic phenomena using ethylene as
the olefinic substrate. Attention will be paid to mechanistic aspects of the co-
polymerization and the question why the cationic palladium complexes contain-
ing cis-chelating ligands lead to such active and selective catalysts for the
copolymerization. Initiation, propagation, and termination of the polymerization
will be discussed and the reasons for the perfectly alternating character of the
polymerization process will be outlined. Aspects of regio- and stereocontrol
in the synthesis of polyketone architectures with higher olefins will be men-
tioned.
As stated above, the discovery of efficient catalysts for the copolymerization of
alkenes originated from a study of the alkoxycarbonylation of ethylene in metha-
nol (MeOH) to methyl propionate (eq. (1)).

H2C=CH2 + CO + MeOH
- -OMe
0
(1)

The catalysts were cationic palladium-phosphine systems prepared from palla-

dium acetate, an excess of triphenylphosphine (PPh3) and a Bronsted acid of a
weakly or noncoordinating anion (e. g., p-tosylate (OTs-); methanol was used
as both the solvent and a reactant. An unexpected change in selectivity was ob-
served upon replacement of the excess of PPh3 by a stoichiometric amount of the
bidentate 1,3-bis(diphenylphosphino)propane (dppp). Under the same conditions,
 2.3.4.3 Copolymerization of Ethylene and CO 347

these modified catalysts led to the production of a perfectly alternating ethylene/

CO copolymer with essentially 100 % selectivity (eq. (2)) [12-141.
r 7

A typical reaction rate would be about lo4 mol of converted ethylene/mol Pd

per h, to give a polymer with an average molecular weight (M,) of -20000.
Under suitable conditions the catalysts are highly stable and total conversions
of more than lo6 mol of ethylene per mol of Pd can be obtained. The product
is high-melting (-260 “C) and is insoluble in most organic solvents; it crystallizes
and precipitates during copolymerization as a snow-white solid.
Variation of the bidentate ligand results in significant changes in both the reac-
tion rate and the molecular weight of the product. For example, Figure 1 shows
the effect of changing the chain length n of the diphosphine, of general formula
Ph2P(CH2),PPh2, on the rate and molecular weight. Many patents deal with
more subtle variations of the diphosphine. In addition, several other types of che-
luting ligands (bipyridines [ 151, bisoxazolines [ 161, thioethers [ 171) can be used.
The counteranions also affect reaction rates; highest catalyst activities are obtained
with weakly or noncoordinating anions (OTs-, triflate (OTf-), trifluoroacetate
(TFA-), BF4-, C104- and “organic” anions such as certain tetraaryl borates).
Best results are observed in protic solvents, such as lower alcohols, but the poly-
merization also proceeds well in some aprotic solvents. The anions can, generally,

Figure 1. Influence of chain length of ligand Ph2P(CH2),PPh2 on polymerization rate and

molecular weight of polyketone.
348 2.3 Reactions of Unsaturated Compounds

conveniently be introduced by adding a Bronsted or Lewis acid, as anion source,

to palladium acetate (eq. (3)).

LzPd(0AC)z + 2HX + L2PdX2 + 2 HOAC (3)

Instead of the free acid it is sometimes advantageous to use a metal salt (e. g., of
Cu” of Ni”) to introduce the anions. Preformed complexes of the type L2PdX2[ 181
and L2Pd(R)X [19] where L2 represents a chelating ligand, X a weakly coordi-
nating anion, and R a hydrocarbyl group (e.g., methyl) have also been tested
as catalysts. The results are, generally, very similar to those obtained with catalysts
prepared in situ.

2.3.4.3.1 Mechanism of Polymerization

Propagation

The catalytically active species in polyketone formation is thought to be a d8

square-planar cationic palladium complex L,PdQ+, where L2 represents the bi-
dentate ligand and @ is the growing polymer chain. The fourth coordination
site at palladium may be filled with an anion, a solvent molecule, a carbonyl
group of the chain (vide infru), or a monomer molecule. The two alternating pro-
pagation steps are migratory insertion of CO in the palladium-alkyl bond [20]
(eq. (4)) and subsequent migratory insertion of ethylene in the resulting palla-
dium-acyl bond (eq. (5)). Propagation “errors” (double CO or ethylene insertion)
are not observed.

Carbon monoxide insertion in a palladium-carbon bond is a fairly common

reaction [21]. Under polymerization conditions, CO insertion is thought to be
rapid and reversible. Olefin insertion in a palladium-carbon bond is a less com-
mon reaction, but recent studies involving cationic palladium-diphosphine and
-bipyridyl complexes have shown that olefin insertion also, particularly in palla-
dium-acyl bonds, appears to be a facile reaction [22]. Nevertheless, it is likely that
olefin insertion is the slowest (rate-determining) and irreversible step (vide infru)
in polyketone formation.
 2.3.4.3 Copolymerization of Ethylene and CO 349

Initiation and Termination

End-group analysis by I3C-NMR of the ethylene/CO copolymer produced in

methanol generally shows the presence of 50 % ester (-COOMe) and 50 % ketone
(-COCH,CH,) groups, in accordance with the average overall structure of the
polymer molecule as depicted in eq. (2). It is not clear a priori which group is
the “head” and which is the “tail” of the molecules. Moreover, GC and MS ana-
lyses of oligomers produced with certain catalysts [13] show, in addition to the
expected keto-ester product (Structure 2), the presence of diester (Structure 3)
and diketone (Structure 4) compounds.

2 3 4
keto-ester diester diketone
n>O n21 n>o

At low temperatures (below -85 “C), the majority of the product molecules are
keto-esters, with only small but balancing quantities of diesters and diketones. At
higher temperatures, the same product molecules are produced in a 2:3:4 ratio
close to 2: 1: 1. These observations have been explained [ 131 by assuming two
initiation and two termination mechanisms for polyketone formation.
One initiation pathway produces ester end-groups. It starts with a palladium-
carbomethoxy species, which can be formed either by CO insertion in a palladium
methoxide or by direct attack of methanol on coordinated CO (Scheme 1).

[L2Pd(OMe)]+ [L2Pd(CO)]2+

t M~OH

co

Scheme 1
350 2.3 Reactions of Unsaturated Compounds

Alternatively, a polymer chain can start by insertion of ethylene in a palladium

hydride (vide infru), producing a ketone end-group. Ethylene insertion in palla-
dium hydride and CO insertion in the resulting ethyl complex are both rapid
and reversible; it is thought that the second ethylene insertion (in the Pd-acyl)
is irreversible and “traps” the acyl complex to start the chain (Scheme 2).

[LpPdH] +
HpC=CH2
- - [LpPd-]’ % [ LZPd L]+
Scheme 2

For ethylene/CO copolymerization, two relevant termination mechanisms have

been proposed. One mechanism, protonolysis of the palladium-alkyl bond, pro-
duces a saturated ketone end-group and a palladium methoxide (eq. (6)). The latter
can again be converted to a palladium carbomethoxide initiator by CO insertion
into the palladium-methoxide bond.

A second mechanism, the alcoholysis of the palladium-acyl bond, gives an

ester end-group and a palladium hydride species (eq. (7)), which is again an
initiator for the next polymer chain.

[ LpPdC(0) -@ ] + - MeOH
[LzPdH]’ + 6’
OMe
(7)

Scheme 3 summarizes the formation of the three possible polymeric products of

Structures 2, 3, and 4 by the two initiation-propagation cycles (A) and (B).Both
cycles produce keto-ester molecules, but the cycles are connected by two “cross”-
termination steps to give diester and diketone products.
The formation of substantial amounts of 3 and 4 at the higher temperatures
demonstrates that transfer between the cycles is rapid and that both cycles contri-
bute with comparable rates [23]. The almost complete absence of the “cross-over’’
products 3 and 4 at lower temperatures indicates that only one initiation and one
termination mechanism must dominate. Rapid protonolysis and slow methanolysis
 2.3.4.3 Copolymerization of Ethylene and CO 35 1

M = methandlysis

Scheme 3

would produce keto-ester 2 via PdCOOMe’ initiation (cycle (A)). On the other
hand, rapid methanolysis and slow protonolysis would produce the same product,
but now via PdH’ initiation (cycle (B)).Thus, product distribution alone is not
sufficient to decide which cycle is responsible for the production of keto-esters
under these conditions. With certain catalysts it has been observed that the
addition of small amounts of a quinone oxidant (at low temperatures) can result
in an increase of the proportion of ester end-groups (up to about 85 %) without
affecting the molecular weight [13]. It is thought that quinones are able to convert
PdH’ species into PdCOOMe’ initiators; the overall reaction can be represented
by eq. (8).
[LzPdH]+ + 0
-
0 - + CHBOH + CO - [ L z P ~ C O O C H ~ ]+’ HO-OH (8)

Since quinone apparently does not affect the termination rate, this implies that
in the absence of quinone the initiator must have been a palladium hydride for
these catalysts. Other catalysts, containing different ligands and/or anions, do
not show a “quinone effect” on end-groups, which suggests that in such cases
PdCOOMe’ is the initiator species and protonolysis the most important termina-
tion mechanism. The interplay between ligand and anion determines in a subtle
way to what extent the cycles (A) and (B) are operative under polymerization
conditions.
Copolymers with predominantly ketone end-groups (i.e., 4) can be produced
either by admitting water to the polymerization or by adding some hydrogen
352 2.3 Reactions of Unsuturated Compounds

[ 131. In aprotic solvents diketones can be produced exclusively. This indicates that
palladium hydrides, generated via water-gas shift reaction (eq. (9)), or by hetero-
lytic hydrogen splitting (eq. (lo)), are indeed efficient initiators and it also shows
that protonolysis andor hydrogenolysis of palladium alkyls can be an efficient
termination mechanism.

[L2PdI2+ + H20 + CO - [L2PdH]+ + H+ + C02 (9)

2.3.4.3.2 The Role of Bidentate Ligands

Under conditions of polyketone catalysis, cationic palladium(I1) catalysts modi-
fied with excess of monodentate phosphine and Brprnsted acids of weakly coordi-
nating anions selectively give methyl propionate with high rates (eq. (1 )). Methyl
propionate formation can be considered as a combination of polyketone initiation
and termination steps without intervening propagation steps. Again, there are two
possible catalytic cycles ( ( A )and (B),Scheme 4). There is no a priori argument to
decide which cycle is actually responsible for methyl propionate formation. The
absence of the cycle-transfer products diethyl ketone and dimethyl succinate
suggests that only one cycle is operative, but it is also possible that both cycles
operate in isolation.
The most obvious difference between monodentate and bidentate ligands is that
the latter are always cis coordinated, whereas the former can also coordinate in a

CO

"methoxy cycle" H = protonolysis "hydride cycle"

M = methanolysis

Scheme 4. Two possible mechanisms for methylpropionate formation.

 2.3.4.3 Copolymerization of Ethylene and CO 353

trans fashion. If bidentate ligands are used, the starting or growing polymer chain
and the "empty" fourth coordination site are always cis to each other, which is the
most favorable position for insertion reactions. Therefore, olefin insertion in the
palladium-acyl is a probable reaction in bidentate phosphine complexes. If
monodentate phosphines are used, both palladium-alkyl and palladium-acyl spe-
cies prefer a trans orientation of the two phosphine ligands, which avoids the
unfavorable situation of a Pd-P bond trans to a Pd-C bond. At the same time,
cisltrans isomerization is expected to be rapid because of the presence of excess
ligand [24]. It is further expected that both the insertion of ethylene in Pd-H and
CO insertion in Pd-alkyl canonly occur when the phosphine ligands are cis to
each other. Immediately after insertion, cisltrans isomerization is likely to
occur which places the "chain" and the fourth coordination site trans and thus
opposes further monomer insertions. Therefore, the palladium-acyl can rapidly
terminate by alcoholysis of the Pd-acyl bond to give methyl propionate. The dif-
ference between polyketone and methyl propionate synthesis can be summarized
in eqs. (11) and (12).

polyketone -- /(:=PdrcoEt 1+
1 1 +1'
L J

[ P
\
dPd,p /Et +2 P
\ /Et
p,Pd\O
P
\
p/pd\co
/Et

[ P, ,COEtl

J
+

d"
Pd\P
L J
methylpropionate

In this scheme, a hydride cycle (cycles ( B ) ,Schemes 3 and 4) has been taken as
an example. However, the same reasoning would apply if a palladium methoxide
were taken as the initiating species in both methyl propionate and polyketone
formation. If cisltruns isomerization is suppressed (by the absence of excess
ligand andlor at low temperature) one could expect a higher tendency to form
oligomers or polymers. Indeed, the results obtained by Sen and Lai [lo], with
[Pd(PPh3)z(CH3CN)2]2+ complexes as catalyst for ethylenelC0 co-oligomerization
at low temperature, can be viewed in this light.
354 2.3 Reactions of Unsaturated Compounds

2.3.4.3.3 The Role of the Anions

Apart from the requirement of cis-chelating neutral ligands (L2), the high-activity
catalyst complexes, L2PdX2,also require weakly or noncoordinating anions (X-)
[lo, 131.
The higher reactivity of catalyst systems formed with such anions is thought to
stem at least partly from the easier access of the substrate molecules to the coor-
dination sites at the metal center. Nevertheless, it is suggested that the anionic
ligands are actively involved in the catalytic cycle. Their presence in the proximity
of the cationic palladium center, forming more or less strongly associated
cation-anion pairs, can have a profound effect on the catalysis at that center. A
contributing factor may be that less strongly coordinating anions, because of
their easier dissociation from the ion-pair, generate a more electrophilic palladium
center. The lower electron density on the palladium center may cause a lower
binding energy with the comonomers because of less back-donation from metal
to ligand. The intermediate palladium species which are involved in the catalytic
cycles would therefore be less stable, with the result that, for instance, carbon
monoxide, occupying vacant coordination sites at the palladium center, can be
displaced by the olefin, and vice versa. At the same time (migratory) transforma-
tions between the various intermediate complexes would require lower activation
energies and so proceed at a higher rate.
Coordination of the anions to the cationic palladium center may strongly depend
on the polarity of the reaction medium. Solvation of the ion-pair by protic solvent
molecules, such as methanol, is expected to facilitate cation-anion dissociation and
therefore render the metal center more electrophilic and more easily accessible for
substrate molecules. In relatively apolar solvents, close-contact ion-pairs are gen-
erally expected to exist. Anion displacement by substrate molecules may then re-
quire the use of noncoordinating anions, such as certain tetraaryl borates [ 191, with
a relatively strong affinity for interaction with the solvent molecules. This will lead
to a reduced barrier for displacement of these anions by monomer molecules.

2.3.4.3.4 Alternation in CO/Ethylene Copolymerization

Chain propagation of CO/ethylene copolymerization proceeds by a strictly alter-
nating insertion of CO and olefin monomers in the growing chain. It is safe to as-
sume that double CO insertion does not occur for thermodynamic reasons [lc].
However, the complete absence of double ethylene insertions is remarkable be-
cause ethylene insertion in a Pd-alkyl species must be exothermic by about
20 kcaVmol (84 kJ mol). The observation of strict alternation is the more surpris-
ing since the same palladium catalysts also efficiently dimerize ethylene to
butenes [25]. The perfect alternation is maintained even in the presence of very
low concentrations of carbon monoxide. When starting abatch polymerization at
a high ethylene/CO ratio, error-free copolymer is produced until all the CO is
consumed; then the system starts forming butenes (with some catalyst systems
at about twice the rate of copolymerization!).
 2.3.4.3 Copolymerization of Ethylene and CO 355

It is reasonable to assume that butene formation starts with a palladium hydride.

This inserts ethylene twice (the first insertion is probably reversible) and then
terminates by p-hydride elimination to regenerate the palladium hydride and
form butene. Thus, butene formation shows that olefin insertion (in a Pd-alkyl
bond) and p-elimination are intrinsically rapid reactions. However, the copolymer
produced in the same experiment shows neither double olefin insertion errors nor
the unsaturated end-groups indicative of p-elimination.
One reason for the perfect alternation is probably the stronger coordination of
CO to palladium(II), compared with ethylene. Once a palladium-alkyl is formed,
the stronger CO coordination ensures that the next monomer to insert will usually
be a CO molecule (assuming similar insertion barriers). Of course, CO also coor-
dinates more strongly to a palladium-acyl but since the CO insertion is thermo-
dynamically unfavorable, there the system will “wait” for an ethylene molecule
to displace CO, to coordinate and insert (Scheme 5).

-
-
co Pd \ /l@
co
competition

Scheme 5. Competition between CO and ethene coordination in polyketone formation.

The necessity for ethylene to compete with CO for a coordination site (at high
CO pressures the rate of copolymerization becomes negative-order in CO) could
also explain the lower rate of copolymer formation compared with dimerization. It
is believed that this explanation cannot be the whole picture, but that internal
coordination of the growing polymer chain to palladium may be responsible for
the observations. Each time, after an ethylene insertion, the polymer chain-end
acts as a chelating ligand, in which the oxygen atom of the chain-end’s carbonyl
group coordinates to the electrophilic palladium ion.
Stable species of this type have recently been observed by spectroscopic
techniques in the studies of olefin insertion in palladium-acyls [2 1, 261. The elec-
trostatic interaction between the positive palladium center and the negative
oxygen atom is probably the main driving force for chelate formation. This inter-
nal chelate coordination is expected to affect the chain propagation in a number of
ways.
356 2.3 Reactions of Unsaturated Compounds

Firstly, the stabilization by chelate formation should increase the exothermicity

of olefin insertion. Since part of the stabilization will already be “felt” in the transi-
tion state, it will reduce the barrier for olefin insertion in a palladium-acyl bond.
Secondly, chelate formation should oppose or slow down termination by a-elimi-
nation from palladium-alkyl. For /3-elimination to occur the /3-H atom has to ap-
proach the palladium ion, but that is opposed by coordination of the carbonyl
group (eq. (13)). Inhibition of P-H elimination in metallacycles is well known [27].

However, in the third place, chelate formation can also oppose insertion of the
next monomer by blocking the fourth coordination site at the palladium center.
The incoming monomer has to displace the carbonyl group first, and this increases
the barrier of insertion. It is thought that olefin coordination to palladium(I1) is too
weak to displace the carbonyl group in this stable five-membered ring structure.
Carbon monoxide, which coordinates more strongly to palladium, can displace
the carbonyl group and insert [26]. This generates a species in which the same
carbonyl group might still coordinate to palladium (Structure 6), but the resulting
six-membered ring should be less stable than five-membered ring Structure 5 .
Ethylene is then able to displace the carbonyl group in 6 and insert to regenerate
the next five-membered ring species.

5
6
In summary, chain propagation involves alternating reversible carbon monox-
ide insertion in Pd-alkyl species and irreversible insertion of the olefin in the
resulting Pd-acyl intermediates. The overall exothermicity of the polymerization
is caused predominantly by the olefin insertion step. Internal coordination of the
chain-end’s carbonyl group of the intermediate Pd-alkyl species, together with
CO/olefin competition, prevents double olefin insertion, and thermodynamics pre-
vent double CO insertions. The architecture of the copolymer thus assists in its
own formation, achieving a perfect chemoselectivity to alternating polyketone.

2.3.4.4 Scope of OlefidCO Copolymerization

One of the unique further features of the catalysts is their ability to catalyze also
the alternating co- or terpolymerization of higher olefins (both simple aliphatic
and heteroatom-functionalized olefins) with carbon monoxide [28-331.
 2.3.4.4 Scope of Olejk/CO Copolymerization 357

Chemoselectivity of copolymerization (e. g., perfect alternation) with these

olefins is governed by similar factors to those discussed for ethylene/CO copoly-
merization, although some differences are noteworthy. Whereas p-H elimination
does not take place to a significant extent with ethylene/CO copolymerization,
this termination pathway can play a significant role in copolymerization with
higher olefins. Another difference is that, under certain circumstances and with
certain ligands, the polymers can be formed in a polyspiroketal structure
(Structure 7), isomeric with polyketones [34, 351.

7
polyspiroketal

Apart from chemoselectivity, regio- and stereoselectivity of olefin insertion are

also important factors to consider with higher olefinKO copolymers.
By a suitable choice of ligands (L2) and anions (X-) it appears possible to con-
trol the regioselectivity of olefin insertion in intermediate Pd-acyl species (1,2- vs.
2,l-insertion) to give polymers with olefin enchainments via CO, varying from
regioirregular to completely regioregular (for example, exclusively head-to-tail
enchainment). The stereochemistry of olefin insertion can also be controlled to
give atactic, isotactic, or syndiotactic olefinKO copolymers (Structures 8 and
9) [36]. Stereoregularity can be achieved by a chain-end control mechanism
[15, 37, 381 or by enantiomorphic site control [16, 291.
O R O R 0

O R O R O R

8
isotactic

O R O R 0

O R O R O R
9
syndiotactic

In contrast to polyolefins such as polypropene, polyketones possess true stereo-

genic centers along the polymer backbone. Therefore, polyketones present a
unique opportunity to use simple monomers in combination with chiral, enantio-
merically pure palladium catalysts to prepare highly isotactic, optically active
polymers (or oligomeric compounds) with main-chain chirality.
358 2.3 Reactions of Unsaturated Compounds

2.3.4.5 Conclusions
The synthesis of alternating olefinKO copolymers, discussed here, presents a new
chapter in the history of olefin polymerization. Moreover, it constitutes an exam-
ple of transition metal-catalyzed carbonylation with potentially almost perfect
control over selectivity. The cationic palladium(I1) complex catalysts derive
their ability to activate the nucleophilic substrate molecules from the electrophilic
nature of the palladium (d8) center. The cis arrangement of the neutral chelate
ligand around the metal center in a square-planar configuration ensures that the
polymer’s chain-end and incoming monomers will also be in the cis configuration
required for chain propagation. The electronic and steric properties of both the
ligand and polymer chain-end together determine the mode of olefin coordination
at the fourth coordination site, which in turn will determine the mode and ease of
(higher) olefin insertion during chain propagation. It is likely that the interaction
between the polar polymer chain-end and the electrophilic palladium center will
play a crucial role not only in achieving the alternating mode of chain propagation
(chemoselectivity), but also in obtaining a high regio- and stereoselectivity for
higher olefin insertion in intermediate palladium-acyls.

Table 1. A comparison of Pd-catalyzed CO/olefin copolymerization and early-transition-

metal-catalyzed olefin polymerization.
Poly olefins”’ Polyketones
Metal ion TiIV,Ze”, Hev Pd”
Ligands 2 cp-, 2 x- 2L, 2 x-
Anions “Noncoordinating” “Weakly or noncoordinating”
Coordination geometry Tetrahedral Square-planar
Active center

a) Cp = cyclopentadienyl.

It is interesting to draw a parallel between the palladium-catalyzed homo-

geneous olefidC0 copolymerization and the modem homogeneous olefin poly-
merization catalyzed by early transition metal complexes [39] (Table l), which
allows the following similarities to be noted.

(1) Both cations have the same ligand coordination number of four. Early transi-
tion metal cations, generally being quadrivalent, require four anionic ligands,
two strongly coordinating Cp- and two weakly coordinating anions, whereas
palladium, being bivalent, requires two neutral and two anionic ligands. The
metal cations are both rendered electrophilic by the use of weakly coordinat-
ing anions. Thus, the monomer activation will in both cases proceed via
electrophilic attack by the metal center.
 References 359

(2) At both active centers, the growing polymer chain and the vacant site for bind-
ing and activation of a monomer require cis positions. In do metallocene com-
plexes, the cis position is automatically arranged by the pseudo-tetrahedral
coordination environment of the metal cation. In the square-planar d8 palla-
dium complexes, cis coordination is enforced by the use of the neutral biden-
tate ligands.

However, there is also a major difference between the two types of catalysts.
The olefin polymerization metallocene catalysts (cf. Section 2.3.1.1) are much
more electrophilic, due to the higher positive charge of the metal ion, than the pal-
ladium(I1) complexes discussed above. For polyketone formation, electrophilicity
needs to be balanced so that olefins can still compete with carbon monoxide for
coordination to the metal cation.
If the metal cation is too electrophilic, CO coordination will be too strong,
possibly by coordination via its oxygen atom, and CO will act as a poison rather
than participating in the polymerization [40]. The moderate electrophilicity of Pd"
catalysts makes them tolerant also to a variety of heteroatom functionalities in the
olefin substrate. In this respect, polyketone catalysis can have a wider applicability
than early transition metal catalysis of polyolefins, which is highly intolerant of
functional groups.
Although the basic principles of polyketone formation are now reasonably well
understood, further studies, both of polymerization characteristics and of the
elementary steps underlying polyketone catalysis, will be needed to exploit
fully the potential of these selective polymerizations.

References
[1] For earlier reviews, see: (a) A . Sen, Adv. Polym. Sci. 1986, 73/74, 125; (b) A. Sen,
CHEMTECH 1986, 48; (c) A. Sen, Acc. Chem. Res. 1993, 26, 303.
[2] (a) C. E. Ash, J. Matel: Educ. 1994, 16, 1; (b) D. Medema, A . Noordam, Chemisch
Magazine, 1995 (March), (in Dutch), 127.
[3] DuPont ( M . M. Brubaker), US 2.459.286 (1950); Chem. Abstr: 1950, 44, 4285.
[4] BASF (W. Reppe, A. Magin), US 2.577.208 (1951); Chem. Abstl: 1952, 46, 6143.
[5] Shell (T. M. Shryne, H. V. Holler), US 3.984.388 (1976) Chem. Abstr: 1976, 85, 178219.
[6] U. Klabunde, T. H. Tulip, D. C. Roe, S. D. Ittel, J. Organomet. Chem. 1987, 334, 141.
[7] BP (B. Driessen, M. J. Green, W. Keim), EPAppl. 407.759 (1992); Chem. Abstl: 1992,
116, 152623.
[8] ICI (A. Gough), GB 1.081.304 (1967); Chem. Abstl: 1967, 67, 100569.
[9] (a) Union Oil (D. M. Fenton),US 3.530.109 (1970) and 4.076.911 (1978); Chem. Abstl:
1970, 73, 110466, and 1978, 88, 153263; (b) Shell (K. Nozaki) US 3.689.460, 3.694.412
(1972); Chem. Abstr: 1972, 77, 152869, 165324; and Shell (K. Nozaki) US 3.835.123
(1974); Chem. Abstr: 1975, 83, 132273.
[lo] A. Sen, T.-W. Lai, J. Am. Chem. Soc. 1982, 104, 3520; A. Sen, T.-W. Lai, Organome-
tallics 1984, 3, 866.
[11] (a) Y. Iwashita, M. Sakuraba, Tetrahedron Lett. 1971, 2409; (b) G. Consiglio, B. Studer,
F. Oldani, P. Pino, J. Mol. Catal. 1990, 58, L9; (c) A. Sen, J. S. Brumbaugh, J. Mol.
Catal. 1992, 73, 297.
360 2.3 Reactions of Unsaturated Compounds

[12] Shell (E. Drent), EPAppl. 121.965 (1984); Chem. Abstr: 1985, 102, 46423.
[ 131 E. Drent, J. A. M. Van Broekhoven, M. J. Doyle, J. Organornet. Chem. 1991, 41 7, 235.
[I41 I3C NMR (9:1 HFIPA/C6D6,250 MHz): 6ro 212.9, 6cH3 35.6 (1:2). Some small reso-
nances due to end-groups can be identified: -COCH2CH3, 6co 217.1, 6 ~ 6.5; 3
-COOCH3, 6co 176.4, 52.0. The ratio of ester to keto end-groups is close to unity.
[15] Shell (E. Drent), EPAppl. 229.408 (1986); Chem. Abstr: 1988, 108, 6617.
[16] (a) M. Brookhart, M. I. Wagner, G. G. A. Balavoine, J. Am. Chem. SOC. 1994, 116, 3641 ;
(b) S. Bartolini, C. Carfagna, A. Musco, Macromol. Rapid Commun. 1995, 16, 9.
[17] Shell (J. A. Van Doom, E. Drent), EP Appl. 345.847 (1989); Chem. Abstr: 1990, 112,
199339.
[18] (a) U. Daum, Ph. D. Thesis, ETH Zurich, 1988; (b) Z. Jiang, G. M. Dahlen, K. House-
knecht, A. Sen, Macromolecules 1992, 25, 2999.
[19] M. Brookhart, F. C. Rix, J. M. DeSimone, J. C. Barborak, J. Am. Chem. SOC. 1992,
114, 5894.
1201 P. W. N. M. Van Leeuwen, C. F. Roobeek, H. Van der Heijden, J. Am. Chem. Soc. 1994,
116, 12117.
[21] See, e. g.: P. M. Maitlis, The Organic Chemistry of Palladium, Academic Press, London,
1971; P. A. Chaloner, Handbook of Coordination Catalysis in Organic Chemistry,
Buttenvorths, London, 1986; A. Yamamoto, Organotransition Metal Chemistry,
Wiley, New York, 1986.
[22] (a) F. Ozawa, T. Hayashi, H. Koide, A. Yamamoto, J. Chem. Soc., Chem. Commun. 1991,
1469; B. A. Markies, J. Boersma, A. L. Spek, G. Van Koten, Reel. Truv. Chim. Pays-Bas
1991, 110, 133; B. A. Markies, M. H. P. Rietveld, J. Boersma, A. L. Spek, G. Van Koten,
J. Organomet. Chem. 1992,424, C12; (b) G. P. C. M. Dekker, C. J. Elsevier, K. Vrieze,
P. W. N. M. Van Leeuwen, C. F. Roobeek, J. Organomet. Chem. 1992, 430, 357;
(c) J. Brumbaugh, R. R. Whittle, M. Parvez, A. Sen, Organometallics 1990, 9, 1735.
[23] Crossover from ( A )to ( B ) must have the same rate as termination within (B), since the
termination rate does not depend on how the chain started. Similarly, crossover from
B to ( A )has the same rate as termination within A. If the ratio of alcoholysis to protolysis
is k, the ratio of the products will be 2:3:4= I+k2:k:k. A ratio of 2: 1 : 1 implies that both
termination steps contribute equally ( k = 1). The absence of 3 and 4 implies that k is
either very large or very small, i.e., that only one of the two termination steps contributes.
[24] See, e.g.: D. G. Cooper, J. Powell, Can. J. Chem. 1973, 51, 1634; D. A. Redfield,
J. H. Nelson, Inorg. Chem. 1973, 12, 15.
[25] E. Drent, Pure Appl. Chem. 1990, 62, 661.
[26] R. Van Asselt, E. C. G. Gielens, E. R. Rulke, K. Vrieze, C. J. Elsevier, J. Am. Chem. Soc.
1994, 116, 977.
[27] J. X. McDermott, J. F. White, G. M. Whitesides, J. Am. Chem. Soc. 1973, 95, 4451 and
1976, 98, 6521.
[28] (a) Shell (E. Drent, R. L. Wife), EP Appl. 181.014 (1985); Chem. Abstr: 1985, 105,
98172; (b) Shell (E. Drent), EP Appl. 322.018 (1988); Chem. Abstr: 1989, I l l ,
221150; (c) Shell (J. A. Van Doorn, P. K. Wong, 0. Sudmeijer) EP Appl. 376.364
(1989); Chem. Abstr: 1991, 114, 24797; (d) Shell (P. K. Wong), EP Appl. 384.517
(1989); Chem. Abstr: 1991,114, 103079; (e) Shell (P. W. N. M. Van Leeuwen, C. F. Roo-
beek, P. K. Wong), EP Appl. 393.790 (1990); Chem. Abstr: 1991, 114, 103034.
[29] (a) A. Batistini, G. Consiglio, U. W. Suter, Angew. Chem. 1992, 104, 306; Angew.
Chem., lnt. Ed. Engl. 1992, 31, 303; (b) M. Barsacchi, A. Batistini, G. Consiglio, U. W.
Suter, Macromolecules 1992, 25, 3604; (c) A. Batistini, Ph. D. Thesis, ETH Zurich,
1991; (d) A. Batistini, G. Consiglio, U. W. Suter, Minisymposium New Advances in Poly-
olefin Polymers, Div. Polymeric Materials: Science and Eng. Inc., 204th ACS Meeting,
Washington DC, 1992, Paper 5b; (e) R. Huter, Diplomarbeit, ETH Zurich, 1992.
 2.3.5.1 Introduction 361

[30] J. C. W. Chien, A. X. Zhao, F. Xu, Polyrn. Bull. 1992, 28, 315.

[31] Shell (E. Drent, H. P. M. Tomassen, M. J. Reynhout), EPAppl. 468.594 (1992); Chem.
AbstK 1992, 117, 52257.
[32] Shell (E. Drent), EPAppl. 272.727 (1988); Chem. Abstr: 1988, 109, 191089.
[33] Shell (E. Drent), EP Appl. 463.689 (1992); Chem. Abstr: 1992, 116, 129879.
[34] P. K. Wong, J. A. Van Doom, E. Drent, 0. Sudmeijer, H. A. Stil, Ind. Eng. Chem. Res.
1993, 32, 986.
[35] A. Batistini, G. Consiglio, Orgunornetallics 1992, 11, 1766.
[36] An isotactic structure is one in which the optically activc ccntcrs of the repeat units all
have the same absolute stereochemistry (G. Natta, P. Pino, P. Corradini, F. Danusso, E.
Mantica, G. Mazzanti, G. Moraglio, J. Am. Chem. Soc. 1955, 77, 1708); in a syndiotactic
polymer, neighboring units have opposite stereochemistry. If an isotactic polyolejin is
drawn in its extended conformation, it will have all its substituents pointing in the
same direction. If an isotactic polyketone is drawn in its extended conformation, the sub-
stituents will alternately point up and down.
[37] P. Corradini, A. De Rosa, A. Panunzi, P. Pino, Chimiu 1990, 44, 52.
[38] (a) M. Barsacchi, G. Consiglio, L. Medici, G. Petrucci, U. W. Suter, Angew. Chem. 1991,
103, 992; Angew. Chem., Int. Ed. Engl. 1991, 30, 989; (b) M. Barsacchi, Ph. D. Thesis,
ETH Zurich, 1991; (c) M. Barsacchi, G. Consiglio, U. W. Suter, Minisymposium New
Advances in Polyolefin Polymers, Div. Polymeric Materials: Science and Eng. Inc.,
204th ACS Meeting, Washington DC, Paper 32, 1992.
[39] See, for example: R. F. Jordan, Adv. Organomet. Chem. 1991, 32, 325.
(401 Some metallocene complexes can undergo alternating insertion of alkynes and carbon
monoxide: A. S. Guram, Z. Guo, R. F. Jordan, J. Am. Chem. Soc. 1993, 115, 4902.

2.3.5 Telomerization (Hydrodimerization) of Olefins

Noria ki Yoshirnu ra

2.3.5.1 Introduction
According to the context of this book telornerization means a polymerization in
which a (solvent) molecule AB (the telogen) reacts with n molecules of an unsa-
turated monomer (the taxogen) to yield oligomers or polymers of relatively low
molecular weight (eq. (1)). If water or compounds with active hydrogen serve
as telogens together with two moles of the taxogen the telomerization becomes
a special hydrodirnerization (eq. (2)):
A-B + nM -+ A-(M)n-B

-
telomerization

H-OH + nM H-(M),-OH
hydrodimerization

Telomerization reactions of dienes are important. While cyclooligornerizations

of butadienes with nickel catalysts are technically important for producing the
precursors of polyamides or polyesters (cf. Section 2.3.6), the telomerization
362 2.3 Reactions of Unsaturated Compounds

(hydrodimerization) of butadiene provides, in good yields, linear dimerization

products to which various active hydrogen compounds have added (eq. (3)) [l].
In particular, with an active hydrogen compound of water (the telogen), the result-
ing product can be hydrogenated to give 1-octanol, which is useful as a raw
material for plasticizers for polyvinyl chloride.

HX = ROH, H20, HOAc, HNR2, etc.

The key reaction of this 1-octanol process is telomerization of butadiene with a

palladium complex catalyst. Known attempts to commercialize the palladium
complex-catalyzed telomerization have failed, in spite of great efforts, for the
following reasons: (1) palladium complex catalysts are thermally unstable and
the catalytic activity markedly decreases when, as a means of increasing the ther-
mal stability, the ligand concentration is increased; (2) a sufficiently high reaction
rate to satisfy industrial needs cannot be obtained; (3) low selectivity; and (4)
distillative separation of reaction products and unreacted butadiene from the
reaction mixture causes polymeric products to form and the palladium complex
to metallize. Kuraray succeeded in 1991 in commercializing the production of
1-octanol using hydrodimerization of butadiene.

2.3.5.2 Development of Technologies

Conventional dimerization of butadiene uses a trivalent phosphine as a ligand. It
has been reported [2] that the catalytic activity in the telomerization is highest
when the molar ratio P P d is kept at 1-2: 1 and rapidly decreases when the ratio
becomes about 6: 1. Also, on telomerization with water (hydrodimerization), the
catalytic activity decreases markedly with increasing P/Pd molar ratio (Figure 1).
On the other hand, in order to increase the thermal stability of a palladium
complex catalyst, it is necessary for a large excess of the phosphine ligand to
be present together with the catalyst. This contradiction was able to be solved
by using a tetravalent phosphonium salt (Structure 1) as a ligand [3].

HCOd

1
 2.3.5.2 Development of Technologies 363

120

=100
2!
E 80
-9
u phosphonium salt

F
C 60
al

40
?
rc
(Y
20

0
10 20 30 40
PlPd molar ratio

Figure 1. Effect of the ligand concentration on the telomerization of butadiene with water in
sulfolane/water (5050, wt./wt.) solution containing 2 mM Pd(OAc)2 and 8 wt.%
triethylamine, at 75 "C for 1 h under 0.5 MPa COz.

110
t

"i; 2 4 6
number of repetitions

Figure 2. The catalytic activity of repeated hydrodimerization. In sulfolane/water (5050)

solution containing 2 m~ Pd(OAc)2 and 8 wt.% triethylamine, at 75 "C for 1 h
under 0.5 MPa C02. Products are extracted with hexane.

With the use of the new phosphonium salt ligand (a salt of triphenylphosphine
monosulfonate, TPPMS, cf. Section 3.1.1. l), increasing the P/Pd molar ratio not
only maintains the reaction rate at a high level (Figure 1) but shows no appreciable
time-dependent deterioration of the catalytic activity upon repeated reactions, as
shown in Figure 2. Another problem associated with the use of a phosphine on
a commercial scale is its conversion, due to the presence of a small amount of
oxygen having mixed into the reaction zone, to the corresponding phosphine
364 2.3 Reactions of Unsaturated Compounds

oxide, that will not act effectively as a ligand. The use of a phosphonium salt can
minimize this type of conversion. Although the mechanism of the action of the
phosphonium salt has not been made clear, it is considered, from the fact that
aryl groups should be present, that a very rapid equilibrium with the corre-
sponding phosphine may occur partially. However, upon analysis of the actual
reaction mixture, no trivalent phosphine is detected either in the reaction solution
or in the palladium complex.
For the hydrodimerization of butadiene with water, attempts have been made to
increase the reactivity by adding acidic solids [4], salts such as sodium phosphate
[ 5 ] ,emulsifiers [6], carbon dioxide [7], or the like, with no satisfactory results. In
particular, the reaction rate increases under a carbon dioxide pressure, but carbon-
ate ions, not carbon dioxide itself, are considered to play an important role in this
effect. It is known that the carbonate ion concentration in water is very low even
under a carbon dioxide pressure. If the carbonate ion is the true reactant, the re-
action rate should increase with the carbonate ion concentration. Since inorganic
carbonates show almost no effect, the addition of various tertiary amines having
no active hydrogen, under a carbon dioxide pressure was tested [8]. Diamines and
bifunctional amines inhibited the reaction. The reaction rate increased only in the
presence of a monoamine having a pK, of at least 7, almost linearly with its
concentration (Figure 3).
Telomerization requires a solvent that can dissolve both water and butadiene.
To select a suitable solvent for this purpose the separability of the reaction prod-
ucts from the catalyst used should be considered. According to past reports, the
selectivity to 2,7-octadien-l-o1, which is of high industrial value, has been 70 %
at most. Use of sulfolane, which had not been studied as a reaction solvent,
realized a high 2,7-octadien-l-ol selectivity of at least 83 % and a high reaction

0,o
0 10 D
triethylamine [MY01

Figure 3. The effect of the concentration of triethylamine on the rate of telomerization of

butadiene with water. In sulfolane/water (80:20) solution containing 2.7 mM
Pd(OAc)2 and 54 mM ligand, at 75 "C for 3 h under 1.5 MPa C02.
 2.3.5.2 Development of Technologies 365

rate (Table 1) [8]. Sulfolane, having both high stability in its aqueous solution and
high solubility for butadiene, is considered to be the most suitable solvent for
industrial long-term use.
For the telomerization of butadiene, distillative separation methods cannot be
employed to separate the product from the reaction mixture containing catalyst,
because the palladium complex catalyst has not such a high thermal stability

Table 1. Effect of solvent on the telomerization of butadiene with water as telogen.”’

Octadienol
Yield Selectivity Ratio
Solvent [mmol] [%I 1 /bb’
Sulfolane 91 92 92: 8
CH3CN 30 60 81:19
t-BuOH 18 67 7 1:29
Acetone 12 49 53:47
Dimethyl sulfoxide 8 65 72:28
Dimethylformamide 9 67 82: 18
Water only 1 71 81:19
a) In solvent/water (55:45) solution (60 ml) containing 230 mmol butadiene, 0.1 mmol
Pd(OAc)*, 12 % triethylamine, 2 mmol ligand, at 75 “C for 3 h under COz.
h, 2,7-octadien- 1-oV1,7-octadien-3-ol.

hexane

unreacted diene

1 distillation

T- r
phase separator

___________

hexane
solution

I I

sulfolane/water
products

Figure 4. Extraction method for separating butadiene hydrodimerization products from

catalyst-containing reaction mixture.
366 2.3 Reactions of Unsaturated Compounds

and high-boiling compounds would accumulate in the catalyst-containing solution

that has been recycled. Therefore an extraction separation method has been chosen
(Figure 4). In the present reaction, water acts as a nucleophile and the product
hardly dissolves in water. Therefore the process is capable of retaining the catalyst
component in the aqueous solution being used and extracting the product selec-
tively. Thus, in order to solubilize the catalyst component in the aqueous sulfolane
solution used, a hydrophilic group (e. g., sulfonic acid salt) was introduced into
the phosphonium salt ligand and the product was extracted with an aliphatic satu-
rated hydrocarbon such as hexane [3, 8-10]. This extraction separation method
has the advantages that: (1) the catalyst and product can be separated without
heating them, so that thermal deactivation is avoided; (2) extraction equilibrium
is achieved for all compounds, so that the accumulation of catalyst poisons and
high-boiling by-products can hardly occur. This method is commercially appli-
cable only when the resultant catalytic lifetimes and the elution losses of catalytic
componentsinto the extractant layer containing the product are within commer-
cially acceptable ranges (cf. Section 3.1.1.1).

2.3.5.3 Process for the Manufacture of 1-Octanol

This process consists of four steps: hydrodimerization, extraction, hydrogenation,
and distillation [9-111. The telomerization step comprises feeding butadiene and
water continuously to the reaction zone in the presence of a separately prepared
palladium catalyst (1-5 mmol/L), a phosphonium salt ligand (40-50 moVmol of
palladium), and a solution of triethylammonium hydrogencarbonate in aqueous
sulfolane, and reacting them at a temperature of 60-80°C under a total pressure
of carbon dioxide of 1-2 MPa, to achieve an 2,7-octadien-l-o1 selectivity of
90-93 % and an 2,7-octadien-3-01selectivity of 4-5 %. In the following extraction
step, 50-70 % of the reaction products are extracted with hexane, and the aqueous
sulfolane containing the catalyst, part of the products, and the triethylammonium
hydrogencarbonate is again circulated to the reaction step. The elution loss of the
catalyst is only several parts per million. The sulfolane concentration is set at
about 40 wt % in view of the extraction ratio of the products, the solubility of bu-
tadiene, and the elution loss of the catalyst. After unreacted butadiene and hexane
have been recovered from the extraction mixture, 2,7-octadien- 1-01 is purified
by distillation. The 2,7-octadien-l-ol obtained is hydrogenated on a fixed bed
in the presence of a nickel catalyst and at 3-8 MPa H2 and 130-180 "C to yield
l-octanol nearly quantitatively.

2.3.5.4 Development and Scope

2,7-octadien-l-o1 is a highly reactive compound having double bonds and a hy-
droxyl group. Reacting this compound in the presence of a copper chromite cat-
alyst at a temperature of 220 "C causes intramolecular dehydrogenationhydroge-
nation, to yield isomerized 7-octenal in a yield of at least 80 % [ 121. This aldehyde
 References 361

is hydroformylated to the dialdehyde, which is then hydrogenated to give I ,9-non-

anediol [13]. The extraction separation method is also applicable to this hydrofor-
mylation. The dialdehyde can also give, on air oxidation in an acetic acid solvent
with a copper catalyst, azelaic acid and, on reductive amination in ammonia in the
presence of a nickel catalyst, 1,9-nonanediamine (eq. (4)).

-+ -+ H20 ' OH +
Hz
Ni
O
H-
c4 c4 CO 8' n-octanol

1 CuCr03

CO HZ

I [Rh(acac)(CO)z]/
TPPMS
(4)

Telomerization with formic acid as a telogen can produce 1,7-octadiene, which

is useful as a modifier for polyolefins. This reaction proceeds with the same sys-
tem that is used for the production of octadienol [14], at a temperature of
50-70 "C, to yield 1,7-octadiene/l,6-octadienein a ratio of 88: 12. Since these
compounds phase-separate together, the product layer can be readily separated
and the sulfolane layer containing the catalyst can be circulated for re-use.

References
[l] J. Tsuji, Adv. Organomet. Chem. 1979, 17, 141.
[2] D. Rose, H. Lepper, J. Organomet. Chem. 1973, 49, 473.
[3] Kuraray Ind. (T. Maeda, Y. Tokitoh, N. Yoshimura), US 4.927.960 (1990), 4.992.609
(1991), 5.100.854 (1991).
[4] Mitsubishi Chem. Ind. (T. Onoda, H. Wada, T. Sato, Y. Kasori), J P 53/147.013 A2
(1 978).
[5] Kureha Chem. Ind. (S. Enomoto, H. Takita, S. Wada, Y. Mukaida, M. Yanaka), J P 49/
35.603 B4 (1974).
[6] Toray Ind. (T. Tsuji, T. Mitsuyasu), J P 4935.603 B4 (1974).
[7] K. E. Atkins, W. E. Walker, R. M. Manyik, Chem. Commun. 1971, 330.
[8] Kuraray Ind. (N. Yoshimura, M. Tamura), US 4.356.333 (1982).
[9] Kuraray Ind. (Y. Tokitoh, N. Yoshimura), US 5.057.631 (1991).
[ 101 Kuraray Ind. (Y. Tokitoh, T. Higashi, K. Hino, M. Murasawa, N. Yoshimura),
US 5.118.885 (1992).
[ l l ] Kuraray Ind. (N. Yoshimura, M. Tamura), US 4.417.079 (1983).
[12] Kuraray Ind. (N. Yoshimura, M. Tamura), US 4.510.331 (1985).
[13] Kuraray Ind. (M. Matsumoto, N. Yoshimura, M. Tamura), US 4.510.332 (1985).
[ 141 Kuraray Ind. (N. Yoshimura, M. Tamura), US 4.334.117 (1 982).
368 2.3 Reactions of Unsaturated Compounds

2.3.6 Cyclooligomerizations and

Cyclo-co-oligomerizationsof 1,3-Dienes
Giinther Wilke, Anette Eckerle

2.3.6.1 Introduction
Thermal cyclooligomerizations of olefins and alkynes require severe and often
dangerous reaction conditions and the yields of cyclic products are usually very
low. Acetylene can be trimerized to benzene at 500 "C [I] and butadiene (BD) di-
merizes at 270 "C and under high pressure to give small amounts of 1,5-cyclo-
octadiene [2].Reppe's discovery in 1940 that acetylene can be cyclotetramerized
to cyclooctatetraene (COT) using a nickel catalyst [3] shows that transition metals
can act as templates for the synthesis of cyclic hydrocarbons from acetylenic or
olefinic building blocks (Scheme 1).

Scheme 1

The first catalytic cyclodimerization of 1,3-butadiene (BD) to 1,5-cycloocta-

diene using modified Reppe catalysts was reported by Reed in 1954 [4], and
only two years later Wilke reported on the titanium-catalyzed synthesis of cyclo-
dodecatrienes from BD [5].It remained for Wilke and his co-workers to show the
tremendous versatility and scope of the nickel-catalyzed cyclooligomerizations of

DVCB

6
VCH

COD

(VCH = vinyl cyclohexene, COD = cyclohexadiene, CDT = cyclododecatriene,

Scheme 2 DVCB = divinyl cyclobutane)
 2.3.6.1 Introduction 369

Table 1. Composition of the oligomerization products of butadiene with nickel-ligand

catalysts”’.
Ligand VCH COD CDT >c12 TON^)

Ph,As 5.8 17 60 14 20
40 41 14 4.8 35
27 64 6.0 2.8 180
7.4 81 9.2 2.3 I00
(o-PhC6H40)3P 3.1 96 0.2 0.2 780
@-PhChH40)3P 6.9 65 18 9.6 75
”) Reaction conditions: ligand: nickel = 1 : 1; 80°C, 3 h, 1 bar.
)’ g butadiene (g Ni)-’ h-I.
‘) Cy = cyclohexyl.

1,3-dienes [6]. The elucidation of the reaction mechanism led to isolation of inter-
mediates ($-allyhickel complexes), which stimulated research into nickel organic
chemistry as well as into catalysis [6b,e].
Cyclooligomerization of 1,3-dienes is now known for many transition metals
but nickel complexes represent the most versatile and useful catalytic systems.
Scheme 2 shows the six cyclooligomers that can be synthesized from BD by
choosing the “right” catalyst. In the case of nickel, this means choice of the appro-
priate ligand. The observations that the steric and electronic properties of a ligand
correlate with a certain product distribution and that in these catalytic reactions
selectivity is closely linked with reactivity (Table 1) demonstrated for the first
time that it is possible to actively direct a catalytic reaction [6a,b, 71 (this is called
“ligand tuning”).
The scope of the butadiene oligomerization reaction has been extended by
adding a second monomer (olefin, diene, or alkyne). This gives rise to an almost
unlimited variety of cyclic (and, depending on the nature of the ligand, linear)
cooligomers as well as medium and large rings.
So far, the industrial application of these catalytic processes seems to be limited
to the production of 1,5-cyclooctadiene (COD) (Ni catalyst; preparation of flame
retardants and polyoctenamers), trans- 1,4-hexadiene (Ni catalyst) and 1,5,9-cy-
clododecatriene (CDT) (Ti catalyst; used in preparation of nylon 12 and Vesta-
midTM)(Huls; Scheme 3). Recent developments are in the preparation of styrene

Scheme 3 laurinlactam VestamideTM

370 2.3 Reactions of Unsaturated Compounds

Scheme 4

from butadiene [8] using a two-step process in which butadiene is first dimerized
to vinylcyclohexene (VCH) and afterwards dehydrogenated (Scheme 4).

2.3.6.2 Cyclodimerization and Cyclotrimerization

of Butadiene and Substituted 1,3-Dienes
1,5,9-Cyclododecatriene (CDT) was mentioned first by Reed [4] in 1954. It has
been claimed that CDT is formed as a by-product during the catalytic dimerization
of BD with Reppe catalysts. However, attempts to isolate CDT from the reaction
mixture failed. In the course of the investigation of Ziegler catalysts, Wilke and
co-workers [5, 9, 101 discovered that certain Ti-A1 systems cyclotrimerize BD
to CDT (mixture of trans,truns,cis- and all-trans isomers) in over 96% yield
(eq. (1)).

r\
/
% AIEt2CI
TiCl., +a0 a
\

all-t-CDT
+ \

C,t, 1-CDT
+ \

C,C,t-CDT
(1)

It must be noted that, under the influence of BD, in contrast to the polymeriza-
tion of ethylene, such Ziegler-type catalysts can no longer be regarded as purely
heterogeneous. When BD is passed through the initial slurry, most of the catalyst
dissolves [ l l , 121.
Soon after the initial discovery of this trimerization reaction, Wilke and co-
workers found that the versatility and reactivity of such catalyses is enhanced
when homogeneous zerovalent nickel catalyst are being used [6b, 131. Catalysts
of this type can either be generated from Nio complexes with ligands that can
easily be substituted by BD (eg., Ni[CDT], Ni[COD],) (“naked” Nickel [6b]), or
from Ni” complexes that are reduced in the presence of BD (almost any reducing
agent will serve) [6] ; a typical example is [Ni(acac),]-Al(OEt)Et2. Condensed
nickel vapor has also been shown to be active [13].
In the absence of a donor ligand, BD is trimerized to a mixture of three isomers
of 1,5,9-CDT with the all-trans isomer being the principal product [6,7]. Addition
of donor ligands (pyridine is an exception) leads to considerable BD-cyclodimer-
ization. Table 2 [7, 141 shows the results of a study of the effects of varying the
ligand on the cyclodimer/cyclotrimer ratio (see also Table 1).
This suggests that CDT formation is mainly controlled by the steric properties
of the ligand: bulky ligands which do not coordinate properly (i-Pr, t-Bu) and
 2.3.6.2 Cyclodimerization and Cyclotrimerization of Butadiene 37 1

Table 2. The cvclodimerization of butadiene.

780 96 3.1 0.2 0.2

600 96 2.6 1.o 0.2

315 91 6.8 1.5

400 92 5.7 1.4 0.6

110 74 8.1 10.8 7.1
70 73 8.8 9.7 8.2
325 90 5.8 3.7 0.3
140 83 7.5 9.3
90 78 10.1 9.6 1.8
190 88 5.8 4.4 2.4
100 81 7.4 9.2 2.3
180 64 27 6.0 2.8
35 41 40 14 4.8

“compact” ligands which tend to disproportionate the 1: 1 complexes (P(OMe)3)

afford CDT as major product, because catalysis takes place on “naked” nickel.
All other ligands lead to cyclodimerization products, whereby product distribution
in the dimer series can be tuned via the steric properties of the ligands. Note that
the reaction rates correlate with selectivity, a quite common principle for catalytic
reactions that was observed here for the first time [7].
The cyclooligomerization reaction is not confined to BD as the monomer. Ac-
tivated or monosubstituted 1,3-dienes also react, but reaction rates are usually
slow, and selectivity and turnover numbers (TONS) are low. Cyclotrimerization
and cyclodimerization of substituted 1,3-dienes - either alone or in admixture
with BD - give numerous isomers of substituted CDT, COD, VCH and divinyl-
cyclobutane (DVCB). For example, isoprene [34], 1,3-pentadiene [35], 2,3-
dimethylbutadiene [36], 1,3-hexadiene [37], and even 1-vinyl- 1-cyclopentene
[38] do react (eqs. (2)-(6)). 2,4-Hexadiene is inert.
312 2.3 Reactions of Unsaturated Compounds

98 Yo

x
100 %
(4)

25 %

Tables 3 and 4 show some other examples [15].

Table 3. The cyclodimerization of methyl-substituted 13dienes.

l,3-Diene Rate C6 ring C8 ring
[g diene (g Ni)-' h-'1 [%I [%I
Butadiene 220 2.3 97.2
Piperylene 31 5.3 90.9
Isoprene 14 34.8 55.1
2,3-Dimethylbutadiene 0.6 86.3 6.1
2,4-Hexadiene 0

Table 4. The codimerization of methyl-substituted 1,3-dienes with butadiene.

1,3-Diene C6 ring C8 ring Dimer of
[%I substituted diene
Piperylene 1.6 86.4 11.5
Isoprene 5.5 84.0 9.8
2,3-Dimethylbutadiene 7.6 92.3 Trace
 2.3.6.2 Cyclodimerization and Cyclotrimerization of Butudiene 373

The cyclooligomerization of isoprene (eq. (7)) has received attention, since the
trimerization products are of interest in the perfume industry [16].

Of course, the catalytic cyclooligomerization of BD is not limited to nickel

as template. Other transition metal catalysts and reaction products are listed in
Table 5 [17-251 and Table 6 [26-301.

Table 5. Cyclodimerization of butadiene.

Catalyst Main product Ref.
~~

[ [ Fe(N0)2C1}2]/electrolysis 4-Vinyl-1-cyclohexene (VCH) ~ 7 1

4-Vinyl- 1-cyclohexene (VCH) [I81
1,5-Cyclooctadiene (COD) ~191
1 ,S-Cyclooctadiene (COD) PO1
[Ni(a ~ a c ) ~ArO),P/reductant
]/( 1,S-Cyclooctadiene (COD) [211
[NiCl(~-totyl)(Et,P)~] 2-Methyl- 1-vinylcyclopentane [221
TiC1,/AIEtl/diethanolamine 4-Vinyl- 1-cyclohexene (VCH) WI
[Mn(biphenyl)Cp] 4-Vinyl- 1 -cyclohexene (VCH) ~ 4 1
Pd(C10.t)z 1,2-Divinylcyclobutane (DVCB) [251

Table 6. Cyclotrimerization of butadiene.

Catalyst Main product Ref.
[Ni(CO),]/benzene t, t, t-Cyclododecatriene 1261
[NiC12(en)JA1Et3 t, t,t-Cyclododecatriene ~ 7 1
[TiCl2(ChH6)]/AlzCl6
(+AlEt,) c, t, t-Cyclododecatriene [281
[T~(OBU)~]/E~~A~~CI~/H~O c,t, t-Cyclododecatriene [291
[Cr(acac)3/A1Et3/co-catalyst c,t, t-Cyclododecatriene ~301
314 2.3 Reactions of Unsaturated Compounds

2.3.6.3 Cyclo-co-oligomerization of 1,3-Dienes

with Olefins and Alkynes
Many transition metals catalyze oligomerization reactions between dienes and ole-
fins or alkynes. Possible reaction products are legion. But it is almost exclusively
with zerovalent nickel that cyclic products are formed. Addition of olefins or al-
kynes to catalysts mentioned in the previous section suppresses the cyclooligo-
merization and instead gives cyclo-co-oligomerization products.

2.3.6.3.1 Cyclo-co-oligomerization of 1,3-Dienes

with Olefins
Cooligomerization of 1,3-dienes with an olefin on a Nio template leads, depending
upon the nature of the ligand, either to linear 1: 1 products (1,4-hexadienes) or
to cyclic 2: 1 products (trans,cis-l,5-cyclodecadienes)(Scheme 5 ) [6, 3 1-33].
A wide variety of dienes and olefins have been studied; the reaction appears to
be limited to strained or monosubstituted olefins or to intramolecular reactions
[49, 501 (eqs. (8)-(10)).

Scheme 5
 2.3.6.3 Cyclo-co-oligomerizationof 1,3-Dienes with Olejins and Alkynes 375

Ni(COD)2/ Ph3P
H&+
90 "C

2.3.6.3.2 Cyclo-co-oligomerizationof 1,3-Dienes

with Alkynes
The cyclo-co-oligomerization of 1,3-dienes with alkynes is characterized by the
relative ease with which rings are formed and by the possibility of incorporation
of more than one alkyne molecule (Scheme 6).

Scheme 6 R

Iron complexes favor the codimerization of BD with alkynes in a 1:1 ratio to

(substituted) cyclohexadienes [39]. Two BD molecules and one alkyne give
cyclodecatrienes with zerovalent nickel catalysts and good electron-donating
ligands such as Ph3P [7, 401. Ten-membered rings are in fact the principal
products of such a reaction; the variety of dienes seems to be limited to BD, iso-
prene and 1,3-pentadiene, whereas numerous alkynes - simple alkyl-substituted
alkynes, alkynes with aprotic functional groups, dialkynes, and cyclic alkynes
376 2.3 Reactions of Unsaturated Compounds

- can be used [6c, 41-43]. Cocyclization of two BD molecules with two alkyne
molecules is described for 2-butyne [44] and acetylenecarboxylic esters [43].
Whether 10- or 12-membered rings are formed depends on thenature of the
substituent at the alkyne and on the nature of the ligand [45]. Vinylcyclohexa-
dienes are the product of a 1:2-cyclization reaction [46, 471. They easily undergo
intramolecular Diels-Alder reactions to strained tricyclic products, of which an
example is given in eq. (14).

R R

R = (CH2)" = R

R R

2 I?-R + - '@R
(14)
R R

2
Me0
O
/-,Me 4. 2 & - MeOCH2

MeOCH2
+ (15)
CH20Me
 2.3.6.4 Mechanistic Considerations 377

Nio
0 -
Me3Si =

2.3.6.4 Mechanistic Considerations

As mentioned above, many transition metals catalyze the cyclooligomerization
of 1,3-dienes. The nickel-catalyzed cyclooligomerization of BD, however, is prob-
ably one of the best-understood reactions in the field of homogeneous catalysis. In
the 40 years since its discovery a mass of evidence has been collected, indicating
that these oligomerizations are the result of a multistep addition-elimination me-
chanism at a nickel atom template, which constantly flips between two oxidation
states. The following strategies played an important role: isolation of key inter-
mediates, “simulation” of the catalytic cycle in a stoichiometric manner, product
analysis, and study of model compounds. Detailed analysis of the intellectual
development of the mechanism is not included here as this can be followed
from excellent reviews [6].
The present-day view of how BD is cyclooligomerized on a nickel template
is shown in Scheme 7. All products result in the last analysis from an intermediate
y3-allyl-y’-alky1-Ni”complex (Structures 2a-2c) which is formed via oxidative

/-

Nio + 2 -
4
I
Ni
I
m
v

CDT / 4
M
Scheme 7a
318 2.3 Reactions of Unsaturated Compounds

[Ni-L] + 2

t I
\

COD

or

Scheme 7b

R-R

YL-p R T

[Ni-L] + 2 - L
’ @
2c
\ J

Scheme 7c 2/+ 5

addition from bis(butadiene) Ni’ (Structure 1). Insertion of another diene on

“naked” nickel [6, 11, 131 leads to the cyclic trimer CDT (route 0). The mecha-
nism of the trimerization of BD is based on the well-characterized intermediate 3
[6e, 111.
 2.3.6.5 Summary 379

In the presence of donor-ligands (usually phosphines and phosphites) BD is di-

merized (route a). The activity of the catalyst as well as the relative amounts of
CDT, COD, VCH, and DVCB in the reaction product is highly dependent upon
the stereoelectronic properties of the ligand used. I ,5,9-Cyclododecatriene is the
favored product with "naked" nickel (formed by reducing [Ni(acac),] with alkyl-
aluminum compounds in the presence of BD). Nio-catalysts with fairly bulky
ligands with good acceptor properties, such as o-substituted aryl phosphites,
yield cod with over 96% selectivity. VCH can be synthesized with Ni catalysts
containing cyclohexyl-phosphines; DVCB can be isolated when conversion is
kept low, or by using special iron(I1)complexes (see Tables 1-3).
Some typical examples of cyclooligomerization catalysts other than nickel are
listed in Table 5 and 6. Examination of these reactions indicates that the mecha-
nisms are closely related to each other. They all seem to proceed via allylic inter-
mediates in a stepwise oxidative insertion (addition)/reductive coupling (elimina-
tion) fashion while the metal center undergoes changes in the formal oxidation
state (viz. Fe"-Fe'"; Ti'I-Ti'"; Ct-Cr"'; Co'-Co"'; Mn'-Mn"'; MoO-MO"; NiO-Ni"
[6bI.
Intermediate 2 can coordinate an additional alkyne (or olefin) to give 5 after
insertion into the Ni-C bond (Scheme 7). Reductive elimination affords the cor-
responding cyclodecatriene derivative. Several related stoichiometric reactions
with certain Ni complexes and alkynes or allene have been observed, thus con-
firming the proposed catalytic cycle (route @) [48] (eqs. (17) and (18)).

/Me
(acac)Ni,
PR3
+ Ph-Ph - PhMMe
(acac)Ni
\
PR3
Ph

2.3.6.5 Summary
Scheme 8 summarizes some cyclooligomerization and cyclo-co-oligomerization
products that had been realized on either "naked" or ligand-containing nickel
templates [51]. They can all be obtained in very high yields and the TON is, in
principle, unlimited. Apart from impurities of the reagents and solvents, there
are - to our knowledge - no intrinsic termination reactiones. Catalytic syntheses
affording Structures 6-8 demonstrate the usefulness of the cyclo-co-oligomeriza-
tions of BD with cyclic alkynes for the preparation of macrocycles: after selective
380 2.3 Reactions of Unsaturated Compounds

DVCB

L'
- L"Ni f
COD

aCDT

[Nil [ N(>

& & \
\ 7

Scheme 8

hydrogenation, the tetrasubstituted double bonds can be cleaved via ozonolysis to

give 20-30-membered rings.
Higher cyclooligomers of BD with ring sizes between 16 and 28 can be synthe-
sized as a mixture using a two-component nickel catalyst [Ni2(y3-allyl),C1] [52].
Fourteen membered rings can easily be obtained from two molecules of BD and
one molecule of 1,3,5-hexatriene on ligand-free nickel catalysts, which are typical
trimerization catalysts (eqs. (19) and (20)) [53].
 References 38 1

References
[ I ] M. Berthelot, Ann. Chim. Phys. (Paris) 1867, 12, 52.
121 K. Ziegler, H. Wilms, Liebigs Ann. Chem. 1950, 567, 1.
[31 (a) W. Reppe, 0. Schlichting, K. Klages, T. Toepel, Liebigs Ann. Chem. 1948, 560, 1;
(b) BASF (W. Reppe, T. Toepel) DE 859.464 (1952) Chem. Abstr: 1956, 50, 7852.
[4] H. W. B. Reed, J. Chem. SOC. 1954, 1931.
[ 5 ] G. Wilke, Angew. Chem. 1957, 69, 397; Studiengesellschaft Kohle mbH (G. Wilke)
DE 1.050.333.
161 (a) Studiengesellschaft Kohle mbH (G. Wilke, E. W. Muller) DE 1.140.569 (1966);
(b) G. Wilke, Angew. Chem. 1963, 75, 10; Angew. Chem., Int. Ed. Engl. 1963, 2,
105; (c) P. W. Jolly, G. Wilke in The Organic Chemistry of Nickel, Academic Press,
New York, 1975, Vol. 2, Chapter 3; (d) P. W. Jolly in Comprehensive Organornetallic
Chemistry (Eds.: G. Wilkinson, F. G. A. Stone, E. W. Abel) Pergamon, Oxford, 1982,
Vol. 8, p. 615; (e) B. Henc, P. W. Jolly, R. Salz, G. Wilke, R. Benn, E. G. Hoffmann,
R. Mynott, J. Schroth, K. Seevogel, J. C. Sekutowski, C. Kriiger, J. Organomet.
Chem. 1980, 191, 425.
[7] W. Brenner, P. Heimbach, H.-J. Hey, W. Muller, G. Wilke, Liebigs Ann. Chern. 1969,
727, 161.
[8] For a review of recent developments see: P. Taffe in Europ. Chem. News 1995, Septem-
ber 21.
[9] H. Breil, P. Heimbach, M. Kroner, H. Muller, G. Wilke, Makromol. Chem. 1969, 69, 18.
[lo] G. Wilke in UllmannS Encycl. Techri. Chem., 3rd ed. 1963, Vol. 14.
[ 111 B. Bogdanovic’, P. Heimbach, M. Kroner, E. G. Hoffmann, J. Brandt, G. Wilke, Liebigs
Ann. Chem. 1969, 727, 143.
[12] G. Wilke, B. BogdanoviC, P. Heimbach, M. Kroner, E. W. Miiller, ACS. Adv. Chem. Ser:
1962, 137, 34.
[13] V. M. Akhmedov, M. T. Anthony, M. L. H. Green, D. Young, J. Chem. SOC., Dalton
Trans. 1975, 1412.
[14] (a) P. Heimbach, J. Kluth, H. Schenkluhn, B. Weimann, Angew. Chem. 1980, 92, 567;
Angew. Chem., Int. Ed. Engl. 1980, 19, 569; (b) P. Heimbach, J. Kluth, H. Schenkluhn,
B. Weimann, Angew. Chem. 1980,92,569;Angew. Chem., Int. Ed. Engl. 1980,19,570.
[I51 P. Heimbach, P. W. Jolly, G. Wilke, Adv. Organomet. Chem. 1970, 8, 29.
[16] (a) S. Akatagawa, T. Taketomi, H. Kumobayashi, K. Takayama, T. Somaya, S. Otsuka,
Bull. Chem. Soc. Jpn. 1978, 51, 1158; (b) H. Morikawa, S. Kitazumi, Ind. Eng. Chem.,
Prod. Res. Dev. 1979,18, 254; (c) Takasago Perfumery Co; S. Akatagawa, T. Moriya, A.
Komatsu, JP 74 56.951 (1974); Chem. Abstl: 1974, 81, 120106; JP 74 56950 (1974);
Chem. Abstr: 1974, 81, 120107; (d) Mitsubishi Petrochem. Co; H. Morikawa, T. Sato,
I. Okada; JP 76 98242 (1976); Chem. Abstl: 1976, 85, 176807.
[17] E. LeRoy, F. Petit, J. Hennion, J. Nicole, Tetrahedron Lett. 1978, 2403.
[18] J. P. Candlin, W. H. Jones, J. Chem. SOC.(C), 1968, 1856.
[19] A. Yamamoto, K. Morifuji, S. Ikeda, T. Saito, Y. Uchida, A. Misono, . IAm.
. Chem. SOC.
1968, 90, 1878.
[20] M. A. Cairns, J. F. Nixon, J. Organomet. Chem. 1974, 64, C19.
[21] BASF, DE 1.244.172 (1967); Chem. Abstr: 1967, 67, 90456.
[22] J. Kiji, K. Masui, J. Furukawa, Chem. Commun. 1970, 1310.
[23] Japan Synthetic Rubber Co., JP 77 08.822 (1977); Chem. Abstr 1977, 87, 40079.
[24] Union Carbide Corp., US 3.168.581 (1965); Chem. Abstl: 1965, 62, 11704.
[25] E. G. Chepaikin, M. C. Khidekel, Izv. Akad. Nuuk SSSR, Ser: Khim. 1971, 1129.
[26] BASF, FR 1.379.251 (1964); Chem. Abstl: 1965, 62, 9007.
[27] Toyo Soda Manufg. Co., JP 70 24.976 (1970); Chem. Abstr: 1970, 73, 109374.
382 2.3 Reactions of Unsaturated Compounds

[28] (a) S. Dzierzgowski, R. Giezynski, P. Pasynkiewicz, M. Nizynska, J. Mol. Catal. 1977, 2,

243; (b) F. Vohwinkel, Trans. N. I: Acad. Sci. 1964, 26, 446; Chem. Abstr: 1964, 61,
10600; (c) V. M. Akhmedov, L. I. Zakharkin, Kinet. Katal. 1967, 8, 331; Chem.
Abstr: 1967, 67, 99385.
[29] (a) Ashai Chem. Ind. Co., JP 75 39.658 (1975); Chem. Abstr: 1976, 84, 164283; (b) Toa
Gosei Ind. Co., JP 74 42.499 (1974); Chem. Abstr: 1975, 82, 155583.
[30] (a) Jap. Synth. Rubber Co., JP 74 48.308 (1974); Chem. Abstr: 1975, 82, 155587;
(b) Columbian Carbon Co., GB 1.244.192 (1971); Chem. Abstr: 1972, 76, 34751.
[31] P. Heimbach, G. Wilke, Liebigs Ann. Chem. 1969, 727, 183.
[32] W. Keim, in Comprehensive Organometallic Chemistry (Eds.: G. Wilkinson, F. G. A.
Stone, E. W. Abel), Pergamon, Oxford, 1982, Vol. 8, p. 403.
[33] P. Heimbach,Angew. Chem. 1973,85, 1035;Angew. Chem., Int. Ed. Engl. 1973,12,975.
[34] G. Wilke, J. Polym. Sci. 1959, 38, 45.
[35] P. Heimbach, P. W. Jolly, G. Wilke, Adv. Organomet. Chem. 1970, 8, 29.
[36] E. LeRoy, D. Huchette, A. Mortreux, F. Petit, Nouv. J. Chim. 1980, 4, 173; Chem. Abstr:
1980, 93, 94729.
[37] H.-J. Hey, Ph. D. Thesis, Ruhr-Universitat Bochum, 1969.
[38] U. M. Dzhemilev, L. Y. Gubaidullin, Issle. Obl. Chim. Visokomol.Soedin. Neftekhim
1977, 12.
[39] A. Carbonaro, A. Greco, G. Dall’asta, J. Organomet. Chem. 1965, 20, 177.
[40] R. Baker, Chem. Rev. 1973, 73, 847.
[41] W. Brenner, P. Heimbach, K. J. Ploner, F. Thomel, Liebigs Ann. Chem. 1973, 1882.
[42] W. Brenner, P. Heimbach, Liebigs Ann. Chem. 1975, 660.
[43] K. J. Ploner, P. Heimbach, Liebigs Ann. Chem. 1976, 54.
[44] W. Brenner, P. Heimbach, G. Wilke, Liebigs Ann. Chem. 1969, 727, 194.
[45] P. Heimbach in Katalysatoren, Tenside und Mineraliiladditive (Eds.: J. Falbe, U. Has-
serod), Thieme Verlag, Stuttgart, 1978, p. 111.
[46] P. Heimbach, W. Brenner, K. J. Ploner, F. Thomel, Angew. Chem. 1969, 81, 744; Angew.
Chem., Int. Ed. Engl. 1969, 8, 753.
[47] P. Heimbach, W. Brenner, K. J. Ploner, F. Thomel, Angew. Chem. 1971, 83, 285; Angew.
Chem., Int. Ed. Engl. 1971, 8, 753.
[48] (a) R. Baker, A. H. Copeland, Chem. Soc., Perkin Trans. 1 1977, 2650; (b) R. Baker,
P. C. Bevan, R. C. Cookson, A. H. Copeland, A. D. Gribble, ibid. 1978, 480;
(c) R. Baker, A. H. Copeland, R. C. Cookson, J. Chem. SOC.,Chem. Commun. 1975,
752; (d) R. Baker, M. G. Kelly, ibid. 1980, 307.
[49] P. A. Wender, N. C. Ihle, C. R. D. Coniea, J. Am. Chem. SOC.1988, 110, 5904.
[50] P. A. Wender, T. E. Jenkins, J. Am. Chem. SOC.1989, I l l , 6432.
[51] G. Wilke, Angew. Chem. 1988, 100, 189; Angew. Chem., Int. Ed. Engl. 1988, 27, 185.
[52] A. Myiake, H. Kondo, S. Tokizane, Special Lectures XXIII, Int. Congr: Pure Appl.
Chem. 1971, 6, 201.
[53] (a) P. Heimbach, Angew. Chem. 1973, 85, 1035;Angew. Chem., Int. Ed. Engl. 1973, 12,
975; (b) P. Heimbach, J. Synth. Org. Chem. Jpn. 1973, 31, 299.
 2.3.7 Catalyzed Polymerisation of Epoxy Resins 383

2.3.7 Catalyzed Polymerisation of Epoxy Resins

Manfred Diiring

Epoxy resins may be cured in the manner of polyadditions, i. e., homogeneously

catalyzed by multifunctional amines and isocyanates, or cyclic anhydride, dicyan-
diamide, or biguanide derivatives. On the other hand epoxy resins are also subject
to homopolymerization. The catalysts represent Lewis bases, preferably tertiary
amines, imidazoles, or ureas (the latter exclusively for the dicyandiamide curing)
[I]. For technical processes this epoxy resin activation occurs too abruptly, often
thus a processing becomes difficult as a single component mixture because of the
short pot lives at ambient temperature. Reduction of the nucleophilic reaction of
the imidazole nitrogen by introduction of bulky alkyl or electron-withdrawing
groups causes only minor reactivity at higher temperatures, too. This is in contrast
to the technological requirement for fast curing at relatively low temperatures of
approx. 120 '. Therefore attempts were made to block the nucleophilic initiator
effect at ambient temperature and to release the catalyst at that temperature. In
order to block the nucleophilic curing initiators reversibly, four classes of
so-called thermally latent catalysts were developed:

(1) mechanical encapsulation of the initiators;

(2) salt formation with acids;
(3) Lewis acid base adducts; and
(4) coordination at metal ions or organometallics.

The first two classes of latent epoxy resin curing agents are covered by a multi-
plicity of patents but are applied very little [2]. On the other hand, ammonium
or imidazolium salts of phosphonic or phosphonic acids are often used because
organophosphorus compounds are also reactive flame retardants and are addition-
ally useful in plastics, particularly in epoxy resins (replacement of brominated
epoxy resins) [ 3 ] . Lewis acids such as BF, or BC13 adducts of tertiary amines
(e. g., benzyldimethylamine) cure epoxies to highly crosslinked materials. Be-
cause of the considerable temperature rise during curing, these latent catalysts
are used in admixture with other hardeners, for instance anhydrides. Applications
include casting resins for encapsulation and electrical insulating varnishes or for
lamination and adhesives [l].
If metal ions are used as Lewis acids, various initiator molecules, particularly
imidazoles, are used to bind coordinatively and to inactivate the catalysts at am-
bient temperatures [4]. By variation of the coordinating compounds (coordination
number, number of imidazole ligands, counterion, or central metals) a very effec-
tive fine tuning of the curing parameters (pot times, curing temperature) and thus
an excellent adjustment of new processing technologies for the epoxy resins may
be achieved. Epoxy resins cured by novel metal complexes with imidazole
ligands (CAT resins) have been shown to be superior to standard epoxy resins
cured with aromatic diamines (diaminodiphenylmethane, -sulfone) [ 5 ] with
regard to storage stability and hot/wet and processing behavior. According to
384 2.3 Reactions of Unsaturated Compounds

DSC measurements, the catalytic curing reaction between the thermal latent
complexes I (di( 1-methylimidazole)cobalt(II)dicyanate) and I1 (di( 1-methylimi-
diazole)-bis(dimethyldioximato)cobalt(III)nitrate) and epoxy resins was demon-
strated to be very fast at lower temperatures compared with curing with stoichio-
metric quantities of 4,4'-diaminodiphenylsulfone (Figure 1) [6].

Figure 1. Curing of tetraglycidyl diaminodiphenylmethane with thermally latent catalysts and

4,4'-diaminodiphenyl sulfone.

In addition, a further compression of the polymer network has been observed

by the application of reactive anionic ligands (catalyst I), which leads to an
increase in the glass transition temperatures. These CAT resins are very suitable
for one-pot applications and curing by microwave heating for the manufacture of
agglutinations (grinding wheel), prepregs (ski manufacture), and for composite
materials by resin injection and resin transfer molding technologies. For curing
the CAT resins and the resins with amine Lewis acid adducts, a mixed mecha-
nism of the cationic and anionic polymerization is found, in which the latter
dominates.
A purely cationic curing can be induced by Lewis acids such as A1C13, BF3,
ZnCI2, Tic&, or FeBr3. The cationic polymerization of the epoxy resins has re-
ceived little attention and is mentioned only in connection with photo- or radiation
chemistry initiation.
Only by application of the electron beam technique in connection with cationic
catalysts like triarylsulfonium or diaryliodonium hexafluoroantimonates, hexa-
 References 385

fluorophosphates, or tetrafluoroborates [7] as efficient initiators for the cationic

epoxy resin polymerization has the interest of users been restored. On this basis
a repair kit for airplane and satellite application has recently been presented by
Air Canada [8].

References
[ I ] B. Ellis, Chemistry and Technology of Epoxy Resins, Blackie Academic, London,
1993.
[2] M. Ogata, N. Kinjo, S. Eguchi, T. Urano, T. Kawata, Netsu Kokasei Jushi 1990, 11, 95.
[3] M. LeBras, G. Camino, S. Bourbigot, R. Delobel, Fire Retardancy of Polymers - The
Use of Intumescence, RSC, Cambridge, 1998; St. Sprenger, R. Utz, J. Adv. Mat.
2001, 33, 24.
[4] J. M. Barton, G. J. Buist, I. Hamerton, B. J. Howlin, J. R. Jones, S. Liu, J. Muter: Chem.
1994, 4 , 379; Ruetgerswerke AG, WO 91/13925 (1991).
[5] C.A. May, Epoxy Resins - Chemistry and Technology, Marcel Dekker, New York,
1988.
[6] M. Renner, V. Altstadt, M. Doring, T. Merz, B. Rackers, SAMPE Znt. Techn. Con$ 2000,
32, 619.
[7] J. V. Crivello, Adv. Polym. Sci. 1984, 61, 1 .
[8] V. J. Lopata, D. R. Sidwell, E. Fidgeon, F. Wilson, D. Bernier, R. Loutit, W. Loutit,
Preliminary Test Results for a Type-Trial Repair on Air Canada Airbus Aircrajl
Fleet; 43rd International SAMPE Symposium, 1998; C. J. Janke, G. F. Dorsey, S. J.
Havens, V. J. Lopata, M. A. Meador, Electron Beam Cured Epoxy Resin Composites
For High Temperature Applications, Proceedings of the PPM and Other Propulsion
R&T Conference, NASA Conference Publication 10193, Cleveland, OH, May 1,
1997. Ref. 1A.
 Applied Homogeneous Catalysis with Organometallic
Edited by Boy Cornils & Wolfgang A. Herrmann
© Wiley-VCH Verlag GmbH, 2002

386 2.4 Oxidations

2.4 Oxidations

2.4.1 Oxidation of Olefins to Carbonyl Compounds

(Wacker Process)
Reinhard Jira

2.4.1.1 Historical and Economic Background

After the Second World War the chemical industry at first continued production in
their remaining or reconstructed plants using their pre-war processes. The main
feedstock for aliphatic organic chemistry was acetylene. However, soon people
were considering how this energy-rich and expensive starting material could be
replaced by the much cheaper ethylene which was becoming more and more avail-
able by the cracking of light naphtha derived from crude oil. Therefore, when a
new process for the production of acetaldehyde - a very important intermediate
for the synthesis of Cz, C4, C6, and C, aliphatic organic compounds - through di-
rect oxidation of ethylene was presented by the Consortium fur Elektrochemische
Industrie GmbH, the research organization of Wacker-Chemie [I], it attracted high
interest in the chemical industry and scientific laboratories, the more so when
Moiseev et al. published the synthesis of vinyl acetate by a similar process [2]
(cf. Section 2.4.2).
In retrospect, the catalytic reaction following eq. (1) has promoted recognition
of organometallic homogeneous catalysis in the bulk-chemicals industry; both
hydroformylation (Section 2.1.1) and the Wacker ethylene oxidation are key
steps in industrial homogeneous catalysis.

2.4.1.2 Chemical Background

2.4.1.2.1 Reaction of Ethylene with Palladium Compounds

This process was discovered at the end of 1956 when, in the laboratory of the
Consortium, ethylene together with oxygen and a trace of hydrogen was passed
over a palladium-on-carbon catalyst and the formation of acetaldehyde was ob-
served. Then, it was found that addition of oxidizing metal salts such as cupric
and ferric chlorides increases the yield of acetaldehyde.
The suggestion that palladium plays the essential role in this reaction was
supported by some earlier publications. Phillips [ 3 ] , when passing ethylene
through an aqueous solution of palladium chloride, observed a black precipitate
 2.4.1.2 Chemical Background 387

of palladium metal and the formation of acetaldehyde. A binuclear complex of

ethylene and PdC12 (Structure l),previously synthesized by Kharasch et al. [4],
is immediately decomposed by water into palladium metal, hydrochloric acid,
and acetaldehyde; an ethylene-platinum complex, the so-called Zeise’s salt
K[PtCl,(n-C,H,)], is decomposed analogously at elevated temperature [5].

Thus, it was assumed that the formation of acetaldehyde observed by the

Consortium is based on eq. (2), and it was found to occur almost stoichio-
metrically [ 1,6]. Other palladium salts, such as the sulfate, nitrate, acetate,
etc., react similarly; even salts of other noble metals such as platinum, rhodium,
and ruthenium give acetaldehyde in the same way but at a distinctly reduced
rate.
PdCIp + H&=CH2 + H20 - A0+ Pd + 2HCI (2)

2.4.1.2.2 Oxidation of Olefinic Compounds

to Carbonyl Compounds
Oxidation of ethylene to acetaldehyde by palladium compounds according to eq.
(2) can be applied to other olefins and olefinic compounds with functional groups
[ 1,7]. This is often called the “Wacker reaction”, and occurs regiospecifically. The
carbonyl group is formed at that C-atom of the double bond where the nucleophile
in a Markovnikov-like addition would enter (eq. (3)). Thus, primary olefins give
methyl ketones.

R- + PdC12 + H20 - R
+ Pd + 2HCI (3)
R = alkyl

The corresponding aldehydes are formed only in an amount of a few percent.

Electron-withdrawing groups direct the carbonyl group into the b-position
(eq. (4)).

R&X + PdC12 + H20 - RL X + Pd + 2HCI (4)

R = H, alkyl; X = NOz, CN, COOH, -CH=CH-
388 2.4 Oxidations

In the case of the reaction of a, P-unsaturated carboxylic acids or amides, etc.,

oxidation is followed by decarboxylation. Examples are given in Table 1.

Table 1. Some examples of the oxidation of olefinic compounds with aqueous palladium
chloride solution.
Substrate Intermediate assumed Product
Ethylene Acetaldehyde
Propene Acetone (propionaldehyde)
1- and 2-Butene Butanone (butyraldehyde)
1-0lefins Methyl ketones (aldehydes)
Cyclopentene Cyclopentanone
Cyclohexene C yclohexanone
Styrene Acetophenone (phenylacetaldehyde)
Acrylic acid OHC-CH2-COOH Acetaldehyde
Crotonic acid CH3-CO-CH2-COOH Acetone
Maleic acid HOOC-CO-CH2-COOH Pyruvic acid
1,3-Butadiene Crotonaldehyde [8]
Nitroethylene Nitroacetaldehyde
Acrylonitrile Cyanoacetaldehy de
Ally1 alcohol OHC-CH2-CHZOH Acrolein [9]
Crotonaldehyde CH3-CO-CH2-CHO 1,3,5-Triacetylbenzene

2.4.1.2.3 Catalytic Oxidation of Olefins

Olefin oxidation with an aqueous palladium chloride solution according to
eqs. (2)-(4) occurs stoichiometrically. A catalytic reaction is only possible if
the metallic palladium can be reoxidized immediately. With gaseous oxygen, con-
ditions to oxidize even finely divided palladium black are not optimal. However,
metal salts such as cupric and ferric chlorides, chromates, heteropolyacids of
phosphoric acid with molybdic and vanadic acids, or other oxidants - e. g., ben-
zoquinone is used in kinetic investigations [lo] - are suitable for reoxidation of
the palladium metal. This fact explains the increase of the yield of acetaldehyde
in the first experiments of the Consortium carried out in the presence of cupric
and ferric chlorides, as mentioned above.
This direct oxidation of olefins was discovered by experiments performed in
a heterogeneous phase and consequently in the first pilot plant the reaction was
carried out by passing a mixture of moist ethylene and oxygen over a solid-bed
 2.4.1.3 Kinetics und Mechanism 389

catalyst. Deactivation and problems over the lifetime of the catalyst, however,
forced activity to be turned toward a homogeneous liquid-phase reaction, which
was then exploited for technical use.
For this purpose cupric chloride has been proved as the most suitable oxidant
for palladium metal (eq. (5a)) since cuprous chloride resulting from this reaction
is easily reoxidized by oxygen (eq. (5b)). Now the catalytic cycle is closed; eq. (6)
(equal to eq. (1)) represents a catalytic reaction consisting of single stoichiometric
reactions.
Pd + 2CuC12 -
PdC12 + 2CuCl (54
2CuCl + 2HCI + ’/202

PdC12 / C U C I ~
- 2CUC12 + H20 (5b)
HzC=CH2 + ’/2 0 2 * A 0
(6) = (2) + (5a) + (5b)
AH = - 58.2 kcal (- 221 .I kJ)

For commercial production of acetaldehyde using a mixture of ethylene and

oxygen in a “single-stage’’ process, very pure starting materials are necessary as
outlined in Section 2.4.1.4.
While developing a commercial process - a pilot plant using this “single-stage’’
reaction was already operating - Wacker-Chemie recognized that pure oxygen
would not be available at the site and time of starting up their first plant. The con-
cept was changed and the effort was focused on developing a “two-stage’’process,
reacting ethylene and oxygen separately. In such a version air can be used instead
of pure oxygen. Thus, ethylene is reacted with the aqueous solution of palladium
and cupric chloride according to eq. (7).
PdC12
H2C=CH2 + 2 C U C I ~+ H20 -0 + 2CuCl + 2HCI
(7) = (2) + ( 5 4
This is a stoichiometric reaction with respect to cupric chloride but catalytic
with respect to palladium chloride. The catalyst solution is then reacted with air
in a second step according to eq. (5b). The technical performance is described
in Section 2.4.1.4. The single-stage process was then used by Hoechst AG.
At first glance it seems somewhat strange that cupric ions should oxidize
palladium in the zero oxidation state according to their oxidation potentials [ 1I].
Evidently chloride ions play an essential role because of stabilization of Pd2+and
Cu’ by complexing. Respective thermodynamic considerations are given in [ 121.

2.4.1.3 Kinetics and Mechanism

2.4.1.3.1 Reaction of Ethylene with Palladium Salts

From the first consideration of ethylene oxidation, it was already concluded that
this specific reaction should take place within the coordination sphere of the
390 2.4 Oxidations

palladium central atom. Oxidation of palladium(0) by cupric chloride and of

cuprous chloride by oxygen are predominantly thermodynamic problems which
seem to be widely understood. The following mechanistic considerations are
therefore focused on the reaction of ethylene with palladium chloride.
In order to explain a reaction mechanism, various data are collected from dif-
ferent sources usually ranging from kinetic investigations, consideration of analo-
gous reactions, isolation or trapping of intermediates, stereochemical investi-
gations of the reaction in question or of analogous reactions, etc. Using and
producing such data, it has to be taken into account that disturbing and reac-
tion-blocking influences should be avoided. They can alter kinetics, a course of
reaction, and the reaction mechanism, for instance by covering of intermediate
steps. Thus, kinetic investigations carried out in more dilute solution will usually
show a more detailed feature of the reaction than those carried out with higher
concentrations of the reactants. For our reaction, various and contradictory pro-
posals for a mechanism have been presented. In the following, a critical view
will be attempted.
There is no dissent that the first step of the reaction should be the complexing of
ethylene to give the palladium complex 2 according to eq. (8).
K
[PdC14I2- + H2C=CH2 ==== [(C2H4)PdC13]- + CI- (8)
L

The next step, however is discussed contradictorily. In the first experiments it

was already found that chloride and hydrogen ions inhibit the reaction between
ethylene and palladium chloride [ 1, 10, 131 and it was concluded that an OH-
ion would attack the complexed olefin. This was confirmed by kinetic studies car-
ried out by Moiseev et al. [14-161 and Henry [17, 181, leading to eq. (9) where K
is the equilibrium constant for eq. (8) and k an overall rate constant.

The twofold inhibiting effect of chloride ions according to their inverse square
concentration in eq. (9) is explained through the replacement of a chloride ligand
by the olefin according to eq. (8) followed by replacement of another chloride
ligand by a water molecule according to eq. (10):

[(C2H4)PdC13]- + H20 * [(C2H4)PdC12(H20)] + CI-

(10)
2 3
Dissociation of acidic hydrogen ion according to eq. (1 1) explains the inhibiting
influence of acids.

[(C2H4)PdC12(H20)] T=== [(C2H4)PdCI2(OH)]- + H+

(11)
3 4
 2.4.1.3 Kinetics and Mechanism 391

The next step (eq. (12)) is the insertion reaction forming a o-bonded P-hydro-
xyethylpalladium species (Structure 5).

[(C2H4)PdCI2(OH)]- + [HOCH2CH2PdC12]- (12)

4 5

This reaction has been considered a cis-ligand insertion reaction with the OH-
ligand attacking the Tc-bonded olefin, although the interacting ligands in inter-
mediate 4 are assumed to be trans to each other. In fact, in complexes like 2,
e. g., in the platinum complex, the rc-bonded ethylene ligand weakens the
chloro-metal bond in the trans position, so in aqueous acidic solution it is easily
substituted by a water molecule from which a hydrogen ion dissociates [19].
However, if eq. (12) should in fact be a ligand insertion reaction, the interacting
ligands should be positioned cis to each other. Evidence for a trans-cis isomeri-
zation of complex 4 was revealed by a more detailed kinetic study of the reaction
of ethylene with aqueous palladium chloride. It could be demonstrated that H’
and C1- ions not only impede but also accelerate this reaction. From these studies
an empirical rate equation (13) was derived [20], which transmutes into the rate
equation (9) at higher H’ and C1- concentrations when the term b can be neg-
lected. The accelerating effect of H+ and C1- ions predominates at their lower con-
centrations.

- -d[C2H41
- - a[H+][CI-]
dt b + [H+]2[CI-]3

According to eqs. (14) and (15) this kinetic behavior can be explained through
another replacement of a chloro ligand by a water molecule which is now in the
cis position relative to the olefin, followed by the dissociation of a H’ ion, while
the accelerating effect is due to the replacement of the OH- ligand in the trans
position by a C1- ion accomplishing the trans-cis isomerization of the OH-
ligand.

+ H20 T== + H+ + CI-

HO ’ Pd
\OH
(14)

4 6

+ H+ + CI- ==== + H20 (15)

6 7
392 2.4 Oxidations

Complex 7 now possesses all the prerequisites for cis-ligand insertion reaction:
a close (cis) position to the interacting ligands, and activation of the n-bonded ole-
fin by weakening the olefin-metal n-bond and the olefin rotation barrier through
the trans effect of the trans-chloro ligand across the complex.
Olefin rotation around its coordination axis in such complexes [19, 201, and
also a weakening of the ethylene-platinum bond in aqueous solution of Zeise’s
salt with increasing C1- concentration [ 181, have been described. Under the
premise of this sequence of reactions, a rate equation quite similar to eq. (13)
for constant Pd and C2H4concentrations could be derived (see [12, pp. 18-19]).
This attempt used the following summarized reactions: Equation (17) is a sum-
marized reaction including the rate-determining step.

[(C2H4)CIPd(OH)2]- + CI- + H+ % cis-[(C2H4)C12PdOH]- + H20 (15a)

K
[PdCI4l2- + 2 H20 + H2C=CH2 & [(C2H4)CIPd(OH)2]- + 3 CI- + 2 H+

(16) = (8) + (10) + (11) + (14)

The rate equation (18) adopts the form:

Due to the experimental finding that in hydrolysis of Kharasch’s ethylene-

palladium complex with D 2 0 the resulting acetaldehyde does not contain any
deuterium [20], intermediate 5 now undergoes a hydride transfer according to

r]
eqs. (19) and (20).
-
[ HO- PdC12]- == +PdHC12 ] (19)
5 8

[“o] --PdHCI2]-

8
= [JPdCI2

9
1-
For the last step a reductive elimination, whether through a carbonium ion
intermediate by heterolysis [12] or by a concerted reaction [23] forming the
hydrate of acetaldehyde, is more a philosophical question (eqs. (21) and (22)).
Both routes would explain the findings of Moiseev and Vargaftik [22] that in
 2.4.1.3 Kinetics and Mechanism 393

C2H50Dor CH,COOD instead of the aqueous medium the acetal or ethylidene

diacetate, respectively, is formed, neither of them containing any deuterium (see
also Section 2.4.2).

- *OH
H
+ [PdCI$

i 1
0
// + H+ Pd + 2CI-

1A OH

PdC12(0H)
2-
- 4 0 H + Pd
OH
+ 2CI-

Heck’s route (eq. (23)) [25] seems to be less likely.

[ P”,,Cl2]
9

Which step of this sequence of reactions is rate-determining? From a low iso-

tope effect when comparing the rates with C2H4 and C2D4 (i. e. k(C2H4)/k(C2D4)=
1.07), Henry [17] concluded that it should be a reaction prior to the cleavage of
a C-H bond in the hydride transfer which is the insertion reaction (12). However,
a low isotope effect can also be expected if the hydride transfer according eqs.
(19), (20) is interpreted as oscillation of the Pd-H between the two carbon
atoms. The hydride species 8 would then be a transition state-like intermediate
of high energy. Rate determining is then suggested [12] for reaction (21) or
(22) resp. which bring about the separation of charges.
Anyway, both sides attribute the rate-determining step to the catalytic palla-
dium-supported interaction of the reactants after the pre-equilibria representing
their activation.
There is another kinetic study carried out by Moiseev et al. [26, 271. They
extended eq. (9) by another term according to eq. (24) and therefore proposed a
binuclear Pd intermediate. They claim that at low [PdCl4I2-and low C1- concen-
trations the second term would predominate. It is noteworthy that of the [Cl-]
concentration in the denominator of the second term is raised to the power of
3, which is also evident in eq. (13). These findings have not been included in
394 2.4 Oxidations

the mechanistic considerations above because they bring no new facts to the
metamorphosis of the complexed olefin until its liberation as acetaldehyde.

A review on kinetic investigations and proposals for the mechanism is given in

[28, p. 771, and another thorough discussion in [29]. Kinetic investigations of
ethylene oxidation in chloride-free systems with phosphomolybdovanadic hetero-
polyacid as oxidant have been carried out by Matveev et al. [30, 311.
cis-Ligand insertion (cis-hydroxypalladation) did not remain without contradic-
tion.

In a stereochemical study E-(ethylene)-d2(C2H2D2)[32] was reacted with pal-

ladium chloride and cupric chloride under extreme conditions, i. e., extremely
high chloride ion concentration as cupric and lithium chlorides. Under such
conditions 2-chloroethanol was formed as the main product from ethylene, be-
sides some acetaldehyde [33] (see Section 2.4.1.5.1); this is not the normal
product of the Wacker reaction. In the above study the formation of cis-1,2-
dideuterioethylene oxide, evidently via threo- 1,2-dideuterio-2-chloroethanol,
suggests trans addition of water (anti-hydroxypalladation).
In another study [34] bis-[(cis-l,2-dideuterioethylene)dichloropalladium]
was reacted with carbon monoxide in aqueous acetonitrile to form trans-
2,3-dideuterio-j?-propiolactone according to eq. (25) via a suggested trans-
hydroxypalladation intermediate.

CH3CN * H D U H D
'12 [(:)==(:)PdCh] + H20 + CO + Pd + 2HCI (25)
2 0
In a third study, 1,2-dimethylcyclohexa-1,4-diene was reacted with bis(aceto-
nitrile) palladium dichloride in aqueous acetone to form predominantly a
trans-n-allylpalladium complex as well as some of the Wacker oxidation
product 3,4-dimethylcyclohex-3-en-l-one (eq. (26)) [35]:

Assuming the same intermediate for both products, the oxypalladation step
should be trans orientated.
MO investigations haven been carried out. In one of them [36], it is concluded
that the OH-nucleophile would attack the complexed olefin within the coordi-
nation sphere of the complex, i. e., cis. From two others [37, 381, attack from
the outer side has been derived, i. e., trans.
 2.4.1.3 Kinetics and Mechanism 395

However, while the kinetics according to eq. (9) have been included in the dis-
cussion [32] concluding that they would be valid for both the cis and trans oxy-
palladation reactions (and accordingly a slight variant for the mechanism had been
proposed), in none of the above papers have the kinetic findings according to eq.
(13) [20] and the conclusions which have been drawn from them [12, 201 been
considered. In the above experimental studies unsuitable model reactions have
been used.
In case (1) the chloride ion concentration was extremly high, which can prevent
the formation of a cis-hydroxyethylene-palladium species like 6 or 7. Accordingly
the reaction takes place only under pressure and high temperature, or as in this
paper at a reaction time of 20-40 h. Even the product was not the normal Wacker
product (acetaldehyde), but 2-chloroethanol.
In case (2) the reaction was carried out in water-poor acetonitrile in the presence
of carbon monoxide both complexing to the palladium and also able to prevent the
formation of intermediates like 6 or 7.
In case (3) it cannot be excluded that the intermediate olefin complex would be
a chelate with both olefinic bonds of the 1,4-cyclohexadiene coordinated to the
palladium, and the oxypalladation product is in fact expected to be trans orien-
tated as rotation of the double bond is blocked as with analogous complexes of
cyclic diolefins such as 1,5-~yclooctadiene,dicyclopentadiene, norbornadiene,
etc. From these, stable trans-oxymetallation products can be obtained [3931];
others are listed in [12, Table IV].
In case (4) for the MO calculations, intermediates like 7 are not considered.
As mentioned at the beginning of this section, both kinetics and reaction me-
chanism are dependent on the reaction conditions and the model reactions used.
For the rate equation (13), no better interpretation than a cis migration for the
hydroxypalladation has been given so far. The cases (1) to (3) show that when
the coordination sites of the palladium are blocked by C1- (high C1- ion concen-
tration), CO or sterically the attack of the OH- (or H20) will be trans. The fact that
in Wacker-type reactions both mechanisms, cis and trans attack, are possible is
also demonstrated by the transvinylation reaction (see Section 3.3.14). This is
supported by a recent study by Henry and co-workers [42]. They showed with
chiral allylic alcohols that the stereochemistry of exchange reactions with hydroxy
and methoxy nucleophiles are different at high and low C1- ion concentrations.
Accordingly they concluded that a syn (cis) addition occurs at low and an anti
(trans) addition at high ( > 2 mol dm-3) C1- ion concentration, in accordance
with our proposal for the mechanism of the Wacker reaction.

2.4.1.3.2 Olefin Oxidation in the Presence

of Cupric Chloride
Kinetic investigations have also been carried out for the reaction in the presence of
cupric chloride, simulating the technical reactions according to eqs. (7) and (6).
Evidently copper ions do not influence the reaction rate to a noticeable extent.
 +4t
396 2.4 Oxidations

Ratio :cu

1.6:l
7.7:1

1.8:1

Tc

0.9 0.8 0.7 C

c u2+
CUtotal

1.5

Ia
0.5

C 0.8 0.7 0.6 0.5

cu2+
CUtotal

Figure 1. Relation between pH value and the rate of the reaction of ethylene with aqueous
PdC12 solutions containing CuCl,.
 2.4.1.4 Technical Applications (Wacker-Hoechst Processes) 397

In fact kinetics substantially follow the rate equation (9) given by Henry and Moi-
seev, which is valid in the presence of a high chloride ion concentration. Thus, rate
equations for ethylene (eq. (27)) [43] and for propylene (eq. (28)) [44] have been
published. In another kinetic study [45] [28, p. 871 a two-term rate equation has
been derived with a linear influence of the copper salt and an influence of the
chloride ions only to the power of -1, probably showing a kind of compensation
for the diverging effects of copper and chloride ions. The two-term equation indi-
cates an oligonuclear Pd-Cu cluster intermediate, which might be responsible for
keeping Pd in the oxidation state Pd" by ligand transfer oxidation (see also [12, p.
291). Except for the fact that for the technical reaction the same influences are pre-
sent as for the basic reaction, which is not surprising, these rate expressions are of
minor value for finding out optimal conditions for the technical procedure. From
eq. (7) written in the form of eq. (7a), if complexing of C1- with the cuprous ions
is neglected and copper ions in the oxidation state Cur or Cu" do not influence the
reaction rate, only the concentration of H' ions is changed when reaction (7) is
proceeding. The technical catalyst contains fewer chloride ions than required
for the stoichiometric ratio in CuCI2, which is CVCu = 2: 1. In this case Cu" exists
partly as copper oxychloride. An insoluble form of it has the composition
[Cu2(0H)3C11.

PdCl
CH*=CH2 + 2Cu2+ + H20 3 bo
+ 2cu+ + 2H+ (74

Comparing the reaction rate, i.e. ethylene consumption with the pH value, both
plotted against the mole ratio ([Cu"]/[Cu'] + [Cu"]), i.e., the degree of oxidation of
the catalyst solution, it has been shown that a reduction in the reaction rate and the
pH value occurs at the same degree of oxidation, depending on the CUCu ratio
(Figure 1). This point is in fact consistent with the neutralization of the copper
oxychloride while the reaction according to eq. (7) proceeds [6, 12, 13, 461,
and is very important for the operation of the Wacker process (see Section
2.4.1.4.1).

2.4.1.4 Technical Applications (Wacker-Hoechst Processes)

2.4.1.4.1 Acetaldehyde from Ethylene

After its discovery this process attracted the highest industrial interest and many
plants have been erected in industrial countries all over the world. It replaced
processes starting from acetylene or ethanol almost completely. The process is
operated in two versions, both in a homogeneous phase [47].
398 2.4 Oxidations

exhaust
gas light ends

I - HO
,

product
acetaldehvde

crude
aldehyde
(1 0 %)
heavy
ends

Figure 2. Acetaldehyde from ethylene, single-stage process: (a) reactor, (b) separating vessel,
(c) cooler, (d) scrubber, (e) crude aldehyde tank, (f) light ends distillation,
(8) condenser, (h) purification column, (i) regeneration.

In the single-stage process (Figure 2) a mixture of ethylene and oxygen is

passed through an aqueous solution of copper chloride and palladium chloride
placed in a towerlike reactor (a). Acetaldehyde is formed according to eq. (6).
In order to avoid an explosive mixture of ethylene and oxygen, ethylene is used
in stoichiometric excess over oxygen, so unreacted ethylene leaves the reactor to-
gether with acetaldehyde formed, cooled in (c), and separated by scrubbing with
water in (d). Ethylene is pumped back to the reactor after being supplied with
fresh ethylene. From the cycle-gas a small amount is withdrawn to avoid accumu-
lation of inert gases and gaseous by-products. High-purity feed gases have to be
used. Crude acetaldehyde is collected in tank (e).
In the two-stuge process (Figure 3), ethylene and oxygen are reacted separately
in separate reactors (a, c). First ethylene is reacted stoichiometrically in (a) with
the catalyst solution, reducing cupric to cuprous chloride according to eq. (7).
In the second stage (c), cuprous chloride is reoxidized by oxygen to cupric chlo-
ride according to eq. (5b).
As both gases are reacted separately, their purity need not be high, so air is
usually used instead of pure oxygen. A procedure utilizing a feed-gas with low
ethylene content has been developed, but a commercial plant has not been oper-
ated so far. The reaction is carried out at about 10 bar, a pressure higher than in the
single-stage process. Acetaldehyde is separated from the catalyst solution by
flashing the pressure to normal (0.1 MPa) in (b) while an acetaldehyde-water mix-
ture is evaporated, then accumulated utilizing the reaction heat in the crude acet-
aldehyde column (e), and collected in tank (g). The catalyst is cycled by a pump.
Exhaust air and gas are scrubbed with water in (h).
For both processes a purification section now follows involving several frac-
tional distillation steps. The yield in both processes is similar, ca. 95 %. Also,
 2.4. I .4 Technical Applications (Wacker-Hoechst Processes) 399

exhaust exhaust
I air gas
light
ends product

I I

a t
I I I

I
u iaste
water

air

Figure 3. Acetaldehyde from ethylene, two-stage process: (a) reactor, (b) flash tower,
(c) oxidation reactor, (d) exhaust-air separator, (e) crude aldehyde column,
(0process water tank, (g) crude aldehyde container, (h) scrubbers for exhaust
air and gas, (i) light ends distillation, (k) condenser, (1) purification column,
(m) regeneration.

gaseous and higher-boiling by-products are the same. Gaseous products are
C02, methyl chloride and ethyl chloride. Environmental regulations require the
removal of the chlorinated by-products from the offstreams; this is efficiently
carried out by catalytic burning, recovering hydrochloric acid. Higher-boiling
by-products are acetic acid, chlorinated acetaldehydes, oxalic acid, and others.
Chlorination is a side reaction caused by cupric chloride, for instance according
to eq. (29).

Monochloroacetaldehyde is a valuable intermediate for the synthesis of orga-

nics. Normally such chlorinated products are burnt thermally or decomposed by
alkali; others are also degraded biologically. Oxalic acid forms insoluble copper
oxalate. It is thermally decomposed continuously by heating a small sidestream
of the catalyst according to eq. (30).

cuc204 + CUCl2 -
AT 2CuCl + 2cop (30)

Other organics such as chlorinated or resinous products are partly decomposed

during normal operation or in this regeneration step, (i) or (m) respectively. Thus,
the catalyst solution shows a kind of self-cleaning behavior. As chlorinated prod-
ucts are removed during the purification of acetaldehyde, a corresponding amount
400 2.4 Oxidations

of chlorine has to be supplied to the catalyst in the form of hydrochloric acid, thus
controlling the chloride ion concentration of the catalyst also.
In order to provide a high reaction rate, a chloride ion concentration is chosen
which corresponds to a CI/Cu ratio less than 2:1 as outlined above. If for a two-
stage catalyst it lies between 1.6 and 1.7, the catalyst is reduced in one cycle to
a degree of oxidation ([Cu2+]/[Cu2+]+ [Cu']) of 0.6 to 0.7. Oxidation is carried
out in one cycle up to a degree of oxidation of 1.9. In the single-stage process oxi-
dation and reduction occur simultaneously. The catalyst solution is reduced to a
stationary degree of oxidation where both reactions take place at an equal rate.
This degree of oxidation is also dependent on the CYCu ratio.
In both cases the catalyst cannot be reduced to a lower degree of oxidation
since trouble will arise due to precipitation of cuprous chloride. Even the palla-
dium salt concentration which can be kept in solution depends on the degree
of oxidation of the catalyst. At lower degrees of oxidation the concentration
decreases due to removal from the catalyst as metallic palladium. Due to the
high corrosive ability of the catalyst solution, titanium is used as construction
material for all catalyst-contaning equipment. The reactor for the single-stage
process is usually resin-(or ceramic)-lined.

2.4.1.4.2 Acetone from Propene

Several plants have been built operating according to the two-stage technology
(Figure 4) [48, 491 quite analogously to the acetaldehyde process described
above, with air as oxidant and a catalyst cycle. An important by-product in ace-
tone manufacture is propionaldehyde. which is separated by extractive distillation

IIi.
propion-
aldehyde

C
L light ends

exhaust

<+j
-I rf
propene
-water

t
Figure 4. Acetone by direct oxidation of propene: (a) reactor (oxygen), (b) separator,
(c) reactor (propene), (d) flash column, (e) light ends distillation, (0acetone
purification.
 2.4.1.4 Technical Applications (Wacker-Hoechst Processes) 40 1

(the extractant is water) and used as feedstock for organic syntheses. Chlorinated
by-products have also to be removed and copper oxalate has to be decomposed in
a regeneration step, as in the acetaldehyde process. The process has been devel-
oped by Hoechst AG.

2.4.1.4.3 Methyl Ethyl Ketone (Butanone)

from 1- and 2-Butene
Both n-olefins give mainly butanone. From 1-butene some butyraldehyde (buta-
nal) is obtained, but 3-chlorobutanone is formed as the main secondary product,
to a particularly high extent [49]. Evidently chlorination by cupric chloride anal-
ogously to eq. (30) is particularly favored at the secondary C-atom. In order to
commercialize this process an outlet for this product has to be found, e.g., in
the synthesis of organics. In this field Wacker-Chemie has been quite successful,
so, despite the fact that no commercial plant for butanone has been erected, this
company now produces 3-chlorobutanone separately through chlorination of
butanone with cupric chloride. For the pilot plant the two-stage technology
was used.

2.4.1.4.4 Olefin Oxidation with Chloride-Free

or Low-Chloride Catalysts
In order to avoid a high amount of chlorinated by-products in butene oxidation,
the Japanese Maruzen Oil Co. developed a catalyst which uses ferric sulphate
as oxidant [50].
Catalytica Associates uses heteropolyoxoacids [5 I] such as H3PMo6V6040as
oxidants; this was first described by Matveev et al. [30] for ethylene and by
Davison et al. [52] for butene oxidation. Catalytica claims this catalyst for the
production of acetaldehyde, acetone, and methyl ethyl ketone, as well as for
higher ketones, and furthermore that it can be used in unmodified Wacker
two-stage plants.
Both catalysts seem to need a small amount of chloride ions as a vehicle for the
reoxidation of palladium.
Numerous patents on usage of such catalysts for olefin oxidation have been
filed by the Japanese companies Maruzen Oil Co., Ltd. and Idemitsu Kosan
Co., Ltd. To the knowledge of the author neither Maruzen and Idemitsu nor
Catalytica are operating their respective plants commercially.
As another possible strategy to avoid high chloride ion concentration electro-
chemical oxidation has been claimed [53, 541.
402 2.4 Oxidations

2.4.1.5 Application of the Olefin Oxidation

to Organic Syntheses
2.4.1.5.1 Oxidative Reactions not Leading
to Carbonyl Compounds
Acetoxylations are described in Section 3.3.14.
Glycol derivatives, e.g., 2-chloroethanol (eq. (31)) are to a small extent by-
products in the technical olefin oxidation. With a very high concentration (ca.
5 m o m ) of cupric chloride and high pressure, 2-chloroethanol is the main product
of ethylene oxidations, besides some acetaldehyde [33]. Cupric chloride is essen-
tial. In its absence, in spite of a high chloride ion concentration absolutely no
2-chloroethanol is obtained. It is assumed that analogously to acetaldehyde for-
mation a b-hydroxyethyl species bonded to a bi- or oligo-Pd-Cu cluster is an
intermediate from which 2-chloroethanol is liberated by reductive elimination.

CH2=CH2 + 2CuC12 + H20 -

PdC12
CI *OH + 2 CuCl + HCI (3 1)

2-Chloroethanol is also formed from ethylene in the presence of pyridine and

necessarily cupric chloride even with low chloride ion concentration [55], whereas
in the absence of CuC12 acetaldehyde is the sole product. With chiral amines and
phosphines as ligands instead of pyridine, optically active chlorohydrins can be
obtained from higher a-olefins [56, 571.

2.4.1.5.2 Oxidation of Olefinic Compounds

As briefly mentioned in Section 2.4.1.2.2, the “Wacker reaction” occurs regio-
specifically. In recent years it has been used widely for the synthesis of carbonyl
compounds, even as a dinstinct step in multistep syntheses of organics and natural
products. The reaction is carried out stoichiometrically as well as catalytically.
Apart from the few examples mentioned, others may be found by reference to re-
view articles or monographs [12, 29, 58-62]. Since catalytic oxidation of higher,
functional, and cyclic olefinic compounds with PdC12 in the presence of cupric
chloride often results in high amounts of chlorinated by- products, chlorine-free
oxidants such as ferric sulphate [ 1, 481, heteropolyacids such as “H3PMo6V6040)’
[30, 51, 52, 63, 641, benzoquinone [2], and others can be used in order to avoid
such chlorinating reactions.
A heterogenized PdS04-VOS04-H2S04-on-coal catalyst has been described
[65] for the oxidation of I-butene to butanone with oxygen, as well as a similar
one consisting of PdC12-V205 on y-A1203 for the oxidation again of 1-butene
[66] and of styrene to benzaldehyde, acetophenone, and trans-cinnamaldehyde
[67]. Tsuji found an effective system with palladium chloridekuprous chloride-
treated with oxygen [61, 62, 681. t-Butyl hydroperoxide or hydrogen peroxide
together with palladium carboxylate is used by Mimoun et al. [69, 701 for the
 References 403

oxidation of terminal olefins (eq. (32)) and by Tsuji et al. [71] for the oxidation
of a,a-unsaturated esters and ketones to b-ketoesters and 1,3-diketones, respec-
tively.

F3CC02Pd00But + + F ~ C C O ~ P ~ O B+U ‘ Jl/v (32)

Quite a surprising reaction has recently been reported [74]. With a catalyst of
palladium metal on carbon in aqueous phase, propene is oxidized with oxygen
to give acrylic acid, probably via ally1 alcohol in a allylic-type oxidation (for
allylic oxidation see Section 3.3.14). In the presence of chloride or oxidants the
normal Wacker-type reaction product acetone arises.

2.4.1.5.3 Future Prospects

Palladium reagents have been proved most variable and useful in organic syn-
thesis and it may be expected that this progress has not yet come to an end.
Among the different synthetic reaction types, acetoxylation has gained particu-
lar importance in preparative as well as in technical application (see Section
3.3.14).
The future of the commercial acetaldehyde processes mainly depends on the
availability of cheap ethylene. Acetaldehyde has been replaced as a precursor
for 2-ethylhexanol (“aldol route”) or acetic acid (via oxidation; cf. Sections
2.1.2.1 and 2.4.4). New processes for the manufacture of acetic acid are the
Monsanto process (carbonylation of methanol, cf. Section 2.1.2.1). the Showa
Denko one-step gas-phase oxidation of ethylene with a Pd-heteropolyacid cata-
lyst [75, 761, and Wacker butene oxidation [77]. Other outlets for acetaldehyde
such as pentaerythritol and pyridines cannot fill the large world production
capacities. Only the present low price of ethylene keeps the Wacker process
still attractive.

References
[la] Consortium fur Elektrochemische Industrie (J. Smidt, W. Hafner, J. Sedlmeier, R. Jira,
R. Riittinger), DE 1.049.845 (1959)
[lb] J. Smidt, W. Hafner, R. Jira, J. Sedlmeier, R. Sieber, R. Riittinger, H. Kojer, Angew.
Chem. 1959, 71, 176.
[2] I. 1. Moiseev, M. N. Vargaftik, Y. K. Syrkin, Dokl. Akad. Nauk SSSR 1960, 133, 377.
[3] F. C. Phillips, Am. Chem. J . 1894, 16, 255.
[4] M. S. Kharasch, R. C. Seyler, F. R. Mayo, J. Am. Chem. SOC. 1938, 60, 882.
[5] J. S. Anderson, J. Chem. Soc. II, 1934, 971.
[6] J. Smidt, W. Hafner, R. Jim, R. Sieber, J. Sedlmeier, A. Sabel, Angew. Chem. 1962, 74,
93; Angew. Chem. Int. Ed. Engl. 1962, I , 80.
[7] J. Smidt, R. Sieber, Angew. Chem. 1959, 71, 626.
404 2.4 Oxidations

[8] Many Pd"-catalyzed 1,4-addition reactions to conjugated dienes used for organic syn-
theses are described by J.-E. Backvall and co-workers, e. g., A.M. CastaAo, B. A. Person,
J.-E. Backvall, Chem. Eur: J. 1997, 3, 482 and references therein.
[9] R. Jira, Tetrahedron Lett. 1991, 17, 1225.
[lo] M.N. Vargaftik, 1.1. Moiseev, Y. K. Syrkin, Dokl. Akad. Nauk SSSR, 1962, 147, 399.
[ 111 W. M. Latimer, Oxidation Potentials, 2nd ed., Prentice Hall, Englewood Cliffs, NJ, 1959.
[12] R. Jira, W. Freiesleben, in Organornetallic Reactions, Vol. 3 (Eds.: E. Becker, M. Tsut-
mi), John Wiley, New York, 1972.
[I31 J. Smidt, Chem. Ind. (London), 1962, 54.
[14] 1.1. Moiseev, M.N. Vargaftik, Y. K. Syrkin, Dokl. Akad. Nauk SSSR 1963, 153, 140.
[15] M. N. Vargaftik, I. I. Moiseev, Y. K. Syrkin, Dokl. Akad. Nauk SSSR 1962, 147, 399.
[I61 M. N. Vargaftik, I. I. Moiseev, Y. K. Syrkin, Izv. Akad. Nauk, Otd. Khim. Nauk SSSR
1963, 1147.
[17] P. M. Henry, J. Am. Chem. Soc. 1964, 86, 3246.
1181 P.M. Henry, J. Am. Chem. Soc. 1966, 88, 1595.
[19] I. Leden, J. Chatt, J. Chem. Soc. 1955, 2936.
[20] R. Jira, J. Sedlmeier, J. Smidt, Liebigs Ann. Chem. 1966, 693, 99.
[21] A.R. Brause, F. Kaplan, M. Orchin, J. Am. Chem. SOC. 1967, 89, 2661.
[22] R. Cramer, J. Am. Chem. Soc. 1964, 86, 217.
[23] R. Jira, in Methodicum Chimicum (Ed.: F. Korte), Georg Thieme, Stuttgart, 1975, Vol. 5,
p. 286.
[24] I. I. Moiseev, M. N. Vargaftik, lzv. Akad. Nauk SSSR, Ser: Khim. 1965, 759.
[25] R.F. Heck, Hercules Chem. 1968, 57, 12.
[26] I. I. Moiseev, M. N. Vargaftik, S. V. Pestrikov, 0.G. Levanda, T. N. Romanova, Dokl.
Akud. Nauk SSSR 1966, 171, 1365.
[27] I. I. Moiseev, O.G. Levanda, M. N. Vargaftik, J. Am. Chem. Soc. 1976, 96, 1003.
[28] M.M. Taqui Khan, A.E. Martell, in Homogeneous Catalysis by Metal Complexes,
Academic Press, New York and London, 1974.
[29] P. M. Henry, in Palladium Catalyzed Oxidation of Hydrocarbons, D. Reidel, Dordrecht,
1980, pp. 41-223.
[30] K. I. Matveev, E. G. Zhizhina, N. B. Shitova, L. I. Kuznetsova, Kinet. Katal. 1977, 18,
380; Kinet. Katal., Engl. Transl. 1977, 18, 320.
[31] K. I. Matveev, Kinet. Katal. 1977, 18, 862, Kinet. Katal., Engl. Transl. 1977, 18, 716.
[32] J. E. Backvall, B. Akermark, S. 0. Ljunggren, J. Am. Chem. Soc. 1979, 101, 2411.
[33] H. Stangl, R. Jira, Tetrahedron Lett. 1970, 3589.
[34] J. K. Stille, R. Divakaruni, J. Organomet. Chem. 1979, 169, 239.
[35] B. Akermark, B. C. Soderberg, S. S. Hall, Organometallics 1987, 6, 2608.
[36] D. R. Armstrong, R. Fortune, P. G. Perkins, J. Catal. 1976, 45, 339.
[37] J. E. Backvall, E. E. Bjorkman, L. Pettersson, P. Siegbahn, J. Am. Chem. Soc. 1984, 106,
4369.
[38] H. Fujimoto, T. Yamasaki, J. Am. Chem. Soc. 1986, 108, 578.
[39] J. Chatt, L. M. Vallarino, L. M. Venanzi, J. Chem. Soc. 1957, 3413.
[40] C. B. Anderson, B. J. Burreson, J. Organomet. Chem. 1967, 7, 181.
[41] J. K. Stille, R.A. Morgan, J. Am. Chem. Soc. 1966, 88, 5135.
[42] 0. Hamed, P.M. Henry, C. Thompson, J. Org. Chem. 1999, 64, 7745 and references
therein.
[43] S. Kiryu, T. Shiba, Lecture Annual Meeting Japan Petr: Inst., Sept. 1961, Tokyo (cited
in [44]).
[44] T. Dozono, T. Shiba, Bull. Japan Petr: Inst. 1963, 5, 8 (in English).
[45] K. I. Matveev, I. F. Bukhtoyarov, N. N. Shul'ts, 0.A. Emel'yanova, Kinet. Katal. 1964,
5, 649; Kinet. Katal., Engl. Transl. 1964, 5, 572.
 References 405

[46] R. Jira, Acetaldehyde, in Ethylene and its Industrial Derivatives (Ed.: S. A. Miller),
Ernest Benn, London, 1969, Chapter 8.
[47] R. Jira, Acetaldehyde, in Ullmann’s Encycl. Ind. Chem. 5th ed. 1985, Vol. A l , p. 31.
[48] J. Wollner, E. Weber, Ullmanns Encycl. Techn. Chem. 4th ed., 1974, Vol. 7 , p. 31.
[49] J. Smidt, H. Krekeler, Hydrocarbon Process. Pet. Refiner 1963, 42, 149.
[SO] Maruzen Oil Co. (H. Hasegawa, M. Triuchijima), DE-OS 1.812.721 (1971),
GB 1.240.889 (1971).
[51] J. H. Grate, D. R. Hamm, S. Mahayan, Mol. Eng. 1993,3, 205-229; Chem. Ind. (Dekker)
1994, 53, 213.
[52] S. F. Davison, B.E. Mann, P.M. Maitlis, J. Chem. Soc., Dalton Trans. 1984, 1223.
[53] T. Inokuchi, L. Ping, F. Hamaue; M. Izawa, S. Torii, Chem. Lett. 1994, 121.
(541 Nippon Zeon Co., Ltd. (J. Tsuji), JP 63.192.736 (1987).
[55] J.W. Francis, P.M. Henry, J. Mol. Catal. A: Chem. 1995, 99, 77.
[56] A. El-Qisairi, 0. Hamed, P.M. Henry, J. Org. Chem. 1998, 63, 2790.
1571 A. El-Qisairi, P.M. Henry, J. Organornet. Chem. 2000, 603, 50.
[58] P. M. Maitlis, The Organic Chemistry of Palladium, Vols. I and 11, Academic Press, New
York, 1971.
[59] J. Tsuji, Organic Synthesis with Palladium Compounds, Springer-Verlag, Berlin, 1980.
[60] J. Tsuji, Synthesis 1984 (3,369.
[61] J. Tsuji, Pure Appl. Chem. 1981, 53, 2371.
[62] J. Tsuji, Palladium Reagents, in Innovation in Organic Synthesis, John Wiley, New York,
1996.
[63] Anon., Proc. Eng. (London) 1992, 73, 21.
[64] H. Ogawa, H. Fujinami, K. Taya, S. Teratani, J. Chem. Soc., Chem. Commun. 1981,
1274.
[65] Y. Izumi, Y. Fujii, K. Urabe, J. Catal. 1984, 85, 284.
[66] E. van der Heide, J. A. M. Ammerlaan, A. W. Genitsen, J. J. F. Scholten, J. Mol. Catal.
1989, 55, 320.
[67] E. van der Heide, J. Schenk, A. W. Gemtsen, J. J. F. Scholten, Rec. Trav. Chim. Pays-Bas
1990, 109, 93.
[68] J. Tsuji, I. Shimizu, K. Yamamoto, Tetrahedron Lett. 1976, 2975.
[69] M. Roussel, H. Mimoun, J. Org. Chem. 1980, 45, 5387.
[70] H. Mimoun, Pure Appl. Chem. 1981, 53, 2389.
[71] J. Tsuji, H. Nagashima, K. Hori, Chem. Lett. 1980, 257.
[72] S. Tilloy, F. Bertoux, A. Mortreux, E. Monflier, Catalysis Today 1999, 48, 245.
[73] G.-J. ten Brink, I. W. C. E. Arends, G. Papadogianakis, R. A. Sheldon, Chem. Commun.
1998, 2359 and references therein.
[74] J. E. Lyons, G. Suld, C.-Y. Hsu, Chem. Ind. (Dekker) (Catal. Org. React.) 1988, 33, 1.
[75] I am indebted to Dr. Akio Mitsutani, Nippon, Chemtec Consulting Inc., 665-0022 Takar-
asuka City, Nogami 3-chome, 11-10, Japan, for making available to me the relevant
chapters of the company’s evaluation reports.
[76] K. Sano, H. Uchida, Catalysts & Catalysis (Japan), 1999, 41, 290.
[77] Europ. Chem. News 1998, 9; Consortium fur Elektrochem. Industrie (C. Riidinger,
H.-J. Eberle), DE-OS 19.823.052 A 1 (1999).
406 2.4 Oxidations

2.4.2 Homogeneous Oxidative Acetoxylation of Alkenes

Ilya I. Moiseev, Michael N. Vargafik

2.4.2.1 Introduction
Oxidative acetoxylation provides a direct access from alkenes to alkenyl esters :
the alkene molecule undergoes replacement of an H atom by an acetate (or
generally OCOR) group in its vinylic (v), allylic (a), or homoallylic (h) position
according to Scheme 1, where Ox is an oxidant such as 02,Cu", p-benzoquinone,
and Red a reduced form of Ox such as H20, Cu', hydroquinone. A typical ex-
ample is the Pd-catalyzed co-oxidation of ethylene and acetic acid to vinyl acetate
(eq. (1)).
CH2 = CH2 + AcOH + '/2 0 2 -
Pd cat.
CH2 = CHOAc + H20 (1)

This reaction (Moiseev reaction; cf. also Section 3.3.14.4 [2] was discovered
in 1960 [l] and commercialized by Bayer, Hoechst, and some other companies
[2]; it can be performed both in the liquid and gas phase. The current industrial
process for vinyl acetate monomer (VAM) is based on the gas-phase version
with the formally heterogeneous Pd(Au-modified) catalyst.

* +RCOOH +OX E* +Red

Scheme 1
Y-
OCOR

The oxidative acetoxylation of ethylene was discovered while studying

the reactivity of palladium(I1) n-complexes [ 11. It was found that n-ethyl-
ene-palladium chloride, the so-called Kharash complex (n-C2H4 . PdC& [3],
is readily decomposed by hydroxyl-containing reagents such as water or alcohols,
yielding Pd metal and acetaldehyde or acetyl, respectively (eq. (2)) [l, 41.

2 CH3CHO + 2 Pdo+4 HCI

(2)
H2C CI CI 2 CH&H(OEt)* + 2 Pdo+4 HCI
+4 EtOH

Hydroxyl-containing reagents like acetic acid are inert toward Pd-alkene

n-complexes [4]. However, when alkaline acetate is added to an AcOH
solution of the n-complex, it readily decomposes to Pdo and vinyl acetate [l,51
(eq. (3)).
-
(n C2H4 PdC12)2+ 4 AcONa - 2 CH2 = CHOAc + 2 Pdo + 4 NaCl + 2 AcOH (3)
 2.4.2.2 Mechanistic Considerations 407

As well as the ethylene-palladium n-complex that can be formed by interaction

between ethylene and a Pd" salt in an AcOH solution, direct reaction between
PdCl, and ethylene in an AcOH solution containing alkaline acetate was found
to produce vinyl acetate [I], along with a minor amount of ethylidene diacetate
(eq. (4)).

1-5%

The Pdo formed can be re-oxidized to Pd" by an oxidant Ox such as p-benzoqui-

none, O2 + Cu", etc. (cf. Section 3.3.14) according to eq. ( 5 ) ,where Red = hydro-
quinone or H 2 0 + Cu', respectively, thus resulting in a catalytic cycle in which
ethylene is converted into vinyl acetate and Pd serves as catalyst (Scheme 2).
Pdo + Ox + 2 CI- = PdClp + Red (5)
Under the conditions of stoichiometric (eq. (4)) or catalytic (Scheme 2) reac-
tions, propylene is oxidized to isopropenyl acetate as the main reaction product,
along with ally1 and cis- and trans-n-propenyl acetates. Higher acyclic alkenes
C4-Cl0 are converted to mixtures of ally1 and vinyl esters [ 5 ] . Cyclic alkenes

p2j,::Pd<..
also produce homoallylic esters [6, 71.
H2C. I

C2H4 CHpCHOAc
LPd"(OAc),

'%Ac

Scheme 2 Red

2.4.2.2 Mechanistic Considerations

The reaction according to eq. (4) seems to proceed via a mechanism which is
common for the homogeneous Pd-catalyzed reactions that are often referred to
as Wucker oxidations (cf. Section 2.4.1, [4, 8, 91). In fact, there are several
liquid-phase olefin oxidations that are catalyzed by Pd complexes, and the nature
of the reaction products depends on the solvent used (Scheme 3).
Route a is the Moiseev reaction; the industrial Wucker oxidation (route b) is
Pd-catalyzed and produces acetaldehyde by ethylene oxidation in aqueous solu-
tion [4, 8, 91.
All three reactions in Scheme 3 proceed via the transformation of the olefin ?t-
complex to an organopalladium intermediate -Pd-CH2CH2CH20H. The hetero-
lytic cleavage of the Pd-C bond in the intermediate Pd organyl, involving hydride
408 2.4 Oxidations

CH2=CHOAc

CH2=CH2 + PdX2 CH3CHO

Scheme 3 CH3CH(OEt)2

X' +
1
Pdo+ CH3CH+-OR

Scheme 4
I
CH3CH=O+R

1,2-shift and possibly assisted by interaction with the Pd atom, gives rise
to Pdo and a carbocation, which converts into the final product of alkene oxidation
(Scheme 4).
The driving force for the key step shown in Scheme 4 is a tendency of the Pd"
atom to be reduced by the acceptance of an electron pair from the organic moiety.
In aqueous solution, the isomerization of the n-complex to the c-bonded Pd orga-
nyl is assumed to proceed a synchronous addition of the Pd-OR group across the
double bond. When this step is suppressed by the presence of excess C1- ligands, an
outer-sphere attack becomes possible [lo]. Recent data [7] suggest that in the case
of oxidative acetoxylation (OR = OAc), the attack of the Pd2+cation on the C-C
double bond and the subsequent addition of OAc- anion are separated in time.
Because of this asynchronism, the n-complex is expected to form a Pd-substituted
carbocation. In the case of alkenes higher than ethylene, the intermediate Pd carbo-
cation (e. g., ( A c O ) ~ P ~ - - C H ~ C H + C H ~ C H ~ C H ~ Ca H
has ~ ) , to isomerize via
chance
a 1,2-hydride shift, giving rise to allylic and homoallylic esters [9] as shown in
Scheme 5 .
.CH2
(OAc)zPd::./l
CHCH~CH~CH~CHS

1.
(AcO)~P~--CH~CH+CH~CH~CH~CHJ
shift
1,2-hydride
(ACO)ZP~--CH~CH~CH+CHZCH~CH~

-H+ 1 /
deprotonation------- 1 -H+

(AcO)~P~--CH~CH=CH~CHCH~CH~(A~O)~P~--CH~CH~CH=CHCHZCHJ

- PdOAc-1 reductive elimination

Scheme 5 allylic ester homoallylic ester

 2.4.2.3 Giant Cluster Catalyzed Reaction 409

At first sight, it makes no difference whether the Pd catalyst is introduced into

the catalytic cycle (Scheme 2) in the form of Pd" or Pdo when the reaction pro-
ceeds in a steady-state regime. However, experiments demonstrated that the selec-
tivity of reaction (1) depends heavily on the nature of the starting Pd species [ 111.
When Pd" compounds (Pd(OAc)i-, Pd2(OAc)g-, or Pd,(OAc),) are used as
starting material, even small additions of water (1-3 %) to the NaOAc/AcOH
solvent give rise to a great deal of acetaldehyde instead of vinyl acetate
[ll-131. In contrast to this, the Pd metal catalysts (e. g., supported Pd or Pd black,
prepared by H2 reduction of Pd" complexes in combination with NaOAc) provide
vinyl ester from alkene and AcOH with high selectivity, regardless of the water
content up to 10% [11, 14, 151. Further differences in the selectivity of reaction
(1) with Pd" and Pdo catalysts were found for the oxidative acetoxylation of higher
alkenes, viz., propylene, I-hexene, and cyclohexene [7]. All these facts apparently
implied that the alkene activation came from two different origins: one from Pd"
and another from Pd metal or, more exactly, low-valent Pd clusters formed upon
Pd" reduction with H2.

2.4.2.3 Giant Cluster Catalyzed Reaction

This suggestion was proved by the experiments with giant Pd clusters (cf. Section
3.1.1.5 [ 1 1, 161). Pd-561 giant clusters were synthesized by successive treatment
of Pd(OAc), with H2 and O2 in AcOH solution containing 0.5 mol of the L ligand
(L = 1,l-phenanthroline or 2,2'-dipyridyl) per Pd atom [11, 171. According to
measurements (elemental analysis data, molecular weight, TEM, HREM, electron
diffraction, STM, NMR, EXAFS, magnetic susceptibility) the experimental
formula of the substance is Pd570i30L63+3(OAc)190-+10, idealized to [Pd561L60]
( O A C ) ~This
~ ~ . Pd-561 cluster molecule consists of a positively charged metal
core approximately 25 A in diameter containing 570 k 30 dense-packed Pd
atoms (or 561 atoms in an idealized five-shell icosahedron- or cuboctahedron-
shaped core), about 60 neutral L ligands, which are bound with the surface of
the metal core, and about 180 outer-sphere OAc- anions; the latter counterbalance
the positive charge of the metal core [17].
The outer-sphere OAc- anions can be replaced by other anions. For instance, the
02-and P& anions readily substitute for OAc- anions in an aqueous solution con-
taining KPF6, affording the giant cluster with the idealized formula
L60060](PF6)60 [11, 16, 171. The Pd-561 clusters exhibit a high catalytic activity
in alkene acetoxylation in an AcOH solution under mild conditions (20-60 "C at
0.1 MPa). Besides reaction (l), the clusters provide the oxidative acetoxylation

CH2 = CHCH3 + - 0 2 + ACOH -

of propylene to ally1 acetate (eq. (6)) or of toluene to benzyl acetate (eq. (7)).
1
CH2 = CHCH20Ac + H20 (6)
PhCH3 +
2
1
-0 2
2
+ AcOH - PhCH20AC + H20 (7)
The selectivity of these reactions with respect to the products of oxidative ace-
toxylation is at least 95-98 %. No decrease in the selectivity was found even in
410 2.4 Oxidations

solutions containing up to 10 % of water. The only side reaction with the Pd-561
catalysts is a subsequent oxidation of alkenyl and benzyl esters to form ethylidene,
allylidene, or benzylidene diacetates, respectively. The soluble Pd-56 1 giant clus-
ters promote side reactions to a lesser extent than supported Pd metal catalysts,
which are active at much higher temperatures [9, 141. The reaction kinetics for
the Pd-561-catalyzed oxidation of ethylene and propylene obeys eq. (8).

The Michaelis-Menten character of the kinetics suggests that the formation of

the reaction product is preceded by reversible coordination of the alkene, 02,and
AcOH molecules by the cluster. The kinetic isotope effects give evidence that
the mechanisms of oxidative acetoxylation (eq. (1)) catalyzed with Pd” and
low-valence Pd clusters are different. On the basis of kinetic data, including the
H D kinetic isotope effects [9], the reaction mechanism represented by Scheme 6
has been proposed for Pd-561-catalyzed reaction.

Scheme 6

The surface of the metal core of giant clusters is substantially screened by phen
ligands that retard access of the reactant and solvent molecules to the cluster metal
core. A study of the influence of different ligands on the rates of the Pd-561 clus-
ter-catalyzed oxidative acetoxylation of C2H4 and C3H6 in solutions of [ l l ]
showed that bulky ligands, which are capable of strong binding to Pd atoms
(PPh3 or phen) have a negligible effect on the rate of alkene oxidation. This is
due to the fact that these ligands cannot reach the sites suitable for the coordina-
tion of the smaller molecules, C2H4,02,or AcOH. The smaller ligands, such as
C2H5SHand SCN-, effectively slow down oxidation.
About 50 “poisonous” ligand molecules per Pd cluster are necessary to stop the
oxidation of C2H4, whereas for the C3H6oxidation only about 15 poison mole-
cules are sufficient for complete inhibition of the reaction. This is in line with
 References 4 11

the estimation of the accessible surface of the cluster metal core based on the idea-
lized model of the cluster molecule: among 252 metal atoms in the outer layer of
the Pd metal core, approximately 20 % (50 of 252) of them can participate in the
catalytic oxidation of ethylene and about 6 % 15 of 252) are implicated in the
reaction with the bulkier C3H6 molecule.
Cluster-catalyzed oxidation of alkenes differs drastically from the oxidation by
Pd". Firstly, the oxidation of alkenes by Pd" is suppressed by donor ligands, even
by such bulky ones as PPh3 and phen, due to strong complexation with Pd", in
contrast to the reaction catalyzed by giant clusters the rate of which is unaffected
by these ligands. Secondly, the rate of alkene oxidation by Pd" in aqueous solution
is inversely proportional to the H' concentration, and the reaction is quenched by
adding 1-2 mol dm-3 mineral acid. Unlike this, alkene oxidation does not occur in
neutral aqueous solutions of the Pd-56 1 clusters. The cluster-catalyzed reaction
starts only after addition of strong acids (HClO, or H2S04),and reaches its max-
imum at the acid concentration which is sufficient to stop the reaction of alkenes
with Pd". Finally, the products of alkene oxidation mediated by Pd" and Pd-561
clusters are different. At 323 K and 0.1 MPa of 1:l alkene/02 gas mixture
ethylene is oxidized in 0.36-1.67 mol dm-3 aqueous H,SO, solution containing
(2.34.6) X lo4 mol dm-3 cluster successively to acetaldehyde and acetic acid
U81 (eq. (9)).
C2H4 + 0 2 - CH3CHO - CH3COOH (9)
Meanwhile, acetaldehyde is scarcely oxidized by Pd" to acetic acid under these
conditions. A more pronounced difference is observed for propylene: in acidic
aqueous solution of the Pd-56 1 cluster propylene is converted successively to
ally1 alcohol, acrolein, and acrylic acid. In contrast to the reaction mediated by
Pd" only traces of acetone are found.

References
[ 11 I. I. Moiseev, M. N. Vargaftik, Ya. K. Syrkin, Doklady Akad. Nauk SSSR 1960, 130, 820
and 133, 377 (in Russian).
[2] B. Cornils, W.A. Herrmann, R. Schlogl, C.-H. Wong (Eds.), Catalysis from A to Z,
Wiley-VCH, Weinheim, 2000, p. 59.
[3] M. S. Kharash, R. C. Seyler, F.R. Mayo, J. Am. Chem. SOC.1938, 60, 882.
[4] J. Smidt, W. Hafner, R. Jira, I. Sedlmeier, R. Riittinger, H. Kojer, Angew. Chem. 1959,
71, 176.
[5] I. I. Moiseev, n-Complexes in Liquid-Phase Olefin Oxidation, Nauka, Moscow, 1970
(in Russian).
[6] H. Grennberg, K. Bergstad, J.-E. Backvall, J. Mol. Catal. A: 1996, 113, 355.
[7] N. Yu. Kozitsyna, M. N. Vargaftik, I. I. Moiseev, J. Organomet. Chem. 2000, 593, 274.
[8] P. M. Maitlis, The Organic Chemistry of Pulladium, Academic Press, New York, 1971,
VOl. 1.
[9] R. Jira, in Organometallic Reactions (Eds.: E. Becker, M. Tsutsui), Wiley, New York,
1972, Vol. 3, p. 44; Applied Homogeneous Catalysis with Organometallic Compounds
(Eds.: B. Cornils, W. A. Herrmann), VCH, Weinheim, 1996, Vol. 1, p. 374.
412 2.4 Oxidations

[lo] J. E. Backvall, B. Wkemark, S. 0. Ljunggren, J. Am. Chem. Soc. 1979, 101, 2411.
[ l l ] M. N. Vargaftik, V. P. Zagorodnikov, I. P. Stolarov, I. I. Moiseev, D. I. Kochubey, V. A.
Likholobov, A. L. Chuvilin, K. I. Zamaraev, J. Mol. Cutal. 1989, 53, 315.
[I21 P. M. Henry, Acc. Chem. Res. 1973, 6 , 16.
[13] I. P. Stolarov, M. N. Vergaftik, 0.M. Nefedov, I. I. Moiseev, Izv. Akad. Nauk SSSR Ser:
Khim. 1983, 1455; Russ. Chem. Bull. 1983, 32, 1327 (Engl. transl.).
[14] S. Nakamura, T. Yasui, J. Catal. 1971, 23, 315.
[15] K. Fujimoto, T. Kunugi, J. Jap. Petrol. Inst. 1974, 17, 739.
[16] I. I. Moiseev, M. N. Vargaftik, in Catalysis by Di- and Polynuclear Metal Complexes
(Eds.: F. A. Cotton, R. Adams), Wiley-VCH, Weinheim, 1998, pp. 395-442.
[ 171 M. N. Vargaftik, I. I. Moiseev, D. I. Kochubey, K. I. Zamaraev, Furaday Discuss. 1991,
92, 13.
[ 181 P. I. Pasichnyk, M. K. Starchevsky, Yu. A. Pazdersky, V. P. Zagorodnikov, M. N. Vargaf-
tik, I. I. Moiseev, Mendeleev Commun. 1994, I , 1.

2.4.3 Synthesis of Oxiranes

Roger A. Sheldon

2.4.3.1 Historical Development

Oxiranes (epoxides), particularly ethylene and propene oxides, are key raw mate-
rials for a wide variety of chemicals (such as glycols, glycol ethers, and alkano-
lamines) and polymers (e.g., polyesters and polyurethanes). The simplest oxirane,
ethylene oxide, is manufactured by vapor-phase oxidation of ethylene with air or
oxygen over a heterogeneously supported silver catalyst [ 11. Unfortunately, this
method is not applicable to propene (propylene), which gives only low yields
of propene oxide owing to competing oxidation of allylic C-H bonds, leading
to a plethora of by-products. Propene oxide producers traditionally employed
the chlorohydrin route (eq. (1)). However, such chlorine- based processes are
currently being subjected to increasing environmental pressure. A method that
is widely used for the laboratory-scale synthesis of epoxides is the Prilezhaev
reaction [2] of an organic peracid with the appropriate olefin (eq. (2)). However,
the cost and/or safe handling of very large amounts of peracids prohibit its use for
propene oxide manufacture.
OH

CI

R
- + H3CCO3H R
<o + H3CCOOH (2)
 2.4.3.2 Metal-Catalyzed Epoxidation with Alkyl Hydroperoxides 413

Metal-catalyzed dihydroxylation of olefins with H202to the corresponding gly-

cols was first reported by Milas in the 1930s [3]. The Milas reagents consisted of
H202in t-butanol in combination with certain transition metal oxides, e.g., Os04,
Moo3, W03, and V205.Subsequent studies [4] showed that epoxide intermediates
were involved in many cases and could become the main product under neutral or
basic conditions. Hawkins [5] was the first to report a metal-catalyzed epoxidation
with an alkyl hydroperoxide, cyclohexene oxide being obtained in 30 % yield
using cumene hydroperoxide in combination with V205. Subsequently, Brill [6]
described the use of t-butyl hydroperoxide (TBHP), in the presence of catalytic
amounts of hydrocarbon-soluble acetylacetonates of molybdenum, vanadium,
and chromium. At roughly the same time Halcon [7] and Atlantic Richfield
(ARCO) [8, 91 independently developed processes for the production of epoxides
using an alkyl hydroperoxide in the presence of homogeneous catalysts based on
molybdenum, vanadium, tungsten, titanium, zirconium, and other metals (eq. (3)).
Molybdenum catalysts gave the highest rates and selectivities. Halcon and ARCO
subsequently formed a joint venture, the Oxirane Corporation, to exploit this tech-
nology for the manufacture of propene oxide.

A + ROOH * <' + ROH (3)

The process is generally referred to as the Halcon or ARCO process or simply

the Oxirane process. Shell, on the other hand, developed and commercialized a
heterogeneous Ti'"/SiO, catalyst for eq. (3) [lo, 111. This solid catalyst has the
added advantage of being suitable for continuous fixed-bed operation. The Oxi-
rane process currently accounts for ca. 45 % of the 3 million tons of propene
oxide produced annually on a worldwide basis. This percentage willprobably in-
crease in the future, at the expense of the chlorohydrin route, as environmental
regulations tighten.

2.4.3.2 Metal-Catalyzed Epoxidation with

Alkyl Hydroperoxides: Kinetics and Mechanism
Metal-catalyzed epoxidations with alkyl hydroperoxides show the following char-
acteristic features [ 12, 131.

(1) Metals with low oxidation potentials and high Lewis acidity in their highest
oxidation states are superior catalysts and show the following order of reactiv-
ity: Mo > W > V > Ti. Metals which readily promote homolytic decomposi-
tion of alkyl hydroperoxides via one-electron pathways, e.g., Co, Mn, Fe, and
Cu, are not effective. Certain main group elements, e.g., B and Sn, exhibit
activity, albeit significantly lower than molybdenum.
(2) The active catalyst contains the metal in its highest oxidation state, e.g., Mo"',
W"', V", and Ti'", and an induction period is sometimes observed during
414 2.4 Oxidutions

which the catalyst precursor, e.g., Mo(CO)~,is oxidized to its highest oxida-
tion state.
( 3 ) Strongly coordinating solvents, particularly alcohols and water, severely retard
the reaction by competing for coordination sites on the catalyst [14]. Conse-
quently, autoretardation by the co-product alcohol (Michaelis-Menten
kinetics) is observed, the extent of which increases in the order W < Mo
< Ti < V. The preferred solvents are hydrocarbons although chlorinated
hydrocarbons give higher rates [ 141.
(4) Reactions are usually performed in the temperature range 8O-12O0C,
although highly reactive substrates, such as allylic alcohols, react at room
temperature.
(5) The rate increases with increasing substitution of the double bond by electron-
donating alkyl groups, consistent with an electrophilic epoxidizing agent. The
structure of R02H generally has only a minor effect on rate and selectivity.
(6) The epoxidation is stereospecific, i.e., cis-olefins give only cis-epoxides.
(7) By-products result primarily from competing metal-catalyzed homolytic de-
composition of R02H via one-electron transfer processes (eqs.(4) and (5)).
Reaction (4) is the slower, rate-determining step. Hence, epoxide selectivities
are governed by the relative rates of eq. (4) and the reaction of the catalyst-
R02H complex with the olefin (eq. (6)). In practice, high R0,Wolefin molar
ratios are often used to suppress nonproductive hydroperoxide decomposi-
tion. Rigorous removal of traces of water also has a beneficial effect on
epoxide selectivities.
M"(R0OH) - slow M"-' + ROO' + H+ (4)

M"-' + ROOH - fast

M" + RO' + HO- ( 51

M"(R0OH) + 6- M"(R0H) + o<

Mn = MeV', Wv', Vv, TiNV,etc.

(8) No pronounced ligand effect is observed in many cases. Thus, the rates of
molybdenum-catalyzed epoxidations were shown [ 151 to be independent of
the structure of the molybdenum compound used, following an initial
phase in which the rates were changing. It was concluded that the same cat-
alytic species was generated in all cases. This was confirmed by recovery of
the catalyst and its identification as a dioxomolybdenum(V1) complex of the
trans- 1,2-diol complex, derived from the epoxide product. By analogy with
other dioxomolybdenum(V1) complexes the complex probably contains the
0x0 groups disposed in a cis arrangement as shown (Structure 1). It is em-
phasized, however, that such 1,2-diol complexes are substitution- labile and
may be displaced by strongly coordinating, oxidation-resistant ligands. In-
deed, the epoxidation is completely inhibited by very strongly complexing
 2.4.3.2 Metal-Catalyzed Epoxidation with Alkyl Hydroperoxides 4 15

ligands. Moreover, the ease of ligand exchange will vary with the particular
metal used. In the active metal-R02H complex one of thecoordination sites
in 1 has to be made available for coordination, e.g. as in Structure 2.
R’ 0 0

R*
R’
1

The Mechanism of Oxygen Transfer

The high selectivities observed with a wide range of olefins and the stereospeci-
ficity of the epoxidation are consistent only with a heterolytic mechanism. There
is general agreement that this involves rate-controlling oxygen transfer from an
electrophilic alkylperoxometal complex to the olefinic double bond. However,
despite extensive studies [ 15-27], the detailed mechanism of the oxygen transfer
step remains controversial. A mechanism, as shown in eq. (7), was proposed by
Sheldon in 1973 [lS]. An appealing feature of this mechanism is its close resem-
blance to that of the Prilezhaev reaction.

k
(7)

Subsequently, Sharpless reasoned [16], on the basis of steric arguments, that the
mechanism according to eq. (8), involving coordination of the alkylperoxo ligand
through the distal rather than the proximal oxygen, was more likely. The mecha-
nism according to eq. (9) is a slight variation of eq. (8) and closely resembles the
mechanism proposed for analogous epoxidations with H202 [ 121. The observed
exceptional reactivities and high syn selectivities observed in the catalytic epoxi-
dation of allylic alcohols can be more easily accommodated with the mechanisms
in eqs. (8) and (9), involving oxygen transfer from an alkylperoxometal group to
the double bond of an allylic alcohol ligand coordinated through its alcohol group.
The exceptional reactivity of vanadium catalysts in the epoxidation of allylic
alcohols [ 171 with alkyl hydroperoxides is consistent with the strong affinity of
vanadium(V) for alcohol ligands. The observed stereoselectivities can be rationa-
lized on the basis of the mechanism shown in eq. (10) [16, 17, 281.
416 2.4 Oxidations

An alternative mechanism for oxygen transfer was proposed by Mimoun

[21-251. In this mechanism (eq. (11)) initial coordination of the olefin to the
metal is followed by its rate-limiting insertion into the metal-oxygen bond giving
a pseudocyclic dioxometallocyclopentane (Structure 3). The latter decomposes to
the epoxide and the metal alkoxide.

(,*.*
0
ib '0
J , -R
8 ,*ol. ibdq
O '0
R
- ,I#....
0
II /OR
/"\
'L-O '0 H M O + (11)

Evidence in favor of olefin coordination was provided by competition experi-

ments with different olefins using the stable t-butylperoxovanadium(V) complex
(Structure 4) as a stoichiometric epoxidizing agent [24].
However, the catalytic activity observed with molybdenum porphyrins [27]
in epoxidations with TBHP favors the mechanisms involving direct attack of
the olefin on the electrophilic oxygen of the alkylperoxometal complex (see ear-
lier). Because of the steric hindrance of the macrocyclic ligand it was considered
 2.4.3.3 Commercial Oxirune Processes 417

R2
4

unlikely that the olefin and the alkylperoxo ligand could both be coordinated to
the molybdenum. The final resolution of this mechanistic dichotomy remains to
be made.

2.4.3.3 Commercial Oxirane Processes

Two variants of the Oxirane process are used (Figure 1) for the commercial
production of propene oxide (PO) [29]. They differ in the hydrocarbon (isobutane
or ethylbenzene (EB)) that is the precursor of the hydroperoxide, and, hence, in
the alcohol co-product. ARC0 operates both processes using a homogeneous
molybdenum catalyst. Shell, in contrast, operates only the EB variant and uses
a heterogeneous Ti1"/SiO2 catalyst.
In the isobutane process the t-butanol (TBA) co-product is converted to the
gasoline additive, methyl t-butyl ether (MTBE), via dehydration to isobutene
and reaction with methanol. The theoretical weight ratio of TBAPO is 1.32:l
but commercial plants produce 2-3 kg TBA per kg, depending on demand.
Because of the very large gasoline pool, marketing 2-3 kg of TBA per kg PO
is not a problem.
Isobutane oxidation is performed in the liquid phase at 130-160 "C and
elevated pressures. Since this exceeds the critical temperature of isobutane
(134 "C), products (TBA, t-butyl hydroperoxide (TBHP)) must be present to
maintain a liquid phase. The epoxidation step is performed at 100-130 "C
using 10-300 ppm of Mo. Since propene is a rather unreactive olefin, a high
propene/TBHP molar ratio is used to suppress nonproductive decomposition of
TBHP. The high propene concentration leads to very high operating pressures
and high recycle costs. The PO and TBA products are purified by a combination
of direct and extractive distillation. TBHP conversion and PO selectivity are
in excess of 90 %.
In the ethylbenzene process the 1-methylbenzyl alcohol (MBA) co-product is
dehydrated to monomeric styrene (SM). The theoretical SM/PO ratio is 1.8:1
and commercial plants operate in the range 2.2-2.7: 1, indicating that the selectiv-
ity of ethylbenzene hydroperoxide (EBHP) formation is much higher than that of
418 2.4 Oxidations

lsobutane route

TBHP

PO TBA MTBE

Ethylbenzene route
OOH

EB
. 0 2 -

OH
01'.+ EBHP

PO MBA SM

Catalyst: homogeneous MoV1 (ARCO)

heterogeneous Tilv / SiOp (Shell)

Figure 1. Commercial PO processes.

TBHP (vide supra). The autoxidation of EB is performed at 120-160 "C and 1-4
bar. MBA and acetophenone (ACP) are formed as by-products via the facile ter-
mination of the secondary 1-methylbenzylperoxy radicals. In order to minimize
by-product formation by further oxidation of MBA and ACP, the autoxidation
is carried out to only low conversions (< 12 %). This solution (ca. 10 %) of
EBHP in EB is used in the epoxidation step, i.e., EB is the solvent for the latter
step. A high propeneEBHP molar ratio is used and reaction conditions are similar
to those of the TBHP process (vide supra). The PO selectivity is reported to be
90 % at 92 % EBHP conversion [30] but in practice it may be higher. For com-
parison the heterogeneous Ti'"/Si02 catalyst in fixed-bed operation reportedly
gives 93-94 % PO selectivity at 96 % EBHP conversion [ 1I]. The products are
separated by distillation and MBA is dehydrated to styrene in the vapor phase
over a Ti02 catalyst.
 2.4.3.4 Scope and Applications in Organic Synthesis 419

2.4.3.4 Scope and Applications in Organic Synthesis

2.4.3.4.1 General
The oxirane technology is widely applicable to the synthesis of epoxides [ 11, 12,
17, 3 11. TBHP has many advantages, compared with other sources of active oxy-
gen, for use in organic synthesis. In contrast to hydrogen peroxide and peracetic
acid it is unreactive toward most functional groups in the absence of catalysts. It
is less sensitive to contamination by trace metals, and therefore safer to handle,
than hydrogen peroxide or peracetic acid. TBHP is completely miscible with
nonpolar organic solvents, such as hydrocarbons, and has high thermal stability
in dilute organic solution (its half-life is 36 days at 115 O C as a 0.2 M solution
in benzene). The co-product, t-butanol, is readily separated from most epoxide
products by simple distillation.
In agreement with the electrophilic nature of the active oxidant (see above) the
rate of epoxidation increases with increasing substitution of the double bond with
alkyl or other electron-donating groups. Allylic compounds containing electron-
withdrawing substituents give, as expected, lower rates of epoxidation. Ally1
chloride, for example, is ten times less reactive than propene [15]. The effect is
more pronounced with strongly electron-withdrawing substituents,such as nitrile
and carboxyl groups. Epoxidation is not seriously impeded, however, when
they are sufficiently removed from the double bond. For example, 4-cyanocyclo-
hexene reacts smoothly to give the epoxide (eq. (12)) [31].

OCN.aCN [Mo"']

89 % yield

Allylic alcohols show anomalous reactivities which, as discussed above, are

due to the coordination of the alcohol group to the catalyst leading to facile intra-
molecular oxygen transfer. Thus, molybdenum(V1)-catalyzed epoxidations are
generally about 100 times faster than the corresponding vanadium(V)-catalyzed
reactions. With allylic alcohols, in contrast, vanadium(V) gives higher epoxidation
rates and better yields than molybdenum(VI), owing to the greater affinity of
vanadium(V) for alkoxy ligands.

mixture of
diastereomers
420 2.4 Oxidations

Regio- and stereoselectivity are important considerations in the epoxidation of

more complex olefin substrates. In this context it is important to distinguish be-
tween two types of effect: those which are attributable to electronic and steric
factors inherent in the substrate and those which are derived from a particular
property of the reagent. An example of the former is the difference in reactivity
of double bonds in nonconjugated dienes due to increasing alkyl substitution, as
illustrated with limonene (eq. (1 3)) [3I].
In the second type of effect, orientation of the substrate by coordination through
a functional group (OH, for example) results in preferential oxygen transfer to a
particular site (regioselectivity) or a particular face (stereoselectivity) of the mole-
cule. Obviously effects of the second type are more important since they set these
reagents apart from, for example, organic peracids. Examples are provided by the
regioselective epoxidations of geraniol (eq. ( I 4)) and linalool (eq. (1 5 ) ) with
TBHPNO(acac):! [32]. Such regioselectivities are not possible with any other re-
agent and the exceptional reactivity of the VO(acac)JTBHP reagent is under-
scored by the fact that reactions (14) and (15) proceed readily at room tempera-
ture. Finally, it should be noted that although catalytic epoxidations with TBHP
have wide applicability in organic synthesis, to our knowledge only the epoxida-

r
tion of propene and the asymmetric epoxidation of ally1 alcohol (see below) have
actually been commercialized.

OH

Y O H

93 YOyield

84 % yield
mixture of diastereomers

2.4.3.4.2 Asymmetric Epoxidation

The synthetic utility of the oxirane technology was further extended by the devel-
opment by Sharpless and Katsuki [33, 341 of the titanium(1V) tartrate catalyst for
the asymmetric epoxidation of allylic alcohols with TBHP (eq. ( 1 6)).
 2.4.3.5 Recent Developments and Future Prospects 42 1

DET = (+) or (-) diethyltartrate 70-90 Yoyield

> 90 % ee

This asymmetric epoxidation technology affords high yields and enantiose-

lectivities with a broad range of allylic alcohol substrates, and has been widely
applied in organic synthesis [34-381. The original procedure [33] required stoi-
chiometric amounts of the titanium tartrate (titanium is a rather unreactive epox-
idation catalyst) but was subsequently improved to the extent that 5-10 wt.% is
sufficient.
Although these reactions obviously involve intramolecular oxygen transfer
within a titanium(1V) tartrate-allylic alcohol-alkyl hydroperoxide complex, ana-
logous to the vanadium-catalyzed epoxidations discussed above, the exact nature
of the catalytic species and the mechanism of enantioselection remain controver-
sial [39, 401.
The asymmetric epoxidation of ally1 alcohol has been commercialized by
ARCO, and more recently the French company Sipsy acquired exclusive rights
to this technology from ARCO [41]. Sipsy is reportedly producing commercial
quantities of both (R)- and (S)-glycidol for ARCO under a toll manufacturing
agreement. Optically pure glycidol derivatives are potentially key intermediates
to a wide variety of enantiomerically pure pharmaceuticals such as beta-blockers,
antitussives and HIV protease inhibitors [41].
In this context it is worth noting that neither the titanium(1V) tartrate catalyst
nor other metal catalyst-alkyl hydroperoxide reagents are effective for the asym-
metric epoxidation of unfunctionalized olefins. The only system that affords high
enantioselectivities with unfunctionalized olefins is the manganese(II1) chiral
Schiff's base complex/NaOCl combination developed by Jacobsen [42]. There
is still a definite need, therefore, for the development of an efficient chiral catalyst
for asymmetric epoxidation of unfunctionalized olefins with alkyl hydroperoxides
or hydrogen peroxide.

2.4.3.5 Recent Developments and Future Prospects

The Oxirane process is a mature technology that has stood the test of time. Both
ARCO and Shell have been successfully operating for more than two decades.
More recently a heterogeneous titanium-substituted silicalite (TS- 1) catalyst
was developed by Enichem [43, 441. In contrast to the Shell Ti1"/SiO2 catalyst,
TS-1 has a hydrophobic surface and is a remarkably effective catalyst for a variety
of liquid-phase oxidations with 30 % aqueous hydrogen peroxide, including
epoxidation [44]. It has been commercialized for the hydroxylation of phenol to
422 2.4 Oxidations

a mixture of catechol and hydroquinone, and the ammoximation of cyclohexanone

with NH3/H202has been developed to pilot-plant scale. Owing to the relatively
high price of H202 it is difficult for this rechnology to complete with the firmly
entrenched alkyl hydroperoxide-based processes for the production of PO.
However, two German companies, Degussa and Krupp Uhde, have recently joined
forces to develop commercial production of propene oxide via a H,O,-based
process.
An added advantage of the TS-1 catalyst, which could have commercial bene-
fits, is the possibility for ac$omplishang shape-selective epoxidations. Owing to
the limited dimensions (5.6 A X 5.4 A) of its micropores, linear olefins are epox-
idized much faster than branched or cyclic olefins, e.g., 1-hexene is smoothly
epoxidized while cyclohexene is virtually unreactive [45]. This reactivity is com-
pletely the opposite to that observed with the metal catalyst-alkyl hydroperoxide
reagents (see earlier). It could be utilized in, for example, the selective epoxidation
of linear olefins in mixtures of linear and branched or cyclic olefins.
Owing to the pore size restrictions TS-1 is not effective with TBHP as the
oxidant. In order to provide heterogeneous catalysts that are effective in the epox-
idation of bulky olefins and/or using TBHP as the oxidant, titanium has been in-
corporated into lTger-pore molecular sieves. For example, titanium-substituted
zeolite beta (7.6 A X 6.4 A) catalyzes the oxidation of cyclohexene with 30 %
aqueous hydrogen peroxide [45] in methanol at 25 "C. However, the product
was the corresponding glycol (ether), formed by ring-opening of the epoxide by
water or methanol, catalyzed by the Bronsted acid sites in the catalyst. Ring-open-
ing can be circumvented and epoxides obtained in high yield, by simply neutra-
lizing the acidic aluminum sites via ion-exchange treatment with an alkali metal
acetate followed by recalcination [46], as shown for 1-hexene in eq. (17). Selec-
tivities with TS- 1 were also improved after ion-exchange treatment.

R=H,Me

Catalyst Conv. (YO) Selectivity (YO)

epoxide glycol
TS-1 95 76 24
Li-TS-1 85 98 0
Ti-AM 48 0 97
Li-Ti-Al-I3 31 87 5
Na-Li-Ti-Al-I3 22 a4 6

Similarly the alkali metal-exchanged titanium beta was shown to be an effective

catalyst for olefin epoxidations with TBHP [47]. Titanium has also been in-
corporated into mesoporous molecular sieves, such as MCM-41, by framework
substitution [48] or by grafting Ti(1V) species to the internal surface by reaction
 2.4.3.5 Recent Developments and Future Prospects 423

with (Cp),TiCl, and subsequent calcination [49]. The resulting materials are
catalysts for epoxidations with alkyl hydroperoxides but are generally ineffective
for epoxidations with aqueous hydrogen peroxide owing to low activity and/or
leaching of the titanium under reaction conditions [50, 511. Apparently the cata-
lytic properties approach those of the Shell catalyst as the pore size of the mole-
cular sieve is increased into the mesopore range.
Mesoporous mixed titania-silica oxides, produces by the sol-gel method with
drying by extraction with supercritical carbon dioxide, have been shown to be ef-
fective catalysts for epoxidations with alkyl hydroperoxides [52]. These so-called
aerogels have high surface areas (up to 700 m2g-*)with well dispersed titania, i.e.
a high proportion of site-isolated titanium species, a key feature commensurate
with high activity as an epoxidation catalyst. Moreover, substantially higher
amounts of Ti can be incorporated compared to supported titanium catalysts (up
to 20% compared to 2 % for the Shell catalyst on a w/w basis). This translates
to a higher acticity per unit weight of catalyst. More recently, additional selectivity
improvements have been achieved by surface modification of these catalysts with
organic bases [53].
A shortcoming of these catalysts, in common with supported titanium catalysts,
is their hydrophilicity which precludes effective catalysis with hydrogen peroxide.
Hence, much effort has been devoted to the synthesis of hydrophobic analogs of
these materials [54] but this has not yet resulted in the synthesis of truly effective
catalysts for epoxidations with hydrogen peroxide. Apparently, hydrophobicity is
not the only requirement for an effective heterogeneous Ti catalyst for epoxida-
tions with hydrogen peroxide.
In yet another approach, titanium(1V) silsesquioxanes were shown to be ex-
cellent homogeneous catalysts for epoxidations with TBHP [5S]. A heterogeneous
variant was prepared by adsorbing the Ti(1V) silsesquioxane in the pores of
MCM-41 that had been silylated with Ph2SiC12to passivate the external surface.
The resulting material was reported to be a stable, recyclable catalyst for epoxi-
dations with TBHP [56].
In recent years considerable progress has also been made in the development
of homogeneous catalysts for epoxidations with hydrogen peroxide. A notable
example is the use of a tungstate catalyst under phase transfer conditions
where Noyori and co-workers [S7] (see also Section 3.2.4) achieved major
improvements in systems originally developed by Venture110 [58] and Ishii
[59]. The combination of sodium tungstate with aminomethylphosphonic acid
and a quaternary ammonium salt comprising a lipophilic cation and an anion
(HSOJ that did not react with the epoxide product (chloride was shown to
react with the epoxide, causing a major change in pH, thereby inhibiting the
reaction) afforded a catalytic system that was active in the epoxidation of a vari-
ety of alkenes, either solvent-free or in a non-halogenated solvent [57]. How-
ever, the scope of this environmentally attractive method is limited, owing to
its relatively high acidity (pH 2-3), to alkenes that do not form acid-sensitive
epoxides.
The discovery of the catalytic activity of methyltrioxorhenium (MTO), by Herr-
mann and co-workers [60], stimulated interest in its application as an (ep)oxida-
424 2.4 Oxidations

tion catalyst (cf. Section 3.3.13) Sharpless and co-workers [61] achieved a major
improvement by adding a large excess of pyridine relative to MTO. This resulted
in a dramatic increase in both activity and selectivity. Even very sensitive epoxides
could be synthesized using this system with aqueous hydrogen peroxide [61,62].
Subsequently, the Herrmann group showed [63] that pyrazole, which has a higher
oxidative stability than pyridines, was an even more effective promoter. A limita-
tion of these MTO-based systems is the requirement for dichloromethane as
solvent, in order to achieve high activities. More recently, even higher activities
have been observed [64] using fluorinated alcohols as solvents (turnover frequen-
cies up to 14000 h-' for cyclohexene at < 10 "C).
Another remarkably active catalyst for epoxidations with aqueous hydrogen
peroxide is the manganese complex of N,N,N-trimethyltriazacyclononane
(tmtacn). The activity of this complex as an epoxidation catalyst was originally
reported by Hage and co-workers [65]. However, a large (100 fold) excess of hy-
drogen peroxide was required, in the epoxidation of styrene, owing to extensive
non-productive decomposition of H202(the catalase reaction). Dramatic improve-
ments were subsequently achieved by De Vos and Jacobs and co-workers [66]
who found that the addition of an oxalic acidoxalate buffer greatly enhanced
the epoxidation activity of the manganese-tmtacn catalyst (possibly by stabilizing
an active monomeric species). The system shows remarkably high activity in the
epoxidation of terminal and electron poor olefins (allylic alcohols, unsaturated
ketones) but is unreactive towards tri- and tetrasubstituted olefins, i. e. comple-
mentary activity to the tungsten- and MTO-based systems described above.
This can be rationalized on the basis of the different types of active oxidants in
these systems (oxometal and peroxometal, respectively).
The activities of these state of the art homogeneous catalysts are compared with
that of TS-1 in Table 1.
Although these homogeneous systems have obvious synthetic potential for the
production of fine chemicals, to our knowledge, none of them have yet been
commercialized.

Table 1. Comparison of TS-1 with state of the art homogeneous catalysts for I-hexene epox-
idaton with aq. H202.
Catalyst S/C") S/H202b) t T Conv. Sel. TOF Productivity
[hl ["C] [%I [%Ic) [h-'1 [g-'h-']
TS- 1 83 1 1.2 25 68 90 49 1.5
MeRe03 1000 0.5 6 25 95 >99 158 63
WV1 8Id' 1.7 0.75 70 53 88 70 10
Mn 666 0.67 0.3 5 99 99 2000 620
(tmtacn)
~ ~~ ~ ~ ~~

Substratekatalyst molar ratio. ') Substrate/H202molar ratio.

Selectivity based on converted alkene. d, 1-Octene as substrate.
 References 425

Finally, it is noted that the direct epoxidation of propene with molecular oxygen
is potentially more economically attractive than all of the coproduct processes
currently in operation. It is indeed a holy grail in oxidation chemistry. Not-
withstanding the extensive research on this topic in the last three decades, an
industrially viable method for the direct epoxidation of propene has not been
forthcoming. Sumitomo has recently announced [67] that they will commercialize
a coproduct free route to PO but this probably involves an alkyl hydroperoxide
(e.g. cumene) oxidant with recycling of the alcohol coproduct [68].

References
[ I ] P. A. Kilty, W. M. H. Sachtler, Cutul. Rev. 1974, 10,1.
[2] D. Swem in Organic Peroxides, Vol. 2 (Ed.: D. Swem), Wiley-Interscience, New York,
1971, p. 355.
[3] N. Milas, J. Am. Chem. Soc. 1937, 59, 2342.
[4] G. B. Payne, C. W. Smith, J. Org. Chem. 1957, 22, 1682.
IS] E. G. E. Hawkins, J. Chem. Soc. 1950, 2169.
[6] W. F. Brill, J. Am. Chem. Soc. 1963, 8.5, 141.
[7] Halcon (J. Kollar), US 3.350.422, US 3.351.635 (1967).
IS] ARC0 (M. N. Sheng, J. G. Zajacek). GB 1.136.923 (1968).
191 M. N. Sheng, J. G. Zajacek, ACS Advan. Chem. Sex 1968, 76, 418.
[lo] Shell Oil (H. P. Wulff) GB 1.249.079 (1971).
[ I l l R. A. Sheldon, J. Mol. Catal. 1980, 7, 107.
[12] R. A. Sheldon in Aspects of Homogeneous Catalysis, (Ed.: R. Ugo), Vol. 4 , Reidel,
Dordrecht, 1981, pp. 3-70.
[13] R. A. Sheldon, J. A. van Doom, J. Catal. 1973, 31, 427.
[14] R. A. Sheldon, J. A. van Doom, C. W. A. Schrarn, A. J. de Jong, J. Cutal. 1973,31,438.
[I51 R. A. Sheldon, Recl. Truv. Chim. Pays-Bas 1973, 253, 367,
[16] A. 0. Chong, K. B. Sharpless, J. Org. Chem. 1977, 42, 1587.
[17] K. B. Sharpless, T. R. Verhoeven, Aldrichim. Acta 1979, 12, 63.
[18] K. A. Jorgensen, Chem. Rev. 1989, 89, 431.
[19] F. Di Furia, G. Modena, Pure Appl. Chem. 1982, 54, 1853.
[20] J. Sobczak, J. J. Ziolkowski, J. Mol. Catal. 1981, 13, 11.
[21] H. Mirnoun in Comprehensive Coordination Chemistry (Eds.: G. Wilkinson, R. D.
Gillard, J. A. McCleverty), Vol. 6, Pergamon, Oxford, 1987, pp. 3 1 7 4 1 0 .
[22] H. Mimoun, Angew. Chem., lnt. Ed. Engl. 1982, 2,734.
[23] H. Mimoun, J. Mol. Catal. 1980, 7, 1.
[24] H. Mimoun, M. Mignard, P. Brechot, L. Saussine, J. Am. Chem. SOC.1986, 108,3711.
[25] H. Mirnoun, Catal. Today 1987, 1 , 297.
[26] R. D. Bach, G. J. Wolber, B. A. Goddens, J. Am. Chem. SOC.1984, 106, 6098.
[27] H. J. Ledon, P. Durbut, F. Varescon, J. Am. Chem. Soc. 1981, 103, 3601.
[28] A. S. Narula, Tetrahedron Lett. 1982, 23, 5579.
[29] J. R. Valbert, J. G. Zajacek, D. I. Orenbuch in Encyclopedia of Chemical ProceJsing and
Design (Ed.: J. McKetta), Marcel Dekker, New York, 1993, Vol. 45, pp. 88-137.
[30] R. Landau, G. A. Sullivan, D. Brown, Chem. Tech. 1979, 9, 602.
[31] G. A. Tolstikov, V. P. Yurev, U. M. Dzhernilev, Russ. Chem. Rev. 1975, 44, 319.
[32] K. B. Sharpless, R. C. Michaelsen, J. Am. Chem. SOC.1973, 95, 6136.
[33] T. Katsuki, K. B. Sharpless, J. Am. Chem. SOC.1980, 102,5974.
426 2.4 Oxidations

[34] For a recent review see: R. A. Johnson, K. B. Sharpless in Catalytic Asymmetric Syn-
thesis (Ed.: I. Ojima), VCH, Weinheim, 1993, pp. 101-158.
[35] R. M. Hanson, Chern. Rev. 1991, 91, 437.
[36] A. Pfenniger, Synthesis 1986, 89.
[37] K. P. Zeller in Methoden der Organischen Chemie (Houben-Weyl) 1988, 4th ed., Vol.
E13, Part 2, pp. 1210-1250.
[38] C. H. Behrens, K. B. Sharpless, Aldrichim. Actu 1983, 16, 67.
[39] S. S. Woodward, M. G. Finn, K. B. Sharpless, J. Am. Chem. SOC.1991, 113, 106.
[40] E. J. Corey, J. Org. Chem. 1990, 55, 1693.
[41] Anon., Pegormance Chemicals, August 1995, 27.
[42] E. N. Jacobsen in Catalytic Asymmetric Synthesis (Ed.: I. Ojima), VCH, Weinheim,
1993, pp. 159-202.
[43] U. Romano, A. Esposito, F. Maspero, C. Neri, M. Clerici, Chim. Ind. (Milan) 1990,
72, 610.
[44] M. Clerici, P. Ingallina, J. Catal. 1993, 140, 71.
[45] A. Corma, M. A. Camblor, P. Esteve, A. Martinez, J. Perez-Pariente, J. Catal. 1994,
145, 151.
[46] T. Sato, J. Dakka, R. A. Sheldon, Stud. S u f Sci. Catal. 1994, 84, 1853.
[47] T. Sato, J. Dakka, R. A. Sheldon, J. Chem. Soc., Chem. Commun. 1994, 1887.
[48] A. Corma, M. T. Navarro, J. Perez-Pariente, J. Chem. SOC.,Chem. Commun. 1994, 147.
[49] T. Maschmeyer, F. Rey, G. Sankar and J. M. Thomas, Nature, 1995, 121.
[50] T. Maschmeyer, Curl: Opin. Solid State Mutel: Sci. 1998, 3, 71.
[51] R. A. Sheldon, in Fine Chemicals through Heterogeneous Catalysis, R. A. Sheldon and
H. van Bekkum, Eds., Wiley-VCH, Weinheim, 2001.
[52] R. Hutter, T. Mallat and A. Baiker, J. Cutul. 1995, 1.53, 177; M. Schneider and A. Baiker,
Catal. Rev. Sci. Eng. 1995, 39, 5 15.
[53] C. Muller, M. Schneider, T. Mallat and A. Baiker, J. Catal., 2000, 189, 221; T. Mallat
and A. Baiker, Appl. Catal. A: General 2000, 200, 3 and references therein.
[54] S. Klein and W. F. Maier, Angew. Chern. Int. Ed. Engl., 1996, 35, 2230; H. Kochkar
and F. Figuras, J. Catal. 1997, 171, 240; C. A. Muller, M. Maciejewski, T. Mallat and
A. Baiker, J. Catal., 1999, 184, 280.
[55] H. C. L. Abbenhuis, S. Krijnen and R. A. van Santen, Chem. Commun. 1997, 31.
[56] S. Krijnen, H. Abbenhuis, R. Hansen; J. van Hooff and R. A. van Santen, Angew. Chem.
1998, 110, 374.
[57] K. Sato, M. Aoki, M. Ogawa, T. Hashimoto and R. Noyori, J. Org. Chem. 1996, 61,
8310; K. Sato, M. Aoki, M. Ogawa, T. Hashimoto, D. Panyella and R. Noyori, Bull.
Chern. SOC. Jpn. 1997, 70, 905.
[58] C. Venturello, E. Alneri and M. Ricci, J. Org. Chem. 1983, 48 3831; C. Venturello and
R. DAloiso, J. Org. Chem. 1988, 19883, 1553.
[59] Y. Ishii, K. Yamawaki, T. Ura, H. Yamada, T. Yoshida and M. J. Ogawa, J. Org. Chem.
1988, 53, 3587.
[60] W. A. Herrmann, R. W. Fischer and D. W. Marz, Angew. Chem. Int. Ed. Engl. 1991, 30,
1638; W. A. Herrmann, R. W. Fischer, M. U. Rauch and W. Scherer, J. Mol. Catal. 1994,
86, 243.
[61] J. Rudolph, K. L. Reddy, J. P. Chiang and K. B. Sharpless, J. Am. Chem. SOC. 1997, 119,
6189; C. Coperet, H. Adolfsson and K.B. Sharpless, Chem. Commun. 1997, 1565.
[62] A. L. Villa de P., D. E. De Vos, C. Montes de C. and P. A. Jacobs, Tetrahedron Lett. 1998,
39, 8521.
[63] W. A. Herrmann, R. M. Kratzer, H. Ding, W. R. Thiel and H. Glas, J. Organometul.
Chem. 1998, 555, 293.
[64] M. C. A. van Vliet, I. W. C. E. Arends and R. A. Sheldon, Chem. Commun. 1999, 821.
 2.4.4.1 General 427

[65] R. Hage, J. E. Iburg, J. Kerschner, J. H. Koek, E. L. M. Lempers, R. J. Martens, U. S.

Racheria, S. W. Russell, T. Swarthoff, M. R. P. van Vliet, J. B. Wamaar, L. van der
Wolf and B. Krijnen, Nature 1994, 369, 637.
[66] D. E. De Vos, B. F. Sels, M. Reynaers, Y. V. Subba Rao and P. A. Jacobs, Tetrahedron
Lett. 1998, 39, 3221.
[67] Japan Chemical Week, 14-9-2000, p. 1; European Chem. News, 18-9-2000, p. 24; Japan
Chemical Week, 1-3-2001, p. 5.
[68] S. Robinson, Eul: Chem. News, 5-11 March 2001, p. 19.

2.4.4 Aliphatic Carboxylic Acids via Aliphatic Aldehydes

Fred Koch

2.4.4.1 General
Numerous aliphatic carboxylic acids were first obtained from natural sources in
the 19th century. These natural sources usually yielded straight-chain acids
containing an even number of carbon atoms. Today fats and oils are still the
most important feedstocks for the production of carboxylic acids with more
than 12 carbon atoms.
The most popular aliphatic carboxylic acid is clearly acetic acid, and since the
development of synthetic production processes it has been the most important.
The major use for acetic acid is in the manufacture of vinyl acetate, which
accounts for more than 40% of the demand. Since the early 20th century the
only routes for the production of acetic acid were natural bacterial oxidation of
ethanol and the wood-coking process. With increasing demand for acetic acid
from the chemical industry, the oxidation of acetaldehyde was developed first
as a batch, then as a continuous process; later the metal iodide-catalyzed carbon-
ylation of methanol, the BASF and Monsanto process [I], was introduced in the
1960s (cf. Section 2.1.2.1). Falling between acetic and the larger (C,,,) acids lie
the C3-Clo carboxylic acids, for which four major large-scale commercial methods
have been developed within recent decades. These are aldehyde oxidation, car-
boxylation of olefins (Koch synthesis, homogeneously but not metal catalyzed;
cf. also Section 2.1.2.2), paraffin oxidation (cf. Section 2.8.1. I), and alkali fusion
of alcohols. Other synthetic routes such as hydrolysis of natural oils, e. g., castor
oil to heptanoic acid, are less important commercially.
Due to the wide availability of aliphatic aldehydes from hydroformylation (cf.
Section 2.1. l), the principal method for the production of C3-Clo carboxylic acids
is the catalytic oxidation of the corresponding aldehyde (eq. 1).

RCHO + '1202 -
cat.
RCOOH (1)
The aldehydes are oxidized by either air or oxygen, whereby the liquid-phase
oxidation in absence of solvent is preferred. Metal ions that can transfer only one
428 2.4 Oxidations

electron can act as oxidation catalysts. The most effective catalysts are those
which have two valence states of equal stability to allow for facile oxidation/
reduction, e. g., Co"/Co"' , Mn"/Mn"', Cu'/Cu". For the liquid-phase oxidation
the metals are most commonly used as the acid salts which are soluble in the
aldehyde, such as naphthenates, stearates, octanoates, and the like [2].
This homogeneously catalyzed process technology is not applicable for the pro-
duction of unsaturated acids, such as acrylic or methacrylic acid. These acids are
more typically produced via gas-phase oxidations utilizing heterogeneous catalyst
systems such as Mo-V-A-Cu oxides at much higher temperatures, 250-300 "C
131. Very few homogeneous catalysts, such as T1(OAc)3, have been described
for the oxidation of olefinic aldehydes with oxygen [4].

2.4.4.2 Catalysts
The homogeneously catalyzed oxidation of aliphatic aldehydes is highly selective,
but there are some side reactions. The major reactions are formation of formates,
ketones, n - 1 hydrocarbons, and alcohols through the loss of C02. Paradoxically,
noncatalyzed oxidation of aldehydes often gives higher yields than the correspond-
ing metal-catalyzed reaction. This depends largely on the structure of the reactant
aldehyde. Linear aldehydes such as butanal or heptanal can be oxidized in high
yield without the aid of catalyst, while a-branched aldehydes such as 2-ethylhex-
anal will give very poor selectivity without the addition of appropriate catalyst [5].
Other suitable catalysts described in the literature are primarily of interest for
laboratory-scale reactions, e. g., bis[ 1,3-di(methoxyphenyl)-l,3-propanedionato]-
-
nickel(I1) [6], K3 [Fe(CN),] H 2 0 [7], Fe'" porphyrin complexes [8], or inorganic
oxides [9].
The aldehydes are usually fed into the oxidation reaction as distilled products,
but in the rhodium-catalyzed hydroformylation of 2,2,4-trimethyl- 1-pentene the
resulting crude aldehyde can be converted directly to the corresponding C9 acid
at temperatures of 40-60 "C without loss of activity of the Rh catalyst [ 101.
Aside from air and oxygen, other oxidizing agents can also be employed for the
homogeneous reaction. Hydrogen peroxidePhSe(0)OH [ 111 and Os04 [ 121 are
examples. These reagents are used primarily when sensitive functional groups
are present in the aldehyde, and then their use is generally limited to labora-
tory-scale operations. The simultaneous oxidation of olefins and aldehydes to
the corresponding carboxylic acids has been described in the literature [13, 141
with soluble Rh complexes being the preferred catalysts. It is possible that the
olefin is not oxidized directly to the acid, but instead goes through the aldehyde
as an intermediate. Examples of phosphine-modified Rh'-catalyzed aldehyde
oxidation also exist for C2-C6 aldehydes [ 15, 161. Two-phase oxidation systems
have also been studied, utilizing methyltrioctylammonium tetrakis(oxodiperoxo-
tungsto)phosphate in combination with hydrogen peroxide as the oxidant [ 171,
or more conventional metal salts with air or oxygen [18]. These systems are
generally preferred for the oxidation of the lower aliphatic aldehydes, owing to
their greater solubility in the aqueous phase.
 2.4.4.3 Kinetics and Mechanism 429

As with many other homogeneously catalyzed reactions, attempts have been

made to attach the catalyst to a solid support (cf. Section 3.1.1) to take advantage
of the performance of a homogeneous catalyst system while eliminating the need
for catalyst separationh-ecovery [19], but so far these systems are limited to the
laboratory scale as well.

2.4.4.3 Kinetics and Mechanism

The oxidation of aldehydes is highly exothermic, liberating between 250 and
300 kJ mol-', with the reactivity of the aldehyde depending upon the value of
-AH. Due to the rapid oxidation, most kinetic studies of aldehyde oxidation
with oxygen are carried out at temperatures of 25 to -90°C with low concen-
trations of aldehyde [20]. Under these conditions the reaction is chemically
rate-limited, and thus oxygen mass transfer is not limiting in any way. Kinetic
studies in conditions more closely approximating those seen in commercial prac-
tice, while difficult, have been attempted also [21].
The liquid-phase oxidation of an aldehyde takes places in two stages, neither of
which requires a catalyst. In the first stage the aldehyde is oxidized via a typical
free radical chain reaction involving homolytic cleavage of interatomic bonds to
produce a peracid. In the second stage the product carboxylic acid is formed
from the peracid and a second mole of aldehyde through a Baeyer-Villiger reac-
tion. The presence of metal ions, especially manganese, can greatly enhance the
rate of formation of the peracid [22, 231.
In the oxidation of acetaldehyde the following sequence of intermediate steps
(eqs. (2)-(6)) can be considered [24, 251.

(1) Formation of the acetyl radical:

CH3CHO + M3+ - H3Cr\\0 + H+ + M2+ (2)

(2) Addition of oxygen to form a peroxyacyl radical:
0

(3) Reaction with acetaldehyde to produce peracetic acid and an acetyl radical:
0 0

(4) Addition of acetaldehyde to the peracetic acid and Baeyer-Villiger rearrange-

ment to produce two moles of acetic acid:

H3C
0
A 0
/OH + CHBCHO -
430 2.4 Oxidations

( 5 ) Regeneration of catalyst:

H3C
0
/ko,OH + 2M2+ + 2H+ - CH3COOH + H20 + 2M3+
(6)

As can be seen from the preceding equations, the metal “catalyst” in aldehyde
oxidation is largely absent from the reaction mechanism, serving more as an ini-
tiator to aid in rapid generation of the original radical flux. In practice, the alde-
hyde and catalyst have an optimum concentration for which rate of formation and
decomposition of the radical chain are equivalent. At certain levels the catalyst
can even become an inhibitor [23] in the chain reaction. Due to their acidic char-
acter, peracids are capable of catalyzing their own decomposition. To avoid an in-
creasing concentration of the peracid a limited range of temperatures and catalyst
concentrations must be maintained.

2.4.4.4 Technical Process

The liquid-phase aldehyde oxidation with air or oxygen is the preferred technical
method for the conversion of aliphatic aldehydes to the corresponding carboxylic
acids. For this process preferred catalysts are Na, K, Mn, and Cu salts. Figure 1

- by-products

2 vent 5 5

acetaldehyde

air or
oxygen feed

catalyst
make up
,
1 .
acetic acid
reactor
. La
1
acetaldehyde
column

catalyst / heavy ends

Figure 1. Continuous oxidation of acetaldehyde to acetic acid.

I1 9
t
acetic acid
column
acetic acid
 2.4.4.5 Future Trends 431

shows a simplified process flow diagram for the production of acetic acid.
Depending on the structure of the reactant aldehyde, the oxidation is carried
out in a tubular flow reactor (1 in Figure 1) at temperatures between 40 and
80°C with a residence time of several hours.
Efficient dispersion of oxygen into the liquid phase, especially in the absence of
catalysts, is extremely important to insure operation in the chemically rate-limited
regime as opposed to becoming mass transfer-limited. Oxygen starvation also
gives a decrease in selectivity due to undesired chain branching reactions instead
of propagation through eq. (3) above.
On a commercial scale, the waste gas from this process is typically drawn off
and burned for fuel value, but special attention is required regarding the explosive
limits of this oxygen-containing mixture. In order to reduce the danger of operat-
ing in the flammable regime, the excess aldehyde is condensed from the reactor
vent and recycled to maintain an oxygen-richlfuel-lean mixture. The oxidation
catalyst is dissolved in a mixture of aldehyde and acid and fed through the reactor
cocurrently with a slight excess of oxygen. The catalyst is separated from the
reaction mixture via distillation and recycled to the oxidation reactor. Catalyst
losses are then only realized through filtering of the catalystheavy ends solution,
during which some catalyst is removed along with the heavy ends.
Distillation of the crude acid normally takes places in two stages. The first col-
umn removes the low-boiling components such as hydrocarbons and alcohols
overhead. Early removal of alcohols is especially important to prevent esterifica-
tion reactions between them and the product acid. The bottoms from this column
are then fed to the final column where pure acid is recovered as the overhead prod-
uct and catalyst and any heavy ends are removed in the bottoms. In the technical
process the reaction temperature lies between 50 and 60 "C and the catalyst con-
centration should be between 0.1 and 0.2 %. Under these conditions, no peracetic
acid is detected at the reactor outlet, thus eliminating an additional peracid decom-
position step. In commercial acetaldehyde oxidation, conversion rates above 98 %
can be achieved along with selectivities between 93 and 98 %.
Technical details of the commercially important oxidations of butyraldehydes
(to butyric acids), valeraldehydes (to C5acids), 2-ethylhexanal (to 2-ethylhexanoic
acid), etc. are the know-how of the manufacturers and are often disclosed only in
the patent literature.
Due to the corrosive nature of carboxylic acids, the oxidation reactor and
associated peripherals must be constructed of corrosion-resistant materials, e. g.,
suitable stainless steels. As with all radical reactions, the surface to volume
ratio of the reactor should be kept to a minimum to minimize radical recombina-
tion which always occurs on surfaces.

2.4.4.5 Future Trends

Even processes that have been in operation for decades have potential for further
developments. For economic reasons, optimization of selectivity and reduction of
losses to off-gases and by-products have to be continual efforts, but this often
432 2.4 Oxidations

leads to increasing complexity of the process. For this reason there is always the
attraction of switching to a completely different system that offers increased per-
formance in the initial, simplified design.
Due to increasing environmental problems, the use of metal catalysts will
gradually be reduced in the future; the reduction in the early use of lead- and
chromium-based catalysts is evidence of this. With stricter regulations governing
the release of metals, the cost of catalyst recovery and environmental remediation
is quickly making noncatalytic processes for the production of carboxylic acids
preferable. Coupled with recent advances in the field of biocatalysis, metal-
mediated oxidations may give way to alternative processes as we enter a new
millennium of chemistry.

References
[ l ] BASF AG (W. Repe, N. von Kutepow), DE 893.499 (1950).
[2] Standard Oil Company (R. H. Hill), US 2.815.355 (1957).
[3] Nippon Shokubai Kagaku (T. Kawajiri, S. Uchirla, M. Wada, H. Onodera), EP Appl.
0.279.374 (1988).
[4] Atlantic Richfield Co. (J. L. Kao, J. J. Leonard), US 4.097.523 (1978).
[5] BASF AG (L. Lorenz, E. Nebe), DE 950.007 (1951).
[6] T. Yamada, 0. Rhode, T. Takai, Chem. Lett. 1991, 1, 5 .
[7] Ruhrchemie AG (B. Comils, W. Dewin, J. Weber), DE 2.931.154 (1981).
[8] Y. Watanabe, K. Takehira, M. Shimizu, T. Hayakawa, H. Orita, J. Chem. Soc., Chem.
Comrnun. 1990, 13, 927.
[9] North Dakota State University (M. P. Sibi, P. Boudjouk, J. Ji), US 5.596.111 (1997).
[lo] BASFAG (K. Schwirten, W. Disteldorf, W. Eisfeld, R. Kummer), DE 2.604.545 (1976).
[ I l l J. K. Choi, Y. K. Chang, S. Y. Hong, Tetrahedron Lett. 1988, 29(16), 1967.
[12] A. J. Bailey, M. G. Bhowon, W. P. Griffith, A. G. F. Shoair, A. J. P. White, D. J. Williams,
J. Chem. SOC., Dalton Trans. 1997, 3245.
[13] Texaco Chemical Co. (J. R. Sanderson, T. E. Marquis), US 5.068.366 (1991).
[14] Eastman Chemical Company (J. R. Zoeller), US 5.977.407 (1999).
[15] Union Carbide Corp. (R. A. Fiato, R. L. Pruett), US 4.343.950 (1982).
[16] E. Kwaskowska-Chec, J. J. Ziolkowski, Ox. Commun. 1988, ll(1-2), 117.
[17] C. Venturello, M. Gambaro, J. Org. Chem. 1991, 56, 5924.
[I81 Melle-Bezons (A. Bouniot), US 3.579.575 (1971).
[I91 ABB Lummus Global Inc. (H. E. Barner, C. Ercan, C. Y. Huang, L. L. Murrell, R. A.
Overbeek, P. Rylandshom, R. E. Trubac, N. Van der Puil, C. Y. Yeh), WO 21.944 (2000).
[20] J. R. McNesby, C. A. Heller, Chem. Rev. 1954, 54, 325.
[21] D. R. Larkin, J. Org. Chem. 1990, 55, 1563.
[22] L. B. Levy, J. Org. Chem. 1989, 54, 253.
[23] R. A. Sheldon, J. A. Kochi, Metal-Catalyzed Oxidations of Organic Compounds, Aca-
demic Press, New York, 1981.
[24] T. Chou, F. Lin, Can. J. Chem. 1983, 61, 1295.
[25] H. L. J. Backstrom, Science 1924, 59, 489.
 2.4.5.1 Oxidation cgArenes to Quinones 433

2.4.5 Oxidation of Arenes and Alkyl-Substituted

Aromatic Compounds

2.4.5.1 Oxidation of Arenes to Quinones

Richard W Fischer

2.4.5.1.1 Introduction
Quinones and, in particular, naphthoquinone derivatives are industrially valuable
products for further processing and for direct use due to their pronounced
bioactivity [ la,b]. 2-Methyl- 1,4-naphthoquinone, vitamin K1 (“menadione”), is
the basis of the vitamin K group (coagulation vitamins). The skeleton of 2-
methyl- 1,4-naphthoquinone is common to all fat-soluble K vitamins. Deriva-
tives of vitamin K promote the formation of prothrombin and other blood coa-
gulation factors. They are used on an industrial scale as supplement in animal
feed, but are also employed in the treatment of Melaena neonatorum in new-
born babies. Trimethyl-p-benzoquinone is a key compound for the synthesis
of vitamin E, active as antioxidant agent. As an example, the current method
of the production of trimethyl-p-benzoquinone on an industrial scale is p-sulfo-
nation of 2,3,6-trimethylphenol followed by stoichiometric oxidation using
Mn02 [ lc].

2.4.5.1.2 Catalysts and Substrates

In general, the preparation of quinones still requires the use of environmentally
unacceptable stoichiometric oxidants such as Cr03/H2S04[ 1d,e], ceric ammo-
nium nitrate or sulfate [2], manganese dioxide, manganese(II1) sulfate, or periodic
acid [3]. Some attempts have been made to drive these reactions catalytically and
thus more cleanly, for example using supported palladium(I1) [4] or peroxyacetic
acid. When H 2 0 2 is used as oxidant, its activation is required and is generally
accomplished with transition metal catalysts or with systems such as hexafluoro-
acetone hydrate/H202, but the space-time yields are still too low for industrial
purposes [5]. As a result, the selective oxidation of arenes to hydroxy-substituted
compounds and consecutively to quinones is still a challenge for catalysis
research.

Oxidation of Naphthalene Derivatives

A novel family of catalysts [6], highly useful for the purpose described above, are
organometallic as well as inorganic rhenium oxides such as methyltrioxorhenium
[CH3Re03] (MTO), Re03, or Re207.
434 2.4 Oxidations

Table 1. Oxidation of benzene and naphthalene derivates with CH3Re03 as catalyst.a'

Entry R' R2 R3 R4 Conversion Yield Selectivityb'
a/b [%I [%I [%I

a-2 CH3 H CH3 H 36 15

a-3 CH3 CH3 CH3 H 60 33
a-4 CH3 CH3 CH3 CH3 56 39
R5 R6 R7 R* R9
b- 1 H H H H 40 61
b-2 H H H H 81 58 86
b-3 CH:, H H H 94 61 98
b-4 H CH3 H H 90 60
b-5 H H CH3 H 91 64
b-6 CH3 CH3 H CH3 78 40
b-7 H H H H 97 31 93
b-8 H H H H
b-8 H H H H 100 95 95
The entries are numbered systematically, corresponding to the formulas of the substrates and
products shown in eqs. (1) and (2).
h, Selectivity of oxidation of the substituted ring.
'' Substrate: 1-hydroxynaphthalene.
Substrate: 1-hydroxy-2-methylnaphthalene.

In acetic acid/H202/CH3Re03, 2-methylnaphthalene is oxidized with high

chemo- and regio-selectivity (85-98 %, see Table 1) preferentially to the 1,4-
quinone [7].
The reaction can be smoothly applied to a broad variety of alkyl-substituted
benzene and naphthalene derivatives: 2,3-dimethyl-, 2,5-dimethyl-, or 2,3,5,8-
tetramethylnaphthalene and 1-hydroxy-2-methylnaphthaleneare converted by
CH3Re03/H202in good to excellent yields (60-100 %); see Table 1 and eqs.
(1) and (2) 17, 81.

0
 2.4.5.1 Oxidation of Arenes to Quinones 435

Naphthalene itself is transformed to naphthoquinone with 60 % yield with

respect on converted educt. The high regioselectivity of the CH3Re03/H202
system is particularly noteworthy: in the industrial synthesis of menadione with
Cr03, producing 18 kg of chromium waste per kg of product, selectivities of
only 40-60 % are reported [ld,e].
Therefore, the method described allows a novel economic as well as ecologi-
cally sound synthesis of quinone derivatives. Higher condensed arenes, e.g.,
anthracene, are converted to the quinones or cleaved to dicarboxylic acids, as
in the case of phenanthrene (yield ca. 50 %). Besides MTO, in principle all
alkyl- and to some extent also aryl-substituted trioxorhenium compounds, e.g.,
cyclopropylrhenium trioxide or cyclopentadienylrhenium trioxide, can be used
as active catalysts. However, until now MTO apparently constitutes the most
active and easy-to-handle catalyst (see Figure 1, p. 439). The solvent of choice
for the reaction and the workup procedure, is concentrated acetic acid, also
used to dilute the H202 (85 wt.%), yielding a water-poor reaction medium
which is advantageous for the catalyst lifetime.

Oxidation of Hydroxy- and Methoxy-Substituted Arenes

Alkylrhenium trioxide-catalyzed oxidations of hydroxy-substituted arenes (i.e.

phenol or naphthol derivatives, discussed as intermediates on the way to the cor-
responding quinones [9]) by 85 % aqueous hydrogen peroxide (diluted in AcOH)
affords the corresponding p-quinones in fair to high yields [lo]. Control experi-
ments without rhenium catalysts yielded very slow oxidations (less than 10 %
conversion). Furthermore, under the conditions of the H202/CH3Re03/AcOHoxi-
dation, the quinones formed are quite stable: thus hydroxy-substituted p-quinones
are not derived from overoxidation of the p-quinones.
The reaction has a pronounced temperature effect on the oxidation: at higher
temperatures the conversion increases while the selectivity drops slightly. Con-
version and selectivity can also be increased by use of higher amounts of hydro-
gen peroxide [ 101. Water retards the H202/MTO/AcOH oxidation system (cf.
also Section 2.4.5.1 S ) . The use of highly concentrated H202 is advantageous.
Since MTO catalyzes the formation of peroxyacetic acid from AcOH and
H202,control experiments demonstrated that authentic peroxyacetic acid is not
an efficient oxidant for the transformation of phenols to quinones. Thus the
MTO/H202 system forms the catalytic active species [7]. It was observed that
the more electron-rich the phenol, the higher the oxidation rate: the oxidation
of simple phenol (85 % conversion) takes twice as long as the oxidation of
2,3,6-trimethylphenoI (100 % conversion). In general, better yields of quinone
436 2.4 Oxidations

are obtained with a higher degree of methyl substitution. Steric effects seem
to play no predominant role: under the same reaction conditions, almost the
same extent of conversion was obtained in the oxidation of 2,6-dimethyl- and
2,6-di(t-butyl)phenol.
Analogously to polycyclic arenes, electron-rich methoxy-substituted arenes
such as 1,2,3-trimethoxy-.5-methylbenzeneare oxidized in fair yields (40-80
%) with AcOH/H202/CH3Re03to the p-benzoquinones with loss of a methoxy
group [ 111. p-Benzoquinones are important for pharmaceutical purposes; for
example, 2,3-dimethoxy-5-methyl-p-benzoquinone constitutes a key intermediate
in the synthesis of coenzyme Q [ l l , 121. Larger amounts of MTO, beneficially
administered to the reaction system in small doses, improve the yields. When
the arenes are treated only with peroxyacetic acid, e. g., formed from MTOI
H202 and AcOH, almost no conversion can be found, as control experiments
showed [ 111. However, under totally acid-free reaction conditions the rates are
very slow. In ethanol as solvent, doped with small amounts of HBF,, 2,3-
dimethoxy-5-methyl-p-benzoquinone can be formed with 67 % selectivity.
Since the oxidation took place under totally peracid-free conditions, the
-
known bis(peroxo) complex CH3Re0(02)* H 2 0 is supposed to be the major
active species. Interestingly, the oxidation of the simple p-methoxyphenol in
ethanol/HBF, gave the best result, with 95 % conversion and 83 % selectivity.
Catalytic oxidation of 2,6-di(t-butyl)-4-methylphenol formed the hydroxylated
2,6-di(t-butyl)-4-methyl-2,5-cyclohexadien-l-on-4-ol in 30 % isolated yield
[ 111. This is comparable with the yields obtained by using dimethyldioxirane
as stoichiometric oxidant. For comparison the less activated but also substitu-
ent-blocked mesitylene is transformed by rhenium catalysts solely to hydroxy-
mesitylene and 1,3-dihydroxymesitylene, respectively [6i, 8, 131. Since an
arene oxide intermediate is postulated for the dioxirane oxidation [14], it is
similarly proposed that the latter MTO-catalyzed transformation also proceeds
via an arene oxide mechanism which could also operate in the MTO-catalyzed
oxidation of alkoxy-substituted arenes to benzoquinones employing phenols as
intermediates.

Inorganic Rhenium Oxides as Catalysts

Similarly to alkyl-substituted rhenium oxides, their simple inorganic counter-

parts Re207 and Re03 work also as selective catalysts in the transformation of
arenes to the corresponding hydroxy compounds or quinones [7, 13, 151. Base-
stabilized Re207 shows a close activity, not much below that of [CH3Re03].
This turns out to be advantageous, because such oxides are more easily acces-
sible than the alkylrhenium oxides. Ionic species such as the ReVII complex
[03Re{ (CH&NC2H4}2NCH3][Re04] occupy an intermediate position in terms
of activity. Here the catalytic active part is assigned to the base-complexed
[Re03]+moiety. In contrast, however, perrhenates (KReO, or NH4ReO4) exhibit
no activity at all. Analogously to [CH3Re031,Re207 or Re03 also catalyzes the
formation of peroxyacetic acid from AcOH/H202.Compared with MTO, Re207
 2.4.5.1 Oxidation of Arenes to Quinones 437

and Re03 seem to bear a slightly higher selectivity in the formation of aromatic
hydroxy compounds if the formation of quinones is blocked, as in the case of
the oxidation of mesitylene to hydroxymesitylene [ 131.

2.4.5.1.3 Active Species and Mechanism

As discussed above and in striking contrast to previous predictions [ 161 and text-
book standards [ 171, simple organometallic (RRe03) or inorganic rhenium oxides
such as Re207 [6d, 6i, 181 and ReO, [13, 151 become active in oxidation chem-
istry upon treatment with dilute (MTO) or concentrated H202(Re2O7, ReO,). The
catalytic active species can be generally described as side- on bound bis(peroxo)
complexes of rhenium-containing species (stoichiometrically performed control
experiments, [6d,i, 7, 151). With MTO as precursor, the active species is repre-
sented by a structurally fully characterized yellow-orange explosive solid of em-
-
pirical formula [CH1Re0(02)2 H20] (see Scheme 1, top) [6c,d,i] and analo-
gously, in the case of Re207as precursor, as a red- orange solid of empirical for-
mula [H4Re2OI3],also structurally fully characterized (see Scheme 1. right) [15].
It is proposed that ReO, is converted by H202 to solvated [ReO,’] [19] which
reacts further to [HORe0(02)2 * H20], “peroxo perrhenium acid’’, derived
from [CH3Re0(02)2* H20] by replacing the OH for CH3 [15] (see Scheme 1,
left-hand side).

Scheme 1
438 2.4 Oxidations

A major advantage of the novel catalyst [CH3Re0(02)2 H20] is that the hy-
drolysis products [CH3Re03] and [CH,ReO(O,) * H20] again react with H202
to regenerate the active species. By way of contrast, the hydrolysis product of
the water-sensitive [H4Re2OI3](derived from Re207 and H202) is perrhenic
acid [H(ReO,)], which does not react with H202again.
The aforesaid peroxo complexes react with 2-methylnaphthalene quantita-
tively to give 2-methyl-l,4-naphthoquinonewith high regioselectivity (>10:1)
in acetic acid. Analogously to the epoxidation of olefins, [CH3Re0(02)2
H20] transfers only one of the peroxide oxygen atoms to the arene substrate,
yielding the mono(peroxo) complex CH3ReO(02) H 2 0 [6d, 71. Since the
MTO/H202 and Re207/H202systems are powerful epoxidizing agents, it has
been discussed whether the initial step of the arene oxidation involves the
formation of arene oxides, as observed in the MTO-catalyzed oxidation of ful-
lerenes to CG0oxide [lOa]. In the case of less substituted arenes, the acid-cata-
lyzed isomerization of the arene oxides will lead to the hydroquinones, and sub-
sequent oxidation affords the quinones. This is illustrated in Scheme 2 [lob].
Here, the formation of intermediary epoxides is also confirmed by the formation
of minor amounts of o-hydroquinones (catechol), o-quinones and muconic an-
hydrides [7, 10, 111.

Q OH

-3-Gi-
H202/[cat.] Rpi$R
0

R
Scheme 2 OH 0

In the case of the rhenium-catalyzed oxidation of methoxy- and hydroxy-sub-

stituted substrates, there is some complementary work concerning the general
mechanism of the arene oxidation [lob, 111. Since the major products in the
oxidation of such arenes or phenols are the quinones, the formation of inter-
mediary epoxides seems to be a predominant reaction step. When p-substituted
phenols such as 2,6-di(t-butyl)-4-methylphenol are treated with the MTO/H202
oxidant and acetic acid as solvent, the formation of hydroxydienones is ob-
served. This is also reported for the oxidation using dimethyldioxirane as oxi-
dant [20]. Since an arene oxide intermediate was postulated for the dioxirane
oxidation, a similar mechanism is plausible here [ll], e. g., for the oxidation
of 1,2,3-trimethoxy-5-methylbenzene(Scheme 3 ) or 2,6-di(t-butyl)-4-methyl-
phenol.
 2.4.5.1 Oxidation of Arenes to Quinones 439

H3c0q
H3CO
\

OCH3
CH3 H202lMTO
AcOH H3c0QcH3
H3CO
OCH3

J
OH
acid

0
H3c0'Jo'cH3

H3CO HsCO
~

Scheme 3 OCH3 0

2.4.5.1.4 Comparison with Other Catalysts and Conclusion

The reported results of the rhenium-catalyzed arene oxidations compare well with
other, partly established, catalytic systems such as supported PdII systems
(naphthalene oxidation [4]), RuC13, H3PMo,2040,CuC12/(C2H5)3N * HC1, CuC12/
py (phenol oxidation [lc, 211) as well as H2S04,CF3C02Hand K3[Fe(CN),] (oxi-
dation of methoxy-substituted arenes [22]) [7, 10, 111. However, the rhenium cat-
alysts show often higher selectivities than alternative catalysts, especially in the
oxidation of naphthalene derivatives. Within the rhenium-based systems, MTO
is the most active one. However, the simple oxides Re03 and Re207 are also

Figure 1. Comparison of the relative activities of different rhenium catalysts in the formation
of 2Jdimethyl- 1,4-naphthoquinone (acidic conditions); L = 2,2'-bipyridine, L' =
4-tert-butylpyridine, L" = pentamethyl(diethy1)triamine ([(CH3)2NC2H4]2NCH3).
440 2.4 Oxidations

very active and easily accessible catalysts. A comparison of the relative activities
of different rhenium catalysts in the formation of 2,3-dimethyl- 1,4-naphthoqui-
none is given in Figure 1 (acidic conditions) [15]. Therefore these new types of
catalysts support a convenient and novel method for various oxidative transforma-
tions of arene systems under environmentally acceptable conditions.

2.4.5.1.5 Recent Developments

Improvement of the Catalyst System

The solvent of choice for the MTO-catalyzed oxidation of aromatics is glacial acetic
acid. The application of acetic acid anhydride (AAA) in combination with acetic
acid (AA) as solvent improves the MTO catalysis procedure considerably [23].
Howevel; it must be pointed out that the handling of acetic acid anhydride
or other organic acid anhydrides with H202, especially in the presence of
MTO, can form explosive and thus harmful organic peroxides! Accordingly,
special safeguards have to be provided.
The use of the inexpensive solvent AAA improves the solubility of naphthalene
derivatives and no co-solvent is needed. No multicomponent mixtures are
produced and the use of drying agents like MgSO, or Na2S04can be avoided.
The water trapping property of AAA is beneficial for the catalyst lifetime. The
AAA/AA ratio has a pronounced effect on the activity of the system. The presence
of AA as a source of H' is necessary for the completion of the oxidation reaction
pathway. In comparison with the standard catalyst (MTO in glacial AA), the
anhydride-promoted system requires lower concentrations of MTO and gives
high regioselectivities (e. g., 90 % in the case of vitamin K). This is a clear advan-
tage over metalloporphyrin-based catalysts [24].

Catalyst Decomposition and Recycling

The general pathway of catalyst deactivation is the decomposition of the peroxo

system CH3Re0(02)2* H 2 0 to HRe04, CH30H, and oxygen. Once the methyl
group is disconnected from the Re center the catalytic activity of the MTO-derived
peroxo system is lost completely. High temperatures and the presence of high
amounts of water accelerate the catalyst deactivation rate. High TONS can be
achieved by controlling the reaction temperature and the use of water-free organic
solvent systems which are able to trap the reaction water formed from H202.
Nevertheless, MTO can also be applied in aqueous solution when a low pH
stabilizes the catalyst.
The established synthesis routes for MTO and its congeners are the direct alkyl-
ation of dirhenium heptoxides with Sn(CH3),, tetraalkyltin or dialkylzinc reagents
yielding highly pure alkylrhenium trioxides (eq. ( 3 ) ) , and the alkylation of Re207
in the presence of trifluoro- or trichloroacetic or carboxy anhydrides (eq. (4)) [6].
 References 44 1

Here the formation of unreactive Re-containing by-products is suppressed, but the

anhydrides used are expensive and rather sensitive.

Re24 + Sn(CH314 reflux-

THF CH3Re03 + (CH3)3SnRe03 (3)

Now, an improved and simple one-pot synthesis for alkylrhenium oxides facil-
itates the use of a wide variety of perrhenates as starting materials [25].According
to eq. ( 5 ) perrhenates M[Re04], with (n = 1,2 and M = K+, Na+, Zn2+,Ca2+,etc.)
are treated with TMSCl [(CH,),SiCl] and tetramethyltin or other alkylating tin or
zinc organyls.
M[Re04] + 2TMSCl + Sn(CH& -+
(5)
CH3Req + (TMS)20 + CISn(CH& + MCI

The key advantage of this improved route is the possibility of an efficient

catalyst recycling in the MTO-catalyzed oxidation processes: the perrhenates
(formed during catalyst deactivation) can be separated from the inactive, ex-
hausted catalyst solution through precipitation of perrhenic acid from the reaction
solution. Generation in situ of the active species, CH3Re0(02)2 H20, starting
from M[Re04], is possible [26]. The improved synthesis strategy represents an
ecological and simple access to organorhenium oxides.

References
[ l ] (a) J. Rodriguez, E. QuifioB, R. Riguera, B. M. Peters, L. M. Abrell, P. Crews, Tetrahe-
dron 1992, 48, 6667; (b) J. W. Suttie, Biofactors 1988, I, 55; (c) K. Takehira, M. Shi-
mizu, Y. Watanabe, H. Orita, T. Hayakaw in New Developments in Selective Oxidations
(Eds.: G. Centi, F. Trifiro), Elsevier, New York, 1990, p. 133; (d) R. A. Sheldon, Top.
Cum Chem. 1993, 164, 21; (e) R. A. Sheldon, J. Dakka, Catal. Today 1994, 19, 215.
[2] (a) T. L. Ho, Synth. Commun. 1979, 237, 9; (b) T. L. Ho, T. W. Hall, C. M. Wong, Chem.
fnd. 1972, 729; (c) Y. H. C. Giza, K. A. Kun, H. G. Cassidy, J. Org. Chem. 1962, 27,
679.
[3] (a) R. H. Thomson in The Chemistry of Quinonoid Compounds, (Ed.: S. Patai) Wiley,
New York, 1974, pp. 132-134; (b) L. M. Jackman, Adv. Org. Chem. 1960, 2, 329; (c)
J. March, Advanced Organic Chemistry, 3rd ed., John Wiley, New York, 1985, pp.
1081 ff; (d) R. A. Sheldon, J. K. Kochi, Metal-Catalyzed Oxidation of Organic Com-
pounds, Academic Press, New York 1981, p. 181; (e) W. J. Mijs, C. R. H. I. de Jonge
(Eds.), Organic Syntheses by Oxidation with Metal Compounds, Plenum Press, New
York, 1986; (f) R. P. Kreh, R. M. Spotnitz, J. T. Lundquist, J. Org. Chem. 1989, 54,
1526; (g) H. Uno, J. Org. Chem. 1986, 51, 350; (h) T. A. Gorodetskaya, I. V. Kozhev-
nikov, K. I. Matveev, RU 1.121.255 (1984); Chem. Abstr. 1985, 102,203.754; (i) J. Skar-
zewski, Tetrahedron 1984, 40, 4997; 0 ) M. Periasamy, M. V. Bhatt, Tetrahedron Lett.
1978, 4561; (k) Y. Asakawa, R. Matsuda, M. Tori, M. Sono, J. Org. Chem. 1988, 53,
5453; (1) W. Chen, Youji Huaxue 1986, (6),432; Chem. Abstr: 1987, 107, 58620.
442 2.4 Oxidations

[4] S. Yamaguchi, M. Inuoe, S. Enomoto, Bull. Chem. Soc. Jpn. 1986, 59, 2884.
[5] W. Adam, P. A. Ganeshpure, Synthesis 1993, 280.
[6] Alkylrheniumoxides are known to be versatile, highly active and efficient catalysts for
the oxidation of various organic substrates such as olefins, alkynes, amines, ketones,
sulfides, or metal carbonyls: (a) Hoechst AG (W. A. Herrmann, D. W. Marz, J. G. Kuch-
ler, G. Weichselbaumer, R. W. Fischer) DE 3.902.357 (1989); (b) W. A. Herrmann,
R. W. Fischer, D. W. Marz, Angew. Chem. 1991, 103, 1706; Angew. Chem., Int. Ed.
Engl. 1991, 30, 1638; (c) W. A. Herrmann, R. W. Fischer, W. Scherer, M. U. Rauch,
Angew. Chem. 1993, 10.5, 1209; Angew. Chem., Int. Ed. Engl. 1993, 32, 1157;
(d) W. A. Herrmann, R. W. Fischer, M. U. Rauch, W. Scherer, J. Mol. Catal. 1994,
86, 243; (e) W. R. Thiel, R. W. Fischer, W. A. Herrmann, J. Organomet. Chem.
1993, 459, C9; (0P. Huston, J. H. Espenson, A. Bakac, Inorg. Chem. 1993, 32,
4517; (g) S. Yamazaki, J. H. Espenson, P. Huston, Inorg. Chem. 1993, 32, 4683;
(h) W. Adam, C. M. Mitchell, C. R. Saha Moller, Tetrahedron 1994, 46, 13121;
(i) R. W. Fischer, Ph. D. Thesis, Technical University of Munich, 1994, pp. 162-167;
(j)W. A. Herrmann, R. W. Fischer, J. D. G. Correia, J. Mol. Catal. 1994, 94, 213.
[7] W. Adam, W. A. Herrmann, J. Lin, C. R. Saha-Moller, R. W. Fischer, J. D. G. Correia,
Angew. Chem., Int. Ed. Engl. 1994, 33, 2475.
[8] Hoechst AG (W. A. Herrmann, W. Adam, R. W. Fischer, J. Lin, C. R. Saha-Moller, J. D.
G. Correia) DE 4.419.799.3 (1994).
[9] S. Yamaguchi, H. Shinoda, M. Inoue, S. Enomoto, Chem. Pharm. Bull. 1986,34,4467.
[lo] (a) R. W. Murray, K. Iyanar, Tetrahedron Lett. 1997, 38, 33; (b) W. Adam, W. A. Herr-
mann, J. Lin, C. R. Saha-Moller, J. Org. Chem. 1994, 59, 8281.
[ 111 W. Adam, W. A. Herrmann, C. R. Saha-Moller, Masao Shimizu, J. Mol. Catal. 1995,
97, 15.
[12] S. Yamada, T. Takeshita, J. Tanaka, Yuki Gosei Kagaku Kyokai Shi 1982, 40, 268.
[13] Hoechst AG (W. A. Herrmann, R. W. Fischer, J. D. G. Correia), DE 4.419.800 (1994).
[I41 W. Adam, S. Shimizu, Synthesis 1994, 560.
[15] W. A. Herrmann, J. D. G. Correia, F. E. Kiihn, G. R. J. Artus, C. C. Romao, Chem. Eur:
J. 1996, 2(2), 168.
[16] K. A. Jorgensen, Chem. Rev. 1989, 89, 431.
[17] (a) W. J. Mijs, C. R. H. I. de Jonge in Organic Syntheses by Oxidation with Metal Com-
pounds, Plenum Press, New York, 1986, pp. 181, 618-619; (b) R. A. Sheldon, J. K.
Kochi, Metal-Catalyzed Oxidations of Organic Compounds, Academic Press, New
York, 1981, pp. 47-48, 166.
(181 S. Wanvel, M. Rusch, M. Sojka, J. Chem. Soc., Chem. Commun. 1991, 1578.
[I91 W. A. Herrmann, P. W. Roesky, F. E. Kiihn, M. Elison, G. Artus, W. Scherer, C. C.
Romao, A. D. Lopes, Inorg. Chem. 1995, 34, 4701.
[20] J. K. Crandall, M. Zucco, R. S. Kirsch, D. M. Coppert, Tetrahedron Lett. 1991, 32,
5441.
[21] (a) S. Ito, K. Ahihara, M. Matsumoto, Tetrahedron Lett. 1983, 5249; (b) M. Shimizu,
H. Orita, T. Hayakawa, K. Takehira, Tetrahedron Lett. 1989, 471; (c) N. Ravasio,
M. Gargano, M. Rossi in New Developments in Selective Oxidations (Eds.: G. Centi,
F. Trifirb), Elsevier, New York, 1990, p. 139.
[22] (a) H. Sugihara, M. Watanabe, Y. Kawamatsu, H. Morimoto, Liebigs Ann. Chem. 1972,
763, 109; (b) S. Terao, Y. Kawamatsu, JP 79-106.440 (1979); Chem. Abstr: 1980, 92,
P41578n; (c) M. Matsumoto, H. Kobayashi, Y. Hotta, J. Org. Chem. 1985, 50, 1766.
[23] W. A. Herrmann et al., J. Mol. Cat. A: 1999, 62, 373.
[24] R. Song, A. Soriokin, J. Bernardou, B. Meunier, J. Org. Chem. 1997, 62, 373.
[25] W. A. Herrmann et al., Angew. Chem., Int. Ed. Engl. 1997, 36, 2652.
[26] R. M. Kratzer, Ph. D. Thesis, Technical University Munich 1998, p. 202.
 2.4.5.2 Oxidation of Alkyl-Substituted Aromatic Compounds with Air 443

2.4.5.2 Oxidation of Alkyl-Substituted Aromatic

Compounds with Air
Richard W Fischer; Freimund Rohrscheid

2.4.5.2.1 Introduction
One of the largest industrial-scale applications of homogeneous catalysis is repre-
sented by the oxidation of hydrocarbons, especially the transition metal-catalyzed
autoxidation of p-xylene to terephthalic acid or its esters (cf. Section 2.8.1.2, [l],
(eq. (1)).

0 I
+ 302
ColMnlHBr
acetic acid
190 205°C
~

15 - 30 bar
COOH

COOH

On a smaller scale m-xylene is oxidized to isophthalic acid. In the field of fine

chemicals, different toluene derivatives and other alkyl-substituted aromatic sys-
tems are oxidized to a variety of substituted aromatic acids, which constitute im-
portant feedstocks to polymers, plastics, fibers, foils, or intermediates for pharma-
ceuticals and agrochemicals.

2.4.5.2.2 Historical
In spite of its topicality, the history of the industrial transition metal-catalyzed
oxidation of alkylaromatic compounds dates back to the early 1920s with the con-
tinuous oxidation of ethylbenzene to acetophenone using manganese acetate as
catalyst. This process was developed by the IG Farben at Uerdingen [2].

Dimethyl Terephthalate by the Witten Process

Originally developed by the Chemische Werke Witten GmbH in the early 195Os,
the large-scale production of dimethyl terephthalate (DMT) marks the start of
industrial air oxidation of alkyl aromatic substrates to the corresponding acids
[3]. However, the technical and chemical improvement of the Witten process is
still a topic of current research activity [3g-1].
The Witten process, which is also known as the Imhausen or Katzschmann
process [3a-fJ, involves the oxidation of p-xylene to p-toluic acid as a reaction
intermediate. For activity reasons, the p-toluic acid is esterified with methanol
to methyl toluate, which is then oxidized to monomethyl terephthalate. The two
oxidation reactions take place simultaneously in one oxidation system; likewise
444 2.4 Oxidations

both esterifications occur together. The mixture of the mono- and bismethyl esters
is separated by distillation, the toluic acid methyl ester is recycled into the oxida-
tion section, and the DMT is recrystallized from methanol or xylene (cf. Section
2.8.1.2).

Terephthalic Acid by the AMOCO MC Process

The AMOCO Chemical Corp. developed from the late' 1950s until the middle of
the 1960s, a liquid-phase oxidation process [3f, 41, performed at 190-205 "C and
1.5-3 MPa, to obtain in one step fiber-grade terephthalic acid (99.99 %) reaching
selectivities of 90 % (see eq. (1)).
Thus, the breakthrough in air oxidation of alkylaromatic compounds can be-
traced to the development of this AMOCO MC method, applying a synergistically
acting C o M n B r catalyst, originally discovered by Saffer and Barker [4a], in
concentrated acetic acid as optimal solvent (vide infru). The bromide ions,
added as NH4Br, tetrabromoethane, CoBr,, MnBr2, or HBr, act as a co-catalyst,
serving as a source of free radicals.

2.4.5.2.3 Catalysts, Solvents, Reaction Conditions,

and General Processing
Catalysts

The liquid-phase oxidation of hydrocarbons with transition metalhromide cata-

lysts, mainly containing cobalt(I1) and manganese(I1) acetates and, depending
on the application, additionally salts of Ce"', H?", Mo"', Ni", Pd", Ti'", V", and
Ze", is one of the major methods of preparing aliphatic and aromatic carboxylic
acids as well as alcohols, acetates, aldehydes, and ketones. The latter compounds
serve mostly as reaction intermediates to the corresponding acids. On a commer-
cial scale, aromatic systems are the most important substrates [5]. In order of
increasing reactivity, the most important catalysts are represented by the systems
MnBr, Co/Br, CoMnBr, Co/Mn/Br/Zr [5, 61. Depending on reaction conditions
and electronic properties of the substrates, the molar ratio of the metals may differ
over a broad range. In the highly active Co/Mn/Zr/Br catalyst a typical ratio is
given by 1:(O. 1-5):0.01:( 1.1-6). Typical catalyst concentrations range from 0.1
to 10 mol% with respect to the substrate. In certain cases, only traces of manga-
nese or zirconium are required. Generally the amount of bromide ions is equiva-
lent to the sum of the metal ions used. However, more bromide is required if high
bromide consumptions occur, which depend on the substrates and the reaction
conditions. Strong catalyst poisons (radical scarvengers) are anions such as iodine,
cyanide, and thiocyanide, or amino and hydroxy groups bound to aromatic sys-
tems.
 2.4.5.2 Oxidation of Alkyl-Substituted Aromatic Compounds with Air 445

Counter Ions and Solvents

The counter anions to the metals play a crucial role in catalyst activity. They
influence the coordination chemistry of the catalytic active metal species and
thus their redox potentials. Best results are obtained with a combination of car-
boxylates and bromide, forming an active species of the general formula
M113'f'[Br(0,CR),,2].
The solvent of choice, with respect to activity, selectivity, and product isola-
tion, is acetic acid. Comparable catalyst activities are also obtained using
longer-chain carboxylic acids such as propionic or valeric acid, but their co-oxi-
dizing properties are expressed much more compared with acetic acid and there-
fore it is often not feasible to use them for commercial applications [ S ] . Water
supresses catalyst activity drastically, thus its application is restricted to certain
cases and substrates.

Reaction Conditions

The reaction conditions can be varied over a wide range with temperatures be-
tween 100 and 250 "C and oxygen partial pressures from 0.02 to 0.6 MPa, to ac-
commodate the changes in the reactivity of the substrates. The oxidations take
place in the liquid phase, to which air is supplied with vigorous stirring. The
usual reactor type is a stirred tank reactor which is usually processed as a batch
system. In the case of high-volume products like terephthalic acid, continuous re-
actors are applied. The reaction heat is removed by cooling the reactor wall and
additionally by partly refluxing the reaction solvent. In most cases the aromatic
acids formed will crystallize from the reaction solvent after cooling and by dosing
the cold substrate into the reaction mixture. The product crystallization constitutes
one of the major advantages of this process. Product separation and purification
are optimally combined in one step. The products are separated by filtration or
centrifugation, washed with acetic acid to remove the catalyst and intermediates
as well as impurities, and subsequently dried. An efficient catalyst and solvent
recycling is only possible with selectivitieshigher than 95 %.

2.4.5.2.4 Scope and Limitations

Depending on the alkyl-substituted aromatic systems - simple toluene derivatives,
condensed or oligomeric compounds - and depending strongly on the ligands pre-
sent, large variations in activity and selectivity may be found. In general toluene
derivatives bearing substituents such as halogens (except iodine), acetoxy, acetyl,
carboxy or carboxy esters, methoxy, nitro (if not in the ortho-position), t-butyl, or
sulfonyl, as well as alkyl or aminosulfonyl, can be oxidized with high selectivities.
Mostly the yields are between 80 and 95 %. In certain cases, e.g., the oxidation of
methylsulfonated toluenes, isolated yields up to 98 % are possible. A general
equation for the process described is given in Scheme 1.
446 2.4 Oxidations

R COOH

S4 + o2
3~2
Co/Mn/Br
acetic acid
100 - 250 "C
-
5 30 bar
- H20

20 2

R = ethyl s

Scheme 1. General scheme for catalytic oxidation of substituted alkylbenzenes.

Besides toluenes, ethyl- or isopropyl-substituted arenes can also be oxidized se-

lectively to acetyl-substituted systems which may be transformed further into the
corresponding carboxylic acids. Even t-butyl groups, as in 4,4'-bis(t-butyl)biphe-
nyl, can be oxidized to the corresponding carboxyl groups [7]. Due to the strong
interest in the commercial production of 2,6- and 1,4-dicarboxynaphthalenes,
there are many patents concerning the oxidation of methyl-, ethyl-, or isopro-
pyl-substituted arenes to the aromatic di-acids [8]. Also, toluenes or xylenes con-
nected by spacer groups like -0-, -S-, isopropyl or hexafluoroisopropyl are of
practical interest for applications in air oxidation reactions (see Section 2.4.5.2.7).

Influence of Substituents

The influence of substituents is summarized in Table 1. The righthand column of

the table shows the substituents whose presence gives high conversions, high
yields, and thus high selectivities for the formation of the corresponding benzoic
acids. Generally such systems are favorable substrates for the commercial produc-
tion of aromatic carboxylic acids. As a result, simple benzoic acids like 2,4- or
2,3-dichlorobenzoic acid, normally produced by ring as well as side- chain chlor-
ination and consecutive hydrolysis, are of increasing interest for the oxidation
route applying air as the oxygen source.
However, the substituents shown in the lefthand column hinder the oxidation of
the toluene derivatives completely. Phenols, thiophenols, anilines, o-phenoxy-,
and iodine-substituted arenes cannot be oxidized to the aromatic acids, for these
substituents act as strong radical scavengers and thus as catalyst and autoxidation
poisons. In contrast to m- and p-nitrotoluene, which can be smoothly oxidized to
the nitro-substituted benzoic acids, o-nitrotoluene and its derivatives turned out be
almost inert. This is due to the high reactivity of the benzylic radical, which ob-
 2.4.5.2 Oxidation of Alkyl-Substituted Aromatic Compounds with Air 447

Table 1. Influence of the substituents on the oxidation of alkvl side chains.

Total radical consumption, Side reactions, Complete conversion,
no yield yield 30-70 % yield 90-98 %

viously reacts faster with its orrho substituent than with dioxygen (“orrho effect”).
Thus different methods have been developed to prepare o-nitrobenzoic acids,
mostly by applying co-oxidations using p-xylene, aldehydes, ketones, or HN03
as auxiliary oxidants [9-111.
The substituents of the central column in Table 1 allow poor to moderate con-
versions of the starting toluenes. Here radical consumption and side reactions are
also prevailing pathways.
Nevertheless, even with the restrictions to the substituents in the righthand col-
umn, a great number of convertible aromatic substrates remain. The possibilities
for different combinations of the various substituents and aromatic systems are
plenty.

2.4.5.2.5 Mechanism
The simplicity of the easily surveyed reaction equation is strongly misleading. The
reaction mechanism of the autoxidation of alkyl-substituted aromatic compounds
consists of several complex steps - free-radical chain reactions triggered by oxi-
dation catalysts. In general, two initiation steps can be distinguished [5, 6, 101:
448 2.4 Oxidations

(1) Electron transfer from the arene to Co3+ions to yield an arene radical cation
which, in turn, forms a benzyl radical by proton loss (eqs. ( 2 ) and (3)).
Ar-CH3 + Co3+
[Ar-CH3]+*
-
-
[Ar-CH3]+*
Ar-CH2* +
+
H+
Co2+ (2)
(3)

(2) Abstraction of benzylic-bound hydrogen atoms by radicals (Rad.) such as Hal-

(esp. BP), R., ROO,ROO-, dioxygen complexes or dioxygen (autoxidation);
see eq. (4), and Scheme 3 in Section 2.8.1.2.
Ar-CH3 + Rad* - + Rad-H
Ar-CH2* (4)
The rate of benzylic hydrogen abstraction at arenes, performed by the radicals
mentioned above, is not very sensitive to the electron density in the aromatic
systems [5, lOa], in contrast to the metal-catalyzed electron-transfer mechanism
[5, 111.
The modification of the initiation step and the reaction mechanism is based
on the high reactivity of the catalytic active transition metal complexes toward
peroxides and peroxy radicals which are formed by autoxidation or from benzylic
radicals which have been trapped by oxygen. To elucidate the combined complex
reaction mechanisms, the impact of the single catalysts will be discussed sepa-
rately.

Catalysis by Co3'

The monomeric Co3+ion is a powerful oxidant (E, = +1.82 V), especially when it
is surrounded by O-donor ligands such as carboxylate (RCOO-) or water. There-
fore, small amounts of water can yield a beneficial effect. It is supposed that the
formation of radical-water complexes hinders the reduction of Co3+by organic
radicals and slows down the rate of oxygen formation from the reaction of two
peroxy radicals. Thus, the potential of the metal ions is influenced by the counter-
anions and complexing solvent molecules present. The acetates of Co3+and Mn3+
are stable in acetic acid, but not in water. Therefore a serious increase of the water
concentration, formed during oxidations of alkyl groups, will hinder or even stop
the oxidation reaction (210 wt. % H20). Therefore oxidations at very high sub-
strate concentrations might stop due to the formation of large amounts of reaction
water before full conversion of the educt molecules is achieved [5, 61.
The cobalt(II1) initiation and catalysis pathways are very effective in many oxi-
dations but suffer some limitations, e.g., Co3+is strongly inhibited by cobalt(I1)
ions, which seem to form dimers with Co3+.Such dimers are only weak catalysts
in arene oxidations. As a result the rate of oxidations is inversely dependent on the
concentration of Co2+in the reaction mixture; thus the cleavage of such dimers by
addition of small amounts of co-catalysts will attain the reaction rate [llc, 121.
Additionally in the case of deactivated, electron-poor systems such as toluic
acid or p-nitrotoluene, cobalt(II1) alone is not an efficient catalyst - synergistic
co-catalysts are necessary to achieve good results.
 2.4.5.2 Oxidation of Alkyl-Substituted Aromatic Compounds with Air 449

The results of numerous kinetic studies on the reaction of cobalt(III), mangane-

se(II1) and various other metal acetates in acetic acid with alkylbenzenes under
anaerobic conditions [13, 141, but especially of course in the presence of di-
oxygen, are compatible with a generally accepted mechanism [12, 14, 151.
Alkyl-substituted benzenes and alkyl-substituted aromatic compounds consti-
tute the starting molecules. Benzaldehydes, benzyl acetates, and to some extent
also benzyl alcohols are the main intermediates; aromatic carboxylic acids are
the desired products. The intermediate benzyl acetates, benzaldehydes, and the
corresponding acids can also be formed in "stoichiometric" reactions with
Co(OAc), in acetic acid in the absence of oxygen.
In the rate-determining step the alkyl-substituted aromatic compound reacts
reversibly with a Co3+ species via electron transfer to a radical cation which
forms the thermodynamically favored benzylic radical by elimination of H+ (see
eqs. (2) and (3)). Benzyl acetate is derived from the subsequent reaction of the
benzyl radical with cobalt(II1) acetate under anaerobic conditions (eq. (5)).
+ [CO(OAC)]~'
Ar-CHp - Ar-CH2-OAc + Co2+ (5)
However, under autoxidizing conditions, the benzyl radical is trapped by di-
oxygen forming the benzylperoxy radical ArCH,OO., which reacts further to
the hydroperoxy species ArCH,OOH, which is then converted to the correspond-
ing aromatic aldehyde. All these steps are catalyzed by monovalent metal species
bearing different oxidation states (see Scheme 2, righthand side, upper half).
Consecutively after metal-catalyzed oxidation, H+ abstraction, and reaction with
dioxygen, benzoylperoxy radicals are formed from aldehyde molecules. These
radicals are transformed by reactions with Co2+/H+, substrate molecules, or
aldehydes to perbenzoic acid ArC(O)OOH, while Co3+, benzyl, and benzoyl
radicals are formed again. Finally the perbenzoic acid reacts rapidly to the cor-
responding aromatic acid by oxidizing Co2+ to Co3+ (see Scheme 2, righthand
side, lower half). Thus, the oxidation of the benzaldehydes with oxygen simulta-
neously regenerates the Co3+oxidant according to eq. (6).
ArCHO + 02 + + 2 HOAc
2 CO"[OAC]~ - ArCOOH + 2 Co"'[OAcls + H20 (6)
Therefore the catalysis of the oxidation of the alkylbenzenes to the correspond-
ing aldehydes is kept alive by the formation of an excess of Co3+,formed by the
oxidation of the aldehydes with oxygen. In general, oxidation intermediates like
aromatic aldehydes and peroxides, which are normally more reactive than the cor-
responding toluenes, can regenerate highly oxidized metal species. Besides the
free-radical mechanism "stoichiometric" and ionic reaction pathways also play
an important role in the oxidation of alkylaromatic compounds. This is shown
with Co3+ as oxidant on the left-hand side of Scheme 2.

Catalysis with Mn3+

In contrast to cobalt, manganese complexes are less active catalysts. Using manga-
nese(II1) catalysts the oxidations proceed more slowly or, as in the case of electron-
450 2.4 Oxidations

co2+ , H + l l - c03+
Co3+ - Co", - H+

(1
b Ph-CH2-OOH

Ph-C'H-OAC
Cop+ - Co(0H)"

021 Ph-CH2-O'
[Co"l(OAc)]'+ - Co2+,- Ac20

Ph-COOH
I t
Ph-CHO +
co3+
- Co2+,- H+
I

I
Co3+ - Co2+,- H+

[Ph-CO]+ +
-
'03+
co2+
i
Ph-C'O - 02
Ph-C(0)-OO'

Co2+,H+ - co3+

OAc- Ph-CH3 - Ph-CH;

Ph-CHO - Ph-C'O

Ph-C(O)-OAc Ph-C(0)-OOH

Scheme 2. Cobalt-catalyzed oxidation of alkylaromatic compounds.

poor systems, not at all [ 10a, 14a, 151. However in combination with cobalt acetate,
Mn3+plays a dominant role as a highly selective synergetic co-catalyst. This effect
of a small amount of manganese upon the cobalt acetate bromide [CO(OAC)~/B~]
can be traced to its ability to accelerate the reduction of Co3+to Co2+by bromide
ions, which are transformed into bromine radicals Br. and which will react again
 2.4.5.2 Oxidation of Alkyl-Substituted Aromatic Compounds with Air 45 1

with substrate molecules by formation of chain-carrying benzyl radicals [ 10a, 14a,

161. Sometimes only very low Mn3+ concentrations are required to obtain bene-
ficial effects - for example, by the production of nitro-substituted benzoic acids.
However, in contrast to cobalt- based catalysts, the Mn"" system is a perfect
catalyst for the oxidation of aromatic-bound acyl groups Ar-CO-R or diketones
Ar-CO-CO-Ar as well as for the oxidation of aldehydes and alcohols. As a result,
an addition of Mn2+improves the catalyst activity and selectivity.

Metal-Doped Catalyst Systems and the Structure of Cobalt(I1,III)

Acetates in Acetic Acid

An improvement of catalyst activity, especially for the oxidation of electron-poor,

deactivated systems like p-toluic acid, can be reached by addition of other transi-
tion metal compounds to the Co/Mn/Br catalyst. The most prominent additive is
zirconium(1V) acetate, which by itself is totally inactive. An addition of zirconi-
um(1V) acetate (ca. 15 % of the amount of cobalt) can yield reaction rates which
are higher than those observed using a tenfold amount of cobalt acetate. This
amazing co-catalytic effect can be attributed to the common ability of zirconium
to attain greater than sixfold coordination in solution, to the high stability of Z P
toward reduction, and to the ability of zirconium or Hf" to redistribute the dimer/
monomer equilibrium of dimerized cobalt acetates (Co2+/Co3+,Co3+/Co3+sys-
tems) by forming a weak complex with the catalytically more active monomeric
Co"' species [ 171.
Furthermore, it is proposed that the active structures of Co2+and Co3+in an-
hydrous acetic acid are represented largely by uncharged sixfold-coordinated
complexes such as CO"(OAC)~(HOAC)~ and CO"'(OAC)~(HOAC)~. An addition
of water, substituted benzaldehydes, benzoic acids, or phenols might result in ex-
change reactions with acetic acid ligands, and influence the catalytic properties
analogously to the effects observed upon addition of zirconium(1V) acetate
[ 1 4 ~ 1Thus,
. only at high cobalt(I1) concentrations catalytically less active dimers
will play a relevant role.
In the case of terephthalic acid production by oxidation with air, an addition of
Zr, Fe, and Ni produces high conversions of p-xylene to almost colorless
terephthalic acid [17, 181. In this context other catalyst components such as Ce,
W, Mo, V, Cr, Be, Al, Bi, Cd, Fe, Pd, and Nd are claimed [ 181.

Catalysis by the M"7"1/Halogenide-System

Bromide, as hydrogen bromide, alkali bromide, NH,Br, or CoBr,, or organically

bound bromide as in bromoform, tetrabromoethane, or monobromoacetic acid, has
an expressed effect on the cobalt- and manganese-catalyzed autoxidations of al-
kylaromatic hydrocarbons. The catalytic activity of the metal ions is drastically
increased by an addition of bromide ions in the right molar ratio, mostly
n(metal)/n(Br-) = 1:1.
452 2.4 Oxidations

The active catalysts seem not to be free cobalt, manganese, or bromide species,
but complexes like Co(0Ac)Br or Mn(0Ac)Br which act additionally as impor-
tant chain carriers. At higher temperatures the activity of the metaV bromide sys-
tems increases [ 161,
A drawback of the hydrogen bromide catalysis is the formation of unwanted
side chain- or ring-halogenated intermediates, or by-products such as methyl bro-
mide. This can be avoided by using a Co3'/Br- ratio of 1:1 and by controlling the
reaction temperature. Above 140 "C the catalytic effect of the bromine species is
optimal. The amount of catalyst can be decreased. Analogously to bromine, chlo-
ride also shows an accelerating effect. This is due to the formation of a catalyt-
ically active [M"~"'OAc]Cl complex which is much less active compared with
Br- and thus reacts only with benzylic hydrogen.
Applying M1131"/halogenid catalysts, two different mechanisms are responsible
for the start of the oxidation reactions [14, 191: the reaction of the substrates to
radicals and the direct hydrogen abstraction by radicals X. formed from
XCO"'(OAC)~.

Synergism in the Co(0Ac)Br- and Mn(0Ac)Br-Catalyzed Autoxidations

The success of the metal bromide catalysts in alkylaromatic autoxidation resides

mainly in their ability to transfer oxidizing power from the various oxidation in-
termediates to bromide ions to produce bromine radicals like BP and
Br2-. finally (see eqs. (7) - (10)) [16].

Br- + Br* - Br2-* (9)

Br2-* + Ar-CH3 - Br- + HBr + Ar-CHp (10)
Small amounts of cobalt on the "manganese acetate bromide" catalyst
[M~"(OAC)~/HB~] promote the oxidation of Mn2' to Mn3' by peracids. The syner-
gistic effect of a little manganese upon [Co"(OAc),/HBr] can be assigned to the
acceleration of the reduction of CoBr3 by bromide with formation of bromine
radicals Br,-..
The relative rates at which cobalt, manganese, and bromide react with peroxy
acids are in the order

cobalt(I1) > bromide = manganese(II1) > manganese(I1)

Thus the sequence of redox reactions that occurs is first the reaction of peracid
with Co" to give Corrl;Co"' then oxidizes Mn" to Mn"' and finally Mn''' oxidizes
bromide to bromine radicals [6, 201. When a peracid is treated only with manga-
nese(I1) acetate bromide, the peracid reacts preferentially with Br- forming bro-
mine - an undesirable reactant for autoxidation purposes - with the manganese
 2.4.5.2 Oxidation of Alkyl-SubstitutedAromatic Compounds with Air 453

playing a purely passive role (eqs. (1 1) and (1 2)). However, when a little cobalt is
present, manganese(II1) becomes a major product (eqs. (13) and (14)). Mn accel-
erates the conversion of Co"' to Co" by reduction with bromide (eq. (16)) and
electron transfer from Mn" to Co"' (eq. (14)). This supplements the simple bro-
mine radical generation pathway by an indirect but overall rapid sequence [16].

Mn2+ + BT + ArC(0)02H -
-
Mn2+ + OBr- + ArCOOH (11)

Mn2+ + Br +
OBr-

Mn2+
Co2+
+

+
+
Br- +
ArC(0)02H

Br- +
2H+

Co3+
-
-
Br2
Mn2+
Mn3+
+ H20

+
+
Br-

Br-
+
+
Co3+

Co2+
+ ArCOO*
(12)
+ OH- (13)
(14)
+ - + (15)
-
Mn3+ Br- Mn2+ Bra

Co3+ + Br- Co2+ + Br* (16)

Thus Mn lowers the steady-state concentration of Co"' which reduces solvent
decomposition and also avoids Co"' rearranging into a less reactive form. Bromine
radicals react rapidly with the methylaromatic compound to generate radicals; in
contrast Co"' and Mn"' react more slowly [16, 201.
However, in spite of broad knowledge of metal-catalyzed autoxidation of aro-
matic compounds, the nature of the major chain-propagating steps is still not to-
tally understood, nor are the relative rates of the dozens of single reaction steps.
Unpredictable couplings of chemical and physical aspects make the reactions
complicated: sometimes oscillatory or even chaotic behavior occurs. Due to mani-
fold back-coupling effects, often solely empirical research techniques can be
applied to lead successfully to the desired oxidations.

Co-oxidations Applying Co3+Catalysis

The sluggish oxidation of p-toluic acid or o-nitro-substituted alkylaromatic com-

pounds is dramatically improved by the simultaneous use of auxiliary organic or
inorganic compounds such as acetaldehyde, methyl ethyl ketone, butane, xylene,
or nitric acid. The principle of co-oxidation is based on the formation of additional
Co3+ions, mediated by the co-oxidizing reagents. More important, the latter act as
a perfect source for radicals.
The co-oxidation using acetaldehyde was originally developed by Eastman
Kodak for the production of terephthalic acid, using 2 moles of acetaldehyde
per molp-xylene [21]. Also the addition of methyl ethyl ketone (MEK) or n-butane
yields an increase in the reaction rate of the autoxidation of toluene derivatives
[22]. Like acetaldehyde, MEK is transformed finally to acetic acid, yielding
Co3+ ions in the course of its own oxidation. Disadvantages are long induction
and reaction times due to the low reaction temperatures, e.g., 70-110 "C. The ca-
talysis using Co"/MEK is strongly linked to an "electron transfermechanism"
which could be demonstrated with the oxidation of p-isopropyltoluene, shown
in Scheme 3. Surprisingly, cuminic acid (p-isopropylbenzoic acid) is formed in
454 2.4 Oxidations

c -Q02
COCHs
I

COOH
< 10%

-9
0
CH2 COOH
I I

LQ 02

A A
Scheme 3. Oxidation of isopropyltoluene. > 90 %

over 90 % yield [23]. Side reactions arise from attack on the isopropyl group,
finally yielding terephthalic acid [24].
Instead of acetaldehyde, other aliphatic aldehydes such as propanal or butanal
can be applied. Besides MEK, diethyl ketone or dibutyl ketone or even simply n-
butane is used. It is worthwhile to point out the significant importance of co-oxi-
dizing processes in the mechanistic course of autoxidation reactions. After a short
induction time, the intermediates formed act as co-oxidants for the remaining
starting molecules.

2.4.5.2.6 Kinetics
For the oxidation of toluene in acetic acid, applying Co(OAc)* as the only catalyst
at comparatively mild conditions (93 "C), the rate law for the first reaction step,
the formation of the benzylic radicals, is given by Hendriks et al. (eq. (17)) [llc]:

- d(ArCH3)/dt = k [Co3+I2[Co2+]-' [ArCH3] (17)

The ratio of Co2+ to Co3+ will be fixed automatically during the course of
the autoxidation reaction. The term [CO"]~ in eq. (17) is due to the fact that
the Co3+ions are active at two stages of the primary reaction of the autoxidation,
i.e., the formation of benzylic radicals. As the equation shows, the first electron-
transfer step is inhibited by Co2+ ions (factor [Co2+]-').However, the overall
kinetics using the Co/Mn/Br system are very complex and can only be expressed
by empirically found formal kinetics. Thus the general rate of autoxidation
reactions (steady-state concentration in ROO-, high kinetic chain length) can be
given by eq. (18) [25],
r = [dn(02)/dt]NR= kd(2kt)0.5[ArCH3](Wi)0.5 (18)
 2.4.5.2 Oxidation of Alkyl-SubstitutedAromatic Compounds with Air 455

with V, as the reaction volume, k, as the rate of radical chain propagation, k, as the
rate of radical chain demolition and Wi as the rate at the start of the autoxidation.
With respect to a short kinetic chain length, the use of oxygen by starting mole-
cules, and the formation of oxygen by chain demolition processes, eq. (18) has to
be corrected by an additional term rn (eq. (19)) [26]:

r = kd(2kt)0.5[ArCH3](Wi)’.’ + m Wi (19)
As a result, the rate of oxidation of alkylaromatic compounds is mainly depen-
dent on the ratio of the rate of radical chain propagation kp and the rate of radical
chain demolition k, with [kd(2kt)o.5],,as a value for a relative oxidizability. For
further discussion, cf. [llb, 19b, 23a, 27-30].

The Influence of the Substituents on the Oxidizability of Various Toluenes

However, the promptness with which the oxidations start and their ease of propa-
gation are not only dependent on the alkyl substituents which are to be oxidized,
but also very much on the type and the position of the substituents in the aromatic
system. The first, rate-determining step of the alkylarene oxidation - either the for-
mation of a radical cation via an “electron-transfer” mechanism, or the direct for-
mation of a benzylic radical by a-hydrogen abstraction - is increased with the
electron density of the aromatic system supported by the substituents present.
Based on numerous experimental observations such as the requirements and
composition of the catalysts as well as variations of the reaction temperature, oxy-
gen partial pressure, substrate concentration, and water content in the reaction
mixture, the following order of activity in the oxidation of para-substituted
toluenes with air is found:

OCH3 > O(C6H,) > CH3 > H > F, C1, Br > CO(C,H,) >SO,R > COOR,
COOH > NO2

Thus, the scale of activating, neutral, and deactivating substituents is in line

with the corresponding Harnrnett substitution coefficients up+.In the case of the
“electron-transfer” mechanism, this empirical activity scale could be based on a
simple theoretical equation (eq. (20)) which can be used to estimate relative or
even absolute rate constants for the primary step of the oxidation reaction (see
eq. (21)) [6a, 11, 14s, 311:

x - (c6H4) - CH3 + c03+ -

lOg(ks/kH) = p gp+
x - [(c6H4)+’] - CHs + c02+
(20)
(21)
with kH = rate constant of the unsubstituted toluene, forming the radical cation,
equivalent to the rate constant for the disappearance of toluene;
ks = rate constant of the substituted toluene, forming the radical cation,
equivalent to the rate constant for the disappearance of substituted
toluene;
456 2.4 Oxidations

4-CH3

\
~

3-CH3

-0.5

I I I I
-1
-1.2 -0.8 -0.4 0 0.4 0.8

o+
Figure 1. Relation between the initial rate constants of the anaerobic oxidation of meta- and
para-substituted toluenes with cobalt(I1I) acetate.

6 --
__

4 -- __

2 --
_-

0 --
-_

-2
-- __
3-Br

I I 1 I
-4

Figure 2. Relation between the initial rate constants of the anaerobic oxidation of metu- and
para-substituted toluenes with manganese(II1) acetate.
 2.4.5.2 Oxidation of Alkyl-Substituted Aromatic Compounds with Air 457

up+= Hammett coefficient, serving as a measure of the ability of the

substituent to influence the electron density at the reaction center
(a+-values are used for systems which come into contact with posi-
tively charged transition states);
e = reaction constant for the influence on the observed reaction of a
change in the electron density, in a given set of conditions (e has al-
ways been found to be negative for this type of reaction, which means
that electron-withdrawing groups result in decreasing rates of oxida-
tion [%I).

As a result, Hendriks et al. [ 1lc] found a relation between the initial rate con-
stants of the anaerobic oxidation of rneta- and para-substituted toluenes by Co"'
acetate and the Hammett substitution constant a+(at 93 "C; Figure 1).
For the reaction of Mn"' acetate with substituted toluenes in acetic acid (130 "C)
under anaerobic conditions, an analogous correlation between log(kIs/klH)and a+
exists (Heiba et al. [ 11a]; Figure 2). Here, however, the reaction is not the direct
interaction of Mn"' with the arene but the reaction of carboxymethyl radicals, gen-
erated from Mn"' acetate, with the a-hydrogen atoms of the alkyl group on the
arene (eqs. (22) and (23)).
M~"'(OAC)~ - M ~ " ( O A C+) *CH2COOH
~ (22)
X --
- (CsH4) - CH3 + *CH2COOH (CsH4) - CHp] + CHsCOOH (23)
A typical @-valueof -0.95 will give typical differences in reactivity [5a] which
can be adjusted by change of temperature, pressure, and catalyst concentration.

Rate-Controlling Factors

The oxidation of durene, ultimately to pyromellitic acid, illustrates the connection

of the reactivity data with the rate-controlling factors temperature and pressure;
see Table 2. Note that the relative reactivity of durene is 20 times higher than
that observed for the corresponding monocarboxylic acid.
However, highly oxidizable substrates such as p-methoxytoluene will consume
the dissolved oxygen very quickly, which may result in total depletion of the re-
action mixture from the oxidant, especially at reaction temperatures that are too
high. This causes subsequent dimerization or electrophilic substitutions in the
arene system. Low yields of yellow to brownish colored products result.
Generalizing, a great number of alkylbenzenes, e.g., electron-rich systems such
as methoxytoluene, ethylbenzene, or cumene, are easily to oxidize and as a result
the rate-determining step is the penetration of the oxygen from the gas phase into
the liquid phase [32]. Therefore, the rate of oxidation is strongly dependent on the
oxygen pressure and on the quality of mixing of the two phases; as the oxidation of
alkylaromatic substrates is a two-phase liquid/gaseous reaction, the mass-transfer
coefficient of the oxygen into the liquid phase must be carefully optimized, espe-
cially in the case of activated, highly oxidizable compounds. Thus, electron-defi-
458 2.4 Oxidations

Table 2. Connection between relative reactivities and controlling factors [5a, 61.
Substrate Relative reactivity Temperature ["C] Pressure [psi]
C6H2(CH3)4 19.0 138 150
C6HZ(CH3)3COZH 0.97 Increase of Increase of
temperature pressure
C6H2(CH3)2(C02H)2 0.78
C&2(CH3)(COd93 0.08 204 450

cient systems often yield the best results, in spite of longer reaction times. The dan-
ger with less reactive feedstocks is that the more drastic reaction conditions that
are required lead to increased decomposition of solvent and substrate.
With a constant but low exhaust gas stream and a fixed catalyst composition
and concentration, the kinetics of the reaction being discussed are strongly depen-
dent on the oxygen mass transfer rate. In this case, the rate of oxidation is faster
than the transport rate of oxygen into the reaction phase. Thus the oxygen concen-
tration in the liquid phase is near zero, the concentration of oxygen in the exhaust
gas is less than 0.1 %. As a result, side reactions may occur; colored products are
often obtained.

Limits of Catalyst Composition

Besides the oxygen transport, it is mainly the catalyst composition that is decisive
for optimal oxidation results. Here in most cases cobalt and manganese can
substitute for each other over a certain range, due to their synergistic behaviour.
Figure 3 shows the reaction times obtained for different CoMn catalyst systems
in the oxidation of 1 mol of 4-chlorotoluene at an oxygen partial pressure of 6 bar
(cf. Section 3.1 S).
Notice that the total reaction time is reduced to 50 % if only 10 % of the cobalt
is substituted by manganese. Interestingly the observed reaction times remain
almost constant until a C o N n ratio of 9:1 is reached. This demonstrates the
synergistic mechanism of the different metal ions. However, at manganese con-
centrations lower than 10 % of the total metal content, the reaction becomes
very slow. This indicates that there is one reaction step in the oxidation sequence
which is strongly catalyzed by manganese ions.

Limits of Catalyst Concentration

In addition to the right CoMn ratio a minimum concentration of catalyst must

be applied; otherwise, side reactions become predominant and decrease the
selectivity of the oxidation reactions. This is shown, for example, in the oxidation
of 4-methoxytoluene at different catalyst concentrations. Figure 4 shows the con-
version of 4-methoxytoluene and the formation of intermediates (both in mol%)
versus the corresponding catalyst concentration.
 2.4.5.2 Oxidation of Alkyl-Substituted Aromatic Compounds with Air 459

250 I I I I

1'
200 --

reaction
time 150 -:
[mini

Figure 3. Reaction times obtained for different C o N n catalyst systems in the oxidation
of 4-chlorotoluene.

h I\
100 I Y

conversion of substrate
80 -- __

60 -- -_

("/I

Z Co,M n [mmollmol]
Co:Mn = (Co+Mn):Br = 1

Figure 4. Conversion of 4-methoxytoluene and the formation of reaction intermediates versus

the corresponding catalyst concentration.
460 2.4 Oxidations

2.4.5.2.7 Applications
Building Blocks for Polymers [33]

The industrial importance of terephthalic acid or DMT, both building blocks for
poly(ethy1ene terephthalate) (PET), and phthalic acid anhydride (PTA) has already
been emphasized in the introduction. PET is a basic monomer for polyester poly-
mers used for the production of end-user products such as bottles, video tapes or
fine fashions, and environmentally beneficial packaging materials. Poly(butene
terephthalate) (PBT) shows thermal and mechanical properties superior to those
of PET because the “hard” segments provided by the linear terephthalate moiety
alternate with “soft” segments introduced by the -O(CH2),0- units of the 1,4-
butanediol component. This structural moiety can be extended to even more
flexible segments by the use of poly(ethy1ene glycol). With sufficiently long
[-O(CH,),O], segments (rn 2 12) one obtains thermoplastic elastomers (TPEs).
An example of a TPE is DuPont’s Hytrel@.
Also pioneered by DuPont, aromatic polyarnides, the so-called ararnides, were
the first in a series of high-performance speciality thermoplastics, derived from
aromatic dicarboxylic, tricarboxylic, or tetracarboxylic acids. Polymers named
Kevlar@(linear, rather rigid, used as fibers in bulletproof vests; the first commer-
cially available liquid crystal polymer, LCP), Nomex’ (less linear but also fairly
rigid structure, used as a substitute for asbestos; both by DuPont) and Twaron’
(Akzo) are generally obtained from the acid chlorides of terephthalic acid and
isophthalic acids, respectively, matched up with p- and rn-phenylenediamines.
For such high-molecular-weight polymers, the polymerization of these acid chlo-
rides and diamines is more troublesome than for other types of polymerization.
Therefore often, when possible, the corresponding acid anhydrides are used as
monomers. In 1984 Dart and Kraft introduced the copolyester Xydar@.In Xydar’
terephthalic acid is combined with 4,4’-biphenol and p-hydroxybenzoic acid to
yield a highly rigid structure (Structure 1).

-I.,o“o-o, 0

] “ ‘‘ / O 0 \

1 n

A whole series of high-performance polyester LCPs was introduced in 1985.

They were assembled from p-hydroxybenzoic acid and 6-hydroxy-2-naphthoic
acid. Polyarylates (PARS) - amorphous phenolic esters derived from aromatic di-
carboxylic acids (mixtures of terephthalic acid and isophthalic acid) and biphenols
such as bisphenol A - are produced by Amoco (Ardel@),Celanese (Durel@)and
DuPont (Arylon@)at a volume of approx. 2000 t/a.
 2.4.5.2 Oxidution of Alkyl-Substituted Aromatic Compounds with Air 461

There have been many efforts to commercialize 2,6-dicarboxynaphthalene for

the preparation of poly(ethylene-2,6-naphthalate) due to its favorable thermoplas-
tic properties compared with PET. Therefore, there are numerous patents in which
2,6-alkyl-substituted (alkyl = methyl, ethyl, isopropyl) naphthalenes are oxidized
to the corresponding aromatic di-acids, applying mostly Co/Mn/Br catalysts with
various co-catalysts such as Zr or Pd in acetic acid as the solvent. The major by-
product is formed by the oxidation of the naphthalene ring to give trimellitic acid
(TMA) [5a, 81. Sumikin Chemical has developed a method to prepare 2,6-naphtha-
lenedicarboxylic acid by oxidation of 2,6-diisopropylnaphthalene(2,6-DIPN) in
the liquid phase with air in a 500 tpy plant. Sumikin uses a newly developed cat-
alyst based on C o N n with an addition of a few ppm of Pd giving advantages such
as yields higher than 90 %, suppression of TMA production to around 1 %, and
thus better catalyst recovery, and reduced consumption of acetic acid.
In this context, Amoco Performance Products, Inc. (APPI) specialized in the late
1980s in the production of new aromatic “fine carboxylic acids” such as 1,2,3-
trimethyl-3-phenylindane-4’,5-dicarboxylicacid (PIDA), 2,6-naphthalenedicar-
boxylic acid (2,6-NDA), 5-t-butylisophthalic acid (5-tBIA), and di(carboxyphe-
nyl) ether. The rigid, unsymmetrical, forcibly nonplanar structure of PIDA can
be used to assemble thermoplastic and thermosetting polyester and polyamide
resins, especially for coating materials. The same is true for 2,6-NDA, which
offers a symmetrical, rigid structural moiety in which the relatively large molecular
area of the naphthalene moiety - compared with terephthalic acid - provides a
greater opportunity for intermolecular associations by a vertical stacking of aro-
matic rings, yielding stronger molecular interactions. Additionally, 2,6-NDA offers
the possibility of preparing a-sulfonated derivatives. Such materials are incorpo-
rated in fibers and films as opticalbrighteners due to their fluorescence properties.
In 1983 Celanese began the production of polybenzimidazole (PBI) by using
diphenyl isophthalate and 3,3’-diaminobenzidine, DAB. PBI is a high-temperature
and flame-resistant fiber, used in the production of safety gloves and various items
of protective clothing as well as for the production of PBI-based membranes for
reverse osmosis and ultrafiltration applications.
The use of trifunctional and higher-functionality carboxylic acids broadens the
horizon of chemical possibilities for such benzenoid building blocks. The trifunc-
tionality of trimesic acid ( 1,3,5-benzenetricarboxylicacid; derived from mesity-
lene by oxidation) opens the opportunity for modification of linear polyesters,
such as PET, by introducing either a small or a high proportion of crosslinking,
which results in a thermosetting polymer. Thus, for example, excellent vehicles
for industrial primers can be made from coating resins based on Amoco trimellitic
anhydride (TMA) [34, 351.
The chemical possibilities of tri- and tetracarboxylic systems are most interest-
ing in the case of vicinal carboxylic groups which can react in unison. Such phtha-
lic acid-type systems, mostly used as anhydrides, can serve as intermediates in the
formation of high-performance polymeric amide-imides and polyimides (PIS).
In the area of high-performance polymers there is a still growing market interest
in sophisticated building blocks bearing multiple carboxylic functionalities on aro-
matic systems, the latter often being connected by flourinated spacer groups as in
462 2.4 Oxidations

the high-price, electronic-grade polyimide building blocks 2,2’-bis(4‘-carboxy-

pheny1)hexafluoropropane or 2,2’-bis(3’,4’-anhydrodicarboxyphenyl)hexafluoro-
propane, both produced via oxidation of the corresponding o-xylene precursors
(Structures 2-4) [36].

HOOC COOH
2

HOOC

COOH

Polycondensation polymers, especially polyimides, derived from multifunctio-

nalized amines and the above-mentioned polyacids are highly temperature-resis-
tant materials that do not behave like “ground firebrick”; this means they resist
extreme conditions but can still be processed, e.g., shaped as desired. These prop-
erties make them suitable for application in electronic devices, turbine blades, or
even spacecrafts. For example, the Allco Chemical Corporation offers 3,3’, 4,4‘-
benzophenonetetracarboxylic dianhydride (BTDA; see Structure 1) as a speciality
building block for high-performance polymers delivering exceptional thermooxi-
dative stability, outstanding electrical properties, increased hardness, and high
chemicalholvent resistance [37]. Further examples for such speciality monomers

fifi
are given in Structures 5-7.

HOOC / / 0

5
/ / COOH 04&
/ *%\
po
\

0 gsiY&
0 0 0

0
7
0 6 0
 2.4.5.2 Oxidation of Alkyl-Substituted Aromatic Compounds with Air 463

Aromatic Carboxylic Acids as Fine Chemicals and Intermediates

for Pharmaceuticals and Agrochemicals

Aromatic carboxylic acids are highly important, synthetically useful fine chemi-
cals, mostly used as intermediates to pharmaceuticals, agrochemicals, and pig-
ments, and as sophisticated high-price monomers for special high-performance
polymers. The obvious commerical importance of the further-developed Amoco
MC technology has thus stimulated an enormous amount of research activity
which has resulted in more than 300 different types of substrates that have been
oxidized using this method. Homogeneous liquid-phase oxidations are superior
to heterogeneous gas-phase alternatives.
A review of the patent literature since the mid 1980s concerning the oxidation
of alkyl-, acyl- or formyl-substituted aromatic compounds with air as oxidant and
heavy metal salts as catalysts reveals trends which may be tentatively summarized
as follows. On the basis of production volume and number of patents, the main
target is the development of new or improved routes to “di- and polycarboxylic”
acids such as terephthalic, phthalic, and isophthalic acids; trimellitic acid; tetracar-
boxybenzene; I,4-NDA or, on a much more important scale, 2,6-NDA from
methyl, ethyl, or isopropyl precursors; naphthalene tetracarboxylic acids; and to
a certain extent 4,4‘-dicarboxybiphenylicacid. Additionally there are increasing
efforts in the field of high-price oligomeric compounds, defined as compounds
of the type [(HO2C),PHI2X where X may be C=O, 0, S, OP(0-), 2,2’-propane
derivatives with dimethyl (6H) or di(trifluoromethy1) (6F) substituents in the
2,2’-position.
Besides the development of new polymer feedstocks, there are several targets in
the area of fine chemicals: thus all kinds of o-nitro configured systems seem to be
interesting; however, they are difficult to synthesize if no nitric acid-supported re-
action is applied. Halogen- and alkyl-, alkylamino- and aminosulfonyl-substituted
benzoic acids are of increasing importance for pharmaceuticals and agrochem-
icals, the latter often bearing comparable substitution patterns [38]. Polyhaloge-
nated aromatic acids are important targets, due to their various substitution possi-
bilities. Thus their production volume is constantly increasing. Benzoic acids car-
rying other alkyl substituents such as ethyl or di- or trimethyl groups are difficult
to synthesize with high selectivities and therefore permanent subjects of research
activity. This is also true for the oxidation of alkyl-substituted pyridine or quino-
line derivatives. Another field of activity is the selective conversion of alkyl-sub-
stituted aromatic aldehydes into the corresponding acids with high space-time
yields.

2.4.5.2.8 Future Developments

Up to now, in the area of fine chemicals the oxidation of alkyl aromatic com-
pounds with air has been performed by batch technology. The step to continuous
oxidation is the next logical development. Standard space time yields (sty) for
batch operation are in the range of 0.05 to 0.1 kg L-’ h-’. By increasing the
464 2.4 Oxidations

temperature from the standard 160" to more than 220", using specially tuned
catalysts, it is possible to increase the sty for batch operation by a factor of
more than ten.
For switching from batch to continuously operated reactor systems, sufficient
reaction rates are essential. This can be realized by properly synchronizing the
catalyst composition and the reaction temperature. To achieve this, reactor geo-
metry, oxygen inlet techniques, stirring geometry, stirrer speed, dosing rate of
the substrate, etc., have to be fine-tuned. Usually conversions higher than 95 %
can be reached without losing too much sty. The quality of conversion is de-
pendent on temperature, oxygen partial pressure, catalyst composition and con-
centration, and the dosing rate of the substrate. Very high substrate conversions
of > 98 % might require the implementation of a second-stage oxidation reactor,
e. g., a tube reactor with special gas inlet devices.
To re-use the mother liquor for multiple recycles, high chemoselectivities must
be ensured, especially when electron-rich aromatic compounds are oxidized.
Brownish or yellowish oxidation products are an indicator that oxygen concentra-
tions are too low during oxidation. High reaction temperatures and unspecified
catalyst compositions can cause full oxygen depletion. To provide best product
quality combined with minimized product and solvent loss, the oxygen consump-
tion should be between 110 and 150% of the theoretical value. The solvent oxi-
dation can be controlled by the catalyst concentration and the temperature.
Besides the developments described, stirred-tank reactors will stay as standard
reactors, but the implementation of other reactor types (e. g., bubble columns)
might be recommended: compared with stirred tank reactors the retention time
characteristics might be beneficial to substrate conversion and sty.

References
[1] (a) R. A. Sheldon, J. K. Kochi, Metal-Catalyzed Oxidations of Organic Compounds,
Academic Press, New York, 1981; (b) R. A. Sheldon, J. Dakka, Catal. Today 1994,
19, 215; (c) G. W. Parshall, S. D. Ittel, Homogeneous Catalysis, The Applications
and Chemistry of Catalysis by Soluble Transition Metal Complexes, 2nd ed.,
Wiley-Interscience, New York, 1992, p. 255-268.
[2] (a) IG-Farben AG (J. Binapfel, W. Krey), DE 522.255 (1931); (b) P. W. Sherwood,
Petrol. Proc. 1953, 8, 905.
[3] (a) Imhausen GmbH, (E. Katzschmann), DE 949.564 (1956); (b) Chemische Werke Wit-
ten GmbH, DE 969.994 (1958); (c) Chemische Werke Witten GmbH (E. Katzschmann),
DE 970.794 (1959); (d) Chemische Werke Witten GmbH (E. Katzschmann), DE
1.041.945 (1958); (e) Hercules Powder Co. (F. T. Parkinson), DE 1.114.472 (1961);
(f) K. Weissermel, H. J. Arpe, Industrial Organic Chemistty, 3rd ed., VCH Weinheim,
1988, p. 415; (8) Dynamit Nobel AG (H. K. Diessel et al.), CA 1.145.738 (1983); (f)
Dynamit Nobel AG (H. Buenger et al.), US 4.372.875 (1983); (h) Dynamit Nobel AG
(R. Modic et al.), US 4.642.369 (1987); (i) Hercofina (S. Takeda et al.), US 4.398.037
(1983); (j) Hercules (K. D. Black et al.), US 4.058.663 (1977); (k) Hoechst AG
(R. Bader et al.), US 4.683.034 (1987); (1) Tejin Ltd. (I. Hirose et al.), US 4.354.037
(1982).
 References 465

[4] (a) Mid-Century Corp. (A. Saffer, R. S. Barker), US 2.833.816 (1959); (b) Mid-Century
COT. GB 810.020 (1959); ( c ) R. Landau, A. Saffer, Chem. Eng. Yrog. 1968, 64, 20; (d)
W. Partenheimer, Catalyses of Organic Reactions (Ed.: D. W. Blackburn), Marcel Dek-
ker, New York, 1990, Chapter 20; (e) W. Partenheimer, ACS Symp. Sex, No 523, chapter
7; (f) Amoco (M. M. Schwartz et al.), US 4.675.438 (1987); (g) Amoco (J. G. Hundley et
al.), US 4.769.487 (1988); (h) Amoco (D. E. James), US 4.782.181 (1988); (i) Mitsui
Petrochemical Ind. (S. Shiraki et al.), EP 261.892 (1988): (j)Amoco (J. K. Holtzhauser
et al.), US 4.786.621 (1988); (k) Mitsui Petrochemical Ind. (S. Shiraki et al.), EP 265.137
(1988); (1) Mitsubishi Chem. Ind. (H. Hashizume et al.), US 4.562.285 (1985); (m)
Mitsubishi Chem. Ind. (H. Hashizume et al.), US 4.772.748 (1988); (n) Amoco (M.
A. Zeitlin et al.), US 4.777.287 (1988): (0) ICI (A. R. Correy et al.), EP 181.127
(1986); (p) Toray Ind. (S. Kanehara et al.), JP Kokai 63-156.755 (1988); (9) Mitsubishi
Chem. Ind. (A. Tamaru et al.), JP Kokai 62-270.548 (1987).
[5] (a) W. Partenheimer, 15th Con$ Catalysis of Organic Reactions, Phoenix, AZ, 1994,
Paper no. 28; (b) D. M. Lewis, F. J. Sebelist, CA 817.445 (1978).
[6] (a) W. Partenheimer, 14th Con$ Catalysis of Organic Reactions, April 27, 1992; (b) J. K.
Darin, A. G. Bemis, US 4.895.978 (1987).
[7] (a) Monsanto Co. (R. A. Periana, G. F. Schaefer), US 5.068.407 (1991); (b) P. D. Riley,
5th Int. Symp. Activation of Dioxygen and Homogeneous Catalytic Oxidation, Texas
A&M University, 1993.
[8] (a) Mitsubishi Gas Chem. KK, JP 1.305.049 A (1988); (b) Mitsubishi Gas Chem. KK, JP
1.265.056 A (1989); (c) Amoco Corp., EP 329.273 (1988); (d) Mitsubishi Gas Chem.
KK, EP 324.342 (1988); (e) Teijin Petrochem., EP 315.100 (1987); (f) Mitsui Petrochem.
Ind. KK, JP 3.1.59.344 A (1986); (g) Teijin Yuka KK, JP 3.104.943 A (1986); (h) Teijin
Yuka KK, JP 3.066.150 A (1986); (i) Sumikin Kako KK, JP 2.255.448 A (1986); (i) Kur-
eha Kagaku Kogyo, GB 2.187.744 (1986); (k) Kureha Kagaku Kogyo, GB 2.187.743
(1986); (1) Mitsubishi Chem. Ind. KK, JP 2.061.947 A (1985); (m) Mitsubishi Chem.
Ind. KK, JP 2.061.946 (1985); (n) Dynamit Nobel AG, DE 3.529.381 (1985); (0) Teijin
Yuka KK, JP 1.246.143 A (1985); (p) Mitsubishi Chem. Ind. KK, JP 1.221.151 A (1985);
(9) Mitsubishi Gas Chem. KK, JP 1.024.541 A (1984); (r) Amoco (J. J. Harper, G. E.
Kuhlmann, K. D. Larson, R. Mcmahon, P. A. SancheL), US 5.183.933, WO 9.308.151
(1993); (s) Y. Kamiya, T. Taguchi, S. Futamura, Nippon Kagaku Kuishi 1987, 10, 1772.
[9] (a) BASF (H. Hagen, J. Dupuis), EP 529.426; (b) Nissan Chem. Ind. KK, JP 2.174.746
(1988); (c) Nissan Chem. Ind. Ltd. Japan (Y. Kamiya, S. Nitamura, S. Takigawa,
S. Araya, N. Tanaka), JP 02.174.746 A2 (1988); (d) Chem. Dynamics Dev., SE
8.700.657 A (1987); (e) BASF, DE 3.409.244 (1984); (f) IHARA, EP 2.749 (1977);
(g) Amoco (D. A. Young, M. E. Volling), US 4.906.771 (1987); (h) BASF, DE
4.128.348 (1991); (i) Amoco, US 4.906.771 (1989); (i) BASF, EP 371.362 (1988).
[ 101 (a) G. W. Parshall, S. D. Ittel, Homogeneous Catalysis, The Applications and Chemistry
of Catalysis by Soluble Transition Metul Complexes, 2nd ed., Wiley Interscience, New
York, 1992, p. 2.58-261: (b) R. A. Sheldon, J. K. Kochi, Adv. Catal. 1976, 25, 272.
[ 111 (a) E. I. Heiba, R. M. Dessau, W. J. Koehl, J. Am. Chem. Soc. 1969, 91, 138; (b) E. I.
Heiba, R. M. Dessau, W. J. Koehl, ibid. 1969, 91, 6830; (c) C. F. Hendriks, H. C. A. van
Beek, P. M. Heertjes, Ind. Eng. Chem., Prod. Res. Dev. 1978, 17, 256.
[ 121 E. J. Y. Scott, A. W. Chester, J. Phys. Chem. 1972, 76, 1520.
1131 (a) T. A. Cooper, W. A. Waters, J. Chem. Soc. B 1969, 687; (b) Y. Ichikawa, G. Yama-
shita, M. Tokashiki, T. Yamaji, J. Eng. Chern. 1970, 62, 38; (c) R. M. Dessau, S. Shih,
E. I. Heiba, J. Am. Chem. Soc. 1970, 92, 412.
[14] (a) R. A. Sheldon, J. K. Kochi, Metal-Catalyzed Oxidutions of Organic Compounds,
Academic Press, New York, 1981, pp. 34-35, 120-129; (b) D. C. Nonhebel, J. C. Wal-
ton, Free Radical Chemistry, CUP, Cambridge, 1974, p. 321; (c) D. Benson, Mecha-
466 2.4 Oxidations

nisms of Oxidation by Metal Ions, Elsevier, Amsterdam, 1976, pp. 41; (d) C. F. Hen-
driks, H. C. A. van Beek, P. M. Heertjes, Ind. Eng. Chem., Prod. Res. Dev. 1978,
17, 260; 1979, 18, 43; (e) C. F. Hendriks, H. C. A. van Beek, P. M. Heertjes, ibid.
1979, 18, 38; (f) A. M. Nemecek, C. F. Hendriks, H. C. A. van Beek, M. A. de
Bruyn, E. J. H. Kerckhoffs, Ind. Eng. Chem., Prod. Res. Dev. 1978, 17, 133; (g) M.
P. Czytko, G. K. Bub, ibid. 1981, 20, 481; (h) W. F. Brill, Ind. Eng. Chem. 1960, 52,
837; (i) A. S. Hay, J. W. Eustance, H. S. Blanchard, J. Org. Chem. 1960, 25, 616;
0 ) V. N. Sapunov, L. Abdenur, Kinet. Katal. 1974, 15, 20; (k) K. Sakota, Y. Kamiya,
N. Otha, Can. J. Chem. 1969, 47, 387; (1) M. Kashima, Y. Kamiya, Bull. Chem. Soc.
Jpn. 1974, 47, 481; (m) Y. Kamiya, M. Kashima, J. Catal. 1972, 25, 326; (n) Y.
Kamiya, M. Kashima, Bull. Chem. Soc. Jpn. 1973, 46, 905; ( 0 ) A. Onopchenko, J.
G. D. Schulz, R. Seekircher, J. Org. Chem. 1972, 37, 1414; (p) E. Baciocchi, L. Man-
dolini, C. Rol, J. Org. Chem. 1980, 45, 3906; (4) A. Onopchenko, J. G. D. Schulz,
R. Seekircher, J. Chem. Soc., Chem. Commun. 1971, 939; (r) A. Onopchenko, J. G. D.
Schulz, J. Org. Chem. 1972, 37, 2564; (s) T. Morimoto, Y. Ogata, J. Chem. Soc. ( B )
1967, 1353; (t) C. F. Hendriks, H. C. A. van Beek, P. M. Heertjes, Ind. Eng. Chem.,
Prod. Res. Dev. 1977, 16, 270; (u) Agency of Industrial Science and Technology,
Sanko Chemical Co. (J. Imamura, M. Takehara, K. Chigasaki, K. Kizawa), DE
2.605.678 (1975); (v) S. S. Lande, C. D. Falk, J. K. Kochi, J. Inorg. Nucl. Chern.
1971, 33, 4101; (w) C. F. Henriks, H. C. A. van Beek, P. M. Heertjes, Ind. Eng.
Chem., Prod. Res. Dev. 1979, 18, 43.
[15] (a) J. Hanotier, H. Hanotier-Bridoux, J. Chem. SOC.,Perkin Trans. 1973, 2, 1036;
(b) R. E. van der Ploeg, R. W. de Korte, E. C. Kooyman; J. Catal. 1968, 10, 52;
(c) H. J. den Hertog, C. E. Kooyman, J. Catal. 1966, 6, 347, 357; (d) R. van Helden,
E. C. Kooyman, Recl. Trav. Chim. Pays-Bas 1961, 80, 57.
[16] G. Jones, J. Chem. Res. 1982, 207.
[17] (a) R. A. Sheldon, J. K. Kochi, Metal-Catalyzed Oxidations of Organic Compounds,
Academic Press, New York, 1981, p. 129; (b) A. W. Chester, P. S. Landis, E. J. Y.
Scott, CHEMTECH 1978, 366.
[I81 (a) Teijin, DE 2.341.147 (1972); (b) Mid-Century, US 2.833.816 (1955); (c) Standard
Oil, US 2.420.960 (1973).
[ 191 (a) D. A. S. Ravens, Trans. Faraday SOC.1959,55, 1768; (b) Y. Kamiya, J. Catal. 1974,
33, 480.
[20] W. Partenheimer, in The Activation of Dioxygen and Homogeneous Catalytic Oxidation
(Eds.: D. H. R. Barton, A. E. Martell, D. T. Sawyer), Plenum, New York, 1993, p. 474.
[21] Eastman Kodak (D. C. Hull), US 2.673.217 (1957).
[22] (a) W. F. Brill, Znd. Eng. Chem. 1960, 52, 837; (b) H. S. Bryant, C. A. Duval, L. E.
McMakin, J. I. Savoca, Chem. Eng. Prog. 1971, 67, 69.
[23] (a) A. Onopchenko, J. G. D. Schulz, R. Seekircher, J. Chem. Soc., Chem. Commun.
1971, 939; (b) A. Onopchenko, J. G. D. Schulz, R. Seekircher, J. Org. Chem. 1972,
37, 1414; (c) A. Onopchenko, J. G. D. Schulz, J. Org. Chem. 1972, 37, 2564; (d) Sumi-
tom0 Chemical Co. (S. Hideaki, T. Hiroshige, 0. Motomasa, T. Kobayashi), JP
53.046.830 B4.
[24] R. A. Sheldon, J. K. Kochi, Metal-Catalyzed Oxidations of Organic Compounds,
Academic Press, New York, 1981, pp. 122-126.
[25] L. Bateman, Quart. Rev. Chem. SOC. 1954, 3, 147.
[26] H. Furst (Ed.), Autoxidution von Kohlenwasserstoflen, VEB Deutscher Verlag fur
Grundstoffindustrie, Leipzig, 1981, p. 21.
[27] (a) J. A. Howard, K. U. Ingold, Can. J. Chem. 1967, 45, 793; (b) J. A. Howard, K. U.
Ingold, M. Symonds, Can. J. Chem. 1967,46, 1017; (c) G. A. Russel, J. Am. Chem. Soc.
1956, 78, 1047.
 References 467

[28] W. Pritzkow, H. Rosner, J. Prakt. Chem. 1975, 317, 990.

[29] H. Furst (Ed.), Autoxidation von Kohlenwasserstoffen, VEB Deutscher Verlag fur
Grundstoffindustrie, Leipzig, 1981, p. 121.
[30] (a) G. S. Serif, C. F. Hunt, A. N. Bourns, Can. J. Chem. 1953, 31, 1229; (b) M. I.
Chmura, B. V. Suvorov, S. R. Rafikov, Zh. Obshch. Chim. 1955, 1418; (c) H. Boardman,
J. Am. Chem. SOC.1962, 84, 1376.
[311 J. March, Advanced Organic Chemistry. 2nd ed., Wiley Interscience, New York, 1977,
p. 253.
[32] (a) H. Furst (Ed.), Autoxidution von Kohlenwasserstoffen, VEB Deutscher Verlag fur
Grundstoffindustrie, Leipzig, 1981, p. 113; (b) R. V. Kucer, M. A. Kovbuz, S. D. Kaz-
min, Ukr: Khim. Z. (Russ. Ed.) 1961, 27, 658; (c) H. Pines, B. Kvetinskas, V. N. Ipatjeff,
J. Am. Chem. SOC.1955, 77, 343.
[33] H. H. Szmant, Organic Building Blocks of the Chemical Industry, 1st ed., Wiley-
Interscience, New York, 1989, Chapter 9, pp. 425475.
[34] Anon., Chem. Eng. News 1995 (March 27), 19.
[35] Patents to Amoco Corp. concerning the production of trimellitic acid and anhydride:
(a) US 4.845.274 (1988); (b) US 4.587.350 (1985); (c) BE 902.545 (1985); US
4.816.601 (1987; (d) US 4.769.488 (1985); (e) US 4.755.622 (1985); (f) US 4.719.311
(1985).
[36] (a) Anon., Hoechst Chemicals Development Products, Marketing Fine Chemicals,
1991/1992, p. 61; (b) Hoechst AG (F. Rohrscheid, G. Siegemund), DE 3.739.797
(1987); (c) Hoechst AG (F. Rohrscheid, G. Siegemund, J. Lau), EP 0.317.884 (1988);
(d) Hoechst AG, EP 361.486 (1988; (e) Daikin Ind. Lim. JP 0.285.160 A3 (1988);
(f) Anon., Chem. Eng. News 1996 (February 19), 41.
[37] Anon., Chem. Eng. News 1995 (May 22), 27.
[38] (a) Hoechst AG (F. Rohrscheid), EP 0.505.965 (1992); (b) E. Ioffe, S. Trusov,
G. Andrejeva, V. Fedotov, 9th Int. Symp. Homogeneous Catalysis, 1994, Abstract
B-9, p. 265; (c) RhGne-Poulenc S. A. Paris (P. Mounier), DE 2.115.944 (1971).
 Applied Homogeneous Catalysis with Organometallic
Edited by Boy Cornils & Wolfgang A. Herrmann
© Wiley-VCH Verlag GmbH, 2002

468 2.5 Reactions with Hydrogen Cyanide (Hydrocyanation)

2.5 Reactions with Hydrogen Cyanide

(Hydrocyanation)
Steffen Krill

2.5.1 Introduction and Scope

The addition of hydrogen cyanide to z-bonded systems is an attractive method
for generating nitriles using readily available reagents. Hydrocyanation com-
monly occurs in the presence of basic catalysts [l-31, as with the cyanide ion
itself. In other cases heterogeneous vapor-phase reactions, employing supported
transition metals, have been described [4-61. a,B-Unsaturated carbonyl com-
pounds and analogs are hydrocyanated with alkyl aluminum as the catalyst
[7, 81. While these catalysts are not active enough for the hydrocyanation of
non-activated olefins, certain transition metal complexes do catalyze this reac-
tion very efficiently. Thus, the feasibility of reaction under the conditions of
homogeneous catalysis offers advantages, such as high reaction rates at low
temperatures and possibilities of influencing the reaction pathway, by choosing
the appropriate catalyst system to achieve the required product. In a number of
reactions the superiority of the homogeneously catalyzed hydrocyanation is
demonstrated, by applying the tool of “ligand tailoring” to give almost perfect
control of regioselectivity as well as stereoselectivity. In this way, methods
have been developed to synthesize nitriles, which serve as valuable precursors
for amines, isocyanates, amides, carboxylic acids and esters. During the last
few decades more and more research work has been focused on this direct
approach to generate nitriles 2a or 2b (eq. (1)) by simply adding hydrogen
cyanide to n-bonded systems such as olefins and related systems (1) in the
presence of transition metal compounds. If carbonyl and imine compounds 3
are used as the substrate, the reaction yields the corresponding cyanohydrins 4
(eq. (1)).
Since the first discoveries by Arthur and Pratt, the pioneers of this topic in
1952 [9], homogeneously catalyzed hydrocyanation has become a powerful
tool in the synthesis of nitriles.
The work of Tolman [lo-151 is an example of meticulous investigations on
reaction intermediates. The commercial importance of the DuPont company’s
large-scale process of adiponitrile synthesis via hydrocyanation of butadiene
has forced a number of closer investigations in this area. Particular efforts are
made to find eligible catalysts. As a consequence the ongoing development of
efficient catalyst systems - mainly based on phosphine ligands, phosphite and
phosphinite complexes of nickel and palladium, respectively - results in a
high degree of product selectivity, suppression of the formation of side products,
improved turnover rates of the catalyst, and reduction of the reaction time.
Although not every detail of homogeneously catalyzed hydrocyanation is under-
stood, there is now a well-founded insight into the reaction mechanism. This
 2.5.2 Mechanistic Aspects of Hydrocyanation 469

enables the development of tailor-made complexes for special, well-defined

purposes.

X
I
H

m u 4 *a
1 R4 I H CN

R’ - R4 = H, alkyl, aryl, vinyl, carbonyl, S02R, CN, NRz, NOz,

OR, SR, Hal
X=O.NR

Some of the earlier reviews summarizing this extensive chemistry are those of
Brown [8, 161, Hubert and Puentes [17], James [18], and Tolman [15]. Low-valent
organonickel chemistry was reviewed by Jolly and Wilke [19]. Newer develop-
ments, especially the employment of bidentate ligands for the generation of
more active catalysts as well as the induction of asymmetry in the product nitriles,
are generally reviewed by Casalnuovo and RajanBabu [20]; the exploration of
water-soluble catalysts for hydrocyanation of butadiene is summarized by
Bryndza and Harrelson [21].

2.5.2 Mechanistic Aspects of Hydrocyanation

There are common steps in the homogeneously catalyzed reaction of olefins,
alkynes, and heteroolefinic substrates with hydrogen cyanide, which facilitate
comprehension of the reaction principle.
Product formation was elucidated by closer examination of the reaction me-
chanism. The reason for the unavailability, for decades, of more pertinent data
was the instability of the reactive intermediates and the lack of suitable precursors
for isolable intermediate catalyst species. Mechanistic considerations had to
explain the question of the stereoselectivity and to give a valid concept for the de-
pendence between catalyst-olefin intermediate structures and product formation.
Basically the mechanism of homogeneous hydrocyanation can be separated
into four principle steps which are demonstrated in eqs. (2)-(5), in which ligands
are omitted for the sake of simplicity [ 161.
470 2.5 Reactions with Hydrogen Cyanide (Hydrocyanation)

(1) Oxidative addition of hydrogen cyanide to the preceding metal(0) complex 5 ,

yielding the corresponding hydride complex 6 (step 1):
HCN + Mo
5
- H-M-CN
6

(2) Successive formation of a n-olefin complex 7 by reaction with the substrate

(step 2):

olefin + H-M-CN
6
- n-olefin
I
H-M-CN
7
(31

(3) Transformation of the n-olefin complex 7 to a a-alkyl complex 7a via

insertion of the olefin into the metal-hydride bond (step 3):
n-olefin
I
H - M - CN
7
- o-alkyl-M-CN
7a
(4)

(4) Reductive elimination, regenerating the catalytic active structure 5 and giving
the alkyl nitrile product 8 (step 4):
o-alkyl-M-CN
7a
- alkyl-CN
8
+ Mo
5
(5)

These simplified equations concentrate on the main features of the reaction and
explain most of the observations made. However, the actual mechanism also
includes the equilibrium constants of each reaction step, for most of them are
reversible [ 151.

2.5.3 Hydrocyanation of Olefins

2.5.3.1 Hydrocyanation of Non-Activated Monoolefins

The first report dealing with a homogeneously catalyzed hydrogen cyanide
addition to non-functionalized olefins goes back as far as 1954 and was published
by Arthur et al. [22, 231. In this paper several olefins such as ethylene, terminal
olefins and derivatives containing a bicyclo[2.2.l]hept-2-ene (norbornene, 9)
structure are transformed to the corresponding nitriles via C O ~ ( C Ocatalysis.
)~
Under these conditions only branched nitriles were accessible; the problem of
anti-Markovnikov addition yielding terminal nitriles was solved when carbon
monoxide-free, low-valent transition metal complexes became available. This in-
itiated further investigations which showed that complexes of metals of the first
and second rows of Groups VIII, VI, and Ib exhibit the most active catalytic prop-
 2.5.3.I Hydrocyanation of Non-Activated Monoolefns 47 I

erties in these reactions. However, this early stage of research was marked by its
empirical character and a lack of mechanistic insight [24].
A number of olefins are converted in the presence of tetrakis(tri-o-tolyl phos-
phite)nickel(O) into the corresponding nitriles. These additions yield the terminal
nitriles predominantly [ 151. Systematic investigations were performed on the hy-
drocyanation of olefins containing the norbornene skeleton 9 as a basic structure.
Table 1 demonstrates the development of catalysts to gain stereocontrol of product
formation.
Even in the early days of homogeneous hydrocyanation the reaction of norbor-
nene with hydrogen cyanide in the presence of tetrakis(tripheny1 phosphite)palla-
dium(0) 12 indicated the influence of steric factors, since exo-5-cyanobicy-
cl0[2.2. llheptane (Structure 10) is obtained stereospecifically. This result was
confirmed in similar reactions showing that the entering cyano group is directed
into the exo-position of the norbornene system [28]. This is due to the complexa-
tion of the palladium(0) center to the em-face of norbornene. Recent experiments
have also utilized the bicyclic system to demonstrate asymmetric hydrocyanation
induced by chiral palladium diphosphine complexes. Depending on the applied
ligand system 11-17, an enantiomeric excess (ee) up to 40% is obtained [25].

Table 1. Catalyst development for the hydrocyanation of norbornene.

9 10

* Catalyst Structure Chemical Optical Ref.

yield [%I yield [%eel

Ni[P(OR)& 11 77 - PI
Pd[P(OPh),l, 12 83 - [81
LzPdPPh2 H 13 68 20 [251

CL2
CO2Bu‘
13
(S, S)-“BPPM”
PdL2 14 60 10

14
(R, R)-“diop”
472 2.5 Reactions with Hydrogen Cyanide (Hydrocyanation)

Table 1. (Continued)
* Catalyst Structure Chemical Optical Ref.
yield I%] yield [%eel

Ni(cod)2/BPh3/L 15 58 38 [26, 271

PdLz 16 6 40

\ \ PPh2

16
(R)-"BINAP'

Ni(cod)2/BPhi/L 17 16 10

17

Q
OMe

To date the highest enantiomeric excess of 48 % reported for this substrate class is
obtained using a BINAPHOS palladium complex [25d]. Norbomene hydrocyana-
tion by acetone cyanohydrin using a Nio complex containing three C2-symmetric
binaphthyl fragments 15 gives, with a borane co-catalyst, the ex0 product in 58 %
chemical yield and an ee of 38 %. An analogous monophosphite-based ligand 17
lowers both chemical yield and optical purity in this reaction [26, 271. There are
 2.5.3.1 Hydrocyanation of Non-Activated Monoolefins 473

indications that it is necessary to use a ligand system which gives a seven-mem-

bered chelate complex with palladium [29], since complexes of palladium with
five-membered chclate diphosphines (e. g., chiraphos and prophos) do not exhibit
any catalytic activity [30-351. It is stated that oxidative addition of hydrogen
cyanide precedes olefin binding and ,8-cis-hydride transfer. Due to the weakness
of alkene-palladium bonds, alkene complexation appears to be the rate-limiting
factor [36].
If a vinylic double bond is connected to the bicyclic skeleton of norbornene, a
competition experiment shows that under the conditions employed hydrogen cy-
anide addition proceeds only at the endocyclic strained double bond. It is also
noted that isomerization of the exocyclic olefinic bond may take place in the
course of the reaction [22, 23, 371. These experiments already reveal the most
important features of homogeneously catalyzed hydrocyanation - the influence
of the steric structure of the substrate and the fact that the catalyst also promotes
isomerizations (cf. Section 2.5.5.1).
The mechanism of NiL4-catalyzed hydrocyanation (kP(O-o-tolyl),) of ethyl-
ene has been studied in detail, offering the advantage that olefin isomerization
is avoided (cf. Scheme 1 [lo]). Scheme 1 contains the main features of the pro-
cess, such as oxidative addition, n-and a-complexes, reductive elimination, and
catalyst deactivation by Ni(CN)* formation.

CH -CHp
Et-Ni-L
I '7-
H-Ni-L2 18
CN I
24 CN
4

HCN
L
L A CHz -CH2
CH =CH2
'T I
I
CH -CHz
'7I
H-Ni-L
I
CN
20
ethane + Ni(CN)2
23 22

Scheme 1. Catalytic loop for the homogeneously catalyzed hydrocyanation of ethylene.

474 2.5 Reactions with Hydrogen Cyanide (Hydrocyanation)

The initial step is dissociation of the tetracoordinated Nio complex, generating a

vacant coordination site. This is occupied by oxidative addition of HCN to the
corresponding pentacoordinated hydrido complex (this sequence is not contained
in the simplified catalytic loop for the hydrocyanation of ethylene). The loss of the
ligand is mainly dependent on the steric interaction between the ligands in the
complex. The formation of nickel hydrides via oxidative addition of protonic
acids across Nio complexes has been studied thoroughly [ l l , 13, 381. Loss of
another ligand renders the coordination site vacant for ethylene to give the n-ole-
fin complex 18. A newer mechanistic concept [ 151 describes the n-ethylene-
nickel complex 19 as the active principle to which HCN is oxidatively added to
give the pentacoordinated 18. Loss of one ligand L yields 20. The insertion of
an ethylene unit into the metal-hydrogen bond gives the complex 21, containing
both a-alkyl and n-ethylene ligands. At this stage an excess of HCN is detrimental
to the catalyst lifetime since non-active nickel cyanide 22 and ethane 23 are
formed. However, the reaction proceeds in the presence of an excess of the ligand
to give 24, the direct precursor for the product, propionitrile 25, and the active
principle 19, which launches the catalytic cycle again. Closer investigations of
this reaction reveal a dependence of the reaction rate upon the electronic nature
of the substrate. This effect is demonstrated by substitution of one hydrogen of
ethylene for a cyano group, which results in an increase in the equilibrium
constant by a factor of 100 [lo].
The involvement of metal-hydride species is acknowledged by the catalytic
activity of H C O ( P R ~complexes
)~ and the observation that products are found
which are formed via catalyst-initiated isomerization of the double bond [S].
Solid evidence is also given by NMR studies on the hydrocyanation of ethylene
catalyzed by tetrakis(ph0sphite)-nickel complexes: the species EtNi(C2H4)CN,
(C2H4)NiL2, (C2H4)NiL3, NiL3, and NIL, as well as the hydrido complex
HNiL3CN are observed at low temperature and give credence to the mechanism
suggested above. The final reaction step (i.e., reductive elimination) results
in product formation which, if L is a phosphite, is not reversible in most cases
(see Scheme 1: dashed arrows imply irreversible reaction). Exceptions are ob-
served when an allylic cyanide is formed [39].
Loss of catalytic activity occurs if the ligand system is not present in excess in
the reaction solution. The competitive reaction of another equivalent of hydrogen
cyanide becomes predominant and the corresponding dicyano complexes do not
exhibit any catalytic activity. This has been examined in the case of palladium
and nickel complexes. With excess ligand the free coordination sites are occupied
by the phosphite ligands rather than by HCN [28]. The use of alkali metals and
tetraalkylammonium borohydrides as promoters was misinterpreted in earlier
studies [40, 411. The perception that Lewis acids have a promoting effect was a
breakthrough in the hydrocyanation of monoolefins [24]. If the olefin is substi-
tuted with strongly electron-withdrawing groups (tetrafluoroethylene or acryloni-
trile), the corresponding q'-alkyl complex RNiL,CN exhibits considerable stabi-
lity, reductive elimination is hindered, and the catalyst is poisoned for hydrocya-
nation [ 141.
 2.5.3. I Hydrocyanation of Non-Activated Monoolefins 475

Newer investigations show the decisive role of the appropriate choice of ligand
system in controlling the reaction selectivity as well as the activity of the catalytic
system, usually expressed in terms of turnover number (TON) and turnover
frequency (TOF). Whereas phosphites are versatile ligands for the hydrocyana-
tion, phosphines form complexes with the corresponding metal catalysts which
exhibit hardly any activity [42]. This rather general finding for monodentate
ligands is explained by the observation that electron-withdrawing ligands like
phosphites and phosphinites facilitate the reductive elimination of the alkyl cya-
nide formed in situ, the rate-determining step in hydrocyanation.
When bidentate phosphines are employed as ligands enforcing wide bite angles
of approximately 100-120 O, the reaction selectivity is improved [43]. In this
connection xanthphos-type compounds enhance the reductive elimination step;
this is shown expressively in a study of the hydrocyanation of styrene, where
yields up to 95 % are obtained when xanthphos-type ligands enforcing large
bite angles of 105-106 O are used [43]. The xanthphos ligands were also applied
successfully in the hydrocyanation of terminal alkenes and w-unsaturated fatty
acid esters [44].
A number of olefins are readily hydrocyanated in the presence of NIL, or NiL4
[15], but usually catalyst turnover rates demanded (i.e., the number of moles of
product formed per mole of catalyst used) and the selectivity tends to be low. It
was found that Lewis acids are effective co-catalysts, which enable the reaction
pathway and therefore the reaction selectivity to be piloted and accelerate the
rate of hydrocyanation [lo]. Investigations on the promoting effect of Lewis
acids (e. g., A1CI3, ZnCI,, BPh3 [ 14, 441) imply the formation of a 1: 1 complex
between Lewis acid and NiL4, since at this ratio the reaction rate reaches a
maximum [40, 41, 451.
The influence of solvent on both selectivity and reaction rate is detectable.
Phenolic solvents were found to have a promoting effect on the reaction rate
and to increase the rate of straighthranched nitriles.
The stereoselectivity of the reaction was the target of several investigations.
The results clearly establish that the addition of hydrogen cyanide to olefins is
stereospecifically syn [33, 46-49]. Thus, reaction of terminal, deuterium-sub-
stituted olefins yields the corresponding syn addition products. Hydrocyanation
of 4-t-butyl cyclohex- 1-ene with deuterium cyanide confirmed these results. It
is found that the stereospecifity is independent of the catalyst metal employed,
since both nickel' and palladium' catalysis give the syn addition products [50].
The influence of steric factors on the reaction course has already been
mentioned; not only is the substituent bulk on the Lewis acid decisive, but also
the spatial demand of the substrate substituents. The influence of the olefin
substitution on the N/B rate (i.e., the ratio of 1inear:branched products) of the
product formation is shown in a study of olefins with differing degrees of steric
hindrance. Even by simply changing the substrate from propene to isobutene
(NiL4:L:A1Cl3 = 1:5:3) the N/B rate changes from 1.5 to > 9 9 [45b]. The
importance of regiocontrol of the hydrocyanation is particularly pronounced in
the synthesis of naproxen and ibuprofen, two antiinflammatory drugs, which
can be synthesized via a nitrile intermediate (see Section 2.5.3.2.1).
476 2.5 Reactions with Hydrogen Cyanide (Hydrocyanation)

2.5.3.2 Hydrocyanation of Functionalized Olefins

2.5.3.2.1 Olefins with Heteroatoms and Aryl-Substituted

Olefins
In contrast to aliphatic substituted olefins, functionalized olefins are normally
not readily hydrocyanated with Ni[P(O-~-tolyl)~]~ at ambient temperatures: espe-
cially, olefins containing halogen, oxygen, ester, ketone, aldehyde, or nitrile
groups directly attached to the olefinic carbon or in allylic positions react hardly
or not at all at 25 "C. Investigations show that in most of these cases the olefins
form stable alkylnickel-cyanide complexes but fail at ambient temperatures to
undergo reductive elimination. Fumaronitrile and maleic anhydride form very
stable (olefin)NiL, complexes, in which oxidative addition of HCN is evidently
suppressed by the strong electron-withdrawing character of the olefin [ 151. In
the case of acrolein cyanohydrin acetate (ACA) the P,y-olefinic bond is not
hydrocyanated, but Nio complexes effectively catalyze an Arbusov-like reaction
with the addition of excess ligand, yielding the corresponding unsaturated nitrile
with a a4A5-phosphorussubstituent in the y-position [511. These results already
indicate that HCN addition, in the presence of transition metal catalysts, does
not tolerate certain functional groups in the substrate.
Despite this general observation there are some exceptions. Chiral aryl diphos-
phite ligands derived from binaphthol form Nio complexes which are success-
fully employed in the hydrocyanation of vinyl acetate, styrene, and diverse
styrene derivatives, yielding good to excellent regioselectivities at moderate
enantioselectivities [52]. The active catalysts are easily synthesized by stirring
a solution of 1 equiv. Ni(COD)2 with the corresponding ligand. They catalyze
the hydrocyanation of vinylarenes such as 4-styrene derivatives, 1-vinylnaph-
thalene, and acenaphthylene to 2-arylpropionitriles efficiently giving excellent
control of regioselectivity when bidentate phosphites are employed [55a,
56d-fl. Trimethylsilylethylene forms the terminal nitrile exclusively. A regio-
specific reaction is also observed when t-butylethylene is employed as the
substrate.

H
solvent r\ 1.~rJ
Ni(COD)2 + P P ------+ P P /J"CN (6)
rt 'Ni/ 2. HCN I solvent Ar Me
(COD) > 95 %

Hydrocyanation of styrene 26 (eq. (7)) has been examined in some detail. With
Ni[P(O-~-tolyl)~]~ 27 the branched nitrile 29 is strongly favored over the linear
one, which is explained by the intermediary formation of a detectable alkyl spe-
cies 28. The stability of this intermediate is attributed to the donation of aromatic
ring electrons to the coordinatively unsaturated metal center. Crystal structures of
related compounds are reported in the literature [53, 541.
 2.5.3.2 Hydrocyanation of Functionalized Olefins 477

r I 1 I

26
ZI
L 28 1 29

The features of homogeneously catalyzed hydrocyanations described above

prompted attempts to prepare 2-aryl-2-propionitriles 32 (eq. (8)). The develop-
ment of a synthesis for naproxen demonstrates the successful application of
“ligand tailoring”, the adjustment of the catalyst ligand system to the demands
of the reaction. In this case it is of particular importance to achieve a high stereo-
selectivity because the R-enantiomer has a number of undesirable health effects
WI.

X
& - ,&icN
/ /
cat.
HCN31

(tab. 2)
/ /
CH3

X = H; OMe s - (-9
30 32

6-Methoxy-2-vinylnaphthalene (MVN) 30 is hydrocyanated under the catalytic

influence of Nio complexes 31a-e of 1,2-diol phosphinites that are derived from
readily available mono- and di-saccharides. The sugar backbone and substitution
of the phosphorus-attached aryl groups have a pronounced effect on the reaction
pathway. It is shown that electron-withdrawing groups on the aryl ligands drama-
tically increase the stereoselectivity. As much as 85 % ee was obtained when

Table 2. Catalyst screening for the enantioselective hydrocyanation of methoxyvinylnaph-

thalene (30).
MVN cat.’_ (S)-naproxene nitrile
31a-e
30b 32b

cat. = Ni(cod)pI L

* Catalyst 31a-e: Solvent Optical purities

benzene 40 % ee
benzene 16 % ee
hexane 77 % ee
benzene 78 % ee
hexane 85 % ee**
** > 99 % ee after crystallization
478 2.5 Reactions with Hydrogen Cyanide (Hydrocyanation)

3,5-(CF3)2C6H3(see 31e) was used as a substituent directly linked to the phos-

phorus centers. Recent publications claim an even higher enantiomeric excess
in this reaction (> 99 % ee after crystallization), a chemical yield of > 90 %
and the regiospecific reaction course. In this case a large-scale ligand tailoring
has been performed, which once again demonstrates the interrelationship between
catalyst design and the desired stereochemical control of the reaction (cf. Table 2)
[561.
Employing a tunable ligand system derived from a-methyl D-fructofuranoside,
the enantioselective synthesis of (R)-naproxen nitrile is described (94 % ee at 0 "C)
~551.
The system was exploited by employing electronically unsymmetrical bis-
(diaryl)phosphinites, giving excess of both enantiomers of naproxen nitrile in
excellent yields (91 % S , 95 9% R). Ligand tuning in the asymmetric hydrocyana-
tion of vinylarenes is comprehensively surveyed by the same authors [57].
Figure 1 illustrates the tunable sites on a sugar-derived ligand.

"'oTz-R
R'O
Y

X
2
R = alkyl, aryl, or other sugar residue
= 0, C, S or N (u-or ,!I-glycoside)
X, Y = OPAr,, N(R)PAr,, OP(OAr),, OAsAr,, Pr,
* = variable configuring the sugar
R' = protecting group

Figure 1. Tunable sites on a sugar-derived ligand.

Other publications deal with the performance of this reaction employing NiL4
or Lewis acid promoters which are employed as an additive to decrease the degree
of polymerization [58,59]. p-Isobutylstyrene (a precursor for ibuprofen) is hydro-
cyanated in the presence of the same catalyst, affording the branched product in
65-70 % yield.

2.5.3.2.2 Cyanoolefins
Non-conjugated cyanoolefins are hydrocyanated in the presence of tetrakis(tri-
p-tolyl phosphite)nickel(O) at 25 "C. Characteristic in this reaction is the relative
stability of the RNiL2CN intermediates which allows spectroscopic observation of
these species either by NMR or IR. The ratio of linearbranched products in the
unpromoted reaction is strongly dependent upon the bulkiness of the substrate
[15] (Table 3).
The addition of triorganoboranes allows - depending on bulk and electronic
properties of the organo-substituent - the control of the reaction regioselectivity
[lo, 151. However, the rate of product formation is reduced and the product
distribution is shifted in favor of the linear product [15, 451.
 2.5.4 Hydrocyanation of Alkynes 479

Table 3. Unpromoted hydrocyanation of cyanoolefins using Ni[P(O-o-tolyl),],.

Olefin Product Ratio NB”’

HCN3-BN
2: 1

NC/J\CN
dCN
2M3BN
16: 1

NC CN
~ ~~

a) Ratio N B = linear(norma1)hranched isomer.

Abbreviations: 3-BN, but-3-ene nitrile, 2M3BN, 2-methylbut-3-ene nitrile.

2.5.4 Hydrocyanation of Alkynes

Alkynes are readily hydrocyanated in the presence of a homogeneous catalyst,
especially a nickel-based catalyst system. However, zerovalent palladium
compounds are reported to catalyze the reaction as well, but are less efficient
[60]. The reaction gives an easy access to the synthetically valuable a$-un-
saturated nitriles. The use of acetone cyanohydrin as a synthetic equivalent for
the difficult-to-handle HCN provides an efficient alternative, but the substrate/
catalyst ratio has to be increased in comparison with the reaction with HCN.
The regioselectivity of the reaction is controlled by steric, electronic, and chelative
effects. Investigations were predominantly performed by changing the substituent
pattern on the acetylenic substrate [61].
The reaction proceeds in general stereospecifically as a cis-addition. Equation
(9) shows exemplarily the addition of deutero-HCN (DCN 34) to hex-1-yne 33.
The cis-position of deuterium and the cyano group is found in both branched
(35)and linear (36) products. When dimethyl acetylenedicarboxylate is used as
the substrate, the product of anti-addition is formed. This indicates a change in
the mechanism as a result of the electron-withdrawing effect of the two functional
groups in direct conjugation with the triple bond [62].

D
H = N DCN (9)
34
33 35 36
ratio 35:36 = 6:1
480 2.5 Reactions with Hydrogen Cyanide (Hydrocyanation)

Steric effects, induced by the substituents of the alkyne derivative, dominate in

general the regioselectivity of HCN addition when bulky alkynes are employed
[63]. The observed selectivity finds its analogy in the hydrocyanation of olefins
already discussed. The decisive step involves formation of an q'-alkenyl-nickel
complex.
The regioselectivity of the hydrocyanation of alkynes is determined by both
steric and electronic effects, though in most cases the steric bulk of the substrate
substituent is the predominant factor of the reaction.
Terminal alkynes with an aliphatic linear substituent yield predominantly the
branched product during hydrocyanation (eq. (9)); it is concluded that the
minor bulk of the aliphatic substituent does not contribute much to control of
the reaction, whereas the regioselectivity reflects the greater stability of the bond-
ing between nickel and the secondary carbon of the triple bond in comparison
with the bond between nickel and the terminal carbon atom. In this case electronic
effects overcome the slight steric hindrance induced by the linear substituent. The
product picture drastically changes when bulkier substituents are introduced to the
alkyne system. This is clearly shown when silicon-based side chains are used to
examine the influence of steric effects. A disubstituted alkyne, carrying a linear
aliphatic chain as well as a bulky triphenylsilyl group, is converted by treatment
with HCN exclusively to the corresponding nitrile with the cyano group remote
from the silyl substituent. This effect is confirmed even when smaller silyl-
based substituents are employed, allowing an excellent regiochemical control
by adjusting the bulk of the substituents. The influence of a silyl substituent pre-
vails, even if a bulkier substituent such as phenyl is introduced into the substrate
system. The reaction of substituted stannyl-alkynes are reported, preferably giving
the expected, sterically less strained, product [50]. When the triple bond is
screened by two bulky substituents, such as two trimethylsilyl units, the yield
decreases considerably (<5 %) [63].
In the hydrocyanation of alkynes containing heteroatoms in the side chain, the
branched isomer predominates unexpectedly. In a series of reactions with alkyne
ethers 37, chelative reaction control is observed. Thus, a reaction pathway is en-
tered, directing to the formation of the nitriles 38 with the cyano group attached to
the carbon next to the oxygen-carrying carbon. Further treatment of the reaction
products with aqueous acid yields the stereospecifically substituted methylene
y-lactones 39a (eq. (10)). Alternatively acetone cyanohydrin can be used as a
source of HCN [61].

R-CH2X -'
HCN

Hz:
Nio
R

37 38 39
R = H or Ph x = -(CH2),0Me, -NHAc
Y = -0-= 39a
Y = -N(H)- = 39b
 2.5.5.1 Adiponitrile Synthesis via Hydrocyanation of Butudiene 48 1

These results could also be transferred to the synthesis of a-lactones, depending

on the oxygen location in the alkyne starting material. Several functional groups
are tolerated, which broadens the synthetic applicability. If nitrogen-carrying
substrates are employed, the two-step reaction results in the formation of the
corresponding y-lactams 39b.
The reduction of intermediately formed, isolable unsaturated nitriles opens
up an easy route to regio- and stereo-chemically pure unsaturated aldehydes.
The overall reaction is a regio- and stereo-selective hydroformy lation of alkynes
[611.
The regioselective hydrocyanation of several phthalimidoalkynes yields unsatu-
rated nitriles which are readily transformed chemically into p- and y-amino acids
[64]. Another method of hydrocyanation of terminal acetylenes proceeds via orga-
nozirconium precursors. The starting material is a zirconium-hydride compound,
and the cyano group is introduced by an isonitrile reagent [65]. Acetylenes
are transformed via organometallic intermediates with high regioselectivity into
the corresponding a,a-unsaturated nitriles. Terminal alkynes preferentially give
the terminal nitrile, the formal anti-Markovnikov product of hydrogen cyanide
addition.
Newer investigations deal with the conversion of a-ketoalkynes to highly
functionalized 3,5-substituted 5-hydroxy-3-pyrrolin-2-ones in a regioselective
synthesis with KCN catalyzed by tetracyanonickelate(0) formed in situ from the
system Ni(CN),/CO/KCN in alkaline aqueous medium. This study is based on
the catalytic hydrocyanation of alkynes in the presence of Ni(CN)z- introduced
by Funabiki and co-workers [66].

2.5.5 Hydrocyanation of Dienes

2.5.5.1 Adiponitrile Synthesis via Hydrocyanation

of Butadiene
The most outstanding example for the application of homogeneously catalyzed
hydrocyanation is the DuPont adiponitrile process. About 75 % of the world’s
demand for adiponitrile is covered by hydrocyanation of butadiene in the presence
of nickel(0) phosphite species. This process is discussed for the addition of HCN
to dienes as an example, because in this case a well-founded set of data is avail-
able. Though it was Taylor and Swift who referred to hydrocyanation of butadiene
for the first time [45], it was to Drinkard’s credit that this principle was fully
exploited for the development of the DuPont adiponitrile process [18]. The overall
process is described as the addition of two equivalents of HCN to butadiene in the
presence of a tetrakisphosphite-nickel(0) catalyst and a Lewis acid promoter. A
phosphine-containing ligand system for the catalyst is not suitable, since addition
of HCN to the tetrakisphosphine-nickel complex results in the formation of
hydrogen and the non-active dicyano complex [67]. In general the reaction can
482 2.5 Reactions with Hydrogen Cyanide (Hydrocyanation)

be separated into three stages [68, 691: (1) synthesis of mononitriles by hydro-
cyanation of butadiene, (2) isomerization, (3) synthesis of dinitriles.
Equation (11) gives mechanistic proposals for the three different stages of the
adiponitrile process. The initiating reaction stage affords via monohydrocyanation
of butadiene two isomeric mononitriles, 3-PN 40 and 2M3BN 41 as the by-prod-
uct (cf. Table 3). A copper-based catalyst has been reported that accomplishes the
reaction at this stage with 90% selectivity to 3-PN [68].

CH3-CH=CH-CH2-CN 70%

-L
100 "C
+ HCN
NiL4
3-PN 40 (11)
H2C=CH-CH-CH3 30 Yo
CN
2M3BN 41 L = (Ar0)3P-

In the first stage Lewis acids are absent and further hydrocyanation of the
monoolefin products 3-PN 40 and 2M3BN 41 does not readily occur. The
monocyanation of butadiene is similar to HCN addition to olefins. An individual
feature of hydrocyanation of conjugated dienes is the intermediate appearance of
n-allylic complexes 43, which participate in the successive carbon-carbon
coupling. Equations (12) and (13) demonstrate the reaction of butadiene with
the hydrido-nickel complex 42 leading to formation of nitrile 40 (a) and explain
the generation of byproducts, i.e., the branched nitrile 41 via an alternative
pathway (b) [68-701.

HNiL3(CN) + -
2
I
NILz
42
+L I
CN
43

- CH3-CH=CH-CH*--CN

- b
40
HzC=CH-CH-CH3
I
CN
43 41

In the second stage the product mixture is isomerized into a mixture of 3- and
4-pentene nitriles 40/41 using a similar nickel(0)-based catalyst system and a
Lewis acid such as ZnC1, as promoter. At this stage it is imperative to avoid
the formation of other isomers. Actually we have to differentiate between two
different isomerization processes: the isomerization of 2M3BN to 3-PN and
successive isomerization of 3-PN to the different n-cyanonitriles. It is crucial
for product distribution to control these distinct equilibrium equations. The
most stable conjugated nitrile, CH3CH2CH=CHCN (2-PN), is reported to act as
a reaction inhibitor in the final stage since it poisons the catalyst. Fortunately
 2.5.5.1 Adiponitrile Synthesis via Hydrocyanation of Butadiene 483

3-PN is isomerized to 4-PN much faster than to 2-PN [lo]. The isomerization of
the 3-PN/2M3BN mixture from the first stage is effectively catalyzed by Lewis
acids to give both isomers in proportions approaching their thermodynamic
ratio of 93:7.
These last steps already contain the isomerization operation which proceed via
the equilibration a and b in eq. (13). The reversibility of CN-carbon bond for-
mation is also crucial. 3-PN itself is equilibrated with 4-pentene nitrile (4-PN,
44), so that in the last step mainly the isomeric straight-chain nitriles are available
for hydrocyanation.
The final step comprises hydrocyanation of the isomeric 3-PN/4-PN mixture to
afford the reaction product adiponitrile (ADN, 48) and as byproducts major
amounts of 2-methylglutaronitrile (2-MGN) 49 and smaller amounts of ethyl
succinonitrile (ESN) 50. Scheme 2 demonstrates the importance of adjusting
the catalyst system as well as the Lewis acid promoter to the reaction demands,
since the equilibria are influenced by structural features of both 1711. The selec-
tivity at the branch point a is insensitive to electronic changes on the Lewis
acid, whereas the bulk of the Lewis acid substituent is crucial for reaction control
[72]. Product formation proceeds via the corresponding n-alkyl-nickel complexes
45-47. Replacement of ZnClz by triphenylboron improves the selectivity to ADN
48 in the last step tremendously, to > 90 %, at a conversion rate of 99 % 1691.
Anhydrous triorganotin salts, R3SnX, with synthetically tunable substituents
R were utilized to examine the steric and electronic effects on the selectivity
in nickel(0)-catalyzed pentene nitrile hydrocyanation [7 11. Synergistic effects
between two Lewis acid promoters, Ph3B/Ph3SnPh3BCNin a ratio of 19.1:1,
are reported to increase the stereoselectivity of adiponitrile formation in the hydro-
cyanation of 3- and 4-PN [72]. The use of water-soluble ligands such as the
sodium salt of tri(m-sulfonatopheny1)phosphine (TPPTS) has been explored for
the hydrocyanation of butadiene to facilitate catalyst recovery and recycle from
these high-boiling organic products [2I].

-CN
40

A = Lewis acid
for ZnClp: ADN 83 % CN*A 47
for Ph3B: ADN > 90 %
0-complexes

Scheme 2. Hydrocyanation of pentene nitriles 3-PN (40) and 4-PN (44).

484 2.5 Reactions with Hydrogen Cyanide (Hydrocyanation)

2.5.5.2 Hydrocyanation of Other Dienes

A number of dienes are hydrocyanated in the presence of Ni[P(O-~-tolyl)~]~ as the
catalyst. Studies are dealing with cumulated, conjugated, and non-conjugated sys-
tems. Table 4 summarizes the results of diene hydrocyanation.

Table 4. Hydrocyanation of dienes in the presence of Ni[P(O-o-tolyl),], [ 151.

Diene Hydrocyanation products

-
7/
CN
Me?EtCN

CN

"&CN
NC

Q NC 4 OCN
 2.5.6 Hydrocyanation of AldehydedKetones 485

Allene hydrocyanation yields the isomeric nitriles (see Table 4) containing two
or three allene units. The product formation arises via allene insertion into a ?I-
ally1 nickel cyanide bond, followed by reductive elimination to give the cor-
responding nitriles. Hughes and Powell discuss an analogous insertion of allene
into a n-allylpalladium acetylacetonate [73]. Hydrocyanation of 1,3- or 1,5-hexa-
diene affords, starting with either diene, the same P,y-unsaturated nitriles as major
products, indicating double-bond migration during the reaction course [74].
Campi and Probert suggest that product formation from hydrocyanation of dienes
may be controlled by the thermodynamic stability of intermediate allylnickel spe-
cies and the kinetics of cyanide transfer of either terminal of such a system. In this
connection the hydrocyanation of 1-phenylbuta- 1,3-diene was investigated, which
gives (E)-2-methyl-4-phenylbuta-3-enenitrile as the sole product [70].
The hydrocyanation of 1,3-~yclohexadienedoes not require the presence of
Lewis acids, in contrast to the results found in the case of HCN addition to mono-
olefins [ l l , 74, 751.

2.5.6 Hydrocyanation of AldehydesXetones

Hydrocyanation of aldehydes opens access to the synthetically valuable cyano-
hydrins, precursors for hydroxycarboxylic acids, a-hydroxyketones and D-ami-
noalcohols. Applying the principles of homogeneous catalysis to this reaction it
is possible to obtain cyanohydrins in the optically active form, depending on
how well the catalyst-ligand system is adapted to the substrate.
Pioneer work on this topic was done by Bredig and Fiske [76], who reacted
benzaldehyde with hydrogen cyanide in the presence of quinine as the catalyst
to yield chiral mandelonitrile. Since this discovery, great progress has been
made, especially in developing new chirality-inducing catalysts. Nevertheless,
asymmetric induction of chiral catalysts such as boryl compounds, D-oxynitrilase,
and synthetic peptides [77,78] are usually not very high, except for mandelonitrile
derivatives, though for some substrates the use of D-oxynitrilase induces high
stereoselectivities for addition [79].
When certain cyclodipeptides are used as catalysts for the enantioselective for-
mation of cyanohydrins, an autocatalytic improvement of selectivity is observed
in the presence of chiral hydrocyanation products [go]. A commercial process
for the manufacture of a pyrethroid insecticide involving asymmetric addition
of HCN to an aromatic aldehyde in the presence of a cyclic dipeptide has been
described [go]. Besides HCN itself, acetone cyanohydrin is also used (usually
in the literature referred to as the Nazarov method), which can be activated cata-
lytically by certain lanthanide complexes [811. Acetylcyanation of aldehydes is
described with samarium-based catalysts in the presence of isopropenyl acetate;
cyclohexanone oxime acetate is hydrocyanated with acetone cyanohydrin as the
HCN source in the presence of these catalytic systems [82].
A high asymmetric induction was found for the silylcyanation of benzaldehyde
in the presence of a slightly altered Sharpless reagent [83]. The classical Sharpless
reagent in the presence of two equivalents of 2-propanol [(~-Dipt(Ti)OPr’),]pro-
486 2.5 Reactions with Hydrogen Cyanide (Hydrocyanation)

vided catalytic feasibility. Equation (14) shows the model reaction of benzalde-
hyde 51 to (R)-mandelonitrile 53 under the conditions described [84]. Trimethyl-
silyl cyanide 52 is employed as an equivalent for HCN.
1. L-DipVTi(Oi-Pr)4
20 mol %
OH,...CN
DCM/O"C/l8h

51 52 53
(R)-mandelonitrile

91 % e e
84 % chern. yield

The same conversion is successfully catalyzed by using in-situ generated com-

plexes of Ti(OPr'), and tridentate Schiff bases (Structure 54), which are derived
from substituted salicylaldehydes with chiral aminoalcohols [85].Another similar
chiral reagent is derived from reaction of titanium tetraisopropoxide and the Schiff
base of 3,5-di-tert-butylsalicylaldehydeand (S)-valinol. The mechanism and
stereoselectivity of these chiral Lewis acids are discussed by Corey and co-work-
ers. Other chiral Ti'" Schiff base complexes have been employed in asymmetric
TMSCN addition to benzaldehyde [ 8 5 ] .

R3FoH R' = H, But

R3 R2 = Pr', But
54 R3=H,Ph

Another efficient process has been described for the silylcyanation of aldehydes
in the presence of salen-titanium alkoxide complexes [86]. When a chiral C2 sym-
metric bis(dihydrooxazo1e)-Mg" complex is employed with aldehydes as sub-
strates, both excellent chemical yields and enantiomeric excesses are obtained
[87]. Chiral titanium complexes are also derived from optically active sulfoxi-
mines and a titanium alkoxide precursor [%I.
Another catalyst system which shows a good performance in catalytic activity
as well as asymmetric induction is formed in situ, starting from titanium(1V) alk-
oxides and the Schiff bases of acyclic dipeptides 55ah.
H

55ah i-pr ;I 55b; R = PhCH2-

(S,S)-configuration at chiral centers

 References 487

A number of aromatic and heteroaromatic aldehydes 56 are hydrocyanated in

the presence of this catalyst to give the corresponding cyanohydrins 57. A good
catalytic activity is found only if the complexes are derived from dipeptides
and if the amino acid fragments attached to the linear complex have identical
absolute configuration (see eq. (15)) [89].
,H

(), + HCN
10 mol% Ti(OEt)4/55a/b

PhCHg-40 "C
*
R' H
56 57
R' = aryl, heteroaryl (R)-cyanohydrin

Titanium tetrachloride and (S)-bisnaphthol form an intermediate catalyst which

catalyzes the reaction of aldehydes (3-methylbutanal, 3-phenylpropanal) and
TMSCN (52), yielding the cyanohydrins in an optical purity as high as 82% ee
~901.
Chiral 1,3-diketones have been designed as ligands of metal complexes exhibit-
ing Lewis acidity as well as catalytic activity in enantioslective silylcyanation. An
yttrium complex of 1,3-bis(2-methylferrocenyl)propane-1,3-dione was employed
in the silylcyanation of benzaldehyde to afford the cyanohydrin in 95 % yield
with 87 % enantiomeric excess [91]; the employment of another asymmetric
Lewis acid catalyst having a cyclopentadienyl (Cp) ring attached to a hemilabile
ether moiety and zirconium as central metal atom gives only negligible enantio-
meric excess in the hydrocyanation of benzaldehyde [92].
The assymetric Strecker reaction of diverse imines, including aldimines as well
as ketoimines, with HCN or TMSCN provides a direct access to various unnatural
and natural amino acids in high enantiomeric excesses, using soluble or resin-
linked non-metal Schiff bases; the corresponding chiral catalysts are obtained
and optimized by parallel combinatorial library synthesis [93]. A rather general
asymmetric Strecker-type synthesis of various imines and a$-unsaturated deriva-
tives is catalyzed by chiral bifunctional Lewis acid-Lewis base aluminum-con-
taining complexes [94]. When chiral (salen)Al(III) complexes are employed for
the hydrocyanation of aromatic substituted imines, excellent yields and enatio-
selectivities are obtained [94].

References
[ l ] D. T. Mowry, Chem. Rev., 1948, 42, 189.
[2] Anon., Cyanides in Organic Chemistry, A Literature Review, Electrochemicals Depart-
ment, E. I. DuPont de Nemours and Co., Wilmington, Delaware, 1962.
[3] P. Kurz, Liebigs Ann. Chem. 1951, 572, 23.
[4] E. I. DuPont de Nemours & Co. (D. D. Davis, L. Scott), US 3.278.575 (1966).
[ S ] E. I. DuPont de Nemours & Co. (D. D. Davis), US 3.278.576 (1966).
[6] E. I. DuPont de Nemours & Co. (D. D. Davis), US 3.282.981 (1966).
488 2.5 Reactions with Hydrogen Cyanide (Hydrocyanation)

[7] For a review see: W. Nagata, M. Yoshioka, Org. React. 1977, 25, 255.
[8] E. S. Brown, in Organic Synthesis via Metal Carbonyls (Eds.: I. Wender, P. Pino), 1977,
p. 672; see references cited therein.
[9] E. I. DuPont de Nemours & Co. (P. Arthur Jr., B. C. Pratt), US 2.571.099 (1951).
[lo] C. A. Tolman, J. Chem. Educ. 1986, 3, 199.
[ l l ] C. A. Tolrnan, J . Am. Chem. SOC.1970, 92, 4217.
[12] C. A. Tolman, J. Am. Chem. Soc. 1970, 92, 6785.
[13] C. A. Tolrnan, J. fnorg. Chem. 1972, 11, 3128.
[14] C. A. Tolman, W. C. Seidel, J. D. Druliner, P. C. Domaille, Organometallics 1984,
3, 33.
[15] C. A. Tolman, R. J. McKinney, W. C. Seidel, J. D. Druliner, W. R. Stevens, Homogenous
Catalyzed Olefin Hydrocyanation, Adv. Catal. Ser., Vol. 33, Academic Press, New York,
1985, p. 1.
[16] E. S. Brown, Asp. Homogen. Catal. 1974, 2, 57.
[17] A. J. Hubert, E. Puentes, Catalysis in C, Chemistry (Ed.: W. Keim), Reidel, Dordrecht,
1983, p. 219.
[ 181 B. R. James, in Comprehensive Organometallic Chemistry (Eds.: G. Wilkinson, F. G. A.
Stone, E. W. Abel), Pergamon, Oxford 1982, p. 353.
[19] P. W. Jolly, G. Wilke, in The Organic Chemistry of Nickel, Vol. 1, Academic Press,
New York, 1974.
[20] (a) A. L. Casalnuovo, T. V. RajanBabu, in Transition Metals in Organic Synthesis (Eds.:
M. Beller, C. Bolm), Wiley-VCH, Weinheim, 1998, p. 91; (b) T. V. RajanBabu, A. L.
Casalnuovo, T. A. Ayers, Adv. Catal. Processes, Vol. 2 (Asymrn. Catal.), JAI Press
Inc. 1997, p. 1.
[21] H. E. Bryndza, J. A. Harrelson, in Aqueous-Phase Orgaizometallic Catalysis (Eds.:
B. Cornils, W. A. Herrmann) Wiley-VCH, Weinheim, 1998, p. 393.
[22] P. Arthur Jr., D. C. England, B. C. Pratt, G. M. Whitman, J. Am. Chem. Soc., 1954, 70,
5364.
[23] E. I. DuPont de Nemours & Co. (P. Arthur Jr., B. C. Pratt), US 2.666.780 (1955); Chem.
Abstl: 1955, 49, 76; idem, US 2.666.748 (1955); Chem. Abstr: 1955, 50, 1774.
[24] E. I. DuPont de Nemours & Co. (W. C. Drinkard Jr., R. V. Lindsey Jr.), GB 1.104.140
(1968); Chem. Abstr: 1968, 68, 77795, US 3.496.215; BE 698.333, NL 67.05556; US
3.496.217 (1968), Chem. Abstr: 1969; 71; 300.92Q.
[25] (a) M. Hodgson, D. Parker, R. J. Taylor, G. Ferguson, Organometallics 1988, 7 , 1761; (b)
T. V. RajanBabu, A. L. Casalnuovo, Comprehensive Asymmetric Catalysis, 1-111,
Springer, Berlin, 1999, Vol. 1, p. 367; (c) A. L. Casalnuovo, T. V. RajanBabu, Chirality
If, Wiley, Chichester, 1997, p. 309; (d) T. Hiriuchi, E. Shirakawa, K. Nozaki, H. Takaya,
Tetrahedron: Asymmetry 1997, 8, 57.
[26] M. J. Baker, P. G. Pringle, Chem. Commun. 1991, 18, 1292.
[27] V. V. Dunina, I. P. Beletskaya, Zh. Org. Khim. 1992, 28(11), 2368.
[28] E. A. Rick, E. S. Brown, J. Chem. SOC.D 1969, 112.
[29] M. Hodgson, D. Parker, J. Organomet. Chem. 1987, C27, 325.
[30] P. S. Elmes, W. R. Jackson, J. Am. Chem. Soc. 1979, 101, 6128.
[31] P. S. Elmes, W. R. Jackson, Aust. J. Chem. 1982, 35, 2041.
[32] W. R. Jackson, C. G. Lovel, Aust. J. Chem. 1982, 35, 2053.
[33] W. R. Jackson, C. G. Lovel, Tetrahedron Lett. 1982, 1621.
[34] R. Thornson, W. R. Jackson, D. Haarburger, E. I. Klabunovsky, V. A. Pavlov, Aust.
J. Chem. 1987, 40, 1083.
[35] G. Parrinello, J. K. Stille, J. Am. Chem. Soc. 1987, 109, 7122.
[36] M. Hodgson, D. Parker, R. J. Taylor, G. J. Ferguson, J. Chem. Soc., Chem. Commun.
1987, 1309.
 References 489

1371 E. A. Rick, E. S. Brown, Abstr: Am. Chem. Soc. Pet. Div. Chem. Reprints 1969, B29, 14.
[38] (a) W. C. Drinkard, D. R. Eaton, J. P. Jesson, R. W. Lindsey, J. Inorg. Chem. 1970, 9,
392; (b) R . A. Schunn, .I. Inorg. Chem. 1970, 9, 394; (c) G. K. McEwen, C. J. Rix,
M. F. Traynor, J. G. Verkade, J. Inorg. Chem. 1974, 13, 2800; (d) C. A. Tolman, J. Am.
Chem. Soc. 1970, 92, 6785; (e) J. D. Dmliner et al., J. Am. Chem. Soc. 1976, 98, 2156.
1391 E. I. DuPont de Nemours & Co. (W. C. Drinkard Jr., B. W. Taylor), BE 723.382; NL
6.815.812, DE 1.807.087 (1969), Chem. Abstr: 1969; 71; 101.304.
[40] E. I. DuPont de Nemours & Co. (W. C. Drinkard Jr.), US 3.496.218; FR 1 S44.658, NL
6.706.555, GB 1.112.539; BE 698.332 (1968) Chem. Abstl: 1968, 69, 26810P.
[41] E. I. DuPont de Nemours & Co. (W. C. Drinkard Jr.), DE 1.806.096; Chem. Abstr: 1969,
71, 30.093; NL 15.560; BE 723.126 (1968).
1421 T. Horiuchi, E. Sirakawa, K. Nozaki, H. Takaya, Tetrahedron: Asymmetiy 1997, 8, 57.
[43] (a) P. W. N. M. van Leeuwen, P. C. J. Kamer, J. N. H. Reek, Pure Appl. Chem. 1999, 71,
1443; (b) W. Goertz, W. Keim, D. Vogt er al., J. Chem. Soc., Dalton Trans. 1998, 2981;
(c) M. Kranenburg, P. C. J. Kamer, P. W. N. M. van Leeuwen et al., J. Chem. Soc., Chem.
Commun. Trans. 1995,2177; (d) P. W. N. M. van Leeuwen et al., Chem. Rev. 2000,100,
2741; (e) P. Dierkes, P. W. N. M. van Leeuwen, J. Chem. Soc., Dalton Trans. 1999, 1519.
[44] W. Goertz, P. C. J. Kamer, P. W. N. M. van Leeuwen, D. Vogt, J. Chem. Soc., Chem.
Commun. 1997, 1521.
[45] (a) C. A. Tolman, J. Am. Chem. Snr. 1974, 96, 2780; (b) B. W. Taylor, H. Swift, J. Catal.
1972, 26, 254.
[46] W. R. Jackson, C. G. Lovel, Aust. J. Chem. 1982, 10, 2053.
1471 J. E. Backvall, 0. S. Andell, J. Chem. Soc., Chem. Commun. 1981, 1098.
[48] W. R. Jackson, C. G. Lovel, Tetrahedron Lett. 1982, 1621.
[49] G. Pamnello, J. K. Stille, J. Am. Chem. Soc. 1987, 109, 7122.
[ S O ] W. R. Jackson, P. Perlmutter, Org. Synth. Interdiscipl. Challenge, (Eds.: Streith Jacques,
H. Prinzbach) IUPAC Symp., 5th Meeting, 1984, 55.
[SI] S. Krill, K. Huthmacher, Degussa AG, unpublished results.
[52] M. Yan, Q. Xu, A. S. C. Chan, Tetrahedron: Asymmetry 2000, 11, 845.
[53] H. Werner, R. Feser, J. Organomet. Chem. 1982, 232, 351.
1541 F. A. Cotton, M. D. LaProde, J. Am. Chem. Soc. 1968, 90, 5418.
[55] (a) T. V. RajanBabu, A. L. Casalnuovo, Pure Appl. Chem. 1994, 66(7), 1535; (b) A. L.
Casalnuovo, T. V. RajanBabu, T. Warren, Chem. Ind. 1995, 62, 569.
[56] (a) 0. Fumiyuki, H. Tamino et al., Kikan Kakagi Sosetsu 1993, 19, 115; (b) W. A. Nu-
gent, T. V. RajanBabu et al., Science 1993, 259, 479; (c) T. V. RajanBabu, A. L. Casal-
nuovo, J. Am. Chem. Soc. 1992, 114,6265; (d) T. V. RajanBabu, A. L. Casalnuovo et al.,
J. Am. Chem. Soc. 1994,116,9869;(e) T. V. RajanBabu, A. L. Casalnuovo, Comprehen-
sive Asymmetric Catalysis I-Ill, Vol. 1, Springer, Berlin, 1999, p. 367; (0A. L. Casal-
nuovo, T. V. RajanBabu, Chirality 11, Wiley, Chichester, 1997, p. 309.
1571 (a) T. V. RajanBabu, A. L. Casalnuovo, J. Am. Chem. Soc. 1996, 118, 6325; (b) T. V.
RajanBabu, A. L. Casalnuovo, T. A. Ayers, Adv. Catal. Processes, Vol. 2 (Asymm.
Catal.), JAI Press Inc. 1997, p. 1 .
[58] W. A. Nugent, R. J. McKinney, J. Org. Chem. 1985, 50, 5370.
[59] W. A. Nugent, R. J. McKinney et al., Am. Chem. Soc. Adv. Chem. Ser:, 1992,230,479.
[60] W. R. Jackson, C. G. Lovel, J. Chem. Soc., Chem. Cornrnun. 1982, 1231.
[61] W. R. Jackson, P. Perlmutter, Chem. Br: 1986, 338.
[62] W. R. Jackson, C. G. Lovel, Aust. J. Chem. 1983, 36, 1975.
1631 G. D. Fallon, N. J. Fitzmaurice, W. R. Jackson, P. Perlmutter, J. Chem. Soc., Chem. Com-
mun. 1985, 4.
[64] W. R. Jackson, P. Perlmutter, A. J. Smallridge, Tetrahedron Lett. 1988, 29, 1983.
[65] S . L. Buchwald, S. J. LaMaire, Tetrahedron Lett. 1987, 28, 295.
490 2.5 Reactions with Hydrogen Cyanide (Hydrocyanation)

[66] (a) N. Rosas, A. Cabrera, P. Sharma, J. L. Arias et al., J. Mol. Catal. A: 2000, 156, 103;
(b) T. Funabaki, H. Sato, N. Tanaka et al., J. Mol. Catal. A: 1990, 62.
[67] W. Keim, A. Behr, J. P. Biol, J. Weisser, Erdol, Kohle, Erdgas, Petrochemie, Brennst.-
Chem., 1982, 35, 436.
[68] R. Pearce, Catal. Chem. Proc. 1981, 2, 194.
[69] R. Whyman, Crit. Rep. Appl. Chem. 1985, 12, 128.
[70] E. M. Campi, P. S. Elmes, W. R. Jackson, C. G. Lovel, M. K. S. Probert, Aust. J. Chem.
1987, 46, 1061.
[71] R. J. McKinney, W. A. Nugent, Organometallics, 1989, 8, 2871.
[72] E. I. DuPont de Nemours & Co. (R. J. McKinney, R. B. Osborne), US 4.874.884,
A 891017, (1989) EP 0. 336.314 A2; Chem. Abstr: 1990, 112, 9 8 0 3 8 ~ .
[73] R. P. Hughes, J. Powell, J. Organomet. Chem. 1973, 60, 409.
[74] W. Keim, A. Behr, H.-0. Luhr, J. Weisser, J. Catal. 1982, 78, 209.
[75] J. E. Backvall, 0. S. Andell, Organometallics 1986, 5, 2350.
[76] G . Bredig, P. S. Fiske, Biochem. Z. 1912, 46, 7 .
[77] See references in K. Narasaka, N. Iwasawa, Organic Synthesis: Theory and Applica-
tions, Vol. 2, 1993, p. 93.
[78] (a) F. Effenberger, J. Eichhorn, J. Roos, Tetrahedron; Asymmetry 1995, 6, 271;
(b) M. Hayashi, T. Miyamoto, T. Inoue, N. Oguni, J. Org. Chem. 1992, 58, 1515;
(c) R. Gregory, S. Roberts et al., Tetrahedron Lett. 1999, 10, 7407.
[79] J. Marcus, G. W. M. Vandermeulen, J. Brussee, A. van der Gen, Tetrahedron Asymmetry
1999, 10, 1617.
[80] (a) E. F. Kogut, J. C. Thoen, M. A. Lipton, J. Org. Chem. 1998, 63, 4604; (b) Shell Oil
Co. (D. W. Stoutamine, C. H. Tieman), US 4.560.515 (1985) and references in [25b].
[81] H. Ohno, A. Mori, S. Inoue, Chem. Lett. 1993, 375.
[82] (a) Y. Kawasaki, A. Fuji et al., J. Org. Chem. 1999, 64, 4214; (b) A. Fuji, Y. Kawasaki
et al., Kidorui 1998, 32, 306.
[83] (a) H. Minamikawa, S. Hayakawa, T. Yamada, N. Iwasawa, K. Narasaka, Bull. Chem.
Soc. Jpn. 1988, 61, 4379; (b) K. Narasaka, Stereocontrolled Organic Synthesis, Black-
well, Oxford, 1994, p. 17.
[84] M. Hayashi, T. Matsuda, N. Oguni, Chem. Commun. 1990, 19, 1364.
[85] (a) M. Hayashi, Y. Miyamoto, T. Inoue, N. Oguni, Chem. Commun. 1991, 24, 1752;
(b) E. J. Corey, D. Barnes-Seeman, T. E. Thomas, Tetrahedron Lett. 1997, 38, 4351;
(c) Z. Guo-Fu, Y. Chemg-Lie, J. Mol. Catal. A: 1998, 132, L1.
[86] Y. Jiang, L. Gong et al., Tetrahedron 1997, 53, 14327.
[87] E. J. Corey, Z. Wang, Tetrahedron Lett. 1993, 43, 4001.
[88] C. Bolm, P. Muller, K. Harms, Actu Chem. Scand. 1996, 50, 305.
[89] A. Mori, H. Nitta, M. Kudo, Sh. Inoue, Tetrahedron Lett. 1991, 32, 4333.
[90] (a) K. Narasaka, T. Yamada, H. Minamikawa, Chem. Lett. 1987, 2073; (b) M. T. Reetz,
S. H. Kyung, C. Bolm, T. Zierke, Chem. Lett. 1986, 824.
[91] A. Abiko, G. Wang, Tetrahedron 1998, 54, 11405.
[92] A. van der Zeijden, C. Mattheis, J. Organomet. Chem. 1999, 584(2),274-285.
[93] (a) M. Sigman, E. N. Jacobsen, J. Am. Chem. Soc. 1998, 120(19), 49014902;
(b) M. Sigman, P. Vachal, E. N. Jacobsen, Angew. Chem., Znt. Ed. 2000, 39(7),
1279-1281; (c) P. Vachal, E. N. Jacobsen, Org. Lett. 2000, 2(6), 867-870.
[94] (a) M. Sigman, E. N. Jacobsen, J. Am. Chem. Soc. 1998, 120, 5315-5316; (b) M. Taka-
mura, Y. Hamashima, H. Usuda, M. Kanai, M. Shibasaki, Angew. Chem., Znt. Ed. 2000,
39(9), 1650-1652.
 Applied Homogeneous Catalysis with Organometallic
Edited by Boy Cornils & Wolfgang A. Herrmann
© Wiley-VCH Verlag GmbH, 2002

2.6.1 .I General Scope and Applications 49 1

2.6 Hydrosilylation and Related Reactions

of Silicon Compounds
Bogdan Marciniec

2.6.1 Hydrosilylation

2.6.1.1 General Scope and Applications

Over the last 50 years numerous reactions of organic compounds catalyzed
by transition metal complexes have been developed (e.g., olefin oxidation -
Wacker Process, hydroformylation, carbonylation, hydrogenation, metathesis,
Ziegler-Natta polymerization and oligomerization of olefins) in which the reac-
tivity of metal-carbon bonds in the active intermediate (organometallics) is
crucial.
In catalytic conversions of (organo)silicon compounds only the hydrosilylation
is a well-known process of industrial importance [l-51. However, since 1985
other reactions of silicon compounds catalyzed by transition metal complexes
have been revealed and spectacularly developed. Most of them occur via a
mechanism involving metal-silicon and metal-hydrogen bonds, only occasionally
accompanied by (or sided) metal-carbon bonds.
This chapter presents the hydrosilylation processes as well as the main types of
reactions related to hydrosilylation (except double silylation) in which inter-
mediates with metal-silicon bonds (i. e., silicometallics vs. organometallics)
play a decisive role with mechanistic implications for both new and well-
known catalytic reactions leading to formation of organosilicon compounds [6].
Double silylation (bissilylation) of unsaturated organic compounds has recently
been reviewed comprehensively [7].
Hydrosilylation (or hydrosilation) is a term describing an addition reaction of
organic and inorganic silicon hydrides to multiple bonds mainly of carbon-
carbon, carbon-oxygen and carbon-nitrogen according to Scheme 1.
The reaction, discovered in 1947 by Sommer [8], is one of the most fundamen-
tal and elegant methods of laboratory and industrial synthesis of organosilicon
compounds and other organic silyl derivatives which are also directly subjected
to organic synthesis. Although the reaction can occur by a free-radical mechanism
generated in the reaction mixture, most catalysts (tertiary amines, Lewis acids
such as metal salts, supported metals, and, predominantly, transition metal
complexes) accomplish the process through a heterolytic mechanism [ 1-51. The
scientific literature provides a number of surveys of hydrosilylation reactions or
particular aspects of such processes. Since 1990, many general reviews, chapters
or books devoted to hydrosilylation have appeared [l-6, 9, 101. The best known
and most common catalyst is a chloroplatinic acid revealed first by Speier (Dow
Coming) in 1957 [ 111 as an effective precursor of a homogeneous catalyst for all
hydrosilylation processes. Chalk and Harrod provided a qualitative generalization
492 2.6 Hydrosilylation and Related Reactions of Silicon Compound5

\ I I \
-Si-C-CH -Si-C=CH-
/ I I / I

/ -Si-0-NH-
/
\
Scheme 1 -Si-N-NH-
/ I

for catalysis of the olefin hydrosilylation by transition metal complexes first

published in 1965 [12].
This mechanism (Scheme 2), originally derived from studies of chloroplatinic
acid as a precursor (Pt catalyst), presents an conventional oxidative addition-
reductive elimination steps to explain the hydrosilylation. The oxidative addition
of trisubstituted silanes, HSiR3 to a metal alkene complex configuration (usually

R’

Scheme 2. Modified Chalk-Harrod mechanism.

 2.6.1.1 General Scope and Applications 493

ds and d") is followed by migratory insertion of alkene into an M-H bond and the
resulting metal(silyl)(alkyl) complex undergoes reductive elimination by Si-C
bond formation and regeneration of the metal-alkene complex in excess of alkene.
Since a facile reductive elimination of silylalkanes from alkyl-[MI-SiR, species
was not well established in stoichiometric reaction, a modified Chalk-Harrod me-
chanism was proposed [ 131 to explain the formation of unsaturated (vinylsilane)
organosilicon products, which involves the alkene insertion into the metal-silyl
bond followed by C-H reductive elimination (Scheme 2) [14].
A recent detailed theoretical study of the platinum-catalyzed hydrosilylation
of ethylene [15] led to a conclusion that this process proceeds through the
Chalk-Harrod mechanism. The rate-determining step in this mechanism is the
isomerization of the Pt(silyl)(alkyl) complex formed by ethylene insertion into
the Pt-H bond, and the activation barrier of this step is 23 kcal mol-' for R =
Me and -26 kcal mol-' for R = Cl). In the modified Chalk-Harrod mechanism,
however, the rate-determining step is ethylene insertion into the Pt-SiR, bond
and its barrier is 44 kcal mol-' for R = Me and 60 kcal mol-' for R = C1.
The Chalk-Harrod mechanism has been widely accepted with various modifi-
cations to account for the hydrosilylation of other multiple bonds (C-C), C=O,
C=N), homogeneously catalyzed by various metal complexes.
The high catalytic activity of transition metal complexes in which an unsatu-
rated compound (e. g., olefin) and silicon hydride take part gives rise to various
side reactions, involving processes of olefins (isomerization, oligo- and poly-
merization, hydrogenation, and metathesis) and/or reaction of silicon hydrides
(redistribution, dehydrocoupling) as well as those reactions in which both sub-
strates are involved (telomerization, dehydrogenative silylation of olefin, reduc-
tion of organic substrate) [2, 16, 171. Some of the reactions mentioned are useful
in the search for novel and efficient methods of synthesis of molecular and macro-
molecular compounds.
However, since a large number of different multiple bonds may be involved in
the hydrosilylation itself, it offers many convenient synthetic routes to organosi-
licon reagents (hydrosilylation of carbon-carbon bonds) and also a unique and
very efficient method for selective reduction of the carbon-heteroatom (oxygen,
nitrogen) bond, including asymmetric synthesis. The real scope and limitations
of hydrosilylation as a synthetic method were recently reviewed in various sur-
veys, particularly those by Ojima [1, 41, Marciniec et al. [2, 31, Lukevics et al.
[ 5 ] , Brook [lo] and Hiyama and Kusomoto [18] (olefins). The formation of the
Si-C bond has been developed for almost 50 years and is based on the addition
of the Si-H bond to the carbon-carbon bond of alkenes, arylalkenes, cyclo-
alkenes, alkadienes and -trienes, and alkynes, as well as all their derivatives
with functional groups. Commercial production of silane coupling agents and
adhesives is based on such processes [19, 201.
The catalytic addition of substituted silanes to olefins occurs predominantly ac-
cording to the anti-Markovnikov rule, resulting in alkylsilanes with terminal silyl
groups, but under some conditions (e. g., with a catalyst such as Pd, Ni complexes
[ 1, 21) this product is accompanied by an a-adduct, i.e., one containing an internal
silyl group.
494 2.6 Hydrosilylution and Related Reactions of Silicon Compounds

An organosilicon derivative synthesized by hydrosilylation of a carbonyl group

(e. g., aldehydes, ketones, esters) or a carbon-nitrogen bond (e. g., imines, oximes,
isocyanates) may be regarded as an intermediate which usually leads, when re-
acted via solvolysis, to the desired organic product. These reactions have been
strongly developed, particularly for complexes of rhodium (e. g., the Wilkinson
catalyst [21]), ruthenium [22], and platinum [23], which are commonly used in
selective and asymmetric hydrosilylation of carbonyl compounds. The direction
of the hydrosilylation is determined by the polarization of the C=O or C=N
group which always yields products in which hydrogen is added to the electrophi-
lic carbon atom and the silyl group is added to the nucleophilic oxygen or nitrogen
atom leading, in the end, to Si-0-C and Si-N-C bonds respectively [1-4].
Asymmetric hydrosilylation of prochiral carbonyl compounds, alkenes,
1,3-dienes, and imines has been extensively studied and remains one of the
most important subjects in the field. This reaction is strongly affected by the
nature of the catalyst (metal, type of chiral ligand) and the substrate as well as
the reaction conditions (solvent, temperature, etc.). In recent years, many papers
have been published on asymmetric hydrosilylation, describing new catalytic
systems (mainly new optically active ligands) and new synthetic applications of
the reaction [4, 241.
Hydrosilylation of unsaturated organosilicon compounds has also found several
applications in molecular and polymer organosilicon chemistry. In particular, the
addition of polyfunctional silicon hydrides to poly (vinyl)organosiloxane, catalyzed
exclusively by Pt compounds and providing an activated cure for silicon rubber
[ 101, has been of great practical importance. Hydrosilylation of the vinyl group
at silicon seems to be effective synthetic method for preparation of oligomers
and polymers with a linear or cyclolinear structure (polyhydrosilylation), and
can occur either via the addition of dihydro-carbosilanes and -siloxanes to divinyl-
silanes and -siloxanes [25, 261 or by intermolecular hydrosilylation [4] (eq. (1)).
7H3

CH3
I
?43
n H-Si-CH=CH-Si-CH=CH2
CH3
I
- H2PtCIe
90-100"c 1::; y 3
Si-CH=CH-Si-CH2-CH2
I AH3
I" (l)
The hydrosilylation of unsaturated polymers (e. g., polybutadiene, polyiso-
prene, polyesters, other polyenes, polycarbonates) with a silane having hydro-
lyzable substituents at Si atoms has been reviewed recently [26]; it leads to poly-
meric systems with enhanced activity toward mineral fillers. Both >C=C< and
carbonyl bonds are capable of hydrosilylation (eq. (2)).
-(CH2CH=CHCH2),- + (R013SiH cat' * (CH2CH2CHCH2)"
I (2)
Si(OR)3

This modification is connected with a reversed use of the silane (siloxane) cou-
pling agents. On the other hand, the hydrosilylation reaction is commonly applied
as a method of crosslinking organic polymers containing vinyl and ally1 groups
with siloxanes and polysiloxanes with Si-H functionality (e. g., [27]).
 2.6.1.2 Homogeneous Catalysts 495

Reactive silicones (those with usually pendant organofunctional groups) are

a whole branch of materials for adhesives, binders, ceramic coatings, dielectric
coatings, encapsulants, gels, membranes, optical coatings, photolithographic ma-
terials, polymer synthesis, sealants, and much more [26, 281. Hydrosilylation is
a major method used for attachment of an organofunctional group to a siloxane
backbone. Intermolecular hydrosilylation, i. e., hydrosilylation of the molecule
with both Si-H and unsaturated functions, can be recognized as hydrosilylation
polymerization leading to oligomeric or polymeric silacarbosilanes [2, 41. Intra-
molecular hydrosilylation, leading to cyclic products, competes with polyaddition.
Generally, alkenylsilanes with an internal >C=C< bond are inert toward
intermolecular hydrosilylation under mild conditions. No ring closure occurs
when a short alkenyl substituent is present on the silicon atom of the substrate
(eq. ( 3 ) ) (e.8.) [291).

Intermolecular hydrosilylation of diethynylsilanes with dihydro-substituted

silicon compounds gives high molecular weight polymers: -SiR,CH=CH-,
(e. g., [30]). The polymeric products obtained in the above-mentioned reactions
are suitable substrates for ceramic and optoelectronic materials.
Catalytic hydrosilylation provides a convenient route to silicon-containing den-
drimers. Combinations of hydrosilylation with alkenylation (usually allylation and
vinylation) and ethynylation give powerful protocols for the rapid and efficient
synthesis of silicon-containing dendrimers (mostly carbosilanes and carbosilox-
anes) [4]. This topic has recently been reviewed by Majoral [31] and Schlenk
and Frey [32]. At present carbosilane dendrimers are the most important class
of Si-based dendrimers (cf. also Section 3.2.2).

2.6.1.2 Homogeneous Catalysts

Most research and industrial syntheses are carried out in the presence of platinum
complexes, with H2PtC16commonly used as the initial precursor. A solution of
this catalyst in isopropanol (]-lo%) is referred to as SpeierS catalyst [ll]. In
addition to isopropanol other solvents (alcohols, ketones, aldehydes, ethers, esters,
THF, hydrocarbons) have also been used in the preparation of active catalysts
from chloroplatinic acid. Since 1957 hundreds of catalysts based on chloroplatinic
acid and other d8-Pt" and d"-Pto complexes have been reported [l-51. The
Karstedt's type of catalyst obtained by treating hexachloroplatinic acid with divi-
nyldisiloxane was discovered in 1973 [33] and has predominated in recent years.
This catalyst has the empirical formula Pt2(CH2=CHMe2SiOSiMe2CH=CH2)3.
Its structure was reported [34, 351.
A general characteristic feature of the H2PtC16-solventcatalytic system is the
induction period which is followed by a fast exothermic reaction. Recent studies
496 2.6 Hydrosilylation and Related Reactions of Silicon Compounds

by Lewis et al. have suggested that various widely used hydrosilylation catalysts
derived from metal halides (e. g., the Karstedt catalyst) are colloidal in character
[36-391. The Karstedt catalyst, under conditions where [Si-HI < [olefin], can
form mononuclear platinum(0) species (M) but under conditions when [Si-HI
> [olefin], platinum intermediates contain Pt-Si and Pt-Pt bonds (cluster (C))
[38, 391. Both forms seem to be responsible for catalysis. Clusters can form
colloids and there may be steps where the sequence in eq. (4) is operative.
(M) olefin
SiH SiH
(c) =====colloid - bulkmetal (4)

Other Pt" and Pto complexes were used as catalysts for the hydrosilylation, e. g.,
PtCl,L, and Pt2C14L2(where L = olefin, nitrile, phosphine, alkyne, etc.); Pt salts
and complexes with alkadienes, norbornadienes, and cycloolefins; as well as
phosphine complexes of Pto [ 1-51. The presence of phosphine ligands protects
against colloid formation.
Of the new Pt catalysts reported since 1990 platinum complexes with new
ligands and activators are noteworthy. Cyclodextrin complexes of platinum (as
host-guest complexes) have been employed as hydrosilylation catalysts active
at elevated temperature after releasing the guest compound [40]. Some other
organic compounds have recently been used as activators (ligands) of Pt com-
plexes, e. g., unsaturated secondary and tertiary alcohols and silylated unsaturated
alcohols [411, alkadiynes, cyclooctadiene [42], and vinylnorbomene as well as
quinones and methylnaphthoquinones [43].
On the other hand, there is a need to use inhibitors of the platinum catalysts
temporarily to reduce their catalytic activity in the presence of hydro- and vinyl-
polysiloxanes in order to stop the curing process at room temperature, but to allow
the platinum catalyst to be activated at elevated temperature. Among the principal
types of compounds reported are alkenyl derivatives, esters of unsaturated acids,
crown ethers, organic nitrogen compounds, phosphines, linear and cyclic vinyl-
siloxanes, and poly(viny1)siloxanes [2], and recently fumarate [44] and maleinate
[33]. New co-activators of the catalysts (precursors) have been revealed in the
1990s to reduce to ppm the levels of platinum required to effect hydrosilylation
curing [45, 461.
Rhodium d8 complexes have been used since the mid- 1960s as highly effective
catalysts, particularly for the hydrosilylation of C=C and C=O bonds. Two types
of rhodium complexes are usually employed: RhX(R,P), (where X=Cl, R=Ph;
Wilkinson's catalyst) and RhX(CO)(R,P),. In addition, dinuclear rhodium com-
plexes containing n-acceptor ligands not involving phosphines have been used,
i.e., Rh2X2Y4(where X=C1, R, Y=C2H4, CsHl4 and other olefins, CO, COD,
P(OR)3, Cp, and Cp*). There are many other Rh' and Rh'" complexes catalyzing
the hydrosilylation reaction, e. g., RhH(PPh,),, RhC13(PPh3)3,RhC13 . 3H20, Rh
(acac)(C2H4)and Rh2(pfb), [l-5, 9, 101.
Cyclopentadienyl complexes of Rh' + Rh" appeared as valuable examples in
the mechanistic study of ethylene hydrosilylation [14, 471. G C N S and NMR
studies as well as deuterium labeling of the substrates allowed an alternative pro-
posal to the Chalk-Harrod mechanism, initiated by a hydrogen shift to form
 2.6.1.2 Homogeneous Catalysts 497

CpRh(C2H5)SiR3[ 141. This reaction cycle unexpectedly involves the generation of

Rh" intermediates and fails to re-form CpRh(C2H4)(SiR3)Hdirectly. Numerous ex-
amples of olcfin insertion into M-Si bonds, which have been demonstrated for Fe,
Co, Ru, and Rh complexes support the generality of this reaction mechanism [6,9].
Cationic rhodium complexes, e. g., [Rh(cod),]+BK [48] and [Rh(coe)]+ClOi
[49], have recently appeared as regio- and stereoselective catalysts for hydrosily-
lation of alkynes and exclusive formation of vinylsilanes instead alkylsilanes in
the hydrosilylation of alkenes.
Siloxy-rhodium(1) complexes of general formula [(diene)Rh@-OSiMe3)I2,
where diene = cod, nbd, showed much higher catalytic activity in the hydrosily-
lation of 1-alkenes [50] and ally1 ethers [5 11 by triethoxysilane than the respective
chloro-rhodium(1) complexes [(diene)Rh(~-Cl)~] suggesting a possible applica-
tion of dimeric bridged siloxy-metal complexes as potent precursors of a variety
of hydrosilylation reactions.
Rhodium-phosphine complexes are usually active and effective in the asym-
metric hydrosilylation of olefins, ketones, and aldehydes, allowing for the virtual
synthesis of optically active alkoxysilanes and organic compounds of high purity.
Chiral rhodium-phosphine catalysts predominate in the hydrosilylation of pro-
chiral ketones. This subject has been comprehensively reviewed by several
authors who have made major contributions to this field [52-541. A mechanism
for the hydrosilylation of carbonyl groups involving the introduction of asym-
metry is shown in Scheme 3 [55].
This mechanism consists of several steps: (1) oxidative addition of hydrosilane
to the rhodium(1) complex; (2) and (3) coordination and insertion of the ketone
into the rhodium-silicon bond to form a diastereomeric a-silyloxyalkylrhodium
intermediate; (4) reductive elimination of alkoxysilane as a primary product;
and ( 5 ) hydrolysis of the alkoxysilane yielding an optically active alcohol. Hydro-
silylation of prochiral ketones by prochirally disubstituted silanes leads to asym-
metry on the silicon atom as well as on the carbon atom and, in the presence of
chiral rhodium complexes, results in optically active monohydrosilanes (eq. ( 5 ) )
[21:
R2 R3
\ \
7iH2 + C=o R1R2Si*(H)OC*HR3R4 (5)
/
R1 R4

Transition metal carbonyls such as Co2(C0)* and COH(CO)~,formed in the

reaction of R3SiH with dimer (but also Fe(CO)5 and M3(CO)12(M = Fe, Ru,
0s)) have been found to be active catalysts for the hydrosilylation of olefins,
dienes, unsaturated nitriles, and esters as well as for hydrosilylation C=O and
C=N bonds [56]. Hydrosilylation of phenylthioacetylenes in the presence
of this catalyst is extremely regioselective [57]. Cobalt(1) complexes, e. g.,
CoH(X),L3 (X = H, N), could be prospective candidates for investigation of
the effectiveness of alkene hydrosilylation by trialkoxysilanes as well as dehydro-
genative silylation [58].Direct evidence for the silyl migration mechanism opera-
tive in a catalytic hydrosilylation pathway was presented by Brookhart and Grant
[59] using the electrophilic Co"' cationic complex.
498 2.6 Hydrosilylation and Related Reactions of Silicon Compounds

YSi'
CI

CI
I

CI

Scheme 3 E (+) DIOP, S solvent

A successful study of non-phosphine iridium complexes I?, I?", and Ir", e. g.,
I r X ( ~ o d [60],
) ~ 1rH2(triso)(SiMePh2),[61, 621, Ir(triso)(coe), (coe = cyclooctene;
triso = tris(diphenyloxophosphoranyl)methanide), I r ( t r i s ~ ) ( C ~ H[6~11,
) ~has de-
monstrated effective hydrosilylation of alkenes and alkynes. Iridium phosphine
complexes, e. g., Ir(C G C P ~ ) ( C O ) ~ P C[63]
~ , and IrCl(CO)(PPh,), [64], are also
found to be active for hydrosilylation of phenylacetylene and 1-hexyne.
Iron triad (Fe, Ru, 0 s ) catalysts, including carbonyl complexes used in the
hydrosilylation of carbon-carbon multiple bonds, exceptionally give such prod-
ucts of hydrosilylation as RuCI2(PPh& [65], but predominantly they give unsatu-
rated silyl olefins which are the products of dehydrogenative silylation. Ru3(CO),
was recently reported to be an effective catalyst for hydrosilylation of 1-octene
[66] and - for production of silane coupling agents - in hydrosilylation of
ally1 chloride [67] by trialkoxysilane. Ru(CO)~(PP~,), appeared to be an effective
catalyst for hydrosilylation of allylamine [68]. OsHC1(CO)PPr3 was found to be
 2.6.1.2 Homogeneous Catalysts 499

a very active and highly selective catalyst for the hydrosilylation of phenyl-
acetylene by triethylsilane [68a].
Numerous complcxes of nickel(I1) and nickel(0) catalyze the addition of the
Si-H bond to olefins. Among such catalysts are nickel-phosphine complexes,
e.g., Ni(PR&X2 (where X=C1, I, NO,; R=alkyl and aryl), Ni(PPh,)4, and Ni-
(C0),(PPhJ2, as well as bidentate complexes of NiC1,-(chelate) and Ni(acac),L
(kphosphine), and Ni(c~d),(Pr,)~[ 1-51. A characteristic feature of nickel-phos-
phine-catalyzed olefin hydrosilylation is side reactions such as H/Cl, redistribution
at silicon and the formation of substantial amounts of internal adducts in addition
to terminal ones [69]. Phosphine complexes of nickel(0) and nickel(I1) are used
as catalysts in the hydrosilylation of olefins with functional groups, e. g., vinyl
acetate, acrylonitrile [ 1-41, alkynes [70], and butadiynes [71].
Palladium complexes are not generally regarded as good hydrosilylation cata-
lysts because of the ease of their reduction to the metal by silicon hydride. How-
ever, many reports have suggested that some phosphine Pdo and Pd" complexes
(e. g., Pd(PR&, PdX2(PR&, Pd(chelate)(PPh&, Pd(RCN)2 + PPh,, etc.) are ac-
tive in the hydrosilylation of alkenes, alkadienes, cycloalkadienes, and especially
conjugated dienes [ 1-61 similarly to nickel complexes. In contrast to unsubstituted
l-alkenes, the hydrosilylation of their derivatives with an electron-withdrawing
substituent, e. g., acrylonitrile, styrene [72] or vinyltrichlorosilane [73], in the
presence of phosphine complexes of palladium leads to the selective formation
of an a-adduct. Hayashi's study on the catalysis by P ~ C I ( V ~ - C , Hof ~the
) ~ hydro-
silylation of olefins proved the reaction occurs via migratory insertion of the olefin
into the Pd-Si bond [74].
Pd-phosphine complexes with chiral phosphines (MDPP, e. g., menthyldiphe-
nylphosphine) may also be used as catalysts for the asymmetric hydrosilylation
of C=C bonds (alkenes, arylalkenes, norbornene, cycloalkadienes, and dienes)
(e. g., [75, 76]), affording a relatively high yield and optical purity.
The Ziegler system ML,-A1(C2Hs), (M=Ni, Co or Fe; n=2, 3; k a c a c or Cl)
has been used mostly in the addition of trialkyl and triphenylsilanes to conjugated
dienes and trienes (especially Ni(aca~)~-Al(C~H~),) as well as in hydrosilylation
of olefins with functional groups (the three-component system with additional
PPhd [2, 51.
Although the vast majority of hydrosilylation catalysts are derived from group
VIII metals, recent results revealed that early transition metal complexes (mainly
metallocenes) are active catalyst-precursors for olefin hydrosily lation. Examples
are organometallic catalysts generated from Cp,MC12 (+ BuLi) with M =
Ti, Zr, Hf [77], and organolanthanide complexes, such as [Cp*NdHI2,
c ~ * N d C H ( s i M e ~[78],
) ~ Cp*YCH,-THF [go], and Cp*zL,,CH(SiMe3)2 where
L, = La, Nd, Sm and Lu [81].
According to the first information on the catalysis of hydrosilylation by orga-
noactinide complexes Cp*,A,Mez (where A,, = Th, U), they are efficient for hy-
drosilylation of terminal alkynes [82]. All catalytic and kinetic examinations of
catalysis by early (do) transition metal complexes (also by metal complexes
with non-Cp ligands, e. g., [83]) support the generally accepted mechanism
involving rapid olefin (acetylene) insertion into an M-H bond followed by a
500 2.6 Hydrosilylation and Related Reactions of Silicon Compounds

slow Si-C bond-forming u-bond metathesis of the resulting metal-alkyl with

silane [83].

2.6.1.3 Immobilized Metal Complexes as Catalysts

Transition metal complexes can be immobilized on organic polymers such as
polystyrene-divinylbenzene, polypropylene, poly(viny1 chloride), etc., as well as
on the surface of inorganic oxides such as silica, y-A1203, glass, and molecular
sieves (cf. Section 3.1.1.3). The metal complexes are attached to the supports via
phosphine (-PR,), amine (-NR,) or other groups (-SH, -CN) linked to organic or
inorganic support, e. g. Structures 1 and 2, where M = Pt, Rh, Pd, Ru, or Ni.
Ph I
I I
@--O-$-(CH2)pPPh,MXm(PPh3)n

Ph
1 2
Early studies of the supported metal complexes utilized as hydrosilylation cata-
lysts focused on the immobilization of H2PtC1, on ion exchangers. Chloroplatinic
acid and other Pt complexes have been used as efficient precursors of the catalysts
anchored to silica or organic materials for the hydrosilylation of 1-alkenes,
styrene, allyl derivatives, and acetylene [2, 84-87].
The sol-gel method was applied for the preparation of heterogenized com-
plexes such as Structure 3 based on the polycondensation of suitable trialkoxy-
silyl-substituted organosulphides, organophosphines, and organoamines bound
as ligands to a given complex (Pt, Rh, Ir, Ru). They were employed in the hydro-
silylation of allyl chloride and other olefins [88].

3
Their advantages are nonswelling properties, resistance to organic solvents and
reagents, and high-temperature stability, and there is a possibility of using them in
aqueous and organic media. Schubert et al. synthesized such a catalyst by poly-
condensation of Rh(CO)CI[PPh,CH2CH2Si(OEt)3]2 with tetraethoxysilane; it
showed similar catalytic activity in the hydrosilylation of 1-hexene to a homoge-
neous analog attached to the surface of silica [89]. Combination of both concepts
for synthesis of new polymeric inorganic supports; i.e., the sol-gel process and
 2.6.1.4 Photo- and Peroxide-Initiated Catalysis by Metal Complexes 501

grafting of organosiloxanyl radicals (Structure 4) aimed at the immobilization of

rhodium(1) complexes bound to the nitrogen and phosphine ligands [90].

4
-2R2 = -N(CH2CH=CH2)2, -PPh2
Supported platinum, rhodium, and ruthenium complex catalysts have been used
extensively in the reaction of trisubstituted silanes with acetylene in the gas phase,
predominantly in a continuous-flow apparatus. Formation of a polymer layer on
the surface after immobilization of the platinum complex has protected the cata-
lyst against leaching in long-term hydrosilylation tests [91].
Rhodium complexes immobilized on inorganic and organic supports constitute
the majority of active heterogenizing hydrosilylation catalysts predominantly used
for mechanistic examinations. A large number of the rhodium precursors have
been employed for immobilization on inorganic oxides, e. g., RhC1(PPh3)3,
Rh2C12(C0)4,RhC13 . 2H20, Rh2C12(C2H4)2 and RhX(C,H,)(acac) [ 1-51. In con-
trast to silica, other inorganic supports such as y-Alz03, zeolites, [92] and porous
glasses do not influence the activity and selectivity [ 1-51. Diphenylphosphine and
ligands with amine and mercapto groups have mostly been used in hydrosilylation.
Organic polymers (particularly styrene-divinylbenzene polymers) containing
the functional groups -PPh2, -NR2 and -CN have also been commonly used to
immobilize Rh complexes [2]. [RhCI(CO),], bound to polyamides containing
aromatic, heteroaromatic, and aliphatic fragments was tested in the hydrosilylation
of alkenes to exhibit much higher thermal stability and high activity than con-
ventional polystyrene supports [93, 941.
Generally, the catalytic activity of all types of immobilized complexes (Pt, Rh,
Ni, Pd and others) is comparable with that of the homogeneous analogues,
although an increase in selectivity and/or activity of heterogeneous catalysts has
been noted. The mechanism of catalysis by supported metal complexes has not
been fully resolved yet. Thus, during the reaction the anchored complex may
be reversibly detached from the support and can act as a homogeneous catalyst
in solution and/or it may act catalytically as part of a heterogeneous system.

2.6.1.4 Photo- and Peroxide-Initiated Catalysis

by Metal Complexes

Photogenerated catalysts, which are defined as those obtained by light-induced

generation of a ground-state catalyst from a catalytically inactive precursor,
have become a topic of current interest in catalysis by transition metal complexes
(cf. Section 3.2.9). Such methods have also been applied in hydrosilylation.
502 2.6 Hydrosilylation and Related Reactions of Silicon Compounds

Cr(C0)6 is active in the 1,4-hydrosilylation of 1,3-dienes to yield allylsilanes

using a method of synthetic utility [1-4]. Wrighton and co-workers have reported
the high catalytic activity of Fe(CO), upon UV irradiation under mild temperature
conditions (0-SO "C) in the hydrosilylation of alkenes [ 131. Ru, Os, and Ir are
effective photocatalysts of the hydrosilylation of acetone, whereas Fe3(C0)12,
C O ~ ( C O )and
~ , C O ~ ( C O )are
, ~ known to be efficient photoactivated catalysts in
the hydrosilylation of olefins. It has been also demonstrated that R u ( C O ) ~ P P ~ ~
and R U ( C O ) ~ ( P Pcomplexes
~~)~ can serve as catalysts for the photochemical
hydrosilylation of benzaldehyde [2].
Low-valent metal complexes containing non-carbonyl ligands also exhibit d-d
transitions in the near-UV, and give rise to similar photodissociative behavior.
When the labilized ligand is a phosphine and the reaction is performed in air, a
secondary photooxidation of the free ligand to phosphine oxide occurs readily
in a manner characteristic of a thermal reaction. UV radiation can lead to genera-
tion of high concentrations of coordinatively unsaturated centres by ligand dis-
sociation and free ligand modification to prevent back-reactions. Photocatalytic
experiments also confirm the previously suggested role of dioxygen as
Wilkinson's complex co-catalyst [9S]. Photochemically induced hydrosilylation
by platinum compounds, e. g., chloroplatinic acid, was reported to increase the
yield (above 90%) of cycloalkylsilane compounds and enable the process to
occur at ambient temperature [96]. Irradiation of platinum bisv-diketonates),
e. g., Pt(acac), [97], in the presence of hydrosilanes and olefins results in olefin
hydrosilylation [97-991.
Molecular oxygen has become a commonly used co-catalyst for inactive or
weakly active transition metal complexes [ 1-51]. In addition, other oxidizing
agents, mainly peroxides, have recently been used in active rhodium complexes
in particular, but also in metal carbonyls, as catalysts for hydrosilylation. The
catalytic activity of bis(triphenylphosphine)carbonylrhodium(I) in the hydrosily-
lation of C=C and C=O bonds can be much increased by the addition of about
a SO % molar excess of tert-butyl hydroperoxide [ 1001. Chromium triad carbonyls
M(C0)6, where M = Cr, Mo, W, have been tested to examine the effect of various
organic peroxides on the hydrosilylation of 2,3-dimethyl- 173-butadiene by
triethyl-, triethoxy- and methyldiethoxysilanes [ 1001. The evidence for organic
oxidant promotion of RhCl(cod)phosphine-catalyzed hydrosilylation of 1-hexene
was demonstrated previously [loll.

2.6.2 Dehydrogenative Coupling Reactions

2.6.2.1 Dehydrogenative Silylation of Alkenes

and Alkynes with Hydrosilanes
The heterocoupling of hydrosilanes with olefins occurs, formally, via two
pathways yielding an unsaturated product as well as either hydrogen or a hydro-
genated olefin (DS-1, DS-2) as presented in eqs. (6), and is usually accompanied
 2.6.2. I Dehydrogenative Silylution of Alkenes and Alkynes with Hydrosilanes 503

by hydrosilylation products. However, in the presence of a nickel complex in

the catalyzed dehydrogenative silylation of vinylsilanes [ 103, 1041 and styrene
[104, 1051 has been shown that the unsaturated product can be formed via the
third pathway involving hydrogenated dimerization of olefins (DS-3). The
catalytic and synthetic aspects of the process have been reviewed recently [6, 9,
1021.
CHzZCHR'

-€FZ
R'CHzCHSiR3 + H2 DS-1

HSiR3 + * CH2=CHR' R'CH=CHSiR3 + R'CH2CH3 DS-2 (6)

+ CH2=CHR' R'CH=CHSiR3 + R'C4HsR' DS-3
"il
In the earliest examinations, group R was the electronegative substituent, e. g.,
styrene [ 1061 or a substituted styrene [ 106, 1071, vinyl-trisubstituted silanes [ 1081,
or trifluoroprene [ 1091. However, dehydrogenative silylation of alkenes also leads
to the respective alkenylsilanes [110]. All the olefins mentioned react with tri-
substituted silanes to give silyl olefins mostly in the presence of members of
the iron and cobalt triads, i. e., Fe, Ru, 0 s and Co, Rh, Ir, although other transition
metal complexes have also recently been reported as dehydrocoupling catalysts,
e. g., Ni [ l l l ] , Pt [112], Pd [113], and early (Ti, Zr, Hf) transition metal organo-
metallics [77].
The number of examples of highly selective dehydrogenative silylation is still
limited. The most convincing examples are RU,(CO)~~- and Fe3(CO),2-cata-
lyzed reactions of styrene [106, 1141 and vinylsilane [115] with HSiEt,,
RuH2(H2)2PCy,)2-catalyzed reaction of ethylene with HSiEt, [ 1161, and cationic
rhodium complex-catalyzed dehydrogenative silylation, e. g., [ 1171, as well as
the nickel equivalent of the Karstedt catalyst [ 1051.
Photocatalyzed hydrosilylation of alkenes by iron-triad carbonyls [ 1181 and
Co(SiR,)(CO), [ 1191 yielding alkyl- and alkenylsilanes has been a good field
for an alternative mechanism different from the Chalk and Harrod concept.
According to a reasonable mechanism commonly proposed and accepted, the
key step involves the insertion of an olefin into the M-Si (or silyl migra-
tion pathway) as an additional elementary process to the insertion into the
M-H bond, followed by competitive elimination of either hydrosilylation or
dehydrogenative silylation products, according to the general scheme shown
in eq. (7).
R
- RCH=CHSiR's + RCH2CH3
R3Si-M-H 2 RCH=CH?,

M = RU
[M{

H H
-
SiR3
RCH2CH2SiR'3 + RCH=CH2
(7)

Dehydrogenative silylation of alkynes also may become a predominant route

under the optimum conditions [l-5, 102, 1201. According to the Crabtree concept,
in the presence of (for example) the cationic iridium complex, [IrH-
(H20)(bq)L2]SbF6(L = PPh3, bq = [7, 8]benzoquinolinato), the above process
504 2.6 Hydrosilylation and Related Reactions of Silicon Compounds

M-SiR3

R’
\
H I
R
=====M>=( H -M-H-R’-
Z Z SiR3
R SiR3
Scheme 4

occurs via the migratory insertion of the C = C bond into the M-Si bond followed
by isomerization of vinylic ligand according to the Scheme 4 [ 1201.

2.6.2.2 Silylative Coupling of Alkenes with Vinylsilanes

Evidence for the migratory insertion of ethylene [121], vinylsilane [122], and
styrene [123] into the Ru-Si bond (yielding vinylsilane and two (1,2- and 1,l-
bis(sily1)ethene) regioisomers, respectively) showed that in the reaction first
reported in 1984 as the “metathesis” (disproportionation) of vinylsilanes and
their “co-metathesis” with olefins [ 1241, instead of the C=C bond cleavage (for-
mally characterizing alkene metathesis (eq. @)), a new type of olefin conversion
was revealed - silylative coupling of olefins with vinylsilanes.

SiR3

(E+Z)

Recent reports on homocoupling of vinyl-substituted silicon compounds and

their heterocoupling (trans silylation, silyl group transfer) with olefins catalyzed
by Ru [121-1231, Rh [125], and Co [126] complexes containing (or generating)
M-H and M-Si bonds have shown that new reactions occur through the cleavage
of the =C-Si bond of vinylsilane and the =C-H bond of the olefin (also vinyl-
silane in the self-disproportionation). A mechanistic scheme of this new type of
silylolefin conversion involves the migratory insertion of styrene (or vinylsilane)
into an M-Si bond (where M = Ru, Rh, Co) or vinylsilane into an M-H bond,
followed by P-H (and P-Si)elimination to give E-phenylsilylethene (and ethylene)
(see Scheme 5 for M = Ru).
This mechanism of catalysis was also proved by the stoichiometric reactions as
well as above all by a new diagnostic tool in this type of the reaction, i. e., an MS
study of the product of the deuterated styrene with vinylsilane[l23, 1241 or deu-
terated vinylsilane with vinyl alkyl ethers [127]. Moreover, similarly to the case
 2.6.2.3 Dehydrocoupling of Hydrosilanes 505

+IR3
R3Si
+ ,SiR3

Sil
H I

Scheme 5. [Ru] = Cl(CO)(PPh3)2Ru; R‘ = alkyl, phenyl, silyl; R3, M, M, Ph3-,,

where n = 0-3, rn = 2-3.

for monovinyl-substituted silanes and siloxanes, divinyl-substituted silicon com-

pounds undergo efficient cross-coupling polycondensation to yield linear oligo-
mers [129] or cyclic dimers [130].
Under the optimum conditions the reaction stereo- and regioselectively gives
silylene-vinylene, siloxylene-vinylene [ 1311, and silazanylene-vinylene [ 128,
129, 13I] as well as silylene-vinylene-phenylene[ 132, 1331 oligomers. This
new, efficient route for preparation of organosilicon linear and cyclic oligomers
as an extension of the silylative coupling (trans silylation) of alkenes to dienes
has recently been overviewed separately [ 1311.

2.6.2.3 Dehydrocoupling of Hydrosilanes

Although the first report of a dehydrocoupling reaction, in which Wilkinson’s cat-
alyst was used, appeared in 1973 [134], real progress in this field began with the
discovery by Harrod and co-workers, that Cp2MMe2 (M = Ti,Zr) initiates the
polycondensation of primary silanes RSiH3 to produce short polymers [ 1351.
For a recent review see [136].
Tilley’s [ 1371 and Corey’s [ 1381 groups, as well as those of Hanod [ 1391 and
Tanaka [ 1401, developed and utilized other active catalytic systems, mainly the
506 2.6 Hydrosilylation and Related Reactions of Silicon Compounds

group 4 metallocenes (but recently also lanthanide metallocenes by Mark’s group

[ 1411) for mechanistic and synthetic studies [ 138a, 140al. The dehydrocoupling
occurs according to eq. (9).

R = H, Me, Bu, Ph; R = Me, Ph

The condensation of secondary silanes requires more rigorous conditions and

no catalyst has yet been reported to couple tertiary silanes efficiently [140]. The
great interest in polysilane polymers and their potential application come from
their unusual electronic, optical, and chemical properties [ 1421, particularly as
preceramic materials [ 1431. The reaction constitutes the only alternative to
Wurtz coupling for the formation of silicon-silicon bonds.
Harrod’s preliminary suggestions for the dehydrocoupling of hydrosilanes
by early transition metal catalysts involved the formation of metal-silylene
intermediates, Cp,M=SiRR’ [ 138al. The most plausible mechanism for the con-
densation reaction, however, has been presented elegantly by Tilley and co-work-
ers [144] and involves a-bond metathesis from M-H species generated from the
catalyst precursor.
Some attempts have been made to prepare polysilazanes via dehydrogenative
coupling of diorganosilanes with ammonia [ 1451 and dehydrogenative polymeri-
zation of oligosilazanes [146], using R U ~ ( C Oas) ~a ~catalyst.

2.6.3 Silylcarbonylation
Silylcurbonylution is a known term describing formally the silicon version of
hydroformylation (cf. Section 2.1.1) discovered by Collenille [ 1471 and later de-
veloped by Murai and co-workers, in which hydrogen is replaced by trialkylsilane,
eq. (10) [148]. The silylformylation of alkenes is catalyzed by C O ~ ( C O[148],
)~
[RhCl(CO),], [ 1491, RhCl(PPh3)3 [150], RU~(CO)~,, ,-
and HRu3(CO)] [ 1511 to
give silyl enol ethers of the homologous aldehydes as the sole products.

+ CO + RSSiH -FSiR
COZ(C0)8
140 ‘C

The silylformylation of oxygen-containing compounds such as aldehydes

and cyclic ethers in the presence of CO*(CO)~ and [Rh(COD)Cl], affords siloxy
derivatives according to eqs. (11) and (12) [148, 1521.

RC?
0
‘H
+ HSiR3 + CO -cat. /
R-CH
OSiR3

‘CHO
 2.6.3 Silylcarbonylation 507

In contrast to hydroformylation of olefin derivatives, the addition of carbon

monoxide and trialkylsilane to alkynes gives carbon-centered silanes exclusively
when catalyzed by, for example, rhodium and Rh-Co carbonyl clusters [153, 1541
and Rh,(pfb), (pfb = perfluorobutyrate) (eq. (13) [153]).
R
R-CECH + R'3SiH + CO + WH (13)
CHO SiR'3

The reaction was successfully extended to the hydroformy lation of propargyl-

type alcohols [ 1541 and propargylamine [ 1551, the silylative cyclocarbonylation of
alkynes [ 1561, silylcarbocyclization of alkenynes and diynes [ 157-1601, and other
transformations of C = C bonds in the presence of HSiR3 and CO (e. g., [161]).
A generalized catalytic cycle for the silylformylation of 1d k y n e s catalyzed by
rhodium-cobalt clusters is illustrated in Scheme 6.
The reactions include the extremely regio-, stereo-, and chemoselective inser-
tion of 1-alkyne into the (M)-Si bond of the silyl(hydrid0)metal intermediate to
form a 2-silylvinyl-(M,,) complex, followed by a facile insertion of CO into the

Y
\

co
Scheme 6. [M,] = Rh2 or RhCo.
508 2.6 Hydrosilylation and Related Reactions of Silicon Compounds

vinyl-metal bond to create a 3-~ilylacryloyl(H)(M)~ complex. A subsequent hy-

dride shift gives the silylformylation product and in the excess of hydrosilanes,
the (HM-sily1)metal species is regenerated.
Rhodium cationic and zwitterionic complexes proved to be superior catalysts
for the hydroformylation of vinylsilanes, producing either a- or p-silyl aldehydes
depending on the reaction conditions [162]. On the other hand, carbonylation of
vinylsilanes in the reaction related to hydrocarboxylation and hydroesterification
afforded a- and a-silyl esters in high yields (eq. (14) [163]).

R 3 S i 4 + CO + R'OH

R3 = Me3, (MeO)3,Ph2F, Me2Et, Ph2Me;R' = H, Et

References
[1] I. Ojima in The Chemistry of Organic Silicon Compounds (Eds.: S . Patai, Z. Rappoport),
John Wiley, New York, 1989, p. 1479.
[2] Comprehensive Handbook on Hydrosilylation (Ed.: B. Marciniec), Pergamon Press,
Oxford, 1992; B. Marciniec, J. Gulihki, J. Organomet. Chem., 1993, 446, 15.
[3] B. Marciniec in Applied Homogeneous Catalysis with Organometallic Cornpounds
(Eds.: B. Cornils, W. A. Henmann), Verlag Chemie, Weinheim, 1996, Chapter 2.6.
[4] I. Ojima, Z. Li, J. Zhu in The Chemistry of Organic Silicon Compounds (Eds., Z .
Rappoport, Y. Apeloig, John Wiley, New York, 1998, Chapter 29.
[5] V. B. Pukhnarevich, E. Lukevics, L. T. Kopylova, M. G. Voronkov in Perspectives of
Hydrosilylation (Ed.: E. Lukevics), Riga, Latvia, 1992, p. 383.
[6] B. Marciniec, Appl. Organnomet. Chem. 2000, 14, 527.
[7] H. K. Sharma, K. H. Pannell, Chem. Rev. 1995, 95, 1351: C. A. Recatto Aldrichimica
Acra 1995, 28, 85: K. A. Horn, Chem. Rev. 1995, 95, 1317; H. Yamashita, M. Tanaka,
Bull. Chem. Soc. Jpn. 1995, 68, 403: M. Suginome, Y. Ito, J. Chem. Soc., Dalton
Trans. 1998, 1925.
[8] L. H. Sommer, E. W. Pietrusza, F. C. Withmore, J. Am. Chem. Soc. 1947, 69, 188.
[9] J. A. Reichl, D. H. Berry, Recent Progress in Transition Metal-Catalyzed Reaction on
Silicon, Germanium and Tin, Academic Press, New York, 1999, p. 197.
[lo] M. A. Brook, Silicon in Organic, Organometallic, and Polymer Chemistry, John n'iley,
New York, 2000, Chapters 4-6, 9, and 12.
[11] J. L. Speier, J. A. Webster, G. H. Barnes, J. Am. Chem. Soc. 1957, 79, 974.
[12] A. J. Chalk, J. F. Harrod, J. Am. Chem. Soc. 1965, 87, 16.
[I31 M. A. Schroeder, M. S. Wrighton, J. Organomet. Chem. 1977, 128, 345.
[I41 S. B. Duckett, R. N. Perutz, Organometallics 1992, 11, 90.
[I51 S. Sakaki, N. Mizoe, M. Sugimoto, Organometallics 1998, 17, 2510; S. Sakaki,
M. Ogawa, Y. Musashi, T. Arey, J. Am. Chem. Soc. 1994, 116, 7258; S. Sakaki,
N. Mizoe, Y. Musashi, B. Biswas, M. Sugomoto, J. Phys. Chem. A 1998, 102, 8027;
S. Sakaki, N. Mizoe, M. Sugimoto, Y. Musashi, Coord. Chem. Rev. 1999, 190-192, 933.
[16] M. D. Curtis, P. S. Epstein, Adv. Organomet. Chem. 1981, 19, 213.
[17] J. L. Speier, Adv. Organomet. Chem. 1979, 17, 407.
[18] T. Hiyama, T. Kusomoto in Comprehensive Organic Synthesis, Vol. 8, (Eds.: B. M.
Trost, I. Fleming), Pergamon, Oxford, 1991, p. 763.
 References 509

[ 191 E. D. Plueddemann, Silane Coupling Agents, Plenum, New York, 1980, p. 31.
[20] Silanes and Other Coupling Agents (Ed.: K. L. Mittal), VSP, Utrecht, 1992.
1211 I. Ojima, M. Nihonyanagi, Y. Nagai, J. Chem. Soc., Chem. Commun. 1972, 938.
[22] R . J. P. Coniu, J. J. E. Moreau, J. Chem. Soc., Chem. Commun. 1973, 38.
[23] K. Yamamoto, T. Hayashi, M. Kumada, J. Organomet. Chem. 1972, 46, C65.
[24] H. Brunner, H. Nishiyama, K. Itoh in Catalytic Asymmetric Synthesis (Ed.: I. Ojima),
VCH, New York, 1993, Chapter 6.
[25] EP 508.610 A2, (1992); EP 503.975 A2, (1992).
[26] M. P. McGrath, E. D. Sall, S . J. Tremont, Chem. Rev. 1995, 95, 390.
[27] US 5.928.794 (1999); EP 566.095 (1993).
[28] R. Drake, I. MacKinnon, R. Taylor in The Chemistry of Organic Silicon Compounds,
(Eds.: Z. Rappaport, Y. Apeloig), J. Wiley, Chichester, 1998; Chapter 38.
[29] R. H. J. Hendriks, R. Payenbroek, E. G. M. Veldman, B. M. W. Voss, A. P. Jekel, J. C.
van de Grampel, Phosphorus, Sulfur and Silicon, 1994, 93-94, 363.
[30] A. Mori, E. Takahisa, H. Kajiro, Y. Nishihara, T. Hiyami, Macromolecules 2000, 33,
1115; D. S. Kim, S. G. Shim, J. Polym. Science, Part A: Polym. Chem. 1999, 37, 2933.
[31] J. P. Majoral, A. M. Caminade, Chem. Rev., 1999, 99, 845.
[32] C. Schlenk, H. Frey, Monatsh. Chem. 1999, 130, 3.
[33] B. D. Karstedt, US 3.775.452 (1973).
1341 P. B. Hitchcock, M. F. Lappert, N. J. W. Warhurst, Angew. Chem., Int. Ed. Engl. 1991,
30, 438.
[35] G. Chandra, P. Y. Lo, P. B. Hitchcock, M. F. Lappert, Organometallics, 1987, 6, 191.
[36] L. N. Lewis, J. Am. Chem. Soc. 1990, 112, 5998.
[37] L. N. Lewis, R. J. Uriarte, N. Lewis, J. Catal. 1991, 127, 67.
[38] L. N. Lewis, J. Stein, K. A. Smith, in Progress in Organosilicon Chemistry (Eds.:
B. Marciniec, J. Chojnowski), Gordon and Breach, Langhorne, USA, 1995, p. 263.
[39] J. Stein, L. N. Lewis, Y. Gao, R. A. Scott, J. Am. Chem. SOC.1999, 121, 3693.
[40] L. N. Lewis, C. A. Sumpter, J. Stein, J. Inorg. Organomet. Chem. 1996, 6, 123.
[41] US 5.486.637 (1996).
[42] US 5.567.848 (1996).
[43] A. Hopf, K. H. Dotz, J. Mol. Catal. 2000, 164, 191.
[44] US 5.164.461 (1992).
[45] US 5.239.035 (1993).
[46] US 5.223.344 (1993).
[47] A. Milan, M. J. Fernandez, P. Bentz, P. M. Maitlis, J. Mol. Catal. 1984, 26, 89.
[48] R. Takeuchi, I. Evata, Organometallics 1997, 16, 3707.
[49] N. A. Donskaya, N. M. Yurjeva, I. P. Beletskaya, Zh. Obshch. Khim. 1997, 33, 962.
[50] B. Marciniec, P. Krzyzanowski, E. Walczuk-GuSciora, W. Duczmal, J. Mol. Catal. 1999,
144, 263.
[5 I ] B. Marciniec, E. Walczuk-GuSciora, P. Blazejewska-Chadyniak, D. Chadyniak M. Ku-
jawa-Welten, S. Krompiec, Proc. 1st European Silicon Days (Munich 2001), p. 73.
[52] H. Brunner, Angew. Chem., Int. Ed. Engl. 1983, 22, 897.
[53] H. Brunner, H. Nishiyama, K. Itoh in Catalytic Asymmetric Synthesis (Ed.: I. Ojima),
VCH, New York, 1993, Chapter 6.
[54] I. Ojima, Pure Appl. Chem. 1984, 56, 99.
[55] H. B. Kagan, Pure Appl. Chem. 1975, 43, 401.
[56] N. Chatani, T. Kodama, Y. Kajikawe, H. Murakami, F. Kakiuchi, S. Ikeda, S. Murai,
Chem. Lett. 2000, 14.
[57] M. Isobe, R. Nishizawa, T. Nishikawa, K. Yoza, Tetrahedron Lett. 1999, 40, 6927.
[58] N. J. Archer, R. N. Haszeldine, R. V. Parish, J. Chem. Soc., Dalton, Trans. 1979, 695.
[59] M. Brookhart, B. E. Grant, J. Am. Chem. Soc. 1993, 115, 2151.
5 10 2.6 Hydrosilylation and Related Reactions of Silicon Compounds

[60] M. J. Fernandez, L. A. Oro, J. Mol. Catal. 1988, 45, 7.

[61] R. S. Tanke, R. H. Crabtree, J. Am. Chem. Soc. 1990, 112, 7984.
[62] R. S. Tanke, R. H. Crabtree, Organometallics 1991, 10, 415.
[63] M. A. Esteruelas, M. Olivan, L. A. Oro, Organometallics 1996, 15, 814.
[64] L. I. Kopylova, V. B. Pukhnarevich, M. G. Voronkov, Zh. Obshch. Khim. 1991,
61, 2606.
[65] H. Watanabe, M. Asami, Y. Nagai, J. Organornetal. Chem. 1980, 195, 363.
[66] H. S. Hilal, S. Khalaf, W. Jondi, J. Organometul. Chem. 1993, 452, 167.
[67] M. Tanaka, T. Hayashi, Z.-Y. Mi, J. Mol. Catal. 1993, 81, 207.
[68] US 4.927.953 (1990).
[68a] M. A. Esterulas, L. A. Oro, C. Valero, Organometallics 1991, 10, 462.
[69] For example, Y. Kiso, M. Kumada, K. Maeda, K. Sumitani, K. Tamao, J. Organomet.
Chem. 1973, 50, 311 and 319.
[70] A. W. Chow, R. D. Hamlin, Y. Blum, R. M. Laine, J. Polym. Sci., Part C 1988, 26, 103.
[71] I. Ojima, S. Inaba, T. Kogure, Y. Nagai, J. Organomet. Chem. 1973, 55, C17.
[72] J. Tsuji, M. Hara, K. Ohno, Tetrahedron 1974, 30, 2143.
[73] B. Marciniec, J. Gulikki, W. Urbaniak, Synth. React. lnorg. Metal-Org. Chem. 1982,
12, 139.
[74] Y. Uozumi, H. Tsuji, T. Hayashi, J. Org. Chem. 1998, 63, 6137.
[75] G. Pido, A. Togni, Tetrahedron Assymmetry 1998, 9, 3903.
[76] Y. Uozumi, K. Kitayama, T. Hayashi, Tetrahedron Assymmetly 1993, 4, 2419.
[77] J. Y. Corey, X. H. Zhu, Organometallics, 1992, 11, 672.
[78] T. Sakakura, H.-J. Lautenschlager, M. Tanaka, J. Chem. Soc., Commun. 1991, 40.
[79] G. A. Molander, J. Winterfield, J. Organomet. Chem. 1996, 524, 275.
[80] G. A. Molander, W. H. Retsch, Organometallics 1995, 14, 4570.
[81] P. W. Fu, Y. Brard, Y. Li, T. B. Marks, J. Am. Chem. Soc. 1995, 117, 7157.
[82] A. K. Dash, J. Q. Wang, M. S. Eisen, Organometallics 1999, 18, 4724.
[83] T. I. Gountcher, T. D. Tilley, Organometallics 1999, 18, 5661.
[84] EP 546.716 A1 (1992).
[85] FR 91.13256 (1991).
[86] X. Lu, Li Zhang, Z. Wang, X. Liu, X. Chen, Chem. Res. in Chinese Univ. 1994,10, 126.
[87] R. Drake, R. Dunn, D. C. Shemngton, S. J. Thomson, Chem. Commun. 2000, 1931.
[88] Dow Coming Ltd. (J. Pfenning, I. Maas, K. H. Meining, G. Spott), DE 2.550.659
(1976).
[89] U. Schubert, Ch. Egger, K. Rosse, Ch. Alt, J. Mol. Catal. 1989, 55, 330.
[90] B. Marciniec, W. Urbaniak, J. Mol. Catal. 1983, 18, 49.
[91] B. Marciniec, Z. Foltynowicz, M. Lewandowski, Appl. Organomet. Chem. 1993, 7, 207.
[92] A. Carmona, A. Corme, M. Iglesias, A. San Jose, F. Sanchez, J. Organomet. Chem.
1995, 492, 11.
[93] Z. M. Michalska, B. Ostaszewski, K. Strzelec, J. Organomet. Chem. 1995, 496, 19.
[94] Z. M. Michalska, K. Strzelec, J. W. Sobczak, J. Mol. Catal. A 2000, 156, 91.
[95] R. A. Faltynek, Znorg. Chem. 1981, 20, 1357.
[96] EP 278.863 (1988).
[97] F. D. Lewis, G. D. Salvi, lnorg. Chem. 1995, 34, 3182.
[98] X. Wu, J. H. Malpert, H. Zang, D. C. Neckers, Tetrahedron Lett. 1999, 40, 8309.
[99] L. D. Boardman, Organometallics 1992, 11, 4194.
[loo] A. D. Calhoun, K. R. Lung, T. A. Nile, L. L. Stokes, S. C. Smith, Trans. Met. Chem.
1983, 8, 365.
[ l o l l B. Marciniec, W. Duczmal, E. Sliwinska, J. Organomet. Chem. 1990, 385, 319.
[lo21 B. Marciniec, New J. Chem. 1997, 21. 815.
[lo31 B. Marciniec, H. Maciejewski J. Organomet. Chem. 1993, 454, 45.
 References 5 11

[lo41 H. Maciejewski, B. Marciniec, I. Kownacki, J. Organornet. Chem. 2000, 597, 175.

[105] B. Marciniec, H. Maciejewski, I. Kownacki, J. Mol. Catal. A: Chemical 1998,135,223.
[lo61 Y. Seki, K. Takeshita, K. Kawamoto, S. Murai, N. Sonoda, J. Org. Chem. 1986,
51, 3890.
[lo71 A. J. Cornish, M. F. Lappert, G. L. Vilatovs, T. A. Nile, J. Organomet. Chem. 1979,
172, 153.
[I081 B. Marciniec, J. Gulinski, J. Orgunomet. Chem. 1983, 253, 349.
[lo91 I. Ojima, T. Fuchikami, M. Yatabe, J. Organomet. Chem. 1984, 260, 335.
[I101 A. Millan, M. J. Fernandez, P. Bentz, P. M. Maitlis, J. Mul. Catal. 1984, 26, 89.
[ I l l ] B. Marciniec, H. Maciejewski, J. Mirecki, J. Organomet. Chem. 1991, 418, 61.
[I121 M. Tanaka, Y. Uchimaru, H.-J. Lautenschlager, J. Organomet. Chem. 1992, 428, 1.
[113] A. M. Lapointe, F. C. Rix, M. Brookhart, J. Am. Chem. Soc. 1997, 119, 906.
[I141 F. Kakiucki, Y. Tanaka, N. Chatani, S. Murai, J. Organomet. Chem. 1993, 456, 45.
[I151 Y. Seki, K. Takeshite, K. Kawamoto, J. Organomet. Chem. 1989, 369, 17.
[116] M. L. Christ, S. Sabo-Etienne, B. Chandret Organometallics 1995, 14, 1082.
[117] R. Takeuchi, H. Yasue, Organometallics 1996, 15, 2098.
[118] F. Seitz, M. S. Wrighton, Angew. Chem., Int. Ed. Engl. 1988, 27, 289.
[119] C . L. Reichel, M. S. Wrighton, Inorg. Chem. 1980, 19, 3858.
[120] C. H. Jun, R. H. Crabtree, J. Organomet. Chem. 1993, 447, 177.
[121] Y. Wakatsuki, H. Yamazaki, M. Nakano, Y. Yamamoto, J. Chem. Soc., Chem. Commun.
1991, 703.
[122] B. Marciniec, C. Pietraszuk, J. Chem. Soc., Chem. Commun. 1995, 2003.
[ 1231 B. Marciniec, C. Pietraszuk, Organometallics 1997, 16, 4320.
[124] B. Marciniec, J. Gulinski, J. Organomet. Chem. 1984, 266, C19.
[125] B. Marciniec, E. Walczuk-GuSciora, C. Pietraszuk, Catal. Lett. 1998, 55, 125.
[126] B. Marciniec, I. Kownacki, D. Chadyniak, Inorg. Chem. Commun. 1999, 2, 581.
[ 1271 B. Marciniec, M. Kujawa, C. Pietraszuk, Organometallics 2000, 19, 1677.
[128] B. Marciniec, M. Lewandowski, J. Polym. Sci. Polym. Chem. Ed. 1996, 34, 1443.
[129] B. Marciniec, E. Malecka, Macromol. Rapid Commun. 1999, 20, 475.
[130] B. Marciniec, M. Lewandowski, E. Bijpost, E. Maiecka, M. Kubicki, E. Walczuk-
GuSciora, Organometallics 1999, 18, 2968.
[131] 8 . Marciniec, Mol. Cryst. Liquid Cryst. 2000, 354, 173.
[I321 M. Majchrzak, Y. Itami, B. Marciniec, P. PawluC, Tetrahedron Lett. 2001, 41, 10303.
[133] M. Majchrzak, Y. Itami, B. Marciniec, P. PawluC, Macromol. Rapid Commun. 2001,
22, 202.
[134] I. Ojima, S. Inaba, T. Kogure, Y. Nagai, J. Organomet. Chem. 1973, 55, C17.
[135] C. T. Aitken, J. F. Harrod, E. Samuel, J. Organomet. Chem. 1985, 279, C11; J. F.
Harrod, Y. Mu, E., Samuel, Polyhedron 1991, 10, 1239.
[I361 (a) J. Y. Corey, J. Braddock-Wilking, Chem. Rev. 1999, 99, 175; (b) J. Y. Corey, in:
Advances in Silicon Chemistry (Ed.: G. Larson), JAI Press: Greenwich, CT, 1991, 327.
[I371 T. D. Tilley, Comments Inorg. Chem. 1990, 37, 10; T. D. Tilley, Ace. Chem. Res. 1993,
26, 22; T. Imori, T. D. Tilley, Polyhedron 1994, 13, 2231; H. G. Woo, J. F. Walzer, T. D.
Tilley, Macromolecules 1991, 24, 6863.
[138] (a) J. Y. Corey in Progress in Organosilicon Chemistry (Eds.: B. Marciniec, J. Choj-
nowski), Gordon & Breach, Basel, 1995, p. 387; (b) B. J. Grimmond, J. Y. Corey,
Organometallics 1999, 18, 2223; (c) G. Warg, J. Y. Corey, Can. J. Chem. 2000, 78,
1434.
[139] V. K. Dioumaev, J. F. Harrod, Organornetallics, 1996, 15, 3859; V. K. Dioumaev, J. F.
Harrod, Organometallics 1994, 13, 1548.
[140] (a) Y. Obore, M. Tanaka, J. Organomet. Chem. 2000, 595,l; (b) N. Choi, S. Onozawa,
T. Sakakura, M. Tanaka, Organornetallics 1997, 16, 2765.
5 12 2.6 Hydrosilylation and Related Reactions of Silicon Compounds

[141] C. M. Forsyth, S. P. Nolan, T. J. Marks, Organometallics 1991, 10, 2543.

[142] R. West, J. Organomet. Chem. 1986, 300, 327.
[143] Y. Mu, R. M. Laine, J. F. Harrod, Appl. Organomet. Chem. 1994, 8, 95.
[144] H. G. Woo, J. F. Walzer, T. D. Tilley, J. Am. Chem. Soc. 1992, 114, 7047.
[145] Y. Blum., R. Laine, Organometallics 1986, 5, 2986.
[146] A. W. Chow, R. D. Hamlin, Y. Blum, R. M. Laine, J. Polym. Sci., Polym. Lett. Ed.
1988, 26, 103.
[147] US 345.073 (1969).
[148] S. Murai, N. Sonoda, Angew. Chem., Int. Ed. Engl. 1979, 8, 837.
[149] S. Ikedo, N. Chatani, Y. Kajikawa, K. Ohno, S. Murai, J. Org. Chem., 1992, 57, 2.
[150] Y. Seki, K. Kawamoto, N. Chatani, A. Hidaka, N. Sonoda, K. Ohe, Y. Kawasaki,
S. Murai, J. Organomet. Chem. 1991, 403, 73.
[151] G. Suess-Fink, J. Reiner, J. Mol. Catal. 1982, 16, 231.
[152] M. E. Wright, B. B. Cochran, J. Am. Chem. SOC. 1993, 115, 2059.
11531 Y. Matsuda, Y. Fukata, T. Tsuchihashi, H. Nagashima, K. Itoh, Organometallics 1997,
16, 4327; I. Matsuda, A. Ogiso, S. Sato, Y. Izumi, J. Am. Chem. Soc. 1989, I l l , 2332;
J. M. Chance, T. A. Nile, J. Mol. Catal. 1987, 42, 91.
[154] I. Ojima, R. J. Ponaran, M. Egucki, W. R. Shay, P. Ingellina, A. Korda, Q. Zeny, Tetra-
hedron 1993, 49, 5431; I. Ojima, P. Ingellina, R. J. Donaran, N. Clos, Organometallics
1991, 10, 38; I. Matsuda, N. Niikawa, R. Kuwabara, H. Inoue, H. Nagashima, K. Itoh,
J. Organomet. Chern. 1999,574, 133;L. Matsuda, A. Ogiso, S. Sato, J. Am. Chem. SOC.
1990, 112, 6120; I. Ojima, Z. Li, R. J. Donovan, P. Ingallino, Znorg. Chim. Acta 1997,
16, 4327.
[I551 I. Matsuda, J. Sakaibara, H. Inone, H. Nagashima, Tetrahedron Lett. 1992, 5799.
[156] I. Matsuda, H. Ishibashi, N. Ii, Tetrahedron Lett. 1995, 241.
[157] I. Ojima, D. Machnik, R. J. Donovan, 0. Mneimne, Inorg. Chim. Acta 1996, 251, 299.
[158] I. Ojima, R. J. Donovan, W. R. Shay, J. Am. Chem. Soc. 1992, 114, 6580.
[159] 1. Ojima, M. Tzamarioudaki, C.-Y, Tsai, J. Am. Chern. SOC.1994, 116, 3643.
[160] I. Ojima, J. Zhu, E. S. Vidal, D. F. Kass, J. Am. Chem. Soc. 1998, 120, 6690.
[161] Y. Fukuta. I. Matsuda, K. Itoh, Tetrahedron Lett. 1999, 40, 4703.
[162] C. M. Crudden, H. Alper, J. Org. Chem. 1994, 59, 3091.
[163] R. Takeuchi, N. Ishi, M. Sugiura, N. Sato, J. Org. Chem. 1992, 57, 4189.
 Applied Homogeneous Catalysis with Organometallic
Edited by Boy Cornils & Wolfgang A. Herrmann
© Wiley-VCH Verlag GmbH, 2002

2.7.2 General Mechanistic Aspects 5 13

2.7 Reaction with Nitrogen Compounds:

Hydroamination
Rudolf Taube

2.7.1 Introduction
Among the addition reactions across the C-C double bond the addition of N-H
bonds is of considerable interest in organic synthesis [l, 221. By this method
amines can be obtained directly without any by-product; cf. eq. (1).
R R
\c=c / + H-N' I I
H-C-C-N, /

/ \ \
R " R

The direct addition of ammonia or simple amines to olefins is thermodynami-

cally feasible, as shown by the data in Table 1. However, in consequence of the
absence of a strong interaction between the reactants, which arises mainly from
the symmetry forbiddance of a HOMO-LUMO overlap in the synchronous addi-
tion reaction, a high activation barrier exists which prevents the reaction in normal
conditions. Furthermore, since the reaction entropy is highly negative, the chemi-
cal equilibrium in eq. (1) is shifted strongly to the starting materials with increas-
ing temperature [2]. Therefore catalysis is indispensable for realization of the hy-
droamination of unactivated olefins, and considerable efforts are undertaken in
order to develop an appropriate, highly effective catalytic route for this reaction,
which is also very attractive from the industrial point of view [ 3 ] .

Table 1. Thermodynamic data for the hydroamination of ethylene [2].

Reaction ARC' [kJ/mol] ARHe [kJ/mol] ARSe [J/mol . K]
C2H4 + NH3 EtNH2 -14.7 -52.7 -127.3
C2H4 + EtNH2 @ Et2NH -33.4 -78.7 -152.2
C7H4 + Et,NH @ Et,N -30.0 -79.5 -166.3

2.7.2 General Mechanistic Aspects

To catalyze the direct hydroamination of olefins according to eq. (1) two basic ap-
proaches have been employed involving primarily the activation either of the
amine or of the olefin. One possible way to activate the amine for catalysis is
the transformation to the much stronger nucleophilic amide ion by deprotonation.
Thus, the amides of strongly electropositive metals, such as alkali metals, alkaline
earth metals, or lanthanides, are able to react with the C-C double bond under
5 14 2.7 Reaction with Nitrogen Compounds: Hydroamination

appropriate conditions by nucleophilic addition to the corresponding highly polar

p-aminoalkyl metal compounds as very reactive intermediates with a strong carb-
anion activity. Therefore the alkylamine can be smoothly generated by protolysis
with the amine and the reformed metal amide can start a new catalytic cycle, as
shown in Scheme 1.

M+

H-

Scheme 1. Catalytic cycle for the hydroamination of olefins with activation of the amine by
N-H deprotonation.

An alternative method of amine activation is opened via the oxidative addition

of the N-H bond to an appropriate transition metal in a lower oxidation state.
After formation of the p-aminoalkyl compound by insertion of the olefin into
the transition-metal-nitrogen bond, the alkylamine can be generated by reductive
elimination (Scheme 2), and with the reformed reduced transition metal complex
the catalytic reaction can run again.

H H
I I I -,R I - R
LxM-C-C-N \ L,M-N(
I I R R

/ /
c=c,
/

Scheme 2. Catalytic cycle for the hydroamination of olefins with activation of the amine by
N-H oxidative addition to the transition metal.
 2.7.2 General Mechanistic Aspects 5 15

As is well known, the nucleophilic addition to the C-C double bond can be
promoted very effectively by n-coordination of the olefin in a cationic low-spin
transition metal complex. Many examples are described in the literature where
amines react smoothly with transition metal-ethylene complexes forming
p-ammonioethyl complexes [ 1-31. Very often these complexes are isolable in
the pure state, and in the case of the platinum(I1) complex [PtCl,(Et,NH)
(CH2CH,NHEt,)] the structure has also been proved by X-ray crystal structure
analysis [4].
From these easily accessible intermediates a catalytic cycle for the hydroamina-
tion might be realized simply by an intramolecular protolytic splitting reaction of
the transition metalkarbon bond, as formulated in Scheme 3 via route 0.

Scheme 3. Catalytic cycle for the hydroamination of olefins with activation of the olefin by
n-coordination to the transition metal.

As a rule, however, carbanion reactivities in the coordinative saturated

b-aminoethyl transition metal complexes are generally kinetically too strongly
suppressed. One possible way of circumventing this barrier is shown in
Scheme 3, along route @. If the transition metal is d-electron-rich and can re-
ceive the proton by oxidative addition, then the alkylamine can be eventually
more easily generated by reductive elimination with formation of the starting
transition metal complex. With these principles of catalytic activation as a guide-
line, the different catalyst systems described in the literature will now be dis-
cussed in some detail.
5 16 2.7 Reaction with Nitrogen Compounds: Hydroamination

2.7.3 The Different Catalyst Systems

2.7.3.1 Catalyst Systems Containing Alkali Metals

Alkali metals, their hydrides, and amides have been proven as catalysts for the hy-
droamination of olefins under various conditions. Some typical examples for the
hydroamination of ethylene as the fundamental reaction, being also of consider-
able industrial interest, are given in Table 2.
Ethylene and ammonia were found to react in the presence of metallic sodium
or sodium hydride at temperatures above 200 "C and at 80-100 MPa pressure in
an inert hydrocarbon medium such as heptane to produce approximately equimo-
lar quantities of ethyl-, diethyl-, and triethylamines. The total conversion, based on
ammonia, was about 40 % and the yield about 70 %; a portion of the ammonia
appeared in the products as sodium amide, to which the sodium was quantitatively
converted.
Lithium, potassium, and their hydrides were similarily active, and propene or
other a-olefins also reacted with ammonia but with lower conversion to the cor-
responding mixtures of alkylamines, in which the addition followed Markovni-
kov's rule.
Amines could also be added, e. g., n-butylamine and ethylene produced diethyl-
n-butylamine in about 50 % conversion besides a small amount of a complex mix-
ture of high-boiling nitrogen-containing materials. The increase of chain length
could result from the nucleophilic attack of ethylene by the a-aminoethyl
anion in competition with the protolytic reaction with the amine.
The amides of rubidium or cesium have been proven as the best catalysts for
the hydroamination of ethylene with ammonia. In liquid ammonia below the cri-
tical temperature (132.5 "C) at 100 "C and an initial pressure of only 11 MPa a
turnover number (TON) of about 4 mol C2H4/(mol CsNH2) per h could be
reached [6].
Similar catalytic activity for the hydroamination with amines could be realized
under low pressures ( < l o MPa) by the use of metal amide catalysts preformed
before the alkylation step. The metal amide can be prepared in situ by reacting
the metal, e. g., sodium, with the amine in the presence of 1,3-butadiene, whereby
the sodium amide is produced and the diene hydrogenated to 2-butene.
The best results were obtained with secondary amines, e. g., diethylamine or
piperidine, using the corresponding lithium amides as catalysts. Tetramethylethyl-
enediamine (TMEDA) was reported to act as a co-catalyst, but its importance is
not clear, since with highly purified amines comparable activities were observed
without any additive [9]. Thus, for the combination Et,NH/LiNEt,/TMEDA in
the ratio 23:1:5 at 80 "C and an initial pressure of 1.1 MPa, total conversion
to Et,N was reached in 18 h. This corresponds to a TON of about 1-2 mol
Et2NH/(mol LiNEt,) per h [6].
With the same combination in the ratio 100: 1 without TMEDA at 120 "C under
a pressure of 5-6 MPa, about 70 % triethylamine was obtained in 5 h giving a
TON of about 15 mol Et2NH/(mol LiNEt,) per h. Piperidine is converted to ethyl-
Table 2. Catalyst systems containing alkali metals for the hydroamination of ethylene.
Catalyst Amine Amine/ Conversion Reaction product P [MPaI T [“C] t [h] Ref.
catalyst [%I”’
Na, NaH 15-20 3040 80-100 200 10
Na 3 75 80- 100 200 10
KNH* 24 2 9-11 100 20
CsNH, 24 17 9-1 1 100 1
NaNBu, 8-15 92 4-5.5 135 5
NaN(CH215 8-15 86 4-5.5 114 2.25
NaNHPh 8-15 37 4-5.5 255 1.9
Ca(NHPh), 8-15 45 4-5.5 300 1.5
LiEt 25 98 20 140 37
KNEt2 90b’ 56 1 45 5
LiNEt,/5 TMED 23 100 1.1 80 18
LiNEt, 100 70 5-6 120 5
LiN(CH2Is 100 90 5-6 120 5
a) Based on charged ammonia or amine. 56
h, In n-octane. z
5 18 2.7 Reaction with Nitrogen Compounds: Hydroamination

piperidine under the same conditions at practically the same rate [9]. From kinetic
measurements for the formation of Et,N in the system C2H4/Et2NH/LiNEt2/
TMEDA the empirical rate law (eq. (2)) has been derived [6]. The observed
order dependencies strongly suggest that the rate-limiting step of these reactions
is the nucleophilic addition of the diethylamide ion to the ethylene, in agreement
with the reaction mechanism in Scheme 1, and an apparent Arrhenius activation
energy E, = 50 kJ mol-' was calculated. The very weak coordinative interaction
of ethylene, and other olefins as well, with alkali metal ions might be the reason
for the low catalytic activity of alkali amides in the hydroamination of ethylene
and other olefins. For industrial application, the alkali metal-based catalyst sys-
tems seem to be inappropriate.

d[Et3N1 = k[Et2NH]o[C2H4]-1[LiNEt2]-1
dt

2.7.3.2 Catalyst Systems Containing Lanthanides

When Marks and co-workers [lo] published their investigations of the organo-
lanthanide-catalyzed intramolecular hydroamination of appropriate a,w-amino-
lefins, the opened a useful synthetic route to different types of cyclic amines
(Scheme 4) in combination with a thorough analysis of the catalytic reaction
mechanism and the structure-reactivity relationships.
The scope of the reaction includes the formation of five-, six-, and seven-
membered heterocycles from primary, secondary, and aromatic amines as the
starting compounds, giving exclusively the exo-methyl product in agreement
with Markovnikov's rule. All reactions are found to proceed equally well in
toluene, benzene, pentane, and related hydrocarbon solvents. In donor solvents
such as THF, catalytic rates are significantly slower. In the series of bis(penta-
methylcyclopentadieny1)lanthanide catalysts, the highest activity was observed
with lanthanum and with lutetium the lowest; the variation of TON spans over
three orders of magnitude.
Skeletal methyl substitution in the aminoolefin can increase the rate of cycliza-
tion very strongly. Thus, for the cyclization of 2,2-dimethyl-1-amino-4-pentene
(eq. (3)) the highest TON of 95 mol amine/(mol La) per h at 25 "C was obtained.
By variable-temperature in-situ NMR studies of the catalytic solution

the rapid formation of the amido complex as the actual catalyst, even at -78 OC,
has been proven, succeeded by the cyclization reaction at ambient temperature to
the amido amine complex, cf. eq. (4), giving strong support to the catalytic reac-
tion mechanism in Scheme 4.
 2.7.3.2 Catalyst Systems Containing Lanthanides 5 19

Cp*zLnR
2 CH2=CH(CH2)nNH*
substrate S

I*

insertion step [TSIt

reaction products
Ln = La, Nd, Sm, Y, Lu; Cp* = C5Me5 (turnover number, 60 "C)
R = H, C3H5,CH(SiMe3)2,N(SiMe3)2
substrate S: n = 3,4, 5
GQ D
H
n=3
H
n=4
H
n=5
(1Wa) (0.3)b)

Scheme 4. Catalytic cycle, structure of the transition state TS in the insertion step, different
cycloaliphatic amines as reaction products, and turnover numbers in mol sub-
strate/(mol Ln) per h, for the organolanthanide-catalyzed intramolecular hydro-
amination of a,w-aminoolefins: (a) with La(C5Me5)2N(SiMe3)2,and (b) with
Nd(Me2Si(C5Me4)2)N(SiMe3)2 as pre-catalyst.

Complexes of this type could be preparatively isolated from pentane solutions

in good yields. The corresponding methylamido amine complex [(C5Me5),La-
(NHMe)(H,NMe)] was characterized by X-ray crystal structureanalysis as a
model compound for the catalyst complex, which obviously contains, besides
the amido group, an additional amine preserving the coordination number 8 of
lanthanum.
520 2.7 Reaction with Nitrogen Compounds: Hydroamination

H2N R R pentane, -78 "C

(C5Me5)2LaCH(SiMe& +
\ -(f~le~Si)~CH2~

R = CH3, H yield: 40-50 % from

1:l ratio of reactants

From kinetic investigations of the cyclization reaction (eq. (3)) the rate law r =
kc,c,.[La][S]owas derived. The reaction rate is independent of the substrate con-
centration and shows first-order dependence solely on the catalyst concentration,
which is consistent with the cyclization under olefin insertion being irreversible
and being the rate-determining step in the catalytic cycle. The activation para-
meters E, = 56.0 kJ/mol, AH* = 53.1 kJ/mol, and AS* = -1 12.9 J/mol K are in
agreement with the assumed concerted, highly organized, polar transition state
(Scheme 4). The bicyclic structure of the transition state with some coordinative
interaction of a proton from the coordinated amine with the partially negatively
polarized a-carbon of the reacting C-C double bond is assumed, to explain the
substantial kinetic NH/ND isotope effects which are observed with deuterated
amines. Additionally, the rapid protolysis of the La-C bond ensuring the irrever-
sibility of the insertion step becomes quite understandable with this structure of
the transition state. Finally, it can be concluded that the relatively high catalytic
efficiency in the organolanthanide-catalyzed cyclic hydroamination arises essen-
tially from the relatively strong interaction between the amide and the olefin in
the coordination sphere of the lanthanide(II1) complex favored by the chelate ef-
fect. For this reason the reaction appears not to be transferable with similar success
to the intermolecular hydroamination of unsubstituted olefins.

2.7.3.3 Catalyst Systems Containing Iridium

The catalytic activation of the amine via amide formation by oxidative addition to
a low-valent transition metal has been performed by Milstein and co-workers [ 111.
Using the iridium(1) complex [Ir(PEt3)2(C2H4)2C1] as an appropriate pre-catalyst in
combination with 0.2 equivalents ZnC1, as co-catalyst in THF, the addition of
aniline to norbornene could be realized. By refluxing the reactants in the ratio
Ir/ZnCI2/aniline/norbornene = 1:0.2: 10:55 in THF for 48 h, 2-6 equivalents
of exo-2-(phenylamino)norbornane as the reaction product could be generated
catalytically. The catalytic reaction mechanism is shown in Scheme 5.
From the bis(ethy1ene) precursor complex the highly reactive unsaturated
14-electron intermediate Ir(PEt&CI is generated as the actual catalyst by
stepwise dissociation of ethylene. Related compounds M(Pr'3P)2C1 (M = Rh,
 2.7.3.3 Catalyst Systems Containing Iridium 52 1

?\\. Et3P-

Et3P
I

CI
NHPh

Scheme 5. Catalytic cycle of the iridium(1) complex catalyzed synthesis of

exo-2-(phenylamino)norbomaneby addition of aniline to norbomene via
N-H activation by oxidative addition in THE

Ir) are known [12]. In the next step, aniline is added oxidatively to
Ir(PEt3)2Cl to form reversibly the hydrido anilido iridium(II1) complex
Ir(PEt,),(H)(NHPh>Cl. This 16-electron intermediate is not observed, but can be
readily trapped with PEt, to give the corresponding tris(triethy1phosphine)
complex Ir(PEt,),(H)(NHPh)Cl, which could be identified NMR-spectroscopi-
cally. With norbornene insertion into the Ir-N bond the azoiridiacyclobutane
complex Ir(PEt3)*(H)(C7H,,NHPh)CI is formed, as a stable isolable compound
whose structure has been established by X-ray crystal structure analysis. In the
final step of the catalytic cycle, by reductive elimination of the norbornylamine
the catalyst Ir(PEt3)2C1is regenerated. This reaction step seems to be rate-limiting
and can be realized under the reaction conditions only by transforming the kineti-
cally inert 1%electron azoiridiacyclobutane complex into a cationic, coordinatively
unsaturated, 16-electron complex by C1- ligand dissociation, which is supported
by the addition of some ZnCI2to the reaction system. Obviously, the final reductive
elimination step marks the critical point in the catalytic cycle, and further system-
atic studies of the structure-reactivity relationships are needed to reach the catalytic
efficiency necessary for practical application.
522 2.7 Reaction with Nitrogen Compounds: Hydroamination

2.7.3.4 Catalyst Systems Containing Iron or Ruthenium

Iron pentacarbonyl and some ruthenium(II1) complexes, such as RuC13 . 3 H 2 0 or
Ru(NH3)4(0H)C12,are claimed in a patent as catalysts for the hydroamination of
ethylene and higher olefins in homogeneous solution [ 131.
In tetrahydrofuran, dioxane or amines as the solvent, with ratios of catalyst
amine of about 1:20-1:lOO at 150-190 "C and under pressures of 1-2 MPa in
6-8 h, conversions of between 20 and 50 % were obtained [5, 6, 81. As a side
reaction, disproportionation of the secondary amines was observed.
The amine conversions obtained correspond to TONS of 1-3 mol amine/(mol
metal) per h, indicating very low activity of the catalyst systems.

2.7.3.5 Catalyst Systems Containing Rhodium

As the first transition metal-based homogeneous catalysis of hydroamination, in
the early 1970s Coulson from the Du Pont laboratories had described the addition
of secondary aliphatic amines to ethylene in the presence of various rhodium com-
pounds [ 15, 161. Definite results were reported with RhC13 . 3 H 2 0 as pre-catalyst
in tetrahydrofuran as solvent under starting ethylene pressures of 5-14 MPa at
180-200 "C for different secondary amines (Table 3).
Apparently the reaction is very sensitive to the nature of the amine. The highest
activity, which was obtained with piperidine, corresponds to a TON of about
20 mol amine/(mol Rh) per h. Ammonia and primary amines did not react with
ethylene under the conditions used, and higher olefins were also found to be
essentially unreactive. For the reaction with piperidine the reaction rate was
found to be independent of the piperidine concentration and first-order with
respect to rhodium trichloride.
More recent investigations in the author's group [2, 171 have shown that under
the reaction conditions the trans-bis(piperidine) ethylene rhodium(1) complex

Table 3. Hydroamination of ethylene with secondary amines in tetrahydrofuran with

RhC13 . H 2 0 as pre-catalyst at 200 oC.a)
Secondary amine PKBH+ N-Ethylated amine [ %]
Piperidine 11.02 70
Dimethylamine 10.73 54
Pyrrolidine 11.27 36b
Diethy lamine 10.49 4
n-Butylethylamine 10.50 3
Morpholine 8.33 <2
~~ ~

a) Molar ratio: Ethylene/amine/RhCl, . 3 H 2 0 = 350: 100:1. Reaction time 3 h.

b, Appreciable side reactions noted.
 2.7.3.5 Catalyst Systems Containing Rhodium 523

[RhC1(C2H4)pip2]is formed as the actual catalyst. The complex, whose structure

is established by X-ray crystal structure analysis [ 181, can be easily prepared by
piperidine addition to the well-known [Rh(C2H4)2Cl]2,which shows identical
catalytic properties. The catalytic efficiency is limited by the thermal instability
of the bis(piperidine) ethylene complex at higher temperatures. The thermal de-
composition proceeds with formation of metallic rhodium, presumably according
to eq. (5).
3 Rh'CI(C2H4)pip2- 2 Rho + Rh'"C13(pip)3+ 3 pip + 3 C2H4 (5)
Quite stable catalytic reaction solutions were obtained in THF with the starting
pressure for ethylene of 6-6.5 MPa at a reaction temperature of 120 "C. Under
these conditions and with the ratios piperidineh-hodium of 100: 1 and 1000: 1 in
36 and 72 h, yields of 70 and SO % ethylpiperidine were reached, which corre-
spond to TONS of 2 and 7 mol amine/(mol Rh) per h, respectively. Total conver-
sion is also possible if the reaction time is prolonged further. As a side reaction,
ethylene dimerization to butene was observed. This indicates the formation of a
hydrido rhodium(II1) complex in the hydroamination reaction, as formulated in
Scheme 3, route 0. Hydrido rhodium(II1) complexes are known as catalysts for
ethylene dimerization [ 191, and if the reductive elimination of ethylpiperidine
from the hydrido-/3-aminoethyl rhodium(II1) complex is the rate-limiting step in
the catalytic cycle of hydroamination, a competitive catalysis of the ethylene di-
merization seems possible. In the context of these mechanistic considerations,
an increase of the catalytic activity for hydroamination requires as much facilita-
tion of the reductive elimination step as possible.
With the cationic bis(tripheny1phosphine) ethylene complex [Rh(C,H4)
(PPh,),(acetone)]PF6, it is possible for the first time that the hydroamination of
ethylene could be catalyzed at room temperature under normal conditions[20].
The complex can be synthesized according to eq. (6) and has also been character-
ized by X-ray crystal structure analysis [21]. The conversion of piperidine to
ethylpiperidine can be catalyzed in a 0.1 M solution of the complex in tetrahydro-
furan under ethylene at normal pressure and ambient temperature. Under these
conditions one equivalent of piperidine is converted practically completely to
ethylpiperidine during 2-3 min. If 10 equivalents of piperidine are added stepwise
in 10 intervals of 10 min, the overall yield of ethylpiperidine amounts to about
70-80 %. No further conversion could be realized. The correspondingly low cat-
alytic productivity arises from a continuous deactivation of the catalyst complex
by reaction with piperidine to the more stable cis- bis(tripheny1phosphine) bis(pi-
peridine) complex [Rh(PPh,),(pip),]PF,, which can be isolated from the reaction
solution in more than 90 % yield if a larger excess of piperidine is applied. The
formation of the bis(piperidine) complex obviously represents a thermodynamic
sink and further investigations are needed to overcome this restriction in the cat-
alytic efficiency of this system.
+ H,/acetone [RhH2(PPh3)2(acetone)2]PF6
[Rh(COD)(PPh3)21PF6 - C8H,6

- f C2H4
- C2H6
[Rh(C2H4)(PPh3)2( a c e t ~ n e ) ~ ] P F ~
(6)
524 2.7 Reaction with Nitrogen Compounds: Hydroamination

2.7.4 Perspectives
Although as a result of the research work since the mid-1950s several catalytic
routes for the hydroamination of ethylene have been realized on the basis of struc-
turally different catalysts, until now the breakthrough in catalytic activity and uni-
versal applicability is missing. The situation marks clearly the real state-of-the-art
in developing tailor-made catalysts. Even for simple reactions like the hydroami-
nation of ethylene the present knowledge in catalytic reaction theory seems to be
insufficient to reach this goal ad hoc. Thus, more comprehensive and thorough
studies of the catalytic reaction mechanism and structure-reactivity relationships
are indispensable to solve this fundamental problem in homogeneous catalysis
appropriately for practical applications.

References
[l] M. B. Gasc, A. Lates, J. J. Pene, Tetrahedron 1983, 39, 703.
[2] D. Steinborn, R. Taube, 2. Chem. 1986, 26, 349.
[3] J. J. Brunet, D. Neibecker, F. Niedercorn, J. Mol. Catal. 1989, 49, 235.
[4] E. Benedetti, A. De Renzi, G. Paiaro, A. Panunzi, C. Pedone, Gazz. Chim. Ital. 1972,
102, 744.
[5] B. W. Howk, E. L. Little, S. L. Scott, G. M. Whitman, J. Am. Chem. Soc. 1954, 76, 1899.
[6] G. P. Pez, J. E. Galle, Pure Appl. Chem. 1985, 57, 1917.
[7] R. D. Closson, J. P. Napolitano, G. C. Ecke, A. J. Kolba, J. Org. Chem. 1957 22, 646.
[8] H. Lehmkuhl, D. Reinehr, J. Organomet. Chem. 1973, 55, 215.
[9] D. Steinborn, B. Thies, I. Wagner, R. Taube, Z. Chem. 1989, 29, 333.
[lo] M. R. GagnC, C. L. Stem, T. J. Marks, J. Am. Chem. Soc. 1992, 114, 275.
[Ill A. L. Casalnuovo, J. L. Calabrese, D. Milstein, J. Am. Chem. Soc. 1988, 110, 6738.
[12] H. Werner, J. Wolf, A. Hohn, J. Organomet. Chem. 1985, 287, 395.
[13] D. M. Gardner, R. T. Clark, US 4.454.321 (1984); Chem. Abstr: 1984, 101, 130217r.
[ 141 B. R. James, Homogeneous Hydrogenation, in Comprehensive Organometallic Chemis-
try (Eds.: G. Wilkinson, F. G. A. Stone, E. W. Abel), Vol. 8, Plenum Press, London, 1982,
p. 285-369.
[ 151 E. I. du Pont de Nemours (D. R. Coulson) US 3.758.586 (1973); Chem. Abstr: 1973, 79,
125808g.
[16] D. R. Coulson, Tetrahedron Lett. 1971, 429.
[ 171 D. Selent, Dissertation, Technische Hochschule Merseburg, 1982.
[I81 D. Selent, D. Scharfenberg-Pfeiffer, G. Reck, R. Taube, J. Organomet. Chem. 1991,
415, 417.
[19] R. Cramer, J . Am. Chem. Soc. 1965, 87, 4717.
[20] E. Krukowka, R. Taube, D. Steinborn, DD 296.909.A5 (1991); Chem. Abstr: 1992, 116,
213993b.
[21] M. Dunaj-Jurco, J. Kozisek, D. Steinborn, E.Krukowka, R. Taube, 28th Znt. C o n , Coord.
Chem., Gem 1990, Proc. 1990, 1, 3.
[22] B. Cornils, W. A. Herrmann, R. Schlogl, C.-H. Wong (Eds.), Catalysis from A to Z,
Wiley-VCH, Weinheim, 2000.
 Applied Homogeneous Catalysis with Organometallic
Edited by Boy Cornils & Wolfgang A. Herrmann
© Wiley-VCH Verlag GmbH, 2002

2.8.1.I Homogeneous Catalysis in the Oxidation of Hydrocarbons to Acetic Acid 525

2.8 Reactions of Hydrocarbons

and Other Saturated Compounds

2.8.1 Oxidations

2.8.1.1 Homogeneous Catalysis in the Oxidation

of Hydrocarbons to Acetic Acid
Charles C. Hobbs, Jr.

2.8.1.1.1 Introduction
Oxidations of low-molecular-weight paraffin hydrocarbons to produce acetic acid
remain important in today’s industrial economy (eq. (1)). Such processes ac-
counted for about 15 % of the installed acetic acid capacity in both the USA
and the UK in 1992. Both n-butane and “light naphthas” (which contain low-boil-
ing hydrocarbons, especially pentanes and hexanes) are heavily utilized for raw
materials. Butane is the raw material of choice in the USA, where it is readily
available. In other areas of the world, light naphtha is often preferred [ 1, 21.

+ 5/202 -
cat.
2CH3COOH + H20 (1)

Even though methanol carbonylation is the favored process for new acetic acid
capacity today, existing paraffin oxidation plants remain quite competitive where
coproducts can be marketed successfully [2, 31. Over half the original capacity of
acetic acid plants based on paraffin oxidation remains in use today. In North
America, Hoechst Celanese operates two facilities using the butane oxidation pro-
cess to make acetic acid. The reported 1994 capacity at Pampa, Texas, is 250000
metric tondyear, while that at Edmonton, Alberta, is 75 000 metric tondyear [4].
There are two plants believed to be using the naphtha oxidation process to make
acetic acid: BP Chemicals in Hull, England, with a capacity of 210000 metric
tondyear [5] and a state complex in Armenia (in the former USSR) with a capa-
city reported to be 35 000 metric tons/year [6].
The significant reductions in acetic acid capacity based on paraffin oxidation
that have occurred include those at (1) the butane oxidation plant operated by
Union Carbide at Brownsville, Texas, (2) butane oxidation processes in the Neth-
erlands and Germany, and (3) a Russian naphtha oxidation plant.
526 2.8 Reactions of Hydrocarbons and Other Saturated Compounds

2.8.1.1.2 Uncatalyzed and Catalyzed Chain Reactions

In this section an attempt is made to rationalize the reported effects of homo-
geneous catalysts in the production of acetic acid by the oxidation of saturated
hydrocarbons. Such oxidations exhibit chain reaction kinetics and differ in funda-
mental ways from more conventional reactions. One of the most striking differ-
ences is that the instantaneous kinetics of chain reactions are frequentlyrelated
in only very indirect ways to the concentrations of the starting materials. Rates
may change rapidly by orders of magnitude with only small or even insignificant
changes in the concentrations of the feed materials. It sometimes happens that just
mixing the starting materials under steady-state reaction conditions of tempera-
ture, pressure, etc., does not result in a detectable reaction rate.
To understand what “catalysis” of chain reactions can accomplish and what
some of the limitations are, one needs to consider the factors that determine the
differences in behavior of chain reactions and conventional reactions. In a very
simplified way, many conventional reactions can be represented by

A+B-+C

In complex cases, series and/or parallel reactions may be going on simulta-

neously; but, in general, the sole source of A and B are the starting materials.
Neither is regenerated in the course of the reaction. The kinetics of reaction
are, more or less, simply related to the concentrations of A and B. If A and B
are mixed under reaction conditions, the reaction will proceed.
The kinetics of the above-mentioned reaction can frequently be altered by
introducing a third substance which may form a complex with either A or B or
both and thus alter the energy of activation of the reaction. In the case of oxida-
tions that occur via chain mechanisms, “catalysts” may have some influence on
product distribution, and yet they frequently have little or no discernible effect
on steady-state reaction kinetics. In some instances, additional catalyst may
actually retard reaction rates [7-91.
Catalysts are not absolutely essential in paraffin oxidations but their use can
have significant advantages such as shifting of the relative magnitude of the
various steps of uncatalyzed reactions. Perhaps it should be noted in passing
that commercial oxidations conducted in metal equipment always have some
adventitious corrosion ions present, so the term “an uncatalyzed reaction” implies
only that no catalyst was deliberately added.

Uncatalyzed Chain Reactions

A basic hydroperoxide chain mechanism proceeds via eqs. (2)-(5):

RH + ROO* - R* + ROOH

R* + 02 - ROO*
2.8.1.1 Homogeneous Catalysis in the Oxidation of Hydrocarbons to Acetic Acid 527

ROOH - RO* + HO. (4)

ROO. + ROO. - non-radical products (5)

A free radical flux is maintained in this system. The predominant member of

the flux is usually the alkylperoxy radical since it is a relatively weak hydrogen
abstractor and, as a result, builds up to the highest concentration [8, 10-121.
Each new molecule of hydrocarbon is brought into the reaction process by under-
going hydrogen abstraction. When this reaction involves an alkylperoxy radical,
the result is the first propagation step, shown in eq. (2). This produces an alkyl
radical and an alkyl hydroperoxide.
In the second propagation step, an alkyl radical reacts with oxygen to regen-
erate the chain-carrying alkylperoxy radical. Except under rather highly oxygen-
starved conditions, alkyl radicals are effectively scavenged by oxygen [8, 10, 131.
Radicals are consumed during the reaction by bimolecular chain termination
steps such as eq. (5). Replacement radicals are produced by chain branching
reactions such as eq. (4). The new radicals (e.g., alkoxy radicals; see below)
can abstract hydrogen to start new chains. At steady state, the radical generation
rate is essentially equal to the radical consumption rate. There have been lively
debates in the literature on the sources of the original radicals; this question is
essentially unresolved [8, 10, 141.
Peroxy radicals are obviously very important in the complex mechanisms of
hydrocarbon oxidations. They propagate the reaction chains (eq. (2)), producing
hydroperoxides. The selectivities of various alkylperoxy radicals in hydrogen
abstractions have been reported to be relatively independent of the alkylperoxy
radicals utilized [12, 151.
Since peroxy radicals are relatively unreactive [ 11, 121, they are also, barring
oxygen starvation, the dominant contributors to the radical population. They are
thus the most likely radicals to undergo bimolecular radical reactions. As oxida-
tion rates increase (and chain lengths decrease), these reactions assume increasing
importance.
There are two bimolecular reactions of peroxy radicals that are of special
significance. The first is a chain termination reaction, widely proposed as the
principal chain termination reaction (eq. (6)) and known as the ‘‘Russell Mecha-
nism” [8, 10, 12, 161:

This reaction “consumes” two alkylperoxy radicals and produces an alcohol

and a carbonyl compound. At least one a-hydrogen atom must be present on
one of the alkylperoxy radicals. If the peroxy radicals involved retain the carbon
skeleton of the starting hydrocarbon, so will the products.
528 2.8 Reactions of Hydrocarbons and Other Saturated Compounds

The second important mechanism for bimolecular reaction of peroxy radicals

(eq. (7)) produces alkoxy radicals [15]:
ROO* + *OOR - RO* + 0 2 + *OR
This is not a termination reaction. It is one means of converting alkylperoxy
(7)

radicals to alkoxy radicals. It is the dominant reaction when neither peroxy radical
contains an a-hydrogen, but it even occurs to a significant extent (in one report
about 40 % of the time [ 171) with peroxy radicals that do contain a-hydrogens.
Alkoxy radicals are vigorous hydrogen abstractors [12]. This appears to be the
main reaction for primary alkoxy radicals; the products are primary alcohols.
Secondary and tertiary alkoxys, however, tend to undergo a competitive b-scission
reaction to a major extent [ 181:

For a secondary alkoxy, the products are an aldehyde and an alkyl radical. In
the oxidation of a straight-chain hydrocarbon, aldehydes are likely to be major
intermediates via this mechanism. They are the major precursors of acids. Because
of the high reactivity of aldehydes, in most cases little aldehyde survives in the
product. The alkyl radicals produced according to eq. (8) make a fresh entry
into eq. (3). Tertiary alkoxys generate ketones, which oxidize much more slowly
than aldehydes, but they, too, produce mostly acids [lo].
Primary and secondary alcohols appear to oxidize rapidly to the corresponding
carbonyl compounds with good efficiencies [lo]. The initial point of attack is
predominantly on the hydrogen on the carbinol carbon atom. Tertiary alcohols
do not have a hydrogen in this position and are relatively resistant to oxidation.
Alcohols, like aldehydes, are usually important intermediates in paraffin oxida-
tions [ 181. They undergo subsequent oxidation somewhat less readily than
aldehydes, but primary and secondary alcohols oxidize much faster than the
starting paraffin(s). Quite unlike aldehydes, however, alcohols do not, in general,
autoxidize readily by themselves. Moreover, the deliberate addition of alcohol to
an oxidation can slow or even stop the reaction [lo, 19-21].
To account for these observations, it has been proposed that hydroperoxy radi-
cals are produced during the oxidation of alcohols containing an a-hydrogen
[22-261. These radicals have a high termination rate constant (>lo9 L mol-' s-';
the reaction is said to be diffusion-controlled [14, 27, 281); they remove radicals
from the system rapidly (eq. (9)):
Re + HOO. - RH + 0 2 (9)
One interesting proposal for how HOO. radicals are formed involves the
assumption that the addition of oxygen to an a-hydroxyalkyl radical is readily
reversible, even at moderate temperature:
OH 0-0-
2.8.1.1 Homogeneous Catalysis in the Oxidation of Hydrocarbons to Acetic Acid 529

If enough hydroxyalkylperoxy radicals are produced and abstract hydrogen, a

hydroxyalkyl hydroperoxide is produced and the hydroperoxide can decompose
to hydrogen peroxide and a carbonyl compound [29]:

-OH R

This is the basis of a hydrogen peroxide process based on isopropyl alcohol.

It should be noted that this process is said to utilize an initiator, i.e., it does not
appear to be self-sustaining.
If, on the other hand, the equilibrium according to eq. (10) is highly displaced
to the left, an alternative reaction, which produces HOO- radicals, may occur
(eq. (12)). This step involves a direct, irreversible reaction between hydroxyalkyl
radicals and oxygen [22]:

Equation ( I 2) is analogous to the proposed mechanism for the high-temperature

oxidation of propane which produces propylene in the temperature region where
the “negative temperature coefficient” is observed (eq. (13)) [ 10, 14, 281:

There is recent plausible evidence, however, that in this case the hydroperoxy
radical is actually produced via a rearrangement of the alkylperoxy radical
followed by decomposition in eq. (14) [30-351:

The reversibility of the oxygen addition reaction for hydrocarbons (analogous

to eq. (10)) is widely accepted, but the source of the HOO- radicals (eqs. (13), (14)
or another) has not been resolved [14, 361.
It is not clear how these observations apply to the oxidation of alcohols.
Moreover, it is not readily apparent why the addition of oxygen to a carbi-
nol-containing radical should be so much more reversible than, say, in the
case of an analogous ether radical. There does not appear to be an inhibition
effect in the oxidation of ethers [20]. It is well known that ethers can build
up dangerous levels of peroxides unless handled carefully. Alcohols do not,
in general, exhibit this problem.
530 2.8 Reactions of Hydrocarbons and Other Saturated Compounds

The ionic character of alcohols suggests that, especially in a solvent containing

hydroxyl groups (e. g., alcohols and/or carboxylic acids), the following reaction
(eq. (15)) could produce HOO- radicals directly:

0
:
0-H
R (15)
* )=o 0-x
R H

Equation (15) does not require an unusual reversibility of oxygen addition,

direct hydrogen abstraction by oxygen, or generation and decomposition of a
hydroperoxide-containing radical. It is also consistent with the observed differ-
ences between alcohols and ethers. The reported rapid unimolecular decomposi-
tion of hydroxyalkylperoxy radicals to HOO. radicals and a carbonyl compound
in aqueous solution under mild conditions appears to lend strong support to this
proposal [25]. The production of HOO. radicals has been proposed to explain
inhibition in a variety of hydrocarbon oxidations [lo, 271.
Once formed, alcohols esterify to some extent with the acids generated in an
oxidation reaction. Except for lactones, esters do not appear to be generated
directly in oxidation mechanisms [lo, 37, 381. The Bayer-Villiger reaction of
intermediate peracids and ketones is sometimes proposed as a source of esters
[39] but it appears to be too slow to be a significant source except in the case
of cycloparaffins [lo, 401. The ester group and its immediate neighboring groups
appear to be remarkably resistant to oxidation.
Aldehydes and ketones are the major immediate precursors of acetic acid in
paraffin oxidation. The reported mechanisms for the oxidations of these inter-
mediates are somewhat involved and are not of primary concern for the present
purpose. A point of interest, however, is that acylperoxy radicals, intermediates
in aldehyde oxidations, are much stronger hydrogen abstractors than alkylperoxy
radicals [8]. Aldehyde oxidations have been more extensively covered elsewhere
[lo, 18, 39, 41-43]. Acetic acid is quite resistant to further oxidation [lo] and
tends to be a “terminal” product.
If the carbon chain of the hydrocarbon is sufficiently long, a “back-biting”
(eq. (16)) reaction may occur:

I
R R
2.8.1.1 Homogeneous Catalysis in the Oxidation of Hydrocarbons to Acetic Acid 53 1

Equation (16) can lead to the formation of difunctional acids, lactones, methyl
ketones with carbon chains shorter than the starting hydrocarbon, and other
compounds [44, 451. Back-biting reactions have the unique characteristic that it
is not possible to dilute the site of a back-biting attack with respect to the attacking
radical. In the normal chain propagation (eq. (2)), such dilution with respect to the
attacking radical can be achieved by, for example, holding the conversion at a
lower level.
In any liquid-phase oxidation conducted with a gaseous oxidant, the mass trans-
fer of the oxidant (usually oxygen) from the vapor to the liquid phase is an impor-
tant consideration, and has been reviewed elsewhere [ 131. Except as noted, this
discussion is restricted to mechanisms that are not “oxygen-starved.’’

The Impact of Homogeneous Catalysis on Chain Reactions

How can the presence of homogeneous catalysts influence the course of the oxi-
dation of paraffins to acetic acid? The basic uncatalyzed reactions will usually
proceed quite well in the absence of added catalysts, giving respectable yields
of acetic acid [3]. Various catalysts can influence features such as induction
periods, minimum operating temperatures, and product distributions, especially
for the intermediate products; it is even reported that catalysts can influence the
extent of the ,&scission reaction of alkoxy radicals [19]. How catalysts do these
things is not as well understood as one would like, but knowledge of the mecha-
nisms is gradually accumulating. One recent reviewer [46] was moved to observe
that the widely varying conditions required to oxidize different substrates selec-
tively do not readily reveal distinct patterns in the roles the metal ions play.
Detailed mechanisms are generally not known. While these observations have
considerable merit, it is safe to say that the role of the metal ion can involve
much more than the catalysis of hydroperoxide decomposition, although that is
frequently an essential part of its function [8, 46-49]. With appropriate caveats,
a brief qualitative summary of some of the more important functions of metal
ion catalysis is presented in Table 1.
Uncatalyzed hydrocarbon oxidations can give high yields of peroxides under
certain conditions. The conditions required are those that favor long chain lengths
with little decomposition of the hydroperoxide. Relatively low temperatures favor
survival of the hydroperoxide and low rates favor unimolecular reaction (eq. (2))
(which produces hydroperoxide) over bimolecular reaction (eq. ( 5 ) ) (which
consumes ROO. radicals without producing hydroperoxide). Of course, enough
hydroperoxide must decompose to provide new radicals to the system at the
rate at which they are removed by chain termination.
Uncatalyzed reactions usually proceed slowly at first as hydroperoxide con-
centrations build up. The rate frequently increases with hydroperoxide concentra-
tion until a steady-state rate is approached. If one initially adds a metal ion which
catalyzes the decomposition of the hydroperoxide, the induction period can be
greatly reduced, but the steady-state rate which is achieved is frequently essen-
tially the same as for the uncatalyzed reaction.
532 2.8 Reactions of Hydrocarbons and Other Saturated Compounds

Table 1. Qualitative comparison of catalyst functions.

Catalyst metal ion
Ce V Mo

X
x x

a) Metal complex with peroxide; formed by ROO. + Mn + ROO-M"+'.

At higher temperatures, chains become short (approaching 1) and limiting rates

are reached in either catalyzed or uncatulyzed reactions. Under these conditions,
kinetic equations for the simple hydroperoxide cycle indicate that the limiting rate
is not a function of catalyst concentration. Many real systems approach this
behavior [ 121.
The metal-ion catalyzed decomposition of the hydroperoxide is thought to
involve the formation of radicals and a higher valence state of the metal ion
(eq. (17)).
M"+ + ROOH - ROO + M("+')+ + OH- (17)

To be effective in a catalytic cycle, the higher valence state of the metal

ion must participate in an oxidation reaction to return to its initial state [47].
In some cases, substrates can be attacked by the higher valence ion (eq. (18)):
2.8.1.1 Homogeneous Catalysis in the Oxidation of Hydrocarbons to Acetic Acid 533

There is some evidence that eq. (18) may sometimes, perhaps, involve a com-
plex between a peroxy radical and the M("+')+ion [12]. According to eq. (19)
M("+I)+ions can also be reduced by reaction with hydroperoxides:
'

ROOH + M("+')+ - ROO- + M"+ + H+ (19)

Manganese and cobalt compounds are particularly effective in decomposing

hydroperoxides (eqs. (17) and (19)) and hence are frequently used as oxidation
catalysts [47]. In spite of their similar abilities in this regard, the results of their
use in a given instance can be quite different. Manganous ions are reported to
have a pronounced ability to reduce peroxy radicals directly to peroxy anions
(eq. (20)) ~501:
ROO* + Mn" - ROO- + Mn"' (20)

These peroxy anions need only pick up a proton to become hydroperoxides.

In view of the importance of ROO. radicals in almost all hydrocarbon oxida-
tions, eq. (20) can have a number of consequences. For example, if the concentra-
tion of ROO. radicals is reduced, the relative importance of chain terminations
(eqs. ( 5 ) and (6)) is reduced. The production of carbonyls and alcohols, especially
those retaining the carbon skeleton of the feed hydrocarbon(s), would be sup-
pressed. More of the reaction would be diverted through alkoxy radicals via eq.
(17). In most cases, the expected radicals would be secondary alkoxys. Again
in most cases, the secondary alkoxy radicals should mostly undergo ,!%scission
(eq. (8)) to give aldehydes and primary alkyl radicals. The primary alkyl radicals
would undergo similar reactions but would produce primary alkoxy radicals from
eq. (17). These would, to a large extent, abstract hydrogen to produce primary
alcohols (eq. (21)) [18]:

R-O. + RH - R-oH + R* (21)

Primary alcohols oxidize rapidly and efficiently to aldehydes. Aldehydes (from

whatever source) oxidize very rapidly indeed to produce acids (eq. (22)), the
likely final product:
0 0
R-OH Lo] R AH
The Mn"' produced in eqs. (17) and (20) must, of course, be reduced to Mn"
to maintain the cycle. Aldehydes are particularly effective in this reduction
(analogous to eq. (1 8)) producing acyl radicals [5 11, although other substrates
may participate as well.
The oxidation of intermediate aldehydes is a high-traffic path in the oxidation
of hydrocarbons, especially those with significant straight-chain content. The
influence of catalysts on the oxidation of aldehydes is a very complex subject
534 2.8 Reactions of Hydrocarbons and Other Saturated Compounds

[43]. The reduction of acylperoxy radicals by Mn", by the analog of eq. (20),
tends to reduce the concentration of acylperoxy radicals in the system:

(204

When acylperoxy radicals participate in the analog of eq. (7), they generate
acyloxy radicals:

Acyloxy radicals largely decompose to R- radicals and CO,. This represents

a major source of inefficiency. Thus, other things being equal, the presence of
manganese ions can improve the efficiency of aldehyde oxidations.
By tending to increase chain lengths by suppressing termination reactions
(such as eq. (6)), manganese-ion catalysts tend to increase the potential reaction
rate of the system. This is especially true for aldehyde oxidations which are fast
anyway. This effect may need attention since it can lead to oxygen starvation or
it may limit the extent to which acylperoxy radical concentrations can be sup-
pressed. An additional expected effect of the peroxy-radical reducing capability
of manganous ions is some diminution in the extent of "back-biting'' reactions
(eq. (16)).
In addition to hydroperoxide decomposition and peroxy-radical reduction, man-
ganese-ion catalysts have a pronounced tendency to promote the rapid oxidation
of carbonyl-containing intermediates via enol mechanisms [49, 52-56] :

Mn"' + JR
- Mn" + H+ + . A (23)

Thus, manganese-ion catalysis would be expected to suppress the rate of

formation of ketones and secondary alcohols (which are ketone precursors) by
eq. (6) and the production of methyl ketones by the "back-biting'' mechanism
(eq. (16)). Moreover, it increases the rate of attack on all ketones, formed by
whatever mechanism. These proposals are consistent with the preferred use of
manganese-ion catalysts for the production of synthetic fatty acids [ 101. Carbonyl
impurities are especially critical for this product.
The use of manganese-ion catalysis frequently results in increased production
of formic acid. This is probably the result of increased rate of production and a
decrease in the relative rate of attack on formic acid [57, 581. Part of the increased
production would be the result of an enol mechanism for the oxidation of methyl
ketones. For example, the manganese-ion catalyzed oxidation of methyl ethyl
ketone (MEK) gives increased amounts of formic and propionic acids at the
expense of acetic acid.
There is evidence that the enol mechanism of manganese-ion catalyzed oxi-
dation of carbonyl compounds is also active to some extent in the oxidation of
2.8.1.1 Homogeneous Cutulysis in the Oxidation of Hydrocarbons to Acetic Acid 535

aldehydes [59]. The predominant path is via attack on the very reactive aldehydic
hydrogen; this is indicated by the good yields of acids. However, it has been
demonstrated that Mn'" can react with aldehydes to produce some a-formylalkyl
radicals (eq. (24)):

In the absence of oxygen, these radicals can be trapped by addition to olefins.

Co"', on the other hand, generates primarily acyl radicals from aldehydes; i.e., the
cobalt catalyzed reaction does not proceed through the enol mechanism.
Cobalt-ion catalysis of oxidations can be divided into two distinct categories:
(1) low concentration (usually less than ca. 0.1-0.2 %); and (2) high concentra-
tions (sometimes > 2 %). In the low-concentration range, the major effect
seems to be the catalyzed decomposition of the intermediate hydroperoxide
(eqs. (17) and (19)) along with effective hydrogen abstraction from intermediate
aldehydes (analog of eq. (18)) [51]. Equation (18) is said to be more facile (with
aldehydes) than eq. (19). Although high concentrations of Co" are postulated to
reduce alkylperoxy radicals, at low concentrations most of the chain terminations
seem to occur through alkylperoxy radicals via eq. (6) [7]. Each of these paths
can lead to carbonyls (see eqs. (6), (27)-(29)). Moreover, since cobalt-ion cata-
lyzed oxidations of carbonyls do not seem to proceed through enol mechanisms,
one would expect greater production of ketones and less formic acid than in the
case of manganese-ion catalysis. In general, the principal impact of cobalt
catalysis at low concentrations, compared with noncatalytic oxidation, would
be the reduction of induction periods and lower steady-state concentrations of
h ydroperoxides.
Oxidations of paraffins with high concentrations of cobalt catalyst have very
special characteristics. Such oxidations will proceed at lower temperatures than
in the case of lower concentrations of cobalt or with other catalysts, or in the
absence of catalysts [ 10, 18, 60-661. For example, the high-concentration
cobalt-ion oxidation of n-butane can be conducted at 100-1 10 "C compared
with 150-180 "C for the other cases. Significantly higher efficiencies to acetic
acid are reported (75-84% vs. about 50-60%). Co-reductants such as acetalde-
hyde, MEK, or p-xylene (especially p-xylene [65]) are reported to be useful,
but not essential [66]. In high-concentration cobalt-ion catalyzed oxidations,
rates are generally lower than in the conventional oxidations.
These differences are explained by proposing that the high-concentration
cobalt-ion oxidation involves a direct initial attack of Co"' on a u-bond of a
paraffin (eq. (25)) via an electron transfer mechanism [60, 631:
kl
RH + Co"' RHO+ + Co"

k' Iki

R* + Ht
536 2.8 Reactions of Hydrocarbons and Other Saturated Compounds

This basic mechanism was originally proposed for oxidation of alkylaromatics

but was thought to require the n-system of the aromatic ring; e.g. according to
eq. (26):

@* + H+

The reactions with paraffins established that the n-system is not required. The
reactions with paraffins and alkylaromatics do differ in two significant respects;
the reactions of alkylaromatics are faster and exhibit a deuterium isotope effect.
This implies that reaction (26) is faster than reaction (25), and the final step of
eq. (26) is rate-limiting. The rate with paraffins is primarily governed by the
ratio kJk2 [67].
Manganese is ineffective as a catalyst under the conditions used in high-con-
centration cobalt cases 1681. It does not appear to take part in an electron transfer
mechanism such as eq. (25). It functions mainly via a free radical pathway [48,
691. The high concentration cobalt-ion catalyst system also exhibits pronounced
steric influences. Hydrogen atoms which are readily abstractable in conventional
oxidations are bypassed in favor of less reactive hydrogenswhich are not sterically
hindered. For example, isobutane is less readily attacked than n-butane.
Following eq. (25), the high cobalt-ion oxidation of n-butane is hypothesized to
proceed largely through MEK [63, 701. A possible sequence is:

o, -CO"'

-4
0
A + CO"

At high cobalt concentrations, reaction (28) can compete with hydrogen

abstraction (eq. (2)) [7]. It removes ROO- radicals from the system in a manner
reminiscent of the reaction with Mn" (eq. (29)). However, instead of producing
a hydroperoxide, the product of reaction (28) goes directly to MEK (eq. (29)).
In contrast, in the conventional oxidation of n-butane, MEK appears to be an im-
portant intermediate but not the major one [lo, 181. Some or most of the MEK is
subsequently oxidized, mostly to acetic acid, in either case. In the conventional
oxidation, the susceptibility of MEK to oxidation is about the same as for butane.
2.8.1.1 Homogeneous Catulysis in the Oxidation of Hydrocarbons to Acetic Acid 537

The relative rate for the high-concentration cobalt case does not appear to have
been reported and is not easily estimated from the data available.
In the high-concentration cobalt systems, cobalt ions are reported to be present
in several configurations, with the Co"' dimer being the most active [71]. Some
non-varivalent metal salts, such as ZrO(OAc),, are reported to promote cobalt
catalyzed oxidations. This may be the result of the influence of the promoter on
coordination number and monomer-dimer equilibria [72, 731.
Chromium-containing compounds have received some attention as catalysts for
liquid-phase oxidation of paraffins. Such catalysts introduce an additional level of
complexity and are even less well understood than manganese- or cobalt-contain-
ing catalysts. With few exceptions, cobalt and manganese ions exhibit only two
valence states in liquid-phase oxidations of paraffins (+2 and +3). Manganese,
of course, can exhibit other oxidation states (up to +7), but these only appear to
be active with oxidation agents other than oxygen [74]. Chromium, on the
other hand, can exhibit +3, +4, +5 and +6 valences [75]. The higher valence states
can be achieved by oxidation by alkyl peroxides and/or peracids. They can pro-
duce carbon-centered radicals via an analog of eq. (18) and the various valences
can participate in hydroperoxide decomposition reactions (eqs. (17) and (19))
[75]. Cr" does not participate in catalytic oxidation cycles; it is a strong reducing
agent and is not regenerated [76].
Most of what known about chromium catalysis is rather empirical in naturebut
seems to fit within this picture. For example, in sharp contrast to manganese,
chromium catalyst appears to favor the formation of carbonyl compounds. This
tendency is likely to be related to the ability of chromium ions to participate
in two-electron change (heterolytic) redox reactions [77, 781 in addition to the
one-electron change (homolytic) reactions noted above. These heterolytic reac-
tions can involve both hydroperoxides and alcohols.
The overall conversion (eq. (30)) of a primary or secondary alkyl hydroperox-
ide to a carbonyl compound is not a redox reaction:

The decomposition could proceed in a heterolytic catalytic manner if, for

example, a lower-valence form of chromium could react with hydroperoxide to
form a chromate ester. Equation (31) shows a simple case.
0

Once formed, the chromate ester can decompose heterolytically to produce

the carbonyl product [79, 801 and regenerate the initial chromium-containing
moiety.
538 2.8 Reactions of Hydrocarbons and Other Saturated Compounds

CrV1,produced by reaction of lower-valence states with hydroperoxides, can

react with alcohols to produce chromate esters. These esters will, of course, de-
compose heterolytically, in the manner described above, to produce carbonyls
and, for example, H,Cr03 [79]. A similar but somewhat altered mechanism of het-
erolytic chromate ester decomposition has been proposed to explain differences
noted among several alcohols in the oxidation of alcohols with Crvl [81]. The
use of chromium-containing catalysts to decompose hydroperoxides to carbonyls
in reactions conducted without autoxidation has been frequently noted [82-85].
Cupric salts have not proven to be particularly useful in hydrocarbon oxidation.
They do, however, exhibit interesting characteristics. Cupric ion has a singular
ability to compete with oxygen for carbon-centered radicals in autoxidation (com-
pare eq. (32), where X can be carboxylate, halide, etc., with eq. (3)):

R* + CuX2 - [complex]
r- RX + CuX

R,+ + HX + CuX
(32)

The branch of eq. (32) that is followed depends on the nature of the radical and
the copper ligands [86]; the reaction removes radicals from the system without
producing hydroperoxide. In most instances this so inhibits an oxidation that
copper salts are not effective catalysts.
There is an interesting exception to this observation. As noted above, aldehyde
oxidations tend to be very fast and to have relatively long kinetic chain lengths.
Most chain terminations occur via bimolecular reactions of acylperoxy radicals
(eq. (7a)); these reactions result in carbon dioxide generation and are inefficient.
If one adds manganese catalyst, some of the acylperoxy radicals will be reduced to
peroxy acid and Mn"' will be produced. MnrIrcan carry the chain via an analog of
reaction (18), but does not participate in chain termination reactions. As a result,
kinetic chain lengths and rates tend to increase.
To some degree, this rate increase reduces the extent to which the concentration
of acylperoxy radicals can be suppressed and limits the efficiency increase that
can be obtained. It can also lead to oxygen starvation. However, if one adds a
cupric-ion promoter, acyl radicals can be intercepted in an analog of eq. (32):

Equation (32a) removes acyl radicals from the system without producing per-
oxy acid. This tends to reduce rates without increasing wasteful chain termination
reactions. In this way, one can obtain an additional increment of efficiency [43,
871. Equation (32a) produces acid anhydrides. Variations of this approach have
been used to produce anhydrides commercially [88, 891.
Probably because of the rate problem, the very active and highly specific
copper-ion reactions apparently have not yet found useful application in paraffin
oxidation processes. This further illustrates the requirement that a viable catalyst
2.8.1.1 Homogeneous Catalysis in the Oxidation of Hydrocarbons to Acetic Acid 539

must possess a balance of properties. The inhibition capabilities of copper cata-

lysts do not mean that they are inert. Consider, for example, the fact that adven-
titious copper corrosion products have been reported to be one of the significant
culprits in the oxidative degradation of lubricating oils [go-931.
As illustrated above, redox catalysts function by changing between two or more
valence states. Since the half-cell potentials for such changes are a function of the
ligand sphere of the ions, one might suppose that varying the nature of the ligands
might offer an elegant means of improving catalytic control of oxidation reactions.
With some exceptions [94, 951, this has not been found particularly beneficial. A
major problem is that the ligands are subjected to vigorous attacks by the radical
flux present in an oxidation. It is unlikely that the ligand has more than a minor
effect in most oxidations since the ligand is, in many cases, destroyed during the
initial stage of reaction [96, 971. An additional problem is that very strong (multi-
dentate) ligand-forming materials such as oxalates are common, even if minor,
products of hydrocarbon oxidations. Many oxalates are highly insoluble. The de-
activation of catalysts by the formation of insolubilizing ligands is somewhat less
of a problem in polar solvents (such as acetic acid) [96], but it can still occur.
It has been reported that other hydrocarbons, e. g., naphthenic naphthas, may
also be suitable for the production of acetic acid [58]. This was studied on a
pilot scale but never, apparently, commercialized. A large number of metal
ions, both varivalent and non-varivalent, were studied. Feeds ranged from pure
to very complex hydrocarbon mixtures. While it is difficult to draw any firm con-
clusions, it was possible to make significant yields of acetic acid. Manganese-ion
catalysts were quite effective; they produced higher formic acid/acetic acid ratios
than cobalt-ion catalysts, as one would expect.
Although there have been contradictory reports about the effect of water on par-
affin oxidations [98, 991, there is some evidence that, above some low concentra-
tion, water can have a strong inhibiting effect [99]. This may be related to the
gem-diols :

R H
+ H20
x""
R,,,,.
OH
(33)

The gem-diol product would, on oxidation, produce dihydroxyalkylperoxy

radicals,- analogous to eq. (10) with alcohols. Such peroxy radicals decompose
to produce HOO. radicals [loo], perhaps by a mechanism analogous to eq. (15).
Aldehydes are important intermediates in most paraffin oxidations. The diversion
of even a small fraction of the aldehydes into an inhibitor-producing reaction
could account for the reported effect.
Acetic acid, as noted above, is rather resistant toward oxidation in a paraffin
oxidation process. It is not, however, completely inert; it can be attacked by the
higher valence states of catalyst ions and by the free radicals in solution. In the
case of Co"', an acetoxy radical is produced (eq. (34)):
540 2.8 Reactions of Hydrocarbons and Other Saturated Compounds

In the case of Mn"', an analog of eq. (34) also occurs. In addition Mn"' can
attack acetic acid by an enol mechanism to produce carboxymethyl radicals:

Reaction (35) is favored by anhydrous conditions and is especially pronounced

with acetic anhydride [49, 54, 551.
All free radical chain oxidations are inevitably co-oxidations of the starting hy-
drocarbon(s) and products. Most acetic acid produced in an oxidation generally
survives in the product. At higher hydrocarbon conversions, however, increasing
amounts of acetic acid are converted to waste products.
Bromide ions have been demonstrated to be effective promoters of alkylaro-
matic hydrocarbon oxidations with cobalt and/or manganese catalysts [ 1011.
They have also been claimed to be beneficial in the oxidation of butane or cyclo-
hexane [102, 1031. The effective mechanism is reported to be the generation of a
bromine atom chain transfer agent [ 1041:

Ac0Co"'Br - AcOCo" + Br*

Br* + RH - R* + HBr

R* + 0 2 - ROO-
0

Ac0Co"'OH + HBr - AcOCoIl'Br + H20

2.8.1.1.3 Other Catalysts

Many other metal ions have been reported as catalysts for oxidations of paraffins
or intermediates. Some of the more frequently mentioned ones include cerium,
vanadium, molybdenum, nickel, titanium, and ruthenium [21, 77, 105, 1061.
These are employed singly or in various combinations, including combinations
with cobalt and/or manganese. Activators such as aldehydes or ketones are
frequently used. The 0x0 forms of vanadium and molybdenum may very well
have the heterolytic oxidation capability to catalyze the conversion of alcohols
or hydroperoxides to carbonyl compounds (see the discussion of chromium,
above). There is reported evidence that Ce'" can oxidize carbonyl compounds
via an enol mechanism [I071 (see discussion of manganese, above). Although
little is reported about the effectiveness of these other catalysts for oxidation of
paraffins to acetic acid, tests conducted by Hoechst Celanese have indicated
that cerium salts are usable catalysts in liquid-phase oxidation of butane [108].
 References 54 1

A homogeneous catalytic solution to the alcohol inhibition problem (see the

discussion under “Uncatalyzed chain reactions” of the oxidation of alcohol inter-
mediates, above) does not appear to have been found. However, the presence of a
heterogeneous oxidative dehydrogenation catalyst has been reported to be effec-
tive in the direct oxidation of alcohols to carbonyls and acids [109, 1101. The me-
chanism probably involves preliminary heterogeneous (oxidative) dehydrogena-
tion of carbinols to carbonyls. If the carbonyl is an aldehyde, it is readily con-
verted to the acid. Platinum, palladium, ruthenium, rhodium, and iridium cata-
lysts, supported on carbon, are reported to be active and selective catalysts for
the purpose [109]. Promoters such as cobalt and cadmium have been reported
to be effective additives.

References
[ l ] F. J. Weymouth, A. F. Millidge, Chem. Znd. (London) 1966, 887.
[2] G. Irick, Acetic Acid and its Derivatives (Chem. Ind. Series, Vol. 49), Dekker, New York,
1993, pp. 27-33.
[3] D. L. Lloyd, P. L. Eve, D. P. Gammer, Erdoel, Erdgas, Kohle 1993, 109(6), 266.
[41 World Petrochemicals Programm, SRI International, Ethylene and Derivatives, Vol. 1,
1995, p. WORL-28.
[51 Ref. [4], p. WORL-32.
[6] Ref. [4], p. WORL-26.
[7] R. A. Sheldon, J. K. Kochi, Metal-Catalyzed Oxidations of Organic Compounds,
Academic Press, New York, 1981, pp. 45-46.
[8] S . Al-Makaika, Atmosheric Oxidations and Antioxidants (Ed.: G. Scott), Elsevier,
Amsterdam, 1993, pp. 45-82.
[9] J. F. Black, J. Am. Chem. SOC. 1978, 100, 527.
1101 C. C. Hobbs, Kirk-Othmer Encycl. Chem. Technol., 4th edn., 1995, Vol. 13, pp.
682-7 17.
[ 111 A. Goosen, C. W. McCleland, D. H. Morgan, J. S. O’Connell, A. Ramplin, J. Chem.
Soc., Perkin Trans. I 1993, (4), 401.
[12] C . Walling, J. Am. Chem. SOC. 1969, 91, 7590.
[13] C. C. Hobbs, M. B. Lakin, Encyclopedia of Chemical Processing and Design
(Ed.: J. J. McKetta), Dekker, New York, 1987, Vol. 26, pp. 351-373.
1141 S . W. Benson, P. S . Nangia, Acc. Chem. Res. 1979, 12(7), 223.
[IS] V. A. Belyakov, G. Lauterbach, W. Pritzkow, V. Voerckel, J. Prakt. Chern./Chern.-Ztg.
1992, 334(5), 373.
[I61 G. A. Russell, J. Am. Chem. Soc. 1957, 79, 3871.
1171 G. Heimann, P. Wamek, J. Phys. Chem. 1992, 96, 8403.
[18] C . C. Hobbs, T. Horlenko, H. R. Gerberich, F. G. Mesich, R. L. Van Duyne, J. A.
Bedford, D. L. Storm, J. H. Weber, Ind. Eng. Chem. Proc. Res. Dev. 1972, 11, 59.
1191 Ref. [7], p. 143.
[20] L. Homer, Autooxidation and Antioxidants (Ed.: W. 0 . Lundberg), Wiley, New York,
1961, Chapter 5 .
[21] S. Murahashi, T. Naota, N. Hirai, J. Org. Chem. 1993, 58, 7318.
[22] F. F. Rust, personal communication, 1970.
[23] J. C. Andre, J. Lemaire, Bull. Soc. Chim. Fr: 1969, 12, 4231.
[24] J. C. Andre, J. Lemaire, C. R. Acad. Sci., Ser: C 1971, 272, 2396.
542 2.8 Reactions of Hydrocarbons and Other Saturated Compounds

[2.5] E. Bothe, D. Schulte-Frohlinde, C. v. Sonntag, J. Chem. SOC.,Perkin Trans. 2 1978,

(5), 416.
[26] E. Bothe, M. N. Schuchmann, N. Man, D. Schulte-Frohlinde, C. v. Sonntag, Photochem.
Photobiol. 1978, 28(4-5), 639.
[27] J. Igarashi, R. K. Jensen, J. Lusztyk, S. Korcek, K. U. Ingold, J. Am. Chem. SOC.1992,
114, 7727.
[28] S. W. Benson, J. Am. Chern. SOC.1965, 87, 972.
[29] Shell Development Co. (W. R. Keeler, D. R. Douslin, C. H. Deal, Jr.), US 2.869.989
(1959).
[30] J. W. Bozzelli, A. M. Dean, J. Phys. Chem. 1993, 97, 4427.
[31] R. A. Geisbrecht, T. E. Daubert, Ind. Eng. Chem., Prod. Res. Dev. 1976, 15(2), 115.
[32] J. C. Dechaux, L. Delfosse, Combust. Flame 1979, 34(2), 169; Chem. Abstr: 1979, 90,
206.71 8g.
[33] R. I. Moshkina, S. S. Polyak, L. B. Romanovich, A. B. Nalbandyan, Kinet. Katal. 1980,
21(6), 1379; Chem. Abstr: 1981, 94, 102.515e.
[34] R. D. Wilk, Chem. Phys. Process. Combust. 1991, 11-1/114; Chem. Abstr: 1992, 116,
238.565b.
[35] I. R. Slagle, J. Y. Park, D. Gutman, Symp. (Int.) Combust. [Proc.] 1984, 733.
[36] S. W. Benson, Oxidation of Organic Compounds I1 (Eds.: R. R. Gould, F. R. Mayo),
American Chemical Society, Washington, DC, 1968, pp. 143-1.53.
[37] S. Blaine, P. E. Savage, Ind. Eng. Chem. Res. 1992, 31(1), 69.
[38] A. Goosen, D. H. Morgan, J. Chem. SOC., Perkin Trans. 2 1994, 3, 557.
[39] F. R. Mayo, Acc. Chem. Res. 1968, 1(7), 193.
[40] G. R. Krow, Org. React. ( N . K ) 1993, 43, 251.[41] N. M. Emanuel, E. T. Denisov,
Z. K. Maizus, Liquid Phase Oxidation of Hydrocarbons, Plenum, New York, 1967.
[42] C. Walling, Free Radicals in Solution, Wiley, New York, 1957, p. 503ff.
[43] D. R. Larkin, J. Org. Chem. 1990, 55, 1563.
[44] R. K. Jensen, S. Korcek, L. R. Mahoney, M. Zinbo, J. Am. Chem. SOC.1981,103, 1742.
[45] R. K. Jensen, S. Korcek, L. R. Mahoney, M. Zinbo, J. Am. Chem. SOC.1979, 101, 7.574.
[46] R. S. Drago, Coord. Chem. Rev. 1992, 117, 185.
[47] Ref. [7], p. 40.
[48] A. Onopchenko, J. G. D. Schulz, J. Org. Chem. 1972, 37, 2564.
[49] W. J. De Klein, Red. Trav. Chim. Pays-Bas 1975, 94(2), 48.
[50] W. J. De Klein, E. C. Kooyman, J. Catal. 1965, 4, 626.
[51] Ref. [7], p. 41.
[52] G. M. Gorter-Laroij, E. C. Kooyman, J. Catal. 1972, 25, 230.
[.53l Ref. [7], p. 365.
[54] W. J. De Klein, Red. Trav. Chim. Pays-Bas 1975, 94(7), 151.
[55] W. J. De Klein, Recl. Trav. Chim. Pays-Bas 1977, 96(1), 22.
[56] H. J. den Hertog, E. C. Kooyman, J. Catal. 1966, 6, 357.
[57] S. P. Prokopchuk, S. S. Abadzhev, V. U. Shevchuk, Ukr: Khim. Zh. 1983, 49(5), 505;
Chem. Abstr: 1983, 99, 4987u.
[58] T. Yamaguchi, Jpn. Chem. Q. 1968, ZV-1, 27.
[59] Ref. [7], p. 141.
[60] A. Onopchenko, J. G. D. Schulz, J. Org. Chem. 1973, 38, 3729.
[61] Amoco Corp. (C. M. Park, N. S. Goroff), US 5.221.800 (1993).
[62] Union Carbide Corporation (J. E. Logsdon, B. W. Kiff), US 4.337.357 (1982).
[63] A. Onopchenko, J. G. D. Schulz, J. Org. Chern. 1973, 38, 909.
[64] A. Onopchenko, J. G. D. Schulz, R. Seekircher, J. Org. Chem. 1972, 37, 1414.
[6.5] Gulf Research & Development Co. (A. Onopchenko, J. G. D Schulz, R. Seekircher),
US 3.644.512 (1972).
 References 543

[66] Gulf Research & Development Co. (J. G. D. Schulz, R. Seekircher), US 4.032.570
(1977).
[671 Ref. [7], p. 138.
[681 Ref. [7], p. 137.
[69] A. Onopchenko, J. G. D. Schulz, J. Org. Chem. 1975, 40, 3338.
[70l Ref. [71, p. 346.
[711 J. R. Chipperfield, S. Lau, D. E. Webster, J. Mol. Catal. 1992, 75(2), 123.
[721 Ref. [7], p. 129.
[73l Ref. [7], p. 320.
[741 Ref. [7], p. 176.
[75] N. Ikeda, K. Fukuzumi, J. Am. Oil Chem. SOC. 1977, 54(3), 105.
[76] Ref. [7], p. 39.
[77] 0. A. Borislavskii, L. Ya. Lyuta, V. Ya. Suprun, E. N. Mokryi, Vestn. L’vov. Politekh.
lnst. 1987, 211, 120; Chem. Abstc 1988, 108, 186.188~.
[78] I. I. Korsak, M. N. Fedorishcheva, T. G. Kosmacheva, G. N. Supichenko, V. E. Agabe-
kov, N. I. Mitskevich, VestsiAkad. Navuk B. SSR, Sex Khim. Navuk 1980,5,37;Chem.
Abstr: 1981, 94, 156.246m.
[79] K. K. Sengupta, T. Samanta, S. N. Basu, Tetrahedron 1986, 42(2),681.
[80] S. V. Krylova, I. I. Ugolev, V. E. Agabekov, E. I. Savitskaya, Oxid. Commun. 1987,
10(34), 243; Chem. Abstr: 1989, 110, 7369a.
[81] J. F. Perez-Benito, C. Arias, An. Quim. 1993, 89(5-6), 636.
[82] RhGne-Poulenc S.A. (J. C. Brunie, M. Costantini, N. Crenne, M. Jouffret),
US 3.719.706 (1973).
[83] RhGne-Poulenc S.A., GB 1.304.785 (1969).
[84] Stamicarbon B. V. (J. Wolters, J. L. J. P. Hennekens), US 4.042.630 (1977).
[85] Stamicarbon B. V., GB 1.535.869 (1978).
[86] J. K. Kochi, Pure Appl. Chem. 1971, 4, 377.
[87] Celanese Corp. (C. C. Hobbs, H. H. Thigpen), DE 3.029.700 (1981).
[88] Hoechst AG (H. Erpenbach, K. Gehrmann, A. Hauser, K. Karrenbauer, W. Lork), DE
2.757.222 (1979).
[89] Mitsubishi Chemical Industries Co. Ltd. (T. Maki), JP 78 112.804 (1978).
[90] A. B. Vipper, 0. L. Glavti, Neftepererab. Nefekhim. (Kiev) 1990, 39, 6; Chem. Abstr:
1992, 116, 63.084q.
[91] N. V. Aleksandrov, Kinet. Katal. 1978, 19(4), 1057; Chem. Abstr: 1978, 89, 179.621r.
[92] H. Yukawa, Y. Fujikawa, Kenkyu Hokoku - Kanagawa-ken Kogyo Shikensho 1982,52,
63; Chem. Abstr: 1982, 97, 75.202d.
[93] D. A. Hutchison, J. L. Thompson, Lubr: Eng. 1990,46(7), 467; Chem. Abstr: 1991,114,
9303f.
[94] J. Haber, T. Mlodnicka, J. Mol. Catal. 1992, 74, 131.
[95] J. F. Lyons, P. E. Ellis, R. W. Wagner, P. B. Thompson, H. B. Gray, M. E. Hughes, J. A.
Hodge, Prepz-Am. Chem. SOC.,Div. Pet. Chem. 1992, 37(1), 307.
[96] Ref. [7], p. 47.
[97] R. A. Sheldon, J. K. Kochi, Adv. Catal. 1976, 25, 272.
[98] Daicel Ltd, (K. Hori, Y. Kondo, S. Tada, K. Baba), JP 75 22.531 (1975).
[99] J. B. Saunby, B. W. Kiff, Hydrocarbon Proc. 1976, 55(11), 247.
[loo] E. Bothe, D. Schulte-Frohlinde, Z. Natugorsch., Teil B 1980, 35, 1035.
[loll Ref. [7], p. 126.
[lo21 Standard Oil Co. (Indiana) (W. J. Zimmerschied), US 4.111.986 (1978).
[lo31 Y. Kamiya, J. Catal. 1974, 33, 480.
[lo41 T. Okada and Y. Kamiya, Bull. Chem. SOC.Jpn. 1979, 52, 3321.
[I051 Mitsui Sekiyu Kogyo K. K. (M. Mukoyama, T. Yanada), JP 04 108.758 (1990).
544 2.8 Reactions of Hydrocarbons and Other Saturated Compounds

11061 S. Murahashi, Y. Oda, T. Naota, J. Am. Chem. Soc. 1992, 114, 7913.
[lo71 Ref. [7], p. 142.
[lo81 F. G. Mesich, D. L. Storm, Hoechst Celanese Chemical Co., private communication.
[lo91 M. Hronec, Z. Cvengrosova, J. Kizlink, J. Mol. Catal. 1993, 83(1-2), 75.
[110] Ref. [7], p. 354.

2.8.1.2 Synthesis of Dimethyl TerephthalateRerephthalic

Acid and Poly(ethy1ene terephthalate)
David A. Schiraldi

2.8.1.2.1 Introduction
The discovery of poly(ethy1ene terephthalate), PET, in the 1940s [I, 21 and its
commercialization initially by DuPont and by ICI in the 1950s created a large
market demand for terephthalic acid and terephthalate esters of polymer purity.
Because dimethyl terephthalate, DMT, is readily purified by distillation [3] (and
also because the p-xylene oxidatiodesterification intermediate, methyl p-toluate,
is more readily kept in solution than is p-toluic acid) the polyester fibers and
films industry was initially based on terephthalate ester. With the development
of improved oxidation and purification technologies, purified terephthalic acid,
TPA, became available in commercial quantities by the mid 1960s. Over 75 %
of the worldwide PET manufacture (total world PET capacity is over six million
tons/year) is currently based on TPA rather than DMT [4]. This preference for
TPA results from the less complicated esterification catalysis and the absence of
methanol handling when the acid is used directly.
The oxidation of p-xylene to TPA/DMT is among the largest industrial-scale
homogeneous catalytic reactions.

2.8.1.2.2 Dimethyl Terephthalate and Terephthalic Acid

Dimethyl Terephthalate (DMT) Production

The first commercial processes for the production of DMT made use of nitric acid
oxidation of p-xylene to crude terephthalic acid, followed by esterification with
methanol and purification by distillation [ 3 ] .Air oxidation of p-xylene displaced
the use of nitric acid with the development of the Witten process [5]. In the Witten
process, p-xylene is air-oxidized at 140-180 "C and 0.5-2 MPa over a homoge-
neous cobalt or cobaltlmanganese catalyst system to give p-toluic acid, which is
then esterified to methyl p-toluate, oxidized again over the cobaltlmanganese cata-
lyst, and finally esterified to DMT (see Scheme 1). The four process steps are
accomplished in two reactors (see Figure 1). The Witten process uses no solvent.
 2.8.1.2 Synthesis of Dimethyl Terephthalatefferephthalic Acid 545

Scheme 1. Witten DMT process.

methyl p-toluate
I
esterification

methanol

water water

Figure 1. Flow sheet for DMT synthesis.

The mechanism of the Witten process is believed to involve an electron transfer

from p-xylene to cobalt(III), followed by loss of proton and addition of oxygen to
give a hydroperoxide radical [6-81. Reduction of the hydroperoxide radical by co-
balt(I1) regenerates cobalt(II1) catalyst, and produces p-tolualdehyde as an inter-
mediate. Under oxidative conditions, the p-tolualdehyde is rapidly oxidized to
p-toluic acid, which is esterified to methyl p-toluate. For the second oxidation
from methyl p-toluate to DMT, an atom transfer step is proposed rather than elec-
tron transfer from cobalt(II1); a hydroperoxy radical from p-xylene oxidation is
proposed to abstract a hydrogen atom from methyl p-toluate to generate a benzylic
radical. This benzylic radical can then react with oxygen, leading to the second
carboxyl group (see Scheme 2).
The kinetics of the Witten oxidation process are complicated by the presence of
several possible radical chain carrying steps and termination steps.A full treatment
of these kinetics has not been published. What is known about the kinetics is that
the initial oxidation of p-xylene to p-toluic acid is inversely proportional to [Co"],
an induction period generally attributed to the oxidation of Co" to Co"' is ob-
served, the rate of conversion of p-xylene to p-toluic acid is faster than that of
methyl p-toluate to monomethyl terephthalate, and the rate of the first oxidation
step (and not the second) can be greatly increased by the addition of radical
sources, such as acetaldehyde or paraldehyde.
Both oxidation steps are reported to yield 95 % of the desired product, resulting
in an overall yield of approximately 90 % from p-xylene to DMT. The major side
product of the Witten process is methyl benzoate (from decarboxylation of inter-
mediates) with radical coupling products accounting for "heavy ends" from pro-
duction.
546 2.8 Reactions of Hydrocarbons and Other Saturated Compounds

COOH COOCH3

CH3 CH3 CHi CH3

8 COOCH3

CHi
-
O2
-+ hydroperoxide - - --+
CH30H
DMT

Scheme 2. Proposed Witten oxidation mechanism.

Terephthalic Acid (TPA) Production

The air oxidation of p-xylene to TPA appears on the surface to be similar to the
Witten process in that it uses a homogeneously dissolved cobalt/manganese cata-
lyst system. The TPA process, originally referred to as the "Mid-Century'' (cf. [9],
[lo]) and now as the "Amoco" process, is actually quite different from the Witten
process described above. The Amoco process uses acetic acid as a solvent for
the oxidation reactions and bromine as a free- radical source, proceeds to TPA
from p-xylene in one step, operates at 175-230 "C/1-2 MPa, obtains overall
yields of approximately 95 %, and of course does not involve an esterification
step [9-121.
The mechanism of the Amoco TPA process is believed to begin with hydrogen
atom abstraction from p-xylene by a bromine atom. The resultant benzylic radical
adds oxygen, and proceeds through the hydroperoxide to p-toluic acid. Hydrogen
atom abstraction from p-toluic acid generates a second benzylic radical, which
follows the same pathway to generate TPA (see Scheme 3).
 2.8.1.2 Synthesis of Dimethyl TerephthalateRerephthalicAcid 547

COOH COOH COOH COOH COOH

Q /+ B r * z Q %/ Q + e-

CH3 CH2' CH200' CHO COOH

Scheme 3. Amoco TPA process.

The roles of manganese in TPA manufacture are better understood than in the
Witten process, and include decomposition of the CH,COOH radical (derived
from the acetic acid solvent) and regeneration of the bromine atom promoter
[ 131. In an effort to eliminate halogen compounds which are highly corrosive to
oxidation equipment, use of acetaldehyde [ 141 and paraldehyde [ 151 has been de-
veloped. These aldehyde promoters are ultimately converted to acetic acid in high
yield. For economic reasons, these aldehyde processes have been abandoned in
favor of the bromine-promoted Amoco process.

Future Developments in DMT/TPA Catalysis

World demand for PET feedstocks is expected to grow significantly over the next
decade, largely due to foodbeverage packaging applications. The potential for in-
creasing yields of terephthalate from p-xylene by as much as 5 % offers a major
economic incentive if new technology can be retrofitted into existing facilities.
The best opportunity for such an improvement in either the Witten or the
Amoco process could probably be realized by the use of more efficient radical
promoters which allow oxidizer temperatures to be lowered without reducing
overall reaction rates. Reduction of oxidizer temperatures would in turn reduce
product losses due to decarboxylation. New alternatives to the use of halogen pro-
moters in TPA synthesis would also be of value in reducing the capital cost of new
facilities to be built in the world's developing regions.
Also under development is use of the alternative feedstock, toluene, for PTA
and/or DMT production. Carbonylation of toluene to produce p-tolualdehyde
was shown to proceed in 90-95 % yield when catalyzed by HF . BF3 [31], or
by higher perfluoroalkyl sulfonic acids [32], or in greater than 99 % yield when
catalyzed by trifloromethanesulfonic acid [33]. The p-tolualdehyde, which is reg-
ularly an intermediate in both the Witten DMT and Amoco TPA processes (see
Schemes 2 and 3 , respectively), can then be readily oxidized with minimal
changes to the oxidation process.
548 2.8 Reactions of Hydrocarbons and Other Saturated Compounds

2.8.1.2.3 Poly(ethy1ene terephthalate)

Poly(ethy1ene terephthalate) (PET) Production

The two commercial routes for the production of PET, based on DMT and on TPA
feedstocks, are known to proceed through a common intermediate, generally
referred to bis(hydroxyethy1) terephthalate, BHET (see Scheme 4).

TPA

direct esterification
1 - 2 H20

BHET

-2CH3OH 1 transesterification
or ester interchange

DMT

X H o m o / ?+'< O-OH

PET

Scheme 4. PET manufacturing routes.

 2.8.1.2 Synthesis of Dimethyl Terephthalatefferephthalic Acid 549

For practical reasons of reaction rates, diethylene glycol by-product production,

and energy usage, ethylene glycolkerephthalate ratios of less than 2:l are com-
mon, giving rise to an intermediate mixture of BHET and its oligomers. Polymers
obtained from the two terephthalate feedstocks are nearly identical, differing only
slightly in the amount of diethylene glycol formed (and subsequently incorporated
into the backbone; higher when TPA is the feedstock), relative abundance of
hydroxyl and carboxyl polymer chain ends (higher carboxyl end concentrations
are typical when TPA is used), and the package of soluble metal catalysts used
in their production [ 161. Though never clearly demonstrated, it is generally be-
lieved that metal phosphate or phosphite salts produced in the DMT process
can serve as nucleating agents which influence PET crystallization rates.
The direct esterification route to BHET from TPA and ethylene glycol requires
no additional catalyst, but proceeds at 240-270 "C with the removal of water. The
kinetics of this process are well established [17].
The transesterification of DMT to BHET requires use of homogeneously
dissolved metal salts, such as the acetates or alkoxides of calcium, magnesium,
manganese, cobalt, zinc, sodium, lithium, lead, cerium and cadmium, and is run
in the melt at 170-220 "C [18-201. A mechanism in which the metal salt co-
ordinates to the carbonyl oxygen of DMT, thereby enhancing the reactivity
toward nucleophilic diol, is believed to occur during transesterification [2 11 (see
Scheme 5).
0 0 ....* ML,
4 4
Ar-C, + ML, ==== Ar-C,
OCH3 OCH3

Scheme 5. Proposed mechanism for DMT transesterification

Once the transesterification step is complete, the metal salt is always deacti-
vated by complexation with a phosphate or phosphite compound [ 181, preventing
unwanted side reactions as the reaction temperature is increased during polycon-
densation. Such side reactions lead to polymer chain scission and loss of molecu-
lar weight, as well as development of unwanted discoloration of the polymer. Care
has to be taken that excess phosphorous compounds are not added to the reaction,
as these compounds can significantly reduce the effectiveness of the polyconden-
sation catalyst.
550 2.8 Reactions of Hydrocarbons and Other Saturated Compounds

The polycondensation of BHET to PET proceeds in the melt at temperatures of

270-305 OC, under vacuum (< 1 mbar absolute pressure) and in the presence of
Lewis acid metal compounds, such as titanium alkoxides, dialkyltin oxide,
gallium oxide, germanium oxide, thallium oxide, lanthanide salts, and most
commonly, antimony oxide [ 1, 2, 22-26]. Under polymerization reaction condi-
tions, these catalysts are generally converted to their alkoxides with ethylene
glycol. Typical of such alkoxides is antimony(II1) glycolate, the active catalyst
for the majority of the world’s PET production [27] (cf. Structure 1).

[ >sb-O-CH2-CH2-O-Sb
1
3 0

Polycondensation catalysts used in PET are not deactivated; reheating solid

PET polymer to temperatures greather than 200 “C will allow additional polycon-
densation to resume (as polymer chain mobility is sufficient at these temperatures
to allow both polycondensation and ethylene glycol migration out of the PET par-
ticles). Such a post-extrusion process is used to “solid-state polymerize” PET to
the high molecular weights necessary for foodbeverage packaging.
The mechanism of polycondensation catalysis by soluble antimony is believed
to involve metal coordination to the ester carbonyl oxygen. This coordination
withdraws electron density and renders the carbonyl more susceptible to nucleo-
philic attack [28] (eq. (1)).

0
ArKowoyAr (1)
0

Other metals which catalyze PET polycondensation are proposed to coordinate

with and activate ester carbonyl groups similarly. That different metals are optimal
for activating the ester carbonyls of DMT and of BHET (i.e., catalyzing transes-
terification and polycondensation, respectively) has been well explained by ac-
counting for differences in carbonyl oxygen basicity between methyl esters and
hydroxyethyValkoxyethyl esters. The optimum catalysts for each step maximize
electronic interactions with the reacting esters [29, 301.

Future Developments in PET Catalysis

While antimony compounds are used almost exclusively throughout the world in
PET manufacturing, they are not as effective as stronger Lewis acids in catalyzing
 References 55 1

this reaction. Use of more effective catalysts, such as the salts of tin and of tita-
nium, could allow for lower metal usage, increased throughput for existing plants,
and/or improved polymer quality (due to lower possible polycondensation tem-
peratures and less thermal degradation of the polymer). Uses of such active
catalysts are currently limited by the formation of highly colored (and hence
undesirable) coordination complexes in trace amounts under reaction conditions.
Development of catalyst or process modifications which eliminate these highly
colored species offers significant economic benefit to PET producers.
Also of potential utility is the discovery that combinations of highly Lewis
acidic metal salts, such as Al"', with less acidic salts, such as Co"', can produce
mixed metal catalysts of high activity for PET polycondensation [34, 351. This
area of mixed metal polycondensation catalysis, which has been explored in
only a limited way to date, may lead to optimized polymer color, stability, and
maximum polymerization productivity during the coming generation.

References
[l] J. R. Whinfield, Nature (London) 1946, 158, 930.
[2] ICI (J. R. Whinfield, J. T. Dickson), GB 578.079 (1946).
[3] Du Pont (R. M. Cavanaugh, J. E. Lufkin), US 2.459.014 (1949).
[4] C. S. Read, Dimethyl Terephthalate (DMT)and Terephthalic Acid (TPA),CEH Market-
ing Research Report, SRI International, Menlo Park, California, 1993.
[5] Chemische Werke Witten (E. Katschmann), US 3.253.017 (1966).
[6] A. Onopchenko, J. G . D. Schultz, R. Seekircher, J. Org. Chem. 1972, 37, 1414.
[7] E. J. Y. Scott, A. W. Chester, J. Phys. Chem. 1972, 76, 1520.
[8] Dynamit Nobel (G. Hoffmann, K. Irlweck, R. Cordes), GB 1.344.383 (1974).
[9] Midcentury Corp. (R. S. Barker, A. Saffer), US 2.833.816 (1958).
[lo] Midcentury Corp. (R. S. Barker, A. Saffer), US 3.089.906 (1963).
[ 111 R. Landau, A. Saffer, Chem. Eng. Prog. Oct. 1968, 64, 20.
[12] Amoco (C. M. Park, D. G. Micklewright), US 4.053.506 (1977).
[13] E. I. Heiba, R. M. Dessau, W. J. Koehl, J. Am. Chem. Soc. 1969, 91, 138.
[ 141 Anon., Hydrocarbon Proc. 1977, 56( 1l), 149.
[15] Anon., Hydrocarbon Proc. 1977, 56(1l), 230.
[16] S. G. Hovenkamp, J. P. Munting, J. Polym. Sci. A-1 1970, 8, 679.
[17] T. Yamata, Y. Imamura, Polym. Eng. Sci. 1988, 28(6), 385.
[ 181 H. Zimmermann, Fuserforsch. Text. Tech. 1962, 13, 48 1.
[19] H. Zimmermann, Faserforsch. Text. Tech. 1973, 24, 445.
[20] J. S. Chung, J. Macromol. Sci., Chem. 1990, A27(4), 479.
[21] K. H. Wolf, B. Kuster, H. Herlinger, C.-J. Tschang, E. Schrollmeyer, Angew. Makromol.
Chem. 1978, 68, 23.
[22] Du Pont (J. H. Haslam), US 2.822.348 (1958).
[23] B. F. Goodrich (F. X. Werber), US 3.056.818 (1962).
[24] Du Pont (R. M. Cavanaugh, J. B. Dempster), US 2.820.023 (1958).
[25] Teijin (S. Kotani, Y. Bandou, J. Takeiski), US 3.489.722 (1970).
[26] ICI (R. P. L. Tanbinger, R. B. Rashbrook), US 4.133.800 (1979).
[27] S. B. Maerov, J. Polym. Sci., Polym. Chem. Ed. 1979, 17, 4033.
[28] R. Lasarova, K. Dimov, Angew. Makromol. Chem. 1976, 55(1), 1.
552 2.8 Reactions of Hydrocarbons and Other Saturated Compounds

[29] K. Tomita, Polymer 1976, 17, 22 1.

[30] K. Yoda, Makromol. Chem. 1970, 136, 311.
[31] Mitsubishi Gas Chemical (S. Fujiyama, T. Takahashi, S. Kozao. T. Kasahara).
US 3.948.998 (1974).
[32] Exxon (R. Y. Saleh, C. L. Becker, R. C. Michaelson, R. H. Schrossberg), WO 00/15.593
(2000).
[33] HNA Holdings (D. A. Schiraldi, J. C. Kenvin), US 5.910.613 (1998).
[34] DuPont (G. R. Goodley), US 5.512.340 (1996).
[35] Dupont (G. R. Goodley), US 5.674.801 (1996).

2.8.2 Halogenations
WolfgangA. Herrmann, Marc0 Stoeckl

2.8.2.1 Introduction
Introduction of halogen into organic compounds is a very important reaction in
industrial chemistry. Halogenated products serve as plastics (PTFE, PVC),
solvents (CH2C12, chlorinated benzenes and toluenes), fungicides, herbicides,
and insecticides (chlorophenols) and are widely used as intermediates. Two
different reaction types are applied for homogeneously catalyzed halogenation
reactions: substitution and addition.

2.8.2.2 Substitution Reactions

In industrial processes free radical substitution is widely used for halogenation of
aliphatic hydrocarbons (e. g., methane chlorination to CH3Cl, CH2C12,CHC13,and
CC14). In these reactions the replacement of hydrogen by halogen is initiated by
heat or irradiation with no catalyst present in the process [l]. Olefins can be radi-
cally halogenated in the allylic position by a number of reagents, of which N-bro-
mosuccinimide (NBS) is by far the most common [2]. Nucleophilic substitution is
observed in the reaction of alcohols with various agents, such as PX3, PX5, POX3,
SOX2, and HX (X = halogen) [ 3 ] .For chlorination of primary and secondary al-
cohols with HCl as catalyst, ZnC12, is usually required. Electrophilic substitutions
take place in the halogenation of aromatic compounds like benzenes, toluenes, and
phenols [ 1, 4, 51. The bromination and chlorination of such aromatic molecules is
often carried out in the presence of a catalyst, usually ferric halide. The mecha-
nism of the electrophilic substitution is shown in Scheme 1. The Lewis-acid cata-
lyst leads to polarization of the bromine. After addition of a Br' to the benzene
(formation of a carbocation) H' is eliminated to give the monohalogenated
product. Further addition leading to higher halogenated benzenes often occurs,
depending on the reaction conditions and the catalyst. However, for active
substrates, including amines, phenols, and naphthalene, no catalyst is needed.
 2.8.2.3 Addition Reactions 553

Scheme 1

In addition to their application as solvents or intermediates in chemical syntheses,

chlorophenols are industrially important due to their broad spectrum of antimicro-
bial properties and their use as fungicides, herbicides, insecticides, ovicides, and
algicides.

2.8.2.3 Addition Reactions

The addition of elemental halogen or hydrogen halides to C-C multiple bonds is
the most important halogenation reaction in industrial chemistry. At present, 1,2-
dichloroethane (DCE, by chlorination of ethylene) is among those chemicals with
the highest production rates and is now used as a starting material for the produc-
tion of poly (vinyl chloride) (PVC, Scheme 2) [6]. Vinyl chloride monomer
(VCM) can be achieved by three different routes.
Up to the early 1980s VCM was produced by addition of hydrogen chloride to
acetylene. In this process the gaseous reactants are brought into contact with the
catalyst at slightly increased pressure and 100-250 "C [I]. Mercury(I1) chloride
on activated carbon is used as a catalyst in this heterogeneous process. Today,
however, this reaction has no economical importance. Nowadays, VCM is exclu-
sively produced by thermal decomposition of DCE.

H+CH2 t Clz

CICHrCH2CI - -
- HCI
CHFCHCI

Scheme 2
554 2.8 Reactions of Hydrocarbons and Other Saturated Compounds

Two combined processes for the synthesis of DCE are well established: the
oxychlorination and the direct chlorination of ethylene. In the oxychlorination
process, ethylene and hydrogen chloride react with oxygen in the presence of
an metal catalyst. In most cases, copper(I1) chloride is used at a temperature
above 200 "C. This reaction has attained commercial importance since the
1960s, when VCM producers began to pursue the ethylene route to VCM, and
HC1 from DCE cracking had to be recovered. It is possible to perform this process
in homogeneous aqueous copper(I1) chloride solution, thus maintaining a uniform
temperature and mild conditions during the whole reaction time [7]. Therefore,
economic space-time yields can be achieved. However, due to the corrosiveness
of the aqueous reaction mixture, in industry the oxychlorination of ethylene has
been realized exclusively as a heterogeneous gas-phase reaction using copper
chlorides supported on alumina, usually in a fluidized bed reactor [S]. Selectivities
up to 91-95% are achievable [9]. The mechanism is shown in Scheme 3. The
reaction sequence proceeds via chlorination of ethylene by copper(I1) chloride,
forming copper(1) chloride and DCE. The copper salt is then regenerated by
oxygen and HC1 [lo].
In the direct chlorination process, ethylene and chlorine are most commonly
reacted in the liquid phase and in presence of a Lewis-acid catalyst. DCE is
used as solvent. A broad range of Lewis-acid catalysts have been patented for
this process, including SnCl,, A1C13, BC13, ZnCl,, SbCI5, CuC12, BiC15, and
TeC1, [Ill. However, the most common catalyst is FeC13 [12]. Depending on
the catalyst, a selectivity for DCE up to 99.9% can be achieved. Oxygen or air
is often added to the reactants, because oxygen was found to inhibit the radical
formation of 1,1,2-trichloroethane and its more highly chlorinated derivatives
[ 131. In the direct chlorination of ethylene, two fundamental process variations
(low-temperature chlorination [LTC] and high-temperature chlorination [HTC])
can be characterized.
In the LTC process, ethylene and chlorine react in DCE as solvent at tempera-
tures below the boiling point of DCE (usually between 20 and 75°C). The re-

2HCI -;I
CuO.CuCI2
v
2 CUCl
DCE

Scheme 3
 2.8.2.3 Addition Reactions 555

bromonium
1:l ncomplex 2:l momplex cation
Scheme 4

action enthalpy has to be removed by cooling with heat exchangers. Due to the
low temperature only low amounts of byproducts are formed during the reaction.
However, the energy requirements are considerably higher in comparison with the
HTC process, because steam is needed for the purification of DCE by rectifica-
tion. The direct chlorination in the HTC process is carried out at temperatures
between 85 and 200 "C. Most preferably, a temperature between 100 and 130 "C
is applied. The heat of reaction is used to distill the DCE produced. In addition,
DCE from the oxychlorination and unconverted DCE from the vinyl chloride
production can be added to the reactor for purification.
From a mechanistic point of view, two different ionic mechanisms have to be
considered (due to the presence of oxygen the radical chain mechanism plays no
role in the technical process): first, the uncatalyzed reaction of ethylene and chlor-
ine and second, the metal halide catalyzed reaction. Both routes compete in this
process. The uncatalyzed halogenation was studied extensively for the bromina-
tion of olefins [ 14, 151 (Scheme 4). It is commonly accepted that the halogenation
of olefins starts with formation of a 1:l n-complex of halogen and alkene fol-
lowed by formation of a bromonium ion. Subsequent nucleophilic attack of a bro-
mine anion leads to the dibromoalkane. However, when highly hindered olefins
(such as tetraneopentylethylene) are used, formation of a 2: 1 n-complex, as an in-
termediate between 1: 1 n-complex and a bromonium ion, is detectable by UV
spectroscopy. In the catalyzed reaction the metal halide polarizes the chlorine
bond, thus leading to formation of a chloronium or carbonium ion. Subsequent
nucleophilic attack of a chloride anion gives the dichloroalkane [ 121 (Scheme 5).
The activity and selectivity of the FeCI3 catalyst is easily increased by addition
of various additives. In the early 1980s it was found that addition of ammonia
556 2.8 Reactions of Hydrocarbons and Other Saturated Compounds

leads to an increase of the selectivity for DCE in the direct chlorination of ethyl-
ene. However, during the process ammonia is converted into tris(2-chloroethy1)-
amine (N-Lost), which is well known as cytostatica. Nowadays, group I and I1
metal chlorides have been established as additives in this industrial process
[ 161. Especially, addition of NaCl to the catalyst solution (Fe/Na = 3: 1) increases
the selectivity, activity, and solubility of FeCI, in DCE.

References
[ l ] M. Rosenberg et al., in UllmannS Encycl. Ind. Chem. 5th ed. 1986, Vol. A6, p. 233.
[2] J. Pizey, in Synthetic Reagents (Ed.: J. Pizey), Wiley, New York, 1974, Vol. 2, p. 1.
[3] G. W. Brown, in The Chemistry of the Hydroxy Group (Ed.: S. Patai), Interscience,
New York, 1971, Vol. 1, p. 593.
[4] F. Muller et al., in Ullmann’s Encycl. Ind. Chem. 5th ed. 1986, Vol. A7, p. 1.
[5] C. Buehler et al., in Survey of Organic Synthesis, Interscience, New York, 1970, p. 392.
[6] Roempp Chemie-Lexikon,Georg Thieme Verlag, Stuttgart, 1995.
[7] L. F. Albright, Chem. Eng. (N. Z) 1967, 74, 219.
181 J. S. Naworski, E. S. Velez, in Applied Industrial Catalysis (Ed.: B. E. Leach), Academic
Press, New York, 1983, Vol. 1, p. 239.
[9] The Distillers Company Ltd. (A. F. Millidge, C. W. Capp, P. E. Waight), DE-OS
1.443.703 (1970).
[lo] H. Heinemann, Chem. Tech. (Heidelberg) 1971, 5, 287.
[ 111 Wacker-Chemie, DE 1 S91.537 (1970); Shell International Research, NL 6.901.398
(1969); Union Carbide (D. B. Benedict), US 2.929.852 (1954); Wacker-Chemie (R. Sie-
ber, A. Maier), DE-OS 1.668.850 (1967); Wacker-Chemie (0.Fruhwirth, L. Schmid-
hammer, E. Pichl), DE-OS 1.768.367 (1968).
[I21 K. Weissermel, H.-J. Arpe, in Industrial Organic Chemistry, 4th ed., Verlag Chemie,
Weinheim, 1994, p. 232.
[ 131 Jefferson Chemical Co. (R. R. Reese), US 2.601.322 (1952).
[ 141 A. Bianchini, C. Chiappe, G. Lo Moro, D. Lenoir, P. Lemmen, N. Goldberg, Chem. Eur:
J. 1999, 5, 1570.
[15] A. Bianchini, C. Chiappe, D. Lenoir, P. Lemmen, R. Herges, J. Grunenberg, Angew.
Chem. Int. Ed. Engl. 1997, 36, 1284.
[I61 Hoechst AG (J. Hundeck, H. Scholz, H. Hennen), EP 1.112.03 (1983).
 Applied Homogeneous Catalysis with Organometallic
Edited by Boy Cornils & Wolfgang A. Herrmann
© Wiley-VCH Verlag GmbH, 2002

2.9.2.1 Terpenes 557

2.9 Asymmetric Syntheses

Ryoji Noyori, Shohei Hashiguchi, Toru Yamano

2.9.1 Introduction
The use of well-designed chemical processes, aided by chiral molecular catalysts,
can provide truly practical and efficient synthetic methods for the production of
bioactive substances and functional materials. In particular, the growing aware-
ness of the importance of chirality to the function of chemical substances has
led to the development of many new chiral molecular catalysts for use in large-
scale production. Chiral molecular catalysts consisting of a metal atom or ion
and a chiral organic ligand(s), under the appropriate conditions, can not only re-
peatedly accelerate organic reactions, but also simultaneously control the absolute
stereochemical outcome [ 11.
This strategy has been applied to a range of homogeneous catalyses, provid-
ing an ideal method for the asymmetric synthesis of chiral compounds. The ben-
efits of the chemical multiplication of chirality include: (1) the high generality in
natural- and unnatural-type reactions, (2) the low substrate specificity, (3) the
unlimited tunability of reactivity and selectivity by ligand permutation, (4) the
chiral flexibility giving either enantiomer, ( 5 ) the high volumetric yield, and (6)
the easy workup. Since chirality is a key element in bioactive molecules, asym-
metric catalysis is particularly significant in the pharmaceutical, agrochemical,
flavor, and fragrance industries. The practical synthesis requires not only high
stereoselectivity but also satisfactory cost-performance, including chemical engi-
neering factors as well as environmental consciousness (cf. Section 3.3.1) [2].
Spectacular enantioselection has been observed in hydrogenation (cf. Section
2.2) [3] and hydrometallation of unsaturated compounds (cf. Section 2.6) [4], ole-
fin epoxidation (cf. Section 2.4.3) [5] and dihydroxylation (cf. Section 3.3.2) [6],
hydrovinylation (cf. Section 3.3.3) [7], hydroformylation (cf. Section 2.1.1) [4a,
81, carbene reactions [9] (cf. Section 3.1. lo), olefin isomenzation (cf. Section
3.2.14) [lo], olefin oligomerization (cf. Section 2.3.1.1) [ 111, organometallic
addition to aldehydes [ 121, allylic alkylation [ 131, Grignard coupling reactions
[ 141, aldol-type reactions [ 151, Diels-Alder reactions [ I2a, 161, and ene reactions
[ 171, among others. This chapter presents several selected examples of practical
significance.

2.9.2 Preparation of Selected Structures

2.9.2.1 Terpenes
A landmark process using a cationic Rh' complex with a BINAP ligand is working
at Takasago International Corporation, Japan, on up to a nine-ton scale.
558 2.9 Asymmetric Syntheses

Scheme 1 illustrates this industrial synthesis of (-)-menthol ( 5 ) from myrcene

(1) using (S)-BINAP-Rh' (6)-catalyzed isomerization of geranyldiethylamine
(2) to (R)-cintronellal (m-enamine (3) as the key step. The optical purity of syn-
thetic citronella1 (4), 96-99 %, is much higher than the highest value of the natural
compound, 82 % [ 181. The turnover number approaches 8000 moVmol Rh cata-
lyst. The Rh catalyst can be recycled to result in an overall efficiency of chiral
multiplication of 400 000 mol productlmol Rh catalyst. This process has been
applied to the synthesis of a number of chiral terpenic substances, resulting in
an annual production of about 2000 tons, of which 1000 tons is (-)-menthol.

1 2

A A
4 5 6
(S)-BINAP-Rh+catalyst; L = THF,
Scheme 1. Industrial synthesis of (-)-menthol. acetone, 1,5-cyclooctadiene, (S)-BINAP

10 11
(R)- and (S)-BINAP-Ru" catalyst

Scheme 2. Asymmetric hydrogenation of allylic alcohols.

 2.9.2.2 Carboxylic Acids 559

In the presence of a BINAP-Ru" complex (Structures 10 and ll),geraniol (7)

or nerol (9) is hydrogenated selectively at the C(2)-C(3) double bond to give
citronellol (8) quantitatively (Scheme 2) [ 191. This hydrogenation is effected in
methanol with a substrate:catalyst ratio as high as 50000: 1 to give either natural
or unnatural compounds in up to 99 % enantiomeric purity.
The Ru" catalyst can also be successfully applied to the sequential introduction
of chirality into the prenyl side chain of vitamin E [20]. In this case, a Ru" complex
with a 2-fury1 MeOBIPHEP ligand is used for the hydrogenation of unsaturated
ketones to give saturated ketones in 94 % ee.

2.9.2.2 Carboxylic Acids

Profens, 2-arylpropionic acids, are significant anti-inflammatory agents re-
presenting a multibillion-dollar-a-year market (Figure 1). One of the industrially
feasible synthetic processes is given in Scheme 3. The aromatic ketone 17 is
convertible to the a-substituted acrylic acid 18 by electroreductive carboxyla-
tion followed by dehydration [21]. Asymmetric hydrogenation of 18 with an
(S)-BINAP-Ru" complex catalyst in methanol under a high pressure gives (S)-
naproxen (13) in 97 % ee and 100 % yield [22].
In order to improve the efficiency of the process, the hydrophilic nature of the
catalyst was increased by introduction of m-sulfo groups into both diphenylphos-
phino groups of the ligand 6. Under the biphasic reaction system which uses a
porous hydrophilic support and conventional organic solvents, the novel catalyst
bearing the sulfonylated ligand remains in the hydrophilic phase and can be sepa-
rated easily. Using the so-called supported phase asymmetric catalyst system, the

12
ibuprofen ketoprofen

flurbiprofen

14
flunoxaprofen

Figure 1. Representative profens.

560 2.9 Asymmetric Syntheses

135 bar H2

CH30H
11

CH3O
XlTH 13
/

Scheme 3. Asymmetric synthesis of naproxen. * Electrolysis (A1 anode, Pb cathode).

high performance of the original homogeneous catalyst systems can be transferred

to a commercially viable process (96 % ee) [23].
Carbonylation of aromatic olefins also provides an attractive route to profens.
The key issues in the hydroformylation reaction (cf. Section 2.1.1 and Scheme 4)
are the branchednormal selectivity and the configurational stability of the
branched aldehydes. When the Pt’I-catalyzed asymmetric reaction is performed
with triethyl orthoformate, the aldehyde product is immediately removed as

Ar- + CO + H2 -
chiral cat.
Ar
branched
+ Ar
wCHO
normal

Chiral catalyst Ar ee [%I Branched: normal

PtCl(SnCl3)[(2S,4S)-DBP-6PPM] > 96‘”’ 17:5

0.9 mol% CH30

Rh(acac)(CO),,(R,S)-BINAPHOS, 92 88:12
0.3 mol% (20)

(a) As diethyl acetal.

8% - p&p\

t-CdH90 A0 19
(2S,4S)-DBP-BPPM (R,S)-BINAPHOS

Scheme 4. Asymmetric hydroformylation.

 2.9.2.2 Carboxylic Acids 561

diethyl acetal without loosing optical purity [24]. Rh' complexes are more reac-
tive, however. Thus, a Rh complex with (R,S)-BINAPHOS (20), a chiral phos-
phine/phosphite hybrid ligand, effects the enantioselective carbonylation of p-iso-
butylstyrene to give a chiral aldehyde in 92% ee which serves as an ibuprofen
(12) precursor [25].
Pd"-catalyzed hydrocarboxylation of aromatic olefins leads directly to the
requisite carboxylic acids (cf. Section 2.1.2.2) under mild conditions (Scheme 5).
The reaction, with the aid of (S)-BNPPA (21), a chiral hydrogen phosphate, gives
regio- and enantioselectively @)-ibuprofen and (S)-naproxen, but the turnover
efficiency as well as the enantioselectivity can still be improved [26].

13 mol % PdCI2,CuC12
21, 0 2 , HCI
A,.- + CO (1 bar) + H20 * Ar
THF

g>p<
~ ~ ~~ ~ ~~

Product Ar ee [%I

Ibuprofen (12) 84

\ /
Naproxen (13)
21
CH3O (S)-BNPPA

Scheme 5. Asymmetric synthesis of profens by hydrocarboxylation of aryl olefins.

The potential naproxen precursor 23 is accessible in 96 % yield and in 85 % ee

by asymmetric hydrocyanation (cf. Section 2.5) of the aromatic olefin 22 cata-
lyzed by a Nio complex with a glucose-derived phosphinite ligand (Scheme 6)
~71.

CH30
\
+ HCN
1-5 mol % Ni(cod)2, L'

hexane
*& CH3O
\ /

22 23

Scheme 6. Asymmetric hydrocyanation of olefins; cod = cyclooctadiene.

562 2.9 Asymmetric Syntheses

Scheme 7 displays a possibility of the synthesis of chiral2-arylpropionic acids

via the oxidative tranformation of (R)-3-aryl-1-butenes. The requisite chiral ole-
fins may be obtained by transition metal-catalyzed asymmetric coupling between
a benzylic Grignard reagent and vinyl bromide (93 % optical yield) [28] or, more
attractively, asymmetric hydrovinylation of an aromatic olefin with ethylene. The
asymmetric combination of styrene and ethylene, giving the adduct 25 in 95 % ee,
has been performed on a 10-kg scale with a dinuclear Ni catalyst formed from
(y3-allyl)NiCI2 and a unique chiral dimeric aminophosphine obtainable from
(R)-myrtenal and (S)- 1-phenylethylamine [7a].

+ CH2=CHBr - 3 0" + CH*=CHz

.
26 27

Scheme 7. Asymmetric synthesis of (R)-3-aryl- 1 -butenes.

The asymmetric hydrogenation of u,P- or B,y-unsaturated carboxylic acids has

been applied successfully to the preparation of some key intermediates for phar-
maceuticals. For example, a Rh' complex with (S,S)-CHIRAPHOS catalyzes
hydrogenation of the sodium salt of unsaturated carboxylic acids, intermediates
for the non-peptide endothelin antagonists SB209670 and SB217242, in 90 %
yield and 94 % ee [29].
A rare example of asymmetric hydrogenation of a tetra-substituted @unsatu-
rated carboxylic acid 28 with a Ru"-(R)-MeOBIPHEP (31) catalyst provides
chiral carboxylic acid 29 in 94% ee; this is a key building block for a novel
class of calcium antagonist, mibefradil(30), used for the treatment of hypertension
(Scheme 8). In this process the enantiomeric excess of the product was highly de-
pendent on hydrogen pressure [20]. On a larger-scale synthesis, the hydrophilic
ligand 32 can be used in a higher space-time, and with reduced reactor volumes,
and it is also feasible to recycle the catalyst, which results in lower production
costs. Although this results in a slight decrease in the enantiomeric purity of
the product 29 (84% ee), crystallization of the sodium salt increases the optical
purity [30].
Hydrogenation of a mixture of a$-unsaturated and P,y-unsaturated carboxylic
acids using a Ru" complex with (S)-H,-BINAP gives a key intermediate for the
synthesis of a non-peptide AVP V2-agonist, OPC-5 1803 (Otsuka Pharmaceutical
 2.9.2.3 Pyrethroids 563

RU - L'
y
2 C Q H + HZ CH30H - N(C2H& 'COpH
\
F
28 29 94 % ee
(84% ee)

mibefradil (30)

Scheme 8. Preparation of the intermediates for mibefradil.

Co.) in 98 % yield with 76 % ee. Enantiomerically pure its (R)-amide is obtained

by recrystallization from methanol [311.
A Rh' catalyst with (R,R)-MeDuPHOS is effective for the asymmetric hydroge-
nation of sterically congested functionalized olefins, a key intermediate in the syn-
thesis of Tipranavir, an HIV protease inhibitor 1321. The cationic Rh' catalyst is
found to enable an highly efficient and enantioselective hydrogenation of a unique
carboxylate for the 12-kg reaction scale production of candoxatril, a cardiovascu-
lar agent 1331.

2.9.2.3 Pyrethroids
Pyrethroids occupy a central position among insecticides because of their high se-
lectivity and low toxicity [34]. Chrysanthemic esters (33), the carboxylic acid com-
ponents of this important class of compounds, can be synthesized by asymmetric
cyclopropanation of olefins (cf. Section 3.1.7) by diazoacetates in the presence
of a chiral Schiff base-Cu complex (Scheme 9 and Structures 34 and 35) 135-371.
This asymmetric carbene reaction has been extended successfully, but in an un-
expected direction [37]. Thus, as illustrated in Scheme 10, the cyclopropane syn-
thesis is now used for the industrial synthesis of Cilastatin (36), which acts as an
excellent in vivo stabilizer of the antibiotic Imipenem (37) (Merck & Co., USA, and
Sumitomo Chemical Co. Ltd., Japan). Chiral bisoxazolidine-Cu complexes (Struc-
tures 38 and 39) also exhibit high efficiency in asymmetric cyclopropanation [38].
564 2.9 Asymmetric Syntheses

0.5-1 mol %
chiral cat.
+ N2CHC02R . .
H C02R
33
R Chiral catalyst ee [%I

Scheme 9. Asymmetric synthesis of chrysanthemic esters.

Chiral catalyst ee [%I

92

38

39 > 99

Scheme 10. Asymmetric synthesis of a Cilastatin intermediate.

 2.9.2.5 Simple Secondary Alcohols 565

2.9.2.4 Prostaglandins
Prostaglandins are autacoids regulating diverse functions in the human body. The
three-component synthesis (Scheme 11) is the most efficient, straightforward
method for the preparation of these naturally scarce substances [39]. The requisite
(R)-4-hydroxy-2-cyclopentenonederivative [(R)-401 is most conveniently ob-
tainable by kinetic resolution of the appropriate racemic allylic alcohol by
BINAP-Ru"-catalyzed hydrogenation. Since 3-hydroxycyclopentanone under-
goes rapid dehydration to give volatile 2-cyclopentenone during the silylation
procedure, enantiomerically pure crystalline (R)-40 is easily separated from the
product mixture [40]. This synthesis is performed on a multikilogram scale (Taka-
sago International CorporationReijin Ltd., Japan). The optically active lower side
chains are obtainable by kinetic resolution by the Sharpless epoxidation [41] or
the BINAL-H asymmetric reduction of the corresponding enones [42].

1. RL
,i + Zn(cH3)~
2. R,I HMPA C02CH3
>

TBDMSO TBDMSO OTBDMS

(4-40
0
W H HQ
G H

A- +
/ /

HO OH HO OH
prostaglandin E prostaglandin F
-
Li
R,Li R,I= I/ - CO2CH3
OTBDMS

TBDMS f-C4H9(CH3)2Si

Scheme 11. Three-component synthesis of prostaglandins.

2.9.2.5 Simple Secondary Alcohols

Chiral secondary alcohols are one of the most valuable key intermediates for the
synthesis of pharmaceuticals and advanced materials. The well-organized molecu-
lar catalyst 43, consisting of BINAP-Ru" and the chiral diamine, effects highly
enantioselective hydrogenation of simple, unfuctionalized ketones to give second-
ary alcohols with over 99 % ee in 100 % yield (Scheme 12) [43]. In the presence
of base, an alkali, the reaction proceeds in 2-propanol at room temperature under
566 2.9 Asymmetric Syntheses

0 (S)-BINAP-RUCI~
y
Ar & -k H2(1-8 bar)
(S)-46, KOH
(CH&CHOH * ArAR
up to 97 % ee

catalyst - K2CO3
&+
\ HP(80atrn) (CH3)2CHOH
41
SIC = 100,000 97% ee

catalyst =

43; Ar = 3,5-(CH3)2C~H3

Scheme 12. Asymmetric hydrogenation of unfunctionalized ketones.

NH-i-C4Hg
0 ?H

44

Scheme 13. Asymmetric hydroboration of ketones. 45

0.1-0.8 MPa of hydrogen with a high substratekatalyst molar ratio, up to 100 000,
and with a high substrate concentration. The catalyst system is notable for its
excellent chemoselectivity of the carbonyl group over olefinic or acetylenic
bonds. Under identical conditions benzalacetone (41) is converted into the (S)-
ally1 alcohol 42 in 97 9% ee [43c].
 2.9.2.5 Simple Secondary Alcohols 567

Hydroboration of simple ketones catalyzed by proline-derived oxazaborolidine

45 provides a practical method for the preparation of chiral secondary alcohols
(Scheme 13). Under this protocol, a key intermediate in the synthesis of
MK-04 17 (44), a water-soluble carbonic anhydrase inhibitor, has been prepared
[44]. Reduction of acetophenone derivatives gives intermediates which are suita-
ble for the preparation of ENA-7 13 (Novartis), an acetylcholinesterase inhibitor
[45]. Chiral chromans are reduced stereoselectively by oxazaborolidine-catalyzed
hydroboration to give the potent antiarrhythmia agent MK-0499, which acts as a
potassium channel blocker [46].
Asymmetric transfer hydrogenation with a chiral ruthenium complex is an alter-
native option for preparation of substituted phenethyl alcohols, which are im-
portant building blocks for the agricultural fungicide, @)-MA20565 [47]. In the
enantioselective synthesis of antidepressant sertraline (50), different chiral second-
ary alcohols have been proposed as pivotal intermediates (Scheme 14). Reduction
of the keto ester 46 catalyzed by oxazaborolidine 45 provides chiral intermediate
47 in 90 % ee [48]. Alternatively, reductive fragmentation of C2-symmetric oxa-
tricyclic alkene 48 with DIBAL catalyzed by a BINAP-Ni' complex generates
a novel intermediate 49 in 88 % yield with 91 % ee [49].
The preparation of aliphatic chiral secondary alcohols by practically feasible
chemical methods is one of the major goals in asymmetric synthesis. Asymmetric
addition of aliphatic functionalized organozinc reagents to aldehydes in the pre-
sence of chiral bis-sulfonamides is a potential and diverse option for the synthesis
of chiral aliphatic secondary alcohols. The requisite oraganozinc reagents can be
prepared by a halogen-free process, comprising hydroboration of terminal olefins
with diethylborane followed by a boron-zinc exchange reaction with diethylzinc
[50].Desymmetrization of a C2-symmetric silyl ethers by ring closure metathesis
reaction catalyzed by chiral molybdenum complexes is a well-designed method
for the preparation of a protected chiral secondary alcohol bearing potential func-
tional groups [Sl].

HO.,, p C 0 2 -t-C4Hg

CI CI

a 46

48
+ DIBAL
47 OH

49
CI
sertraline (50)

Scheme 14. Preparation of simple secondary alcohols.

568 2.9 Asymmetric Syntheses

2.9.2.6 Amino Alcohols and Related Compounds

Stereoselective synthesis of optically active ,&amino alcohols is highly desirable,
because such units are seen ubiquitously in the structures of many biologically
active compounds represented by neurotransmitter antagonists, antimicrobials,
and pain killers. Hydroboration of the a-bromo ketone 51 promoted by the
amino alcohol 54 gives a key intermediate 52 for the synthesis of the (R,R)-isomer
of Formoterol (53),a long acting P,-agonist used in the treatment of asthma
(Scheme 15) [52].
Asymmetric reduction of p- or y-functionalized alkyl aryl ketones provides a
wide variety of chiral amino alcohols. Commercial p-chloropropiophenone is
reduced with borane-tetrahydrofuran adduct catalyzed by oxazaborolidine 45 to
provide the chlorohydrin in over 99 % yield with 94 % ee. The resulting alcohol
is a key intermediate for synthesis of the R form of fluoxetine (Prozac'), a
serotonin-uptake inhibitor [53]. Using hydrogenation processes the functionalized
amino ketones are converted directly into the respective products [S, 43el.
Under the influence of chiral phosphine-transition metal complexes, a-amino
ketones are hydrogenated to the corresponding optically active P-amino alcohols
(Scheme 16). Biologically active amino alcohols are obtainable in > 90 % ee by
the Rh- and Ru-catalyzed homogeneous hydrogenation [43e, 54-56] using 55 or
56 as ligands.
Other chiral phosphine/transition metal complexes catalyze the hydrogenation
of a-pyridyl ketones (to biologicaly active amino alcohols like (R,S)-Mefloquine,
an antimalarial agent (Hoffmann-La Roche [30]) or of a-benzamide ketones to

ligand =

54

Scheme 15. Preparation of formoterol.

 2.9.2.6 Amino Alcohols and Related Compounds 569

R’
N
0
,)R2R3 + -
H~ chiral cat. R’ &NR2R3

R’ R2 R3 Chiral catalyst H2 MPa e e [ % ]

Rh(NBD)[(R)-(S)-BPPF-OH]CIO,
3,4-(HO)zC& CH3 H 95
(1 rnol%), N(C2H5)3
CH3 CH, (R)-BINAP-Ru” (0.2 mol%) 10 95

2 91

CH3 CH3 43 0.8 93 (S)

\ I
P(C6H5)2 CONHCH3
55 56
(R)-(S)-BPPF-OH (2S,4S)-MCCPM

Scheme 16. Asymmetric hydrogenation of a-amino ketones.

(R)-Denopamine [43e]. Kinetic resolution is also a potential process for the

preparation of chiral a-amino alcohols [43] or other chiral building blocks
(such as (R)-(-)-phenylephedrine as a potent adrenergic agent with the help of
Co-salen [57, 581). The Sharpless expoxidation (cf. Section 3.3.2) offers a route
to the fluorine-containing broad-spectrum antibacterial agent Florfenicol (Sche-
ring-Plough [59]). The enantioselective hydrogenation of imines with ligand-mo-
dified Ir complexes has been used successfully for the commercial synthesis of the
herbicide (S)-Metolachlor by Novartis [60].
An (S)-BINAP-Ru catalyst promotes hydrogenation of the chloro keto ester
very rapidly at 100 “C to give the (R)-chlorohydrin in 97 % ee and 91 % yield
(Scheme 17) [61]. This serves as an intermediate for the synthesis of carnitine
(57), an important agent responsible for the transport of long-chain fatty acids
through the mitochondria1 membrane. In a like manner, hydrogenation of acetol
in the presence of an (R)-BINAP-Ru catalyst affords (R)-1,2-propanediol in
94% ee [%I, which is now used for the industrial synthesis of the antibacterial
Levofloxacin (58) (Daiichi Pharmaceutical Co./Takasago International Corpora-
tion, Japan). The asymmetric hydrogenation of an a-hydroxy ketone to (R)-diol
acts as a key step in the asymmetric synthesis of the broad-spectrum fungicide
Propiconazole (59) [34].
p-Adrenergic blocking agents including Propranolol(62), for example, are now
among candidate drugs for “racemic switches” (drugs that are currently marketed
as racemates but, for pharmacological reasons, are to be switched to the pure
enantiomers) [62]. Scheme 18 shows an approach to solve this practical problem.
570 2.9 Asymmetric Syntheses

100 "C, 4 min 57

HoA Hz, (R)-BINAP-Ru

*HO\/\
OH
--
CZHSOH

58

,,& Hz, (R)-BINAP-Ru

CH30H
9 H
OH
O A --
CI

Scheme 17. Asymmetric hydrogenation of functionalized ketones.

Hoe
+ f-C4HgOOH
Ti(O-i-C3H7)4
(S,S)-diethyl tartrate *
C H ~ C ~ ~
Hoa

Scheme 18. Asymmetric synthesis of /3-blocker intermediates.

 2.9.2.6 Amino Alcohols and Related Compounds 57 1

The Sharpless asymmetric epoxidation of allyl alcohol gives the glycidol deri-
vative 61 in 90% ee after in situ tosylation of 60 [63]. This process is working
on a multiton-a-year scale (Arco Co., USA), facilitating the synthesis of a variety
of ,&blockers. Asymmetric dihydroxylation of the allyl ether 63 catalyzed by a
combined system of Os04 and the cinchona alkaloid-based ligand 65 allows the
commercial synthesis of the propranolol intermediate 64 in 91 % ee (Sepracor Co.,
USA) [64].
The asymmetric nitroaldol reaction between naphthoxyacetoaldehyde and
nitromethane (1 :50 ratio) is effected by the (R)-BINOL-La complex 67 to give
66 with 92 % ee in 80 % yield, an intermediate for (S)-Propranolol (Scheme 19)
[65,66] (cf. Section 3.2.5).

%O
C
,H
,O + CH3N02
10 mol % 67
THF, -50 "C
~ koJN
k2 60 h
66

67

Scheme 19. Asymmetric nitroaldol reaction.

e,,,
8
OH

1 mol % Mn"'L* (69)

* 4-

+ NaOCl CH&, pH 11.3

Scheme 20. Asymmetric synthesis of Indinavir.

572 2.9 AsymmetricSyntheses

The enantioselective ring opening of epoxides with salen-Cr complexes yields

intermediates for the manufacture of (R)-9-[2-(phosphonomethoxy)propyl]ade-
nine [67] (a prophylactic against SIV infection). 0s-catalyzed asymmetric amino-
hydroxylation (ligand modified by cinchona alkaloids) leads to a-hydroxy-b-
phenylalanine, a derivative for the C13 chain of taxol [68].
Due to the demand for inexpensive anti-HIV agents, several reactions for the
synthesis of Indinavir (70, an HIV protease inhibitor of Merck & Co.) have
been reported. Enantioselective epoxidation of simple alkenes with bleach is
achievable in the presence of the Mn"' complex 69 possessing a well-designed
chiral salen ancillary [69]. Scheme 20 exemplifies its application to the synthesis
of Indinavir (70), by way of indene oxide (68) in 88 % ee [69]. This method is also
useful for the asymmetric synthesis of a chromene epoxide in 97 % ee serving as
an intermediate for Lemakalim, a K'-channel opening agent [70].

2.9.2.7 Amino Acids

Enantiomerically pure amino acids are naturally abundant and also available
by biotechnology. However, since bioactive peptides or their mimics composed
entirely of natural amino acids are readily metabolized in vivo, extensive studies
have been done to create more cultivated drugs containing unnatural nonpro-
teinaceous amino acids. The requisite unnatural components in > 90 % ee are
most efficiently obtained when chiral phosphine-Rh+-catalyzed asymmetric hy-
drogenation of a-acylaminoacrylic acids or esters is the key step (Scheme 21).
Kagan's pioneering work in this field has encouraged the design of a range
of chiral phosphine ligands, especially those having a C2 symmetry [71]. In
addition to the DIOP ligand, CHIRAPHOS [72], DIPAMP [73], BINAP [lfl,
and DuPHOS [74] (Structures 71-75) and others [75-781 are particularly effective
in this context.

chiral phosphines: pyOCH3

71 72 73 74 75
(FI)-BINAP (R,R)-CHIRAPHOS (R,R)-DIPAMP DuPHOS (SS-DIOP

Scheme 21. Asymmetric synthesis of amino acid derivatives.

 2.9.2.7 Amino Acids 573

OH OCOCH3
Z isomer

I
OCOCH3 oH 76

Scheme 22. Industrial synthesis of L-DOPA.

77
Scheme 23. Asymmetric synthesis of Clozylacon.

Scheme 22 illustrates an industrial synthesis of L-DOPA (76) by Monsanto,

USA. Other intermediates are manufactured similarly [79]. Relevantly, an (S)-
BINAP-Ru" catalyst effects enantioselective hydrogenation of the suitable
enamide (substrate:catalyst = 4000: 1) to give, after recrystallization, optically
pure Clozylacon (77), an excellent fungicide (Scheme 23) [34].
Valuable intermediates 78 for a novel synthesis for (+)-biotin (79), which is
referred to as vitamin H, are obtained effectively by use of a rhodium catalyst
with the ferrocenyl diphosphine 70 (Scheme 24) [80]. The optimized process is
suitable for industrial production.
Enantioselective synthesis of Cilazapril, an angiotensin converting enzyme
inhibitor, is another successful example of hydrogenation of dehydroamino acids.
A tetrahydropyridazinecarboxylic acid is hydrogenated using a substratekatalyst
molar ratio of 40 000 to give 95 to 97 % ee. A single crystallization affords the
enantiomerically pure isomer in > 95 % yield [20]. Asymmetric aminohydroxyla-
tion of styrenes is employed successfully in the syntheses of enantiomerically pure
a-arylglycines to investigate the inhibition of nitric oxide synthase [811.
574 2.9 Asymmetric Syntheses

R=HorCH3 a R = H ; 90% ee

- - H
HN NH
R = CH3 ; 98% de

v ' H - C obiotin
2 (79) H

80

Scheme 24. Asymmetric synthesis of biotin.

The glyoxylate-ene reaction, promoted by the Ti-BINOL complex, produces

chiral a-hydroxy esters, which provide an easy access to the corresponding
carboxylic acid derivatives bearing a chiral center at the a position. The adduct
between the glyoxylate and ex0 olefin is roposed as a key intermediate of
B
the collagenase-selective inhibitor, Trocade (Hoffmann-La Roche) [20].This
remarkable process has been developed for large-scale production.

2.9.2.8 Alkaloids
In the presence of a catalytic amount of RuX,[(R)- or (S)-BINAP] (X = anionic
ligand), a wide array of (Z)-2-acyl-2-benzylidene-l,2,3,4-tetrahydroisoquinolines
(81) are hydrogenated to give the saturated product 82 in very high (up to
100 %) optical yield (Scheme 25) [82].The discovery of this method has realized
a general asymmetric synthesis of isoquinoline alkaloids including morphine (83)
and its analogues such as morphinans (84) and benzomorphans (85).
Hydrogenation of the enamide 86 with a Ru catalyst and MeOBIPHEP 31 gives
a feasible approach to the antitussive agent dextromethorphan (89) (Scheme 26).
The readily available imine substrate 87 is hydrogenated using an Ir catalyst with
the ferrocenyl diphosphine 88, albeit with a relatively low substratekatalyst molar
ratio of 1500 and an ee of 89% [20].
Metal-catalyzed allylic substitution has been demonstrated to be one of the
most versatile procedures for constructing C-C, C-0, and C-N bonds enantio-
selectively. Since the a-allylpalladium intermediate generated in situ is C,-
symmetric, the sense of the substitution is controlled by the chiral environment
 2.9.2.8 Alkaloids 575

HO

HO..,,

., .: NR
H A
83 84 85

Scheme 25. General asymmetric synthesis of isoquinoline alkaloids.

H2 -
RU-31
98% ee
%bL* 89% ee

OCHq OCH3 OCH3

86
H3(? H 11 X=COCHB,H
87

OCH3
PAr2 dextromethorphan (89)
88 ; Ar = C6H2-3,5-(CH3)2-4-(OCH3)

Scheme 26. Asymmetric synthesis of dextromethorphan.

induced by the ligand. Starting from a racemate-catalyzed allylic amination in the

presence of 5.6 mol % of (S)-BINAPO followed by Zr-promoted diene cyclization
gives an attractive approach to (-)-Mesembnne [83].
Another application of enantioselective allylic substitution is seen in the syn-
thesis of (-)-galanthamine, the parent member of the galanthamine-type Ama-
ryllidaceae alkaloids. Displacement of the carbonate group in the racemate with
the phenol is accomplished by the Pd catalyst in the presence of the chiral ligand
1841.
576 2.9 Asymmetric Syntheses

2.9.2.9 Carbapenem Antibiotics

The BINAP-Ru-catalyzed asymmetric hydrogenation of the a-substituted b-keto
ester 90 provides a powerful tool for the synthesis of carbapenems of type 93,
a new generation of /?-lactam antibiotics (Scheme 27). Under hydrogenation
conditions, configurationally labile 90 readily undergoes stereo-inversion at the
a position. In addition, the BINAP-Ru catalyst facilely discriminates between
the enantiomers of 90, giving preferentially the syn hydrogenation product 91.
Consequently, the reaction of racemic 90 catalyzed by (R)-BINAP-Ru complex
results in (2S,3R)-91 with 93 % selectivity among four stereoisomers in an
enantio- and diastereoselective manner. The chiral product 91 can be converted
to 92, a common intermediate for synthesis of carbapenem antibiotics [85b].
Takasago International Corporation, Japan, is now producing 80 tons a year of
92 using this stereoselective hydrogenation via dynamic kinetic resolution [55b,
85c, 861.

C02CHB (R)-BINAP-Ru"
100 bar H2
CHpCIp
~ /r.(co*cH3
--
TBDMSO

*NH

NHCOCGHS NHCOCGHS
(+)-go 91

RuCI~ TBDMSO
CH3CO3H

-
CH3COzH

Y O C H 3
SR

TBDMw
Scheme 27. Asymmetric synthesis of a carbapenem intermediate.

H H2 TBDMSO

- NH
Ru catalyst

NH
4-

N /
SR

94 95 96 COPH

Ru catalyst b:a

Ru(OCOCH~),[(R)-TOI-BINAP] 99.9:O.l
Ru(OCOCH~),[(S)-TO~-BINAP] 22:78

Scheme 28. Stereoselective synthesis of a ID-methylcarbapenem intermediate.

 2.9.2.10 Sulfoxides 577

The BINAP-Ru-catalyzed hydrogenation of the allylic alcohol 94 results in the

diastereoselective formation of 95, an intermediate for ID-methylcarbapenems
(96) possessing an improved stability toward dehydropeptidase (Scheme 28).
The combined effects of the intermolecular asymmetric induction caused by the
(R)-Tol-BINAP-Ru catalyst (Tol-BINAP = p-tolyl analog of BINAP) and the in-
tramolecular asymmetric induction originating from the pre-existing chiral moiety
in the substrate 94 cooperate in the generation of the extremely high diastereos-
electivity, P:a = 99.9:0.1, to form the P-methylated isomer 96 [87].

2.9.2.10 Sulfoxides
Chiral sulfoxides have become an important class of compounds as chiral
auxiliaries in asymmetric syntheses, as metabolites of sulfide-containing drugs,
and also as biologically active ingredients themselves. Kagan’s modification of
the titanium-tartrate reagent by adding one mole equivalent of water has paved
the way for a practical synthesis of chiral sulfoxides [88].
The recently launched Esomeprazole (97, AstraZeneca), which is the (S)-isomer
of the anti-ulcer drug, Omeprazole (a typical racemic switch agent) is effectively
synthesized by employing diethyl tartrate (DET), titanium tetraisopropoxide, and
cumene hydroperoxide with > 9 0 % yield and >90% ee (Scheme 29) [89].
Under optimal conditions an amazing cost performance is realized to produce
Esomeprazole cheaper than the racemic Omeprazole [89b].
Other intermediates for an ACAT inhibitor RP73 163 (RhBne-Poulenc Rorer)
[90] and a potassium channel opener RP52891 (RhGne-Poulenc Rorer) [91] are
obtained in a similar manner. An intermediate for OPC-29030 (Otsuka Pharma-
ceutical Co.), which exhibits potent inhibition of platelet adhesion, requires
mandelic acid as the alternative chiral ligand, instead of DET [92].

(S,S)-diethyl tartrate
Ti(O-kC3H7)4
w

CH30 H20

esomeprazole (97)
>90% yield
>90% ee

Scheme 29. Preparation of biologically active chiral sulfoxides.

578 2.9 Asymmetric Syntheses

2.9.2.11 1,2-Diols and Related Compounds

Asymmetric dihydroxylation (AD) represents a general and reliable tool for
obtaining chiral 1,2-diols, due to its high enantioselectivity and substrate toler-
ance. The AD reaction of special olefins using (DHQD),PHAL 65 affords
the diol, which is an intermediate for the potent COX-2 inhibitor L-784512
(Merck & Co.), in 90% yield with 79% ee [93].
The synthetic utility of the AD reaction will be significantly upgraded when
recycling of the toxic and costly osmium compounds and oxidants is achieved
by considering environmental and chemical engineering factors. Recently, oxygen
or air has been employed in the reoxidation process of 0s'" (Scheme 30). At
slightly elevated oxygen pressure (3 bar) with 0.1 mol % of catalyst, the AD
reaction of a-methylstyrene proceeds in good yields, albeit with lower enantio-
selectivity [94].

93% yield
Scheme 30. Asymmetric dihydroxylation by oxygen. 79% ee

A synthesis of phyllodulcin, which is a sweet component of the amacha plant in

Japan that exhibits antimicrobial activity, relies on an AD reaction using commer-
cially available AD-mix-a [95]. Another practical application of an AD reaction
using N-methylmorpholine N-oxide as a reoxidant has been reported for the
2.5-kg scale synthesis of a chiral diol [96].

2.9.2.12 Miscellaneous
The BINAP-Ru-catalyzed hydrogenation has also been used in the synthesis of
a novel melatonin agonist TAK-375 (Takeda Chemical Industries), which is a
new agent for sleep disorders. Hydrogenation of an allylic amide, which is an unu-
sual class of substrate, proceeds smoothly with excellent enantioselectivity of
95 % [97]. The process for the enantioselective synthesis of (+)-&-methyl
dihydrojasmonate, which is the only stereoisomer out of the four diastereomers
that has a fragrant smell (Firmenich S.A, Hedion@),relies on hydrogenation in
the presence of a Ru-chiral diphosphine catalyst [98]. Use of suitable diphosphine
ligands and tert-butyl methyl ether as solvent is essential for obtaining good
enantioselectivity.
 2.9.2.12 Miscellaneous 579

Asymmetric epoxidation is applied to the synthesis of the novel ferroelectric

liquid crystals 99 that have the chiral truns-2,3-epoxy hexyl group as a core
moiety (Scheme 3 1). The (2S,3S)-epoxy alcohol 98, conveniently obtained in
86% ee, is transformed into the desired material in two steps [99]. A formal
synthesis of Brefeldin A (102), which shows a variety of biological activity re-
presented by antitumor, antifungal, and antiviral activity, is accomplished via a
highly enantioselective intramolecular hydroacylation of racemic pentanal 100
with 0.9% of cationic Rh[(S)-binap]'BF,-. A 1:l mixture of trans- and cis-
cyclopentanones 101 is obtained with a high enantiomeric excess of 96% for
each (Scheme 32). In the following step, the undesired cis-isomer is converted
into the thermodynamically favored truns-isomer for further transformation
[loo].

HO / t-C4H902H
Ti(O-X3H7)4
(R,R)-diethyl tartrate
*
HO-:
Hd
:

98
.a

86% ee

99

Scheme 31. Asymmetric synthesis of ferroelectric liquid crystals.

Rh[(S)-binap]+BF4-
OCH2CeHs
0Hc*0cH2c6H5 OTBDMS CH2C12, 3 h OTBDMS

100 101
96% ee
(cisltrans = 1/1)

brefeldin A (102)

Scheme 32. Asymmetric synthesis of an intermediate for brefeldin A.

580 2.9 Asymmetric Syntheses

2.9.3 Conclusions
Suitably designed chiral metal complexes can precisely discriminate between en-
antiotopic atoms, groups, or faces in achiral molecules and catalyze the formation
of a wide range of natural and unnatural substances of high enantiomeric purity.
Certain racemates can also be resolved by reactions with the chiral molecular cat-
alysts. Desymmetrization of C,-symmetric substrates and dynamic kinetic resolu-
tion of facile epimerizable substrates by chiral metal complexes are ingenious op-
tions for truly practical industrial production. Here proper combination of the me-
tals and chiral organic ligands is crucially important for obtaining a high degree of
stereoselectivity. Thanks to the diverse catalytic activities of metallic species,
coupled with the virtually unlimited permutability of the organic ancillaries, the
opportunities that asymmetric catalysis offers are enormous. Assisted by the pro-
gress in architectural and functional molecular engineering one can create tailor-
made molecular catalysts for the ideal production of chiral materials. The general
principle of achieving maximum chiral multiplication has in fact provided a major
breakthrough in modem organic synthesis. This synthetic strategy is now widely
utilized as access to optically active compounds at both academic and industrial
levels, because the efficiency rivals, or in certain cases exceeds, that of biological
processes. Although the utility has amply been demonstrated as exemplified
above, this chemistry is still young and full of promise.

References
[ I ] (a) H. B. Kagan, Comprehensive Organometallic Chemistry (Eds.: G. Wilkinson,
F. G. A. Stone, E. W. Abel), Vol. 8, Pergamon, Oxford, 1982, Chapter 53; (b) Asymmetric
Catalysis (Ed.: B. Bosnich), Martinus Nijhoff, Dordrecht, 1986; (c) I. Ojima, N. Clos,
C. Bastos, Tetrahedron 1989, 45, 6901; (d) Catalytic Asymmetric Synthesis (Ed.:
I. Ojima), VCH, New York, 1993; (e) H. Brunner, W. Zettlmeier, Handbook of Enantio-
selective Catalysis, VCH, Weinheim, 1993; (0 R. Noyori, Asymmetric Catalysis in
Organic Synthesis, John Wiley, New York, 1994; (g) Comprehensive Asymmetric Cata-
lysis I-IZI (Eds.: E.N. Jacobsen, A. Pfaltz, H. Yamamoto), Springer, Berlin, 1999;
(h) J. M. J. Williams in Catalysis in Asymmetric Synthesis, Sheffield Academic Press,
Sheffield, UK, 1999; (i) M. Wills, H. Tye, J. Chem. SOC.,Perkin Trans. 1 1999, 1109;
(j) Catalytic Asymmetric Synthesis (Ed.: I. Ojima), 2nd ed., Wiley-VCH, Weinheim,
2000: (k) L. Haughton, J. M. J. Williams, J. Chern. SOC.,Perkin Trans. 1 2000, 3335;
(1) H. Tye, J. Chem. Soc., Perkin Trans. 1 2000, 275.
[2] Reviews on practical applications: (a) S. L. Blystone, Chem. Rev. 1989, 89, 1663;
(b) J. Crosby, Tetrahedron 1991, 47, 4789; (c) W. A. Nugent, R. J. McKinney, F. W.
Hobbs, Jr., F. J. Waller in Homogeneous Transition Metal Catalyzed Reactions
(Eds.: W. R. Moser, D. W. Slocum), American Chemical Society, Washington, DC,
1992, Chapter 32; (d) J. Carey, Chem. BI: 1993, 29, 1053; (e) W. A. Nugent, T. V. Ra-
janBabu, M. J. Burk, Science 1993, 259,479; ( f ) S. Kotha, Tetrahedron 1994, 50, 3639;
(e) W. A. Nugent, T. V. RajanBabu, M. J. Burk, Science 1993, 259, 479; ( f ) S. Kotha,
Tetrahedron 1994, 50, 3639; (g) Chirality in Industry ZI (Eds.: A. N. Collins, G. N. Shel-
drake, J. Cosby), John Wiley, New York, 1997.
 References 58 1

[3] Reviews: (a) J. M. Brown, P. A. Chaloner in Homogeneous Catalysis with Metal

Phosphine Complexes (Ed.: L. H. Pignolet), Plenum, New York, 1983, Chapter 4;
(b) K. E. Koenig in Catalysis of Organic Reactions (Ed.: J. R. Kosak), Marcel Dekker,
New York, 1984, Chapter 3; (c) K. E. Koenig in Asymmetric Synthesis (Ed.: J. D. Mor-
rison), Vol. 5 , Academic Press, Orlando, 1985, Chapter 3; (d) R. S. Dickson, Homoge-
neous Catalysis with Compounds of Rhodium and Iridium, D. Reidel, Dordrecht,
1985, Chapter 3.10; (e) H. Brunner, Top. Stereochem. 1988, 18, 129; (f) R. Noyori,
M. Kitamura in Modern Synthetic Methods (Ed.: R. Scheffold), Vol. 5 , Springer, Berlin,
1989, p. 115; (g) R. Noyori, Science 1990,248, 1194; (h) H. B. Kagan, M. Sasaki in The
Chemistry of Organophosphorus Compounds, Vol. 1 (Ed.: F. R. Hartley), John Wiley,
New York, 1990, Chapter 3; (i) D. Amtz, A. Schafer in Metal Promoted Selectivity in
Organic Synthesis (Eds.: A. F. Noels, M. Graziani, A. J. Hubert), Kluwer Academic,
Dordrecht, 1991, p. 161; (i) H. Takaya, T. Ohta, K. Mashima in Homogeneous Transition
Metal Catalyzed Reactions (Eds.: W. R. Moser, D. W. Slocum), American Chemical
Society, Washington, DC, 1992, Chapter 8; (k) J. Albrecht, U. Nagel, Angew. Chem.,
Int. Ed. Engl. 1996, 35, 407; (1) S. Itsuno in Organic Reactions, Vol. 52 (Eds.: L.A.
Paquette et al.), John Wiley, New York, 1998, Chapter 2; (m) J. P. GenEt, Curr: Trends
Org. Synth., Int. Con$ 12th 1999, 229; (n) R. Noyori, T. Ohkuma, Angew. Chem. Int.
Ed. Engl. 2001, 40, 40.
141 Reviews: (a) I. Ojima, K. Hirai in Asymmetric Synthesis (Ed.: J. D. Momson), Vol. 5 ,
Academic Press, Orlando, 1985, Chapter 4; (b) H.-G. Schmalz, Comprehensive Organic
Synthesis (Eds.: B. M. Trost, I. Fleming), Vol. 4, Pergamon, Oxford, 1991, Chapter 1.5;
(c) K. Burgess, M. J. Ohlmeyer, Chem. Rev. 1991, 91, 1179; (d) K. Burgess, M. J. Ohl-
meyer in Homogeneous Transition Metal Catalyzed Reactions (Eds.: W. R. Moser,
D. W. Slocum), American Chemical Society, Washington, DC, 1992, Chapter 11;
(e) T. Hayashi, Y. Uozumi, Pure Appl. Chem. 1992, 64, 191I ; (0S. Wallbaum, J. Mar-
tens, Tetrahedron: Asymmetry 1992, 3, 1475.
[S] Reviews: (a) B. E. Rossiter in Asymmetric Synthesis (Ed.: J. D. Morrison), Vol. 5 ,
Academic Press, Orlando, 1985, Chapter 7; (b) W. Adam, M. J. Richter, Acc. Chem.
Res. 1994, 27, 57; (c) P. Besse, H. Veschambre, Tetrahedron 1994, 50, 8885; (d) T. Kat-
suki, V. S. Martin in Organic Reactions, Vol. 48 (Eds.: L. A. Paquette et al.), John Wiley,
New York, 1996, Chapter 1.
[6] Reviews: (a) B. B. Lohray, Tetrahedron: Asymmetry 1992, 3, 1317; (b) H.C. Kolb,
M. S. VanNieuwenhze, K. B. Sharpless, Chem. Rev. 1994, 94, 2483; (c) R. A. Johnson,
K. B. Sharpless in Catalytic Asymmetric Synthesis, 2nd ed. (Ed.: I. Ojima), Wiley-
VCH, Weinheim, 2000, Chapter 6D, p. 357.
[7] Reviews: (a) G. Wilke, Angew. Chem., Znt. Ed. Engl. 1988,27, 185; (b) T. V. RajanBabu,
N. Nomura, J. Jin, B. Radetich, H. Park, M. Nandi, Chem. Eul: J . 1999, 5, 1963.
[8] Reviews: (a) J. K. Stille, Comprehensive Organic Synthesis (Eds.: B. M. Trost, I. Flem-
ing), Vol. 4, Pergamon, Oxford, 1991, Chapter 4.5; (b) I. Ojima, C.-Y. Tsai, M. Tzamar-
ioudaki, D. Bonafoux in Organic Reactions, Vol. 56 (Eds.: L. E. Overman et al.), John
Wiley, New York, 2000, Chapter 1.
[9] Reviews: (a) G. Maas, Top. Cum Chem. 1987, 137, 75; (b) J. Salaun, Chem. Rev. 1989,
89, 1247; (c) A. Demonceau, A. J. Hubert, A. F. Noels in Metal Promoted Selectivity in
Organic Synthesis (Eds.: A. F. Noels, M. Graziani, A. J. Hubert), Kluwer Academic,
Dordrecht, 1991, p. 237; (d) M. P. Doyle in Homogeneous Transition Metal Catalyzed
Reactions (Eds.: W. R. Moser, D. W. Slocum), American Chemical Society, Washington,
DC, 1992, Chapter 30; (e) A. Padwa, D. J. Austin, Angew. Chem., Znt. Ed. Engl. 1994,
33, 1797.
[lo] Review: S. Otsuka, K. Tani in Asymmetric Synthesis (Ed.: J. D. Morrison), Vol. 5 ,
Academic Press, Orlando, 1985, Chapter 6.
582 2.9 Asymmetric Syntheses

[ 111 Reviews: (a) W. Keim, A. Kohnes, T. Rothel in Organic Synthesis via Organometallics
(Eds.: K. H. Dotz, R. W. Hoffmann), Vieweg, Braunschweig, 1991, p. 15; (b) H.-H.
Brintzinger in Organic Synthesis via Organornetallics (Eds.: K. H. Dotz, R. W. Hoff-
mann), Vieweg, Braunschweig, 1991, p. 33; (c) R. L. Halterman, Chem. Rev. 1992,
92, 965.
[12] Reviews: (a) D. A. Evans, Science 1988, 240, 420; (b) R. Noyori, M. Kitamura, Angew.
Chem., Int. Ed. Engl. 1991, 30, 49; (c) K. Soai, S. Niwa, Chem. Rev. 1992, 92, 833;
(d) L. Pu, H.-B. Yu, Chem. Rev. 2001, 101, 757.
[13] Reviews: (a) G. Consiglio, R. M. Waymouth, Chem. Rev. 1989, 89, 257; (b) J . C. Fiaud
in Metal Promoted Selectivity in Organic Synthesis (Eds.: A. F. Noels, M. Graziani, A. J.
Hubert), Kluwer Academic, Dordrecht, 1991, p. 107; (c) M. Sawamura, Y. Ito, Chem.
Rev. 1992, 92, 857; (d) 0. Reiser, Angew. Chem., Int. Ed. Engl. 1993, 32, 547;
(e) B. M. Trost, D.L. V. Vranken, Chem. Rev. 1996, 96, 395.
[ 141 Reviews: T. Hayashi, M. Kumada in Asymmetric Synthesis (Ed.: J. D. Morrison), Vol. 5,
Academic Press, Orlando, 1985, Chapter 5.
[15] Reviews: (a) T. Bach, Angew. Chem., Int. Ed. Engl. 1994, 33, 417; (b) S.G. Nelson,
Tetrahedron: Asymmetry 1998, 9, 357; (c) P. Arya, H. Qin, Tetrahedron 2000, 56,
917; (d) T. D. Machajewski, C.-H. Wong, Angew. Chem. Int. Ed. Engl. 2000, 39, 1352.
[16] Reviews: (a) L. A. Paquette in Asymmetric Synthesis (Ed.: J. D. Morrison), Vol. 3,
Academic Press, Orlando, 1984, Chapter 7; (b) E. J. Corey, Pure Appl. Chem. 1990,
62, 1209; (c) K. Narasaka, Synthesis 1991, 1 ; (d) H. B. Kagan, 0. Riant, Chem. Rev.
1992, 92, 1007; (e) B. B. Lohray, V. Bhushan, Angew. Chem., Int. Ed. Engl. 1992,
31, 729; (f) U. Pindur, G. Lutz, C. Otto, Chem. Rev. 1993, 93, 741; (8) L. Deloux,
M. Srebnik, Chem. Rev. 1993, 93, 763; (h) H. Waldmann, Synthesis 1994, 535;
(i) T. Oh, M. Reilly, Org. Prep. Proc. Int. 1994, 26, 129; (j)K. A. Jerrgensen, Angetv.
Chem., Int. Ed. Engl. 2000, 39, 3558.
[17] Reviews: (a) K. Mikami, M. Shimizu, Chem. Rev. 1992, 92, 1021; (b) K. Mikami,
M. Terada, S. Narisawa, T. Nakai, Synlett 1992, 255; (c) K. Narasaka, N. Iwasawa in
Organic Synthesis: Theory and Applications (Ed.: T. Hudlicky), Vol. 2, JAI Press,
Greenwich, 1993, p. 93; (d) K. Mikami, M. Terada, M. Shimizu, T. Nakai, J. Synth.
Org. Chem. Jpn. 1990, 48, 292.
[18] (a) K. Tani, T. Yamagata, S. Akutagawa, H. Kumobayashi, T. Taketomi, H. Takaya,
A. Miyashita, R. Noyori, S. Otsuka, J. Am. Chem. Soc. 1984, 106, 5208; (b) S. Otsuka,
K. Tani, Synthesis 1991, 665.
[19] H. Takaya, T. Ohta, N. Sayo, H. Kumobayashi, S. Akutagawa, S. Inoue, I. Kasahara,
R. Noyori, J. Am. Chem. Soc. 1987, 109, 1596.
[20] R. Schmid, M. Scalone in Comprehensive Asymmetric Catalysis 111 (Eds.: E. N. Jacob-
sen, A. Pfaltz, H. Yamamoto), Springer, 1999, p.1439.
[21] A. S. C. Chan, CHEMTECH 1993, 23(3), 46.
[22] T. Ohta, H. Takaya, M. Kitamura, K. Nagai, R. Noyori, J. Org. Chem. 1987, 52, 3174.
[23] (a) K. T. Wan, M.E. Davis, Nature (London) 1994,370, 449; (b) K.T. Wan, M. E. Davis,
Tetrahedron: Asymmetry 1993, 4, 2461; (c) K. T. Wan, M. E. Davis, J. Chem. Soc.,
Chem. Commun. 1993, 1262.
[24] J. K. Stille, H. Su, P. Brechot, G. Paninello, L. S. Hegedus, Organometallics 1991,
10, 1183.
[25] N. Sakai, S. Mano, K. Nozaki, H. Takaya, J. Am. Chem. Soc. 1993, 115, 7033.
[26] H. Alper, N. Hamel, J. Am. Chem. Soc. 1990, 112, 2803.
[27] (a) T. V. RajanBabu, A. L. Casalnuovo, J. Am. Chem. Soc. 1992, 114, 6265; (b) A. L.
Casalnuovo, T. V. RajanBabu, T. A. Ayers, T. H. Warren, J. Am. Chem. Soc. 1994,
116, 9869.
[28] T. Hayashi, A. Yamamoto, M. Hojo, Y. Ito, J. Chem. Soc., Chem. Commun. 1989, 495.
 References 583

[29] M. A. McGuire, S. C. Shilcrat, E. Sorenson, Tetrahedron Lett. 1999, 40, 3293.

[30] R. Schmid, E.A. Broger, M. Cereghetti, Y. Crameri, J. Foricher, M. Lalonde, R.K.
Miiller, M. Scalone, G. Schoettel, U. Zutter, Pure Appl. Chem. 1996, 68, 131.
[31] T. Shinohara, K. Kondo, H. Ogawa, T. Mori, K. Nozaki, T. Hiyama, Chirality 2000,
12, 425.
[32] M. J. Burk, Symposium “Chiral USA 2000“, Boston.
[33] M. J. Burk, F. Bienewald, S. Challenger, A. Derrick, J. A. Ramsden, J. Org. Chem. 1999,
64, 3290.
[34] G. M. Ramos Tombo, D. BelluS, Angew. Chem., Znt. Ed. Engl. 1991, 30, 1193.
[35] H. Nozaki, S. Moriuti, H. Takaya, R. Noyori, Tetrahedron Lett. 1966, 5239.
[36] R. E. Lowenthal, S. Masamune, Tetrahedron Lett. 1991, 32, 7373.
[37] T. Aratani, Pure Appl. Chem. 1985, 57, 1839.
[38] D. A. Evans, K. A. Woerpel, M. M. Hinman, M. M. Faul, J. Am. Chem. Soc. 1991,
113, 726.
[39] M. Suzuki, Y. Morita, H. Koyano, M. Koga, R. Noyori, Tetrahedron 1990, 46, 4809.
[40] M. Kitamura, I. Kasahara, K. Manabe, R. Noyori, H. Takaya, J. Org. Chem. 1988,
53, 708.
[41] S. Okamoto, T. Shimazaki, Y. Kobayashi, F. Sato, Tetrahedron Lett. 1987, 28, 2033.
[42] R. Noyori, I. Tomino, M. Yamada, M. Nishizawa, J. Am. Chem. Soc. 1984, 106, 6717.
[43] (a) T. Ohkuma, H. Ooka. S. Hashiguchi, T. Ikariya, R. Noyori, J. Am. Chem. Soc. 1995,
117,2675; (b) T. Ohkuma, H. Ooka, T. Ikariya, R. Noyori, J. Am. Chem. Soc. 1995, 117,
10417; (c) T. Ohkuma, M. Koizumi, H. Doucet, T. Pham, M. Kozawa, K. Murata,
E. Katayama, T. Yokozawa, T. Ikariya, R. Noyori, J. Am. Chem. Soc. 1998, 120,
13529; (d) T. Ohkuma, M. Koizumi, M. Yoshida, R. Noyori, Org. Lett. 2000, 2, 1749;
(e) T. Ohkuma, D. Ishii, H. Takeno, R. Noyori, J. Am. Chem. Soc. 2000, 122, 6510.
[44] (a) T. K. Jones. J. J. Mohan, L. C. Xavier, T. J. Blacklock, D. J. Mathre, P. Sohar, E. T. T.
Jones, R. A. Reamer, F. E. Roberts, E. J. J. Grabowski, J. Org. Chem. 1991, 56, 763;
(b) P. J. Reider, Symposium “Chiral ’93 USA”, Virginia, 1993, p. 65.
[45] C.-P. Chen, K. Prasad, 0. Repic, Tetrahedron Lett. 1991, 32, 7175.
[46] (a) Y.-J. Shi, D. Cai, U.-H. Dolling, A. W. Douglas, D. M. Tschaen, T. R. Verhoeven, Tet-
rahedron Lett. 1994, 35, 6409; (b) D. M. Tschaen, L. Abramson, D. Cai, R. Desmond,
U.-H. Dolling, L. Frey, S. Karady, Y.-J. Shi, T. R. Verhoeven, J. Org. Chem. 1995, 60,
4324.
[47] (a) M. Miyagi, J. Takehara, S. Collet, K. Okano, Org. Process Res. Dev. 2000,4,346; (b)
K. Tanaka, M. Katsurada, F. Ohno, Y. Shiga, M. Oda, M. Miyagi, J. Takehara, K. Okano,
J. Org. Chem. 2000, 65, 432.
[48] (a) J.-C. Caille, M. Bulliard, B. Laboue in Chirality in Industry II (Eds.: A. N. Collins,
G. N. Sheldrake, J. Cosby) John Wiley, New York, 1997, p. 398; (b) G. J. Quallich, T. M.
Woodall, Tetrahedron 1992, 48, 10239.
[49] M. Lautens, T. Rovis, J. Org. Chem. 1997, 62, 5246.
[50] F. Langer, L. Schwink, A. Devasagayaraj, P.-Y. Chavant, P. Knochel, J. Org. Chem.
1996, 61, 8229.
[Sl] S.S. Zhu, D.R. Cefalo, D.S. La, J.Y. Jamieson, W.M. Davis, A.H. Hoveyda, R.R.
Schrock, J. Am. Chem. Soc. 1999, 121, 8251.
[52] (a) C. H. Senanayake, Symposium “Chiral USA 2000“, Boston; (b) R. Hett, Q. K. Fang,
Y. Gao, S. A. Wald, C.H. Senanayake, Org. Process Res. Dev. 1998, 2, 96.
[53] E. J. Corey, G. A. Reichard, Tetrahedron Lett. 1989, 30, 5207.
[54] T. Hayashi, A. Katsumura, M. Konishi, M. Kumada, Tetrahedron Lett. 1979, 425.
[55] (a) M. Kitamura, T. Ohkuma, S. Inoue, N. Sayo, H. Kumobayashi, S. Akutagawa,
T. Ohta, H. Takaya, R. Noyori, J. Am. Chem. Soc. 1988, 110, 629; (b) T. Miura in
Aspects of Industrial Chiral Technology (Eds.: T. Nakai, T. Ohashi), 1998, CMC, p. 143.
584 2.9 Asymmetric Syntheses

[56] H. Takahashi, S. Sakuraba, H. Takeda, K. Achiwa, J. Am. Chem. SOC.1990, 112, 5876.
[57] M. K. Gurjar, L. M. Krishna, B. V.N.B. S. Sarma, M. S. Chorghade, Org. Process Res.
Dev., 1998, 2, 422.
[58] (a) M. Tokunaga, J.F. Larrow, F. Kakiuchi, E.N. Jacobsen, Science, 1997, 277, 936;
(b) S.C. Stinson, Chem. Eng. News 2000, 78, 35.
[59] G. Wu, D. P. Schumacher, W. Tormos, J. E. Clark, B. L. Murphy, J. Org. Chem. 1997,
62, 2996.
[60] (a) H.-U. Blaser, F. Spindler in Comprehensive Asymmetric Catalysis III (Eds.: E. N.
Jacobsen, A. Pfaltz, H. Yamamoto), Springer, Berlin, 1999, p. 1427; (b) F. Spindler,
H.-U. Blaser, Enantiomer, 1999, 4, 557.
[61] M. Kitamura, T. Ohkuma, H. Takaya, R. Noyori, Tetrahedron Lett. 1988, 29, 1555.
[62] S.C. Stinson, Chem. Eng. News 1999, 77, 101.
[63] J. M. Klunder, S. Y. KO, K. B. Sharpless, J. Org. Chem. 1986, 51, 3710.
[64] (a) E. N. Jacobsen, I. Mark6, W. S. Mungall, G. Schroder, K. B. Sharpless, J. Am. Chem.
SOC. 1988, 110, 1968; (b) K. B. Sharpless, W. Amberg, Y. L. Bennani, G. A. Crispino,
J. Hartung, K . 3 . Jeong, H.-L. Kwong, K. Morikawa, Z.-M. Wang, D. Xu, X.-L. Zhang,
J. Org. Chem. 1992, 57, 2768; (c) K. B. Sharpless, Symposium “Chirul ’94 USA”,
Virginia, 1994, p. 17.
[65] (a) H. Sasai, T. Suzuki, S. Arai, T. Arai, M. Shibasaki, J. Am. Chem. Soc. 1992, 114,
4418; (b) H. Sasai, T. Suzuki, N. Itoh, K. Tanaka, T. Date, K. Okamura, M. Shibasaki,
J. Am. Chem. Soc. 1993, 115, 10372.
[66] N. Yoshikawa. Y. M. A. Yamada, J. Das, H. Sasai, M. Shibasaki, J. Am. Chem. Soc. 1999,
121, 4168.
[67] J.F. Larrow, S.E. Schaus, E.N. Jacobsen, J. Am. Chern. SOC.1996, 118, 7420.
[68] H. C. Kolb, K. B. Sharpless in Transition Metals for Organic Synthesis, V01.2 (Eds.:
M. Beller, C. Bolm), Wiley-VCH, Weinheim, 1998, p. 243.
[69] (a) W. Zhang, J. L. Loebach, S. R. Wilson, E. N. Jacobsen, J. Am. Chem. SOC. 1990, 112,
2801; (b) S. Stinson, Chem. Eng. News 1994, 72(20), 6; (c) D. Askin, M. A. Wallace,
J. P. Vacca, R. A. Reamer, R. P. Volante, I. Shinkai, J. Org. Chem. 1992, 57, 2771;
(d) C. H. Senanayake, F. E. Roberts, L. M. DiMichele, K. M. Ryan, J. Liu, L. E. Freden-
burgh, B. S. Foster, A. W. Douglas, R. D. Larsen, T. R. Verhoeven, P. J. Reider, Tetra-
hedron Lett. 1995, 36, 3993; (e) I. W. Davies, P. J. Reider, Chem. Ind. 1996, 412.
[70] E. N. Jacobsen, W. Zhang, A. R. Muci, J. R. Ecker, L. Deng, J. Am. Chem. SOC.1991,
113, 7063.
[71] H.B. Kagan, T.-P. Dang, J. Am. Chem. SOC.,1972, 94, 6429.
[72] M. D. Fryzuk, B. Bosnich, J. Am. Chem. SOC.1977, 99, 6262.
[73] (a) W. S. Knowles, Acc. Chem. Res. 1983, 16, 106; (b) W. S. Knowles, M. J. Sabacky,
B. D. Vineyard, D. J. Weinkauff, J. Am. Chem. SOC.,1975, 97, 2567.
[74] (a) M. J. Burk, J. Am. Chem. SOC.1991, 113, 8518; (b) M. J. Burk, J. R. Lee, J. P.
Martinez, J. Am. Chem. SOC.1994, 116, 10847.
[75] U. Nagel, Angew. Chem. Int. Ed. Engl. 1984, 23, 435.
[76] T. Imamoto, J. Watanabe, Y. Wada, H. Masuda, H. Yarnada, H. Tsuruta, S. Matsukawa,
K. Yamaguchi, J. Am. Chem. Soc. 1998, 120, 1635.
[77] M. J. Burk, J. E. Feaster, R. L. Harlow, Tetruhedron:Asymmetiy 1991, 2, 569.
[78] J. Holz, M. Quirmbach, U. Schmidt, D. Heller, R. Stunner, A. Borner, J. Org. Chem.
1998, 63, 8031.
[79] M. Adamczyk, S. R. Akireddy, R. E. Reddy, Org. Lett. 2000, 2, 3421.
[80] (a) A. Togni, Angew. Chem. Znt. Ed. Engl. 1996, 35,1475; (b) J. McGarrity, F. Spindler,
R. Fuchs, M. Eyer, JP 06.340.669 (Chem. Abstr. 1995, 122, 81369).
[81] (a) R.N. Atkinson, L. Moore, J. Tobin, S.B. King, J. Org. Chem., 1999, 64, 3467;
(b) K. L. Reddy, K.B. Sharpless, J. Am. Chem. SOC.1998, 120, 1207.
 References 585

[82] M. Kitamura, Y. Hsiao, M. Ohta, M. Tsukamoto, T. Ohta, H. Takaya, R. Noyori, J. Org.

Chem. 1994, 59, 297.
[83] M. Mori, S. Kuroda, C . 3 . Zhang, Y. Sato, J. Org. Chern. 1997, 62, 3263.
[84] B.M. Trost, F. D. Toste, J. Am. Chem. Soc. 2000, 122, 11262.
[85] (a) R. Noyori, T. Ikeda, T. Ohkuma, M. Widhalm, M. Kitamura, H. Takaya, S. Akuta-
gawa, N. Sayo, T. Saito, T. Taketomi, H. Kumobayashi, J. Am. Chem. Soc. 1989, 111,
9134; (b) S. Murahashi, T. Naota, T. Kuwabara, T. Saito, H. Kumobayashi, S. Akuta-
gawa, J. Am. Chem. Soc. 1990, 112, 7820; (c) R. Noyori, M. Tokunaga, M. Kitamura,
Bull. Chern. SOC.Jpn. 1995, 68, 36.
[86] T. Matsumoto, T. Murayama, S. Mitsuhashi, T. Miura, Tetrahedron Lett. 1999,40,5043.
[87] M. Kitamura, K. Nagai, Y. Hsiao, R. Noyori, Tetrahedron Lett. 1990, 31, 549.
[88] (a) S. H. Zhao, 0. Samuel, H. B. Kagan, Tetrahedron 1987,43,5135;(b) H. B. Kagan in
Catalytic Asymmetric Synthesis, 2nd ed. (Ed.: I. Ojima), Wiley-VCH, Weinheim, 2000,
p. 327.
[89] (a) E. M. Larsson, U. J. Stenhede, H. Sorensen, P.0. S.V. Unge, H. K. Cotton, WO 96/
02.535 (Chem. Abstr. 1996, 125, 585 16); (b) H.-J. Federsel, Symposium “ChiraSource
2000“, Lisbon, Portugal, 2000.
[90] P. Pitchen, C. J. France, I. M. McFarlane, C. G. Newton, D. M. Thompson, Tetrahedron
Lett. 1994, 35, 485.
[Y 11 (a) P. Pitchen in Chirality in Industry f I (Eds.: A. N. Collins, G. N. Sheldrake, J. Cosby),
John Wiley, New York, 1997, Chapter 19, p. 381; (b) P. Pitchen, Symposium “Chiral
‘95 USA”, Boston, 1995, p. 9.
[92] M. Matsugi, N. Fukuda, J. Minamikawa, S. Otsuka, Tetrahedron Lett. 1998, 39, 5591.
[93] L. Tan, C. Chen, R. D. Larsen, T. R. Verhoeven, P. J. Reider, Tetrahedron Lett. 1998,
39, 3961.
[94] C. Dobler, G. M. Mehltretter, U. Sundermeier, M. Beller, J. Am. Chem. Soc. 2000, 122,
10289.
[95] A. Ramacciotti, R. Fiaschi, E. Napolitano, J. Org. Chem. 1996, 61, 5371.
[96] L. Ahrgren, L. Sutin, Org. Proc. Res. Dev. 1997, I , 425.
[97] S. Ohkawa, 0. Uchikawa, K. Fukatsu, R. Tokunoh, M. Kawada, K. Matsumoto,
Y. Imai, K. Kato, H. Nishikawa, M. Miyamoto, XVI Int. Symp. Medicinal Chemistry,
Bologna, Italy, 2000, p. 384.
[98] (a) D. A. Dobbs, K. P. M. Vanhessche, E. Brazi, V. Rautenstrauch, J.-Y. Lenoir, J.-P.
GenEt, J. Wiles, S. H. Bergens, Angew. Chem. Int. Ed. 2000, 39, 1992; (b) V. Rauten-
strauch, fnt. Sym. Chirality, Cambridge, UK, 1999.
[99] D.M. Walba, R.T. Vohra, N.A. Clark, M.A. Handschy, J. Xue, D.S. Parmar, S.T.
Lagenvall, K. Skarp, J. Am. Chem. Soc. 1986, 108, 7424.
[loo] P. Ducray, B. Rousseau, C. Mioskowski, J. Org. Chem. 1999, 64, 3800.
 Applied Homogeneous Catalysis with Organometallic
Edited by Boy Cornils & Wolfgang A. Herrmann
© Wiley-VCH Verlag GmbH, 2002

586 2.10 Ferrocene as a Gasoline and Fuel Additive

2.10 Ferrocene as a Gasoline and

Fuel Additive
Wolfgang A. Herrmann

2.10.1 Introduction
Numerous organometallic catalysts have been employed in industrial syntheses of
organic compounds. Most famous are the Wilkinson catalysts, representing the
standard systems for the hydrogenation and hydroformylation, respectively, of
olefins.
While it is true that the majority of organometallic catalysts are generated
in situ, reliable synthetic procedures are available. Reference monographs [ 1, 21
can be consulted for details. Large-scale preparations are rarely described in the
literature, mainly because the respective companies keep their know-how secret.
Beyond that, little has been revealed in patents. In this Section, the industrial
catalyst ferrocene 1, an important catalytic fuel additive, is described.

2.10.2 Commercial Synthesis

Bis($-cyclopentadieny1)iron 1, called ferrocene to emphasize the benzene-analo-
gous reactivity (e. g., electrophilic alkylation and acylation), is not only the pio-
neer compound of organometallic chemistry [3-51. It is also a platform for a
plethora of derivatives and an efficient fuel additive, predominantly used in diesel
fuels. This commercial use is based on the property that ferrocene undergoes
homolytic decomposition under the conditions of fuel combustion. Ferrocene low-
ers the formation of soot particles upon combustion of diesel and ordinary fuel.
Ferrocene is a crystalline, largely air- and water-stable compound (mp.
172-173 "C and bp. 249 "C). It is oxidized chemically and electrochemically to
the stable monocation [(C5Hs),Fe]+', the fenicinium cation containing trivalent
iron; this one-electron step is fully reversible. Ferrocene is the only organoiron
compound which is soluble in mineral oil and gasoline. At the same time, it is
inert to all components in the oil tank.
For large amounts of ferrocene, none of the conventional laboratory-scale pre-
parations was sufficient: neither the iron-based conversion of dicyclopentadiene
(eq. (1)) is technically feasible on a large scale, nor the more expensive two-
step synthesis via sodium cyclopentadienide (eq. (2)).
 2.10.2 Comnzercial Synthesis 587

Fe CI0Hl2 - (C5H5)2Fe t H2

-
t (1)
Fe Br2 FeBr2 (24
-
t

FeBr2 t 2Nat[C5H5r (C5H5)2Fe t 2NaBr (2b)

While eq. (1) works only under harsh temperature conditions with concomitant
partial decomposition, the preparation of the sodium cyclopentadiene required by
eq. (2) is too expensive, with the purification process demanding Soxhlet extrac-
tion of the ferrocene with hydrocarbons. The same applies to the otherwise
convenient laboratory synthesis according to eq. (3), which avoids the step of
the sensitive sodium cyclopentadienide. Here, the acidic hydrogen of cyclopenta-
diene is stripped off by N-bases such as diethylamine.

Fe t Br2 - FeBq (34

FeBr2 t2 (C2H5)2NH t 2 C5Hs + (C5H5)2Fet 2 [(C2H5)2NH2]tBi (3b)

A technical synthesis was developed from 1965 until 1989 at the Chemische
Betriebe Pluto GmbH at Heme (Germany) [6]. Here, the divalent iron is first
generated by synproportionation. The useless NaCl is again the major drawback
of this approach. Also, elemental sodium is required.
In 1989, a novel, electrochemical process developed jointly with the Max-
Planck-Institut fur Kohlenforschung at M u l h e i a u h r (Germany) went into
operation. The process is based on earlier work of Lehmkuhl and Eisenbach
[7] and follows eq. (4). An iron anode is first used to form the reactive inter-
mediate iron(I1) ethoxide Fe(OC,H,), as an ethanol adduct. (The ethanol serves
as solvent and reactant.) Due to the Lewis-basic ethoxy ligands, (monomeric)
cyclopentadiene is deprotonated under mild conditions to form high-purity
ferrocene directly. This process has the advantage that the iron(I1) precursor
compound is not to be synthesized but is rather formed in situ without further
purification. Typical conditions of electrolysis are 120 A at 13 V at 0.8 rn2 X
10 mm iron anodes. A pilot plant converts 2.5 kg of iron per day. The working
temperature is 60 "C.

Fe
(anode)
t 2C2H50H - Fe(OC2H5)2t H2

Fe(OC2H5)2t 2C5Hs - (C5H5)2Fe t 2C2H50H

(recycled)
(4b)

Fe t 2 C5H6 - (C5H5)2Fe t H2 (4)

NaBr (0.15 M) is used as the conducting salt. The iron(I1) ethoxide must be
separated from the electrolyte. The work-up by sublimation follows. A flow
scheme of the technical process is shown in Figure 1 [7d].
588 2.10 Ferrocene as a Gasoline and Fuel Additive

1 synthesis I
electrolysis
I
I

anode 1 w I distillation

I
I
I
I

I
I

I
Retro-DielsAlder Cracking I
.
r
of dicyclopentadiene to reaction solution

Figure 1. Industrial synthesis of ferrocene: @ ligand preparation; @ electrosynthesis of

Fe(OC2H&; @ synthesis of (C5H5)*Fe.

2.10.3 The Gasoline and Fuel Additive

Ferrocene is distributed by Octel Deutschland GmbH, Heme (Germany), under
the tradename PLUTOcen@ [6] as a catalyst for chemical oxidation processes,
e. g., in mineral oil, diesel fuel, raw oil, “Bunker C” (ship diesel), and pyrotech-
nical devices. It acts as octane-booster in Otto gasoline, and reduces the burning
and smoke formation of plastics. Normally, additive amounts of 15-120 ppm are
sufficient [6]. Positive effects of PLUTOcen@additives are, e. g., higher burnout
of carbon and hydrocarbons (fuel efficiency), constant turbocharger efficiency,
increased time between overhauls, or reduced risk of exhaust gas boiler fires.
It can be seen from Figure 2 that only 30 g of ferrocene per ton of gasoline
(30 ppm) raises the MON by ca. 1.0 units and the RON by ca. 1.4 units. The
lower the octane number of the gasoline, the more efficient is this particular
additive. Conventional organic booster additives (e. g., cyclohexane, methyl
t-butyl ether, benzene) increase the volume of the gasoline, but this does not
apply to ferrocene. This is shown in Figure 2. Toxicological studies on the
exhaust gases show no disadvantage of ferrocene with regard to the untreated
gasoline [8].
 2.10.4 Related Antiknocking Additives 589

1,5

05

0,o 0,o
0 15 30 0 15 30
C ferrocsns (ppm) C krrocsns (pprn) __+

Figure 2. Effect of ferrocene (upper curves) upon the octane number of gasoline (average
through 50 brands of gasoline and motor fuels): motor octane number (MON);
research octane number (RON). The MON corresponds to high rotational speed,
the RON corresponds to the engine acceleration [ 121.

Diesel engines have a 25-30 times higher carcinogenic potential compared with
Otto engines. This is due to the carbon particles consisting of soot and high-boil-
ing condensed aromatics. For this purpose, particle filters are used that must be
regenerated intermittently by heating beyond 500 "C. Since diesel engines reach
these temperatures only under full power, there is once again a demand for addi-
tives. Ferrocene is extremely efficient: the oxidation of soot has already started at
ca. 300 "C. Ferrocene-doped particle filters (e. g., in engines used for tunnel con-
struction) retain 98-99 % of the ultrafine, toxicologically hazardous particles. The
soot extrusion is reduced by 97-98 % with the filter alone, while the reduction is
99.9 % (based on the particle number) when the gasoline is charged with ferrocene
(see above). Ferrocene also improves the ignition and combustion behavior of
low-quality mineral oil. The total hydrocarbon emission is generally reduced.
Regarding the mechanism [9], there is evidence for the formation of iron oxides
encapsulated by the soot particles. These particles seem to maintain a catalytic
cycle. X-ray diffractometry showed that ferrocene decomposes in the colder
flame zones to iron oxide.

2.10.4 Related Antiknocking Additives

For some time, methylcymantrene ($-CH3CSH4)Mn(C0)3(MMT) has been used
as a substitute for the highly toxic tetraethyllead (C2H&Pb as a gasoline additive.
For one period, 40 % of the car gasoline sold in the United States contained MMT.
It has been claimed by General Motors, however, that MMT is disadvantageous
590 2.10 Ferrocene as a Gasoline and Fuel Additive

for catalytic converters [ 101. However, there is evidence of toxic combustion

products [lo], mainly manganese itself, for which reason MMT was prohibited
in California in 1977 [lo, 111. There is still a dispute on the toxicity, especially
in the range of 0.5 ,ug manganese per m3 air, attributed to the MMT additive.

References
[ l ] G. Wilkinson, Org. Synth. 1956, 36, 34.
[2] W. P. Fehlhammer, W. A. Herrmann, K. Ofele, in Handbuch der Pruparativen Anorgu-
nischen Chemie, Enke Verlag, Stuttgart 1981, Vol. 111, pp. 1842-1843.
[3] (a) T. J. Kealy, P. L. Pauson, Nature (London) 1951, 168, 1039; (b) S. A. Miller, J. A.
Tebboth, J. F. Tremaine, J. Chem. Soc. 1952, 632; (c) J. M. Birmingham, Adv. Organo-
met. Chem. 1964, 21, 365.
[4] Gmelin, Handbuch der Anorganischen Chemie, 8th ed. Suppl., Vol. 14, Part A, Springer,
Heidelberg, 1974.
[S] (a) Ref. [ l b], pp. 1843-1847; (b) Ref. [2], Vol. 1, p. 136.
[6] H. Jungbluth, G. Lohmann, Nachr: Chem. Techn. Labor. (Weinheim, Germany) 1999,47,
532-536.
[7] (a) Studiengesellschaft Kohle (W. Eisenbach, H. Lehmkuhl, G. Wilke), DBP 2.349.561
(1972); (b) Studiengesellschaft Kohle (H. Lehmkuhl, W. Eisenbach), DE 2.720.165
(1977); (c) W. Eisenbach, H. Lehmkuhl, Elektrolyse von Ferrocen, Dechema Mono-
graphien, Verlag Chemie, Weinheim, 1985, p. 269; (d) W. Eisenbach, H. Lehmkuhl,
Chem.-Ing. -Tech. 1982, 54, 690-69 1.
[8] U. Heinrich, ITA Fraunhofer Institute fur Toxikologie, Hannover (Germany), 1995.
[9] (a) P. Boncyk, United Technologies Report No. R 87-957464-A, 1987; (b) K. E. Ritrievi,
J. P. Longwell, A. F. Sarofim, Combust. Flume 1987, 70, 17; (c) J. B. A. Mitchell, D. M.
Miller, M. Sharpe, Combust. Sci. Technol. 1991, 74.
1101 Cf. Nachr: Chem. Techn. Labor: (Weinheim, Germany) 1977, 25, 224 and 692.
[11] Cf. Chem. Eng. News 1977, 84(16), 17.
[ 121 K. P. Schug, H. J. Guttmann, A. W. Preuss, K. Schadlich, Effects of Ferrocene as a
Gasoline Additive on Exhaust Emission and Fuel Consumption of Catalyst Equipped
Vehicles, SAE Paper No. 900154, 1990.
 Applied Homogeneous Catalysis with Organometallic
Edited by Boy Cornils & Wolfgang A. Herrmann
© Wiley-VCH Verlag GmbH, 2002

2.11.2 Advantages and Drawbacks 591

2.11 The Suzuki Cross-Coupling

Wolfgang A. Herrmann

2.11.1 Introduction
The so-called Suzuki coupling reaction [l] is considered one of the most impor-
tant synthetic tools to make unsymmetrical biaryl building blocks [2]. It comprises
the coupling of aryl- or vinyl halides with arylboronic acids according to eqs. (1a)
and (lb). Palladium compounds are the catalysts of choice.

+ x
X R 2 -
- X-B(0H)p RZ

The products have a very high impact in organic fine chemicals synthesis, since
compounds displaying a biaryl linkage cover a broad spectrum of applications,
ranging from materials science (e. g., in non-linear optics) to pharmaceuticals.
For this reason, an intensive search for efficient coupling catalysts started in
around the time, when the first edition of this book appeared (1 996).

2.11.2 Advantages and Drawbacks

Not only is the scope of the Suzuki reaction broad, there is also an exceptional
tolerance of functional groups and an ability to couple sterically demanding sub-
strates. Furthermore, boronic acids are generally non-toxic and thermally, air- and
moisture-stable. They are easily available from aryl Grignard compounds and
methyl borate. The Suzuki coupling is largely unaffected by water (as opposed
to the Grignard cross-coupling) and proceeds regio- and stereoselectively. Simple
ligand-modified palladium salts, preferentially Pd" acetate, perform well as homo-
geneous catalyst precursors. A major drawback is the failure of alkyl halides to
couple with the arylboronic acids, mainly because of P-hydrogen elimination
upon oxidative addition to the Pd catalyst. Also, the low reactivity of aryl (and
vinyl) chlorides still necessitates significant improvements to the catalyst.
592 2.11 The Suzuki Cross-Coupling

2.11.3 Catalysts, Substrates, Conditions

2.11.3.1 Current Status

The standard Suzuki catalysts are complexes of zerovalent Pd of which Structures
1 and 2 are most frequently used.

II

In situ generation of Pdo species is also achieved by mixtures of Pd(OAc)2 and

organophosphines (under not strictly anhydrous conditions, to achieve the
Pd" 4 Pdo reduction). Reaction conditions are within a broad range, largely
depending on the nature of the organohalide to be C-C coupled. Typically,
basic conditions, e. g., K2C03, NaOH, TlOH, KOAc, K3P04,are applied at tem-
peratures from ambient to 130 "C. Dimethoxyethane and N,N-dimethylformamide,
1,4-dioxane, and toluene are most frequently seen as solvents.

2.11.3.2 Recent Catalyst Improvements

2.11.3.2.1 Palladacycles
Phenylboronic and 4-chloroacetophenone combine efficiently according to eq. (2)
at certain palladacycle catalysts (Structure 3), which are easily available from
Pd(OAc), and appropriate phosphines PR3 (e. g., R = o-tolyl). Turnover numbers
(TONS) of 75 000 are achieved with only 0.001 mol% 3 [3]. Several reports on
the catalysts of type 3 have substantiated the discovery of 1995 [3a]. As in
the Heck coupling, no aryl scrambling is observed with the palladacycle catalysts
[41.
Mechanistic considerations were communicated [4].

mQH
Cat. 3
(2)
+ c l ~ ( c H 3 - 130°C 3

K2C03
- CIB(OH)2 82 %
(at 0.1 mol-% 3)
 2.11.3.2 Recent Catalyst Improvements 593

2.11.3.2.2 N-Heterocyclic-Carbene-Palladium Catalysts

After the first report in 1998 [ 5 ] , Pd complexes of N-heterocyclic complexes
demonstrated their high catalyst efficiency in the Suzuki coupling [6-81. Both
isolated Pdo/Pd"-complexes such as Structures 4-6 [5-71 and in situ systems
like 7 and 8 [9, 101 have been used. N-Heterocyclic carbenes as ligands in transi-
tion-metal catalysis were also described [ 1I].

Ph, ,CH3
CH

I
CH R R
Ph' 'CH3

4 5 6
R = CH3, CC3H,, f-C4H9,
c-C6Hj1, mesityl

CH3
I

I
N
Pdz(dba)3 / H-C@l
Y

""9 CH3

7
H3

The least reactive aryl chlorides can thus be activated. For example, the cou-
pling following eq. (3) yields up to 90 % of the desired products [6]. The catalyst
loading of 0.02-0.05 mol % Pd is the lowest known as yet for the Suzuki coupling
594 2.11 The Suzuki Cross-Coupling

of aryl chlorides. TONS up to lo6 were observed for the coupling of 4-bromo-
acetophenone with phenylboronic acid [6].

(SB(0H)Z + CR
-I Cat. 5 m R (3) (3)
- - Xylene, 130°C - -
K2CO3 or C s ~ C 0 3
- CIB(OH)*
R = H, OCH3, C(=O)CH,

The in situ catalysts 7 and 8 - that clearly form Pd' catalytic species like 6 via
salt metathesis - were employed in subsequent work to couple non-activated aryl
chlorides at 80°C in 1,4-dioxane using Cs2C03as a base [9, LO]. Yields were as
high as 89-99 %. Extremely high reaction rates were recorded for the Suzuki
coupling of phenylbroronic acid with p-chlorotoluene using catalyst 6, R =
'C4H9: TON = 552 [mol prod . mol Pd-' . h-'I, the highest observed as yet [7].
Unfortunately, the catalyst lifetime is still low.

2.11.3.2.3 Phosphine-Palladium Catalysts

Aryl chlorides exhibiting electron-withdrawing substituents (e. g., NOz, C=N,
C(=O)CH,, C02CH3, C(=O)H, CF3, ArS02) undergo Suzuki coupling in the
presence of the phosphine catalysts 9 and 10 at 100-120°C, using N-methyl/
pyr NMP as the solvent and CsF as the base [12]. However, 5 mol% Pd was
necessary in most cases to furnish good yields.

P ~ ( O A CI )dppp
~ Pd2(dba), I P

9 10 11

The catalyst system 11, with an optimized P/Pd ratio of 1.0-1.5, does not
require electron-withdrawing substituents. Instead, p - and o-substituted aryl
chlorides having R = CH3, OCH3, NH2 give typical yields between 82 and
92% [13]. The electron richness and the steric bulk of tris(t-buty1)phosphane
seem to be the origin of the good catalytic performance. Obviously, only a single
phosphine is attached to the zerovalent Pd in the active state of the catalyst.
Bisarylphosphines combined with Pd(OAc)2 or Pd2(dba)3 - for example,
Structure 12 - have proven successful in the Suzuki coupling of non-activated
aryl chlorides, too [14-171. Related catalysts work with 0.5-2.0 mol% Pd at
80-130°C [18]. Ortho-substitution on one or both of the coupling partners is
possible, and both electron-donating and electron-withdrawing functional groups
are tolerated. It seems that P,O-chelation occurs in these particular catalysts
[19, 201.
 2.11.3.4 Suzuki-Related Coupling 595

(CH3)2N
13
12

Excellent activities in the coupling of all kinds of aryl chlorides were achieved
by use of catalyst 13 containing the bulky bis(adamantyl)(n-buty1)phosphane.
TONs of lo4 to 2 X lo4 were recorded even for non-activated aryl chlorides [23].
Quite recently, phosphine oxides according to the equilibrium in eq. (4) were used
with Pd2(dba)3in the Suzuki coupling of aryl chlorides, while a hydroxyphosphine
complex/Ni(COD), catalyzes the Kumudu coupling of the same substrates [26].

2.11.3.3 Two-Phase Catalysis

The polar, water-soluble phosphine TPPTS (trisodium salt of triphenylphosphane
m-trisulfonate, P(C6H4-m-S03Na)3;cf. Section 3.1.1.1) was the model for aryl-
B-0-glycosides of glucose, galactose, and glucosamine used as ligands L in the
two-phase Suzuki coupling of eq. (5). With P d L = 1:3, TONs of 8700 at 87 %
yield were observed with L = 14 [21].

- BrB(OH)2

OH loAC

14

2.11.3.4 Suzuki-Related Coupling

The introduction of the methylenecarboxylic group into functionalized molecules
is of particular interest for pharmaceuticals. GooBen [22] found that the bulky
ligand tris(a-naphthy1)phosphane effects C-C coupling according to eq. (6) in
the presence of Pd(OAc)2 under very mild conditions. Little biaryl coupling
596 2.11 The Suzuki Cross-Coupling

was observed. As seen from the yield-improving effect of small amounts of water,
a Pd' species formed in situ seems to carry the catalytic cycle.

- BrB(OH)2
R = OCH3, CN,NO*,C(=O)CH3
napht = a-naphthyl

2.11.4 Mechanism
There is strong evidence that zerovalent Pd is present in the active catalyst species,
although speculations on Pd" @ Pd'"equi1ibria are not unreasonable in the case of
the above-mentioned palladacycles (cf. [4]). The accepted mechanism is summar-

precursor

"X-B(OH)i'

Scheme 1. Textbook mechanism of the Suzuki coupling [4]

 References 597

ized in Scheme 1: Pdo species stabilized by at least one but typically two donor
ligands oxidatively add the aryl (vinyl) halide (Pd' + Pd") with consecutive
transmetallation by the arylboronic acid. The specific advantages of the N-hetero-
cyclic carbenes is seen in the strong C + Pd bonds, which undergo dissociation
much more reluctantly than in the case of alkylphosphines of similar a-basicity.
The ideal case is a chelating, strongly coordinated a-type ligand as in catalyst 4
PI.

2.11.5 Commercial Application and Further Development

The Suzuki reaction has already found a first industrial application [24], after the
catalyst Pd(TPPTS)3 . II H 2 0 became available [25]. In a two-phase procedure,
the water-soluble catalyst effects the C-C coupling of arylboronic acis with aryl
chlorides to form pharmaceutical intermediates. The Suzuki C-C cross-coupling
is on the way to industrial perfection. Since the basic mechanistic features are
clear by now, it is desirable that the catalysts are easy to prepare, easy to handle,
and cheap, and that they bear a-donor type ligands of which at least one does not
dissociate from the metal throughout the catalytic cycle. Thus the Suzuki coupling
will be seen in the syntheses of a growing number of fine chemicals and pharma-
ceuticals in due course.

References
(a) N. Miyaura, A. Suzuki, Chem. Commun. 1979, 866; (b) N. Miyaura, T. Yanagi,
A. Suzuki, Synth. Commun. 1981, 11, 513.
Reviews: (a) A. Suzuki, Pure Appl. Chem. 1991,63,419; (b) S. P. Stanforth, Tetrahedron
1998, 54, 263; (c) A. R. Martin, Y. H. Jang, Acta Chem. Scand. 1993, 47, 221;
(d) N. Miyaura, A. Suzuki, Chem. Rev. 1995, 95, 2457; (e) A. Suzuki, J. Organomet.
Chem. 1999, 576, 147; (f) N. Miyaura, in: Advances in Metal-Organic Chemistry
(Ed.: L. S. Liebeskind), London, 1998; (g) A. Suzuki, in Metal-Catalyzed Cross-
Coupling Reactions (Eds.: F. Diederich, P. J. Stang), Chapter 2, Wiley-VCH, New
York, 1998.
[3] (a) M. Beller, H. Fischer, W. A. Herrmann, K. Ofele, C. Brossmer, Angew. Chem., Znt.
Ed. Engl. 1995, 34, 1848; (b) T. H. Riermeier, A. Zapf, M. Beller, Top. Catal. 1997,
4, 301; (c) W.A. Henmann, Ch. Brossmer, T. Priermeier, K. Ofele, J. Organomet.
Chem. 1994, 481, 97.
[4] W. A. Herrmann, V. P. W. Bohm, C.-P. Reisinger, J. Organomet. Chem. 1999, 576, 23.
[5] W. A. Henmann, C.-P. Reisinger, M. Spiegler, J. Organomet. Chem. 1998, 557, 93.
[6] T. Weskamp, V. P. W. Bohm, W. A. Henmann, J. Organomet. Chem. 1999, 585, 348.
[7] V.P. W. Bohm, Ch. W.K. Gstottmayr, Th. Weskamp, W.A. Herrmann, J. Organomet.
Chem. 2000, 595, 186.
[8] Reviews: (a) W. A. Herrmann, Ch. Kocher, Angew. Chem. Int. Ed. Engl. 1997,36,2162;
(b) W. A. Henmann, Th. Weskamp, V. P. W. Bohm, Advan. Organomet. Chem. 2002, in
press; (c) W. A. Henmann, Angew. Chem. 2002, in press.
598 2.11 The Suzuki Cross-Coupling

[9] C. Zhang, J. Huang, M. L. Trudell, S. P. Nolan, J. Org. Chem. 1999, 64, 3804.
[lo] C. Zhang, M.L. Trudell, Tetrahedron Lett. 2000, 41, 595.
[ I l l Hoechst AG (W.A. Herrmann, M. Elison, J. Fischer, Ch. Kocher, K. Ofele),
DE 4.447.066 (1994).
[ 121 W. Shen, Tetrahedron Lett. 1997, 38, 5575.
[ 131 (a) A. F. Littke, G. C. Fu, Angew. Chem., Int. Ed. 1998,38,3387; (b) A. F. Littke, Ch. Dai,
G. C. Fu, J. Am. Chem. SOC. 2000, 122, 4020.
[14] D. W. Old, J. P. Wolfe, S. L. Buchwald, J. Am. Chem. Soc. 1998, 120, 9722.
[IS] J. P. Wolfe, R. A. Singer, B. H. Yang, S. L. Buchwald, J. Am. Chem. SOC. 1999, 121,
9550.
[16] J.P. Wolfe, S.L. Buchwald, Angew. Chem. 1999, 111, 2570; Angew. Chem., Int. Ed.
1999, 38, 2413.
[ 171 S. L. Buchwald, J. M. Fox, The Strem Chemiker, 2000, 18(I), 1.
[18] X. Bei, H. W. Turner, H. Weinberg, A. S. Guram, J. L. Petersen J. Org. Chem. 1999,
64, 6797.
[19] See, for example: X. Bei, T. Uno, J. Norris, H. W. Turner, J. Org. Chem. 1999, 64,4699.
[20] W. H. Weinberg, A. S. Guram, J. L. Petersen, Organometallics 1999, 18, 1840.
[21] M. Beller, J.G. E. Krauter, A. Zapf, Angew. Chem., Int. Ed. 1997, 36, 772.
[22] L. J. GooBen, Chem. Commun. 2001, 7, 679.
[23] A. Zapf, A. Ehrentraut, M. Beller, Angew. Chem., Int. Ed. 2000, 39, 4153.
[24] Hoechst AG (S. Haber, H.-J. Kleiner), DE 19.527.118 (July 25, 1995); cf. also Org. Proc.
Res. Dev. 1998, 2, 121.
[2S] (a) Hoechst AG (W. A. Herrmann, J. Kulpe, J. Kellner, H. Riepl), DE 3.840.600 (1988);
EP 0.672.674 (1989); (b) W. A. Herrmann, J. A. Kulpe, W. Konkol, H. Bahrmann,
J. Organomet. Chem. 1990, 389, 8 5 ; (c) W.A. Herrmann, in Synthetic Methods in
Organometallic and Inorganic Chemistry (Ed.: W. A. Henmann), Vol. 9, pp. 153-177,
Enke Verlag, Stuttgart, 2000.
[26] G.Y. Li, Angew. Chem. 2001, 113, 1561; Angew. Chem., Int. Ed. 2001, 40, 1513.
 3
Recent Developments
in Homogeneous Catalysis
 Applied Homogeneous Catalysis with Organometallic Compounds
Edited by B. Cornils and W. A. Herrmann
Copyright 0 Wiley-VCH Verlag GmbH, D-69469 Weinheim, 2002

3.1 Development of Methods

3.1.1 Homogeneous Catalysts and

Their Heterogenization or Immobilization
Boy Cornils, Wolfgang A. Herrmann

Besides the influence on the electronic and steric properties of organometallic

complex catalysts of suitable central atoms or ligands, the variation of the appli-
cation phase has been another subject of intensive research on homogeneous cata-
lysis ever since its beginning. Originally not recognizing the nature of that spe-
cial type of catalysis, the early 0x0 researchers, for example, started the hydrofor-
mylation reaction in a heterogeneous mode using fixed beds of Fischer-Tropsch
catalysts [ 11 - the other way of varying the application phase. Accordingly, appro-
priate techniques (“diaden” or “two-tower’’ processes [2]) have been used for
longer periods since they allowed an apparently elegant separation of catalyst,
substrates, and product.
Taking hydroformylation as a typical, homogeneously catalyzed process, Fig-
ure 1 demonstrates the different methods for the separation and the recycling of
the catalyst. Obviously, the shortest and thus least costly recycle and the minimal
thermal stress are achieved with the biphasic operation.
Together with the necessity of a low-cost separation of catalyst and product,
this shortcoming of homogeneous catalysis was always the impetus to try the
homogeneous mode with “heterogenized”, “immobilized’, or “anchored” cata-
lysts. Figure 2 demonstrates schematically the different approaches, once more
taking hydroformylation, as the most systematically investigated homogeneous
catalysis, as an example.
A fundamental distinction is to be made between “anchored” catalysts (lefthand
side of Figure 2) and the intrinsic phase variation. Anchored catalysts on fixed
supports are dealt with in Section 3.1.1.3. The more modern and obviously
more successful method of phase variation is with “multiphase catalysts” (a mod-
ification of which - “triphase catalysts” (TPC [3,4]) - are a genetic link between
heterogeneous and phase-transfer catalysis; cf. Section 3.2.4) as well as “two-
phase catalysts”, i. e., homogeneous catalysts on “mobile” supports. These
catalysts are divided into “aqueous biphasic systems” (cf. Section 3.1.1.1)
and “nonaqueous biphasic systems” (Section 3.1.1.2), among which are the
liquid/liquid biphasic variants which have already found industrial application
as aqueous biphasic systems. Intensive research work is presently underway on
liquid/liquid modifications of nonaqueous systems (cf. Section 3.1.1.2). Solid/
liquid and solid/gaseous variations of nonaqueous catalysts (e. g., for the oxychlori-
nation of methane, vinyl-chlorination of ethane, manufacture of monosilane, hy-
droformylation of ethylene - all in molten salt media [5, 61 - catalyst separation
as metal [7], or “precipitation” of the catalyst metal from homogeneous polymer-
izations by grafting of the polymer on the catalyst site or the wall of the apparatus
602 3.1 Development of Methods

Feedstock (substrate) S Reactant A-8

separation
Product P

c
Cat.
Membrane

Regeneration
J

Product P

OH- Steam O2
$.
-- Product P

+
Metal

Cat. + S

do 1 @ I Product P

Figure 1. The different methods of separation and recycling of 0x0 catalysts for the reaction
S + A-B -+ P [73]: @ aqueous biphasic operation; @ membrane technique;
@ thermal methods; @ chemical methods.

(“fouling”) [S]) are, like “solid supported catalyst”, links between homogeneous
and heterogeneous catalysis.
The transitions of “supported liquid-phase catalysts” (SLPC)and “supported
aqueous-phase catalysts” (SAPC) are dealt with in Section 3.1.1.3, while special
aspects of clusters and colloids are discussed in Sections 3.1.1.4 and 3.1.1.5 and
those of aqueous-phase, re-immobilized catalysts in Section 3.1. I .6. The com-
bination of heterogeneous catalysis with aqueous (biphasic) techniques is also
under investigation, e. g., [209].
 3.1.1.I Immobilization by Aqueous Catalysts 603

Homogeneous

Anchored [ P h a s e T a t io n l

Multiphase Catalysts

Two phase Catalysts

Tri P
y4-HCatalysts (PTC)

A
Liquid / Liquid
+- * .*

Figure 2. Different approaches of the variation of the application phase of 0x0 catalysts.
FBS = fluorous biphase [multiphase] system; PEG = polyethylene glycol;
NAIL = non-aqueous ionic liquid.

3.1.1.1 Immobilization by Aqueous Catalysts

Boy Cornils, Wolfgang A. Herrmann

3.1.1.1.1 Fundamentals
One of the most important developments of the last 15 years in homogeneous cat-
alysis is the introduction of the aqueous two-phase (“biphase”) technique. This
method uses a homogeneous catalyst, dissolved in water, as a “mobile” phase
(“mobile support”). By simple phase separation (decantation), catalyst and reac-
tantsheaction products are separated just after reaction and at approximately the
same temperature (cf. Figure 1). In relation to the reaction products the catalyst
is thus “immobilized” as well as “heterogenized” on “liquid supports”, but not
“anchored”. So the manifold advantages of homogeneous catalysis are supple-
mented by the argument that catalyst and reaction products may be separated
immediately after reaction without any chemical stress [9]. Only those systems
604 3.1 Development of Methods

(1) which use no additional measures - except for moderate temperature gradients
- to ensure the phase separation (e. g., application of solvents or co-solvents,
chemical derivatization), and
(2) which make possible the immediate start of new catalyst cycles in the same
phase and without any additional steps

are biphasic systems in the strict definition. There are plenty of processes with in-
termediate biphasic steps which are not in fact biphase catalytic conversions, e. g.,
the solution of catalyst precursors, the extraction of the homogeneous catalyst
with water after reaction, etc. [lo-151. In all these examples the homogeneous cat-
alyst or part of its cycle leaves the biphase. This ambiguity is the reason why the
search for literature about biphasic operation is often incomplete. Biphasic pro-
cesses which include temperature-induced phase separations may gain in impor-
tance (cf. Section 3. I . 1.1.2), as may reagent-controlled radical reactions as well
[210].
Some condensed papers [16, 17, 2111 review the fundamentals, the applica-
tions, and the limitations of aqueous-phase homogeneous catalysts and the special
role of water [21, 167, 201, 204, 2121. Various papers substantiate the advantages
of aqueous-biphasic versus purely homogeneous techniques, the effectiveness of
water-soluble over organic-soluble ligands for special substrates (e. g., [67,
213]), or the role of counter-ions within the ligands [215 a, b, 218 h, 244 k] or
of co-additives [2 15 c, d]. The overall solvatation capability (solvation power,
ETN)of various solvents from nonpolar, aprotic tetramethylsilane (TMS) to water,
which influences the reactivity considerably, is shown in Figure 3 (213 b]. Special

CI H P H IHzOJ
0 Acetm
DMF

DMSO
1-PrOH

EOH
CH20H

MeOH

.",",""",".,".."" L I \r V I i L '!l'Il'r 1' '11*"1*"11111

+ 1-
MeNHz CI (130 "C)

Figure 3. Empirical polarity values ETN

 3.1.1.1 Immobilization by Aqueous Catalysts 605

investigations have clarified the scene of the action (interfacial versus bulk of the
liquid [ 130, 2161). Not surprisingly, many papers from academic authors have
been published years after Manassen’s first proposal of the concept 1181 and
J6o’s 1281 and Baird’s follow-ups 1751, but also - remarkably - even years
after the first industrial application by Shell’s SHOP process (biphasic but not
aqueous [ 191) and RuhrchemieRhBne-Poulenc’s 0x0 process [9, 20, 1771. In
fact, this variation of the application phase completes the variation of homoge-
neous catalysts by ligand modification or by variation of the central atoms in a
conceptual way: the advantageous variation of the application phase normally re-
quires a preceding influence on the organometallic complex by ligand variation.
Aqueous homogeneous catalysts depend on the development of polar, and thus
water-soluble, ligands and their incorporation into organometallic complexes.
Therefore, the history of biphasic homogeneous catalysis begins with preparatory
work on various water-soluble ligands (cf. Table 1).
The solubility in water is usually achieved by introduction of highly polar sub-
stituents such as -S03H, -COOH, -OH, or -NH2 (or their salts) intothe phosphine
ligands [16-18, 21-23]; in other words and according to Cintas [214]: ... the “

[aqueous] approach can better be described as the chemistry of ligands and

supported reagents.”. By variation of the nature and number of suitable substi-
tuents and by choice of the conditions of the aqueous phase, almost any desired
ratio of hydrophilic and hydrophobic properties may be obtained, thus achieving
a “tailor-made” set of attributes for complex-forming ligands. For example, sulfo-
phenylphosphines dissolve in aqueous media at any pH, while carboxy- or amino-
substituted phosphines dissolve only in basic or acidic solutions, respectively.
The solubility of hydroxy phosphines depends on the nature of the parent
phosphine and on the number of hydroxy substituents. An especially fine tuning
of the ratio of hydrophilicity to hydrophobicity and an increase in hydrophilic
characteristics of the ligand is observed following the series

TPPMS < TPPDS < TPPTS

while introducing one (mono-, M), two (di-, D) or three (tri-, 7‘) rnetu-positioned
sulfo groups in triphenylphosphine. The water solubility of the ligands may be im-
parted to the metal complex catalysts via incorporation in complexes. The thermo-
dynamics of complex formation and the different ability of the transition metal
ions to bind different ligands forming “in-situ catalysts” have been investigated
carefully [25-30, 32-39, 74-76, 781. The syntheses of appropriate compounds
for water-soluble ligands and complexes have been reviewed by Herrmann and
Kohlpaintner [ 161. TPPTS will be supplied from customs/fine chemicals manufac-
turers (e. g., Aldrich) and is already the subject of standard preparative instructions
12241. A list of a variety of new water-soluble ligands is compiled in Table 2.
Higher (and supramolecular) ligands based on sugar, porphyrin, dendrimers,
cyclodextrins, calix[4]arenes, etc., have also been tested for water-soluble conver-
sions, the hydroformylation of water-insoluble olefins included [219]. In some
cases the water-soluble, macromolecular cpds. act as inverse phase-transfer cata-
lysts, e. g., when crown ethers are involved [269].
606 3.1 Development of Methods

Table 1. Water-soluble ligands for 0x0 homogeneous catalysts

[20, 22, 24-34, 74, 76, 77, 192, 1931.

COOH

1945 Gilrnan. Brown

1 12

[ O~P-(CHZ)~-COOH
1952 Mann, Millai
1964 Pettit, Irving

1977 Shaw
1976 Podlahova
et al.

1958 Ahland, Chatt

1975 JOo, Beck
1978 Wilkinson

TPPMS

1975 Kuntz / RhBne Poulenc

1987 Kuraray Corp.
2
TPPDS

1975 Kuntz / Rhone Poulenc

1982 Cornils / Ruhrchemie
3
TPPTS

op~CHzOCOCH~
1973 Chatt, Leigh, Slade
CHpOCOCHs

amphos

1973 Chatt et al.

1989 Harrison et al.

Ligands and complex catalysts derived therefrom may catalyze reactions under
circumstances which require aqueous or “mild” conditions, such as bioorganic
substrates (bioorganometallic conversions; cf. Section 3.3.10.2). However, the
great advantage of w ater-soluble catalysts is that they overcome the basic problem
of homogeneously catalyzed processes: the separation of the product phase from
the (molecular) catalyst itself, which is soluble in it. The unit operations necessary
to achieve this usually include thermal operations such as distillation, decomposi-
tion, transformation, and rectification, process steps which normally cause thermal
 3.1.1.1 Immobilization by Aqueous Catalysts 607

Table 2. New ligands for aqueous-phase catalysis [220].

Type of ligand Used for Ref.
[HO-alkyl-P(CH,)-] Hydrogenation [218 a]
Ph2P-a1 kylene-COOH Hydrogenation 1218 b]
Ph2P-CH*CH(R ' )C(=0)-R2 Hydrogenation [218c]
(PPhdiN' Hydrogenation [218d]
(Pheny1ethynyl)phosphonates Hydrogenation [218e]
Sulfonated BDPP"' Hydrogenation 1218 fl
Ph,P-aryl-OH (COOH) Hydroformy lation [217a, 218gl
PNS ') Hydroformy lation 1218 h]
BINAP type Hydroformy lation 1218 i]
NAPHOS type Hydroformy lation [218r]
Sulfonated xantphos Hydroformy lation 1218jl
Sulfonated DPPP" Copolymerization [218k]
(Ph2P-p-aryl-PO3)*-Me*+ Carbonylation 121811
Sulfonated bathophenantrolines Oxidation [218m]
Cinchona alkaloids Oxidation/dihydroxy lation 1218~1
Tris(pyrazolyl)methanesulfonates Enzyme-analog reactions 1218111
NaSPd' Rh and Pd complexes 121801
PPM" on polyacrylic acid Hydrogenation 1218Pl
Water-soluble polymers Various 1218ql
Carbohydrate-substituted phosphines Heck reaction
Suzuki coupling [218t]
BDPP = Bis( 1,2-diphenylphosphino)pentane,
'I PNS = Ph2P-CH&C( =O)NHC(CH3)2-CH2-S03Me.
DPPP = Bis( I ,2-diphenylphosphino)propane.
dl NaSP = Mono-, Bis-, or Tris-[2-(3-Na sulfonatopropy1)thioethyI diphenylphosphines.
PPM = (2S,4S)-4-diphenylphosphino-2-diphenylphosphinomethyl pyrrolidine.

stress on the catalyst (cf. Figure 1). This can accelerate decomposition reactions
and progressive deactivation during the lifetime of the catalyst. Furthermore, ther-
mal separation processes seldom ensure quantitative recovery of the catalyst,
which consequently causes loss of productivity through loss of catalytically active
metal.
Product separation is easier for biphasic systems, especially (but not only) those
incorporating the aqueous biphasic and water-soluble catalysts. Figure 4 (below)
608 3.1 Development of Methods

Figure 4. General principle of biphasic catalysis in water. The metal complex catalyst (C),
which is solubilized by hydrophilic ligands, converts the substrates (in this case
propene [S] and syngas [A-B]) to the products, which can be separated from the
catalyst (medium) by phase separation.

shows a hydrophilic catalyst which is insoluble in the organic product phase; it is

an (organometallic) coordination complex, and as such is molecularly well defined
like conventional homogeneous catalysts. It brings about the catalytic reactions -
e. g., C-C couplings - in the aqueous phase or at the phase boundary, and is re-
moved from the desired product at the end of the reaction by simple phase separa-
tion (cf. Ref. [16]). Because of the high polarity of the water-soluble catalyst and
its consequent insolubility in the organic phase, the loss rate is often below the
limits of detection. In this respect this biphasic “heterogenized” catalyst shows
no leaching, which so far is typical and disadvantageous for other heterogenized
and anchored catalysts. Characteristic data for metal removal from biphasic
hydroformylations have been given for RuhrchemieRhBne-Poulenc’s 0x0 pro-
cess [9].
Reaction rates achievable with biphasic systems are strongly dependent on the
polarity of the reacting substrates. For example, the Rh-catalyzed hydroformyla-
tion of propene using the water-soluble complex catalyst HRh(CO)(TPPTS),
(TPPTS = triphenylphosphine trisulfonate) takes place with the apparent activa-
tion energy of a homogeneous reaction, whereas with 1-hexene the rate-determin-
ing step appears to be mass transfer [40]. Therefore, although overall reaction
rates are sometimes lower than in homogeneous reactions, the simplicity of the
process for separating the product from the catalyst compensates for this disadvan-
tage.
The technical concept of biphasic catalysis is simple and allows an elegant pro-
cess design. Regarding the reciprocal miscibilities of the substrate and the catalyst
solution (S and C in Figure 5 ) , three basic modifications of the two-phase process
under the introductory prerequisites may be considered.
In all cases of the “ideal” biphasic operation (Figure 5 a), the reactor is shown
on the left, followed by the separation device and any further processing for purity
 3.1.1. 1 Immobilization by Aqueous Catalysts 609

Figure 5. Simplified flow diagrams for biphasic catalyses [16]: (a) product(s) P is completely
insoluble in the catalyst containing medium C - e. g., RuhrchemieRh6ne-Poulenc’s
0x0 process; (b) P is soluble or partly soluble in C; (c) the second phase is formed
during the catalytic process - e. g., Shell’s SHOP process.

or other properties, e. g., a distillation. An additional extraction isrequired in the

case of Figure 5 b, where the product P is partly soluble in the catalyst phase
C. This extraction is preferably done with fresh feedstock S, when S is insoluble
in C. It is also possible that a two-phase system forms from an initially uniform
phase during the reaction, because the product P is insoluble in the original
medium of the catalyst (Figure 5 c). Only when the products P are partly soluble
in the catalyst medium C, the separation unit is a solvent extraction step (related
to the distillative workup) that is necessary for the whole contents of the reactor.
A typical example for the “pure” version of this biphasic operation is Ruhrchemiel
Rh6ne-Poulenc’s 0x0 process [9, 20, 201, 2021, and for the version in Figure 5
(c), Shell’s SHOP process [ 191. Other examples are given by Behr et al. and others
[41, 174, 175, 2171.
The aqueous biphasic processes require a minimum solubility of the reac-
tants S in the catalyst phase [ 196, 2051. Therefore, hydroformylation of higher
olefins (approx. > C,) or functionally substituted olefins is more difficult but
offers various advantages, such as the simplification of reaction sequences and
reduced expenditure for the catalyst cycle. So far, work on these biphasic pro-
cesses for the conversion of higher olefins, except for Kuraray’s recent devel-
6 10 3.I Development of Methods

opments, has not attained successful commercial realization (cf. Section 2.3.5
and [15, 42-44, 10.51). In early work on biphasic 0x0 processes with ligand-
modified Rh catalysts, high-molecular olefins played a role (Wilkinson and
co-workers [29] used triphenylphosphine monosulfonate, TPPMS ; Kuntz at
RhGne-Poulenc used the corresponding trisulfonate, TPPTS [45, 681). Using
these reactions among others as examples, the early researchers reported, espe-
cially in comparison with the conversion of lower olefins, a minor reaction rate
as well as emulsifying surface-active properties of the ligands. The decreasing
miscibility of the aqueous catalyst solutions with increasing C-number of the
higher olefins ought to be responsible for the lowering of the conversion
rate [196]. The following changes should improve the solubilities and thus
the conversion of biphasic processes:

(1) variation of the water-soluble ligands by means of surfactant or solubilizing

properties ;
(2) addition of solvents and/or co-solvents;
(3) introduction of other means to improve the miscibility and thus the solubility.

Often ligand variation in biphasic processes has simultaneous duties : to en-

hance the solubility in the aqueous phase, to influence the electronic/steric ligand
properties, and thus to increase the selectivity (e. g., [46-50, 70, 7 1, 1051). A link
to solubility-improving ingredients added externally are water-soluble ligands
(e. g., triphenylphosphine trisulfonate, TPPTS), the hydrophilic substituents of
which have been modified by quatemization [5 1-53]. Proposals for additives to
increase the reciprocal solubility include, following an early suggestion of Man-
assen [56], cationic or nonionic tensides (amphiphilic detergents) [54, 55, 1051,
covering other central atoms as well [57]. Complex catalysts with inherent sur-
face-active attributes (such as surface-active phosphines), i. e., compounds com-
bining an appropriate electronic and steric environment as well as detergent prop-
erties [58-601, are a particularly elegant answer. According to Fell [59], the effect
of these ligands (e. g. tris(2-pyridy1)phosphine) or their N-substituted derivatives
is a consequence of a solubilization of the water- immiscible high-molecular ole-
fins, thus increasing the mass transport. The abilities of detergents aggregating and
forming micelles (“micelle solubilization”) is the subject of special theories [56]
and might be helpful [55, 105, 1971.
A relatively weak effect (except for biphasic hydrogenations; cf. Section
3.1.1 .1.2) has been observed using solely solvents or co-solvents such as EtOH
or BuOH as solubilizers [61, 62, 671 (not to mention the occurrence of side-
reactions such as acetal formation during hydroformylation). For example,
TPPTS as a standard water-soluble ligand proves especially efficient only in
combination with amphiphilic and micelle-forming surfactants together with
co-solvents [63].Years after pertinent patents [72], Hanson reviewed scientifically
the importance of other factors such as salt effects, ionic strengths, etc., for
biphasic hydroformylation reactions [64, 65, 68, 691. Ultrasound treatment is a
well-suited measure for persistent reactants [66]. According to a proposal by
Chaudhari, Delmas, and co-workers, even triphenylphoshine (TPP), dissolved in
 3.1. I. I Immobilization by Aqueous Catalysts 6 11

the organic phase, acts as a co-solvent and as a co-ligand (“promoter ligand”) and
as reaction rate-increasing additive. The role of mixed complexeslike
HRh(CO)TPPTS,,,TPP, is uncertain [ 130, 2051. The influence of the substrates
themselves on the rates of biphasic reactions was discussed by Mortreux and
co-workers which reported higher rates of the biphasic hydroformylation of spe-
cial feedstocks as compared to the monophase operation [144]. The scene of the
action (interfacial reaction versus conversion in the bulk of the liquid) has been
discussed above [ 130,2161). In view of the considerable costs for recycling of sol-
vents and/or co-solvents (approx. 5 US cents/kg in large scale operation) their use
has decreased in process proposals and is only viable in laboratory protocols
[218h, 219c, 2211.
Membrane technology is a recent development to separate (or concentrate)
water-soluble catalysts (mainly hydroformylation catalysts) [ 147, 1491, although
a prior art is known [194, 1951. There are proposals for the use of immobilized
or re-immobilized aqueous phases for large-scale processes (cf. Ref. [222] and
Section 3.1.1.6). Carbon dioxide as a solvent for biphasic hydroformylations
has been described by Rathke and Klinger [184], although the use of CO, for
hydroformylation purposes was described earlier [ 1851. For the use of supercriti-
cal COz cf. Section 3.1.13; with non-aqueous ionic liquids cf. Section 3.1.1.2.2.
Investigations with supercritical water are in an early state (e. g., Ref. [223]).

3.1.1.1.2 Practice of Aqueous-Phase Catalysis

Hydrogenations

Taking hydrogenations of C=C and C=O bonds (and selective hydrogenations, for
instance of unsaturated carbonyl compounds) as examples, a method for biphasic
catalyses has been proposed [ 181 and developed [28, 29, 561. After first reviews
by Sinou [79] and Southern [21], Kalck and Monteil - with a focal point on me-
chanistic backgrounds [ 171 - and Herrmann and Kohlpaintner - with special em-
phasis on chemical aspects [16] - reported the state-of-the-art up to 1993. Kalck
stated correctly that an important stimulant toward biphasic hydrogenations was
the possibility of working under normal pressure, especially for bio-organometal-
lic applications.
The literature of biphasic hydrogenations contains plenty of substrates (al-
kenes and cycloalkenes, arylaliphatic olefins, carbonyl compounds, etc.), mainly
with TPPMS as water-soluble ligand (solubility approx. 200 g/l [150] as com-
pared with 1100 g/l with TPPTS [37]). So far, no industrial process has been
derived from these studies. Besides the development of the basics of biphasic
operation, the research concentrates on fundamental work concerning the ques-
tion of where the reaction takes place: phase boundary, organic phase, or aqueous
phase. Wilkinson [29] concluded from his hydrogenation tests with hexenes or
cyclohexenes in the presence of TPPMS that the somewhat lower rate of hydro-
genation as compared with monophasic conversion should be due to the neces-
sary diffusion of the hydrogen to the alkene/water interface. In this way the iso-
612 3.1 Development of Methods

merization, which is the substantially slower reaction, can compete with the hy-
drogenation. Following this theory no co-solvent ought to be necessary. How-
ever, the hydrolytic cleavage of the dioxolane ring in PGE-17-DIOP does not
support the slow reaction rates [SO], as the reduction in reactivity applies to
many water-soluble hydrogenation catalysts. For more recent examples cf. Sec-
tions 2.9 or 3.3.1.
Dror and Manassen [82] stated that the reaction depends on the alkene solubi-
lity in the aqueous phase and that a co-solvent should be helpful. This leads to the
recommendation of co-solvents (e.g. [29, 35, 75, 811). Delmas, Jenck and co-
workers [83] investigated the influence of co-solvents or hydrogen on alkene (oc-
tene) solubility in the aqueous phase, using predicted liquid/liquid equilibria
within the frame of a thermodynamic model. The distinction of two types (A
and B) of ternary diagrams, depending on the slope of the lines, with various oc-
tene-in-water and water-in-organic phases, explains the ambiguous statements in
the literature about the effectivity of solvents.

Type A: EtOH, acetonitrile, ethylene glycol, n-propylamine, acetone, etc.

Type B : THF, cyclohexanol, PrOH, n-butylamine, etc.

Thermodynamic predictions of liquid/gas equilibria show only moderate effects

of the co-solvents. When ligand oxidation by water and mass transfer limitations
can be suppressed, an increase of the concentration of phosphorus ligands yields
initial kinetics which show first-order reaction rates with respect to H2 and octene
dissolved in the aqueous phase. Although this work is convincing, the sensitivity
of nonindustrially manufactured TPPMS (and TPPTS, too) has to be considered
(this was a remarkable source of irritation during the development of an indus-
trially suited 0x0 process [ 16, 84]), as well as differing statements about catalyti-
cally active membranes or colloidal suspensions of polyhydroxylated Rh particles
made from Rh/TPPTS complexes [7, 851. Some of this work may also be the rea-
son for erroneous conclusions, which in fact might be only a consequence of im-
pure TPPTS, since the role of colloidal metals dispersed in the aqueous phase and
their responsibility for catalytic activity is still uncertain [7]. So far, it is not known
whether self-association of water- dissolved metal complexes according to eq. (1)
plays an important role [16, 225, 226c, 2661.
[Catlrnicelles &==[catlrnonorner -
- [Catlrnernbranes (1)

While the hydrogenation of alkenes, etc., was important for the development
of biphasic methodology, the more valuable applications will be selective re-
ductions according to eqs. (2)-(4), using water-soluble Rh or Ru complexes,
respectively [28, 87-93, 178, 181, 186, 189, 224 b]. Double bonds besides keto
or carbonyl groups and vice versa, double bonds in acids, or triple bonds may
be hydrogenated selectively. For systematic reasons the hydrogenation of cin-
namaldehyde (and other unsaturated, functional derivatives) is still investigated
often (Ru, Rh, Os, Pd catalysts, tensioactive additives, etc., 1213c, 215 c,
21 8 h, 2301).
 3.1.1.1 Immobilization by Aqueous Catalysts 613

CH3 CH3
I
CH3-C'CH-CHO TfiI CHB-C'CH-CH,nH

3-methyl-2-buten-1-al 3-methyl-2-buten-I-01
"Prenol"

-
H
H-C-COOH
Rh
I
TPPMS H-C-COOH
I
H

fumaric / maleic acid succinic acid

COOH H,_,COOH
,.I Pd
CI

ii
C
P
propylene-
carbonate C
II
(4)
I H' 'COOH
COOH
acetylene di- maleic acid
carbonic acid

Sodium or ammonium formates are also suitable as hydride donors for the
hydrogenation of a$-unsaturated and aromatic aldehydes with water-soluble Ru
complexes [88, 931. With [RuC~~(TPPMS)~], both the catalyst and the formate
are in the aqueous phase; the phase-transfer problem associated with catalysts
not soluble in water and aqueous formate solutions does not arise [93, 941.
These systems offer interesting theoretical aspects [87, 95, 1861.
There now exists evidence for the extension of two-phase catalysis into the new
area of C,-chemistry. Thus, Leitner an co-workers [206] described the biphase hy-
drogenation of CO, to formic acid (cf. Section 3.3.4). Two-phase hydrogenations
of aromatic nitro compounds with Pd or Rh catalysts are examined by Tafesh and
co-workers [207] and others [212 f, 218 d, 2261.
During the past decade numerous studies have been devoted to the hydroge-
nation of prochiral substrates in the presence of chiral water-soluble Rh com-
plexes. Among interesting precursors for amino acids, a-amidoacrylic acid and
amidocinnamic acid have often been selected [16, 171. So far the reaction rates
and enantiomeric excesses (ee) with biphasic methods are lower than with their
homogeneous counterparts; the achievable yields are lower [80, 96-102, 186,
189, 213 d, 218 f, p]. Addition of tensides is also recommended [225]. At the
focus of aqueous-phase hydrogenation reactions are sugars (mainly with Ru
[227]), alkenes or low-molecular-polymers [218 b, 219 h, 2281, or aromatic com-
pounds [229]. Even water-soluble bimetallic catalysts (Pd-Pt) have been tested
[226 b]. An overview of two phase tranfer hydrogenations is offered by Nomura
614 3.1 Development of Methods

[212 fl. The transfer to SLP or SAP catalysts is possible, as has been proven for
the hydrogenation of 2-(8 ’-methoxy-2’-naphthyl)acrylicacid to (S)-naproxen
[103]. For details see [16, 17, 2631 and Sections 2.1.1, 2.2, 2.9, 3.1.1.3 and 3.3.1.

C-C Couplings

Hydroformylations

The industrially most important, homogeneously catalyzed, biphasic C-C cou-

pling reaction is hydroformylation (0x0 or Roelen reaction) [73]. The Ruhrche-
mieRhBne-Poulenc process is an industrial application of this reaction using or-
ganometallic complexes as catalysts, modified by TPPTS (see below and Section
2.1.1). The success of RuhrchemieRhBne-Poulenc’s commercial 0x0 process and
the comparison of this process [lo41 with the monophasic Rh-catalyzed 0x0 pro-
cess (“LPO” processes of Union Carbide, BASE Celanese; e. g. [lOS]) prove that
the drop in activity of the biphasic system on recycle of catalyst is more signifi-
cant in the case of the single phase, as stated by Chaudhari and co-workers [67].
On using functionally substituted olefins, Mortreux [ 1441 realized a reaction ac-
celeration with TPPTS as compared with TPP. Other authors report deactivation,
manipulation of the alcohol formation, etc., on using aqueous biphasic systems
for hydroformylations : a clear reference to uncertainties, ambiguities, and contra-
dictions of the experimental work, even if only reaction rates and not the species
of substrates [ 1441, their reciprocal miscibilities (propene in water: approx.
7 X kmol/m3; 1-octene in water: 2.4 X kmol/m3), the water-gas shift
reaction (water as a H2 source, cf. Section 3.2.11), etc., are considered [67, 70,
106, 1071.
Following the recommendations of Manassen [ 181 the history of biphasic hy-
droformylation began with work on various water-soluble ligands (Table 1).
After this preparatory work on various aspects [30], Kuntz [22, 1991 expressed
the basic idea of a new generation of water-soluble 0x0 catalysts with triphenyl-
phosphine trisulfonate (TPPTS, as the Na salt, as compared with TPPMS and
TPPDS, the mono- and disulfonate) as ligands for a Rh-based 0x0 process, mainly
for the hydroformylation of lower olefins such as propene (eq. (5)).
CH3
HzC=CH-CH~+ CO + H2 Rh CH3-CHz-CHz-CHO
TPPTS
+ \CH-CHO
propene syngas n- C H ~iso-
(5)
butyraldehyde

So far, TPPTS is the most ideal ligand modifier known for the 0x0-active
HRh(CO),. Without any expensive preformation steps, three of the four CO
ligands can be substituted by the readily soluble (1100 g/l [37]), nontoxic (LD50,
oral: 5000 mgkg) TPPTS, which yields the hydrophilic 0x0 catalyst
HRh(CO)[P(m-~ulfophenyl-Na)~]~ as an “in-situ catalyst” [ 1981 (cf. Figure 6).
An appropriate process has been commercialized by Ruhrchemie AG (see Section
3.1.1.1.3).
 3.1.1.1 Immobilization by Aqueous Catalysts 6 15

Figure 6. The 0x0-active catalyst HRh(CO)[P(m-sulfophenyl-Na)3]3.

Together with TPPTS, TPPMS and TPPDS maintain their importance for other
applications. With their different grades of sulfonation, they allow a fine tuning of
the hydrophilickydrophobic ratio of the catalyst during biphasic operation, when
necessary (e.8. [14, 1091).
The development of ligands for 0x0 processes has not come to an end (cf.
Table 2). The work of Herrmann and colleagues may be quoted as one example
among others : they introduced different water-soluble ligands such as BISBIS
(bis-[phenyl(sulfonatophenyl)phosphinomethyl]disulfonatobiphenyl,1; NORBOS
(tris(sulfonatophenyl)dimethylphosphanorbornadien, 2; or BINAS (bis[disul-
fonatophenylphosphinomethyl]tetrasulfonatobinaphthene; 3. Using these ligands
a further improvement in activity and selectivity (dim [= linearhranched]
ratio) was achieved [16, 39, 40, 110-1121.

Na03S

BlSBlS
1

A novel group of ligands for biphasic organometallic reactions, such as C-C

couplings, especially hydroformylations, was discovered by Herrmann [ 152 a]
on using carbene complexes (4; cf. also Section 3.1.10).
6 16 3. I Development of Methods

S03Na

BlNAS
3

R'

"1
"y
N;c-{h-co
co
Ft.'
4

The bond between carbon and rhodium is extremely stable, thus allowing
mono- or biphasic hydroformylations without any excess of ligands. Due to this
stability, for the first time ever an anchoring to a polymer support seems possible
without leaching. These N-heterocyclic carbenes appear to be excellent ligands to
stabilize catalytically active metals even under harsh temperature conditions, e. g.
Heck C-C-coupling reactions at 130 "C [152 b].
Quite a number of contributions to ligand research in 0x0 chemistry are known
(e.g., [16, 17, 23, 37, 38, 46, 49, 79, 80, 96, 113-119, 153]), as well as those
in respect of other central atoms, binuclear complexes, photosensitized hydro-
formylations, or other starting olefins, including bioorganometallic applications
(e.g., [38, 116, 120-123, 145, 146, 1511). The substitution of Na by Li, K or
other cations in TPPTS-derived or other processes is claimed to be advantageous
(e. g., [124, 1251). According to some observations [126] the kinetics of hydro-
formylations in aqueous phase may be different from those in nonaqueous
media, as suspected by Chaudhari and co-workers [ 1271. Special aspects, mainly
the behavior, control, and organization of the phases of aqueous biphasic
processes, are dealt with in special papers [31, 41, 128, 1291.
In early work on biphasic 0x0 processes with ligand-modified Rh-catalysts,
high-molecular-mass olefins already played a role. The investigators of the hydro-
formylation of higher olefins expected lower reaction rates in comparison with the
conversion of lower olefins, as indicated above. They tried to overcome the de-
creasing miscibility of the aqueous catalyst solutions with the increasing chain
length of the higher olefins by variation of the water-soluble ligands (by means
of surfactants or solubilizing properties), by addition of solvents and/or co-
solvents, or by special measures to improve the solubility. These issues have
been discussed in the previous section.
Intensive research has been done by RusseVJohnson Matthey to develop a bi-
phasic 0x0 process for I-dodecene as an example for higher olefins [54, 105, 1181.
 3.1.I . 1 Immobilization by Aqueous Catalysts 6 17

Favorable results could only be obtained when high concentrations of amphiphilic

additives (additiveRh ratios of 20: 1) were used. No commercial (i. e., econom-
ical) process emerged from this work. According to Jin, another approach is to
use the “cloud point” of P-bonded poly(alky1ene glycol) ethers which serve as
ligands of 0x0-active Rh complexes (5 [49, 108, 2051). Within recent years Jin
and others have done a considerable amount of work on this [233, 2341, and
the use of special poly(ethy1ene glycol)-bonded ligands and hydroformylations
in PEG-containing reaction mixtures (i. e., for higher alkenes) has been described,
too [235]. Above their cloud point, the ligands lose their hydrate shell, thus be-
coming water-insoluble and ensuring a hydroformylation of water-nonmiscible
olefins in the monophase. On reduction of the temperature the hydrate shell is
reversibly restored, the monophase is separated into two phases, and the complex
catalyst returns to the water phase.

Ethoxylated tris(p-hydroxpheny1)phosphine
5

Despite vigorous interest in the use of PEG ligands and of PEG as additive or
co-solvent no process has emerged so far, this being also a consequence of the
costs of their separation before their recycling (cf. p. 611).
With knowledge of the discussion about the site of the - biphasic - action
(interfacial conversion versus reaction in the bulk of the liquid [130, 2161) the
aqueous phase hydroformylation of higher (“heavier”) alkenes is still much in-
vestigated (e.g., Refs. [216 b, 217 a, 218 g, 219 f, h, 2311). There is a certain
trend to recommend high-molecular ligands for this purpose (e. g., calix[4]arenes,
dextrins, etc.). Other papers describe the hydroformylation of special alkenes
using Co or Ru catalysts [232].
There are even some proposals for the application of new techniques and
processes for the conversion of higher-molecular olefins or their functional
substitutes. Exxon described the “aldolizing 0x0 synthesis”, a variant of the
former Aldox process [73], including the conversion of higher olefins of C-
number n to aldehydes C2n+2in a one-step process consisting of hydroformyla-
tion and subsequent aldolization, followed by hydrogenation. Thus the valuable
“dimeric” plasticizer alcohols can be obtained using a biphasic procedure with
diethylene glycol as second phase and special ligands [131]. Union Carbide
claimed a biphasic “oxidative hydroformylation” for the direct conversion of
olefins C, to carboxylic acids Cn+l by using oxygen-containing syngases
[ 1321. Special ligands such as tri(n-octy1)phosphine oxide (TOPO) are essential
for example for the manufacture of propionic acid and propionic anhydride
from ethylene.
Other 0x0 reactions of unsaturated functional derivatives (acrylic acid or acrylic
esters, polyisobutenes, oleic alcohol, high-molecular fatty acids, etc.) have been
described [128, 129, 139-141, 143, 144, 208, 218 h, 2361.
6 18 3.1 Development of Methods

According to HorvAth, the problems arising from the limited reciprocal solubi-
lities of the water phase and higher olefins should be overcome by application of
the SAPC technique [138, 1441. For this and other biphasic - but nonaqueous -
processes, see Sections 3.1.1.2 and 3.1.1.3. A new concept concerning inner
lipophilic cavities and hydrophilic surfaces of a-cyclodextrins may offer new
possibilities for the hydroformylation of higher olefins [ 1421. Asymmetric hydro-
formylations are dealt with in Section 2.9.

Carbonylations

C-C coupling reactions include Pd-catalyzed carbonylations as well as

Heck reactions. Biphasic operations are reported as being particularly efficient.
Ally1 and benzyl chlorides have been converted in two-phase systems to the
corresponding acids with or without phase-transfer catalysts (eq. (6)) [ 154-1 57,
2371.
R-CHP-CI + CO + R‘OH *T R-CH1-COOR’ + HCI
(6)
R = CH2=CH-, C6H5
R‘ = H, CH3, C2H5-

Water-soluble Ru-EDTA complexes are active carbonylation catalysts for the

conversion of amines to amides [ 1581. TPPTS (and other water-soluble ligands,
other additives included) have been used for special carbonylations [ 159, 203,
2381. For other types of carbonylation and Heck reaction, see Sections 2.1.2.3
and 3.1.6.

Oxidations

Because of relatively low yields, oxidations are among the reactions which
deserve special cultivation. Early aqueous-phase oxidations have been
described with fatty alcohols (to aldehydes or acids [174, 1751). Sheldon
reviewed the scene in 1998 [239]. Under the heading “greener oxidations” actual
work concentrates on alcohol oxidation toward ketones with ligand-modified
Pd catalysts or with PhI=O/KBr [218m, 2401. Much work has been done
in dihydroxylation of alkenes with ligand-modified 0 s catalysts and dioxygen
[218 s].
Under the name OxoneTMan oxidation agent has been introduced, consisting of
KHS04-K2S04-2KHS05. Solid Oxone converts methylenic functions under an-
hydrous, biphasic conditions to carbonyl compounds under the catalytic influence
of ligand-modified Mn porphyrins and phase-transfer catalysts (e. g., acetophe-
none is obtained from ethylbenzene). In the case of cyclohexane, s-caprolactone
results as well as cyclohexanol and -one ([219 b, 2411; cf. also Baeyer-Villiger
oxidation). Biphasic oxidations with methyltrioxorhenium (e. g., to epoxides)
are reviewed in Section 3.3.13 [244 i].
 3.1.1. I Immobilization by Aqueous Catalysts 6 19

-+ -+ H20 -
Pd, TPPMS
‘ OH -
Hz
Ni
-OH
c4 c4 C8 ‘8 n-octanol
I
1 CuCr03

O
H
H
O
- 2
- 0
CO HZ

I /
[Rh(a~ac)(CO)~]
TPPMS

‘0
C9 Ni C9

Scheme 1. The Kuraray process.

Telomerizations

Telomerizations have been among the first reactions tested under biphasic condi-
tions [45, 1901, starting with butadiene and methanol on Pd/TPPMS catalysts and
yielding 1-methoxy-2,7-octadiene. The telomerization in the presence of water as
reactant (hydrodimerization; cf. Scheme 1) has been commercialized [ 15, 3 1,
42441. These biphasic developments of the Kuraray Corporation yield 1-0ctanol
or 1,9-nonanediol, respectively (cf. [15, 31, 4 2 4 4 , 86, 133, 137, 244 e] and
Section 2.3.5). Similar developments (but without technical realization) have
been described by BASF [134], Mitsubishi [135], and Shell [136], and others
[215 d, 242, 2681. The telomerization of butadiene and ammonia may also be
biphasic [243].

AlkeneICarbon Monoxide Copolymerization

The alternating copolymerization of alkenes with CO is on its way to commercial-

zation (cf. Section 2.3.4) [244 a]. This reaction can also be performed in aqueous
media; the catalyst of choice is based on ligand-modified Pd [218 k, 2451.

Other C-C Couplings

Corresponding to a Michael addition from activated double bonds in dienes and

C-H acidic compounds, functionalized derivatives are available [ 160-1 631
(eq. (7)).
620 3.1 Development of Methods

R - C H ~ - C - C H ~ -CH* -CH
FH2
R = H, CH3, R--CHP-C-CH=CH~ 2'
Z-CH2-Z' = acetylacetone, hydroxyacetone, phenols, morpholine

With optimized process operation the reaction is strongly regioselective. The

process is commercialized by RhGne-Poulenc using Ruhrchemie's TPPTS and
yields precursors for vitamin E; cf. Section 3.1.1.1.3 [163, 1641 Sc or Y triflates
catalyze aqueous biphasic reactions which are alternatives to base-catalyzed pro-
cesses such as aldol or Michael-type conversions [257].
Biphasic hydrocyanations were described as early as 1976 using Ni/TPPTS cat-
alysts [165, 244 d]. Adipic dinitrile and methylglutaronitrile are obtained from
3-pentene nitrilehutadiene (see Section 2.5).
Water-soluble polymers have been obtained via C-C couplings in biphasic
reactions by means of Pd/TPPMS catalysts (see Section 3.3.10.1 [166]). These
reactions include aqueous ring-opening metathesis polymerizations (ROMPS;
eq. (8) [167, 2581) as described by Novak and Grubbs [168], and other oligo-
or polymerizations [ 188, 1911 Section 2.3.3).

* PTS = ptoluene sulfonate

Pdo species and TPPTS are excellent catalysts for allylic substitution with a
variety of nucleophiles (carbon and hetero nucleophiles) in nitrile-water media
(Tsuji-Trost reaction; eq. (9) [182, 1831).

Other aqueous biphasic organometallic reactions include fat-chemical pro-

cesses, such as the Ru-catalyzed oxidation of fatty alcohols to the corresponding
aldehydes or acids [174, 175, 244 g]. Oxidation reactions of water-soluble ligands
in aqueous biphasic reactions (especially TPPTS) have been investigated by
Larpent, Patin and co-workers [176]. Recent examples of other aqueous biphasic
reactions are compiled in Table 3.
 3.1.1.I Immobilization by Aqueous Catalysts 62 1

Table 3. Recent examples for aqueous biphasic reactions catalyzed with ligand-modified
transition metals.
Type of reactionhfetal involved Ref.

Heck-type reactions/Pd [218 t, 220, 234 b, 244 c]

Suzuki couplingPd 1218 t, 2461
Carbonylative coupling 12651
Amination of aromatic halidespd 12471
Hydroaminomethy 1ationRh-Ir 12721
Grignard reactiondsn-Rh ~481
Cycloaddition/cyclotrimerizatiodCo 1249, 2551
Wacker synthesis/Pd (V, Mo, Cu) 12501
Reformatsky reactiodzn 12511
Wittig reaction ~2521
AldolizatiodSc 12531
Hydrosily lation/Pt 12541
HydrodesulfurizationRu [244 h, 255, 2671
PolymerizatiodW, Mo 1244 j, 2591
Dihydroxylation/Os [218 s, 2611
EpoxidatiodCo, W, Re [2621
Isomerizations/Ni W41

Bio-Organometallic and Other Reactions

The hydrogenation of unsaturated fatty acids as part of membrane structures of a

wide range of lipid classes offers important opportunities [16, 17, 169, 170,244 fl.
Water-soluble catalysts are much more suitable than their lipophilic derivatives, as
no solvent vector such as THF or DMSO is needed for the transport of the metal
complexes into the membranes. Furthermore, water-soluble catalysts are easier or
remove from the still-intact membrane at the end of the reaction, and even the
polarity of the catalyst may be controlled by suitable choice of ligand, thus offering
a bundle of advantages over monophasic hydrogenations [ 1731.
Work in bioorganometallic research was initiated by Madden and Quinn in
1978 [ 169, 1701, considerably later than purely “chemical” applications, thus
proving that chemistry in this field was started earlier than biochemistry, and
not vice versa as often stated. The hydrogenation activity of the catalyst
RhCl(TPPMS)3 on phosphatidyl choline from soya lecithin was determined for
622 3.1 Development of Methods

the vesicles produced by ultrasound or mechanical perturbation. The water-soluble

metal complex has amphiphilic character due to its sulfonated phosphine ligands
and the unsubstituted phenyl groups. This bipolarity facilitates the transition
between the polar aqueous phase and the lipophilic hydrocarbon phase. Thus nor-
mally all double bonds of the phospholipids can usually be hydrogenated, even
including those deep inside the membrane layer. Vigh and 560 [ 171, 1721 com-
pared Rh and Ru catalysts for the hydrogenation of membranes. Under normal
conditions the complex RuC12(TPPMS)* ist more active than RhC1(TPPMS)3,
which becomes superior to the Ru analogue above 30 “C. Details of these bio-
organometallic reactions, including conversions in living cells, are given in
Section 3.3.10.2.

3.1.1.1.3 Industrial Applications

After preparatory work on different aspects, Kuntz [22, 301 expressed the basic
idea of a new generation of water-soluble Rh-based 0x0 catalysts with triphe-
nylphosphine trisulfonate (TPPTS) as ligand for a Rh-based hydroformylation
process (cf. Figure 6). Ruhrchemie AG took over the idea and transferredit
to an industrially viable and highly sophisticated process [199]. Thus Rh/
TPPTS is the base for RuhrchemieRhGne-Poulenc’s 0x0 process for the hy-
droformylation of propene, which has been developed and commercialized
by Ruhrchemie within only two years. The first plant started operation in
1984, together with Ruhrchemie’s commercial TPPTS production on a standar-
dized basis [9, 20, 177-1791. Almost 3 million tonnes of n-butanal were pro-
duced within more than ten years of production and prove the power of the
aqueous-phase 0x0 concept and the high activity of the aqueous-phase catalyst.
This process is environmentally benign and has been licenced [180, 201, 2031.
The flow diagram of the RuhrchemieRhGne-Poulenc (RCHRP) process as
the most typical example of a biphasic process with an organometallic, ligand-
modified catalyst is shown in Figure 7.
As a consequence of the solubility of the Rh complex in water and its insolu-
bility in the 0x0 products, the 0x0 unit is essentially reduced to a continuous
batch reactor, followed by a phase separator (decanter) and a strip column
(described in [9, 201, 2021). The 0x0 reaction is smooth and highly efficient as
far as activity and selectivity are concerned: the n/iso ratio (the ratio between
the desired n-butanal and isobutanal, equivalent to the normal [linearlhranched
ratio) is as high as 97:3. The catalyst formed in situ [198] is indeed
“immobilized” and Rh losses are low and in the ppb range, as is the Rh content
of the crude aldehyde, which corresponds to losses of less than g k g n-bu-
tanal [9]. This means that the disadvantages of all earlier attempts at “anchoring”
the homogeneous 0x0 catalyst on fixed supports (leaching, inactive catalyst spe-
cies with decreasing selectivity) have been overcome by the biphasic operation
with “mobile” supports. For more details, see Section 2.1.1. The scene has
recently been reviewed [260].
 3.1.1.1 Immobilization by Aqueous Catalysts 623

n-butyraldehyde vapors
n-butyraldehyde

I - vent
- i-butyral-
dehyde

propyleni

syngas
n-butyraldehyde
4

Figure 7. Flow diagram of the RCH/RP process [9].

Rh6ne-Poulenc runs a process for the production of geranylacetone by

Rh/TPPTS-catalyzed addition of ethyl acetoacetate to myrcene [ 160-1 64, 1871
(eq. (10)). Two subsequent reaction steps convert geranylacetone to vitamin E
[203].

myrcene ethyl acetoacetate COOEt

hydrolysis
decarboxylation
1
Vitamin E --
C13 geranylacetone

The biphasic Suzuki coupling is commercialized by Clariant AG (the former

Hoechst AG) [260]. Despite interesting proposals (e. g., [271]), no other industrial
realizations of aqueous biphasic processes emerged.
624 3.1 Development of Methods

3.1.1.1.4 Recent Developments

The principle of two-phase catalysis was cut down to a two-phase catalyst separa-
tion mode by researches of Union Carbide [200]. Since higher olefins have no
solubility in water, a homogeneous medium consisting of a nonpolar solvent and
“solubilizing” agents such as N-methylpyrrolidone (NMP) or polyalkylene glycols
was chosen. Rhodium catalysts using alkali salts of mono-sulfonated triphenyl-
phosphane (TPPMS) are soluble in such a medium. However, the homogeneous
system can be easily induced to separate into nonpolar (product) and polar phases
(catalyst), thus providing an effective means of catalyst recovery. Sometimes
separation is induced by raising the temperature. In the preferred case of NMP-
based systems, a sharp separation is effected by excess water or methanol.
The key advantage here is the combination of a homogeneous catalytic process
(hydroformylation) with a catalyst separation/recycling by virtue of phase-separa-
tion. Water extraction reduces the rhodium concentration to < 1 ppm-levels, and
the catalyst can be recovered by adsorptioddesorption on silica and anion-
exchange resins. C,- through Cl5-aldehydes have been made in > 90% olefin
efficiencies, with the final effluent being lower than 20 ppb in rhodium. Typical
conditions of 90-110 “C and CO pressures of 5-30 psia were applied. The
Union Carbide technology once again broadens the scope of ionic catalysts
(e. g., rhodiudsulfonated phosphanes) by introducing them into “true” homo-
geneous catalysis. So far, this process remains a proposal [270].

References
[ l ] B. Cornils, W. A. Herrmann, M. Rasch, Angew. Chem. 1994,106,2219; Angew. Chem.
Int. Ed. Engl. 1994, 33, 2144.
[2] Chemische Verwertungsgesellschaft mbH, Oberhausen (A. Gemassmer, H. J. Nienburg
et al.), DE 896.341 (1953); DE 902.491 (1954).
[3] S. L. Regen, Angew. Chem. 1979, 91, 464. Aizgew. Chem. Int. Ed. Engl. 1979, 18, 421.
[4] Montecatini Edison S.p.A. (M. Foa, L. Cassar, G. P. Chiusoli), DE 2.035.902 (1979).
[5] J. Falbe, H. Bahrmann, Chem. uns. Zeit 1991, 15, 37.
[6] G. W. Parshall, J. Am. Chem. SOC.1972, 94, 8716.
[7] C. Larpent, H. Patin, J. Mol. Cutul. 1988, 44, 191.
[8] For example, Patents to Mitsubishi Chem., DE 2.302.962; Showa Denko KK, DE
2.535.597; Philipps Petroleum Comp., US 4.068.054, US 3.995.097, US 3.956.257;
Chisso Corp., DE 1.904.815; or Ruhrchemie AG, DE 1.195.496.
[9] E. Wiebus, B. Cornils, Chem.-Ing.-Tech. 1994, 66, 916; CHEMTECH 1995, 25, 33.
[ 101 Chemische Verwertungsgesellschaft mbH, Oberhausen (H. Nienburg, H. J. Waldmann,
E. Plauth et al.), DE 953.606 (1956); Ruhrchemie AG, GB 736.875 (1952).
[11] Chemische Venvertungs GmbH, Oberhausen (H. Nienburg, H. J. Waldmann, E. Plauth
et al.), DE 933.338 (1955).
[12] Montecatini Edison SpA (G. Gregorio, A. Andreetta), DE 2.313.102 (1973).
[13] DSM NV (0.E. Sielcken, N. F. Haasen), PCT-WO 94/14747, (1994).
[14] Union Carbide Chem. Plast. Techn. Corp. (J. E. Babin, D. R. Bryant, A. M. Harrison,
D. J. Miller), EP 0.552.797 (1992), EP 0.358.922 (1988).
 References 625

[15] N. Yoshimura, M. Tamura in Successful Design of Catalysts (Ed.: T. Inui), Elsevier,

Amsterdam, 1988, p. 307.
[16] W. A. Herrmann, C. W. Kohlpaintner, Angew. Chem. 1993, 105, 1588; Angew. Chem.
Int. Ed. Engl. 1993, 32, 1524.
[17] P. Kalck, F. Monteil, Adv. Organomet. Chem. 1992, 34, 219.
[18] J. Manassen, in Catalysis: Progress in Research (Eds.: F. Basolo, R. L. Burwell),
Plenum Press, London, 1973, pp. 177, 183.
[19] Shell Oil Co. (W. Keim, R. S. Bauer, H. Chung, P. W. Glockner, H. van Zwet et al.), US
3.635.937, US 3.637.636, US 3.644.563, US 3.644.564, US 3.647.914, US 3.647.906,
US 3.647.915, US 3.661.803, US 3.3.686.159 (all of 1972); W. Keim, Chem.-1ng.-
Tech. 1984, 56, 850.
[20] B. Cornils et al., Proc. 41h Int. Symp. on Homogeneous Catalysis, Leningrad 1984,
p. 487; Preprints Int. Symp. High-pressure Chemical Engineering, Erlangen 1984,
p. 129; Abstract, I" IUPAC Symp. Organic Chemistry, Jerusalem, 1986 p. 295; DE
3.234.701, 3.235.029, 3.235.030, 3.412.335, 3.341.035, 3.43 1.643, 3.412.336,
3.443.474, 3.511.428, 3.546.123, 3.630.587, 3.640.614, 3.726.128, etc. (filed between
1982 and 1994).
[21] T. G. Southern, Polyhedron 1989, 8 (4), 407.
[22] E. Kuntz, CHEMTECH 1987, 17 (9), 570.
[23] F. Mercier, F. Mathey, J. Organomet. Chem. 1993, 462, 103.
[24] H. Gilman, G. E. Brown, J. Am. Chem. Soc. 1945, 67, 824.
[25] T. Jarolim, J. Podlahova, J. Inorg. Nucl. Chem. 1976, 38 (l), 125.
[26] F. G. Mann, I. T. Millar, J. Chem. SOC.1952, 4453.
[27] S. Ahrland, J. Chatt, N. R. Davies, A. A. Williams, J. Chem. SOC.1958, 276; S. Ahrland,
J. Chatt, N. R. Davies, Quart. Rev. 1958, 12, 265.
[28] F. Job, M. Beck, React. Kinet. Catal. Lett. 1975, 275; Proc. Symp. Rhodium in Homo-
geneous Catalysis, VeszprhJHungary, Sept. 1978, p. 5 1 ; F. Job, Z. Toth, J. Mol. Catul.
1980, 8, 369.
[29] A. F. Borowski, D. J. Cole-Hamilton, G. Wilkinson, Nouv. J. Chem. 1978, 2, 137.
[30] RhGne-Poulenc Ind. (E.Kuntz et al.), FR 2.230.654 (1983), FR 2.314.910 (1975), FR
2.338.253 (1976), FR 2.349.562 (1976), FR 2.366.237 (1976), FR 2.473.504 (1979),
FR 2.478.078 (1980), FR 2.550.202 (1983), FR 2.561.650 (1984); DE 2.627.354 (1976).
[31] For example: Kuraray Co. Inc. (Y. Tokitoh, N. Yoshimura), US 4.808.756 (1989).
[32] J. Chatt, G. J. Leigh, R. M. Slade, J. Chem. SOC.,Dalton Trans. 1973, 2021.
[33] R. T. Smith, M. C. Baird, Transition Met. Chem. 1981,6, 197, R. T. Smith, R. K. Ungar,
M. C. Baird, Transition Met. Chem. l982,7,288.[34]K. N. Hamson, P. A. T. Hoye, A. G.
Orpen, P. G. Pringle, M. B. Smith, J. Chem. SOC.,Chem. Commun. 1989, 1096.
[35] F. Job, Z. Toth, J. Mol. Catal. 1980, 8, 369.
[36] L. D. Pettit, H. M. N. H. Irving, J. Chem. Soc. 1964, 5336.
[37] 0. Herd, K. P. Langhans, 0. Steltzer, W. Weferling, W. S. Sheldrick, Angew. Chem. 1993,
105, 1097;Angew. Chem., Int. Ed. Engl. 1993, 32, 1058.
[38] T. Bartik, B. Bartik, B. E. Hanson, I. Guo, I. Toth, Organornetallics 1993, 12, 163;
J. Orgunornet. Chem. 1994, 480, 15.
[39] W. A. Herrmann, J. Kellner, H. Riepl, J. Organomet. Chem. 1990, 389, 8 5 , 103; W. A.
Henmann, J. A. Kulpe, J. Kellner, H. Riepl, H. Bahrmann, W. Konkol, Angew. Chem.
Int. Ed. Engl. 1990, 29, 39 1 .
[40] W. A. Herrmann, C. W. Kohlpaintner, H. Bahrmann, W. Konkol, J . Mol. Catal. 1992,
73, 191.
[41] A. Behr, W. Keim, Erdd, Erdgas, Kohle, Petrochem. 1987, 103, 126; A. Behr, Paper
presented on the occasion of Prof. Keim's 601h birthday, Aachen, Germany, Dec. 1994;
A. Behr, J. Organornet. Chem. 1991,403,215; A. Behr, Fat. Sci. Technol. 1990,92,375.
626 3.1 Development of Methods

[42] Kuraray Corp. (M. Matsumoto, M. Tamura et al.), US 4.215.077 (1980) and U S
4.567.305 (1 986).
[43] N. Yoshimura, Y. Noriaki, M. Matsumoto, M. Tamura, Nippon Kagaku Kaishi 1993,
(2), 119.
[44] Kuraray Corp. (N. Yoshimura, M. Tamura et al.), US 4.356.333 (1982), US 4.417.079
(1983), US 4.927.960 (1990), US 5.057.631 (1991), EP 0.287.066 (1988); EP
0.436.226 (1990), FR 2.499.978 (1982); GB 2.074.156 (1980).
[45] Rh6ne-Poulenc Ind. (E. Kuntz), FR 2.366.237, (1976).
[46] T. Bartik, B. Bartik, B. E. Hanson, I. Guo, I. T6th, Organometallics 1993, 12, 164.
[47] Yeda Research and Development Co. (J. Manassen, Y. Dror), US 4.415.500 (1983).
[48] R. T. Smith, R. K. Ungar, M. C. Baird, Transition Met. Chem. 1982, 7, 288.
[49] Y. Yan, H. Zhou, Z. Jin, Fenzi Cuihua 1994, 8 (2), 147; Chem. Abstr: 121, 111875.
[SO] BASF (H. J. Kneuper, M. Roeper, R. Paciello), DE 4.230.871 (1993); EP 0.588.225
(1993).
[51] Hoechst AG (H. Bahrmann, P. Lappe), EP 0.602.463 (1994).
[52] Ruhrchemie AG (B. Comils, W. Konkol, H. Bahrmann, H. W. Bach, E. Wiebus), DE
3.41 1.034 (1984), 3.443.474 (1985); Ruhrchemie AG (H. Bahrmann, J. Weber, H. W.
Bach, L. Bexten), EP 0.216.315 (1986).
[53] Hoechst AG, CN 85-105.102 (1985).
[54] Johnson Matthey plc. (M. J. H. Russel, B. A. Murrer), GB 2.085.974 (1980), U S
4.399.312 (1983), DE 3.135.127 (1990); M. J. H. Russel, Chemie-Technik (Heidelberg)
1988, 17 (6), 148.
[551 G. Oehme, E. Paetzold, R. Selke, J. Mol. Catal. 1992, 71, L1; Tetrahedron 1993, 49,
6605; Angew. Chem. 1994, 106, 2272; DD 259.194 (1987).
[56] Y. Dror, J. Manassen, Stud. S u Sci.~ Catal., (Pt.B, New Horiz. Catal.) 1981, 7, 887.
[57] Y. Matsui, M. Orchin, J. Organomet. Chem. 1983, 244, 369.
[58] H. Ding, B. E. Hanson, T. Bartik, B. Bartik, Organometallics 1994, 13, 3761; J. Mol.
Catal. 1994, 88, 43.
[59] B. Fell, G. Papadogianakis, J. Mol. Catal. 1991, 66, 143.
[60] Hoechst AG (H. Bahrmann, B. Fell, G. Papadogianakis), DE 3.942.954 (1989).
[61] J. Wu, G. Yuan, Q. Zhou, Shiyou Huagong 1991,20 (2), 79; Chem. Abstr: 115, 321659.
[62] P. Punvanto, H. Delmas, Paper presented at the symposium Catalysis in Multiphase
Reactors, Lyon, France, Dec. 1994; Catal. Today 1995, 24, 135.
[63] Eniricerche S.p.A. (L. Tinucci, E. Platone), EP 0.380.154 (1990).
[64] Ruhrchemie AG (B. Cornils, W. Konkol, H. W. Bach, G. Dambkes, W. Gick, W. Greb,
E. Wiebus, H. Bahrmann), DE 3.413.427 (1984), DE 3.546.123 (1985).
[65] H. Ding, B. E. Hanson, J. Chem. SOC.,Chem. Commun. 1994, 2747.
[66] Ruhrchemie AG, (B. Cornils, H. Bahrmann, W. Lipps, W. Konkol), EP 0.173.219 (1985),
DE 3.511.428 (1985).
[67] R. M. Deshpande, S. S. Divekar, B. M. Bhanage, R. V. Chaudhari, J. Mol. Catal. 1992,
75 (l), L19.
[68] RhGne-Poulenc S. A. (E. Kuntz), DE 2.627.354 (1976).
[69] Hoechst AG (B. Cornils, H. Bahmann, E. Wiebus et al.), EP 0.158.246 (1984).
[70] P. Escaffre, A. Thorez, P. Kalck, New J. Chem. 1987, 11, 601; P. Kalck, P. Escaffre,
F. Serein-Spirau, A. Thorez, New J. Chem. 1988, 12, 687.
[71] T. Bartik, B. Bartik, B. E. Hanson, J. Mol. Catal. 1994, 88, 43.
[72] For example, Ruhrchemie AG (B. Cornils, E. Wiebus et al.) DE 3.640.614 (1986).
[73] B. Comils, New Syntheses with Carbon Monoxide (Ed.: J. Falbe), Springer, Berlin, 1980;
M. Beller, B. Cornils, C. D. Frohning, C. W. Kohlpaintner, J. Mol. Catal. A ; 1995,
104, 17.
[74] R. T. Smith, M. C. Baird, Inorg. Chim. Acta 1982, 62, 135.
 References 627

[75] R. T. Smith, R. K. Ungar, L. J. Sanderson, M. C. Baird, Organometallics 1983, 2,1138.

[76] C. J. Hawkins, 0. Monstedt, J. Bjenum, Acta Chem. Scand. 1970, 24, 1059.
[77] H. D. Empsall, E. M. Hyde, D. Pawson, B. L. Shaw, J. Chem. Soc., Dalton Trans. 1977,
1292.
[78] I. T. Horvhth, R. V. Kastrup, A. A. Oswald, E. J. Mozeleski, Catal. Lett. 1989, 2, 85.
[79] D. Sinou, Bull. Soc. Chim. Fr 1987, 3 (1/2), 480.
[80] Y. Amrani, D. Sinou, J. Mol. Catal. 1984, 24, 231.
[81] V. R. Parameswaran, S. Vancheesan, Proc. Indian Acad. Sci., Chern. Sci. 1991, 103 (I),
1; Chem. Abstl: 114, 228.209.
1821 Y. Dror, J. Manassen, J. Mol. Cutul. 1977, 2, 219.
[83] I. Hablot, J. Jenck, G. Casamatta, H. Delmas, Chem. Eng. Sci. 1992, 47, 2689.
[84] Ruhrchemie AG (R. Giirtner, B. Comils et a].), DE 3.235.029 (1982), DE 3.235.030
(1982).
[85] C. Larpent, F. Brisse-Le Menn, H. Patin, New J. Chem. 1991, 15, 361.
[86] RhGne-Poulenc (E. Kuntz), FP 2.366.237 (1976), DE 2.735.516 (1978).
[87] J. M. Grosselin, C. Mercier, G. Allmang, F. Grass, Organometallics 1991, 10, 2126.
[88] A. Benyei, F. Job, J. Mol. Catal. 1990, 58, 151.
[89] F. Job, Z. Tbth, J. Mol. Catal. 1980, 8, 369; F. Job, Z. Tbth, M. T. Beck, Inorg. Chim.
Acta 1977, 25, L 61.
[90] F. Job, L. Somsik, M. T. Beck, J. Mol. Catal. 1984, 24, 71.
[91] F. Job, E. Trbcsinyi, J. Organomet. Chem. 1982, 231, 63.
[92] A. Behr, H. Schmidtke, Chem. Ing. Tech. 1993, 65, 568.
[93] F. Job, A. BCnyei, J. Organomet. Chem. 1989, 363, C 19.
[94] R. Bar, L. K. Bar, Y. Sasson, J. Blum, J. Mol. Catal. 1985, 33, 161.
[95] J. M. Grosselin, C. Mercier, J. Mol. Catal. 1990, 63, L 25.
[96] (a) Abstracts of the NATO Advanced Research Workshop, Aqueous Orgunometallic
Chemistry and Catalysis, Debrecen, Hungary, Aug./Sept. 1994; (b) Aqueous Organo-
metallic Chemistry and Catalysis, (I. Horvith, F. Job, Eds.) Kluwer, Dordrecht/Boston/
London 1995.
[97] J. Haggin, Chem. Eng. News 1994, (Oct. lo), 28
[98] B. Comils, Nuchr Chem. Tech. Lab. 1994, 42, 1136.
[99] A. Kumar, G. Oehme, J. P. Roque, M. Schwarze, R. Selke, Angew. Chem. 1994, 106,
2272; Angew. Chem., lnt. Ed. Engl. 1994, 33, 2197.
[ 1001 Takasago Int. Corp. (T. Ishizaki, H. Kumobayashi), EP 0.544.455, 1992.
[I011 Y. Amrani, L. Lecomte, D. Sinou, Organometallics 1989, 8, 542.
[I021 R. G. Nuzzo, S. L. Haynie, M. E. Wilson, G. M. Whitesides, J. Org. Chem. 1981, 46,
2861.
[I031 K. T. Wan, M. E. Davis, Nature (London) 1994, 370, 449.
[I041 M. Beller, B. Comils, C. D. Frohning, C. W. Kohlpaintner, J. Mol. Catal. 1995,104, 17.
[ 1051 M. J. H. Russel, Chemie-Technik (Heidelberg) 1988, 17, 148; Appl. Catal. 1989, 46,
177; PEP review No. 90-3-4 (Process Economics Program of SRI, Menlo Park, CA);
Platinum Metals Rev. 1988, 32, 179.
[lo61 P. Escaffre, A. Thorez, P. Kalck, J. Chem. Soc., Chem. Commun. 1987, 146.
[I071 T. Bartik, B. Bartik, B. E. Hanson, J. Mol. Catal. 1993, 85, 121.
[lo81 Z. Jin, Y. Yan, H. Zhuo, B. Fell, J. Prakt. ChemKhem. Ztg. 1996, 338, 124.
[lo91 Z. Wang, G. Yuan, Q. Zhou, Shiyou Huagong 1987, 16 (lo), 691; Chern. Abstr 109,
109832.
[ 1101 W. A. Henmann, G. Albanese, R. Manetsberger, F. Lappe, H. Bahrmann Angew. Chem.,
1995, 107, 893, Angew. Chem. Int. Ed. Engl. 1995, 34, 811; W. A. Henmann, C. W.
Kohlpaintner, R. B. Manetsberger, H. Bahrmann, H. Kottmann, J. Mol. Catal. 1995,
97, 65.
628 3.1 Development of Methods

[111] W. A. Herrmann, C. W. Kohlpaintner, H. Bahrmann, W. Konkol, J. Mol. Catal. 1992,

73 (2), 191; W. A. Herrmann, R. Schmid, C. W. Kohlpaintner, T. Priermeier, Organo-
metullics 1995, 4, 1961.
[ 1121 Hoechst AG (W. A. Herrmann, C. W. Kohlpaintner, H. Bahrmann et al.), EP 0.477.747
(1991), EP 0.491.240 (1991), EP 0.571.819 (1993), EP 0.575.785 (1993), and DE
3.840.600 (1988).
[113] T. Bartik, B. Bartik, B. E. Hanson, J. Mol. Catal. 1994, 88, 43.
[114] RhBne-Poulenc Ind. (B. Besson, P. Kalck, A. Thorez), EP 420.169 (1985).
[115] BASF AG (H. J. Kneuper, M. Roeper, R. Paciello), DE 4.230.871 (1992).
[ 1161 P. Kalck, Polyhedron 1988, 7, 2441.
[ 1171 B. Fell, G. Papadogianakis, J. Prukt. Chem./Chem.-Ztg. 1994, 336, 591.
[118] Johnson Matthey plc (M. J. H. Russel, B. A. Murrer), BE 890.210 (1982), FR 2.489.308
(1982), DE 3.135.127 (1981), NL 81/03989 (1981).
[119] R. S. Dickson, T. De Simone, E. M. Campi, W. R. Jackson, Inorg. Chim. Acta 1994,
220 (1-2), 187.
[I201 J. Gao, C. T. Au, S. Wang, C. Yin, K. R. Tsai, Fenzi Cuihua 1990, 4 ( I ) , 68.
[121] I. Willner, R. Maidan, J. Chem. SOC., Chem. Commun. 1988, 876.
[ 1221 Hoechst AG (H. Bahrmann, E. Wiebus et al.), EP 0.562.450 and 0.562.451 (1993), EP
0.216.315 (1986), EP 0.576.905 (1993).
[123] P. J. Quinn, C. E. Taylor, J. Mol. Catal. 1981, 13, 389.
[124] Exxon Chem. Patents Inc. (E. Suciu, J. R. Livingston, E. J. Mozeleski), US 5.300.617
(1993).
[ 1251 Union Carbide (A. G. Abatjoglou, D. R. Bryant), US 4.73 1.486 (1986).
[126] C. D. Frohning, H. W. Bach, E. Wiebus (Hoechst AG), unpublished results.
[127] S. S. Divekar, R. M. Deshpande, R. V. Chaudhari, Catal. Lett. 1993, 21, 191.
[128] M. Roeper, Paper presented on the occasion of Prof. Keim’s 60th birthday, RWTH
Aachen, Germany, Dec. 1994.
[129] A. Behr, Fat Sci. Technol. 1990, 92 (lo), 375.
[130] R. V. Chaudhari, B. M. Bhanage, R. M. Deshpande, H. Delmas, Nature (London)1994,
373, 501.
[I311 Exxon Research and Engineers Co., (I. Huang, R. Drogin), WO 80/01691 (1980).
[132] Union Carbide Corp. (R. A. Fiato, R. L. Pruett), EP 0.026.998 (1980).
[133] N. Nojiri, M. Misono, Appl. Catal. 1993, A 93, 103.
[ 1341 BASF AG (M. Roeper, W. Bertleff, D. Koeffer), US 4.962.243 (1990), US 5.043.487
(1991).
[135] Mitsubishi Kasei, US 4.990.698 (1991).
[136] Shell Oil Co., US 5.030.792 (1991).
[I371 Kuraray Co. (Y. Tokitoh, N. Yoshimura), US 4.808.756 (1989); JP 3.287.554 (1991);
EP 0.088.955 (1983).
[138] I. T. Horvhth, Catal. Lett. 1990, 6, 43.
[ 1391 A. Behr, Paper presented on the occasion of Prof. Keim’s 60thbirthday, RWTH Aachen,
Germany, Dec. 1994.
[I401 BASF AG (R. Kummer, D. Franz, H. P. Rath), EP 0.244.616 (1987).
[I411 Kuraray Co. (T. Kitamura, M. Matsumoto, M. Tamura), DE 3.210.617 (1981); Chem.
Abstr: 1983, 98, 106.821.
[142] J. R. Anderson, E. M. Campi, W. R. Jackson, Catal. Lett. 1991, 9, 55.
[143] S . D. Burke, J. E. Cobb, Tetrahedron Lett. 1986, 27 (36), 4237.
[ 1441 G. Fremy, E. Montflier, J. F. Carpentier, Y. Castanet, A. Mortreux, Angew. Chem. 1995,
107, 1608; Angew. Chem., Int. Ed. Engl. 1995, 34, 1474.
[I451 P. Kalck, P. Escaffre, F. Srein-Spirau, A. Thorez, New. J. Chem. 1988, 12, 687.
[146] M. M. Taqui Khan, S. B. Halligudi, S. H. R. Abdi, IN 167.684 (1987).
 References 629

[I471 Exxon Chem. Patents Inc. (F. J. Healy, J. R. Livingston, E. J. Mozeleski, J. G. Stevens
et al.), US 5.298.669 (1993), US 5.288.819 (1993), WO 93/04029 (1993).
[148] L. W. Gosser, W. H. Knoth. G. W. Parshall, J. Mol. Catal. 1977, 2, 253.
[I491 Ruhrchemie AG (W. Greb, J. Hibbel, J. Much, V. Schmidt et al.), DE 3.630.587 (1986),
DE 3.842.819 (1989); EP 0.263.953 (1987).
[ISO] T. Okano, Y. Moriyama, H. Konishi, J. Kiji, Chem. Lett. 1986, 1463.
[I511 N. V. Kolesnichenko, A. I. Teleshev, E. V. Slivinskii et al., Izv. Akad. Nauk. SSSR, Sex
Khim. 1991, ( S ) , 1026.
[152] (a) Hoechst AG (W. A. Henmann et al.), DE Appl. 4.447.066 bis 4.447.070 (1994). -
(b) W. A. Herrmann, J. Fischer, M. Elison, Ch. Kocher, G. A. J. Artus, Angew. Chem.
1996, 107, 2602; Angew. Chem., Int. Ed. Engl. 1995, 34, 2371.
[153] N. Winkhofer, U. Ritter, M. Noltemeyer, H. W. Roesky, Angew. Chem. 1996,108, 591;
Angew. Chem., Int. Ed. Engl. 1996, 35, 524.
[154] L. Cassar, M. FOB, A. Gardano, J. Organomet. Chem. 1976 121, C 5 5 ; L. Cassar, Chim.
Ind. (Milan) 1985, 67, 256.
[I551 J. Kiji, T. Okano, W. Nishiumi, H. Konishi, Chem. Lett. 1988, 957.
[156] T. Okano, I. Uchida, T. Nakagaki, H. Konishi, J. Kiji, J. Mol. Catal. 1989, 54, 65.
[157] M. M. Taqui Khan, S. B. Halligudi, S. H. R. Abdi, J. Mol. Catal. 1988, 44, 179.
[158] M. M. Taqui Khan, S. B. Halligudi, S. H. R. Abdi, S. Shukla, J. Mol. Catal. 1988, 48,
25, 325.
[159] Hoechst AG (M. Beller, C. W. Kohlpaintner), DE Appl. 4.415.681 and 4.415.682
(1994).
[160] RhGne-Poulenc Ind. (D. Morel), FR 2.486.525 (1980), FR 2.505.322 (1980).
[ 1611 Anon., Actualite' Chimique 1990 (Mar./Apr.).
[162] D. Morel, G. Mignani, Y. Colleuille, Tetrahedron Lett. 1985, 26, 6337; 1986, 27, 2591.
[163] Anon., Informations Chimie Hebdo. 1988, 939 (Nov. 10) p. 1.
[164] C. Mercier, P. Chabardes, Pure Appl. Chem. 1994, 66, 1509.
[165] RhBne-Poulenc Ind. (E. Kuntz), FR 2.338.253 (1976).
[166] T. I. Wallow, B. M. Novak, J. Am. Chem. SOC.1991, 113, 7411.
[167] A. Lubineau, J. AugC, Y. Queneau, Synthesis 1994, 8, 741.
[168] B. M. Novak, R. H. Grubbs, J. Am. Chem. SOC.1988, 110, 7542.
[169] T. D. Madden, P. J. Quinn, Biochem. Soc. Trans. 1978, 6, 1345.
[170] P. J. Quinn et al., J. Biochem. Biophys. Methods 1980, 2, 19; Eur: J. Biochem. 1981,
118, 335.
[171] L. Vigh, F. Job, P. R. van Hasselt, P. J. C. Kuiper, J. Mol. Catal. 1983, 22, 15.
[172] L. Vigh, F. Job, A. CsCpl6, Eur: J. Biochem. 1985, 146, 241.
[I731 D. Chapman, P. J. Quinn, Proc. Natl. Acad. Sci. USA 1976, 23, 3971.
[174] A. Behr, Fat Sci. Technol. 1990, 92, 375.
[175] A. Behr, K. Eustenviemann, J.Mol. Catal. 1991, 403, 209, 215.
[176] C. Larpent, R. Dabard, H. Patin, Inorg. Chim. 1987,26, 2922; New J. Chem. 1988, 12,
907; C. R. Acad. Sci. Paris, Ser: 2 1978, 304 (17), 1055.
[177] H. W. Bach, H. Bahrmann, W. Gick, W. Konkol, E. Wiebus, Chem.-Ing.-Tech. 1987,
59, 882.
[178] K. H. Schmidt, Chem. Znd. 1985, 37, 762; A. Behr, M. Roeper, Erdol-Kohle-Erdgas-
Petrochem. 1984, 37, 485.
[179] A. Chauvel, B. Delmon, W. F. Holderich, Appl. Catal. A: General 1994 115, 173.
[180] Anon., Eur: Chem. News 1995 (Jan. 15), 29; Europa-Chemie 1995, ( l ) , 10.
[181] Z. T6th, F. Jo6, M. T. Beck, Inorg. Chim. Acta 1980, 42, 153.
[182] Ref. [96a], p. 25; Ref. [96b], p. 221.
[183] E. Blart, J. P. GenCt, M. Safi, M. Savignac, D. Sinou, Tetrahedron 1994, 50, 505.
[184] Argonne Natl. Lab. (J. W. Rathke, R. J. Klinger), US 5.198.589 (1994).
630 3.1 Development of Methods

[185] Ruhrchemie AG (B. Cornils, W. Konkol, H. W. Bach, E. Wiebus et a].), DE 3.415.968

(1984).
[I861 D. Sinou, M. Safi, C. Claver, A. Masdeu, J. Mol. Cutul. 1991, 68, L9.
[187] G. Mignani, D. Morel, Y. Colleuille, C. Mercier, Tetrahedron Lett. 1986, 27, 2591.
[188] Z. Jiang, A. Sen, Macromolecules 1994, 27, 7215.
[189] R. Benhamza, Y. Amrani, D. Sinou, J. Orgunornet. Chem. 1985, 288, C37.
[190] G. Pfeiffer, S. Chhan, A. Bendayan, J. Mol. Cutul. 1990, 59, 1.
[191] W. Baidossi, N. Goren, J. Blum, H. Schumann, H. Hemling, J. Mol. Cutul. 1993,
85, 153.
[I921 J. Podlaha, J. Podlahova, Coll. Czech. Chem. Commun. 1973, 38, 1730.
[193] S. Ganguly, J. T. Mague, D. M. Roundhill, Inorg. Chem. 1992, 31, 3500.
[194] ICI Ltd., GB 1.432.561 (1972).
[195] Shell Int. Res. NL 87/00881 (1987).
[196] Ruhrchemie AG (B. Cornils, H. Bahrmann, E. Wiebus et a].), DE 3.411.034 (1984),
EP 0.157.316 (1985), DE 3.447.030 (1984), DE 4.242.723 (1992).
[I971 H. Ding, B. E. Hanson, J. Bakos, Angew. Chem. 1995, 107, 1728; Angew. Chem. Int.
Ed. Engl. 1995, 34, 1645.
[198] Ruhrchemie AG (B. Cornils, H. Bahrmann, E. Wiebus et al.), DE 3.412.335 (1984),
DE 3.616.057 (1986).
[199] B. Cornils, E. Kuntz, J. Orgunornet. Chem. 1995, 502, 177.
[200] J. Haggin, Chem. Eng. News, April 17, 1995, 25; A. G. Abatjoglou, 209th ACS
National Meeting, Anaheim, USA, 1995.
[201] B. Cornils, E. Wiebus, Recl. Trav. Chim. Pays-Bus 1996, 115, 211.
[202] B. Comils, E. Wiebus, Hydroc. Process 1996, March, 63.
[203] G. Papadogianakis, R. A. Sheldon, New J. Chem. 1996, 20, 175.
[204] A. Lubineau, Chem. & Ind. 1996, (4), 123.
[205] B. Cornils, Angew. Chem. 1995, 107, 1709; Angew. Chem., Int. Ed. Engl. 1995,
34, 1575.
[206] F. Gassner, W. Leitner, J. Chem. SOC.Chem. Commun. 1993, 1465.
[207] A. M. Tafesh, M. Beller, Tetrahedron Lett. 1995, 36, 9305.
[208] B. Fell, Ch. Schobben, G. Papadogianakis, J. Mol. Cutul. A 1995, 101, 179.
[209] Asahi Kasei KKK (K. Yamashita et a].), EP 0.552.809 (1992); J. R. Anderson, E. M.
Campi, W.R. Jackson, Z.P. Yang, J. Mol. Cutul. A: 1997, 116, 109.
[210] A. Gansauer, H. Bluhm, Chem. Rev. 2000, 100, 2771.
[211] (a) Aqueous-Phase Orgunometullic Catalysis, Eds.: B. Cornils, W. A. Herrmann,
Wiley-VCH, Weinheim, 1998; (b) E Job, E. Papp, A. Katho, Top. Cutul. 1998, 5,
113; (c) D. Sinou, in Transition Metal Organic Synthesis, Eds.: M. Beller, C. Bolm,
Wiley-VCH, Weinheim, 1998.
[212] (a) C.-J. Li, Chem. Rev. 1993, 93, 2023; (b) R.A. Sheldon, Chem. & Ind. (London)
1997, Jan. 6, 12; (c) Organic Synthesis in Water, Ed.: P. A. Grieco, Blackie Academic
& Professional, London, 1998; (d) R. Thomas, W. Tumas, Science 1999, 284, 1477;
(e) C.A. Eckert, C.L. Liotta, J. S. Brown, Chem. & Ind. (London) 2000, Feb. 7 , 94;
(f) K. Nomura, J. Mol. Cutul. A: 1998, 130, 1 .
[213] (a) R. Breslow, Acc. Chem. Res. 1991, 24, 159; (b) C. Reichardt, Nuchr: Chem. Tech.
Lab. 1997,45, 759; (c) R. A. Sanchez-Delgado et al., J. Mol. Cutal. A: 1997, 116, 167;
(d) S. Trinkhaus et al., J. Mol. Cutul. A: 1999, 144, 15; (e) G. Fremy et al., J. Mol.
Cutul. A: 1998, 129, 35 and Angew. Chem. 1995, 107, 1608.
[214] P. Cintas, Chem. Eng. News 1995, March 20, 4.
[215] (a) S. Kolaric, V. Sunjic, J. Mol. Cutul. A: 1996, I l l , 239; (b) L. Lavenot, A. Roucoux,
H. Patin, J. Mol. Cutul. A: 1997, 118, 153; (c) K.-C. Tin et al., J. Mol. Catul. A: 1999,
137, 113; (d) Elf Atochem, US 5.345.007 (1995).
 References 63 1

[216] (a) 0. Wachsen, K. Himmler, B. Cornils, Catal. Today 1998, 42, 373; (b) P. Kalk,
M. Dessoudeix, S. Schwarz, J. Mol. Catal. A: 1999, 143, 41; (c) C. Larpent,
E. Bernard, F. Brisse-le Menn, H. Patin, J. Mol. Catal. A: 1997, 116, 277.
[217] (a) A. Buhling, P. C. J. Kamer, P. W. N. M. van Leeuwen, J. W. Elgersma, J. Mol. Catal.
A: 1997, 116, 297; (b) B. DrieBen-Holscher, P. Wasserscheid, W. Keim, Cattech 1998,
June, 47; (c) A. Behr, Chem. lng. Tech. 1998, 70, 685; (d) P. W.N.M. van Leeuwen,
P.C. J. Kamer, J. N. H. Reek, Cattech 2000, 3(2), 64; (e) R. V. Chaudhari, A. Bhatta-
charya, B. M. Bhanage, Catal. Today 1995, 24, 123.
[218] (a) G.T. Baxley et al., J. Mol. Chem. A: 1997, 116, 191; (b) D. C. Mudalige, G.L.
Rempel, J. Mol. Catal. A: 1997, 116, 309; (c) L. Lavenot, M. H. Bortoletto et al., J. Or-
ganomet. Chem. 1996, 509, 9; (d) F. Ragaini, S. Cenini, J. Mol. Catal. A: 1996, 105,
145; (e) S. Lelikvre, F. Mercier, F. Mathey, J. Org. Chem. 1996, 61, 3531; (f) C. Len-
sink, E. Rijnberg; J. G. de Vries, J. Mol. Catal. A: 1997, 116, 199; (g) P. W.N.M. van
Leeuwen et al., J. Organomet. Chem. 1996, 522, 69, J. Mol. Catal. A: 1995,98, 69; (h)
J. J. Ziolkowski et al., J. Organomet. Chem. 1995,505, 11, J. Mol. Catal. A: 1998, 132,
203 and 1999,148,59; (i) B. N. Hanson et al., J. Mol. Catal. A: 1997,124,21; (i) M. S.
Goedheijt, P. C. J. Kamer, P. W. N. M. van Leeuwen, J. Mol. Catal. A: 1998, 134, 243;
(k) Z. Jiang, A. Sen, Macromolecules 1994, 27, 7215; (1) T. L. Schull, J. C. Fettinger,
A.D. Knight, lnorg. Chem. 1996, 35, 6717; (m) G.-J. ten Brink; I. W.C. E. Arends,
R.A. Sheldon, Science 2000, 287, 1636; (n) W. Klaui, M. Berghahn, G. Rheinwald,
H. Lang, Angew. Chem. Int. Ed. 2000, 39, 2464; (0) E. Paetzold, M. Michalik, G.
Oehme, J. Prakt. Chem. 1997, 339, 38; (p) T. Malmstrom, C. Anderson, Chem. Com-
mun. 1996, 1135 and J. Mol. Catal. A: 2000, 157, 79; (4) Hoechst AG, US 5.310.786
(1994); D. E. Bergbreiter, CHEMTECH 1987, (1 l), 686; E. Bayer, V. Schurig, Angew.
Chem. lnt. Ed. Engl. 1975,14,493 and CHEMTECH 1976, (3), 212; J. Chen, H. Alper,
J. Am. Chem. Soc. 1997, 119, 893; D. E. Bergbreiter, J.-G. Franchina, B. L. Case, Org.
Lett. 2000, 2, 939; J. W. Caraway, D. E. Bergbreiter, in Catalysis of Organic Reactions
(Ed.: R. E. Malz), Dekker, New York, 1996, p. 361; (r) R. W. Eckl, T. Priermeier, W. A.
Henmann, J. Organomet. Chem. 1997, 532, 243; W. A. Henmann et al. in Ref. [96b],
p. 127; (s) M. Beller et al., J. Am. Chem. Soc. 2000, 122, 10289; M. Beller et al., Tetra-
hedron Lett. 2000, 41, 8083; M. Beller et al., Angew. Chem. Int. Ed. 1999, 38, 3026;
[218t] M. Beller, J. G. E. Krauter, A. Zapf, S. Bogdanovic, Catul. Today 1999, 48, 279.
[219] (a) M. Beller et al., Angew. Chem. 1997, 109, 793; (b) L. Cammarota et al., J. Mol.
Catal. A: 1999, 137, 155; (c) S. Uk Son, J. W. Han, Y. K. Chung, J. Mol. Catal. A:
1998, 135, 35; (d) A. Gong et al., J. Mol. Catal. A : 2000, 159, 225; (e) E. Monflier,
G. Fremy, Y. Castanet, A. Mortreux, Angew. Chem. 1995, 107, 2450 and Tetrahedron
Lett. 1995, 36, 9481; (f) S. Shimizu et al., Angew. Chem. lnt. Ed. 2000, 39, 1313;
(g) S. Tilloy, F. Bertoux, A. Montreux, E. Monflier, Catal. Today 1999, 48, 245; (h)
M.T. Reetz, Catal. Today 1998, 42, 399; DE 19.631.322 and 19.960.802 (1998).
[220] F. Job, A. Kathb, J. Mol. Catal. A: 1997, 116, 3; B. M. Bhanage, F.-G. Zhao, M. Shirai,
M. Arai, Tetrahedron Lett. 1998, 9509.
[221] (a) S. Paganelli, M. Zanchet, M. Marchetti, G. Mangano, J. Mol. Chem. A: 2000, 157,
1 ; (b) S.-Kanagasabapathy, Z. Xia, G. Papadogianakis, B. Fell, J. Prukt. Chem. 1995,
337. 446.
[222] H. Bahrmann, B. Comils, in Aqueous-Phase Organometallic Catalysis (Eds.: B. Cor-
nils, W. A. Herrmann), Wiley-VCH, Weinheim, 1998, Chapter 4.4, p. 189; H. Bahrmann
et al., J. Organomet. Chem. 1997, 545-546, 139; T. Muller, H. Bahrmann, J. Mol.
Chem. A: 1997, 116, 39.
[223] P. Krammer, S. Mittelstadt, H. Vogel, Chem. lng. Tech. 1998, 70, 1559; A. A. Galkinj,
B. G. Kostyik, V. V. Lunin, M. Poliakoff, Angew. Chem. lnt. Ed. 2000, 39, 2738.
632 3. I Development of Methods

[224] W. A. Herrmann, C. W. Kohlpaintner, Inorg. Synth. 1998, 32, 8; W. A. Herrmann, in

Synthetic Methods of Organometallic and Inorganic Chemistry (Ed.: W. A. Herrmann),
Thieme, Stuttgart, 2000, Vol. 9, p. 153.
[225] A. Kumar et al., Angew. Chem. 1994, 106, 2272; F. Robert, G. Oehme, I. Gassert,
D. Sinou, J. Mol. Catal. A: 2000, 156, 127.
[226] (a) Hoechst AG, DE 19.529.874.8 (1995); Hoechst internal number Hoe 95R 185K;
(b) H. Jiang et al., J. Mol. Catal. A: 1999, 142, 147; (c) A.M. Tafesh, J. Weiguny,
Chem. Rev. 1996, 96, 2035.
[227] S. Kolaric, V. Sunjic, J. Mol. Catal. A: 1996, 110, 189 and 111, 239; A. W. Heinen et al.,
J. Mol. Catal. A: 1999, 142, 17.
[228] D. C. Mudalige, G. L. Rempel, J. Mol. Catal. A: 1997, 123, 15; Z. Yang, M. Ebihara,
T. Kawamura, J. Mol. Catal. A : 2000, 158, 509.
[229] E. G. Fidalgo, L. Plasseraud, G. Suss-Fink, J. Mol. Catal. A: 1998, 132, 5.
[230] (a) F. Lopez-Linares, M. G. Gonzales, D. E. Piez, J. Mol. Catal. A: 1999, 14.5, 61;
(b) A. Andriollo et al., J. Mol. Catal. A: 1997, 116, 157; (c) M. Hernandez, P. Kalck,
J. Mol. Catal. A: 1997, 116, 131; (d) F. JoO, J. Kovics, A. C. BCyei, A. Kath6, Angew.
Chem. 1998, 110, 1024; B. Driessen-Holscher, J. Heinen, J. Organomet. Chem. 1998,
570, 141.
[231] R. M. Deshpande, Purwanto, H. Delmas, R. V. Chaudhari, J. Mol. Catal. A: 1997, 126,
133; H. Chen et al., J. Mol. Catal. A: 1999, 149, 1.
[232] J.-X. Gao et al., J. Mol. Catal. A: 1999, 147, 99; M. Beller, J. G. E. Krauter, J. Mol.
Catal. A: 1999, 143, 31; DSM, WO 94/14.747 (1994).
[233] Z. Jin, in Aqueous-Phase Organometallic Catalysis (Eds.: B. Comils, W. A. Herr-
mann), Wiley-VCH, Weinheim, 1998, p. 233; Z. Jin et al., J. Prakt. Chem. 1996,
338, 124; Z. Jin, in et al., J. Mol. Catal. A: 1997, 116, 55, 1999, 147, 131 and 149,
113, 2000, 157, 111; Z. Jin et al., Catal. Today 1998, 44, 175; Z. Jin et al., J. Organo-
met. Chem. 1998, 571, 201.
[234] (a) E. A. Karakhanov, Yu. S. Kardasheva, E. A. Runova, V. A. Semernina, J. Mol. Catal.
A: 1999, 142, 339; (b) B.M. Bhanage, M. Shirai, M. Arai, J. Mol. Catal. A: 1999, 145,
69; (c) D. E. Bergbreiter, Li Zhang, V. M. Mariagnanam, J. Am. Chem. Soc. 1993, 115,
9295; (d) Q.-H. Fan et al., J. Mol. Catal. A: 2000, 159, 37.
[235] U. Ritter, N. Winkhofer, H.-G. Schmidt, H. W. Roesky, Angew. Chem. Int. Ed. Engl.
1996, 35, 524; T. Borrmann, H. W. Roesky, U. Ritter, J. Mol. Catal. A: 2000, 153,
31 and DE 19.728.944 (1997) and 19.521.936 (1996); Hoechst AG, DE 19.700.804
and 19.700.805 (1997); V. S. Nair, B.M. Bhanage, R. M. Deshpande, R. V. Chaudhari,
Stud. S u g Sci. Catal 1998, 113, 529.
[236] For example, B. Fell, D. Leckel, Ch. Schobben, Fat. Sci. Technol. 1995, 97, 219.
[237] F. Bertoux, E. Monflier, Y. Castanet, A. Mortreux, J. Mol. Catal. A: 1999, 143, 11;
R. Comes da Rosa, J.D. Ribeiro de Campos, R. Buffon, J. Mol. Catal. A: 2000,
153, 19; C.W. Kohlpaintner, M. Beller, J. Mol. Catal. A: 1997, 116, 259; Hoechst
AG, DE 4.415.681 (1995).
[238] M. Beller, J. G. E. Krauter, in Aqueous-Phase Organometallic Catalysis (Eds.: B. Cor-
nils, W. A. Herrmann), Wiley-VCH, Weinheim, 1998, p. 373; G. Papadogianakis,
L. Maat, R.A. Sheldon, J. Mol. Catal. A: 1997, 116, 179; F. Bertoux, E. Montflier,
Y. Castanet, A. Mortreux, J. Mol. Catal. A: 1999, 143, 23, 53.
[239] R. A. Sheldon, G. Papadogianakis, in Aqueous-Phase Organometallic Catalysis (Eds.:
B. Comils, W. A. Herrmann), Wiley-VCH, Weinheim, 1998, p. 506.
[240] H. Tohma, S. Takizawa, T. Maegawa, Y. Kita, Angew. Chem. Int. Ed. 2000, 39, 1306.
[241] E. Bolzonella, S. Campestrini, F. Di Furia, P. Ghiotti, J. Phys. Org. Chem. 1996, 9, 539;
A. Cagnina, S. Campestrini, F. Di Furia, P. Ghiotti, J. Mol. Catal. A: 1998, 130, 221.
 References 633

[242] N. Yoshimura, in Aqueous-Phase Orgunometullic Catalysis (Eds.: B. Cornils, W. A.

Herrmann), Wiley-VCH, Weinheim, 1998, p. 408.
[243] T. Prinz, W. Keim, B. Driessen-Holscher, Angew. Chem. 1996, 108, 1835 and EP
0.773.211 (1997).
[244] W. A. Herrmann, W. C. Schattenmann, in Aqueous-Phase Organometallic Catalysis
(Eds.: B. Cornils, W.A. Herrmann), Wiley-VCH, Weinheim, 1998: (a) p. 453;
(b) p. 340; (c) p. 383; (d) p. 393; (e) p. 408; (0418; (g) p. 455; (h) p. 477; p. 513;
(i) p. 529; (j)p. 577; p. 105, 123.
[245] G. Verspui, J. Feiken, G. Papadogianakis, R. A. Sheldon, J. Mol. Catal. A: 1999, 146,
299; G. Verspui, G. Papadogianakis, R.A. Sheldon, Chem. Commun. 1998, 3, 401;
G. Verspui, F. Schanssema, R.A. Sheldon, Angew. Chem. 2000, 112, 825; Angew.
Chem. Int. Ed. 2000, 39, 804.
[246] Cf. Ref. [244], p. 448; E. Paetzold, G. Oehme, J. Mol. Cutul. A: 2000,152,69; Hoechst
AG, DE-OS 19.527.118 A1 (1995); M. Beller, J.G.E. Krauter, A. Zapf, Angew. Chem.
Int. Ed. 1997, 36, 772.
[247] G. Wiillner, H. Jansch, S. Kannenberg, F. Schubert, G. Broche, Chem. Conzmun. 1998,
1509.
[248] C.-J. Li, Y. Meng, J. Am. Chem. Soc. 2000, 122, 9538.
[249] B. Heller, Nachl: Chem. Tech. Lab. 1999, 47, 9.
[250] E. Monflier et al., J. Mol. Cutul. A: 1996, 109, 27;
[25 I ] A. Chattopadhyay, A. Salaskar, Synthesis 2000, 56 1.
[252] M. G. Russell, S. Warren, J. Chem. Soc., Perkin Trans. 2000, 4, 505.
[253] S. Nagayama, S. Kobayashi, Angew. Chem. Int. Ed. 2000, 39, 567.
[254] A. Behr, N. Toslu, Chem. Ing. Tech. 1999, 71, 490.
[255] B.R. Eaton, M.S. Sigmann, A. W. Fatland, J. Am. Chem. Soc. 1998, 120, 5130.
[256] I. Rojas, F. Lopez Linares, M. Valencia, C. Bianchini, J. Mol. Cutul. A: 1999, 144, 1.
[257] S. Kobayashi et al., Tetrahedron Lett. 2000, 41, 3107.
[258] A. Romerosa, M. Peruzzini, Orgunometullics 2000, 19, 4005; R. Grubbs et al., J. Am.
Chem. Soc. 1998, 120, 1627; M.C. Schuster et al., J. Mol. Catal. A: 1997, 116, 209.
[259] M. Al-Jahdali et al., J. Mol. Cutul. A: 2000, 159, 51.
[260] B. Cornils, Org. Proc. Res. Dev. 1998, 2 , 121; B. Cornils, C. W. Kohlpaintner, E. Wie-
bus, Encyclopedia of Chemical Processing and Design, Dekker, New York, 1999,
Vol. 66, p. 273; B. Cornils, J. Mol. Cutal. A: 1999, 143, 1; B. Cornils, Ind. Cutul.
News 1998, 2 , 7; H. Bohnen, B. Cornils, Adv. Catalysis, 2002, in press.
[261] T. With, Angew. Chem. Int. Ed. 2000, 39, 334.
[262] I.V. Kozhevnikov, G.P. Mulder, M.C. Steverink-de Zoete, M.G. Oostwal, J. Mol.
Catal. A: 1998, 134, 223; H. Rudler et al., J. Mol. Cutul. A: 1998, 133, 255; W.A.
Herrmann et al., J. Orgunomet. Chem. 1997, 549, 319; G. Pozzi, F. Montanari,
S. Quici, Chem. Commun. 1997, 69.
[263] D. Sinou et al., Catal. Today 1998, 42, 471.
[264] H. Bricout, A. Mortreux, E. Monflier, J. Organornet. Chem. 1998, 553, 469.
[265] J. Kiji, T. Okano, H. Kimura, K. Saiki, J. Mol. Catal. A: 1998, 130, 95.
[266] G. Ma, H. Freiser, S. Muralidharan, Anal. Chem. 1997, 69, 2827; R. V. Chaudhari et al.,
US 5.6.50.546 (1997).
[267] C. Bianchini, A. Meli, V. Patinec, V. Sernau, F. Vizza, J. Am. Chem. Soc. 1997, 119,4945.
[268] J. Cermak, M. Kvicalova, V. Blechta, Collect. Czech. Commun. 1997, 62, 355.
[269] G. Bellucci, C. Chiappe, G. Lo Moro, Synlett 1996,880; Tetrahedron Lett. 1996,37,4225.
[270] A. G. Abatjoglou, R. R. Petersen, D. R. Bryant, in Catalysis of Organic Reactions
(Ed.: R. E. Malz), Dekker, New York, 1996.
[27 13 Enichem, US 6.07 1.848 (2000).
[272] B. Zimmermann, J. Herwig, M. Beller, Angew. Chem. Int. Ed. 1999, 38, 2372.
 Applied Homogeneous Catalysis with Organometallic Compounds
Edited by B. Cornils and W. A. Herrmann
Copyright 0 Wiley-VCH Verlag GmbH, D-69469 Weinheim, 2002

634 3.1 Development of Methods

3.1.1.2 Immobilization by Other Liquids

3.1.1.2.1 Fluorous Phases

Istvan 7: Horvath

Aqueous catalysts offer facile catalyst separation for many homogeneous catalytic
reactions [ 13 and several new processes have been commercialized (cf. Section
3.1.1.1). However, aqueous media cannot be used for chemical systems in
which a component of the system undergoes undesired chemical reactions with
water. Furthermore, the low solubility of many organic compounds in water
could limit the applications of aqueous catalysts. Nonaqueous biphasic systems
could overcome these limitations, provided the catalyst is preferentially soluble
in the catalyst phase at the conditions under which the catalyst phase is separated
from the product phase. It should be noted that there may be some catalyst loss
into the product phase. The acceptable level of catalyst leaching depends on the
quality specifications of the product, whether the residual catalyst could cause
any health and/or environmental hazards, and the cost of the catalyst. When the
leached catalyst has to be removed from the product phase, the cost of additional
conventional catalyst separation and recycling must be considered also.
Since the formation of a liquid-liquid biphase system is due to a sufficient dif-
ference in the intermolecular forces of two liquids [2], the selection of a nonaqu-
e m s catalyst phase depends primarily on the solvent properties of the product
phase at a high conversion level. For example, if the product is apolar the catalyst
phase should be polar, and vice versa: if the product is polar the catalyst phase
should be apolar. The success of any nonaqueous biphase system depends on
whether the catalyst could be designed to dissolve preferentially in the catalyst
phase. Perhaps the most important rule for such design is that the catalyst has
to resemble the catalyst phase, since it has been known for centuries that “similia
similibus solvuntur,” of “like dissolves like” [3].
The solvent properties of alcohols with short carbon chains are similar to those
of water and such alcohols could be used as the nonaqueous catalyst phase when
the products are apolar in nature. The first commercial biphasic process, the Shell
Higher Olefin Process (SHOP) developed by Keim et al. [4], is nonaqueous and
uses butanediol as the catalyst phase and a nickel catalyst modified with a diol-
soluble phosphine, R2PCH2COOH.While ethylene is highly soluble in butane-
diol, the higher olefins phase-separate from the catalyst phase (cf. Section
2.3.1.3). The dimerization of butadiene to 1,3,7-octatriene was studied using
triphenylphosphine-modified palladium catalyst in acetonitrile/hexafluoro-2-phe-
nyl-2-propanol solvent mixtures [5]. The reaction of butadiene with phthalic
acid to give octyl phthalate can be catalyzed by a nonaqueous catalyst formed
in-situ from Pd(acac)2 (acac, acetylacetonate) and P(OC6H40CH3)3in dimethyl
sulfoxide (DMSO). In both systems the products are extracted from the cata-
lyst phase by isooctane, which is separated from the final products by distillation
PI.
 3.1.1.2 Immobilization by Other Liquids 635

Perfluorinated alkanes, ethers, and tertiary amines are unusual because of their
nonpolar nature and low intermolecular forces. Their miscibility with toluene, tet-
rahydrofuran (THF), acetone, and alcohols is low; thus these materials could form
biphase systems under appropriate conditions [2]. A novel concept for performing
chemical transformations, including transition-metal- catalyzed reactions, that is
based on the limited miscibility of partially or fully fluorinated compounds with
nonfluorinated compounds was recently developed and reported in detail [6].
The fluorous biphase system consists of a fluorous phase containing a dissolved
catalyst and a second phase, which may be any organic or inorganic solvent
with limited solubility in the fluorousphase (Figure 1). The term “fluorous” is in-
troduced, in analogy to the term “aqueous”, to emphasize the fact that the chemi-
cal transformation is primarily controlled by a catalyst dissolved preferentially in
the fluorous phase. The fzuorous phase is defined as the fluorocarbon-rich phase
of a biphase system (this fluorocarbon most frequently consisting of perfluori-
nated alkanes, ethers, and tertiary amines). The most effective fluorous solvents
are perfluorinated alkanes, perfluorinated alkyl ethers, and perfluorinated trialkyl
amines [6, 71. The use of perfluorinated polyalkyl ethers such as Hostinert@, a
fluorous solvent developed by Hoechst, for fluorous biphase catalysis has been
recently demonstrated by Vogt [8].
Although most soluble homogeneous catalysts could be made fluorous-soluble
by attaching fluorous ponytails to the catalyst core in appropriate size and number
[9], transition metal complexes have mostly been converted to fluorous-soluble
through ligand modification [ 101. The most effective fluorocarbon moieties are
linear or branched perfluoroalkyl chains with high carbon number that may con-

Other phase

A+B <

Fluorous phase Jvv\r=-(CF2)XF:

Figure 1. Diagrammatic representation of a fluorous biphase system.

CA(F),CBCF),and Cp(F)are the concentrations of reactants A and B and product P in
thefluornus phase. CA(o,,CB(0)rand Cp(o)are the concentrations of reactants A and
B and product P in the other phase.
636 3.1 Development of Methods

tain other heteroatoms (the fluorocarbon tethers or “fluorous ponytails”). The suc-
cessful development of fluorous biphase organometallic catalysts requires an easy
access to ligands with appropriate (absolute and/or relative) fluorous solubility.
Their relative solubility can be quantified with fluorous partition coefficients or
related terms, such as fluorophilicity or specific fluorophilicity [Ill. In order to
avoid significant leaching of fluorous reagents and catalysts, the partition proper-
ties of all fluorous catalytic intermediates involved should be tuned for high
fluorous-phase affinity. Some empirical rules for designing fluorophilic reagents
and catalysts have been summarized [lo, 121. It should be emphasized that per-
fluorouryl groups do offer dipole-dipole interactions, making them less com-
patible with the fluorous biphase concept than perfluorulkyl groups. The insertion
of two or three -CH2- groups before the fluorous ponytail may be necessary to
decrease the strong electron-withdrawing effects of the fluorous ponytails, an
important consideration if catalyst reactivity is desired to approximate to that
observed for the unmodified species in traditional single-phase hydrocarbon
solvents.
A fluorous biphase reaction could proceed either in the fluorous phase or at the
interface of the two phases, depending on the solubilities of the reactants in the
fluorous phase. When the solubilities of the reactants are very low in the fluorous
phase, the chemical reaction may still occur at the interface or appropriate phase-
transfer agents may be added to facilitate the reaction. It should be emphasized
that a fluorous biphase system might be changed to a one-phase system by
increasing the temperature. Thus, the advantages of one-phase catalysis with
biphase product separation could be combined for a fluorous catalyst by running
the reaction at higher temperatures and separating the products at lower tempera-
tures.
Fluorous ligand-modified biphase catalysts have been successfully used in
allylic nucleophilic substitutions [ 141, cross-coupling reactions [ 151, Diels-Alder
reaction [ 161, epoxidation of olefins [17-201, Friedel-Crafts acylation [ 161, Heck
heterocoupling [2 11, hydrogenation [22-251, hydroformylation [6, 7, 13, 261,
hydroboration [27], hydrosilylation [28], intramolecular cyclization of unsaturated
esters [29], Kharasch addition reaction [30], living radical polymerization [3 11,
oligomerization [8], oxidation of alcohols [32], oxidation of aldehydes [ 181, oxi-
dation of alkanes [19, 331, oxidation of sulfides [7, 181, Stille couplings [34, 351,
and Wacker oxidation of alkenes [36]. In addition several chiral catalysts have re-
cently been developed for alkylation of aromatic aldehydes [37, 381 and epoxida-
tion of olefins [39]. The common feature of these catalytic systems is the easy
separation of the product(s) and the facile recycling of the fluorous catalyst.
Fluorous solvents are generally considered to be too expensive for large-scale
commercial processes. However, their nontoxic nature and the significant simpli-
fication of the separation step could make a fluorous technology very attractive for
the production of fine chemicals and pharmaceuticals. One should also consider
the fact that a simple separation technology could result in significant savings
on initial investments on hardware, and energy savings during separation. In ad-
dition, successful investment of the savings during the plant construction period
could result in enough earnings for a state-of-the-art fluorous technology to be
 References 637

financially beneficial over technologies using a hardware-intensive separation

method such as distillation.
Another important and rapidly growing area of nonaqueous biphasic catalysis is
based on the application of molten salts or ionic liquids as the catalyst phase. The
most attractive ionic liquids for transition metal catalysis are those that have a
melting point near to room temperature. Generally, such ionic liquids are either
organic salts or mixtures of organic cations, such as substituted pyridinium or imi-
dazolium cations, and inorganic weakly or noncoordinating anions, such as BF4-
or PF6- [40]. They could provide a polar but nonprotic and noncoordinating
environment that could be beneficial in catalytic reactions involving ionic or
polar intermediates. The nonvolatile nature of ionic liquids eliminates containment
problems frequently associated with most common organic solvents. In addition,
they are relatively cheap and easy to prepare, making them suitable for commer-
cial applications. Various ionic liquids have been used for dimerization of olefins
[41] and dienes [42], oligomerization of olefins [43], various C-C coupling reac-
tions [44], hydroformylation [45], hydrogenation [46], and oxidations [47]. The
usability of ionic liquids in biphasic catalysis is ultimately dependent on the parti-
tion of the catalyst between the ionic liquid phase and the product phase. The ionic
nature of the catalyst or the attachment of ionic groups to the ligands of transition
metal complex catalysts could ensure effective separation from the products (cf.
Section 3.1.1.2.2).
In conclusion, the possibility of selection from various biphase systems pro-
vides a powerful portfolio for catalyst designers to develop novel and commer-
cially attractive catalysts. It is important to recognize that the initial selection
should be governed by the separation of the product from the catalyst phase
followed by the solubility of the reactants in the catalyst phase.

References
[ l ] F. Job, Z. Tbth, J. Mol. Catal 1980, 8, 369; E. G. Kuntz, CHEMTECH 1987, 17, 570;
W.A. Henmann, C.W. Kohlpaintner, Angew. Chem., Int. Ed. Engl. 1993, 32, 1524;
Aqueous Organometallic Chemistry and Catalysis (Eds.: I. T. HorvBth, F. Job), Kluwer,
Dordrecht, 1995; Aqueous-Phase Organometallic Catalysis (Eds.: B. Cornils, W. A.
Henmann), Wiley-VCH, Weinheim, 1998.
[2] J. H. Hildebrand, J. M. Prausnitz, R. L. Scott, Regular and Related Solutions, Van
Nostrand Reinhold, New York, 1970, Chapter 10.
[3] C. Reichardt, Solvents and Solvent Efsects in Organic Chemistry, 2nd ed., VCH,
Weinheim, 1990.
[4] Shell International Research (W. Keim, T. M. Shryne, R. S. Bauer, H. Chung, P. W.
Glockner, H. van Ywet), DE 2.054.009 (1969); W. Keim, Chem. Zng. Techn. 1984,
56, 850.
[5] W. Keim, A. Durocher, P. Voncken, Z. Erdol Kohle 1976, 29, 31.
[6] I.T. HorvBth, J. RBbai, Science 1994, 266, 72.
[7] Exxon Research and Engineering Co. (I. T. HorvBth, J. RBbai), US 5.463.082 (1995).
[8] M. Vogt, Ph.D. Thesis, Rheinisch-WestfalischeTechnischeHochschule, Aachen, Germany
(1991).
[9] M. C. A. Van Vliet, W.C. E. Arends, R. A. Sheldon, Chem. Commun. 1999, 263.
638 3.1 Development of Methods

[lo] I.T. HorvBth, Acc. Chem. Res. 1998, 31, 641; E. De Wolf, G. van Koten, B.-J. Deel-
man, Chem. SOC. Rev. 1999, 28, 37; M. Cavazzini, F. Montanari, G. Pozzi, S. Quici,
J. Fluorine Chem. 1999, 94, 183; R. H. Fish, Chem. Eul: J . 1999, 5, 1677.
[11] C., Rocaboy, W. Bauer, J. A. Gladysz, Eur: J. Org. Chem. 2000, 2621; C. Rocaboy,
D. Rutherford, B. L. Bennett, J. A. Gladysz, J. Phys. Org. Chem. 2000, 13, 1;
L. E. Kiss, I. Kovesdi, J. RBbai, J. Fluorine Chem. 2001, 108, 95.
[12] L.P. Barthel-Rosa, J.A. Gladysz, Coord. Chem. Rev. 1999, 190, 587.
[13] I. T. Horvath, G. Kiss, R. A. Cook, J. E. Bond, P. A. Stevens, J. RBbai, E. J. Mozelski,
J. Am. Chem. Soc. 1998, 120, 3133.
[14] R. Kling, D. Sinou, G. Pozzi, A. Choplin, F. Quignard, S. Busch, S. Kainz, D. Koch,
W. Leitnec Tetrahedron Lett. 1998, 39, 9439.
1151 B. Betzemeier, P. Knochel, Angew. Chem., Int. Ed. 1997, 36, 2623.
1161 J. Nishikido, H. Nakajima, T. Saeki, A. Ishii, K. Mikami, SYNLETT2998, 1347.
[17] G. Pozzi, S. Banfi, A. Manfredi, F. Montanan, S. Quici, Tetrahedron 1996, 52, 11879;
G. Pozzi, I. Colombani, M. Miglioli, F. Montanari, S. Quici, Tetrahedron 1997, 53,
6145; G., Pozzi, F. Montanan, S. Quici, Chem. Commun. 1997, 69; S . Quici, M. Cavaz-
zini, S. Ceragioli, F. Montanari, G. Pozzi, Tetrahedron Lett. 1999, 40, 3647.
[18] I. Klement, H. Liitjens, P. Knochel, Angew. Chem., lnt. Ed. Engl. 1997, 36, 1454.
[I91 J.-M. Vincent, A. Rabion, V. K. Yachandra, R. H. Fish, Angew. Chem., Int. Ed. Engl.
1997, 36, 2346.
[20] B. Betzemeier, F. Lhermitte, P. Knochel, SYNLETT1999, 489.
[21] L. K. Yeung, R. M. Crooks, Nano Lett. 2001, I , 14.
[22] D. Rutherford, J. J. J. Juliette, C. Rocaboy, I.T. HorvBth, J.A. Gladysz, Catal. Today
1998, 42, 38 1.
[23] E.G. Hope, R.D.W. Kemmitt, D.R. Paige, A.M. Stuart, J. Fluorine Chem. 1999,
95, 125.
[24] B. Richter, B.-J. Deelman, G. van Koten, J. Mol. Catal. A: Chemical 1999, 145, 317;
B. Richter, E. de Wolf, G. van Koten, B.-J. Deelman, J. Org. Chem. 2000, 65, 3885.
[25] V. Chechik, R.M. Crooks, J. Am. Chem. Soc. 2000, 122, 1243.
[26] W. Chen, L. Xu, J. Xiao, Chem. Commun. 2000, 839.
[27] J. J. J. Juliette, I. T. Horvath, J. A. Gladysz, Angew. Chem., Int. Ed. Engl. 1997,36, 1610;
J. J. J. Juliette, D. Rutherford, I. T. Horvith, J. A. Gladysz, J. Am. Chem. SOC. 1999, 121,
2696.
[28] L. V. Dinh, J. A. Gladysz, Tetrahedron Lett. 1999, 40, 8995.
[29] F. De Campo, D. LastCcoueres, J.-M. Vincent, J.-P. Verlhac, J. Org. Chem. 1999, 64,
4969.
[30] H. Kleijn, J. T. B. H. Jastrzebski, R. A. Gossage, H. Kooijman, A. L. Spek, G. van Koten,
Tetrahedron 1998, 54, 1145.
[31] D. M, Haddleton, S. G. Jackson, S. A. Bon, J. Am. Chem. Soc. 2000, 122, 1542.
[32] B., Betzemeier, M. Cavazzini, S. Quici, P. Knochel, Tetrahedron Lett. 2000, 41, 4343.
[33] G., Pozzi, M. Cavazzini, S. Quici, Tetrahedron Lett. 1997, 38, 7605.
[34] D.P. Curran, M. Hoshino, J. Org. Chem. 1996, 61, 6480; M. Hoshino, P. Degenkolb,
D.P. Curran, J. Org. Chem. 1997, 62, 8341; M. Larhed, M. Hoshino, S. Hadida, D.P.
Curran, A. Hallberg, J. Org. Chem. 1997, 62, 5583.
[35] S. Schneider, W. Bannwarth, Angew. Chem., lnt. Ed.. 2000, 39, 4142.
[36] B. Betzemeier, F. Lhermitte, P. Knochel, Tetrahedron Lett. 1998, 39, 6667.
[37] H. Kleijn, E. Rijnberg, J. T. B. H. Jastrzebski, G. van Koten, Organic Lett. 2000, I , 853.
[38] Y. Nakamura, S. Takeuchi, Y. Ohgo, D. P. Curran, Tetrahedron 2000, 56, 35 1; Y. Naka-
mura, S. Takeuchi, Y. Ohgo, D. P. Curran, Tetrahedron Lett. 2000, 41, 57.
[39] G. Pozzi, M. Cavazzini, F. Cinato, F. Montanan, S. Quici, Eur: J. Org. Chem. 1999,
1947.
 References 639

[40] T. Welton, Chem. Rev. 1999, 99, 207 1; P. Wasserscheid, W. Keim, Angew. Chem., Int.
Ed. 2000, 39, 3772.
1411 Y. Chauvin, B. Gilbert, I. Guibard, Chem. Commun. 1990, 1715; Y. Chauvin, H. Olivier-
Bourbigou, CHEMTECH 1995, 25, 26; Y. Chauvin, S. Einloft, H. Olivier, Ind. Eng.
Chem. Res. 1995, 34, 1149; S . Einloft, F. K. Dietrich, R. F. de Sourza, J. Dupont,
Polyhedron 1996, 19, 3257.
1421 S. M. Silva, P. A. Z. Suarez, R. F. de Souza, J. Dupont, Polym. Bull. 1998, 40, 401.
[43] H. Olivier, P. Laurent-GCrot, J. Mol Cutul. A: Chemical 1999, 148, 43.
[44] D.E. Kaufmann, M. Nouroozian, H. Henze, SYNLETT 1996, 1091; W.A. Herrmann,
V.P. Bohm, J. Orgunornet. Chem. 1999, 572, 141; V.P. Bohm, W.A. Herrmann,
Chem. Eur: J . 2000, 6, 1017; L. Xu, W. Chen, J. Xiao, Orgunornetullics 2000, 19,
1123, A. J. Carmichael, M. J. Earle, J. D. Holbrey, P. B. McCormac, K. R. Seddon,
Org. Lett. 1999, I , 997.
1451 J. F. Knifton, J. Mol. Cutul. 1987, 43, 65; J. F. Knifton, J. Mol. Cutul. 1988, 47, 99;
N. Karodia, S. Guise, C. Newlands, J.-A. Andersen, Chem. Commun. 1998, 2341;
W. Keim, D. Vogt, H. Waffenschmidt, P. Wasserscheid, J. Cutul. 1999, 186, 481.
[46] G. W. Parshall, J. Am. Chem. Soc. 1972, 94, 8716; P.A.Z. Suarez, J.E.L. Dullius,
S. Einloft, R. F. de Souza, J. Dupont, Polyhedron, 1996, 15, 1217; Y. Chauvin, L. Muss-
mann, H. Olivier, Angew. Chem., Znt. Ed. Engl. 1995, 34, 2698; P. J. Dyson, D. J. Ellis,
D. G. Parker, T. Welton, Chem. Commun. 1999, 25.
[47] J. Howarth, Tetrahedron Lett. 2000, 41, 6627; G.S. Owens, M.M. Abu-Omar, Chern.
Commun. 2000, 1165; C. E. Song, E. J. Roh, Chem. Commun. 2000, 837.

3.1.1.2.2 Non-Aqueous Ionic Liquids

Volker P W Bohm

Introduction
Ionic liquids are solvents that are composed entirely of ions. They have virtually
no vapor pressure, a high ionic conductivity, and a broad electrochemical window,
and can be tuned to be liquid over a wide range of temperatures. Furthermore,
they are good solvents for organic, inorganic and polymeric compounds, resem-
bling an environmentally benign alternative to conventional, molecular solvents.
Most frequently, the term ionic liquid refers to 1-alkyl-3-methylimidazolium
salts [RMIMIX (Strucutre 1) and pyridinium salts 2 (R = CnHZn+,, X = anion,
e.g., AlCl,, SnC13, BF,, PF6, C1, HS04, CF,SO,) but other molten salts such as
ammonium and phosphonium salts have also been used. Meanwhile, a variety
of both comprehensive and short reviews have covered the physical properties
of ionic liquids as well as their use as alternative solvents [l].

1 2
640 3.1 Development of Methods

Generally, ionic liquids consist of a large cation with low symmetry and prefer-
entially a bulky anion. Thus, the lattice energy of the salt crystal is reduced, and
hence its melting point is lowered [I b]. Most ionic liquids are easily prepared,
inexpensive, and convenient to recycle. The individual properties of different
ionic liquids, such as melting point, viscosity, density, and hydrophobicity can
be fine-tuned by variation of the anion as well as the cation (e.g., by changing
the alkyl group R). The strong influence of the anion is demonstrated in a series
of l-ethyl-3-methylimidazoliumsalts [EMIMIX: the chloride salt (X = Cl) has a
melting point of 87 "C [2] whereas the trifluoroacetate salt (X = CF,COO) melts
at -14 "C [3], intermediate melting points being obtained with other anions. Mis-
cibility properties of the ionic liquids can be tuned as well by varying the anion or
cation, e. g. longer alkyl chain residues R make the ionic liquid less polar. In this
manner, biphasic or even triphasic systems with water or organic solvents can be
prepared. Supercritical CO, and l-butyl-3-methylimidazoliumhexafluorophos-
phate [BMIM]PF6 is an example of a biphasic system [4].

Homogeneous Transition-Metal Catalyzed Reactions

in Ionic Liquids
Despite the early use of phosphonium salt melts as reaction media [12, 18, 2.51, the
use of standard ionic liquids of type 1 and 2 as solvents for homogeneous transi-
tion metal catalysts was described for the first time in the case of chloroaluminate
melts for the Ni-catalyzed dimerization of propene [5] and for the titanium-cata-
lyzed polymerization of ethylene [6]. These inherently Lewis-acidic systems were
also used for Friedel-Crafts chemistry with no added catalyst in homogeneous [7]
as well as heterogeneous fashion [8], but ionic liquids which exhibit an enhanced
stability toward hydrolysis, i. e., most non-chloroaluminate systems, have been
shown to be of advantage in handling and for many homogeneously catalyzed
reactions [la]. The Friedel-Crafts alkylation is possible in the latter media if
Sc(0TQ3 is added as the catalyst [9].
Due to the good solubility of organometallic compounds, ionic liquids have
been used as reaction media, replacing traditional molecular solvents, or as the
catalyst-supporting phase in a biphasic system. Influences of the ionic liquid on
the reaction rate and selectivity can mostly be explained by the reactivity of the
anion, which can be noncoordinating or coordinating as well as Lewis-acidic,
Lewis-basic or neutral. The cation, in contrast, is considered to be essentially non-
coordinating and innocent.

Hydrogenation and Oxidation

Pd, Pt, Rh, and Ru complexes were used as catalysts for the hydrogenation of
alkenes with molecular hydrogen. In many cases, higher activity and enhanced
selectivity for the desired reaction were accompanied by successful re-use of
the ionic liquid and the catalyst. Examples are reported for cyclohexadiene [lo],
 3.1.1.2 Immobilization by Other Liquids 641

butadiene [lo b, 111, mono-olefins [ 11, 121, arenes [13], acrylonitrile-butadiene

rubber [ 141 and sorbic acid [ 151. In the case of the hydrogenation of cyclohexa-
diene [ 10 a] and of sorbic acid [ 151 the reactions exhibit an extraordinary product
selectivity (eq. (1)).
Also, enantioselective hydrogenation was performed using Rh/DIOP [ 10 a] and
Ru/BINAP as catalysts [16]. For the latter catalyst, an example is the industrially
feasible synthesis of (S)-Naproxen. PdC12 on silica was used in [NBu4]C1to hy-
drodechlorinate CC14, giving alkanes and alkenes [17]. The reduction of CO to
ethylene glycol is possible in quaternary phosphonium salts with hydrido mthe-
nium carbonyl clusters being the catalytically active species [ 181.

H2
[Cp*Ru(diene)]CF3S03
-COOH + n C-O O H (1)

MTO [methyltrioxorhenium(VII), cf. Chapter 3.3.131 can be used as a catalyst

for the epoxidation of olefins with urea hydroperoxide in [EMIM]BF4 [19]. The
activity is reported to be comparable with the reaction in organic solvents but
side reactions are suppressed. The use of an ionic liquid as a co-solvent in
CH2C12for the enantioselective Mn-salen complex-catalyzed epoxidation of ole-
fins with Na(OC1) was reported to result in enhanced reaction rates at no loss of
enantioselectivity [20]. Cr-salen complexes can further be used for the asym-
metric kinetic resolution of epoxides by ring-opening with azide [21].

Hydroformylation (0x0 Reaction) and Carbonylation

At room temperature the Rh-catalyzed hydroformylation of butadiene [22] and of

I -pentene is possible (eq. (2)) [ 10 a]. In the latter case, [Rh(CO),(acac)] in the
presence of triphenylphosphine achieves slightly higher turnover frequencies
(TOF) as compared to reactions in toluene. The product ratio of n:iso-aldehyde
was not influenced by the solvent. The use of the monosulfonated triphenyl-
phosphine (tppms), however, reduced the activity of the catalyst drastically
although its use allowed a more efficient recycling of the catalyst [ l o a].
CO I H2

[Rh(C0)2(acac] I ligand R
R- + * R-CHO + yCHO (2)
[
in C4H9 N%CH,] pF,'

In contrast, the use of cobaltocenium bis(dipheny1)phosphine 3 results in

increased activity and selectivity toward the n-aldehyde [23]. In an alternative
approach, Rh2(OAc)4 was used as the catalyst in a phosphonium salt melt 1241.
642 3.1 Development of Methods

Ru clusters can be used in a phosphonium salt melt [25] and the platinum-
catalyzed hydroformylation can be performed in chlorostannate ionic liquids
which serve as the solvent and (via the anion) as the catalyst activator at the
same time [ 12, 261.
The Pd-catalyzed alkoxycarbonylation of styrenes was achieved in the biphasic
system [BMIM]BF,-cyclohexane [27]. High regioselectivity of up to 199: 1 in
favor of the iso-ester was observed after optimization of the phosphine ligand.
This reaction can also be run in chlorostannate melts using a platinum catalyst
[121.

Vinylation, Allylation, and Cross-Coupling Reactions

Aryl bromides as well as aryl chlorides show increased reactivity in the Mizo-
roki-Heck vinylation (eq. (3)) with various olefins when the reaction is performed
in molten ammonium or phosphonium salts [28] (see also Section 3.1.6). Many
common catalysts, including ligand-free Pd salts, show a substantial increase in
activity and thermal stability.
2 mol% PdCI2

0" + B r a Na(0Ac)
in [NBu4]Br
* @ (3)

150 "C
- HBr 94 YOyield (2 h)

The use of imidazolium salts 1 is also possible although the activity of the
catalyst tends to decrease [28 c, 291. Thus, only activated aryl halides like iodo-
benzene can be coupled, but the recycling of the solvent and the catalyst is
very easy.
The Tsuji-Trost allylic substitution catalyzed by Pd complexes using CH-
acidic nucleophiles can be performed in an ionic liquid of type 1 alone [30]
as well as in a biphasic system [31]. In the latter case the use of trisulfonated
triphenylphosphine (TPPTS) prevents the catalyst from leaching into the
organic phase. In comparison with water as the catalyst-supporting phase,
the ionic liquid system exhibits higher activity and selectivity. The enantio-
selective version of the allylic substitution with dimethyl malonate can also
be performed in ionic liquids with a homochiral ferrocenylphosphine as the
ligand [32].
The formation of unsymmetric biaryls via catalytic cross-coupling of aryl
halides and organometallic compounds has been shown to proceed in ionic liquids
with enhanced activity. The Suzuki-Miyaura cross coupling (cf. Section 2.11)
 3.1.1.2 Immobilization by Other Liquids 643

employing arylboronic acids and aryl bromides can be performed in imidazolium

salts 1 at room temperature [33].
Additionally, the Negishi cross-coupling of arylzinc reagents and aryl iodides
using Pd(dba)2 and the cationic phosphine ligand 4 was performed in a biphasic
system of an imidazolium salt 1 and toluene [34].

Telomerization, Oligomerization, and Polymerization

The Pd-catalyzed dimerization of butadiene in the presence of water yields octa-

dienols (cf. Section 2.3.5). This type of reaction is referred to as telomerization
and can be performed with high selectivity for 2,6-octadien- 1-01 in ionic liquids
like 1 leaving the product separated from the reaction medium [35].
The oligomerization of olefins is mostly catalyzed by cationic complexes
which are very soluble in ionic liquids. The Pd-catalyzed dimerization of buta-
diene [36] and the Ni-catalyzed oligomerization of short-chain olefins [ S , 371,
which is also known as the “Difasol” process [l d] if chloroaluminate melts are
used, can be run in imidazolium salts 1 [38, 391. Here, the use of chloroaluminate
melts and toluene as the co-solvent is of advantage in terms of catalyst activity,
product selectivity, and product separation. Cp2TiC12[6] and Tic& [40] in con-
junction with alkylaluminum compounds were used as catalyst precursors for
the polymerization of ethylene in chloroaluminate melts. Neither Cp2ZrCI2 nor
Cp2HfC12was catalytically active under these conditions. The reverse conversion
of polyethylene into mixtures of alkanes is possible in acidic chloroaluminate
melts without an additional catalyst [41].

Cycloadditions and Rearrangements

Although cycloadditions and rearrangements often proceed without catalysts, the

selectivity of the reaction and the reactivity of very reluctant molecules can be en-
hanced by a Lewis acid. The Diels-Alder reaction can be performed at enhanced
reaction rate in ionic liquids with the addition of ZnC1, (eq. (4)) [42]. The Claisen
rearrangement was also reported to be superior if catalyzed by Sc(OTf), in ionic
liquids [43].

[
5 mol% Zn12
n
in C , H , . ~ Q ~ . CH,].

r.t., 6 h
9
9
P F ~

major isomer
(4)
644 3.1 Development of Methods

Conclusions
Ionic liquids represent a new class of polar reaction media for homogeneous cat-
alysis, especially for biphasic applications. By variation of the ionic liquid as well
as the addition of co-solvents, the properties can be conveniently fine-tuned. With
the advantages of phase separation and nonvolatility, ionic liquids can help to
reduce solvent and catalyst consumption.
In many examples, the replacement of an organic solvent was not only shown
to be more convenient in terms of reaction processing but also of beneficial effect
on the activity and selectivity of the catalyst. Taking advantage of the good solu-
bility of gases and the stability of the ionic liquids towards most reagents, like,
e.g., oxidizing agents, allows reactions to be performed which are not possible
in a variety of organic solvents. Additionally, even enzyme catalyzed reactions
can be performed in neutral ionic liquids [44].

References
[1] (a) P. Wasserscheid, W. Keim, Angew. Chem. 2000, 112, 3926; Angew. Chem. Int.
Ed. 2000, 39, 3772; (b) M.J. Earle, K.R. Seddon, Pure Appl. Chem. 2000, 72,
1391; (c) T. Welton, Chem. Rev. 1999, 99, 2071; (d) H. Olivier, J. Mol. Catal. A:
1999, 146, 285; (e) Y. Chauvin, H. Olivier-Bourbigou, Chemtech 1995, 25 (9), 26;
(f) C.L. Hussey, Pure Appl. Chem. 1988, 60, 1763; (g) H. Olivier, in Aqueous-
Phase Organometallic Catalysis (Eds.: B. Cornils, W. A. Herrmann, Wiley-VCH,
Weinheim, 1998, p. 555.
[2] J. S. Wilkes, J. A. Levisky, R. A. Wilson, C. L. Hussey, Inorg. Chem. 1982, 21, 1263.
[3] P. BonhGte, A . 2 Dias, N. Papageorgiou, K. Kalyanasundaram, M. Gratzel, Inorg. Chem.
1996, 35, 1168.
[4] L. A. Blanchard, D. Hancu, E. J. Beckman, J. F. Brennecke, Nature 1999, 399, 28.
[5] Y. Chauvin, B. Gilbert, I. Guibard, J. Chem. Soc., Chem. Commun. 1990, 1715.
[6] R. T. Carlin, J. S. Wilkes, J. Mol. Catal. 1990, 63, 125.
[7] (a) J. A. Boon, J. A. Levisky, J.L. Pflug, J. S. Wilkes, J. Org. Chem. 1986, 51, 480;
(b) C. J. Adams, M. J. Earle, G. Roberts, K.R. Seddon, Chem. Commun. 1998, 2097.
[8] C. DeCastro, E. Sauvage, M. H. Valkenberg, W. F. Holderich, J. Catal. 2000, 196, 86.
[9] C.E. Song, W. H. Shim, E. J. Roh, J. H. Choi, Chem. Commun. 2000, 1695.
[lo] (a) Y. Chauvin, L. Mussmann, H. Olivier, Angew. Chern. 1995, 107, 2941; Angew.
Chem., Int. Ed. Engl. 1995, 34, 2698; (b) J. Dupont, P.A.Z. Suarez, A. P. Umpierre,
R.F. de Souza, J . B r a . Chem. Soc. 2000, 11, 293.
[ l l ] (a) P. A. Z. Suarez, J. E. L. Dullius, S. Einloft, R. F. de Souza, J. Dupont, Inorg. Chim.
Acta 1997, 255, 207; (b) P. A. Z. Suarez, J. E. L. Dullius, S. Einloft, R. F. de Souza,
J. Dupont, Polyhedron 1996, 15, 1217.
[I21 G. W. Parshall, J. Am. Chern. Soc. 1972, 94, 8716.
[I31 P. J. Dyson, D. J. Ellis, D. G. Parker, T. Welton, Chem. Commun. 1999, 25.
[ 141 L. A. Miiller, J. Dupont, R. F. de Souza, Macromol. Rapid Commun. 1998, 19, 409.
[I51 S. Steines, P. Wasserscheid, B. DrieBen-Holscher, J. Prakt. Chem. 2000, 342, 348.
[ 161 A. L. Monteiro, F. K. Zinn, R. F. de Souza, J. Dupont, Tetrahedron: Asymmetry 1997,
8, 177.
[I71 X. Wu, Y. A. Letuchy, D. P. Eyman, J. Catal. 1996, 161, 164.
 References 645

[ 181 J. F. Knifton, J. Am. Chem. SOC.1981, 103, 3959.

[19] G. S. Owens, M. M. Abu-Omar, Chem. Commun. 2000, 1165.
[20] C. E. Song, E. J. Roh, Chem. Commun. 2000, 837.
[21] C.E. Song, C.R. Oh, E.J. Roh, D.J. Choo, Chem. Commun. 2000, 1743.
[22] W. Keim, D. Vogt, H. Waffenschmidt, P. Wasserscheid, J. Cutul. 1999, 186, 481.
[23] C. C. Brasse, U. Englert, A. Salzer, H. Waffenschmidt, P. Wasserscheid, Organometallics
2000, 19, 3818.
[24] N. Karodia, S. Guise, C. Newlands, J.-A. Andersen, Chem. Commun. 1998, 2341.
[25] (a) J. F. Knifton, J. Mol. Catul. 1987,43,6.5;(b) J. F. Knifton, J. Mol. Cutul. 1988,47, 99.
[26] P. Wasserscheid, H. Waffenschmidt, J. Mol. Catal. A: 2000, 164, 61.
[27] D. Zim, R. F. de Souza, J. Dupont, A. L. Monteiro, Tetrahedron Lett. 1998, 39, 7071.
[28] (a) D. E. Kaufmann, M. Nouroozian, H. Henze, Synlett 1996, 1091; (b) W. A. Henmann,
V.P.W. Bohm, J. Organomet. Chem. 1999, 572, 141; (c) V.P.W. Bohm, W.A.
Henmann, Chem. Eur:J. 2000, 6 , 1017: (d) V. Calb, A. Nacci, L. Lopez, N. Mannarini,
Tetruhedron Lett. 2000, 41, 8973.
[29] (a) A. J. Carmichael, M. J. Earle, J. D. Holbrey, P. B. McCormac, K. R. Seddon, Org. Lett.
1999, 1, 997; (b) L. Xu, W. Chen, J. Xiao, Organometullics 2000, 19, 1123: (c) L. Xu,
W. Chen, J. Ross, J. Xiao, Org. Lett. 2001, 3, 295.
[30] (a) W. Chen, L. Xu, C. Chatterton, J. Xiao, Chem. Commun. 1999, 1247; (b) J. Ross,
W. Chen, L. Xu, J. Xiao, Organometallics 2001, 20, 138.
1311 C. de Bellefon, E. Pollet, P. Grenouillet, J. Mol. Cutal. A: 1999, 145, 121.
[32] S. Toma, B. Gotov, I. Kmentova, E. Solcaniova, Green Chem. 2000, 2, 149.
[33] C. J. Matthews, P. J. Smith, T. Welton, Chem. Commun. 2000, 1249.
[34] J. Sirieix, M. OBberger, B. Betzemeier, P. Knochel, Synlett 2000, 1613.
[35] J. E. L. Dullius, P. A. Z. Suarez, S. Einloft, R. F. de Souza, J. Dupont, J. Fischer, A. De
Cian, Orgariometullics 1998, 17, 8 15.
[36] S. M. Silva, P. A.Z. Suarez, R.F. de Souza, J. Dupont, Polymer Bull. 1998, 40, 401.
[37] (a) S. Einloft, F. K. Dietrich, R. F. de Souza, J. Dupont, Polyhedron 1996, 15, 32.57;
(b) Y. Chauvin, H. Olivier, C.N. Wyrvalski, L.C. Simon, R.F. de Souza, J. Catal.
1997, 165, 275; (c) L.C. Simon, J. Dupont, R.F. de Souza, Appl. Catal. A: 1998,
175, 215; (d) B. Ellis, W. Keim, P. Wasserscheid, Chem. Cornmun. 1999, 337.
[38] Y. Chauvin, R.F. de Souza, H. Olivier, EP 0.753.346 (1997); US 5.723.712 (1997).
1391 P. Wasserscheid, W. Keim, WO 9.847.616 (1997).
[40] R. T. Carlin, R. A. Osteryoung, J. S. Wilkes, J. Rovang, Inorg. Chem. 1990, 29, 3003.
1411 C. J. Adams, M. J. Earle, K. R. Seddon, Green Chem. 2000, 2, 21.
[42] M. J. Earle, P. B. McCormac, K. R. Seddon, Green Chem. 1999, 1, 23.
[43] F. Zulfiqar, T. Kitazume, Green Chem. 2000, 2, 296.
[44] (a) M. Erbeldinger, A. J. Mesiano, A. J. Russell, Biotechnol. Prog. 2000, 16, 1129;
(b) R. Madeira Lau, F. van Rantwijk, K.R. Seddon, R.A. Sheldon, Org. Lett. 2000,
2 , 4189.
 Applied Homogeneous Catalysis with Organometallic Compounds
Edited by B. Cornils and W. A. Herrmann
Copyright 0 Wiley-VCH Verlag GmbH, D-69469 Weinheim, 2002

646 3.1 Development of Methods

3.1.1.3 Immobilization
Peter Panstel; Stefan Wieland

3.1.1.3.1 Introduction
Over a period of more than 20 years, starting in the late 1960s, intensive research
work has been devoted to the development of so-called "supported" (anchored or
immobilized) metal complex catalysts. The very first publications to be mentioned
in this field came from Acres [l], Rony [2], and Haag [3]. In the meantime a num-
ber of surveys have appeared [4-191. The investigation of this new type of catalyst
(hybrid catalyst [ll]) has been driven by the vision of combining the positive
aspects of a homogeneous catalyst [20], i.e., high activity, high selectivity, good
reproducibility, with those characteristic of a heterogeneous catalyst, i.e., long life-
time and ease of separation (cf. Section 3.1.1.4 as well).
Up to now a broad variety of common organic and inorganic polymer systems
have been used as a solid support for immobilized metal complex catalysts. Dur-
ing the first period of the development work the need for a tailor- made support to
meet the requirements of this application became apparent, e. g., with respect to
general and structural stability, nature and degree of functionalization, functional
group distribution and density, and accessibility of the functional sites [ 171.
As will be discussed in more detail, the anchoring of a homogeneous catalyst to
a support can be achieved by different methods. Most frequently applied is the
fixation via donor ligands anchored to the support (covalent bonding). To a certain
extent, fixation to a support by ionic bonds and by chemi- and physisorption has
been accomplished. Furthermore, anchoring has been carried out by impregnation
of a solid support with a liquid medium containing a dissolved homogeneous
catalyst. This medium can be either of organic nature (supported liquid-phase
catalyst; SLPC) or water (supported aqueous-phase catalyst; SAPC).
A brief summary of the actual situation in this field will be given before enter-
ing into a more detailed description of the different immobilization techniques.
In spite of the initial enthusiasm and the large amount of work that has been
carried out in the meantime, any important practical application of an immobilized
metal complex catalyst is not known so far. Promising and really satisfying results
could only be obtained to a small extent in selective hydrogenation reactions in the
synthesis of chemical specialities and pharmaceutical products and in polymeri-
zation reactions with immobilized metallocene catalysts [211. The situation for
the latter type of reactions, however, is different.
In other reactions, particularly where strongly complexing reactants, e. g., car-
bon monoxide, are involved, leaching of the immobilized metal center may take
place. Generally, the parameters to be considered in a polymer-anchored metal
complex catalyst are of a manifold nature. It is still an unsolved problem and
an incompatible situation that, on the one hand, a leaching process should be
avoided while, on the other hand, sufficient activity and the selectivity necessary
for industrial applications are to be maintained. As a consequence it has become
 3.1.1.3 Immobilization 647

evident that immobilization is not a universal solution to the problems inherent to

homogeneous catalysis.
Future development work is needed to prove the possibilities of new concepts
that have been created during recent years. The investigation of systems which
work homogeneously but which can be separated easily [22] must be mentioned
in this context (cf. Section 3.1.1.1). The introduction of multidentate ligands and
the evaluation of polymer systems containing more than one metal complex site,
which cooperate eventually in the catalysis of parallel or sequential reactions
[23-251, are among these concepts. In addition, the formation of new or normally
unstable catalytic species [26, 271 attached to polymer supports, or the formation
of immobilized metal complexes as intermediates of defined metal clusters [28],
should be studied further (cf. Section 3.1.1.5).

3.1.1.3.2 Fixation to Supports via Covalent Bonding

Use of Functional Organic Polymers

In order to achieve chemical linkage between a soluble metal complex catalyst and
an organic polymer, a suitable functionality, forming covalent bonds, has to be intro-
duced into the original polymer. Exceptions whereby an unmodified polymer is di-
rectly applied to anchor a homogeneous catalyst [29,30], e. g., polybutadiene to an-
chor iron pentacarbonyl[3 13 (eq. (l)),are known, but lack of universal applicability.

By far the most frequently used organic supports are polystyrene and styrene-
divinylbenzene copolymer beads with diphenylphosphine, tertiary amino [32],
cyanomethyl [33], thiol [34], and cyclopentadienyl [35] functional groups. Start-

-LiPPhp

P -LiPPhp
&=+H2CI

@- = polymer or polymeric network

648 3.I Development of Methods

ing from the unmodified polymer, two phosphination routes have been used to
introduce -PPh2 [36] and -CH2PPh2 [37] groups (eqs. (2) and (3)), respectively.
A number of concepts, most of which are of fairly general applicability, have
been applied to graft metal complexes on to polymer supports bearing typical
donor groups such as tertiary phosphine and amine. The direct reaction of the
functionalized polymer with a metal halide [37] (eq. (4)) is an example.

The more often practiced routes to polymer-anchored complex catalysts include

the displacement of a ligand already coordinated to a soluble metal complex by a
polymer-bonded ligand [38] (eq. (5)), or the splitting of a weakly bridged dimeric
metal complex [34] (eq. (6)).

Other polymers have been used instead of polystyrene, especially polyvinyls

[37, 391, polyacrylates [32, 401, and cellulose [4 11. Suitable complexing groups
can be introduced into these polymers by well-known methods of organic syn-
thesis [ 121; preferably theses are diphenylphosphine groups.
Covalent bonding between a metal complex unit and an organic support is re-
presented by donor-acceptor interaction in nearly all cases. Only a few examples
are known where the metal center is directly bonded to a carbon atom of the poly-
mer backbone [ 5 ] (eq. (7)).

P P
 3.1.1.3 Immobilization 649

The nature of the organic support can have a very strong influence on the per-
formance of the immobilized metal complex catalyst [ 121. Among the organic
supports, phosphinated polystyrene seems to have the highest versatility in de-
signing the structure of the anchored catalyst. The latter can be determined by
the synthesis route, the density of the donor groups within the polymer, and the
flexibility of the organic chain, which can be adjusted by changing the amount
of crosslinking agent. A certain amount of crosslinking agent (divinylbenzene)
in polystyrenes is necessary to avoid too high a degree of flexibility of the poly-
mer chain, resulting in undesired interaction of the functional groups [42], e. g.,
eq. (8).

On the other hand, if crosslinking is too high, a sufficient swelling of the poly-
mer is impossible as the polymer chains are too tightly bonded and therefore the
entry of substrate molecules into the polymer becomes more and more restricted.
As a consequence, a significant decrease in activity is observed [38, 431.
Collman [44] and Grubbs [35] studied the formation of different types of an-
chored rhodium and iridium complexes upon variation of the degree of crosslink-
ing in the range 2-20 %. Naaktgeboren et al. [45] identified six different polymer-
bonded metal species by performing 31P-NMRstudies after reaction of a phosphi-
nated styrene-divinylbenzene copolymer with [RhC1(C2HJ2I2.A close relation-
ship between the flexibility of the polymer chain, the phosphine group density
on the inner and outer polymer surface areas, and the phosphine group/metal
ratio, can be seen. These parameters determine the “ligand efficiency,” being of
importance for activity and selectivity of a polymer-anchored metal complex cat-
alyst [46]. However, the formation of a coordinatively unsaturated metal center
must still be possible, as this is a key step in catalytic cycles.
A number of catalytic investigations have been carried out using polymer-
anchored metal complexes. In particular, they deal with hydrogenation, hydro-
formylation, hydrosilylation, dimerization, oligomerization, cyclooligomeriza-
tion, polymerization, and acetoxylation reactions [ 121. Catalytic hydrogenation
of olefinically unsaturated compounds is effected typically by immobilized rho-
dium, ruthenium, platinum, palladium, and indium systems. In principle, homo-
geneous catalysts bound to organic matrices are well suited to hydrogenation
reactions under mild conditions, as the affinity between nonpolar olefins and
the organic matrix is reasonably high [43]. In general, the chemoselectivities
of immobilized metal complex catalysts are similar, whilst the activities are
650 3.1 Development of Methods

lower than those of the corresponding homogeneous systems. This is due to

diffusional restrictions [25], even though several cases are known in which a higher
activity was observed [27, 35, 47, 481. As hydrogenation particularly takes
place on the inner surface of the polymer support, the hydrogenation of smaller and
less sterically hindered olefins is much more rapid than that of larger or substituted
olefins. This discrimination can be enhanced by the degree of crosslinking [49].
As to the regio- and stereoselectivity, a significant change compared with the
corresponding homogeneous catalysts can be gained with immobilized metal
complex catalysts by shape discrimination effects, i.e., steric and electronic inter-
actions within the matrix or by integrated chirality centers. Such centers can be
inherent to the matrix, e. g., in natural polymers such as cellulose or polypeptides,
or they can be incorporated into the binding group of the metal, in the side chain
of the polymer backbone, or in both. The optical yields obtained with resin-
anchored chiral phosphines [50, 5 11, e. g., 2,3-O-isopropylidene-2,3-dihydroxy-
1,4-bis(diphenylphosphine)butane (DIOP), pyrrolidine-based bisphosphines, and
other types, exceed 90% and are quite comparable with results obtained under
homogeneous conditions. However, systems with chirality centers in the (natural)
polymer backbone [41] or in the side chain [52] have led to insufficient optical
yields.
Interest has also been focused on the evaluation of polymer-supported hydro-
formylation catalysts, especially of the rhodium phosphine [53, 541 but also of
the cobalt carbonyl type [23, 36, 391. Important parameters of that reaction, be-
sides the overall yield, are the ratio of linearbranched aldehydes and the amounts
of hydroformylated olefin isomenzation products that are formed. In the hydrofor-
mylation of 1-pentene, Pittman et al. [55] found that the selectivity toward the lin-
ear aldehyde can be higher with polystyrene-bonded RhH(CO)(PPh,), (nli =
6-1 2) than that obtained with the homogeneous analog (n/i = 2 4 ) , depending
on the temperature (using the same phosphine excess, and the same phosphine,
as well as the same rhodium concentration).Other aspects such as the decrease
of activity at high P/Rh ratios and the observed metal leaching are not as promis-
ing [55, 561.
A remarkable example of the cooperation of different active sites in a polyfunc-
tional catalyst is the one-step synthesis of 2-ethylhexanol, including a combined
hydroformylation, aldol condensation, and hydrogenation process [ 171. The cata-
lyst in this case is a carbonyl-phosphine-rhodium complex immobilized on to
polystyrene carrying amino groups close to the metal center. Another multistep
catalytic process is the cyclooligomerization of butadiene combined with a subse-
quent hydroformylation or hydrogenation step [24,25] using a styrene polymer on
to which a rhodium-phosphine and a nickel-phosphine complex are anchored
(cf. Section 3.1.5).
An interesting concept has been demonstrated by Moffat, who used a cobalt
carbonyl-loaded poly(2-vinylpyridine) as a “catalyst reservoir” from which the
active catalyst species is released reversibly at higher carbon monoxide pressures
[29, 391.
The original idea to apply insoluble polymers as supports for immobilized
metal complex catalysts was abandoned by Bayer [57] and Bergbreiter [22]. In
 3.1.1.3 Immobilization 65 1

order to avoid diffusional limitation and catalyst leaching, they initiated another
approach using soluble polymers as catalyst ligands. The reaction of interest is
carried out under homogeneous conditions. Separation of the high-molecular-
weight metal complex from the product is carried out by membrane filtration or
precipitation of the metal complex-containing polymer by addition of a solvent
in which the polymer is insoluble.

Heterogenization by Formation of Polymeric Organic Matrices

An alternative concept for preparing metal complex catalysts anchored to or-
ganic polymer systems involves polymerization or polycondensation of suitably
functionalized monomeric metal complexes. An advantage of this route is the
fact that the problem of structural inhomogenity inherent to the previously
described methods can be avoided, as the catalytic active unit can be preformed
in the appropriate manner. A general disadvantage of this concept, possibly
being the reason for the rarity of its application, is the necessity to adjust
the desired physical properties (e. g., with respect to the accessibility of the
active sites) of the resulting polymer in the presence of the polymer-anchored
catalyst. Other limitations that can arise are low yields and the partial solubility
of the catalyst due to an insufficient degree of polymerization. Examples of this
procedure have been demonstrated by Pittman et al. [31, 581 (eqs. (9) and (10)).

Further examples include homo-, co- and terpolymers of manganese carbonyl,

iron carbonyl or cyclopentadienyl, and ruthenium-phosphine complexes [31, 59,
601.

Use of Common Inorganic Materials

Inorganic polymers have been used less often than organic polymers as supports
for immobilized metal complex catalysts, although the better physical properties
of the former in general more than compensate for the better chemical properties
652 3.1 Development of Methods

of the latter [61]. Advantages of the oxide supports are their rigid structure, which
prevents deactivation of the bound catalyst through intermolecular interaction, and
a higher temperature, solvent, and aging stability. Finally, a defined pore structure
independent of solvent, temperature, and pressure gives a greater control over dif-
fusional factors. A possible disadvantage is to be seen in the limited number of
reactive surface groups which are available for further functionalization. Inorganic
matrices provide an upper limit of functional groups of 1-2 meq/g of polymer,
whilst organic polymers can carry up to 10 meq/g of polymer [13]. Typical inor-
ganic supports are silica, clay, y-alumina, magnesia, glass, and ceramics. Zeolites
have pores which, although they are well defined, are often too small. Therefore
they have turned out to be only of limited applicability [28]. y-Alumina and mag-
nesia have been applied in certain cases, especially when their strong acid/base
sites are favorable [14, 281.
In terms of availability, number, and nature of surface groups, surface area, pore
size, pore volume, and form and size of the particles, silica has been undoubtedly
the most preferred inorganic support. Suitable modification is possible via the sur-
face silanol groups, which can react either directly with an appropriate metal com-
plex or with an intermediate ligand group. Direct surface bonding has often been
practiced, e. g., for the anchoring of metal carbonyl complexes [ 141 (eq. (1 l)), car-
bony1 clusters [26], polymerization catalysts [21, 621, or other special systems,
e. g., n-ally1 complexes [63] or metalloporphyrins [64].

9? Q?
@-0-Si-OH + MO(CO)~ -cd @O-Qi-O-Mo(CO)5H (11)
0 0
6
The real nature of the anchored metal complexes and their catalytic mecha-
nisms often remain unclear, even though particularly interesting results have
been obtained in alkane hydrogenolysis, olefin isomerization, hydrogenation
and hydroformylation [64], Fischer-Tropsch, water gas shift [26], polymerization,
metathesis [14, 261, and epoxidation [65] reactions. A more common technique
than direct surface bonding is the application of a spacer group which is anchored
to the support on one side and acts on the other side as a ligand group. In realizing
this structural concept two alternative approaches have been used: following route
1, which is demonstrated in eqs. (12) and (13) [12], a ligand group is attached to
the support in a first step. In a second step the reaction of the phosphine-function-
alized silica (which can also be derived in a multistep solid-phase synthesis [61])
with a monomeric metal complex is carried out [65].

9 Q
0
@-0-4i-OH
0
+ (H5C20hSi - ( C H Z ) ~ - P P ~ ~ -
- CZHSOH
0
I t
@-0-Qi-O-Si-(CH2)2-PPh2
0 '
6
 3.1.1.3 Immobilization 653

?
@-0-Si-0-9-
?
I
(CH2)2 -PPh2
+ Rh(C0)2acac -
- co
0
I I
@-O-Si-O--Si-(CH2)2
?
I
-P(Ph)2-)Rh(CO)acac

Phosphine-substituted organosilanes of the type shown in eq. ( I 2), or the homo-

logous compounds with a propene spacer group, have often been used, because of
their straightforward synthesis starting from commercially available organosilanes
[67, 681.
Route 1 can be practiced easily. Its main disadvantage has already been
described for polystyrene and includes the possibility of creating different sites
and the difficulty of determining their structure. Murrell [69] discussed four pos-
sible surface complexes as a result of the reaction between phosphinated silica
with [Rh(CO),CI],. The uniformity of the catalytically active surface centers
can be guaranteed by route 2, which involves the reaction of a preformed complex
bearing silicon-substituted ligands [69] (eq. (14)).

@-O-Si-OH
9
0
+ [(H5C20)3Si *pph,], Rh(C0)CI -
- CzH50H
Rh(C0)CI

In order to avoid undesirable side reactions on the support after surface modi-
fication according to route 1 or 2, the remaining silanol groups can be treated with
a nonfunctionalized silylating agent. Thus, at the same time, the surface layer
becomes more lipophilic [70] (cf. Section 2.6).
Many immobilized complexes of rhodium, iridium, palladium, platinum, and
cobalt with phosphine, amine, cyano, mercapto, alkene, and cyclopentadienyl li-
gands have been synthesized by applying one of the two routes. Detailed evalua-
tions of the parameters determining their catalytic behavior have been carried out
[12, 14, 15, 611. Capka [61] made a comparison with respect to the hydrogenation
activity between a neutral homogeneous rhodium catalyst and its immobilized
analogs prepared via routes 1 and 2. The immobilized type obtained via route 1
was found to have the highest activity, in spite of the expected presence of
non-uniform catalytic sites. This result was ascribed to dimerization and deactiva-
tion of catalytic centers in the two other cases. Route 2, however, was preferred
when applying cationic complexes [61]. Furthermore, it was found by the same
author that immobilized rhodium catalysts were generally less sensitive to deacti-
vation processes than the homogeneous ones andyielded higher selectivities in the
hydrogenation of cinnamaldehyde [61].
The two anchoring methods described above can be used to study the effect of
the length of the spacer group on catalytic activity. This is of conceptional interest
654 3.1 Development of Methods

since the close proximity of the metal complex to the surface can block the acces-
sibility of the active sites. Long and flexible ligand chains make this support effect
less likely. On the other hand, long spacer groups with enhanced mobility favor
the intermolecular interaction between anchored groups. As a consequence, aggre-
gation, coordinative blocking, and limitation of accessibility can occur. The ex-
perimental results on this issue are contradictory: in hydroformylation reactions
the highest activities were obtained by Murrell et al. [69, 711 with long spacer
groups, whilst Capka reported that C, spacer groups led to the highest activities
not only in hydrogenation but also in hydrosilylation reactions [61].
A comparison between phosphinated polystyrene and phosphinated silica cata-
lysts used in hydrogenation [8, 381 and hydrosilylation [72] reactions indicated,
in either case, a higher reaction rate for the silica-supported analogs. This was
expected and has been attributed to the better accessibility of the active sites
on the silica surface.
Compared with immobilized chiral metal complexes bound to organic poly-
mers, only a few evaluations have been carried out dealing with analogous sys-
tems based on silica supports [61, 731. This is surprising: with respect to industrial
application of the catalysts for the production of valuable chemicals, promising
results have been obtained with immobilized cationic rhodium(1) complexes con-
taining bidentate phosphine ligands, e. g., based on 1,3-dioxolane (such as DIOP)
[73], pyrrolidine [74], or glucopyranoside [61] derivatives. Although the activities
are lower compared with the homogeneous systems, optical yields of up to 100 %
can be obtained. In addition, metal leaching seems to be suppressed by the chelat-
ing effect of the ligand system. Further improvements seem possible when the
ionic metal chelate complex is anchored to silica via ionic bonding. However,
the results with silica-anchored monodentate chiral phosphine ligands were not
satisfying with respect to optical yield and metal leaching [61].
Application of phosphinated silica-supported metal complexes, e. g., in hydro-
formylation [69], cyclooligomerization [75], and Heck olefination [76] reactions,
did not reveal any surprising effects.

Heterogenization by Preparation of Specially Designed Inorganic Matrices

In order to overcome the disadvantages of organic and inorganic materials as sup-

ports for immobilized metal complex catalysts, specially designed supports based
on organofunctionalized polysiloxanes have been developed [68]. Polycondensa-
tion (sol-gel process) of suitable phosphino- [77], amino- [78] and sulfido-func-
tionalized [79] organosilane monomers leads to solids with a siliceous matrix and
a high concentration of anchored ligand groups. Immobilized metal complexes
based on these ligand supports can be synthesized using two basic concepts, as
is illustrated for rhodium in Figure 1.
According to route A, functionalized organosilanes, derived from a commer-
cially available precursor [68], are first reacted with a suitable metal compound,
e. g., a rhodium cyclooctadiene complex, resulting in the formation of a mono-
meric metal-phosphine complex bearing alkoxysilyl groups. Subsequently in a
 3.1.1.3 Immobilization 655

Route A

I
Q

Route B 6
Figure 1. Strategies for synthesis of immobilized metal complexes on the basis of
organofunctionalized polysiloxanes.

polycondensation process the monomeric metal complex is converted into a poly-

meric metal-phosphine complex. Following route B the monomeric phosphine is
polycondensed in a first step. In a second step the reaction with a soluble metal
compound is carried out. The physical and chemical properties of these polymeric
ligand supports can be tailor-made to meet certain catalytic requirements. The
metauigand ratio does not need to be stoichiometric. Control of the metal com-
plex and eventual excess ligand density is possible by incorporating so-called
crosslinking agents into the matrix, e. g., tetraalkyl silicates and titanates or
trialkyl aluminates. The metal content of the polymer can be varied in a range
of 0.1-10%. By a new forming process the polysiloxane-supported metal com-
plexes obtained via either route A or B have been synthesized as abrasion-resistant
microspheres for use in suspension or as spheres with diameters up to 2 mm for
fixed-bed applications [80]. Furthermore, the catalysts are characterized by their
high porosity, large pore diameters (>20 nm) and high BET surface areas. Stabi-
lity properties with respect to temperature, pressure, and solvent are excellent. A
large number of immobilized metal complexes with other transition metals and
different ligand systems have been synthesized.
After having studied the aforementioned results obtained with catalysts based
on inorganic supports it is not surprising that route A turned out to be superior
to route B with respect to structural homogeneity, stability, and catalytic behavior
656 3.1 Development of Methods

of the immobilized metal complex. This has been demonstrated especially in che-
moselective hydrogenations of unsaturated aldehydes to unsaturated alcohols
using immobilized iridium and ruthenium complexes [81] and in regio- and stero-
selective hydrogenations of steroids applying immobilized Wilkinson-type cata-
lysts [82]. In either case, highest selectivities, a comparably long lifetime, and no
leaching of the metal have been observed. Even in the hydroformylation of 1-oc-
tene, which was carried out with a polysiloxane-based rhodium phosphine-amine
system in a trickle-bed reactor over a running time of 1000 h, only a negligible
amount of dissolved rhodium could be determined in the liquid phase after a
steady state was reached. This is a consequence of a stabilizing and trapping effect
of the polysiloxane matrix. The nli ratio of 1.4-1.6, however, confirmed that due
to the rigid structure of the inorganic matrix no interaction between additional
ligands and the anchored metal complex takes place, even though a significant
ligand excess is present in the matrix. In the homogeneously catalyzed hydro-
formylation reaction an excess of phosphine ligand leads to the formation of a
high amount of the linear aldehyde.
The positive situation with respect to catalyst life and metal leaching has been
confirmed by a comparison of results obtained in a hydrosilylation reaction carried
out with a homogeneous rhodium catalyst, a similar catalyst anchored to silica,
and a corresponding organopolysiloxane-based system synthesized via route A
1831.

3.1.1.3.3 Chemical Fixation to Supports via Ionic Bonding

A common and very simple immobilization technique of catalytically active
metal complexes is by ionic bonding. Various ionic complexes are known to
be good homogeneous catalysts, e. g., anionic rhodium and cationic palladium
complexes for carbonylation reactions, and cationic ruthenium or rhodium com-
plexes for hydrogenation reactions. The method of ionic fixation is especially
used when dealing with chiral metal complexes, to perform enantioselective
syntheses in pharmaceutical applications. Various supports with ion-exchange
capabilities can be used, including standard organic or inorganic ion-exchange
resins, inorganic materials with polarized groups, and zeolites. The application
of such materials is limited by the ion-exchange equilibria, as the ionic bonding
of the metal complexes is generally not as efficient as a fixation via strong donor
ligands attached to a support. Besides the limitation arising from the leaching of
the ionic species, this approach is worthwhile with tailor-made metal complexes
bearing expensive ligand systems that cannot otherwise be recovered from the
reaction medium. The use of chiral cationic rhodium complexes is extensively
reviewed by Hetflejs [73]. The metal leaching is of minor importance in the
hydrogenation reactions studied. The supports that have been used include poly-
styrene resins with varying degrees of crosslinking as well as inorganic materials
such as the layer-lattice silicate mineral hectorite, where cationic rhodium-phos-
phine complexes have been intercalated and are reported to display high hydro-
genation activities.
 3.1.1.3 Immobilization 657

Another application of ionic bonding of metal complexes, recently reviewed,

involves supported metal clusters, e. g., anionic carbonyl compounds. Many of
the supported carbonyl clusters are anions, often dispersed in ion-pairs on basic
metal oxide surfaces [28]. Anionic metal complexes can also be supported on in-
organic polymers suitably functionalized with organic groups, as is the case with
organofunctional polysiloxanes. The rhodium complexes immobilized in this way
[84] are active catalysts for carbonylation reactions, e. g., formation of acetic acid
from methanol. Well known is also the immobilization of cationic ammonia com-
plexes of Pd or Pt (e.g., [Pt(NH3)4]2’) on acidic ion-exchange resins or within
zeolite cages. However, the catalytic active speciesare often derived from such
systems by reduction to form bifunctional supported metal catalysts rather than
immobilized metal complex catalysts [85].

3.1.1.3.4 Fixation to Supports via Chemi- or Physisorption

and Entrapping in Porous Materials
In contrast to the previously described methods of immobilization, in this sec-
tion surface-bonded species are only mentioned briefly, in the knowledge that
the distinction between physically adsorbed, absorbed, chemisorbed, and even
ionically bonded species may not be clearly drawn in a given case. Surface
bonding via impregnation with a liquid containing the metal complex and sub-
sequent removal of the solvent is one of the elementary techniques especially
used with inorganic supports and metal carbonyls [14]. Other techniques in-
volve sublimation of metal carbonyls on to the support [86]. The absorbed
metal complexes may remain stable on the support, but may also undergo sub-
stitution reactions with surface groups, e. g., silanol groups, as is the case with
metal carbonyls. This can go so far as to produce metal particles, e.g., using
Cr(CO)6 on alumina [87], or may lead to intermediate compositions on the
basis of a reaction scheme [88] with subsequent CO desorption equilibria.
The effectiveness of supported rhodium carbonyl clusters in olefin hydroformy-
lation has been demonstrated, and although upon pyrolysis the formation of dis-
persed rhodium particles has been shown, infrared studies under reaction
conditions suggest the recombination to partially decarbonylated Rh clusters
[89]. Such systems are often prepared as “intermediates” between homogeneous
catalysts and conventional supported metal catalysts that consist of dispersed
metal particles supported on a carrier rather than of immobilized, well-defined
complexes.
Adsorption of standard-type homogeneous complexes on supports [90], such as
Vusku’scomplex, is possible but these catalysts clearly cannot be used with sol-
vents that dissolve the complex. These studies, however, have to be seen in the
context of supported liquid-phase catalysts.
Other approaches use metal-atom synthesis (metal-vapor synthesis, MVS [9 1,
921) to produce labile complexes that are absorbed in porous supports and form
catalytically active metal cluster compounds.
658 3.1 Development of Methods

The capture of metal complexes is achieved in the synthesis of clusters within

the porous network of zeolites, where the reactants are small enough to enter the
large cavities, but the clusters formed are too large to escape (“ship- in-the-bottle’’
synthesis). The cages limit the size of the cluster compounds that can be formed
and the entrance to the porous channels prevents the departure from the cages.
Other methods of encapsulating metal complexes utilize polymerization or poly-
condensation reactions such as the sol-gel process. The metal complex is dis-
solved in the medium to be polymerized and is therefore trapped in the matrix
formed [93] (cf. Section 3.2.2). The limitations clearly arise from the porosity
of the polymer formed. A pore structure with pores that are too wide cannot pre-
vent the leaching of the complex, whereas a pore diameter that is too small results
in mass-transfer limitations.

3.1.1.3.5 Immobilization via Supported Liquids

Those immobilization procedures generally yielding supported solid-phase cata-
lysts (SSPCs) have already been described in the preceding sections; this section
deals with catalytically active species (e. g., Wilkinson’s or Vaska’s complex) that
are dissolved in liquids (therefore the catalyst is exactly the same as in homoge-
neous catalysis) or are even liquids themselves supported on porous solids. The
principal structure of such an SLPC and the principal difference from an SAPC
(Supported Aqueous-Phase Catalyst) is shown in Figure 2.
In the case of separate and immiscible phases containing the reaction compo-
nents and products on one side and the homogeneous catalyst on the other side,
the separation does not represent a severe problem. However, given the catalyst
is very active, a corresponding rate of reaction requires a large interfacial transfer
area per unit reactor volume. Since this is only possible with a high-energy input
into the reaction system, an advantageous dispersion of thecatalyst-containing
liquid phase by preparation of a supported liquid-phase catalyst (SLPC) [2, 941
or a supported aqueous-phase catalyst (SAPC) is a worthwhile alternative. This
creates a large gas-liquid transfer or interfacial (liquid-liquid) area, and therefore
a better mass transfer of the reactants to the catalytically active center is achieved
(cf. Section 3.1.1.1).
The requirement to be met for systems in which the reactants and products are
in the gaseous state is that the volatility of the supported liquid is negligible. For
systems in which the reactants and products are liquids themselves, the sup-
ported liquid must be insoluble in the reaction medium and must not be extracted
into it from the porous structure of the support. The reaction itself takes place in
the supported liquid or at the interface of the supported liquid film and the gas
phase or organic phase when dealing with SLPC or SAPC, respectively. There-
fore, the conversion is proportional to the interfacial area. Investigations have
shown that variation of the liquid loading of the support highly influences the
reaction rates of a given reaction. The optimum is determined by the accessibility
of the catalyst solution within the porous system [96]. In going to a very low
liquid loading (y-value, defined as the ratio of the actual liquid amount to the
 3.1.1.3 Immobilization 659

Figure 2. Schematic of a supported liquid-phase catalyst [102]. The liquid or water

absorbed on the porous support forms a film on the inner surface of the support.
SLPC: phase A is a nonvolatile organic solvent, e. g., R = H for typical purposes;
phase B is a gas phase, especially light olefins and CO/H2. SAPC: phase A is water,
e. g., R = S03Na; phase B is an organic liquid, e. g., a higher olefin. (Reprinted
with permission from CHEMTECH, 2(8), 1992, American Chemical Society).

pore-filling volume), the liquid is distributed in the pore space as a thin film. The
observed decrease in catalytic activity can be explained firstly by a reduction in
metal complex mobility and secondly by mass-transfer limitations at the inter-
facial area (coming into play when dealing with a very active metal complex
species).
At high q-values a reduction of the interfacial "gas-liquid" area also reduces the
mass transfer and slows down the reaction rates of SLPC [97]. This argument
applies in the same way to SAPC as the water content approaches the upper
limit that is given by the total water uptake of the support.

Supported Liquid-Phase Catalysts (SLPC)

The solution of the homogeneous catalyst in a solvent of low vapor pressure (e. g.,
phthalic acid esters) is distributed in the pore space of the porous support under
the action of capillary forces [95].
Upon practical application of the catalyst, one has to take care that the cata-
lyst concentration in the solution is not altered by evaporation of the solvent.
660 3.1 Development of Methods

Irreversible deactivation of SLPC by drying processes can be avoided by satur-

ating the gas stream passed over the catalyst [98]. Additional requirements arise
from the pore size of the support. In precious-metal complex-catalyzed reac-
tions, rearrangements in the coordination sphere of the metal occur that lead
to volume changes upon associative or dissociative reaction steps. Therefore,
the pore space of the support must not be too small in comparison with the het-
erogenized metal complex. In small-pore systems it may happen that the com-
plex molecule is not sufficiently mobile to pass the catalytic cycle and therefore
is inactive [95, 991. This restriction arising from the pore system of the support
can also be an advantage, in that these catalysts exhibit a shape-selectivity
[loo]. Most of the literature describes the use of SLPC in the hydroformylation
of ethylene, propene or butene using rhodium-phenylphosphine complexes and
excess PPh3. The effect of additives, the kinetics, the use of different supports
(silicas, Si02-A1203, kieselguhr, and polystyrene resins), as well as calculations
and a predesign of a large-scale SLPC plant (but never realized), have been
reported [ 1011.

Supported Aqueous-Phase Catalysts (SAPC)

As previously mentioned, the drawback of SLPC is that they are inapplicable with
reactants or products miscible with the nonvolatile organic solvents being used. In
contrast, SAPC, consisting of a thin film of an aqueous solution of water-soluble
organometallic complexes, covering a hydrophilic support of high surface area
(e. g., controlled-pore glasses, surface-modified silica), are specially designed
for conversion of liquid-phase reactants [ 1021. The catalytically active metal com-
plex contains ligands that ensure the hydrophilic properties of the entire system.
The ligands make the complex water-soluble and stabilize the hydrophobic char-
acter of the organometallic species. Section 3.1.1.1 deals with these metal com-
plexes in detail; typical systems use triphenylphosphinetrisulfonate (TPPTS)
ligands. Several reactions are reported using HRh(CO)-(P[m-C6H4S03Na],)3 im-
mobilized as an SAPC [103]. Extensive work on hydroformylation of liquid-
phase olefins (e. g., oleic alcohol [104]) has been carried out, demonstrating the
absence of leaching of rhodium into the organic phase (limit < 1 ppb) and the in-
fluence of the water content of the SAPC. In principal, this work has led to the
same results as those discussed for SLPCs. If the water content of the SAPC is
too high, a decline in activity is observed. A similar decline in activity is also ob-
served in going from porous supports to less porous ones, or in going to very low
water contents of the SAPC. In the latter case the SAPC behaves like a supported
solid catalyst. Although this section is principally concerned with catalytically ac-
tive immobilized metal complexes, in the discussion of SAPC it should be men-
tioned that, until now, the industrial application of SAP catalysts has been in the
field of supported liquid acids, such as H3P04on Si02, which is used on a large
scale for ethylene hydration.
 References 66 1

References
[I] G. J. K. Acres, G. C. Bond, B. J. Cooper, J. A. Dawson, J. Catal. 1966, 6, 139.
[2] P. R. Rony, J. Catal. 1969, 14, 142.
[3] Mobil Oil Corp. (W. 0. Haag, D. D. Whitehurst), BE 721.686 (1968).
[4] N. Kohler, F. Dawans, Rev. Inst. Fr. Petrole 1972, 27, 105.
[5] C. U. Pittman Jr., G. 0. Evans, CHEMTECH. 1973, 560.
[6] J. C. Bailar Jr., Catal. Rev.-Sci. Eng. 1974, 10, 17.
[7] E. M. Cernia, M. Graziani, J. Appl. Polym. Sci. 1974, 18, 2725.
[8] Z. M. Michalska, D. E. Webster, Platinum Met. Rev. 1974, 18,65; Chem. Technol. 1975,
117.
[9] D. Commerenc, G. Martino, Rev. Inst. Fr. Petr. 1975, 30, 89.
[lo] F. Dawans, Inform. Chim. 1977, 163, 191.
[I11 R. H. Grubbs, CHEMTECH 1977, 512.
[ 121 F. R. Hartley, P. N. Vezey in Adv. Organomet. Chem. 1977, 15, 189.
[ 131 D. D. Whitehurst, CHEMTECH 1980, 44.
[14] D. C. Bailey, S. H. Langer, Chem. Rev. 1981, 81, 109.
[15] F. R. Hartley, Supported Metal Complexes, Reidel, Dordrecht, 1985; Y. I. Yermakov,
B. N. Kuznetsov, V. A. Zakharov (Eds.), Catalysis by Supported Complexes, Elsevier,
Amsterdam, 1981.
[16] F. Ciardelli, G. Braca, C. Carlini, G. Sbrana, G. Valentini, J. Mol. Catal. 1982, 14, 1.
[I71 G. Braca, Chim. Oggi 1988, 11, 23.
[ 181 F. S. Dyachkovskij, A. D. Pomogailo, Homogen. Heterog. Catal. Proc. Int. Symp. 1986,
447.
[I91 A. D. Pomogailo, Platinum Met. Rev. 1994, 38, 60.
[20] L. H. Pignolet, Homogeneous Catalysis with Metal Phosphine Complexes, Plenum, New
York, 1983.
[21] A. A. Montagna, J. C. Floyd, Hydrocarbon Proc. 1994, 57; W. Kaminsky, F. Renner,
Makromol. Chem., Rapid Commun. 1993, 14, 239.
[22] D. E. Bergbreiter, CHEMTECH 1987, 686.
[23] J. Haggin, Chem. Eng. News 1982, 60, 11.
[24] C. U. Pittman Jr., L. R. Smith, J. Am. Chem. Soc. 1975, 97, 1749.
[25] C. U. Pittman Jr., L. R. Smith, R. M. Hanes, J. Am. Chem. Soc. 1975, 97, 1742.
[26] S . L. Scott, J. M. Bassett, J. Mol. Catal. 1994, 86, 5.
[27] G. Braca, F. Ciardelli, G. Sbrana, G. Valentini, Chim. Ind. (Milan) 1977, 59, 766.
[28] B. C. Gates, Chem. Rev. 1995, 95, 51 1.
[29] A. J. Moffat, J. Catal. 1970, 18, 193.
[30] C. U. Pittman Jr., Chem. Eng. News 1970, 48, 36.
[31] C. U. Pittman Jr., CHEMTECH 1971, 416.
[32] M. Capka, P. Svoboda, M. Kraus, J. Hetflejs, Chem. Ind. (London) 1972, 650; I. Dietz-
mann, D. Tomanova, J. Hetflejs, Collect. Czech. Chem. Commun. 1974, 39, 123.
[33] M. Kraus, Collect. Czech. Chem. Commun. 1974, 39, 1318.
[34] L. D. Rollmann, Inorg. Chim. Acta 1972, 6, 137.
[35] R. H. Grubbs, C. Gibbons, L. C. Kroll, W. D. Bonds, C. H. Brubaker, J. Am. Chem. Soc.
1973, 95, 2373.
[36] G. 0. Evans, C. U. Pittman, Jr., R. McMillan, R. T. Beach, R. Jones, J. Organomet.
Chem. 1974, 67, 295.
[37] K. G. Allum, R. D. Hancock, I. V. Howell, R. C. Pitkethly, P. J. Robinson, J. Organomet.
Chem. 1975, 87, 189.
[38] R. H. Grubbs, L. C. Kroll, J. Am. Chem. Soc. 1971, 93, 3062.
[39] A. J. Moffat, J. Catal. 1970, 19, 322.
662 3.1 Development of Methods

[40] N. Takaishi, H. Imai, C. A. Bertelo, J. K. Stille, J. Am. Chem. Soc. 1976, 98, 5400.
[41] H. Pracejus, M. Bursian, DDR 92031 (1972); K. Kaneda, T. Imanaka, Trends Org.
Chem. 1991, 2, 109.
[42] T. D. Mitchell, D. D. Whitehurst, 3rd. Am. Con$ Catalysis Society, San Francisco, 1974.
[43] R. H. Grubbs, L. C. Kroll, E. M. Sweet, J. Makromol. Sci., Chem. 1973, 7, 1047.
[44] J. P. Collman, L. S. Hegedus, M. P. Cooke, J. R. Norton, G. Dolcetti, D. N. Marquardt,
J. Am. Chem. Soc. 1972, 94, 1789.
[45] A. J. Naaktgeboren, R. J. M. Nolte, W. Drenth, J. Am. Chem. Soc. 1980, 102,
33S0.[46]M. Bartholin, C. Graillet, A. Guyot, J. Mol. Catul. 1981, 10, 361.
[47] S. Jacobson, W. Clements, H. Hiramoto, C. U. Pittman Jr., J. Mol. Catal. 1975, I , 73.
[48] C. U. Pittman Jr., S. E. Jacobsen, H. Hiramoto, J. Am. Chem. Soc. 1975, 97, 4774.
[49] G. Innorta, A. Modelli, F. Scagnolari, A. Foffani, J. Organomet. Chem. 1980, 185, 403.
[50] S. J. Fritschel, J. J. Ackerman, T. Keyser, J. K. Stille, J. Org. Chem. 1979, 49, 3152.
[Sl] H. W. Krause, React. Kinet. Catal. Lett. 1979, 10, 243.
[S2] C. Carlini, G. Sbrana, J. Mucromol. Sci., Chem. 1981, A16, 323.
[S3] M. Capka, P. Svoboda, M. Cerny, J. Hetflejs, Tetrahedron Lett. 1971, 4787.
[S4] W. 0. Haag, D. D. Whitehurst, Proc. 5th Znt. Cong. Catul. 1972, 465.
[ S S ] C. U. Pittman Jr., A. Hirao, C. Jones, R. M. Hanes, Q. Ng, Ann. N. E Acad. Sci. 1977,
15, 295.
[S6] C. U. Pittman Jr., W. D. Honnick, J. J. Yang, J. Org. Chem. 1980, 45, 684.
[S7] V. Schurig, E. Bayer, CHEMTECH 1976, 212.
[S8] C. U. Pittman Jr., P. Grube, 0. E. Ayers, S. P. McManus, M. D. Rausch, G. A. Moser,
J. Polym. Sci., Polym. Chem. Ed. 1972, 10, 379.
[S9] C. U. Pittman Jr., in: Organometallic Polymers (Eds.: C. E. Carraher Jr., J. E. Sheats,
C. U. Pittman Jr.), Academic Press, New York, 1978.
[60] G. Valentini, A. Cecchi, C. Di Bugno, G. Braca, G. Sbrana in Homogeneous and Hetero-
geneous Catalysis (Eds.: Yu. Yermakov, V. Likholobov), VNU Science Press, Utrecht,
1986.
[61] M. Capka, Collect. Czech, Chem. Commun. 1990, 55, 2803.
[62] F. Ciardelli, A. Altomare, G. Conti, Macromol. Symp. 1994, 80, 29.
[63] J. P. Candlin, H. Thomas, ACS Adv. Chem. Ser: 1974, 132, 212.
[64] J. Hjortkjaer, M. S. Scurrell, P. Simonsen, J . Mol. Catul. 1981, 10, 127.
[6S] B. Meunier in Catalysis by Metal Complexes (Eds.: F. Montanan, L. Casella), Vol. 17,
Kluwer Academic, Dordrecht, 1994, p. 1.
[66] K. G. Allum, R. D. Hancock, I. V. Howell, S. McKenzie, R. G. Pitkethly, P. J. Robinson,
J. Orgunomet. Chem. 1975, 87, 203.
[67] H. Niebergall, Makromol. Chem. 1962, 52, 218.
[68] U. Deschler, P. Kleinschmit, P. Panster, Angew. Chem., Znt. Ed. Engl. 1986, 25, 236.
[69] L. J. Boucher, A. A. Oswald, L. L. Murrell, Prepr:, Div. Petrol. Chem., Am. Chem. Soc.
1974, 19, 162; L. L. Murrell in Advanced Materials in Catalysis (Eds.: J. L. Burton,
R. L. Garten), Academic Press, New York, 1977.
[70] E. J. Corey, A. J. Venkateswarlu, J. Am. Chem. Soc. 1972, 94, 6190.
[71] A. A. Oswald, L. L. Murrell, L. J. Boucher, Prepr:, Div. Petrol. Chem., Am. Chem. Soc.
1974, 19, 155.
1721 Z . M. Michalska. J. Mol. Catul. 1977/78. 3. 12.5.
[73j J. Hetflejs in Cutalytic Hydrogenation (Ed.: L. Cerveny), Elsevier, Amsterdam, 1986,
D. 497.
[74] 6. Nagel, E. Kinzel, J. Chem. Soc., Chem. Commun. 1986, 1098.
[7S] K. G. Allum, R. D. Hancock, S. McKenzie, R. C. Pitkethly in Catalysis (Ed.: J. W. High-
tower), North-Holland, Amsterdam, 1973, p. 1.
[76] P. Yi, Z. Zhuangyu, H. Hongwen, J. Mol. Catal. 1990, 62, 297.
 References 663

[77] Degussa AG (P. Panster, P. Kleinschmit), DE 3.029.599 (1980).

[78] Degussa AG (P. Panster, P. Kleinschmit), DE 3.131.954 (1981).
[79] Degussa AG (P. Panster, W. Buder, P. Kleinschmit) DE 2.834.691 (1978).
[80] Degussa AG (P. Panster, S. Wieland) DE 3.925.359, DE 3. 925.360 (1989); Degussa
AG (P. Panster, R. Gradl), DE 4.035.032 (1990); Degussa AG (P. Panster, R. Gradl,
P. Kleinschmit) DE 4.035.033 (1990).
[81] E. Fache, C. Mercier, N. Pagnier, B. Despeyroux, P. Panster, J. Mol. Catal. 1993, 79,
117.
[82] S. Wieland, P. Panster in Catalysis of Organic Reactions (Eds.: M. G. Scaros, M. L.
Prunier), Marcel Dekker, New York, 1995.
[83] U. Schubert, New J. Chem. 1994, 18, 1049.
[84] Degussa AG (P. Panster, R. Gradl), DE 3.643.894 (1986).
[85] T. Uematsu, M. Umino, S. Shimazu, M. Miura, H. Hashimoto, Bull. Chem. SOC.Jpn.
1986, 59, 3637.
[86] A. Brenner, R. L. Burwell Jr., J. Cutal. 1978, 52, 353.
[87] R. F. Howe, Inorg. Chem. 1976, 15, 486.
[88] A. Brenner, R. L. Burwell Jr., J. Am. Chem. Soc. 1975, 97, 2565.
[89] M. Ichikawa, J. Catal. 1979, 59, 67.
[90] C. Meyer, A. Hoffmann, D. Hesse, Chon.-Ing.-Tech. 1992, 64(6), 563.
[91] J. R. Blackborrow, D. Young, Metal Vapor Synthesis in Organometallic Chemistry,
Springer, Berlin, 1979.
[92] K. J. Klabunde, Chemistry of Free Atoms and Particles, Academic Press, New York,
1980.
[93] U. Schubert, C. Egger, K. Rose, C. Alt, J. Mol. Catal. 1989, 55, 220; A. Rosenfeld,
D. Avnir, J. Blum, J. Chem. Soc., Chem. Commun. 1993, 583.
[94] P. R. Rony, Chem. Eng. Sci. 1968, 23, 1021; J. Villadsen, H. Livbjerg, Catal. Rev.-Sci.
Eng. 1978, 17, 203; C. N. Kenny, ACS Symp. Sex 1978, 72, 37.
[9S] M. Hoffmeister, D. Hesse, Chem. Eng. Sci. 1990, 45(8),2575.
[96] F. Gottsleben, M. Hoffmeister, D. Hesse, Katalyse Dechema MonogruphienNo. 122,
1991, p. 269.
[97] C. Meyer, A. Hoffmann, D. Hesse, Chem.-Ing.-Tech. 1992, 64(6), 563; C. Meyer,
U. Richers, D. Hesse, Hung. J. Ind. Chem. 1994, 223, 191.
[98] C. Jutka, R. Brusewitz, D. Hesse, Fluidized Processes, AIChE Symp. Ser No. 289,
1992, p. 122.
[99] D. Hesse, M. S. Redondo de Beloqui, Dechema Monographien No. 118, 1989, p. 305.
[ 1001 B. Gronewold, D. Hesse, Chem.-Ing.-Tech. 1995, 67( 1), 82.
[ 1011 J. Hjortkjaer, M. S. Scurrell, P. Simonsen, J. Mol. Catal. 1979, 6(6), 405; L. A. Gerrit-
sen, W. Klut, M. H. Vreugdenhil, J. J. F. Scholten, J. Mol. Catal. 1980, 9(3),265; L. A.
Gemtsen, J. M. Herman, J. J. F. Scholten, J. Mol. Catal. 1980, 9(3), 241; J. Hjortkjaer,
Proc. Int. Symp. Relat. Homogen. Heterog. Catal. 1986, 563; J. M. Herman, A. P. A. F.
Rocourt, P. J. van den Berg, P. J. van Krugten, J. J. F. Scholten, Chem. Eng. J. 1987,
35(2),83.
[lo21 M. E. Davis, CHEMTECH 1992, 22, (8), 498.
[lo31 I. T. Horvath, Catal. Lett. 1990, 6 , 43.
[lo41 J. P. Arhancet, M. E. Davis, J. S. Merola, B. E. Hansen, J. Catal. 1990, 121, 327.
 Applied Homogeneous Catalysis with Organometallic Compounds
Edited by B. Cornils and W. A. Herrmann
Copyright 0 Wiley-VCH Verlag GmbH, D-69469 Weinheim, 2002

664 3. I Development of Methods

3.1.1.4 Surface Organometallic Chemistry

Jean-Marie Basset, Gerald l? Niccolai

3.1.1.4.1 Introduction
The expanding field of su$ace organometallic chemistry (referred to as SOMC,
or by its French acronym, COMS) offers new possibilities to homogeneous and
heterogeneous catalysis. The philosophy of SOMC is based on the concept that
the supported catalyst is a kind of “supramolecular” entity which belongs to
both the molecular and the solid states. Ideally one ceases to speak of “the immo-
bilization of a catalyst” or of “the modification of a surface” but rather one con-
siders the entire continuum - support, metal, and ligands - as a supramolecular
species responding, primarily, to fundamental rules derived from organometallic
chemistry but also, to a smaller extent, to the rules of solid-state chemistry. Sur-
face organometallic chemistry preserves some of the advantages of traditional sup-
ported catalysis such as the ease of separation of the catalyst from the substrate/
product and the heightened stability with respect to homogeneous analogs. As
with traditional techniques, one can vary such parameters as the surface area, po-
rosity, and electrophilicity of the support, and the identity of the metal. Surface
organometallic chemistry offers much more precise control of other metal-cen-
tered factors such as the oxidation state and coordination geometry of the catalytic
site. The stoichiometric nature of SOMC syntheses often leads to catalytic systems

Schematic Model of Surface

Supported Organometallic Complex

^f a quasi-molecular
organometallic fragment ...
7
.................................................................................
... linked covalently
...............

or ionically ...
.......................................................
... to one or several atoms of
the support surface
0 M‘

M‘= Si, Al, Nb, Zr, ... M’ = RU ,Rh, Pt, ...

Figure 1. Representation of a surface organometallic fragment on an oxide (left) and on a

metal particle.
 3.1.1.4 Surjiuce Organometullic Chemistry 665

with very high percentages of active catalytic sites in contrast with most classical
heterogeneous catalysts.
The surface organometallic complex is represented schematically in Figure 1.
An organometallic fragment, bearing one or many “traditional” ligands, is
bound to the surface “ligand” by one or several ionic or covalent bonds. Given
this construct, there is a number of parameters available when considering the
type of system best adapted to a particular catalytic application: notably, the
choice of metal (identity, oxidation state), ligands (number, electrophilicity, labi-
lity, hapticity, etc.), the type of ligand-surface bond (ionic, dative, covalent, van
der Waals), and the surface (a metal surface, an amorphous inorganic oxide, a zeo-
lite, etc.).
Surface organometallic chemistry methods have been the subject of a number
of reviews [1-4]. Below, some of the general methods of synthesis of catalysts
and catalyst precursors by surface organometallic chemistry on oxide and on
metal surfaces are highlighted. Some breakthrough examples of catalytic reactions
and other potential industrial applications are also described.

3.1.1.4.2 Oxide-Supported Organometallic Chemistry

General Strategy

Inorganic oxides may present several different types of reactive functional groups,
among them several kinds hydroxyl groups, strained rings, 0x0 groups, and
Lewis-acidic vacant sites. The occurrence and relative abundance of these differ-
ent sites depend primarily on the identity of the oxide (silica, alumina, niobia,
etc.), the synthesis and conditioning of the oxide, and the eventual calcination
and other thermal treatment of the solid immediately before use.
The most commonly used grafting reaction in surface organometallic chemistry
is the reaction of a surface silanol with an alkylmetal complex ([5-131; cf. Stmc-
tures 1-12) which has led to the synthesis of a wide variety of surface organo-
metallic complexes. In some cases the catalytic activity of these surface species
can be studied directly [7, 10, 131 while in others the initially obtained species is
converted to the desired catalytically active species by clean, quantitative reactions.
Grafting, transformation, and application of a surface organometallic complex
(Zr hydrides) will be described in detail, then summarized and augmented by
some other applications of oxide-supported organometallic species in catalysis.
Sublimation of Zr[CH,C(CH,),], to silica, partially dehydroxylated at 500 “C
(silica(500,),results in the electrophilic cleavage of a Zr-C bond by surface protons,
with formation of a grafted species formulated 5Si-O-Zr[CH,C(CH,),], [5]
(Structure 13). The reaction of this species with dry hydrogen (450 mbar,
150 “C) leads to hydrogenolysis of the Zr-C bonds with formation of a surface
supported zirconium hydride species, (=Si0)3ZrH, with simultaneous formation
of surface >SiH, fragments, methane, and ethane [6].
Analogous methods have been used to synthesize and characterize Ti and Hf
compounds [5, 81.
666 3.1 Development of Methods

o/s+oo Si..,,,,
'0 \o" "HSi
2 4

'Bu

I P
o,s+oo o,skoo
6 8

d
I o,"<60I
,Si
0 bg
.,,/

9 10 11

NP
I
Zr ..,,,,
/ \ NP
0 NP
I
Si
O'"""/
0
' Np = neopentyl
0
13

An analogous chemistry has been studied for complexes of tantalum, leading to

a number of new surface structures, including the first clearly defined surface or-
ganometallic carbene complexes [ 11 a]. This synthesis was accompanied by the
observation of a new grafting mechanism involving the addition of surface sila-
nols across a Ta-C double bond. The hydrogenolysis of the silica-supported car-
bene complex gives (-SiO)*TaH. This hydride is formally a complex of Ta"' with
an electron count of eight. Interestingly the Ta is strongly bound to only two 0
atoms of the silica, which makes it very unsaturated in terms of coordination
number and perhaps electrophilicity.
 3.1.1.4 Surjiuce Orgunometullic Chemistry 667

Hydrogenolysis of Alkanes

It is perhaps not surprising that the surface hydride complexes are capable of the
low-temperature activation of simple alkane C-C bonds. The grafted hydrides
(=Si0)3M-H (M = Ti, Zr, Hf) have a formal valence electron count of eight
and are thus expected to be very electrophilic. It might be considered that the silica
surface occupies one half of the coordination sphere of the metal (i. e., has a cone
angle of 180 "), but the other coordination hemisphere bears only the hydride
ligand and thus should be sterically very accessible to reactants. These properties
are undoubtedly responsible for the extraordinary reactivity of the Zr hydride
complex toward the inactivated C-H bonds of CH, (lOO'C), propane, and
cyclooctane (25 "C) [14]. The reaction is believed to be obeying a a-bond meta-
thesis mechanism, well known in molecular chemistry. The further observation of
catalytic cleavage of C-C bonds, at room temperature in the case of Hf, was
certainly unexpected.
Indeed, the reaction was first observed in the synthesis of the hydrides. As men-
tioned above, when 5 is heated under dry hydrogen to 150°C for three hours,
(=Si0)3ZrH (14) is formed together with nine equivalents of methane and three
equivalents of ethane. The formation of methane and ethane rather than neopen-
tane was clear evidence of hydrogenolysis under the synthesis conditions [5, 15,
161. It was observed that the reaction of neopentane occurred by stepwise forma-
tion of firstly isobutane and methane, then conversion of the former to a second
equivalent of methane and propane which is further converted to ethane and a
third equivalent of methane. The C-C bond of ethane cannot be cleaved by p-
methyl elimination because a surface metal-ethyl fragment has no methyl group
in the P-position.
With (=SiO),TaH, hydrogenolysis of simple alkanes also occurs at rather mod-
erate temperatures but, in contrast with group 4 metals, ethane is also cleaved,
which suggests an alternative mechanism to P-alkyl elimination for C-C bond
cleavage [ 171. This surprising shift in reactivity implies a completely different me-
chanism of C-C cleavage which we believe to be closely related to that of alkane
metathesis (vide infru).

Ziegler-Natta Depolymerization

The P-alkyl elimination step can considered as analogous to the more familiar p-
hydride elimination in which a C-C bond is broken instead of a C-H bond. Note
that this reaction is the microscopic reverse of the propagation step in the mecha-
nism of the Ziegler-Natta polymerization of olefins (eq. (I)).
668 3.1 Development of Methods

It was thus logical to attempt the hydrogenolytic degradation of polymers cata-

lyzed by surface-supported group 4 metal hydrides. In particular, it was found
that a silica-alumina supported analogue of 5 was capable of polymerizing ethyl-
ene and propylene [18]. (=SiO)3ZrH is also an active catalyst for the polymeri-
zation of olefins. The hydride supported on silica-alumina was prepared directly
from the corresponding alkyl complex and this latter hydride was used for the
hydrogenolytic degradation of polymers.

Skeletal Isomerization of Alkanes

It was noted during the formation of the titanium hydride complex that methane
and ethane were not formed in a 3 : 1 ratio, but rather in a 1 :1 ratio. Detailed stu-
dies on the hydrogenolysis of neopentane and isobutane catalyzed by this hydride
proved that this result was due to the isomerization of neopentane during the hy-
drogenolysis cycle [5 a]. Following an initial step of C-H bond activation the sur-
face alkyl fragment can undergo b-methyl elimination. In the case of Ti, the inter-
mediate metal-alkyl-olefin complex persists long enough (relative to olefin rota-
tion) to undergo reinsertion of the rotated olefin into the metal-carbon bond
(Scheme 1). This isomerization step is illustrated for the neopentyl fragment.
Thus the remarkable activity of these surface complexes with respect to C-C
bonds is thus more interesting given the possibility of light hydrocarbon isomeri-
zation at very mild temperatures.

Scheme 1. Possible mechanism of skeletal isomerization of neopentane (crucial steps).

Alkane Metathesis (or Alkane Disproportionation)

The Ta hydride has been shown to catalyze an entirely unexpected and potentially
very interesting reaction, the metathesis or disproportionation of simple alkanes,
under very mild conditions [19]. For example, when ethane is heated to 150°C
 3.1.1.4 Surjiuce Orgunometullic Chemistry 669

in the presence of (=SiO)2TaHthe appearance of principally methane and propane

but also traces of n-butane and isobutane (diso = 4) is observed. The experiment
was repeated with "C-monolabeled ethane. Nonlabelled, monolabelled, di-
labelled, and trilabelled propane were all observed ( 5 :44:43 :8) which clearly
demonstrates the cleavage of the 12C-'3C bond of ethane and redistribution of
the I3C atoms into the propane product [20, 211.
In order to account for the results obtained, a mechanism has been proposed
which is indicated in Scheme 2. The key step of C-C bond cleavage is represented
as one of simple a-bond metathesis between the Ta-alkyl bond and the C-C bond
of an alkane. This elementary step has no precedent that we are aware of, and
could easily be represented as, for example, oxidative addition and reductive elim-
ination This u-bond metathesis mechanism predicts product distributions based on
steric constraints quite simply. Thus we find it useful and so will continue to use
the hypothesis for discussion of our results.
When higher alkanes were submitted to the same treatment, several higher and
lower homologues were produced due to the presence of a larger number of dif-
ferent C-H and C-C bonds in the substrate. For example, the metathesis of pro-
pane yielded mainly n-butane and isobutane (nliso = 4) together with ethane, but
also produced both higher and lower homologues. This suggests that the transfer
of methyl fragments is more facile than the transfer of longer chains. Secondary
reactions would account for some but not all of the higher and lower homologues.
The importance of steric considerations in product distribution has also been

metathesis

metathesis

Scheme 2. Possible mechanism for ethane metathesis (productive and degenerate).

610 3.1 Development of Methods

demonstrated in the metathesis of isobutane. The initial C-H bond activation re-
action step can produce either a surface isobutyl fragment or a surface tert-butyl
fragment. Second-step a-bond metathesis from a tert-butyl intermediate would
produce neopentane, a product that is not observed. Substantial amounts of iso-
pentane are however obtained, implying that either the C-H bond activation
step or the C-C bond cleavage step is hindered by the crowding around the ter-
tiary carbon of isobutane. Various four-center transition states are involved in
the mechanism proposed, and the most difficult is that where there are three
sp3 C and the Ta in the transition state.

Olefin Metathesis

Surface organometallic species have also been used for the olefin metathesis
reaction [lo, 131. In the case of molybdenum, the molecular complex
N=Mo[CH,C(CH,),], showed very little activity for the metathesis of simple ole-
fins, presumably because the catalytically active carbene complex did not form
under reaction conditions. The reaction of this complex with silica, however, pro-
ceeds by the addition of the silanol0-H bond over the Mo=N triple bond leading
first to a trisalkyl Mo complex which undergoes a-elimination of neopentane to
produce a carbene complex which was found to exhibit a significant activity
for the metathesis of internal olefins according to eq. (2) [lo].

=SOH + N=Mo[Np], +. -SiOMo[=NH][Np], +.

=SiOMo[=NH][=CH'Bu][Np] (2)

-
The aesthetically pleasing silica-supported alkyl, alkylidene, alkylidyne Re""
complex SiORe[ =C'Bu][=CH'Bu] [CH2'Bu] (Scheme 3, Structures 15-17), pre-
pared from the molecular precursor, has also been found to be highly reactive for
the metathesis of propene [ 131. Moreover, the evolution of roughly one equivalent
of a 1:3 mixture of 3,3-dimethylbutene and 4,4-dimethyl-2-pentene is consistent
with a cross-metathesis of the neopentylidene ligand of 1 and propene. The turn-
over obtained also exceeds those obtained with classical heterogeneous catalysts
such as W03/Si02used industrially for decades (Lummus process).
'B,U
'Bu

15 16 17

Scheme 3. Synthesis of -SiORe[ -C'Bu][=CH'13u][CH2%u]; 17 is identical with 8.

 3.1.1.4 Su@ace Organometallic Chemistry 67 1

Alkene Epoxidation

In the literature there has been much debate regarding the role of the lattice or ex-
tralattice Ti in Ti silicalite for a variety of oxidation reactions. In order to have a
more precise idea of the role of the ‘‘lattice’’or “surface” Ti and more specifically
of the role of the coordination sphere of Ti, a series of monopodal and tripodal
titanium surface complexes (i. e., =SiOTi(OR), and (=SiO),TiOR) were derived
by the reaction of the Ti alkyl (Structure 1) and hydride species with water, oxy-
gen, methanol, and tert-butanol. The resulting complexes were then used in the
epoxidation of 1-octene by tert-butyl hydroperoxide. Tripodal complexes, espe-
cially (=SiO),Ti(%u), were found to be significantly more active and more selec-
tive for the epoxidation of 1-octene than their monopodal counterparts [22].
The exact reason why tripodal Ti with a t-butoxy ligand is by far the most
active is not yet completely clear.

Enantioselective Epoxidation of Allylic Alcohols

The well-known Sharpless system for the enantioselective epoxidation of ally1

alcohols has been investigated [23]. This system employs a tetra-alkoxy titanium
precursor, a dialkyltartrate as an auxiliary, and an alkyl hydroperoxide as oxi-
dant, to effect the enantioselective epoxidation. The key intermediate is thought
to be a dimeric complex in which titanium is simultaneously coordinated to the
chelating tartarate ligand, the substrate in the form of an oxygen bound v’-allyl-
oxide and an y2-tert-butylperoxide.
While the molecular tantalum catalyst Ta(OCH2CHJ5 exhibited very poor
activity for epoxidation under Sharpless conditions, the surface-supported ana-
logue [a mixture of 70 % =SiOTa(OCH2CH3)4and 30 % ( =Si0)2Ta(OCH2CH3)3]
was shown to have activity comparable with that of the molecular Ti catalyst.
Furthermore, excellent enantiomeric ee values (up to 94%, compared with
96 % for Ti[OCH(CH3)2]4under the same conditions) were obtained. An inversion
of the the major enantiomer obtained was observed for both the molecular and
supported tantalum catalysts, i. e., the association of tetraisopropyltitanium and
(+)-diisopropyltartrate produces (R)-epoxide whereas the Ti catalyst with
(+)-diisopropyltartrate produces the (S)-epoxide. The putative active species,
-SiOTa(OCH2CH,),[(+)-(DET)] (Structure 18) has also been synthesized and
tested (eq. (3) [23 a]) Further improvements of catalyst activity have been
obtained by modification of the support and refinement of the synthesis of the
supported tantalum alkoxide precursor.
OEt

/ Si< “ ) I /
‘ \
L
1. O Y

18
672 3.1 Development of Methods

Supported Zirconocenes for Ethylene Polymerization

Surface organometallic chemistry has been used in industry to prepare well-

defined "single-site catalysts" (cf. Section 2.3.1.1). One strategy developed by
Exxon consists of the preparation of floating zirconocene cationic species. The
resulting catalysts were found to be quite active in ethylene polymerization. An
ideal supported complex of this type might be one in which a zirconium alkyl
complex was anchored to the surface by a sigma bond, and in which the presented
Lewis acidic sites capable of the abstraction an anionic ligand (a methyl group) to
produce a cation, thus rendering the addition of a cocatalyst unnecessary. This
logic was applied for the production of a supported Zr polymerization catalyst
[7]. Thus, a series of complexes resulting from the reaction between oxides (silica,
silica-alumina, alumina, niobia in various states of dehydroxylation) and zircono-
cene precursors (Cp2ZrMe2and Cp*ZrMe3) were synthesized and fully character-
ized by 13C-NMR. Depending on the oxide, the temperature of dehydroxylation

*
of the oxide, and zirconium loading, different mixtures of surface products
were obtained. Examples of complexes formed by the reaction of Cp*ZrMe3
and alumina(500,are shown in Structures 19-21. The relative reactivity of different
catalysts for the polymerization of ethylene correlated nicely with the hypothesis
that methyl group abstraction is a necessary precondition to high olefin poly-
merisation activity.
- -
.I\\\ h,
,W
Ill

/
S@ Zr..
$"'he /g '''I//Me
0, z r v m
11""
0 Me 0
Me
I ---
I
Al Al ZI 8 0 Al
Al@
19 20 21

Metal-Supported Surface Organometallic Chemistry

From an applied perspective, metals are probably the most important surfaces in
SOMC. Whereas in SOMC on oxides we introduce the active site, in SOMC on
metals the metals themselves are the active catalysts. Organometallic chemistry
provides the means to modify the often unselective metal surface by introduction
of organometallic complexes (most often chemically inert) to the surface and
eventually by transforming the initially obtained species by thermal or chemical
means. For example, the hydrogenolysis of cyclic hydrocarbons, in particular
cyclohexane, on the surface of unmodified Ir particles supported on a silica carrier
has been studied and clearly indicated to bimetallic mechanism of C-C bond clea-
vage (Scheme 4) [24, 251.
 3.1.1.4 Sufuce Organometullic Chemistry 673

0 C-H
Activation
~ 9
M
Eli=
r-H
"2 9 Reductive
Eli%tion
- /\/\/
M M M M M
Scheme 4

Another interesting possibility in the surface organometallic chemistry on

metals is to use the organometallic fragment on the metal surface as a means of
orienting molecules which have several different reactive groups. In this way,
for example, chemoselectivity, regioselectivity, and eventually enantioselectivity
may be conferred to an existing, relatively unselective catalyst of, for example,
the hydrogenation of a single double bond of a polyunsaturated molecule. Surface
organometallic chemistry has provided evidence for some of these effects. The
basic scheme is to react a clean metal particle (that is, usually, one covered in
hydrogen atoms (22), with an organometallic, then treat the initially physisorbed
species to remove partially (23) or totally (24) the hydrocarbon ligands and pro-
gressively form new metal-metal bonds, eventually leading to a surface alloy (25)
and finally a bulk alloy [26]. Variations and partial transformations have been
published for other combinations of metals [27,28].

An example of the use of an alkyl-bearing inert metal fragment 23 to direct the

reaction of a polyunsaturated substrate can be found in the Rh-tin (SnBu2)Rh/
SiOz system. The introduction of SnBu4 to silica-supported highly dispersed rho-
dium metal leads first to physisorption then to a stepwise hydrogenolysis reaction
evolving one to four equivalents of butane [27 a]. When the dealkylation reaction
is performed at 100°C, a species with the empirical formula (SnBu2)Rh/Si02 is
present on the surface and has been characterized by electron microscopy, XPS,
EAXFS, Mossbauer spectroscopy, adsorption measurements [27 b].
This particular complex proved to be quite interesting. The hydrogenation of
citral, an a,w-unsaturated aldehyde with a supported monometallic Rh catalyst,
leads to a variety of products (Scheme 5). A dramatic increase in the selectivity
for geraniol was achieved using the aforementioned bimetallic surface complex,
(Bu3Sn)2SnRh/Si02[29]. This increase in selectivity can be attributed to two po-
tential actions of the surface tin: (1) an electronic effect, in which coordination and
activation of the aldehyde function of citral is enhanced by the presence of butyl-
tin moieties, and (2) a steric effect, in which limited access to the metal surface
favors hydrogenation at the less hindered double bond of citral, i. e., the aldehyde
function.
674 3.1 Development of Methods

uo, geraniol

Scheme 5. Some of the possible products of citral hydrogenation.

The utility of having inert surface adatoms (24) was clearly demonstrated with
the isomerisation of terpenes over a modified monometallic nickel catalyst in
which the addition of 0.03 Sn atoms per surface nickel reduced the loss of ter-
penes to parasitic side reactions from 30 % to 7 % [30]. A similar use of organotin
reagents was used to increase regioselectivity in the hydrogenation of cetaloxopro-
megestone over a Pt/Sn/Si02 catalyst [3 11.
Thermal treatment of tin containing catalysts can eventually lead to surface
alloys (25) in which tin atoms and metal atoms form a distinct crystallographic
phase on the surface of the particle in which active monometallic sites surrounded
by inert metal atoms. Thus reactions such as hydrogenolysis, which depend on
two or more contiguous active metal atoms on the surface [24] can be supressed
while structure insensitive reaction like dehydrogenation can proceed. Thus, the
selectivity for the dehydrogenation of isobutane to isobutene over platinum is
increased from 92.8 % over unmodified platinum to 99.3 % over an analogous bi-
metallic tin-platinum catalyst [32]. Site isolation by formation of a surface alloy
was also used to produce a selective RhSn/Si02 catalyst for the dimerisation of
propene which does not produce olefin homologation or hydrogenolysis as the
analogous monometallic RWSi02 catalyst does [33].
In some cases, the progression from physisorption through the surface organo-
metallic fragment (23) to surface (25) and then bulk alloy is very rapid and the
intermediates are difficult to detect. This behavior in and of itself can be very use-
ful. For example, the reaction of organoarsines and organomercuric compounds
with the surface of alumina supported nickel falls into this category [34]. This
rapid reaction of triphenylarsine with the metallic nickel on alumina, characterised
by SOMC techniques, is to be applied in the removal of mercury and arsenic from
hydrocarbon feeds as a means of prolonging downstream catalysts’ productive
lifetimes [35].

3.1.1.4.4 Conclusion
Surface organometallic chemistry is at a very preliminary stage. From an organo-
metallic standpoint, it now seems possible to develop on surfaces of oxides, zeo-
lites, or metals a unique chemistry which leads to expected, and sometimes very
 References 675

unexpected, surface structures. The simple rules of organometallic syntheses can

be applied to the production of highly selective heterogeneous catalysts. Examples
of these “expected” structures include supported Ti and Ta alkoxides for olefin
epoxidation, supported zirconocenes for olefin polymerization, and supported
Re-carbenes for olefin metathesis. The generalization of this methodology can
be envisaged as a means of rendering molecular catalysis more practical.
The examples of new and unexpected catalytic reactions are probably more in-
teresting. Surfaces are able to stabilize organometallic fragments which have no
equivalent in molecular organometallic chemistry. This situation is due to the
fact that surfaces, due to their rigidity, prevent bimolecular interactions. Thus
highly reactive species are stable and exhibit quite unexpected reactions in the
field of C-H and C-C bond activation such as alkane metathesis, Ziegler-Natta
depolymerization, methane activation, and several others.
The same type of reaction of organometallic species can also be used to modify
the reactivity of small metal particles. In this way, one can for example selectively
poison some metal catalytic sites, one can affect the orientation of incoming sub-
strates prior to reaction at the metal surface, and one can isolate metal atoms or
small reactive areas on the metal surface.

References
[ 11 C. Coptret, J. Thivolle-Cazat, J.-M. Basset, in Fine Chemicals through Heterogeneous
Catalysis (Eds.: Sheldon, R. A., van Bekkum, H.), Wiley-VCH, Weinheim, 2001.
[2] F. Lefebvre, J. Thivolle-Cazat, V. Dufaud, G. P. Niccolai, J.-M. Basset, Appl. Catal. A:
1999, 182, 1.
[3] G. P. Niccolai, J.-M. Basset, in Catalytic Activation and Functionalisation of Light
Alkanes, Kluver Academic, Dordrecht, 1998, p. 111.
[4] F. Lefebvre, A. de Mallmann, J.-M. Basset, Eur: J. Inorg. Chem. 1999, 361.
[S] ESiOTiNp, [Np = CH,C(CH,),]: (a) The synthesis is described in C. Rosier, G.P.
Niccolai, J.-M. Basset, J. Am. Chem. Soc. 1997, 119, 12408; (b) The full characterization
of the species is soon to be published: C. Rosier, Doctoral Thesis, Universitt Claude
Bernard-Lyon I (1999).
[6] =SiOZrNpl: see (a) F. Quignard, C. Lecuyer, C. Bougault, F. Lefebvre, A. Choplin,
D. Olivier, J.-M. Basset, Inorg. Chem. 1992, 31, 928; (b) J. Corker, F. Lefebvre,
C. Lecuyer, V. Dufaud, F. Quignard, A. Choplin, J. Evans, J.-M. Basset, Science 1996,
271(5251), 966.
[7] =SiOZr(r-C,H,),(CH,) and =SiOZr(r-CS(CH,),)(CH,),: see M. Jezequel, V. Dufaud,
M. Ruiz-Garcia, F. Carrillo-Hermosilla, U. Neugebauer, G. P. Niccolai, F. Lefebvre,
F. Bayard, J. Corker, S. Fiddy, J. Evans, J.-P. Broyer, J. Malinge, J.-M. Basset, J. Am.
Chem. SOC.2001, 123, 3520.
[8] =SiOHfNp, and (=SiO),HfNp2: see L. d’Omelas, S. Reyes, F. Quignard, A. Choplin,
J.-M. Basset, Chem. Lett. 1993, 1931; S. Reyes, Doctoral Thesis, Universidad Centrale
de Venezuela, 1996.
[9] =SiOCrNp,: A. Baudouin, J. Thivolle-Cazat, J.-M. Basset, unpublished results. The
synthesis is analogous to that of the zirconium analogue.
[lo] =SiOMo(=NH)(=CHC(CH,),)Np: see W. A. Henmann, A. W. Stumpf, T. Priermeier,
S. Bogdanovid, V. Dufaud, J.-M. Basset, Angew. Chem., Int. Ed. Eng. 1996, 35, 2803.
676 3.1 Development of Methods

[ 111 =SiOTa(=CHC(CH3)3)Np, and ( =Si0)2Ta(=CHC(CH3)3)Np:see (a) V. Dufaud, G. P.

Niccolai, J. Thivolle-Cazat, J.-M. Basset, J. Am. Chem. Soc. 1995, 117,4288; (b) L. Le-
fort, M. Chabanas, 0. Maury, D. Meunier, C. CopCret, J. Thivolle-Cazat, J.-M. Basset,
J. Organomet. Chem. 2000, 593, 96.
[I21 =SiORh(r]-C,H,),: see P. Dufour, C. Houtman, C.S. Santini, C. Nedez, J.-M. Basset,
L. Y. Huu, S.G. Shore, J. Am. Chem. Soc 1992, 114, 4248 and 9242.
[ 131 -SiORe( =CC(CH,),)(=CHC(CH,),)Np: see M. Chabanas, A. Baudouin, C. CopCret,
J.-M. Basset, J. Am. Chem. Soc. 2001, 123, 2062.
[I41 (a) F. Quignard, C. Lecuyer, A. Choplin, D. Olivier, J.-M. Basset, J. Mol. Catal. 1992,
74, 353; (b) G. P. Niccolai, J.-M. Basset, Appl. Catal. A: General 1996, 146, 145.
[15] C. Lecuyer, F. Quignard, A. Choplin, D. Olivier, J.-M. Basset, Angew. Chem., Int. Ed.
Engl. 1991, 30, 1660.
[16] L. d'Ornelas, S. Reyes, F. Quignard, A. Choplin, J.-M. Basset, Chem. Lett. 1993, 1931.
[ 171 M. Chabanas, V. Vidal, C. Coperet, J. Thivolle-Cazat, J.-M. Basset, Angew. Chem., Int.
Ed. 2000, 39, 1962.
[l8] V. Dufaud, J.-M. Basset, US 6.171.475; FR 95 08552 (1995).
[ 191 V. Vidal, A. ThColier, J. Thivolle-Cazat, J.-M. Basset, J. Corker, J. Am. Chem. SOC.1996,
118, 4595.
[20] L. Lefort, C. Coperet, M. Taoufik, J. Thivolle-Cazat, J.-M. Basset, Chem. Commun.
2000, 663.
[21] 0. Maury, L. Lefort, V. Vidal, J. Thivolle-Cazat, J.-M. Basset, Angew. Chem., Int. Ed.
1999, 38, 1952.
[22] Conditions: 60 mg of catalysts 0.70 % Ti, all derived from the same lots of titanium alkyl
and hydride surface complexes; 150 mol TBHP/mol Ti; 20 mol I-octene/mol TBHP,
80 "C. Initial activity was defined as the tangent of the TOF vs. time curve at the origin.
Selectivities are mol epoxide/mol TBHP consumed. Yield = conversion X selectivity.
[23] (a) D. Meunier, Doctoral Thesis, UniversitC Claude Bernard - Lyon I (1999); (b) D. Leu-
nier, A. Piechaczyk, A. de Mallmann, J. M. Basset, Angew. Chem., Int. Ed. 1999,39,3540.
[24] F. Locatelli, J.-P. Candy, B. Didillion, G. Niccolai, D. Uzio, J.-M. Basset, J. Am. Chem.
SOC. 2001, 123, 1658.
[25] (a) J. Toyir, M. Leconte, G. P. Niccolai, J.-M. Basset, J. Catal. 1995, 152, 306; (b) Le-
conte, M. J. Mol. Catal. 1994, 86, 205; (c) E. Rodriguez, M. Leconte, J. Catal. 1991,
131, 457; (d) E. Rodriguez, M. Leconte, J.-M. Basset, J. Cutul. 1991, 132, 472; (e)
E. Rodriguez, M. Leconte, J.-M. Basset, J. Catal. 1989, 119, 230; (f) F. Hugues,
B. Besson, P. Bussikre, J.-A. Dalmon, J.-M. Basset, D. Olivier, Nouv. J. Chim. 1981,
5, 207; (g) F. Hugues, B. Besson, J.-M. Basset, J. Chem. Soc., Chem. Commun. 1980,
719; (h) D. Commereuc, Y. Chauvin, F. Hugues, J.-M. Basset, D. Olivier, J. Chem.
SOC.,Chem. Commun. 1980, 154.
[26] Pt/Sn: F. Humblot, B. Didillion, F. Lepeltier, J.-P. Candy, J. Corker, 0. Clause, F. Bayard,
J.-M: Basset, J. Am. Chem. SOC. 1998, 120, 137.
[27] Rh/Sn: M. Agnelli, P. Louessard, A. El Mansour, J.-P. Candy, J.P. Bournonville, J.-M.
Basset, Catal. Today 1989,6,63;(b) M. Agnelli, J.-P. Candy, J.-M. Basset, J. P. Bournon-
ville, 0.A. Ferretti, J. Catal. 1990, 121, 236; (c) 0.A. Ferretti, J. P. Bournonville, G. Ma-
bilon, G. Martino, J.-P. Candy, J.-M. Basset, J. Mol. Catal. 1991, 67, 283; (d) A. El Man-
sour, J.-P. Candy, J. P. Bournonville, 0.A. Ferretti, G. Mabilon, J.-M. Basset, Angew.
Chem., Int. Ed. Engl. 1989, 28, 347; (e) A. El Mansour, J.-P. Candy, J. P. Bournonville,
0.A. Ferretti, G. Mabilon, J.-M. Basset, Angew. Chem., Int. Ed. Engl. 1989, 28, 347.
[28] Ni/Sn/SiO,: Refs. [27 b] and [30].
[29] B. Didillon, J.-P. Candy, A. El Mansour, C. Houtman, J.-M. Basset, J. Mol. Catal. 1992,
74, 43.
[30] P. Lesage, J.-P. Candy, C. Hirigoyen, F. Humblot, J.-M. Basset, J. Mol. Catal. 1996,112,431.
 3.1.1.5 Ligand-Stabilized Clusters and Colloids 677

[31] Yu. A. Ryndin, C. C. Santini, D. Prat, J.-M. Basset, J. Catal. 2000, 190, 364; (b) V. Ger-
tosio, C. C. Santini, M. Taoufik, F. Bayard, J.-M. Basset, J. Buendia, M. Vivat, J. Catal.
2001, 199, 1.
[32] F. Humblot, J.-P. Candy, B. Didillion, F. Lepeltier, J.-M. Basset, J. Cutal. 1998, 179,459.
[33] J.Toyir,M.Leconte, G. P.Niccolai, J.-P.Candy, J.-M. Basset, J.Mol. Catu1.A:1995,100,61.
[34] Yu. A. Ryndin, J.-P. Candy, B. Didillon, L. Savary, J.-M. Basset, J. Catal. 2001,198, 103.
[35] Yu. A. Ryndin, J.-P. Candy, B. Didillon, L. Savary, J.-M. Basset, C. R. Acad. Sci. Paris,
Se‘rie Ilc, Chimie/Chemistry 2000, 3, 423.

3.1.1.5 Ligand-Stabilized Clusters and Colloids

Giinter Schmid

Metal particles of diameters in the size range of approximately 10-100 nm are

usually called colloids. Colloids normally show more or less broad size distribu-
tions and are characterized by a polycrystalline structure like the bulk materials.
Clusters can roughly be defined as being built up by a distinct number of ordered
atoms. These conditions are mostly realized in particles smaller than 3 4 nm. In
between there exists a region where particles may be considered to be clusters as
well as colloids because of the lack of a precise borderline.
Metal clusters and colloids cannot be isolated in an unprotected form, as coa-
lescence processes set in immediately by contact between particles to give amor-
phous or polycrystalline powders. Therefore, colloids have always been used in
highly diluted dispersions, in polymers or in matrices [l]. Clusters are well
known as stable compounds if they are protected by a shell of appropriate ligands.
To make colloids available as isolable “molecules” (e. g. for homogenous cata-
lysts), one developed a method to stabilize them by a ligand shell similar to
that of clusters [2-4]. Colloids thus became applicable for numerous chemical
and physical investigations [2, 51. Even bimetallic particles have been stabilized
and made useful in various practical applications [ S ] .
The use of nuked but supported colloids and clusters is well established in het-
erogeneous catalysis [6]. Normally, the metal particles are directly generated on
the support from metal salts. Such catalysts usually possess high activities; how-
ever, compared with homogeneously working catalysts, they show considerably
reduced selectivities. This is due to a broad particle size distribution as well as
to the lack of ligand molecules influencing the selectivity decisively.
Ligand-stabilized clusters could be suited to solve several problems in catalysis
simultaneously by virtue of their uniform size, their solubility, their use on different
supports, and the control of their selectivity by varying their ligand shells.
The advantage of a uniform size must be qualified for colloids, having a size
distribution per se which, however, can be relatively narrow in some cases. In
principle the solubility of ligand-protected clusters and colloids makes their use
as homogeneous catalysts possible. But as it has turned out, cluster solutions
tend to decompose during catalytic processes. The isolation of an unchanged clus-
ter material after a homogeneously catalyzed reaction is indicated in only a very
678 3.1 Development of Methods

few recent examples [7, 81. However, the solubility of ligand-protected clusters
can favorably be used to immobilize them by adsorption on different supports
from solution. In the following, only ligand-stabilized clusters and colloids and
their use as immobilized catalysts will be described by means of a few examples
to illustrate the potential of these novel and promising materials for future devel-
opments in catalysis.
Well-defined ligand-stabilized clusters which have been used in a heterogenized
form for various catalytic reactions have become known as “full-shell clusters”.
Such clusters consist of close-packed metal atoms, arranged round a central
atom with the coordination number 12, as in the bulk. The first shell of 12
atoms is enveloped by a second shell of 42 atoms, and so on. The nth shell con-
sists of 10n2 + 2 atoms. Various full-shell clusters of different noble metals could
be isolated by the reduction of appropriate metal complexes in the presence of a
distinct amount of suitable ligand molecules. Besides several M55 two-shell clus-
ters of gold [9], rhodium and platinum [lo, 111, four-, five-, seven- and eight-shell
clusters of platinum [ 121 and palladium [ 13-15] have been prepared and investi-
gated [16, 171. Most of the physical investigationsconcern the study of quantum
size effects as a consequence of the particle size reduction. However, it can be ex-
pected that these apparent academic questions will be of fundamental interest with
respect to catalytic properties, which are of course dominated by the electronic
conditions in a particle.
Figure 1 illustrates the structural principles of some existing full-shell clusters.
Scheme 1 describes the synthesis of some palladium full-shell clusters with dif-
ferent ligands. The ligand molecules influence not only the cluster size but, as will
be shown, especially the catalytic selectivity [6].

Pd(0Ac)Z + H2/02 Pd5 + Pd7

Pd5 + Pd8

Scheme 1. Synthesis of five-, seven-, and eight-shell palladium clusters using

different ligand types.
 3.1.1.5 Ligand-Stabilized Clusters and Colloids 679

M2057 (eight-shell)
[ 151
Example: Pd205,phen840,,600

Figure 1. Examples of ligand-stabilized full-shell clusters.

680 3.1 Development of Methods

As 1,lO-phenanthroline and its derivatives only coordinate edge and corner

atoms, it is necessary to protect the remaining surface atoms by other groups.
Best suited is oxygen, which is found to coordinate the Pd atoms as 022-
groups. The use of oxygen as an additional ligand is of advantage (a) to pre-
vent uncontrolled oxidation of the clusters by air contact and (b) by its easy
removal by gaseous hydrogen, e. g., in the course of hydrogenation reactions.
Thus, very reactive uncoordinated metal atoms are generated during a short
initial period.
Ligand-stabilized clusters are soluble in solvents related in nature to the ligands.
For instance, A U ~ ~ ( P P ~is~most ) , ~soluble
C ~ ~ in dichloromethane or tetrahydro-
furan, whereas its derivative A u ~ ~ [ P ~ ~ P ( ~ - C ~ 12C16
H ~ Scan
O ~easily
N ~ )be] dis-
solved in water [ 131. The palladium clusters with 1,lO-phenanthroline or phenan-
throline derivatives as ligands can be dissolved in a 10: 1 water/ pyridine mixture.
From such solutions they are spontaneously adsorbed by materials such as A1203,
Ti02, CaC03, or active carbon. Catalysts with 1-5 wt. % of cluster material thus
become available. They can be used for gas- phase or liquid-phase heterogeneous
catalyses. A few examples of liquid-phase hydrogenation reactions, using seven-
and eight-shell Pd clusters with different ligand shells, will be discussed below (cf.
also Section 2.4.2.3) [6, 181.
2-Hexyne is best suited to study activity and selectivity of a hydrogenation
catalyst. A mixture of 1,lO-phenanthroline-stabilizedseven- and eight-shell Pd
clusters (Pd 7/8) on Ti02, dispersed in ethanol, catalyzes the transformation of
2-hexyne to cis-2-hexene with ca. 95 % selectivity and a turnover frequency
(TOF) of 35 min-'. As can be seen from Figure 2, trans-2-hexene, n-hexane,
and other hexene isomers are only formed in consecutive reactions. If the phenan-

100
q-
8
75

50

25

0
0 25 50 75 100 125 min 150

Figure 2. Hydrogenation of 2-hexyne in ethanol using 1 wt % of 1,lO-phenanthroline-

stabilized Pd7/8 clusters on TiOz at room temperature and 1 bar of H2 pressure.
 3.1.1.5 Ligand-Stabilized Clusters and Colloids 68 1

100
-8
q

75

50

25
trans-2-hexene n -hexme

0
0 500 1000 I500 2000 2500 3000
min
Figure 3. Hydrogenation of 2-hexyne in ethanol using I wt % of 3-butyl- 1,l O-phenanthroline-
stabilized Pd7 clusters on active carbon at room temperature and 1 bar of H2
pressure.

throline molecules are substituted by n-butyl or n-heptyl groups in the 3-position,

the activity decreases to a TOF value of only 3 min-', whereas the selectivity
increases to ca. 98 %. The most peculiar result is, however, that the consecutive for-
mation of other compounds is almost depressed, as can be seen from Figure 3.
This result shows impressively that small changes at the ligand molecules may
cause drastic effects in selectivity. The reason for the deactivation of the catalyst
towards cis-2-hexene hydrogenation is still not completely understood.
A 1 wt. % Pd 8 catalyst with di[2,9-(2-methylbutyl)]- 1,lO-phenanthroline-pro-
tected clusters on active carbon hydrogenates acetophenone to phenylethanol at
room temperature and at a pressure of 0.1 MPa of hydrogen quantitatively with
a TOF value of 45.5 h-'. Substitution of the 1,lO-phenanthroline by (-)-cinchoni-
dine ligands leads to an almost complete deactivation of the catalyst. Even
temperatures of 60 "C and hydrogen pressures up to 10 MPa do not change the
catalyst's activity. On the other hand, the same (-)-cinchonidine-protected
eight-shell Pd clusters catalyze the hydrogenation of various unsaturated carbonic
acids.
Summarizing these experiments, the use of different ligand molecules, covering
identical metal clusters, can lead to remarkable differences in activity and selec-
tivity. The fact that ligand-stabilized clusters can be synthesized, modified, and
investigated in advance of their immobilization on supports distinguishes these
catalysts in a decisive manner from established metal catalysts.
Iridium cluster mixtures in the size range of 1-4 nm, stabilized by poly-
oxoanions and butylammonium cations, have very recently been described
and used as catalysts. Hydrogen reduction of the polyoxoanion-supported
682 3.1 Development of Methods

iridium compound (Bu,N),Na,[( 1,5-COD)IrP2W15Nb3062] [8, 19, 201 in acetone

solution results in the formation of 3.0 nm clusters. The particles are
isolable and can be redissolved. An averaged chemical formula can be written
as [Ir-900(P4W30Nb6012316~)-60](B~4N)-660Na-300). The clusters are built up
by cubic close-packed metal atoms, as could be expected. Iridium clusters
2 nm in sizeand with the averaged formula [Ir-,00(P4W30Nb60,2,'6-)-33]-
( B U , N ) - ~ ~ ~ Nare
~ -generated
,~~ during the catalytic hydrogenation of cyclohex-
ene from the same COD-iridium complex. These isolable, stable clusters cata-
lyze the reduction of polyoxoanions to blue, WV-containing species. The fact
that these reactions happen in solution and the cluster particles can be isolated
without recognizable changes, and can be used again, makes these results
remarkable as they show that immobilization is not indispensable to keep the
clusters alive.
Cluster mixtures of broader size distributions, stabilized by tetraalkylammo-
nium cations, are available by the reduction of various metal salts (e.g., CrC13,
MnC12, RuCI,, CoBr2, RhCl,, NiBr,, PdC12, PtC1,) by tetraalkylammonium
triethylhydroborate in THF [21, 221, as follows from eq. (1).

MXn + n [R4N][BEtaH] -THF

Mcoll + n [R4N]X + n BEt3 + "12 H2 (1)

The cluster materials can be adsorbed on different supports from solution and
successfully used as catalysts for the hydrogenation of CO, C=C-, O=C-, and
N=C-multiple bonds as well as for the hydrogenation of aromatic compounds
~231.
Ligand-stabilized species can be described as colloids, according to the defini-
tion given above. Colloids used in polymer matrices or other stabilizing liquid
media are not considered here. Continuing the principle of ligating metal particles
of cluster size, only such metal particles are taken into account which exist as
individuals outside the liquids in which they are produced.
As an example designed to make the attraction of ligand-stabilized metal par-
ticles still more plausible, a bimetallic colloid will be discussed. Again, in contrast
to established bimetallic catalysts, well-defined and ligand-stabilized bimetallic
colloids give much more insight into the decisive catalytic step. Starting from
an aqueous solution of easily available gold colloid, particle size ca. 18 nm, a sec-
ond metal, in this case palladium, can be precipitated on the gold germs to give
shell-structured bimetallic particles. Like the monometallic colloids, they can
be protected by water-soluble ligands such as Ph2P(m-C6H4S03Na(TPPMS),
P(m-C6H4S03Na)3(TPPTS) or p-H2NC6H4S03Na.Stabilized in such a manner,
the colloids are isolable as solids of metallic appearance which can be redispersed
in water in any concentration [2, 41. The thickness of the palladium shell is deter-
mined by the amount of palladium salt used for the reduction. Such colloids have
been selected to observe alloy formation and at the same time to study the change
of catalytic activity and selectivity. The 18 nm gold colloids were covered by only
1-2 atomic Pd layers on average, stabilized by a shell of p-H2NC6H4S03Naligand
molecules. It should be mentioned that these colloids have to be used as unsup-
ported powders because the applied physical methods demand high concentra-
 3.1.1.5 Ligand-Stabilized Clusters and Colloids 683

A i-Butene /+ , 8
0 trans-2 Butene
0 cis-2 Butene
0 n-Hexane .
+
Benzene J x 0.5

0
24

101
+
300 400 500 600 700 a 1 300 400 500 600 700 8
Annealing Temperature / K Annealing Temperature / K

Figure 4. Product yields from acetylene Figure 5. Temperature dependence of the

over ligand-stabilized AuPd selectivity of AuPd colloids
colloids as a function of toward C6 product formation [ 5 ] .
preannealing temperature [ 5 ]
(corrected for GC sensitivity).

tions. In spite of this fact, the particles can be considered as “immobilized”, as

only gas-phase techniques have been used [ 5 ] .
The Au(core)Pd(shell) colloids are highly active catalysts for the cyclization
of acetylene at room temperature. However, preannealing procedures lead to
a big increase in the overall activity. The preannealing temperature range is
300-573 K. Temperatures up to 873 K lead to the formation of larger alloy-like
particles. The intermixing of Au and Pd between 300 and 573 K has been studied
by X-ray powder diffraction (XRD) and EXAFS. Figure 4 shows the formation
of products from acetylene over the AuPd colloids as a function of temperature.
Benzene formation dominates that of other products, especially at temperatures
around 500 K. When particle growth begins, the selectivity toward n-hexane
and isobutene formation increases.
The selectivity of the AuPd colloids toward C6 product formation is shown in
Figure 5. It demonstrates clearly the preferred formation of benzene compared
with n-hexane, with increasing alloy formation.
Ligand-stabilized clusters and colloids are going to open a new route in cataly-
sis. The advantages are obvious. They can often be used in monodispersed form or
at least in very narrow size distributions. The use of special ligands enables the
control of selectivity. Ligand-protected clusters may gain importance if fine tuning
is necessary to reach special goals.
684 3.1 Development of Methods

References
[ 13 J. S. Bradley in Clusters and Colloids, From Theory to Applications (Ed.: G. Schmid),
VCH, Weinheim, 1994, pp. 459-544.
[2] G. Schmid, Chem. Rev. 1992, 92, 1709.
[3] G. Schmid, A. Lehnert, Angew. Chem., Int. Ed. Engl. 1989, 28, 780.
[4] G. Schmid, A. Lehnert, J.-0. Malm, J.-0. Bovin, Angew. Chem., Int. Ed. Engl. 1991,
30, 874.
[ 5 ] A. F. Lee, Ch. J . Baddeley, Ch. Hardacre, R. M. Ormerod, R. M. Lambert, G. Schmid,
H. West, J. Phys. Chem. C. 1995, 99, 6096.
[6] G. Schmid, S. Emde, V. Maihack, W. Meyer-Zaika, St. Peschel, J. Mol. Catal., in press.
[7] R. A. T. M. van Benthem, Thesis, University of Amsterdam 1995.
[8] Y. Lin, R. G. Finke, J. Am. Chem. Soc. 1994, 116, 8335.
[9] G. Schmid, Inorg. Synth. 1990, 7, 214.
[lo] G. Schmid, U. Giebel, W. Huster, A. Schwenk, Inorg. Chim. Actu 1984, 85, 97.
[ l l ] G. Schmid, W. Huster, Z. Natuforsch., Teil B 1986, 41, 1028.
[12] G. Schmid, B. Morun, J.-0. Malm, Angew. Chem., lnt. Ed. Engl. 1989, 28, 778.
[13] G. Schmid, B. Morun, J.-0. Malm, Polyhedron 1988, 7, 2321.
[14] G. Schmid, Muter: Chem. Phys. 1991, 29, 133.
[I51 G. Schmid, M. Harms, J.-0. Malm, J.-0. Bovin, J. van Ruitenbeck, H. W. Zandbergen,
W. T. Fu, J. Am. Chem. Soc. 1993, 115, 2046.
[16] G. Schmid in Clusters and Colloids, From Theory to Application (Ed.: G. Schmid),
VCH, Weinheim, 1994, pp. 178-211.
[17] L. J. de Jongh (Ed.), Physics and Chemistry of Materials with Low-Dimensional Struc-
tures, Vol. 18: Physics and Chemistry of Metal Cluster Compounds, Kluwer Academic,
Dordrecht, 1994.
[18] G. Schmid, V. Maihack, F. Lantermann, St. Peschel, J. Chem. SOC.Dalton Trans. 1996,
589.
[19] M. Pohl, D. K. Lyon, N. Mizuno, K. Nomiya, R. G. Finke, Inorg. Chem. 1995,34, 1413.
[20] Y. Lin, R. G. Finke, Inorg. Chem. 1994, 33, 4891.
[21] H. Bonnemann, W. Brijoux, R. Brinkmann, E. Dinjus, Th. JouBen, B. Korall, Angew.
Chem., Int. Ed. Engl. 1991, 30, 1312.
[22] H. Bonnemann, R. Brinkmann, R. Koppler, P. Neikler, J. Richter, Adv. Muter: 1992,
4, 804.
[23] H. Bonnemann, W. Brijoux, R. Brinkmann, R. Fretzen, Th. JouBen, R. Koppler, B. Korall,
P. Neiteler, J. Richter, J. Mol. Cat. 1994, 86, 129.

3.1.1.6 New Generation of Re-Immobilized Catalysts

Helmut Bahrmann

3.1.1.6.1 Background
In the course of introducing the immobilized ligand TPPTS (triphenylphosphine
trisulfonate) on an industrial production scale it was found that cations, especially
ammonium and ammonium derivatives, have an extreme influence on the proper-
ties of the TPPTS salts. Even slight variations within the cations have a tremen-
 3.1.1.6 New Generation of Re-Immobilized Catalysts 685

dous effect. By changing the size and type of the ions, a total change of physical
properties occurs. For example, the substitution of an alkyl group on the nitrogen
by hydrogen will shift the whole system from a water- soluble to an insoluble sys-
tem (Figure 1).
First of all, these properties were used to separate the sulfonated phosphine
from the excess of sulfuric acid after sulfonation by forming a triisooctylammo-
nium salt in toluene, which is totally insoluble in water [l]. Later it was discov-
ered, that the “re-immobilized ligand” in toluene as well as the “immobilized
ligand” in water are useful and remarkably stable catalyst systems. As classical
homogeneous catalysts they are very active, e. g., for the hydroformylation of
higher olefins and olefins with internal double bonds.
The re-immobilized ligands are “trifunctional.” The first function is the classi-
cal biphyllic donor ability of P”’. The second function consists of the presence of
sulfonic or carboxylic acid groups which introduce an ionic structure into the mo-
lecule. With alkali or alkaline earth cations as counterions, these ligands are water-
soluble and used as “immobilized catalysts” with the benefit of facile catalyst re-
cycling by simple phase separation (cf. Section 3.1.1.1). In this connection the use
of quaternary ammonium cations (see Figure 1, lefthand side) brings up phase-
transfer properties within the two-phase system in order to enhance the activity
of higher olefins [2-lo].
These counterions are more than simple tools for improving the activity in
the two-phase catalysis. In contrast to simple metal cations, ammonium ions as
countercations of the chemical functional groups contain, via the alkyl groups
R3 of the nitrogen atom, an additional potential of variability which can be
used principally as a third function of a ligand and which introduces unique
and very useful new properties into the ligand and the corresponding catalyst
systems.
Generally the countercations could be considered as some kind of
“homogeneous backbone” for the functionalized ligands. Not least with regard

R’ R3
I
I
#-N+-R’

R‘
I
I
R’

RZ-P+-R’
-
I
R’
R’= alkyl (nC14) functionalized phosphine anion R3 = alkyl (CSz2)
R2 alkyl (nC14) TPPTS’

immobilized system re-immobillred system

water soluble insoluble in water

Figure 1. Influence of cations on the properties of TPPTS salts.

‘Triphenylphosphine trisulfonate.
686 3.1 Development of Methods

to the homogeneous backbone function of these ligands, the corresponding metal

complex catalysts are called "re-immobilized catalysts."

3.1.1.6.2 Basic Principles and Chemical Applications

The re-immobilized ligands are generally prepared according to eq. (1).

immobilized ligand re-immobilized ligand

aqueous phase organic phase

By introducing different amines into an organic solvent such as toluene the

sodium cations of the sulfonates can be exchanged by addition of sulfuric acid.
Sodium hydrogensulfate is formed as a by-product. As immobilized phosphorus
ligand TPPTS is used in most cases.
As may be seen from Table 1, many different amines can be used. It is possible
to use primary as well as secondary amines instead of tertiary ones. In all cases the
P"'-yield (transition into the organic phase) is good. Upon increasing the molecu-
lar weight of the amines, the pH value is generally lower. The last three amines are
multifunctional. Perhaps because of the large distance between the amine groups,
they do not tend to polymerize as do the lower amines (see below).
According to eq. (l), besides amine changes many variations are possible:
(1) variation of immobilized phosphorus ligand;
(2) variation of acids;
(3) variation of solvents and
(4) variation of preparation procedure.
Besides TPPTS as the immobilizing phosphorus compound other ligands have
been used.
In the application of membrane technology (cf. Section 3.2.3) for the separation
of the Rh complexes and the re-immobilized ligands after the reaction, a further
remarkable enlargement of the ligands was desirable. Unfortunately, the combi-
nation of diamines with TPPTS yields highly crosslinked polymeric materials,
which cannot be handled. A reduction of the degree of crosslinking is possible
by use of the disulfonated TPPDS (cf. Section 3.1.1.1). So, in a combination
with TCD-diamine (tricyclodecane diamine) a salt was formed that was partly
soluble in toluene and soluble in THE The same was the case with the use of
N,N'-dimethyl-TCD-diamine. These salts may be useful in water-free two-phase
catalyst systems.
Instead of sulfuric acid, phosphoric acid can also be used as the acid. Under
special circumstances the olefin for the further catalysis may serve as a
solvent itself. This concept was successfully realized with dicyclopentadiene
(DCP).
In some cases it is desirable and necessary to use P compounds with low
basicity such as phosphites. In order to prepare ionic phosphites of the structure
 3.1.1.6 New Generation of Re-Immobilized Catalysts 687

Table 1. Ligand preparation: variation of amines.

Amine Mol. Temp. P" Addition P"' content of
mass ["C] of i- phases [%I
Start End C3H7OH Lower
Upper
aqueous
Triisoocty lamine 353.7 20 3.5 0.0 100
Methylditallowamine 513.6 60 7.3 3.5 0.8 100
Distearylamine 522.0 65 7.7 2.6 0.0 100
Methy ldistearylamine 536.0 60 9.0 3.6 93.9
Jeffamine M 600 600.0 20 10.0 1.8 1.6 88.6
Tricetylamine 690.3 20 7.5 3.5 6.6 98.7
Tristeary lamine 740.8 60 5.7 1.0 0.6 87.0
Tri-n-octadecy lamine 774.5 75 6.8 1.0 1.8 90.6
Triicosy lamine 858.6 75 6.8 0.0 1.1 95.5
Tridoicosylamine 942.8 80 3.5 0.1 94.3
Jeffamine D 2000 2000 20 9.7 3.6 8.9 88.0
Jeffamine T 3000 3000 20 9.0 3.6 93.2
Jeffamine D 4000 4000 20 9.5 3.4 16.0 73.0
Solvent: 2.7 g toluene/g amine; phosphorus source: TPPTS: 0.33 moles/mole amine;
acid: sulfuric acid.

mentioned above, the preparation procedure can be modified [ I l l as outlined in

eqs. (2) and (3).

Using the hydroformylation of various olefins a variety of olefins was tested

with the triisooctylamine-TPPTS salt [12, 131. It could be shown that different
olefinic compounds and structures (cycloaliphatic, internal, functionalized) can
be used with the re-immobilized catalyst system (see Table 2).
Ionic phosphites (triisooctylamine salts of p-sulfonated phosphorous acid tri-
phenyl ester (TPPpS-TIOA salt) were investigated by Fell and Papadogianakis
[14]. Table 3 shows a direct comparison with TPP and acetone as solvent in the
hydroformylation of n- 1-tetradecene. A significantly better ratio of linear/
Table 2. Olefin testing with triisooctylamine-TPPTS salts: hydroformylation of various olefins. %
03
Alkene Rh P"'/Rh ratio Pressure Con- P"'/Rh ratio"' vb ratiob) Ligand separation by
version [diso] cation interchange"'
[ppml [moVmolI [MPaI [%I [mol/mol] Recovery [%I
cu
L

Cyclohexene 9 120 27.0 100 <I 31 b

m
Dimersol 9 124 27.0 81 <1 32 2
F
h
Diisobutene 26 36 27.0 99 <1 42 2
Dicyclopentadiene 53 60 27.0 100 79
t
R
1 -Hexened' 10 100 2.5 77 1.o 64/36 74
Limon en e 132 120 27.0 98 93
1-Decene 44 118 27.0 99 2.1 65/35 100
Oleoylic alcohol" 44 70 27.0 98 12.3 92
Methyl acrylateO 100 60 27.0 100 96/4g' 87
Reaction conditions: temp. 130 "C; reaction time 6 h.
a) After reaction.
b, Ratio of linear to branched.
Extraction with aqueous NaOH, phase separation, and subsequent re-extraction with toluene-amine and H2S04.
dl Reaction time 2.5 h.
e, HD-ocenol 90/95@of Henkel Corp.
Reaction time 2 h.
g, Ratio of a-formylpropionate to b-formylpropionate.
 3.1.1.6 New Generation of Re-Immobilized Catalysts 689

Table 3. Ligand testing by hydroformylation: ionic phosphites (direct comparison with

triphenylphosphine).
P R h ratio Triphenylphosphine TPPpS-TIOA salt")
[mollmol] (TPP)
40 80 40 80
Conversion [%I 81 83 71 70
L/b ratiob' 7 2128 7212 8 83/17 87113
Solvent Acetone Acetone Acetone Acetone
Reaction conditions: n-1-tetradecene; pressure 5 MPa; Rh concentration 20 ppm;
temp. 125 "C; reaction time 3 h.
a) Triisooctylamine salts of para-sulfonated phosphorous acid triphenylester.
b, Linearhranched.

branched compounds (llb)ratio was achieved with the TPPpS-TIOA salt as com-
pared with TPP.
Reversing the ligand preparation, the re-immobilized catalysts (including
degradation products and the rhodium complex) can generally be immobilized
by treatment with aqueous sodium hydroxide according to eqs. (4 a)-(4 c).
NaOH (aq.)
O=P(R'S03HNR3)3 -H,O O=P(R'S03Na)3 + 3 NR3

NaOH (aq.)
- H20
+ 3NR3

NaOH (aq.)
* [Rhlaq

organic phase aqueous phase organic phase

The concentration of the aqueous sodium hydroxide has a tremendous influence

on the extraction figures. At very low concentrations (0.01 %) only the phosphine
oxides are extracted selectively, whereas at a 0.05 % concentration 20 % of the
phospine is discharged, too.
This result offers the opportunity for a process for the simple selective separa-
tion of phosphine oxide in continuous operation in order to increase the lifetime of
the catalyst system. Beside the separation of phosphine oxide it should be possible
to separate degradation products as well. The aqueous phase canbe submitted to
the oxidative treatment for Rh recovery according to [15-171.
The amine content of the organic phase can be separated by distillation and
recycled again by treatment with fresh sulfonated phosphine and sulfuric acid.
This recovery is an important advantage over conventional ligands where, e. g.,
after degradation by oxygen all of them must be discarded. So the use of more
sophisticated functional variations on the amine becomes ecologically and
economically beneficial.
690 3.1 Development of Methods

3.1.1.6.3 Technical Applications

The general advantage of the technique of separating small organometallic com-
plex compounds such as HRhCO(PBu& by means of membranes, while allow-
ing small organic molecules to permeate under reverse osmosis (RO) condi-
tions, was claimed for the first time in BP patents in 1968-1970 [18-211.
RO conditions mean high pressure (5-10 MPa), low flow rate ( 1 4 Wm2 . h),
and a solute rejection of about 78-94%. Similar results were reported by
Monsanto [22]. By using RO conditions a special opportunity to generate
transition metal complexes bearing weakly bonded ligands, e. g., dinitrogen
according to eq. ( 5 ) , was offered by Gosser et al. [23-251. A general break-
through with respect to membrane technology was achieved by Bayer [26]
when he changed from the RO method to ultrafiltration (UF conditions with
lower pressure (2 bar), higher flow rates (20 L/m2 . h) and a superior metal
retention). He used anchored catalysts on “mobile supports” such as soluble
macromolecularly P-functionalized polystyrene with a high molecular mass of
about 10000 and low posphorush-hodiumratios. Since the processing of real estab-
lished catalytic systems needs high P R h ratios for stabilization, membranes and
ligands in the cut-off range of a molecular mass between 1000 and 10000,
which enable a good retention of metal complexes and free ligands, have to be
developed.

New polyaramide membranes with outstanding properties (membrane UF-PA-5)

met all requirements [27].
Tricyclodecane dialdehyde (TCD-dial) the starting product for TCD-diamine, is
formed by hydroformylation of dicyclopentadiene, DCP. This hydroformylation
was used as a test reaction for re-immobilized catalysts in membrane techniques
(eq. (6)).

With unmodified rhodium carbonyl catalyst, a high yield of dialdehyde can nor-
mally be achieved. After the reaction, the crude aldehyde is separated from the
rhodium by distillation. Because of the two aldehyde groups and the high boiling
point of the product, much high-boiling residue is formed too, which is difficult to
handle with respect to the recovery of the rhodium. Therefore, a remarkable
amount is lost. In order to solve this problem, re-immobilized catalysts were
developed and tested especially with this product. At first, it was found that
re-immobilized catalysts as well as TPP-modified Rh catalysts could be used,
if the rhodium concentration was raised from about 30 to 80 ppm with a
reaction time prolonged from 2 to 4 h.
 3.1.1.6 New Generation of Re-Immobilized Catalysts 691

Table 4. Ligand testing of amine-TPPTS salts by hydroformylation of DCP.

Amine Mol. Conversion Selectivity P"'1Rh pH value
mass [%I dialdehydel ratio"' after
monoenal reaction

Triisooctylamine 353.7 99.9 9911 74

Methylditallowamine 513.6 99.6 9218 41 4.0
Distearylamine 522.0 98.4 9713 72 4.0
Methyldistearylamine 536.0 99.4 9515 63 4.3
Jeffamine M 600 600.0 98.8 40160 51 3.3
Tricetylamine 690.3 98.7 9614 78
Tristearylamine 740.8
Tri-n-octadecylamine 774.5 98.5 9119 84
Triicosylamine 858.6 99.0 9515 103
Tridoicosylamine 942.8 99.7 90110
Jeffamine D 2000 2000 98.1 6913 1 7.6 4.0
Jeffamine T 3000 3000 98.4 63/37 3.9 6.2

Reaction conditions: feed, reaction product of hydroformylation of dicyclopentadiene; solvent

= about 50% toluene; phosphorus source = TPPTS, 0.33 moYmol amine; pressure = 27 MPa;
Rh conc. = 60 ppm; P/Rh ratio = 100; reaction temp. = 130 "C; reaction time = 4 h.
a' After reaction.

From the beginning, in the subsequent membrane separation step the first test
with the re-immobilized catalysts yielded a much better Rh retention of 96 % as
compared to the Rh/TPP-system with only 56 9% [28].
A variety of amines were tested at first in the hydroformylation reaction with
respect to conversion and selectivity to dialdehyde. Table 4 shows some results.
As the molecular mass of the amines increase, a lower yield of dialdehyde is
observed. Distearylamine was used as a standard in further experiments. Some
medium-sized amines tend to precipitate below 40 O C , which offers the possibility
of catalyst separation by cooling and filtration.
With respect to succeeding membrane separation it was found that generally an
increase of the molecular mass of the amines leads to improved retention of rho-
dium, of phosphorus ligand and, last but not least, of the amines. It can be demon-
strated that an increase in molecular mass does have a contradictoryeffect on the
overall efficiency. A high amount of permeate corresponds to a lower flux of
permeate due to the higher concentration of compounds within the retentate
(osmotic pressure). Traces of amine in the permeate are the result of a very low
temperature-dependent dissociation of the ammonium salts into amine and free
acid according to eq. (7).
692 3.1 Development of Methods

In order to stabilize the ammonium salts, the presence of free amine in the system
is recommended. With respect to this additional requirement, an ideal system must
have the same good retention for amines as well as for phosphorus and rhodium.
Therefore the choice of distearylamine could only be regarded as a good com-
promise of hydroformylation requirements and membrane separation properties.
The separation of the Rh-distearylamine-TPPTS catalyst system by membranes
was tested on pilot plant scale with crude aldehyde from the hydroformylation of
DCP. Figure 2 shows the principle of the membrane separation step. Within the
module, the mixture of crude oxoaldehyde, toluene, free ligands, and the Rh cat-
alyst complex coming from the reactor is parallel- pumped to the surface of the
membrane. Only aldehyde and higher-boiling products pass through the mem-
brane. The concentrate of Rh complex and ligands is recycled back to the reactor.
In order to realize high retention for rhodium and ligands, a two-stage mem-
brane unit was used successfully (see Figure 3) [30].
The viscosity of the mixture was adjusted by the addition of approximately
50% of toluene. The pilot plant consist of 0x0-reactor and the membrane unit,
which was directly connected to the reactor. Standard plate modules from
Dow (Type DDS 30-4.5) were used. The conditions of the membrane separation
were: overflow: - 200 l/h, separation temperature: 40 "C, transmembrane pres-
sure: 1 MPa. The unit was continuously operated over a period of 12 weeks.
No decrease of activity of the catalyst was observed. In order to obtain a dialde-
hyde selectivity > 9070, the Rh concentration must be increased to 100 ppm.
Most of the loss of ligand was due to traces of oxygen, which could not excluded
totally on pilot scale.

z
L
u
m membrane module
t

catalyst complex

-- 0 r--
concentrate =
rhodiumcomplex

0 0

permeate = product
Figure 2. Membrane separation mechanism. t
 References 693

TCD-dial
OX0
reactor

> 95 % Rhodium 4 % Rhodium

olefin > 94 % ligands 4 % ligands
DCP

COIH2 -
Figure 3. Pilot plant run - membrane process.

3.1.1.6.4 Future Prospects

The formation of re-immobilized ligands on the basis of a simple addition of ions
has so far only been evaluated in the hydroformylation reaction. The transfer to
other reactions in homogeneous catalysis may deliver useful new results. Chelat-
ing ligands as strong complexing agents generally need only a low excess of free
uncomplexed ligands for the stabilization of the active catalyst complex. They
make it possible to perform the hydroformylation reaction at a very low P R h
ratio, so this property should be extremely useful in the application of membrane
separation technology.
Due to low prices for transition metals, it becomes increasingly true that with
the development of effective and efficient ligands the costs of these ligands exceed
those of the transition metals. Appropriately modified, asymmetric, re-immobi-
lized ligands which yield a lower enantioselectivity in an aqueous medium [29]
may therefore have a good chance in the future in connection with membrane
technology.

References
Ruhrchemie AG (R. Gartner, B. Cornils, H. Springer, P. Lappe), EP 0.107.006 (1982).
Ruhrchemie AG (H. Bahrmann, B. Cornils, W. Konkol, W. Lipps), DE 3.420.491 (1984).
Hoechst AG (H. Bahrmann, B. Cornils, W. Lipps, P. Lappe, H. Springer), EP 0.163.233
(1984).
Hoechst AG (H. Bahrmann, B. Cornils, W. Konkol, W. Lipps), EP 0.157.316 (1984).
Hoechst AG (B. Cornils, W. Konkol, H. Bahrmann, H. Bach, E. Wiebus), DE 3.41 1.034
(1984).
Hoechst AG (H. Bach, H. Bahrmann, B. Cornils, V. Heim, W. Gick, W. Konkol, E. Wie-
bus), EP 0.302.375 (1988).
Hoechst AG (B. Cornils, W. Konkol, H. Bach, W. Gick, E. Wiebus, H. Bahrmann),
EP 0.186.075 (1985).
694 3.1 Development of Methods

[8] Hoechst AG (B. Comils, W. Konkol, H. Bahrmann, H. Bach, E. Wiebus), EP 0.156.253

(1984).
[9] Hoechst AG (D. Kampmann, J. Weber, H. Bahrmann, C. Kniep), EP 0.444.481
(1991).
[lo] Hoechst AG (H. Bahrmann, P. Lappe), EP-OS 0.602.463 (1993).
[ l l ] Hoechst AG (H. Bahrmann, B. Fell, G. Papadogianakis), EP 435.071 (1989).
1121 Hoechst AG (H. Bahrmann, W. Konkol, J. Weber, H. Bach, L. Bexten), EP 0.216.315
(1985).
1131 Hoechst AG (H. Bahrmann, B. Comils, W. Konkol, J. Weber, L. Bexten, H. Bach),
DE 3.534.317 (1985).
[14] Hoechst AG (H. Bahrmann, B. Fell, G. Papadogianakis), EP 0.435.084 (1989).
1151 Hoechst AG (L. Bexten, D. Kupies), EP 0.255.673 (1986).
[ 161 Hoechst AG (G. Diekhaus, H. Kappesser), EP 0.322.661 (1987).
[17] Hoechst AG (J. Weber, L. Bexten, D. Kupies, P. Lappe, H. Springer), EP 0.367.957
(1988).
[18] BP (M. Th. Westaway, G. Walker), DE-OS 1.912.380 (1968).
[19] BP (A. Goldup, M. Th. Westaway), DE-OS 2.029.625 (1969).
[20] BP (A. Goldup, M. Th. Westaway), BP 1.266.180 (1969)
[21] BP (J. E. Ellis), BP 1.312.076 (1970).
[22] Monsanto (E. Perry), DE-OS 2.414.306 (1973).
[23] Du Pont (L. W. Gosser), US 3.853.754 (1974).
[24] Du Pont (L. W. Gosser), US 3.966.595 (1974).
[25] L. W. Gosser, W. H. Knoth, G. W. Parshall, J. Mol. Cutul. 1977, 2, 253.
[26] E. Bayer, V. Schurig, Angew. Chem., Int. Ed. Engl. 1975, 14, 493; E. Bayer, W. Schu-
mann, J. Chem. Soc., Chem. Commun. 1986, 949.
1271 Hoechst AG (M. Haubs, F. Herold, C. P. Krieg, D. Skaletz), EP 0.325.962 (1988).
[28] Hoechst AG (H. Bahrmann, M. Haubs, W. Kreuder, Th. Muller), DE-OS 3.842.819
(1988).
[29] K. T. Wan, M. E. Davis, Nature (London) 1994, 370, 449.
[30] H. Bahrmann, M. Haubs, T. Muller, N. Schopper, B. Comils, J. Organomet. Chem. 1997,
545/546, 139.

3.1.1.7 New Reactions

Jiirgen Henvig

Recently, many papers have been published in the field of biphasic catalysis, espe-
cially in the aqueous version. A number of new reactions have also appeared.
They can be subgrouped either by reaction type or by the different effects
which can be accomplished by applying two-phase catalysis in water:
(1) the separation of the catalyst from the products;
(2) the suppression of consecutive reactions via extraction; and
(3) the control of the selectivity or rate of the reaction via the pH of the
water phase.
Whereas (1) is the most prominent and obvious effect of two-phase catalysis,
(2) and (3) have been attracting more interest recently.
 3.1.1.7 New Reactions 695

3.1.1.7.1 Separation of the Catalyst from the Product

Oxidation of Alcohols to Ketones and Carboxylic Acids

Oxidation of alcohols to ketones or carboxylic acids is normally achieved through

stoichiometric oxidants in homogeneous phase. For fine-chemical synthesis a two-
phase process which allows for easy catalyst separation would be highly desirable.
Simple biphasic processes with high TOFs and air as the oxidant have been
described (eq. (1) [l, 21).

Nonactivated secondary alcohols were oxidized to the corresponding ketones

with initial TOFs up to 100 mol mol-’ h-’. Even less water-soluble and less reac-
tive alcohols like 2-octanol could be oxidized with rates up to 20 mol mol-’ h-’.
Primary alcohols were oxidized to the corresponding acids. By adding TEMPO
(2,2,6,6-tetramethylpiperdinyl-l-oxyl)the intermediate aldehyde could be
trapped. As catalyst, the Pd complex of bathophenanthroline disulfonate (Struc-
ture 1) was used (bathophenanthroline is commercially available at approx. US
$ 300/5 g).

1
This “green” system will be very useful in fine-chemical synthesis [2 b]. With
the biphasic technique, contamination of the product with heavy metals could be
minimized and recovery of the expensive Pd metal could be facilitated.

Isomerization of Alkenes

Ni complexes have rarely been applied to two-phase catalysis. An example is the

commercially interesting isomerization of aryl substituted alkenes according to
eq. (2) [31.
696 3.1 Development of Methods

Ni(C0D)z ; HX
ArzP-(CH2)4-PArz

cis and trans

With the Na salt of tetrasulfonated 1,4-bis(diphenylphosphino)butane (DPPB)

in acids like HC1 or CF,COOH, TOFs of 106 h-' were obtained when isomerizing
allylbenzene to cis- and trans-/%methylstyrene. The isomerization of 1- to 2- and
3-hexene was also demonstrated. With TPPTS (cf. Section 3.1.1.1 .l) only poor
results were achieved. For the conversion a Ni hydride mechanism is assumed
in analogy to the known homogeneous isomerization.

3.1.1.7.2 Suppression of Consecutive Reactions

via Extraction of Products
Telomerization of Butadiene and Ammonia

The simultaneous homogeneous telomerization of butadiene with ammonia cata-

lyzed by Pd complexes (see also Section 2.7) normally leads to a mixture of
mono-, di-, and trioctadienylamines [4].Hydrogenation of the 2,7-octadienyl-
amine yields commercially important n-octylamine (eqs. (3) and (4)).

Pd cat.
2 N -NH~ +
(3)
2 3
Pd cat.
2+3 ___) secondary and tertiary octadienylamines (4)
NH3

Because the primary octadienylamines react faster than ammonia itself, the
main products of this homogeneous reaction are the secondary and tertiary octa-
dienylamines. By application of the two-phase concept, primary octadienylamines
became the main products [5]. Table 1 shows the remarkable difference between
the homogeneous and the two-phase reaction.
Even though a high excess of butadiene was applied in the two-phase
reaction the primary octadienylamine was the main product. The low solubi-
lity of the monooctadienylamines in water prevents the consecutive reaction
to secondary octadienylamines. If an excess of ammonia is applied and
CH2C12 is used as an extraction solvent, the selectivity to primary octadienyl-
amines can be as high as 98-99 %, illustrating the industrial potential of this
reaction.
 3.1.1.7 New Reactions 697

Table 1. One-phase versus two-phase telomerization.

Technique Selectivity for amine Yield [% rel. to ammonia]

~~

Homogeneous 2 4 61 21
Two phase 32 26 1.5 24

Hydroaminomethylation of Alkenes

The direct amination of olefins (hydroamination; cf. Section 2.7) has only been
achieved efficiently for alkenes with a tertiary carbon atom (e. g., isobutene) or
ethylene [6]. Furthermore, the equilibrium of the hydroamination is not favorable
in many cases, so first-pass yields can be low with a need for a high recycle
stream.
Another one-step route to amines is hydroaminomethylation, which is a
sequence of hydroformylation and reductive amination of the intermediate
aldehyde in a one-pot reaction (Scheme 1).

R1,R2,R3= Alkyl, H

Scheme 1. Hydroaminomethylation sequence.

This hydroaminomethylation has only been applied in homogeneous one-phase

systems until now. The reaction will mostly lead to secondary and tertiary amines,
because the intermediate primary amines will further react with the aldehyde
formed to secondary amines. The synthesis of the technically important primary
amines from ammonia and alkenes via hydroaminomethylation was investigated,
but only low selectivities ( 3 2 % ) and TOFs (9 h-’) to primary amines could be
achieved, despite the high excess of ammonia. Other side products, e. g., via aldo-
lization, are also observed.
The consecutive reaction to secondary amines can be suppressed by using
the two-phase concept and a dual catalyst system (RMr) [7]. This system
can achieve hydroformy lation as the first step (Rh) and a quick hydrogenation
of the imine resulting from the reaction of the aldehyde with ammonia (Ir).
Ligands such as TPPTS (trisodium 3,3’,3”-tris[benzenesulfonate])or BINAS
(for both ligands; cf. Section 3.1.1.1) can be used to keep the metals in the
water phase. With an excess of ammonia, the main products are primary
amines. In the case of BINAS excellent n h o selectivities were achieved.
The ratio of primary and secondary amines is dependent on the chain length
of the resulting amine - clearly an effect of the increasing lipophilic character.
698 3.1 Development of Methods

The biphasic hydroaminomethylation with BINAS seems to be a good way of

producing di-n-butylamine.

3.1.1.7.3 Control of Selectivity of the Reaction

via the pH of the Water Phase
Selective Hydrogenation of a$-Unsaturated Aldehydes

In many papers concerning biphasic catalysis in water, the pH of the water phase
is not measured. Because many reactions are pH-dependent, it should be mo-
nitored closely, even over the course of the reaction, e. g., during biphasic hydro-
formylation, in order to control the formation of aldolization products.
The importance of controlling the pH in a two-phase reaction was demonstrated
by Jo6 and co-workers [8, 91. During their investigation of the hydrogenation of
unsaturated aldehydes (Scheme 2) with Ru/TPPMS complexes, they observed a
remarkable switch in selectivity on changing the pH.

RO
-H
R*o
\ RO
-H
/
R=Aryl

Scheme 2. Hydrogenation of unsaturated aldehydes.

At lower pH, the dominant product is the saturated aldehyde, at higher pH the
unsaturated alcohol. The rate of hydrogenation is also influenced. At pH 5 6 the
rate is roughly one order of magnitude lower than at pH 2 7. The selectivity could
be correlated with the equilibrium of different Ru hydride complexes; the equi-
librium distribution of these hydride complexes (Structures 2 and 3) is strongly
dependent on the pH of the solution according to eq. (5). The authors were
able to quantify the protons liberated during the above reaction and to identify
the different complexes via 'H and 31PNMR spectroscopy: 2 is the major species
in acid solution, whereas 3 is dominant in solution at pH > 9. This clearly shows
the importance of controlling the pH in two-phase reactions.
 References 699

Hydrogenation of C 0 2 to Formic Acid [lo]

Without the addition of amines, Jo6 et al. were able to reduce HC03- as NaHC03

HCO3- + H2 -
to formate in an homogeneous solution at high rates (eq. (6) [ l l , 121).
HCOO- + H20 (6)

Water-soluble complexes like [HRuCl(TPPMS),] (TPPMS = 3-sulfonatophe-

nyldiphenylphosphine; cf. Section 3.1.1.1)) and [RhCl(TPPMS),] were tested
and a dependence of the reaction rate on the pH of the catalyst solution was
observed. At higher pH (> 6) the rate drops dramatically with increasing pH.
The reason could be the lower HC03- concentration due to the pH-dependent
HCO;/C032- equilibrium or a different concentration of the active species.
If all the NaHC0, is converted to formate, the rate drops then as well. At this
point the pH also will drop due to the formation of free formic acid.

References
[I] R.A. Sheldon, G.-J. ten Brink, I.W.C.E. Arends, Science 2000, 287, 1636; R.A.
Sheldon, G.-J. ten Brink, I. W. C. E. Arends, G. Papadogianakis, J. Chem. Soc. Chem.
Commun. 1998, 2359.
[2] (a) R. A. Sheldon, I. W. C. E. Arends, A. Dijksman, Catal. Today 2000,57, 157; (b)R. A.
Sheldon, H. van Bekkum, Fine Chemicals through Heterogeneous Catalysis, Wiley-
VCH, Weinheim, 2000.
[3] H. Bncout, A. Mortreux, E. Monflier, J. Organomet. Chem. 1998, 553, 469.
[4] T. Mitsuyasu, M. Hara, J. Tsuji, J. Chem. Soc., Chem. Commun. 1971, 345; J. Tsuji,
M. Takahashi, J. Mol. Catal. 1981, 10, 107.
[5] T. Prinz, W. Keim, B. DrieRen-Holscher, Angew. Chem. 1996, 108, 1835; Bayer AG
(T. Prinz, W. Keim, B. DrieBen-Holscher, H.-J. Traenckner, J.-D. Jentsch) EP 0.773.3 11
B1 (1996).
[6] T. Miiller, M. Beller, Chem. Rev. 1998, 98, 675.
[7] J. Herwig, M. Beller, Angew. Chem., Znt. Ed. 1999, 38, 2372.
[8] F. Job, G. Laurenczy, J. KovBcs, A. Cs. BCnyei, A. Katho, Angew. Chem., Znt. Ed. 1998,
37, 969.
[9] F. Job, J. Kovics, A. C s . BCnyei, A. Kath6, Catal. Today 1998, 42, 441.
[lo] W. Leitner, Angew. Chem., Znt. Ed. 1995, 34, 2207.
[ l l ] F. Job, G. Laurenczy, L. Nidasdi, J. Elek, J. Chem. Soc., Chern. Commun. 1999, 971.
[I21 F. Job, G. Laurenczy, L. NBdasdi, Znorg. Chem. 2000, 39, 5083.
 Applied Homogeneous Catalysis with Organometallic Compounds
Edited by B. Cornils and W. A. Herrmann
Copyright 0 Wiley-VCH Verlag GmbH, D-69469 Weinheim, 2002

700 3.1 Development of Methods

3.1.2 Molecular Modeling in Homogeneous Catalysis

Rochus Schmid, Wolfgang Hieringel; Dieter Gleich,
Thomas Strassner

3.1.2.1 Molecular Modeling Techniques

Rochus Schmid

The enormous growth of computational power in the last couple of decades is

usually expressed in terms of the exponential nature of Moore’s Law: the speed
of “state-of-the-art” computer hardware roughly doubles every one and a half
years [I]. Much more complex computational projects can be tackled nowadays
by parallel supercomputers. Examples are weather forecasts, world climate mod-
els, the simulation of astrophysical events or the protein-folding problem. On the
other hand, the computational power of simple desktop personal computers in-
creased significantly, which made it possible to perform numerically demanding
calculations in a routine fashion for everyone. As for any other field of science
and engineering this had a significant impact on chemical research:
“computational chemistry” or “molecular modeling” is nowadays an integral
part of the arsenal of methods to study chemical systems. It is important to
note that the increase in computer speed is not the only reason for the growing
importance of theoretical methods in chemical research. In addition, the computer
programs became more efficient due to the development of better theoretical mod-
els and numerically less demanding algorithms. This is highlighted by the Nobel
price in chemistry awarded to John Pople and Walter Kohn in 1998. It was very
much the achievement of Kohn to develop Density Functional Theory (DFT) into
a practical tool 12, 31. Since it is especially transition metal systems that can be
treated efficiently and accurately by DFT this was of prime importance for mole-
cular modeling in homogeneous catalysis.
In this contribution it is attempted to give a rough overview of current theore-
tical methods in molecular modeling and examples for applying these to “real life”
chemical problems. It is not intended to be a detailed review on molecular mod-
eling or to discuss the underlying physical concepts in great depth, but to elucidate
the basic concepts as well as the limitations of current computational methods [4].
It is focused especially on chemical systems involved in homogeneous catalysis.
In order to convince the reader about the usefulness of molecular modeling, a
large section is dedicated to a discussion of the application of computational meth-
ods in the investigation and optimization of some important catalytic processes.

3.1.2.1.1 Concepts of Molecular Modeling

In analogy to every other field of computational science (e. g., fluid dynamics or
world climate) molecular modeling means in the first instance to derive a model
 3.1.2.1 Molecular Modeling Techniques 701

measurement
measuremen-

Figure 1. Relationship between models and the real system.

for a chemical system based on physical principles. The model may include ap-
proximations or rely on empirically determined parameters in order to reduce
computational effort, but it must be able to simulate the real chemical system in
the desired accuracy. The criterion for the quality of the model is to which extent
certain properties of the real system can be predicted. This is schematically de-
picted in Figure 1: a model is only able to simulate, and thus “predict”, a specific
property of a real system for which it was designed. As a matter of fact, a “model”
which perfectly simulates all properties of a real system is equivalent to the real
system itself. Very often, higher resolution or higher accuracy is related to a higher
numerical effort, which means one has to choose the right model carefully for a
certain question to be addressed.
To become more specific, the term “real chemical system” stands for any sort
of arrangement of atoms, such as solids, surfaces, molecules, or ensembles of
molecules. In homogeneous catalysis research the focus lies on molecules and
their transformations. In Figure 2 the hierarchy of various types of models in
terms of their resolution in time and space is depicted schematically. Models
that resolve the electrons in a molecule form the finest level of resolution of
chemical interest. Due to the necessity to describe electrons quantum mechani-
cally, these are generally referred to as quantum mechanical (QM) models.
Relying heavily on physical principles, these methods are numerically most
demanding, but are also able to simulate accurately the breaking and formation
of covalent bonds. On the next level so-called molecular mechanics (MM) mod-
els just describe atoms and their effective interactions, usually in an empirically
parameterized way. Above that “mesoscale methods unite a whole segment or
”

subgroup of a molecule, such as a residue of a protein or a repetition unit in a

polymer. This is probably the coarsest resolution of chemical models. On a
larger scale, transport phenomena, e.g., of liquids in a reaction vessel, can be
simulated by computational fluid dynamics (CFD), which is definitely of impor-
702 3.1 Development of Methods

Figure 2. Hierarchy of models in terms of their resolution in time and space.

tance in chemical engineering and macrokinetics, but is no longer related to

molecular modeling.
It should be noted that the axes in Figure 2 are also related to the maximal size
of a system and simulation time that can technically be reached for a given model.
However, as mentioned in the introduction, because of improvements in computa-
tional power and algorithmic efficiency these upper limits steadily increase.
From a nalve point of view, it is not obvious which property of molecules a
chemical model should focus on. From an experimental point of view, quantities
like heat of formation, structural or spectroscopic parameters, and stability or ac-
tivity of a catalyst come to mind. There are some very specific and completely
empirical models (such as the increment rules for NMR chemical shielding)
that are able to describe only a single experimentally accessible property. How-
ever, most important chemical models are focused on the (internal) energy of a
molecule as the fundamental property to be simulated. Most other properties men-
tioned above can be derived from this energy or its derivatives with respect to ex-
ternal perturbations. In this context the term “molecule” must be generalized as
the arrangement of atoms in space, which does not necessarily form a stable mo-
lecule from an experimental point of view. A chemical model is therefore an ana-
lytical function or numerical method that delivers an internal energy for a given
spatial arrangement of atoms. It defines the multidimensional potential energy
suguce (PES) (3N - 6 degrees of freedoms for N atoms) according to eq. (1)
with RNfor the positional vector for N atoms.

E = f(RN) (1)
 3.1.2.1 Moleculur Modeling Techniques 703

It is very important to remember that this definition of a PES is based on the

assumption that the atomic positions can be exactly specified, which is the ulti-
mate condition for the “structure” or “shape” of a molecule. This means adoption
of the Born-Oppenheimer (B. 0.)approximation, in which the nuclei are viewed
as stationary point charges, whereas the electrons are described quantum mechani-
cally [5]. This approximation is justified by the fact that the electrons are much
lighter than the nuclei and hence are moving faster. The classical nature of the
atomic nuclei is usually a valid approximation, but the zero-point vibrational en-
ergy of molecules or the tunneling effect, for example, make it evident that it does
not always hold.
The question now is what this functionf(RN)looks like. The answer leads to the
most fundamental, general QM model, in which the enFrgy is basically the
expectation value of the electronic Hamilton operator H that parametrically
depends on the nuclear positions (eq. (2)), where !P is the multi electron wave
function.
E = f(RN) = CYIh(RN)lY> (2)

In order to calculate the internal energy for a given I?&), one has to find the
multielectron wave function K with the lowest energy. Since the nonrelativistic
Hamiltonian is exactly known, this problem can in principle be solved. In practice,
this is however still too time-consuming even for smaller molecules and approx-
imations of this exact approach are used throughout. All models that explicitly
treat the electronic wavefunction by some kind of approximation are called QM
models. They can be divided into the so-called ab initio methods, that are
based only on fundamental physical constants, and semiempirical methods,
which employ Hamiltonians partly based on empirically derived constants.
With an increasing extent of approximations and a growing number of empirical
parameters, the numerical effort drops and allows larger and larger systems to be
simulated. However, on the down side this also results in a coarser resolution,
lower accuracy, or a decrease in the generality of the model. Nevertheless, even
every ab initio method is not exact, but approximate in nature.
The QM Hamiltonian can be approximated by a sum of terms that depend only
on one (or two) internal coordinates, such as bond, bond lengths angles, or di-
hedrals. These potential terms can now be described by empirically parameterized
analytic functions (resembling mechanical potentials such as Hook’s spring poten-
tial) and are usually valid only close to equilibrium. This results in the purely
empirical molecular mechanics (MM) models (Figure 3) that completely sacrifice
the evaluation of an electronic energy for the sake of numerical efficiency. These
jorcefield models have proven to be quite successful for the simulation of organic
molecules, but suffer from the fact that the energy function depends not only on
the atomic positions but also on the connectivity of the atoms. Therefore, they are
widely used to simulate proteins or other large biomolecules, for example, but it is
impossible to describe the breaking or formation of covalent bonds by standard
force field methods (with certain modifications to include some QM effects, the
breaking and formation of certain bonds can also be simulated [6, 71).
704 3.1 Development of Methods

Figure 3. Schematic representation of molecular mechanics energy terms.

3.1.2.1.2 Theoretical Methods for the Simulation

of Catalytic Processes
In contrast to the problem of simulating the molecular shape of large molecules
like proteins, in catalysis there are always covalent bonds broken or formed dur-
ing the conversion of substrates to the desired product. Therefore, QM models
with an explicit treatment of the electrons must be employed. In addition, most
homogeneously catalyzed reactions involve transition metal complexes with
occupied d-orbitals, which are generally difficult to treat quantum mechanically.
This is the reason why molecular modeling in the field of homogeneous
catalysis mostly relies on QM methods based on eq. (3), with T = kinetic
energy of electrons, Vex, = Coulomb attraction of nuclei (depends on RN),
J = Coulomb repulsion of electrons, and K = exchange interaction due to
antisymmetric Y .
mYI = VKl + V€.xt[YI + J[YI + K[YI (3)

The basis of these ab initio methods is the Hartree-Fock (HF) approximation

[8]. As an ansatz for the multielectron wavefunction a product of single-electron
wavefunctions is used, which is antisymmetrized by forming a Slater determi-
nant (in order to fulfill the Pauli exclusion principle). More intuitively, this ap-
proximation means that each electron is moving in the mean potential exerted
by all the other electrons. The corresponding optimal energy is called the HF
limit. The deviation from the exact energy that is found with the correct multi-
electron wavefunction (dropping the approximation of an “averaged” mean
field) is termed correlation energy. From a practical point of view, the simula-
 3.1.2.1 Moleculur Modeling Techniques 705

tion of molecules on the HF level of theory is well established and tractable

even for larger systems, but the inclusion of correlation effects is connected
with a rapidly increasing computational effort. It is not our intention to discuss
the various so-called post-HF methods (such as configuration interaction or
perturbation theory) and their advantages and drawbacks here in detail, but
refer to the corresponding textbooks [9]. It must be noted, however, that for
transition metal complexes correlation effects are often significant and their
accurate and efficient inclusion is of utter importance for the accuracy of any
molecular modeling approach in this field.
An additional approximation, which is necessary to perform these types of cal-
culations in practice, is the fact that the single-electron wavefunctions are usually
expressed in terms of a linear combination of various basis functions, which to-
gether are called basis set. If an unbalanced or inappropriate basis set is employed
in a calculation, the wavefunction does not have the flexibility to adopt the
“shape” necessary to minimize the energy. Since the energy is variational,
which essentially means a lower energy will be found for a better wavefunction,
the quality of the basis set can be monitored by increasing it until the energy is
converged. Due to the fact that the basis functions are just mathematical entities
created in order to describe the shape of the single-electron wavefunctions, a num-
ber of different implementations exist. On the one hand, they should be adapted to
the physical problem to represent a wavefunction in a molecule or a solid, but on
the other hand, they must allow for an effective numerical treatment. Again, the
following discussion is not to be complete, but just intended to give an overview
of the most common concepts.
For molecular systems the predominant form of basis functions employed are
atom-centered, with a spherical dependence analogous to the solutions of the hy-
drogen-like atomic problem (spherical harmonics Y,,). This is due to the fact that
the single-electron wavefunctions or orbitals closely resemble simple linear com-
binations of atomic orbitals, and are therefore a natural choice, especially for mo-
lecules. In order to allow the wavefunction to adapt to various electronic situations
it must be able to “grow” or “shrink” in its radial extent. This is achieved by using
two (double zeta: DZ) or more (e. g. triple zeta: TZ) basis functions with different
radial extent. Polarization functions with higher angular momentum are included
to mimic aspheric deformations. In order to treat (for example) anions properly,
so-called difluuse functions with very large radial sizes must be included. For
the radial part either Slater-type (STO) or Gaussian-type (GTO) functions
(eqs. (4) and ( 5 ) ) are generally used. Since STOs originate from the solution of
the hydrogen problem, they are superior in the description of real wavefunctions
(cusp and tail behavior). In contrast, GTOs neither have the correct cusp at the
nuclear position, nor do they show the proper decay in the tail of the wavefunc-
tion. Therefore a contraction of more then one GTO is employed, which results in
a larger number of integrals to be evaluated. However, since the product of two
GTOs is a GTO again, the numerical effort involved in calculating these integrals
is significantly smaller then in the case of STOs. This is the reason why the
majority of quantum chemical programs nowadays use GTOs as atom-centered
basis functions.
706 3.1 Development of Methods

A very different approach is the use of non-atom-centered basis functions such

as plane waves. Due to their intrinsic periodic nature, they are mostly employed
for electronic structure calculations of periodic solids [ 101. A more recent devel-
opment is the usage of real-space wavefunctions either by discretization on real-
space grids or in afinite-element fashion [ l I]. In a non-atom-centered basis, the
basis set obviously does not depend on the atomic positions, which makes it ide-
ally suited for ab initio molecular dynamics simulations, since the forces acting
on the nuclei can be evaluated much more easily than in an atom-centered
basis [lo].
In the context of the discussion of basis functions, especially for transition
metal compounds, it is important to keep the following two problems in mind:

( 1) heavy elements have many core electrons, which increase the computational
effort but do not significantly contribute to bonding interactions, and
(2) these core electrons have to be treated by a relativistic hamiltonian.

In order to overcome these problems, the core electrons are often excluded from
the calculation (frozen-core approximation), and their effect on the valence elec-
trons is “parameterized” in the form of a pseudo potential based on a relativistic
atomic calculation [12]. In connection with GTO basis sets, the most common
form of pseudo potential is the effective core potential (ECP) using Gaussian-
type radial functions to describe the potential [ 13-1 61.
It has already been mentioned that the inclusion of correlation effects by post-
HF methods is numerically cumbersome, but necessary for transition metal sys-
tems. A very important way out of this dilemma is based on the recent advances
in densityfunctional theory (DFT). It is founded on the Hohenberg-Kohn theo-
rem, which states that the ground-state energy is an exact functional of the elec-
tron density [3]. From a formal point of view, this is a completely different ap-
proach than the ab initio methods, since only the electron density but no wave-
function is needed for the description of the system. If the exact functional
were known, one would just have to find the density with the lowest energy. How-
ever, the exact functional is unfortunately unknown and DFT was for a long time
only used in solid-state calculations in a very approximate form [ 171. The major
source of error is the fact that no functional for the kinetic energy of a given elec-
tron density is known. It was the ingenious idea of Kohn and Sham to realize that
by expanding the electron density in terms of single-electron wavefunctions
(Kohn-Sham orbitals) and by using the kinetic energy operator known from ab
initio theory, an accurate and working approximation can be derived. The remain-
ing unknown part of the total density functional is the exchange correlation (XC)
functional, which describes both electronic exchange, due to the antisymmetry of
the wave function, and electronic correlation in an approximate way. For the ideal-
ized situation of a homogeneous electron gas, this functional is known, and the
 3.I .2.1 Molecular Modeling Techniques 707

corresponding theory is called the local density approximation (LDA) [ 18-20]. It

turned out to be a very accurate tool for the calculation of molecular geometries,
and, because of the approximate inclusion of correlation via the XC functional, to
be especially suited for transition metals. Because of the inhomogenity of the elec-
tron density in molecules, bond energies on the LDA level of theory are not very
accurate. However, by the use of the so-called generalized gradient approxima-
tion (GGA), leading to gradient-corrected XC functionals, this could be improved
dramatically [17, 21-23]. It is important to note that, despite the very different ori-
gin, the total energy expression in KS-DFT closely resembles the HF energy ex-
pression; only the exchange integrals K must be replaced by a numeric integration
of the XC functional. This is the reason why every issue concerning basis func-
tions discussed in the previous section is still valid for KS-DFT theory also. In
addition, most ab initio programs just needed limited extensions in order to be
able to perform KS-DFT-type calculations (eq. (6))
Ebl = T [ q + Vextbl + Jbl + Excbl (6)

with the electron density p = c Y 2 ;T = kinetic energy of electrons; Vext

= Coulomb attraction of nuclei (depends on R N ) ; J = Coulomb repulsion of
electrons and Ex, = XC functional.
This success story led to a theory that made it possible to treat transition metals
with an accuracy similar to post-HF methods, but with an effort roughly equiva-
lent to the standard HF approach. The downside of DFT, however, is that the exact
XC functional is unknown. In contrast to ab initio theory, where the exact solution
is known in principle and systematic improvements are possible (here the term
“ab initio methods” is used only to differentiate HF-based methods from DFT
methods, which does not imply that DFT is not ab initio in some sense), the qual-
ity of various XC functionals can only be judged by comparing the results with
experimental values. Recently, a number of improvements have been introduced.
Most prominent are the hybridfunctionals of Becke et al., where in addition to a
gradient-corrected XC functional a contribution of exact exchange (from HF the-
ory) is added [24]. Especially in the form of the B3LYP functional, this approach
is superior to most other pure density functionals for organic molecules [25].
However, the parameters determining the strength of this mixing have been ad-
justed on the basis of experimental data, which do not include transition metals.
Therefore, the approach is somewhat “semi-empirical” and the applicability to
transition metal complexes is debated.

3.1.2.1.3 Simulation of Properties by Theoretical Methods

In Section 3.1.2.1.1 various types of molecular models with their general target
to determine an accurate internal energy for a given arrangement of atoms have
been described. This internal energy, however, refers to an arbitrary reference
point. This section focuses on how experimentally accessible properties can
be derived from theoretical calculations. First of all, minima on the potential
708 3.1 Development of Methods

energy surface are identified as molecular species. This is again approximate be-
cause experimentally only an average over an ensemble of molecules at a finite
temperature can be measured. Nevertheless, it is a working approximation and
structural parameters of molecules can be derived from theoretical models by
geometry optimization using different algorithms to search for a minimum on
the PES. It is important to note that these search strategies generally just lead
to the stationary point closest to the starting geometry, which is defined by a
zero gradient of the PES, and which is not necessarily a minimum. The local
topology of the surface can in turn be clarified by calculating the matrix of sec-
ond derivatives, i. e., the curvature of the surface (Hessian matrix). If this matrix
possesses only positive eigenvalues it is a true energy minimum. A transition
state is a stationary point with exactly one negative eigenvalue of the Hessian
matrix. Based on the harmonic approximation of the vibrational modes derived
from the Hessian matrix, the zero point energy (ZPE) of the nuclei can be es-
timated. Additional contributions of thermal excitation as well as entropic con-
tributions can be derived from it, which is reasonable as long as this harmonic
approximation around the stationary point gives a faithful representation of the
true energy surface populated at the given temperature.
It must be stressed again that all these energies are mere numbers in the first
place, since they refer to an arbitrary reference point. However, as depicted in
Figure 4 the energy difference between two minima on the same PES is a thermo-
dynamic parameter and can be compared with values derived from experimental
measurements of equilibrium constants. Furthermore, the energy difference
between minimum and transition state is the kinetic parameter of the activation

>r Transition State

0)
L
a,
S
w

I Minimum

4 b
Side Reaction Reaction
Figure 4. Connection between calculated energies of stationary points and thermodynamic
and kinetic parameters.
 3.1.2.I Molecular Modeling Techniques 709

energy. The energy difference between two transition states, leading from one
molecule to different products, gives thermodynamic information about the selec-
tivity of a reaction, which is of high importance for catalytic systems.
At this point it is important to note that the global topology of a PES is not ac-
cessible by theoretical methods apart from a very time-consuming scan over all
areas. Since gradient-based optimization methods generally just lead to the closest
stationary point, it depends on the choice of the initial geometry and therefore
greatly on chemical knowledge and intuition, whether all relevant minima are
identified. This is called the global minimumproblem, which is quite significant,
for example, for catalysts with a large and flexible ligand backbone. Very related
is the question of the “stability” or general “existence” of a certain molecule. This
is not solely answered by the bare existence of a corresponding minimum on the
PES, but also depends on the activation energy of every possible decomposition
pathway. Therefore, in order to clarify this question, all transition states leading
away from the minimum will have to be identified, which is very difficult task
in most practical cases.
In addition to structural and energetic parameters there are quite a number of
observables such as electron density distribution, dipole moment, or polarizability
that can be derived from theoretical calculations. By a diagonalization of the
mass-weighted Hessian matrix, the normal modes and the corresponding vibra-
tional frequencies can be calculated. The intensity in IR and Raman spectra
can be estimated by the changes in dipole moment and polarizability for a defor-
mation along a given normal mode. Under certain approximations the effect of
external magnetic fields can be calculated, and thereby NMR parameters such
as chemical shielding can be simulated. This list is far from complete, but it
should be mentioned that the results of a theoretical calculation could also
serve as a basis for an analysis of the electronic structure of the molecule (i.e.,
frontier orbitals), which is not related to any observable. A very important
point is the analysis of orbitals such as the HOMO and LUMO in order to
gain insight into the principle reactivity, e.g., of a catalyst. Tools like atomic
charge analysis, bond orders, or the topological analysis of the electron density
should be mentioned here [26].

3.1.2.1.4 Limitations and Recent Developments

In the previous discussion it has been pointed out that for practical reasons all
theoretical methods rely on approximations. However, experience shows that
quantum mechanical methods of both post-HF and DFT types are available to
predict, for example, bonding energies close to chemical accuracy. Nevertheless,
a number of severe simplifications are made in comparison with real systems.

(1) Only isolated gas-phase species can be treated; especially, solvent effects
(which are important in homogeneous catalysis) are generally neglected.
(2) Temperature effects are included in a very restricted way and usually no Sam-
pling over Boltzmann-averaged ensemble properties is performed.
7 10 3.I Development of Methods

(3) Transition metal complexes are mostly reduced to model systems, excluding
steric interactions of large organic ligands in order to make the computations
affordable.

Some quite new concepts in molecular modeling to overcome these approxima-

tions are briefly mentioned here.
The most significant solvent effect is the shielding of electrostatic interactions
in polar solvents. Since the net influence of a solvation shell is mainly due to an
average of a very large number of nearly equivalent configurations, solvation is
usually treated by so-called continuum methods [27]. Different algorithms can
be used to construct the solvent-accessible surface around the solute. The electro-
static interaction of the solute with the continuum outside this surface and having
a certain dielectric constant can then be approximated. However, in some cases
specific molecular interactions between solute and solvent have to be included,
which cannot be handled merely by the continuum model. Furthermore, it is
known from experiment that solvents of identical dielectric constant lead to
very different reactivity. The COSMO-RS method by Klamt is based on the con-
tinuum method COSMO (conductor-like screening model) [28] and is intended to
resolve these effects [29, 301. It already allows one to predict (for example) mix-
ing energies of organic molecules with reasonable accuracy, and further improve-
ments in this field can be expected.
The most straightforward way to describe molecular systems at finite tempera-
ture is by a true sampling of the configurational space, mostly done by molecular
dynamics (MD) or Monte Carlo (MC)-type simulations, which is routine for or-
ganic molecules when using molecular mechanics models. However, due to the
significantly larger number of energy evaluations compared with “static” methods
of energy optimization and the like, the corresponding ab initio molecular dy-
namics (AIMD) is still a computationally difficult task. It was Car and Parrinello
who introduced the idea of a fictitious dynamic propagation of the wavefunction
along with the atomic positions using plane-wave basis sets [ l l , 311. This allows
one to perform ab initio Car-Parinello MD (CPMD) simulations of quite large
systems on the DFT level, which was employed especially in investigations of
solid-state systems. The extension of CPMD by the projector-augmented wave
(PAW) formalism introduced by Blochl made it possible to simulate also first
row elements and transition metals with good accuracy and efficiency, which
was somewhat problematic in the original CPMD approach [32]. Thus, homoge-
neously catalyzed reactions have also been studied by the PAW method [33-371.
The last point concerns the computationally efficient inclusion of steric effects
of large organic ligand systems. Due to the scaling properties of all current quan-
tum chemical models it is very cumbersome to include, for example, all the phenyl
rings of a coordinating triphenylphosphine into the QM calculation. On the other
hand, the steric interactions and conformational energies of these organic frag-
ments, which are not part of the bond breaking and bond formation in the catalytic
process, are well described by good molecular mechanics force fields. It has been
realized quite early that a solution of this problem would be the partition of the
molecule into a core described on some QM level and a “surrounding” part simu-
 References 7 11

lated by MM methods. Quite a number of different implementations of these

QMMM calculations have been developed meanwhile [38]. They differ not only
in the type of theory used for the QM and the MM parts but mostly by the
way the coupling between QM and MM atoms is treated. Apart from nonbonding
interactions between atoms in the QM and MM region, bonds crossing that
boundary are a delicate problem. Most implementations handle it by satisfying
the QM system through the introduction of fictitious capping atoms (mostly
just hydrogen). This can, however, introduce significant deviations in the electron-
ic structure of the simulated molecule (consider the basicity of PH3 as compared
with triphenylphosphine). Nevertheless, the QMMM method is already an integral
part of theoretical calculations, especially of catalytic systems, and it can be ex-
pected that improved strategies for the coupling problem will be developed
[39-41].

References
[ 1 ] G. Moore, http://www.intel.com/update/archive/issue2/feature.htm(1965).
[2] W. Kohn, L. J. Sham, Phys. Rev. A 1965, 140, 1133.
[3] P. C. Hohenberg, W. Kohn, L. J. Sham, Adv. Quantum Chem. 1990, 21, 7.
[4] F. Jensen, Introduction to Computational Chemistry, John Wiley, Chichester, 1999.
[5] M. Born, R. Oppenheimer, Ann. Physik 1927, 87, 457.
[6] J.K. Hwang, G. King, S. Creighton, A. Warshel, J. Am. Chem. SOC.1988, 110, 5297.
[7] A. Warshel, R.M. Weiss, J. Am. Chem. SOC.1980, 102, 6218.
[8] A. Szabo, N. S. Ostlund, Modern Quantum Chemistry: Introduction to Advanced Elec-
tronic Structure Theory, McGraw-Hill, New York, 1989.
[9] T. Helgaker, P. Jorgensen, J. Olsen, Molecular Electronic Structure theory, John Wiley,
New York, 2000.
[ 101 J. Hutter, D. Marx, in NIC Series (Ed.: J. Grotendorst), John von Neumann Institute for
Computing, Julich, 2000.
[ l l ] T. L. Beck, Rev. Mod. Phys. 2000, 72, 1041.
[12] J. C. Phillips, L. Kleinman, Phys. Rev. 1959, 116, 287.
[ 131 W. R. Wadt, P. J. Hay, J. Chem. Phys. 1985, 82, 284.
[14] P. J. Hay, W. R. Wadt, J. Chem. Phys. 1985, 82, 270.
[ 151 P. J. Hay, W. R. Wadt, J. Chem. Phys. 1985, 82, 299.
[16] D. Andrae, U. Haeussermann, M. Dolg, H. Stoll, H. Preuss, Theor: Chim. Acta 1990,
77, 123.
[17] T. Ziegler, Chem. Rev. 1991, 91, 651.
[18] D. M. Ceperley, B. J. Alder, Phys. Rev. A 1980, 24, 1628.
[19] S. J. Vosko, L. Wilk, M. Nusair, Can. J. Chem. 1980, 58, 1200.
[20] J.P. Perdew, A. Zunger, Phys. Rev. B 1981, 23, 5048.
[21] J.P. Perdew, J. Wang, Phys. Rev. B 1986, 33, 8800.
[22] C. Lee, W. Yang, R.G. Pan; Phys. Rev. B 1988, 37, 785.
[23] A.D. Becke, Phys. Rev. A 1988, 38, 3098.
[24] A.D. Becke, J. Chem. Phys. 1993, 98, 5648.
[25] P. J. Stevens, F. J. Devlin, C. F. Chablowski, M. J. Frisch, J. Phjs. Chem. 1994, 98, 429.
[26] R. F. W. Bader, Atoms in Molecules - A Quantum Theory, Oxford University Press, New
York, 1990.
7 12 3.1 Development of Methods

[27] C. J. Cramer, D. G. Truhlar, Chem. Rev. 1999, 99, 2161.

[28] A. Klamt, G. Schueuermann, J. Chem. Soc., Perkin Trans. 2 1993, 799.
[29] A. Klamt, V. Jonas, T. Buerger, J. C. W. Lohrenz, J. Phys. Chem. A 1998, 102, 5074.
[30] A. Klamt, J. Phys. Chem. 1995, 99, 2224.
[31] R. Car, M. Paninello, Phys. Rev. Lett. 1985, 55, 2471.
[32] P. E. Bloechl, Phys. Rev. B: Condens. Matter 1994, 50, 17953.
[33] H. M. Senn, P. E. Bloechl, A. Togni, J. Am. Chem. Soc. 2000, 122,4098.
[34] T. K. Woo, P. E. Bloechl, T. Ziegler, J. Phys. Chem. A 2000, 104, 121.
[35] P. Margl, J. C. W. Lohrenz, T. Ziegler, P. E. Bloechl, J. Am. Chem. Soc. 1996, 118, 4434.
[36] P. Margl, T. Ziegler, P.E. Bloechl, J. Am. Chem. Soc. 1996, 118, 5412.
[37] M. Cheong, R. Schmid, T. Ziegler, Organornetallics 2000, 19, 1973.
[38] Combined Quantum Mechanical and Molecular Mechanical Methods. (Proceedings of
a Symposium held at the 214th National Meeting of the American Chemical Society,
7-11 September 1997, in L a Vegas, Nevada) (Eds.: J. Gao, M.A. Thompson), in
ACS Symp. Ser. 1998, p. 712.
[39] X. Assfeld, J.-L. Rivail, Chem. Phys. Lett. 1996, 263, 100.
[40] G. Monard, M. Loos, V. Thery, K. Baka, J.-L. Rivail, Znt. J. Quantum Chem. 1996,
58, 153.
[41] V. Thery, D. Rinaldi, J. L. Rivail, B. Maigret, G. G. Ferenczy, J. Comput. Chem. 1994,
15, 269.

3.1.2.2 Applications

3.1.2.2.1 Modeling of Homogeneous Olefin

Polymerization Catalysts
Rochus Schmid

The discovery of the “Aujbaureaktion” by Ziegler led to the industrially very

important olefin polymerization reaction utilizing the heterogeneous so-called
Ziegler-Natta catalysts [ 1, 21. More then 20 years later it was found that a simi-
lar reaction could be catalyzed in homogeneous conditions by group 4 metallo-
cene dihalides, activated with an excess of methylalumoxane (MAO) [3]. In the
meantime the continuous research effort had led to a wide variety of so-called
“single-site catalytic polymerization systems and their activity increased by
”

about two orders of magnitude (cf. Section 2.3.1.2). Some of them have been
established in industrial processes [4]. In contrast to the heterogeneous systems,
the homogeneous polymerization catalysts always allowed a detailed structural
characterization of the catalyst precursors. Thus, from the very beginning,
research was conducted by a detailed analysis of the relationship between struc-
ture and reactivity. Early attempts to visualize substrate-catalyst interactions
quite naturally led to the simulation of the systems by the emerging theoretical
methods.
This contribution on the application of molecular modeling is not intended as a
detailed review of the theoretical research in the field [5, 61, rather just to give an
 3.1.2.2 Applications 7 13

overview on how theoretical methods have contributed to elucidate the reaction

mechanism on a molecular level. Much “common knowledge” in the field is ac-
tually based purely on theoretical findings, because experimental insight into the
nature of the active cationic complexes or the structural properties of transition
states is rather limited. The research area of olefin polymerization also demon-
strates the overall development of theory as discussed in Section 3.1.2.1. It was
a couple of years after the discovery of metallocene polymerization catalysts,
when the first very simplified ab initio investigation appeared [7-91. Meanwhile,
the models employed have grown significantly, including more and more details
of the real systems. The newest experimental results are generally accompanied by
theoretical investigations (mostly based on DFT methods) within the same year.
However, even now the level of detail simulated is still far from what really
goes on in a technical-scale olefin polymerization reactor.

The Olefin Polymerization Mechanism

The essential mechanistic step in olefin polymerization is the insertion of an olefin

into the metal-carbon bond of the catalyst leading to an extension of the polymer
chain by one monomer unit (Scheme 1). In the simplest case of ethylene this step
is exothermic by about 20 kcal/mol, which of course is independent of the cata-
lyst. The catalyst complex is usually a cationic complex (the restriction to early
transition metals is no longer valid) with an empty coordination site, which has
to be formed from the inactive precursor complex.
This simple picture might lead to the impression that the accurate calculation of
the activation barrier of this reaction would be sufficient to describe the olefin
polymerization process. However, not only the chain propagation reaction via ole-
fin insertion but also olefin bonding, as well as the probability of chain termina-
tion reactions, determine the activity of a catalyst and the molar weight distribu-
tion formed. A listing of further important effects, reactions, and interactions (ef-
ficiency of catalyst activation starting from the inactive precursor, catalyst decom-
position reactions, formation of inactive resting states [e. g., dimerization of neu-
tral catalysts], solvent interactions, entropy effects [e. g., solvent cage rearrange-
ment], interaction of the catalyst with individual solvent molecules [competition
with olefin bonding], interaction of the catalyst [and the counterion] with the

*
9 Q +

Scheme 1
7 14 3.1 Development of Methods

Figure 5. Some of the species and interactions involved in olefin polymerization.

forming polymer chain [lo00 to 10 000 monomer units], interactions with the
counterion, etc.) is definitely far from being complete. Figure 5 gives a schematic
representation of the species and interactions involved. It is evident that this
attempt at simulating this complex network as a whole is beyond reach even
for present-day theoretical methods.

Modeling the Basic Mechanism

Early attempts at molecular modeling, apart from mere visualization of steric in-
teractions, focused on the elucidation of the insertion step, which is a [2+2] pro-
cess and should lead over a four centered transition state (see Scheme 1). CossCe
and Arlman suggested the basic reaction mechanism as early as 1964 [lo-121.
Hoffmann et al. used the qualitative EHT scheme to investigate the basic frontier
orbital interactions and could explain why a low insertion barrier is achieved by
the presence of an empty d-orbital of proper symmetry [13, 141. First ab initio
calculations on the HF level were restricted to the model complex [Cl,Ti(CH,)]+,
where the Cp rings in the metallocene were substituted by chlorine atoms and the
polymer chain represented by just a methyl group [7-91. These very crude but
quantitative calculations corroborated the observations by Hoffmann. In 1994
more reliable calculations on the metallocene complexes [Cp2MCH3]+ with
M = Ti (on the MP2 level of theory [15]) and with M = Zr (using DFT with
GGA functionals [16]) both gave surprisingly low ethylene insertion bamers (in
the order of 1 kcaVmol and below). In the same year the first ab initio CPMD in-
vestigation of the system [H2SiCp2Zr(CH3)+]and ethylene showed the insertion
event after only 150 fs without any biasing of the system [17]. At least for
these model systems with a truncated polymer chain, the olefin complex is barely
 3.1.2.2 Applications 715

a real intermediate and, compared with the experimentally observed turnover fre-
quencies, the insertion cannot be the rate-determining step of the overall olefin
polymerization process.
In the majority of theoretical studies an a-agostic interaction between one of
the methyl C-H bonds and the Lewis-acidic metal center was observed. This
interaction is preserved during the reaction stabilizing the transition state and
leading directly to the y-agostic product. This direct insertion product, however,
rearranges to the most stable P-agostic alkyl complex. In order to explain the
discrepancy between calculated insertion barriers and observed turnover fre-
quencies the P-agostic alkyl complex was assumed to be the resting state. It
was speculated that the next olefin insertion step would have to be initiated
by an exothermic rearrangement into the a-agostic state, possibly additionally
complicated by steric interactions between the polymer chain and the auxiliary
ligands.

Towards More Realistic Models

One important improvement towards a more realistic description of olefin poly-

merization in molecular modeling studies was the inclusion of a larger polymer
chain model stabilizing the cationic catalyst by agostic interactions. Ziegler et
al. [ 181 first investigated insertion directly into the most stable P-agostic resting
state, which demonstrated that an a-agostic intermediate is not necessary for the
olefin insertion. In this case, a number of possible insertion transition pathways
are possible, termed frontside and backside insertion depending on whether the
olefin inserts into the M-C bond from the side of the agostic interaction or oppo-
site to it. These calculations revealed higher insertion barriers much more in line
with experimental observations.
H H

frontside backside
1 2

In the meantime, a large number of different catalysts in do-electron configura-

tion as well as in dOf"-configurationwith various ligand systems have been inves-
tigated theoretically [19-221. One intriguing result is the fact that neutral group 111
complexes were calculated to have lower insertion barriers in comparison with the
similar cationic group IV systems. However, experimentally the neutral systems
are significantly less active, which could be attributed to a possible dimerization
reducing the amount of active catalytic sites in the case of the group I11 systems.
7 16 3. I Development of Methods

This nicely demonstrates the strong and the weak points of theoretical investiga-
tions in general. On the one hand, information hardly accessible by experimental
means can be calculated quite accurately now. On the other hand, any comparison
with experimental findings must be done with great care, as the simulations focus
only on a limited microscopic part of the overall reaction mechanism, often
neglecting important effects.
The introduction of a larger polymer chain model with a a-agostic ethyl or
propyl group allowed the investigation of possible termination mechanisms.
This is of utmost importance for simulating the “performance” of a polymeriza-
tion catalyst by theoretical means, as the relative rates of chain propagation and
chain termination (and thus the energy difference between the corresponding
transition states) determine the molecular weight distribution of the catalyst. A
significant energetic separation of these competing reactions is a prerequisite
for olefin polymerization. In contrast to chain propagation, there are quite a
few possible termination processes apart from catalyst deactivation or decompo-
sition. The a-hydride elimination (BHE; cf. eq. (7)) was thought to be the main
termination step. It is essentially the reverse of the olefin insertion starting from
the B-agostic resting state, and leads to a hydrido-olefin complex. By replace-
ment of the a-olefinic polymer chain by a monomer unit, chain propagation is
terminated. Brinzinger at al. first proposed a different mechanism based on the
experimental observation of a molecular weight distribution independent of the
olefin concentration [23]. A direct P-hydride transfer (BHT; eq. (8)) to the in-
coming monomer transforms the growing chain into a detachable a-olefin and
leads to a termination of the chain propagation. Since this process has the
same rate dependence on olefin concentration as the chain propagation, molecu-
lar weight distribution would consequently be independent of it as observed ex-
perimentally. This second alternative especially was first systematically investi-
gated by Ziegler’s group [24]. For most catalysts, both pathways were found
to be viable termination processes, with BHT being mostly more favorable
then BHE. The BHT pathway starts from the P-agostic frontside olefin complex
and forks from the frontside insertion pathway leading to a transition state where
the transferred hydride is quite close to the metal and therefore stabilized by
empty d-orbitals [211. In this case theoretical calculations could strongly support
a proposed microscopic reaction mechanism, which was based solely on macro-
scopic observations. However, the question of the correct termination pathway is
not solved yet as some systems show a molecular weight dependence on olefin
concentration inconsistent with the theoretical findings. In addition, it should be
noted that there are other possible termination pathways, as for example the sub-
stitution of the polymer alkyl chain with a methyl group from the activator and
counterion MAO.
 3.1.2.2 Applications 7 17

“ I + *‘ W

Selectivity in Propene Polymerization

The classical heterogeneously catalyzed propene polymerization as discovered by

Natta is a stereospecific reaction forming a polymer with isotactic microstructure.
During the development of single-site polymerization catalysts it was found that
C2-symmetric chiral metallocene complexes own the same stereospecificity. An
analysis of the polymer microstructure by means of NMR spectroscopy revealed
that misinsertions are mostly corrected in the next insertion step, which suggests
stereocontrol (Figure 6) by the coordination site, as opposed to an inversion of
stereospecificity by control from the previous insertion steps (chain-end control).
In addition, it was found that C,-symmetric metallocene catalysts lead to syndio-
tactic polymer since the CosCe-Arlmann chain flip mechanism induces an inver-
sion of the stereospecificity at every insertion step. This type of polymer was in-
accessible by classical heterogeneous systems.
This type of selectivity originates solely from steric interactions between the
auxiliary ligands, polymer chain, and the incoming propene. It was first explained
qualitatively by means of visualization of the structure of the catalyst precursors.
A more quantitative approach led naturally to molecular mechanics models in
order to explain and even predict the stereospecificity of catalysts with different
ligand environments. Due to the limitations of MM models to describe metallo-
cene complexes as well as bond brealung and bond formation processes (see Sec-
tion 3.1.2. l), the models were initially based on some rigid core structures derived
from the measured structures, e. g., of the dichloride precursors [25, 261. In order
to achieve more accurate results, core structures, calculated by ab initio methods,
were employed later. A further step in this direction is the joint description of the

misinsertion
1
site
control
iSotadC

control

syndiotadc

Figure 6. Stereospecificity of propene polymers.

7 18 3.1 Development of Methods

reacting core of the system by QM and the outer ligand sphere by MM methods in
terms of a hybrid QMMM model. The significant improvements in this field were
recently revisited in detail in a review by Angermund et al. [5]. It is apparent that
selectivities and especially stereoselectivities originating from steric interactions
can already be modeled quite accurately by a combination of theoretical methods,
even for metallorganic systems such as metallocene polymerization catalysts. It is
a general feature of molecular modeling that relative activities are much more ac-
curate then absolute activities. Therefore, the question of the stereospecificity of a
given catalyst can theoretically be answered much more precisely then that about
its activity.

Recent Developments: Other Metal Atoms

For a long time it was a general belief that early transition metal catalysts with a
do-electron configuration are a necessary prerequisite for the polymerization of
olefins. Filled d-orbitals lead to a stabilization of the olefin n-complex by back-
donation and therefore high insertion barriers can be expected. Due to an overall
lowering of the d-orbital energy level when going to the right of the PSE this
effect is reduced for late transition metals. However, Ni or Pd, for example,
was known to oligomerize only ethylene. The quite recent discovery of very
active Ni and Pd polymerization catalysts by Brookhart and co-workers changed
this picture [27]. The difference from earlier inactive systems was the use of
very bulky ligand systems. Very soon after the discovery of these catalysts,
first theoretical investigations by the groups of Morokuma and Ziegler were per-
formed on model systems [28-301 and also on the real systems by QMMM
methods [31-33]. The results calculated by Ziegler’s group convincingly explain
the reaction mechanism and the necessity for the bulky ligands (Figure 7) [33].

Figure 7. Calculated energies of activation for insertion vs. termination (via BHT) for a
Ni catalyst (all energies in kcaVmol; values in parentheses are the corresponding
experimental estimates) [33].
 3.1.2.2 Applications 719

As expected, 3t back-donation from filled d-orbitals significantly stabilizes the

olefin complex, transforming it into the resting state. Thus, the olefin insertion
barrier is higher then for the do systems, but still reasonable to allow for efficient
chain propagation. However, without steric encumbrance, the lowest termination
pathway of BHT has a lower activation barrier than olefin insertion. By QMMM
calculations of the full system it became clear that the BHT transition state is
much more destabilized by steric interactions than the insertion transition
state. Thus, for the active catalysts the activation energy for the termination
pathway was pushed above that of chain propagation. The numbers calculated
by Ziegler et al. were actually quite close to those measured by Brookhart et
al., demonstrating the accuracy achievable with molecular models in the mean-
time.
The most recent new polymerization catalysts are the Fe and Co systems found
by Brookhart and Gibson [27]. Again, a large sterically demanding ligand system
seems to be the key to catalytic activity. In the same year as their discovery,
theoretical investigations of these systems were published [34, 351. However,
the picture is by far not as clear and convincing as in the case of the preceding
studies on the Ni and Pd catalysts. This is largely due to the fact that in the
case of Fe and Co a number of electronic states are possible and “hopping”
between individual potential energy surfaces is possible even during individual
elementary steps. In addition to the growing size of the systems and the large
number of degrees of freedom, this is another factor complicating the search for
the correct reaction mechanism.

Completing the Picture

Propelled by the improvements in computer hardware as well as by the develop-

ment of new theoretical methods, more and more elaborate molecular systems
have now been simulated. Nevertheless, the discrepancy between the actual reac-
tions and interactions taking place in the real system (see Figure 5 ) and the ones
taken into consideration in molecular modeling is still rather large, as the list
below indicates.

(1) The steric effects of large ligand systems have been considered by hybrid
QMMM methods [31-351. The accuracy of these methods is still somewhat
limited but improvements can be expected. Studies of the interactions of the
grown polymer chain with the catalyst might be possible but have not been
undertaken yet.
(2) Finite temperature effects are accessible by ab initio molecular dynamics
methods, but the simulation times yet achieved are still at least an order of
magnitude too small to give accurate numbers [36]. Again, particularly the
development of massive parallel computer hardware and algorithms will
change this situation in the near future.
(3) Another important point is the activation and deactivation of the catalyst,
which has gained less attention in theoretical investigations than chain propa-
720 3. I Development of Methods

gation and termination. In principle, however, it should be possible to model

these reactions by the established methods with the same accuracy.
(4) A number of approximate solvation models are available by now. However,
most of these methods focus on the description of the electrostatic effects
of charged species in a solvent such as water, with a high dielectric constant.
In the case of olefin polymerization nonpolar solvents are used. In addition,
delicate interactions can be expected between individual solvent molecules
like toluene with the cationic catalyst [37].
( 5 ) Probably the most important point in this list is the structure and reactivity of
the counterions, namely M A 0 (methylalumoxane). The exact constitution and
structure of M A 0 as used in technical polymerization is still not completely
clear. Some structurally characterized model compounds are available. Theo-
retical models have therefore been used to investigate structure and stability of
different MA0 aggregates. However, initial investigations on possible interac-
tions between the counterion and the catalytic site have been undertaken, but
especially in the case of the technically important MAO, these attempts must
be seen as only the first steps [3840].

Olefin polymerization is a field of research where theory has been established

as an essential tool for the investigation and optimization of catalytic systems. It
demonstrates how the combination of different theoretical methods for different
problems has established a more and more elaborate picture. It can be expected
that the need to gain insight into the processes involved in olefin polymerization
on a molecular level will also in the future drive theoretical method development.

References
[l] K. Ziegler, E. Holzkamp, H. Breil, H. Martin, Angew. Chem. 1955, 67, 541.
[2] G. Natta, Macromol. Chem. 1955, 16, 213.
[3] W. Kaminsky, K. Kuelper, H.H. Brintzinger, F.R. W.P. Wild, Angew. Chem. 1985,
97, 507.
[4] W. Kaminsky, Catal. Today 2000, 62, 23.
[5] K. Angermund, G. Fink, V.R. Jensen, R. Kleinschmidt, Chem. Rev. 2000, 100, 1457.
[6] A. K. Rappe, W. M. Skiff, C. J. Casewit, Chem. Rev. 2000, 100, 1435.
[7] H. Fujimoto, T. Yamasaki, H. Mizutani, N. Koga, J. Am. Chem. SOC. 1985, 107, 6157.
[8] C.A. Jolly, D. S. Marynick, J. Am. Chem. SOC. 1989, I l l , 7968.
[9] H. Kawamura-Kuribayashi, N. Koga, K. Morokuma, J. Am. Chem. SOC.1992,114,2359.
[lo] E. J. Arlman, J. Catal. 1964, 3, 89.
1111 P. CossCe, J. Catal. 1964, 3, 80.
[I21 E. J. Arlman, P. CossCe, J. Catal. 1964, 3, 99.
[I31 J. W. Lauher, R. Hoffmann, J. Am. Chem. SOC.1976, 98, 1729.
1141 D.L. Thorn, R. Hoffmann, J. Am. Chem. Soc. 1978, 100, 2079.
1151 H. Weiss, M. Ehrig, R. Ahlrichs, J. Am. Chem. Soc. 1994, 116, 7274.
1161 T. K. Woo, L. Fan, T. Ziegler, Organometallics 1994, 13, 225.
[17] R. J. Meier, G. H. J. v. Doremaele, S. Iarlori, F. Buda, J. Am. Chem. Soc. 1994, 116, 7274.
[18] J. C. W. Lohrenz, T. K. Woo, T. Ziegler, J. Am. Chem. Soc. 1995, 117, 12793.
 3.1.2.2 Applications 721

P. Margl, L. Deng, T. Ziegler, Organometallics 1998, 17, 933.

P. Margl, L. Deng, T. Ziegler, J. Am. Chem. Soc. 1998, 120, 5517.
P. Margl, L. Deng, T. Ziegler, J. Am. Chem. Soc. 1999, 121, 154.
P. Margl, L. Deng, T. Ziegler, Top. Catal. 1999, 7, 187.
U. Stehling, J. Diebold, R. Kirsten, W. Rdl, H. H. Brintzinger, S. Jungling, R. Miilhaupt,
F. Langhauser, Organometallics 1994, 13, 964.
P. Margl, J. C. W. Lohrenz, T. Ziegler, P. E. Bloechl, J. Am. Chem. Soc. 1996, 118,4434.
T. Yoshida, N. Koga, K. Morokuma, Organometallics 1996, 15, 766.
H. Kawamura-Kuribayashi, N. Koga, K. Morokuma, J. Am. Chem. Soc. 1992, 114, 8687.
S.D. Ittel, L.K. Johnson, M. Brookhart, Chem. Rev. 2000, 100, 1169.
D.G. Musaev, R.D.J. Froese, M. Svensson, K. Morokuma, J. Am. Chem. SOC. 1997,
119, 367.
D.G. Musaev, M. Svensson, K. Morokuma, S. Stroemberg, K. Zetterberg, P.E.M.
Siegbahn, Organometallics 1997, 16, 1933.
L. Deng, P. Margl, T. Ziegler, J. Am. Chem. Soc. 1997, 119, 1094.
D. G. Musaev, R. D. J. Froese, K. Morokuma, Organometallics 1998, 17, 1850.
R. D. J. Froese, D.G. Musaev, K. Morokuma, J. Am. Chem. Soc. 1998, 120, 1581.
L. Deng, T. K. Woo, L. Cavallo, P. M. Margl, T. Ziegler, J. Am. Chem. Soc. 1997, 119,
6177.
P. Margl, L. Deng, T. Ziegler, Organometallics 1999, 18, 5701.
L. Deng, P. Margl, T. Ziegler, J. Am. Chem. Soc. 1999, 121, 6479.
T.K. Woo, P.M. Margl, P.E. Bloechl, T. Ziegler, J. Phys. Chem. B 1997, 101, 7877.
M. S. W. Chan, K. Vanka, C. C. Pye, T. Ziegler, Organometallics 1999, 18, 4624.
E. Zurek, T. Ziegler, Inorg. Chem. 2001, 40, 3279.
M. L. Ferreira, P. G. Belelli, D. E. Damiani, Macromol. Chem. Phys. 2001, 202, 495.
I. I. Zakharov, V. A. Zakharov, Macromol. Theory Simul. 2001, 10, 108.

3.1.2.2.2 Palladium-Catalyzed C-C Coupling Reactions:

The Heck Reaction
Wolfgang Hieringer

Palladium has proven to be one of the most versatile metals in homogeneous cat-
alysis, and has found wide application not only in every-day organic synthesis, but
also in the industrial production of fine and bulk chemicals in its various forms.
The advantages of palladium as a catalyst metal have been demonstrated in a
vast number of examples [ 11. While studies on simple model reactions involving
palladium complexes have been performed since the early days of computational
chemistry, only recently have studies on catalytic cycles emerged [2]. This can be
put down to the fact that the supposed reaction mechanisms are often very com-
plicated, and details of the molecular mechanism are difficult to obtain from ex-
perimental investigations. With the advent of advanced quantum chemical meth-
odology and growing computer power, however, even complex reaction mecha-
nisms such as those encountered in homogeneous catalysis came into reach.
To date, several homogeneously catalyzed processes involving palladium com-
plexes as catalysts have been studied in considerable detail by computational
methods. Examples comprise illustrative work on the industrially important oxida-
722 3.1 Development of Methods

tion of ethylene by air (Wacker process; cf. Section 2.4.1) [ 3 ] , olefin polymeriza-
tion (Section 2.3.1) [4], copolymerization of CO and ethylene (Section 2.3.4) [ 5 ] ,
and generic C-C coupling reactions such as the Heck reaction (e.g., Sections
2.1.2 and 3.1.6) [6, 71. The latter is the most prominent example of a general-pur-
pose palladium-catalyzed synthetic reaction.
Mechanistic data derived from experimental studies of the Heck reaction have
been reviewed in Section 3.1.6. The commonly accepted catalytic cycle comprises
four basic steps, i. e., oxidative addition, olefin insertion, P-H elimination (includ-
ing release of the coupling product) and base-promoted reductive elimination to
regenerate the Pdo catalyst [6]. The catalytic cycle is a rather complex sequence
of elementary reactions of general interest. The initial step of oxidative addition
not only plays a central role in the classical Heck reaction, but it is also believed
to activate the substrate in cross-coupling reactions. Migratory olefin insertion is
the central chain propagation step in palladium-catalyzed olefin polymerization
and has been extensively studied in this context. Likewise, P-H elimination is
one of the termination processes of polymer chain growth. Figure 8 summarizes
the mechanistic pathways of the Heck reaction, as they have been studied with
computational methods so far.
The first step of the catalytic cycle constitutes the oxidative addition of the or-
ganic halide to the Pdo catalyst, yielding a cis-palladium(I1) species, which subse-
quently isomerizes to the more stable trans form [8]. Theoretical studies so far
have focused on the molecular mechanism of C-X bond activation and the influ-

L-Pd-L

I I
L X

A
+B
+ !Ax-
- [HB]' L-
P p<+

/ L R

l+ J
H
L-Pi<,R
I
L
- L-Pd4,.
i
R l+

Figure 8. A catalytic cycle for the Heck reaction.

 3.1.2.2 Applications 723

ence of ligands on the observed activation barriers, leaving the isomerization step
aside [9-111.
In their pioneering work, Bickelhaupt et al. have studied the mechanism of
oxidative addition of chloromethane to a bare Pdo atom in order to elucidate

-
the intrinsic reactivity of the metal without ligands (eq. (9)) [9].

Pd + CH3CI CIPdCH3 (9)

They have compared the reaction energy profiles of five different reaction
paths, including oxidative insertion, nucleophilic substitution, and single-electron
transfer mechanisms involving radical species, both in the gas phase as well as
using an electrostatic continuum model to include the effect of a solvent in an
approximate fashion (Structures 3-5).

Pdn oCH3
8

Cl

Oxln sN2 SNZlra

3 4 5

The most favorable process for oxidative addition in this simple model system
is oxidative insertion (OxIn, 3) of the palladium atom into the C-C1 bond of
chloromethane (C,-symmetric transition state), which is associated with an activa-
tion barrier of 8.4 kcallmol. In the gas phase, straight sN2 substitution (Structure
4) is highly unfavorable due to the charge separation involved in this process
(145.2 kcal/mol), which is not compensated by any solvent. The barrier is drasti-
cally reduced, however, if one assumes that the ions are not completely separated
in the substitution process, but rather remain coordinated as an ion pair (SN2/ra
mechanism, Structure 5 ) . Still, the activation energy associated with the corre-
sponding transition state is much higher than that of the insertion mechanism
(29.6 kcallmol). Moreover, the reactive intermediates of two distinct single-elec-
tron transfer mechanisms are highly endothermic (29.3 kcaumol, 46.9 kcallmol),
making a radical path an unlikely alternative. As expected, the activation barriers
for the substitution processes are considerably reduced in polar solvents, while
neither the insertion nor the radical mechanisms are substantially affected by
the solvent, due to their neutral charge balance.
Oxidative addition of C-X bonds to Pdo is an exothermic reaction, at least in
the cases studied so far. From a theoretical point of view, it is important to note
that relativistic effects are essential for the accurate theoretical prediction of the
reaction enthalpy of oxidative addition, while the influence on the activation
barriers appears to be much smaller [ 111. These effects can nowadays be included
in a standard way using commonly available program packages.
A step towards more realistic systems in the context of the Heck reaction was
taken by Herrmann's group [lo]. They have studied the mechanism and activation
barriers of oxidative addition of vinyl halides and halobenzenes to Pdo complexes
with simple ligands of varying donor/acceptor characteristics (eq. (lo)).
124 3.1 Development of Methods

Oxidative insertion remains the most favorable mechanism of C-X bond acti-
vation for these substrates, even if solvent effects are taken into account in an
approximate fashion. In fact, well-known experimental trends such as the relative
ease of C-X activation (X: I > Br > Cl) and the activating or deactivating effect
of ring substituents in the para position with respect to the leaving group (lower
activation barrier for -CHO, higher barrier for -NH2) are readily reproduced on
the basis of the oxidative insertion mechanism. The donor/acceptor charac-
teristics of the ligands in the Pdo complexes PdLL' (L, L' = PH3, PMe3,
C(NH,),; L = PH3 and L' = C1-) have a pronounced effect on the activation
barrier of oxidative addition: electron-donating ligands lead to reduced barriers.
A particularly strong reduction of the activation barriers is predicted for anionic
ligands such as C1- and OH- in the complexes [(PH,)PdX]-. The typical barriers
calculated for vinyl halide oxidative insertion are higher than those for phenyl
halide activation.
The effect of anion assistance has also been investigated by the group of Bickel-
haupt for the model reaction of chloromethane with the anionic complex PdCI-
[ 111. Within this system, a two-step substitution/rearrangement process becomes
even more favorable kinetically than the usual insertion mechanism, the activation
barrier of which is also lowered compared with the neutral system, in accord with
the results reported above. An analysis of the results in terms of the activation
strain/transition state interaction (ATS) model reveals that, while the energy
needed for the deformation of the substrate (CH,Cl) toward the transition state
geometry remains almost constant, the stabilizing interaction of the catalyst
with the distorted substrate is strongly increased in the anionic system, thus lead-
ing to a lower barrier.
Rosch et al. have studied the Heck coupling of ethylene with bromobenzene
catalyzed by a Pdo catalyst bearing two donor-substituted carbenes, C(NH2)2
[12]. This catalyst is believed to model theoretically a catalyst class using two
N-heterocyclic carbenes as ligands, which was recently introduced by Henmann
et al. [13]. Since those ligands show a lower tendency to dissociate from the
metal center than the commonly used phosphines, a cationic reaction pathway
was investigated, allowing the two carbene ligands to remain bound to the palla-
dium center (Figure 8). All postulated intermediates in the resulting catalytic cycle
(with the exception of the last step, base-promoted reductive elimination) have
been characterized structurally as well as energetically, although transition states
have only been calculated for the olefin insertion and a-H elimination steps.
Oxidative addition of bromobenzene to the Pdo catalyst is an exothermic pro-
cess (-34.1 kcallmol). In order to facilitate the uptake of the olefin to the resulting
Pd" complex, a vacant coordination site has to be provided by dissociation of a
ligand. Considering the high binding constants of the metal-carbene bonds, the
authors investigated a cationic pathway which is initiated by dissociation of a
 3.1.2.2 Applications 725

bromine ligand, thus leaving an unsaturated, cationic Pd" complex which readily
coordinates the olefin (-1 9.5 kcal/mol). The highly exothermic nature of the olefin
uptake step, however, is somewhat reduced (to -5.3 kcal/mol) if the bromide
counterion is kept in the vicinity of the complex, thus forming an ion-pair
which might be a realistic scenario in solvents of little or no polarity. The follow-
ing C-C bond forming step of the catalytic cycle, i. e., insertion of the coordinated
ethylene into the Pd-phenyl bond, is associated with a gas-phase barrier of
8.3 kcal/mol in the cationic system. A similar barrier of 11.5 kcaVmol is calculated
for the ion-pair mechanism. The resulting palladium-alkyl complex is finally con-
verted into the olefinic product (styrene) by P-H elimination, which succeeds an
endothermic rotation around the Pd-C bond and the formation of a P-agostic in-
termediate. The barrier for the P-H elimination step from this intermediate is es-
timated to be 4.4 kcaVmol(9.0 kcaVmol with respect to the insertion product). The
remaining step of the catalytic cycle, base-assisted regeneration of the Pdo cata-
lyst, has not been considered in this study. In the same study, Rosch et al. have
also investigated the mechanism of the Heck reaction using a bidentate carbe-
ne-phosphine ligand (1-methylenephosphine-imidazol-2-ylidene).This ligand
system combines a strongly coordinating, electron-donating carbene ligand with
a more labile phosphine ligand. Creation of the necessary vacant coordination
site, which must precede olefin coordination to the complex, is possible via rup-
ture of the Pd-phosphine bond and requires 25.9 kcal/mol. The overall reaction
energy profile is similar to that of the neutral dicarbene system described
above, and similar conclusions are drawn. In summary, the study has demon-
strated that the Heck reaction can readily proceed via cationic (or ion-pair) as
well as neutral pathways, depending on the dissociation behavior of the ligands
involved. The crucial steps of olefin insertion and P-H elimination are associated
with rather low barriers.
The final step of the catalytic cycle, base-assisted reductive elimination, has
been addressed by Deeth et al. [14]. In their calculations, the authors investigated
palladium complexes with the chelating diaminomethane H2N(CH2)NH2and di-
phosphinomethane H2P(CH2)PH2ligands. Within this system, they found that
the postulated hydrido-olefin complex, which is usually formed by P-H elimina-
tion of the B-agostic
. - insertion product, is in fact not a stable minimum structure in
this particular case (eq. (11)) 1141.

- ~ ~ c. p H- ~_______~-.-)-
.~

'AH2

As an alternative to the classical reaction mechanism, they investigated the pos-

sibility of a direct deprotonation of the P-agostic insertion product by the amine
base, which is usually required for successful Heck coupling reactions. The
new proposal actually replaces the last two steps of the classical catalytic cycle,
P-H elimination and base-assisted reductive elimination of HX (Scheme 2).
126 3.1 Development of Methods

INR3

Scheme 2. Base-assisted reductive elimination: classical two-step mechanism (top) and a

single-step direct deprotonation of the agostic proton (bottom) as proposed in [14];
counterions are omitted.

The hydrogen atom involved in the b-agostic bonding is kinetically more acidic
than the non-agostic proton, i. e., the barrier for deprotonation by the base (NH,) is
lowered due to the agostic bond. The resulting olefin dissociates from the Pdo cen-
ter in a subsequent step, thereby reforming the Pdo catalyst. A comparison of the
estimated kinetic barrier for this mechanism with those of the two-step mechanism
investigated in the study discussed above suggests that direct deprotonation might
indeed be a realistic alternative. Which mechanism in the product-forming step is
actually operative, however, has to be clarified in future studies, since the result is
likely to depend on the precise structure of the catalyst used.
All the mechanistic steps in the classical catalytic cycle of the Heck olefination
reaction have now been studied in some detail, providing considerable insight into
how these reactions may proceed at a molecular level. However, for these results
to become meaningful for the design of new, improved catalysts, still more has to
be done. Based on the results available so far, it will be feasible in future work to
study the effect of different ligands on all the mechanistic steps of the Heck reac-
tion. It will thus be possible to suggest new improved ligands and catalysts, and
actually to test them in computer simulations before they have to be synthesized in
the laboratory. Nowadays, suitable methodology and interpretative tools, but also
the necessary computer resources, exist to study and predict the performance of
even complex ligands such as those found in many modern catalysts.

References
[ 11 J. Tsuji, Palladium Reagents and Catalysts, Wiley, Chichester, 1995.
[2] For an overview, see: A. Dedieu, Chem. Rev. 2000, 100, 543.
[3] Theoretical studies on the Wacker process: (a) P.E.M. Siegbahn, J. Am. Chem. SOC.
1995, I1 7, 5409; (b) P. E. M. Siegbahn J. Phys. Chem. A 1996, 100, 14672; (c) D. D.
Kragten, R. A. van Santen, J. J. Lerou, J. Phys. Chem. A 1999, 103, 80; (d) D. D. Krag-
ten, R. A. van Santen, M. Neurock, J. J. Lerou, J. Phys. Chem. A 1999, 103, 2756.
 3.1.2.2 Applications 727

[4] For studies on palladium-catalyzed olefin polymerization, see: (a) D. G. Musaev,

M. Svensson, K. Morokuma, S. Stromberg, K. Zetterberg, P. E. M. Siegbahn, Organome-
tallics 1997,16, 1933; (b) S. Stromberg, K. Zetterberg, P. E. M. Siegbahn, J. Chem. Soc.,
Dalton Trans. 1997, 4147; (c) D. G. Musaev, R. D. J. Froese, K. Morokuma, New J.
Chem. 1997, 21, 1269; (d) R.D.J. Froese, D.G. Musaev, K. Morokuma, J. Am.
Chem. SOC.1998,120, 1581; (e) D. G. Musaev, R. D. J. Froese, K. Morokuma, Organo-
metallics 1998, 17, 1850.
[5] For studies on ethylene-CO copolymerization, see: (a) P. Margl, T. Ziegler, J. Am. Chem.
Soc. 1996, 118, 7337; (b) P. Margl, T. Ziegler, Organometallics 1996, 15, 5519; (c) M.
Svensson, T. Matsubara, K. Morokuma, Organometallics 1996, 15,5568; (d) K. Nozaki,
N. Sato, Y. Tonomura, M. Yasutomi, H. Tayaka, T. Hiyama, T. Matsubara, N. Koga,
J. Am. Chem. Soc. 1997, 119, 12795.
[6] For reviews on the Heck reaction see, for example: (a) R. F. Heck, Palladium Reagents in
Organic Synthesis, Academic Press, London, 1990; (b) A. de Meijere, E E . Meyer,
Angew. Chem. 1994, 106, 2473; Angew. Chem., Int. Ed. Engl. 1994, 33, 2379;
(c) I. P. Beletskaya, A. V. Cheprakov, Chem. Rev. 2000, 100, 3009.
[7] General reviews on theoretical studies of transition metal complexes and catalysis:
(a) N. Koga, K. Morokuma, Chem. Rev. 1991, 91, 823; (b) T. Ziegler, Chem. Rev.
1991, 91, 651; (c) S. Q. Niu, M. B. Hall, Chem. Rev. 2000, 100, 353; (d) M. Torrent,
M. Soli, G. Frenking, Chem. Rev. 2000, 100, 439.
[8] A. L. Casado, P. Espinet, Organometallics 1998, 17, 954.
[9] F. M. Bickelhaupt, T. Ziegler, P. v. R. Schleyer, Organometallics 1995, 14, 2288.
[lo] (a) W. Hieringer, W.A. Herrmann, unpublished results; (b) W. Hieringer, PhD Thesis,
Technische Universitat Miinchen, Germany, January 2000.
[ 111 (a) A. Diefenbach, F. M. Bickelhaupt, G. Frenking, unpublished results; (b) A. Diefen-
bach, PhD Thesis, Philipps-Universitat Marburg, Germany, December 2000.
[12] K. Albert, P. Gisdakis, N. Rosch, Organometallics 1998, 17, 1608.
[13] (a) V. P. W. Bohm, C. W. K. Gstottmayr, T. Weskamp, W. A. Henmann, J. Organomet.
Chem. 2000,595, 186; (b) T. Weskamp, V. P. W. Bohm, W. A. Henmann, J. Organomet.
Chem. 2000, 600, 12.
[14] R. J. Deeth, A. Smith, K. K. Hii, J. M. Brown, Tetrahedron Lett. 1998, 39, 3229.

3.1.2.2.3 Hydroformylation
Dieter Gleich

Hydroformylation is one of the largest-scale processes of industrial homogeneous

catalysis (cf. Section 2.1.1, particularly the basic eq. (1)) and therefore it is espe-
cially attractive for theoretical investigations. Besides activity, selectivity plays a
key role. Apart from chemoselectivity (e. g., hydration instead of hydroformyla-
tion), regioselectivity is important because terminal olefins yield either linear ( n )
or branched (iso) aldehydes. In the case of the bulk substrate propene, only n-bu-
tanal can be converted to the PVC-softening agent 2-ethylhexanol. If the substitu-
ent R differs from H or CH3 in eq. (l), the iso-aldehydes become chiral. Since the
fine chemicals, e. g. pharmaceuticals such as ibuprofene or naproxene, would be
conveniently accessible, stereoselective (asymmetric) hydroformylation is a great
challenge, all the more as no industrial process has been realized up to now [l].
The present contribution focuses on theoretical approaches aiming at insights
728 3.1 Development of Methods

that are not available by experiment. Thus, advances as well as drawbacks of theory
in the field of hydroformylation will be elucidated. The catalytic systems modeled
are mainly of the Rh-phosphine type, which dominates today’s industry. Other in-
vestigations (in particular on cobalt systems) are discussed in a recent review [2].

Activity

Relative energies of reaction intermediates and transition states in the course of a

catalytic cycle give basic information about the activity. For example, the highest
barrier between an intermediate and the subsequent transition state should be the
rate-determining step of the reaction. QM energy calculations on isolated mole-
cules in the gas phase have become an important standard of such theoretical
studies [2].
The first calculation of the complete hydroformylation cycle with Rh-phos-
phine catalysts (substrate = ethylene, model ligand = PH3) was published in
1997 [3]. The QM methods used are HF and MP2, respectively (cf. Section
3.1.2.1). Hybrid DFT methods such as B3LYP [4], however, are more appropriate
in terms of both accuracy and efficiency [5, 61 (cf. Section 3.1.2.1). Therefore, the
same model system was recalculated [7] on the level B3LYP functional/DZVP
basis set [8]/quasi-relativistic pseudopotentials on rhodium [9]. Since homologous
Ir catalysts are interesting alternatives from an economic point of view [lo], cal-
culations with the central metal Ir were also made. This comparative treatment is
supported by the experimental assumption of a common mechanism [ 111, which
equals the Heck-Breslow mechanism of the cobalt-catalyzed reaction [ 121.
The catalytically active species are supposed to be formed either directly by the
18-electron complex MH(C0)2(PPh3)26 (“associative” pathway in Figure 9 [ 111)
or by dissociation of one ligand L (CO or PH3) from 6 yielding the 16-electron
complex 7 (“dissociative” pathway [ 1I]).
The dissociative pathway was chosen for theoretical investigations since it fits
experimental data sufficiently [ 14, 151 and several test calculations disfavor the
associative counterpart [7]. Reaction 6 -+ 7 was studied in detail on different le-
vels of theory [7, 131. The B3LYPDZVP total reaction energy of hydroformyla-
tion including zero-point correction is -33.2 kcal mol-l, which agrees well with
the experimental mean value of -28 kcal mol-’ per double bond [16]. Figure 10
contains the total reaction profiles of Rh- and Ir-catalyzed hydroformy lation
[7, 171. Because of their low barriers [18], transition states of ligand associations/
dissociations are omitted.

Rhodium

CO association 9 + 10 is the thermodynamically most favorable catalytic step

(= -15 kcal mol-I), which corresponds to about half of the total reaction energy
(cf. above). Olefin association 7 + 8 and olefin insertion 8 + 9 follow next
(= -6 kcal mol-I), whereas CO insertion 10 + 11 as well as oxidative hydrogen
 3.1.2.2 Applications 729

I
I
L--‘-LL
L--‘-L 7
\
\
H
L*,.I
,M-co
L I
L

o+, J I1 9
I L-M-L
L-M-L I
I L
L

Figure 9. Dissociative hydroformylation mechanism with the model substrate ethylene

(M = Rh, Ir; L = CO, PH,; cf. [7]).

addition 11 + 12/reductive aldehyde elimination 12 + 7 are only weakly exo-

thermic/thermoneutral. The activation energies of all catalytic steps are similar
except for the kinetically facilitated hydrogen addition 11 -+ 12. Therefore,
with respect to the model system, the rate-determining step is not obvious.
However, experimental results are ambiguous, too [ 14, 151.
When interpreting the results of gas-phase calculations, one should keep in
mind that the solvent clearly influences the reaction rates. However, there exists
no spectroscopic hint of solvent coordination to the central metal rhodium [14].

Iridium

The most intriguing difference is the thermodynamically as well as kinetically fa-

cilitated hydrogen addition ll -+12 that hampers the last catalytic step, i. e. reduc-
tive aldehyde elimination 12 + 7. In contrast to rhodium, Olefin/CO insertions
8 + 9/10 + 11 are thermoneutrallendothermic, whereas OlefinKO associations
7 -+ 8/9 + 10 are significantly more exothermic. In summary, the total reaction
730 3.1 Development of Methods

\\ 4
9 10 10,Il 11 11,12 12 12,7 7

+ Rh
* Ir

Reaction Coordinate

Figure 10. Total reaction profiles of rhodium- and iridium-catalyzed hydroformylation (71.

profile looks less balanced. As a consequence of relativistic effects [19, 201,

changes in coordination number and oxidation state are thermodynamically as
well as kinetically complicated, which, however, is essential for good hydrofor-
mylation activity. This theoretical result is in full agreement with experiment
[ 111. Additional calculations indicate that variations of electronic ligand and sub-
strate properties may increase the catalytic activity but cannot bridge the gap to
rhodium [7].

Selectivity

Olefin insertion 8 + 9 (cf. Figure 9) leads to linear and branched alkyl complexes,
which in turn give rise to the formation of n- and iso-aldehydes. For that reason,
this catalytic step is crucial for any theoretically founded determination of regio-
and stereoselectivities. If one assumes an irreversible reaction and no changes in
the n:iso distribution after the insertion step - two conclusions suggested by ex-
periment [15, 21, 221 - it is straightforward to set up formulas that connect the
kinetic regioselectivity Sn..isoor the total stereoselectivity (i. e., the ee of the alde-
hyde) with the energy differences AE# of corresponding transition states 8, 9 [7,
23-25]. Although barrier heights, i.e., activities, are not considered by this ap-
proach [7], it is more promising than to calculate n:iso distributions of the inser-
tion products 9 [26] or of idealized alkyl complexes [27]. Furthermore, solvent
 3.1.2.2 Applications 73 1

effects are less important [23], which means that isolated systems in the gas phase
would again be enough for a first attempt. AE#,,, values, however, are rarely
accessible within a simple QM model system for the interactions between the
coordination sphere of 8 - especially the phospine ligands - and the olefinic
substrate have to be handled carefully. Apart from rapidly increasing com-
putational costs, DFT calculations are no method of choice for complexes of
real size since they are often unable to describe nonbonding interactions ade-
quately [28]. MM methods, however, fail in the direct reproduction of electronic
effects. Therefore, an appropriate combination of QM and MM methods must be
found.
The following results stem from DFT calculations on model rhodium com-
plexes. Based on these model system transition states, force-field calculations
were carried out in order to incorporate steric effects. The global energy minima
of the new systems were searched for by MD simulations (cf. Section 3.1.2.1).
This QMMM method with frozen reaction centers (FRC) is related to approaches
recently discussed in the literature [29]; cf. [23] for more details.

Regioselectivity

Results with different ligands and substrates [7, 231 are summarized in Table 1.
Investigation of the bidentate chelates DIPHOS L1, BISBI L2, and NAPHOS
L10 (cf. structures in Scheme 3) has been invigorated by a previous study with
contradictory experimental and theoretical results [22].
Experimentally observed regioselectivity tendencies of propene vs. 3,3,3-tri-
fluoropropene/styrene can already be explained by systems with the model ligand
PH3. Postulated allylic coordination modes [30, 311 only occur in the case of a
crude model system without any ligands. Therefore, in contrast to other arguments
[30, 311, kinetic peculiarities of styrene seem not to be due to a deviating insertion

Table 1. Regioselectivities with different ligands (L) and substrates.

Ligand Substrate sit :i.w
Calc. Exp.
PH3 Propene F;j 1:la)
3,3,3-Trifluoropropene < 1:Ia)
Styrene < 1:l"' -
PPh3 Propene > 1:lb) > 1:l
3,3,3-Trifluoropropene > l:lb) < 1:1
Styrene > 1:Ih) < 1:l
L1 (DIPHOS) Propene See text See text
~ 2 4 (BISBI)~)
~ ) Propene See text See text
LIO-(R) ( N A P H O S ~ Propene See text See text
"'DFT method (cf. [7, 231). "FRC method (cf. [23]). "Only one enantiomer is mentioned.
732 3.1 Development of Methods

CPPh2
PPhp

L1

PPh2

spcy2
FPP
L3 14

PCY2

L5 16

> c c P P h PPh2
2 g p p h 2

PPh,

L7 L8 19 110

112

pw
Scheme 3
R-2=
111
R-l= P

p
 3.1.2.2 Applications 733

mechanism. Replacement of ligand (PPh3 vs. PH3) and method (FRC vs. QM)
shifts the calculated regioselectivity for propene correctly, whereas the wrong ten-
dencies are obtained for 3,3,3-trifluoropropene/styrene.The regioselectivity rank-
ing SL1< SL2= SLlo(substrate = propene) agrees again with experiment [22].
Apparently, these inconsistencies are caused by electronic effects, which cannot
be described by the FRC method. This deficiency notwithstanding, the FRC
results are conceptually better than the previous approach and also question the
natural bite angle concept [23, 32, 331.

Stereoselectivity

Although some monodentate ligands achieve significant asymmetric inductions

[34, 351, intrinsically bulkier bidentate chelates have a better starting position.
The chiral bidentate ligands L3-Ll2 (cf. Scheme 3) discussed here may be
split into two classes, namely C1- and C2-symmetric ones. The C1-symmetric
BINAPHOS L3, presented first in 1993 [36], is still the only ligand which com-
bines ee values of about 90% with a broad variety of substrates. Unfortunately,
the reaction conditions for L3 are not satisfactory, so that it remains without
industrial application.
If one wants to estimate the ee via&?,, (cf. Regioselectivity), it is necessary to
consider all possible ligand coordination modes (for example, all possible coordi-
nation modes (axial-equatorial ae/equatorial-equatorial ee) are shown in transition
states 8,9 for a C2-symmetric bidentate phosphine ligand (e.g., L10). In the case of
C, symmetry, each coordination mode is duplicated). Each coordination mode con-
tributes with its asymmetric induction to the total stereoselectivity. To achieve high
ee values, at least one of the following requirements should be met [7, 371.

H+----H ' ,#L3 8,9-ae-I: L' = L2 = P(-P), L3 = CO

iH.--Rh, 8,9-ae-2: L' = L3 = P(-P), L2 = CO
R
II' [I L 8,9-ee: L' = CO, L2 = L3 = P-P

( 1) Requirement of preferred asymmetric induction (RPAI): One coordination

mode with high asymmetric induction is preferred, which could be enhanced
by solvent effects. The RPAI calls for a hitherto impracticable theoretical
approach.
(2) Requirement of synchronous asymmetric inductions (RSAI):All coordination
modes favor transition states with equally directed asymmetric inductions
(strong definition). The cases of synchronous asymmetric inductions/preferred
asymmetric induction/zero total stereoselectivity have been corroborated
mathematically for ligands with two coordination modes [7]. If there are
more than two coordination modes, the RSAI is already valid if at least the
two most stabilized transition states have synchronous asymmetric inductions
(weak definition). The advantage of the RSAI is that a high total stereoselec-
tivity can be predicted independently of solvent effects. Any antagonism
734 3.1 Development of Methods

Table 2. Stereoselectivities with ligands L3-Ll2 (substrate = styrene).

Ligand"' Symmetry RSAI fulfilled? ee [%lb)
L3-(R,S) (BINAPHOS) CI Yes 90 (R) [361
L3-(R,R) (BINAPHOS) C1 No 20 ( R ) [361
L44R) c, No -

L5-(R,S) (JOSIPHOS) c, No 30 ( R ) [351

LB(R,S) CI No 60 (9 [351
L7-(S,S) (CHIRAPHOS) c
2 No 20 ( R ) t421
LS-(R) (BINAP) C2 No Low [43]
L9-(R,R) (DIOP) c
2 No 10 ( R ) [421
L10-(R) (NAPHOS) C2 No 30 ( S ) [441
Lll-(R) (THEOPHOS-2) c
2
No -
L124R) (THEOPHOS-1) CZ Yes 0 ~411
") Only one enantiomer is mentioned. b, Approximate values.

should damage the stereodifferentiation, provided that the RPAI is not met
strongly.
(3) Requirement of reduced coordination modes (RRCM): Bite angle, backbone
flexibility, and symmetry may lower the number of possible coordination
modes (see above). This requirement also supports the RSAI and can often
be roughly estimated.

Results with the ligands L3-Ll2 and the substrate styrene (a model substrate in
asymmetric hydroformylation [34]) are summarized in Table 2. Unlike the styrene
regioselectivity results, the FRC energies of is0 transition states with identical
connectivities and hence minor electronic changes are now reliable [7,23]. Never-
theless, the problem of neglected electronic effects still exists [7, 371.

C,-Symmetric Ligands

BINAPHOS L3 and its derivative L4, which has not been tested experimentally so
far, possess two and one chiral axes, respectively, whereas JOSIPHOS L5 and its
constitutional isomer L6 combine planar chirality with a carbon stereocenter. In
the case of L3, the relative configuration of the two chiral axes decides the
total stereoselectivity. Synergistic/antagonistic backbone-substrate interactions
are the main reason for the goodhad performance of L3-(R,S)/L3-(R,R) and
their enantiomers L3-(S,R)/L3-(S,S). This is reminiscent of the matched/
mismatched concept [38]. Furthermore, one chiral axis, as in L4, seems to be
insufficient for a high ee.
The ferrocenylphosphine ligands L5 and L6 are formally equivalent to L3 but
do not fulfill the RSAI. Although one derivative of L5 (ortho-anisyl instead of
 3.1.2.2 Applications 735

phenyl rings) achieves more than 70% ee [35], the influence of the carbon con-
figuration is weaker than that of the second chiral axis in L3 [39].

C2-Symmetric Ligands

The chirality of CHIRAPHOS L7 and DIOP L9, which are selective in asym-
metric hydroformylation but not in hydrogenation, is generated by modification
of an achiral backbone, whereas the backbone of BINAP LS and NAPHOS
L10 is axial-chiral by itself. The ring size increases from L7 to L10 and ensures
a further variation. THEOPHOS-2 L11 and THEOPHOS-1 L12 are derivatives of
NAPHOS L10 with sterically more demanding (naphthyl instead of phenyl) phos-
phorus substituents. L7 and LS have small and stiff chelate rings complying well
with the RRCM (only two axial-equatorial coordination modes; see above). How-
ever, both ligands are only able to overcome partially the cancellation of asym-
metric inductions as in the case of the achiral ligand DIPHOS L1. The
performance descent from hydrogenation to hydroformylation seems to be a
consequence of deviating reaction mechanisms [40].
The chelate rings of L9-Ll2 are bigger and more flexible. Opposite asym-
metric inductions contradict the RSAI, with the exception of L12, whose decisive
improvement as against L11 is caused by different backbone conformations. Un-
fortunately, L12 fails in experiment [41], which reveals one of the essential disad-
vantages of every theoretical approach: a model can only be as accurate as the as-
sumptions made beforehand. L12 presumably does not coordinate in a bidentate
manner [41] as is assumed by theory.

Generally, C2-symmetric ligands have the advantage of reduced coordination

modes but the disadvantage of minor stereodifferentiation. C1 symmetry, on the
other hand, is just as poor a cure-all as the accumulation of chirality centers
(cf. L4 vs. L5-L7). Moreover, the blind transfer of a chirality concept guarantees
no success (cf. L3 vs. L5 and L6). The RSAI classification does not enable a ra-
tional ligand design but relieves asymmetric hydroformy lation from its predomi-
nantly empirical character. This significant progress will be accelerated by the
development of new theoretical methods that include solvent influences as well
as a unified description of steric and electronic effects.

References
[ 1] K. Nozaki, Hydrocarbonylation of Carbon-Carbon Double Bonds, in Comprehensive
Asymmetric Catalysis (Eds.: E. N. Jacobsen, A. Pfaltz, H. Yamamoto), Springer, Berlin,
1999, Vol. 1, p. 381.
[ 2 ] M. Torrent, M. Sol& G. Frenking, Chem. Rev. 2000, 100, 439.
[3] T. Matsubara, N. Koga, Y. Ding, D. G. Musaev, K. Morokuma, Organometallics 1997,
16, 1065.
[4] (a) A.D. Becke, J. Chem. Phys. 1993, 98, 5648; (b) A. D. Becke, J. Chem. Phys. 1993,
98, 1372.
736 3.1 Development of Methods

[5] R. K. Szilagyi, G. Frenking, Organometallics 1997, 16, 4807.

[6] A.C. Scheiner, J. Baker, J.W. Andzelm, J. Comput. Chem. 1997, 18, 775.
[7] D. Gleich, PhD Thesis, Technische Universitat Munchen, 1999.
[8] N. Godbout, D.R. Salahub, J. Andzelm, E. Wimmer, Can. J. Chem. 1992, 70, 560.
[9] (a) R. B. Ross, J. M. Powers, T. Atashroo, W. C. Ermler, L. A. LaJohn, P. A. Christiansen,
J. Chem. Phys. 1990, 93, 6654; (b) M. M. Hurley, L. F. Pacios, P. A. Christiansen, R. B.
Ross, W.C. Ermler, J. Chem. Phys. 1986, 84, 6840.
[ 101 A. Behr, in Ullrnann’s Encyclopedia of Industrial Chemistry, VCH, Weinheim, 1991,
Vol. A 18, p. 215.
[Ill (a) C. K. Brown, G. Wilkinson, J. Chem. SOC. (A) 1970, 2753; (b) D. Evans, J. A.
Osborn, G. Wilkinson, J. Chem. SOC. ( A ) 1968, 3133.
[12] R. F. Heck, D. S. Breslow, J. Am. Chem. Soc. 1961, 83, 4023.
[13] (a) R. Schmid, W. A. Herrmann, G. Frenking, Organometallics 1997, 16, 701; (b)
R. Schmid, PhD Thesis, Technische Universitat Miinchen, 1997.
[14] G. Kiss, E. J. Mozeleski, K. C. Nadler, E. VanDriessche, C. DeRoover, J. Mol. Cutal. A
1999, 138, 155.
[15] S . C. van der Slot, P. C. J. Kamer, P. W. N. M. van Leeuwen, J. A. Iggo, B. T. Heaton,
Organometallics 2001, 20, 430.
[16] B. Comils, in New Syntheses with Carbon Monoxide (Ed.: J. Falbe), Springer, New
York, 1980, p. 1.
[I71 Various ligand coordination types and complex isomers exist; cf. 17, 141. In Figure 9,
only the energies (including zero-point corrections) for the catalyst constitution 1XL
= CO, 2XL = PH3 are depicted.
[18] F. Abu-Hasanayn, K. Krogh-Jespersen, A. S. Goldman, J. Am. Chem. Soc. 1994,116,5979.
[19] N. Kaltsoyannis, J. Chem. SOC., Dalton Trans. 1997, 1 .
[20] P. Pyykko, Chem. Rev. 1988, 88, 563.
[21] T. Horiuchi, E. Shirakawa, K. Nozaki, H. Takaya, Organometullics 1997, 16, 2981.
[22] C. P. Casey, L. M. Petrovich, J. Am. Chem. SOC. 1995, 117, 6007.
[23] D. Gleich, R. Schmid, W. A. Herrmann, Organometallics 1998, 17, 4828.
[24] G. Consiglio, P. Pino, Top. Curr: Chem. 1982, 10.5, 77.
[25] S. Glasstone, K. J. Laidler, H. Eyring, The Theory @Rate Processes, McGraw-Hill, New
York, 1941.
[26] L. A. Castonguay, A. K. RappC, C. J. Casewit, J. Am. Chem. Soc. 1991, 113, 7177.
[27] (a) R. Paciello, L. Siggel, M. Roper, Angew. Chem., Int. Ed. 1999, 38, 1920; (b) R. Pa-
ciello, L. Siggel, H.-J. Kneuper, N. Walker, M. Roper, J. Mol. Catal. A 1999, 143, 85.
[28] S. Kristyin, P. Pulay, Chem. Phys. Lett. 1994, 229, 175.
[29] K. Nozaki, N. Sato, Y. Tonomura, M. Yasutomi, H. Takaya, T. Hiyama, T. Matsubara,
N. Koga, J. Am. Chem. Soc. 1997, 119, 12779.
[30] A. van Rooy, E. N. Orij, P. C. J. Kamer, P. W. N. M. van Leeuwen, Organometallics 1995,
14, 34.
[31] M. Tanaka, Y. Watanabe, T. Mitsudo, Y. Takegami, Bull. Chem. Soc. Jpn. 1974,47, 1689.
[32] P. Dierkes, P. W. N.M. van Leeuwen, J. Chem. Soc., Dalton Trans. 1999, 1519.
[33] C. P. Casey, G. T. Whiteker, Isr: J. Chem. 1990, 30, 299.
[34] F. Agbossou, J.-F. Carpentier, A. Mortreux, Chem. Rev. 1995, 55, 2485.
[35] (a) F. A. Rampf, W. A. Herrmann, J. Organomet. Chem. 2000,601, 138; b) F. A. Rampf,
PhD Thesis, Technische Universitat Miinchen, 1999.
[36] (a) K. Nozaki, N. Sakai, T. Nanno, T. Higashijima, S. Mano, T. Horiuchi, H. Takaya,
J. Am. Chem. Soc. 1997, 119, 4413; (b) N. Sakai, S. Mano, K. Nozaki, H. Takaya,
J. Am. Chem. SOC.1993, 11.5, 7033.
[37] D. Gleich, W. A. Hemnann, Organometallics 1999, 18, 4354.
[38] S. Masamune, W. Choy, J. S. Petersen, L. R. Sita, Angew. Chem., Int. Ed. Engl. 1985,24, 1 .
 3.1.2.2 Applications 737

[39] D. Gleich, unpublished results.

[40] C.R. Landis, S. Feldgus, Angew. Chern., Znt. Ed. 2000, 39, 2863.
[41] J. Shi, W. A. Hemnann, unpublished results.
[42] G. Consiglio, F. Morandini, M. Scalone, P. Pino, J. Organomet. Chern. 1985, 279, 193.
[43] R. Eckl, W. A. Hemnann, unpublished results.
[44] R. W. Eckl, T. Priermeier, W. A. Herrmann, J. Organomet. Chern. 1997, 532, 243.

3.1.2.2.4 C-H Activation

Thomas Strassner

The activation of C-H bonds is one of the elementary steps in chemistry. Intensive
research has lead to homogeneous as well as heterogeneous systems which can
activate the strong C-H bonds (cf. Section 3.3.6). There are numerous experimen-
tal studies which have more recently often been accompanied by theoretical cal-
culations. The two best known examples for the activation of methane are the so-
called Shilov system K2PtC1, [ l], which was one of the first systems reported, and
the [Pt(bpym)CI2] system of Periana, which is currently the most active system
reported for the direct, low-temperature, oxidative conversion of methane to
methanol by platinum salts such as dichloro(~-2-[2,2'-bipyrimidyl])platinum(II)
[Pt(bpym)Cl,] with yields of more than 70 % and a selectivity of 80 % [2].

Shilov System

For the Shilov system a mechanism was proposed which consists of three basic
steps: (1) activation of the alkane by a Pt" species, followed by ( 2 ) a two-electron
oxidation forming a Pt'" intermediate and (3) reductive elimination of the oxidized
alkane as shown in Scheme 4.

Scheme 4
138 3.1 Development of Methods

This general mechanistic scheme is widely accepted, but there are several dif-
ferent pathways possible for each of the three steps. For example, the reductive
elimination could proceed via an SN2mechanism or via a concerted mechanism
involving a three-center transition state. Many research activities have been
devoted to the investigation of these detailed questions, which have been
reviewed extensively by Stahl [3], while here only a summary is given: ( I )
for the reductive elimination it could be concluded that an SN2 mechanism is
operative; (2) the oxidation of RPt" to RPtIV does not occur by alkyl transfer,
but by a two-electron transfer from RPt" to PtrV;and (3) the electrophilic activa-
tion of the alkane is the most difficult part to investigate. At present none of
proposed pathways shown in Scheme 5 could be discounted; also, the experi-
mental observation of H/D exchange in methane can be explained by both
mechanisms.

All experimental results indicate that both intermediates are present, the Pt"
a-adduct and the [Pt"(R)(H)] species; the formation of RPt" is the result of the
deprotonation of [Pt"'(R)(H)].
Theoretical calculations by Siegbahn and Crabtree [4] found the barrier for the
reaction via the [PtIV(R)(H)]intermediate to be a little lower in energy compared
with a one-step mechanism, while a study by Hill and Puddephatt favors a-type
interactions [5]. The most recent theoretical study was conducted by Hush and
co-workers using density functional theory (B3LYP functional) calculations
with double-c to polarized double-[ basis sets [6]. They also studied solvation
effects by a dielectric continuum method.
In contrast to the results of Siegbahn and Crabtree [4] the replacement of an
ammonia ligand was found to be effectively rate-determining with the energy bar-
riers to C-H activation comparable with those of the initial substitution reaction
(34 and 44 kcal/mol for cis- and trans-platin). For cis-platin the energy barriers
 3.1.2.2 Applications 739

for the oxidative addition and a-bond metathesis-type mechanisms were found to
be comparable, while for trans-platin oxidative addition is strongly preferred over
a-bond metathesis, which, interestingly also proceeds through a Pt'" methyl
hydrido complex as an intermediate. It was found that the Pt-H and Pt-CH,
bonds are best described as covalent bonds with a preference to be cis to each
other. The results show that the oxidative addition of methane to Pt" catalysts
is thermodynamically feasible.

Periana System

The Periana system is currently the most active catalytic system for the C-H ac-
tivation of methane. The proposed reaction mechanism (Scheme 6) is also based
on three steps, C-H activation, oxidation, and functionalization. An important fea-
ture of the overall process is that the methyl ester is less reactive with the catalyst
than methane. This is attributed to greater inhibition of the presumed electrophilic
reaction of the C-H bonds of methylbisulfate in comparison with methane as a
result of the electron-withdrawing ability of the bisulfate group.

cH3?

SO2 + H20 SO3 + 2 HL

Scheme 6 L = CI, HSO,

740 3.1 Development of Methods

The mechanism proposed by Periana postulates an equilibrium between the pre-

cursor [Pt(bpym)CI,] and a "T complex", which is supposed to be the active spe-
cies. It was never identified but is believed to be a bisulfate complex, where the
chloride ions of the original complex have been completely replaced. The com-
plex reacts with one of the C-H bonds in methane, binding the resulting methyl
(formally as an anion) to Pt. Oxidation of this complex by bisulfate results in a
hexacoordinate complex, from which the methyl bisulfate is eliminated in the
third step, regenerating the catalyst. Theoretical studies by Hush's group [7]
could show that electrophilic attack on CH, by an intermediate which may be
regarded as a tetracoordinate solvated analogue of a gas-phase, T-shaped, three-
coordinate Pt" species, followed by oxidation of the resulting methyl complex
to a methyl bisulfate ester, is thermodynamically feasible. This is generally in
agreement with the mechanism proposed by Periana et al. While the alternative
mechanism of oxidative addition does not appear to be feasible for Pt" catalysts,
Pt'" species are predicted on thermodynamic grounds to be a viable pathway for
catalysis.

References
[ 11 (a) A. E. Shilov, in Activation and Functionalization of Alkanes (Ed.: C. L. Hill), Wiley,
New York, 1989; (b) A. E. Shilov, in Activation and Functionalization of Saturated Hy-
drocarbons, Riedel, Dordrecht, 1984; (c) L. A. Kushch, V. V. Lavrushko, Y. S. Misharin,
A. P. Moravskii, A.E. Shilov, Now. J. Chim. 1983, 7, 729.
[2] R.A. Periana, D.J. Taube, S. Gamble, H. Taube, T. Satoh, H. Fuji, Science 1998,
280, 560.
[3] S. S. Stahl, J. A. Labinger, J. E. Bercaw, Angew. Chem. 1998, 110, 2298.
[4] P.E.M. Siegbahn, R.H. Crabtree, J. Am. Chem. Soc. 1996, 118, 4442.
[ 5 ] G. S. Hill, R. J. Puddephatt, Organometallics 1998, 17, 1478.
[6] K. Mylvaganam, G.B. Bacskay, N.S. Hush, J. Am. Chem. Soc. 2000, 122, 2041.
[7] K. Mylvaganam, G.B. Bacskay, N.S. Hush, J. Am. Chem. Soc. 1999, 121, 4633.

3.1.3 High-Throughput Approaches to Homogeneous

Catalysis
Vince Murphy, Howard W Turner; Thomas Weskamp

3.1.3.1 Introduction
Combinatorial chemistry and high-throughput screening (HTS) were originally
developed within the pharmaceutical industry, where long development times
and high research costs forced the establishment of new techniques to accelerate
the discovery process. The basic concept of combinatorial chemistry is the cre-
 Applied Homogeneous Catalysis with Organometallic Compounds
Edited by B. Cornils and W. A. Herrmann
Copyright 0 Wiley-VCH Verlag GmbH, D-69469 Weinheim, 2002

740 3.1 Development of Methods

The mechanism proposed by Periana postulates an equilibrium between the pre-

cursor [Pt(bpym)CI,] and a "T complex", which is supposed to be the active spe-
cies. It was never identified but is believed to be a bisulfate complex, where the
chloride ions of the original complex have been completely replaced. The com-
plex reacts with one of the C-H bonds in methane, binding the resulting methyl
(formally as an anion) to Pt. Oxidation of this complex by bisulfate results in a
hexacoordinate complex, from which the methyl bisulfate is eliminated in the
third step, regenerating the catalyst. Theoretical studies by Hush's group [7]
could show that electrophilic attack on CH, by an intermediate which may be
regarded as a tetracoordinate solvated analogue of a gas-phase, T-shaped, three-
coordinate Pt" species, followed by oxidation of the resulting methyl complex
to a methyl bisulfate ester, is thermodynamically feasible. This is generally in
agreement with the mechanism proposed by Periana et al. While the alternative
mechanism of oxidative addition does not appear to be feasible for Pt" catalysts,
Pt'" species are predicted on thermodynamic grounds to be a viable pathway for
catalysis.

References
[ 11 (a) A. E. Shilov, in Activation and Functionalization of Alkanes (Ed.: C. L. Hill), Wiley,
New York, 1989; (b) A. E. Shilov, in Activation and Functionalization of Saturated Hy-
drocarbons, Riedel, Dordrecht, 1984; (c) L. A. Kushch, V. V. Lavrushko, Y. S. Misharin,
A. P. Moravskii, A.E. Shilov, Now. J. Chim. 1983, 7, 729.
[2] R.A. Periana, D.J. Taube, S. Gamble, H. Taube, T. Satoh, H. Fuji, Science 1998,
280, 560.
[3] S. S. Stahl, J. A. Labinger, J. E. Bercaw, Angew. Chem. 1998, 110, 2298.
[4] P.E.M. Siegbahn, R.H. Crabtree, J. Am. Chem. Soc. 1996, 118, 4442.
[ 5 ] G. S. Hill, R. J. Puddephatt, Organometallics 1998, 17, 1478.
[6] K. Mylvaganam, G.B. Bacskay, N.S. Hush, J. Am. Chem. Soc. 2000, 122, 2041.
[7] K. Mylvaganam, G.B. Bacskay, N.S. Hush, J. Am. Chem. Soc. 1999, 121, 4633.

3.1.3 High-Throughput Approaches to Homogeneous

Catalysis
Vince Murphy, Howard W Turner; Thomas Weskamp

3.1.3.1 Introduction
Combinatorial chemistry and high-throughput screening (HTS) were originally
developed within the pharmaceutical industry, where long development times
and high research costs forced the establishment of new techniques to accelerate
the discovery process. The basic concept of combinatorial chemistry is the cre-
 3.1.3.2 Principal Workflow 741

I Instrumentation I
High Throughpul
- Inorganic Chemistry
-1 Automation I- -
An a lysis
Engineering
Organic Chemistry
-
*
Organometallic Chemistry
* Physics
Physical Chemistry

Database
Database Soflware
* Automation Soflware
* Engineering

Figure 1. Building blocks for an efficient high-throughput screening of homogeneous

catalysts.

ation of large libraries of structurally or compositionally diverse compounds that

can be rapidly processed and screened for desired characteristics in high-through-
put fashion. Combinatorial chemistry represents a powerful research strategy to be
applied to problems where a large parameter space influences the key properties of
a desirable compound or formulation.
In the last few years, this technology has been extended to materials science for
the rapid discovery and optimization of, e. g., polymers, catalysts, and electronic
materials [ 11. Homogeneous catalysis, where catalyst performance can be influ-
enced through choices in ligand, metal, and reaction conditions, represents a
very important subset of this broad field.
The key for the efficient screening of thousands of materials is clearly an inte-
grated workflow considering not just the conventional chemical part of organic,
inorganic, and organometallic synthesis, but also issues such as engineering,
data management, and analytics (Figure 1).

3.1.3.2 Principal Workflow

The concept for HTS of catalysts is based on the idea of creating as many mean-
ingful data as possible at the front end of conventional catalyst research, i.e.,
before typical lab reactors start to play a role (Figure 2).
To ensure the clear identification of good catalysts amongst very large numbers
of formulations, a three-step approach of primary, secondary, and tertiary screen-
ing is typically applied (Figure 3 ) .
The primary screen - up to thousands of reactions per day typically on a micro-
liter scale - provides information about potential “hits” and serves as a tool to rule
out quickly catalyst formulations that perform poorly. The primary screening filter
should be suitably high-throughput to cover a selected parameter space rapidly,
although to achieve this it is often necessary to tolerate certain compromises
regarding the precision of data from such a screen.
742 3.1 Development of Methods

Increasing l o Screen
HTS
Data Precision Approach

Conventional
Approaches

Number of
Formulations

Figure 2. High-throughput screening provides a broader funnel and additional filters at the
front end of conventional catalyst research.

The secondary screen - about 50 to 100 reactions per day on a milliliter scale -
is intended as a follow-up of the “hits” gained in the primary screen for their
further validation. Having filtered away the poorly performing catalysts, it is
necessary to investigate in more detail the relative performance features of the
remaining candidates. Thus, a higher quality of data is required of the secondary
screen. Promising candidates (“leads”) that pass this additional filter are finally
handed to typical lab reactors (tertiary screen), the stage where the conventional
catalyst research starts.

I 1,000’s - 10,000’s
ofentities I
2O Screening

10’s - 100’s
of entities
Characterization

pGEE-q

Candidate

Figure 3. Three-step process for the identification of a developmental candidate.

 3.1.3.2 Principal Workflow 743

For HT experimentation as depicted in Figure 3 to be effective, the entire work-

flow for catalyst discoveries has to be developed around relatively new principles
for materials discovery, such as automatization, miniaturization, high-throughput
analysis, and efficient data administration.

3.1.3.2.1 Preparation of Homogeneous Catalysts

in a High-Throughput Format
On the chemical side, HTS of homogeneous catalysts requires an archive of the
two inevitable features of a homogeneous catalyst: metal precursors and ligands.
The ligand archive is desired to be highly diverse with respect to the substructures
of the organic molecules. Once a certain ligand class has been identified to be ef-
fective for a certain transformation, focused libraries of this ligand class can serve
for further optimization. There are different philosophies on how to create diver-
sity within a ligand archive. Basically, the approaches can vary from the creation
of well-defined and isolated low-molecular weight-ligands, such as those used in
conventional coordination chemistry, to enzyme-mimetic approaches and directed
evolution [2].
For the HT synthesis of metal-ligand complexes, an archive of suitable metal
precursors that readily react with a diverse ligand set is of equal importance to
the ligand archive itself. Carefully designed organic ligand and metal precursor
archives are necessary to create well-defined, pure precatalysts in a reproducible
fashion, directly in the microtiter plate without time-consuming purification meth-
ods. Ideally, a drop-in system that works for every metal-ligand combination in a
certain library has to be developed. This, of course, is not always possible, and
thus effective strategies must be adopted to prevent high numbers of “false
negatives”. One strategy employed at Symyx is to screen multiple versions of
each substructure using various logical synthetic routes in a highly automated
fashion. Additionally, “scoping” studies with selected ligands of a library are
typically carried out to ascertain the suitability of certain metal precursors and
the appropriate complexation conditions.
It is very important to stress that the large parameter space in homogeneous
catalysis is not represented by the number of metal-ligand combinations alone.
To discover a cost-effective scalable process for many transformations, many
other parameters have to be considered and optimized. For example, consider
the choice of the following important reaction parameters for a given transforma-
tion: four different ligand/metal ratios, four different pressures, three different
substrate/metal ratios, three different solvents, and two different temperatures.
The inclusion of these parameters into a HT screen will result in almost 300
experiments for each metal-ligand combination !
144 3.1 Development of Methods

3.1.3.2.2 Screening of Homogeneous Catalysts Against

a Chemical Transformation

Primary Screen

A typical format for a primary screen is a 96-well plate with an 8 X 12 array of

1-mL vials. These can be modified to allow high-pressure reactions and/or
reactions at elevated temperatures (Figure 4).
The protocol for screening selected metal-ligand combinations usually starts
with the layout of a 96-element ligand set that is multiplied to create several ligand
daughter plates (Figure 5). Addition of (various) metal precursors to each of these
daughter plates creates the precatalyst plates that are essentially ready for screen-
ing for any given transformation.
The virtual layout of the plates is generally performed on a computer with spe-
cially developed software, and subsequently executed by a robot. Therefore, it is
desirable that all the reagents and protocols are registered in a searchable database.

Figure 4. Microtiter plate for high-pressure reactions.

Secondary Screen

As mentioned above, the secondary screen is usually a scale-up of the hits coming
from the primary screen. The number of “hits” to be followed up is dependent on
several factors. One of them is the reliability of data in the primary screen. If the
error of these data is very small and the reproducibility high, only the clearly best-
performing catalysts have to be picked for further optimization. However, if the
primary screen is designed to give orders of magnitude or focuses on one of sev-
eral important performance characteristics to guarantee a higher throughput, more
catalyst formulations have to be transferred to the secondary screen.
Reactors for this stage of screening are typically highly automated and indivi-
dually controlled with respect to, e. g., temperature and pressure, and ideally they
allow on-line monitoring of the course of the reaction. The layout of the libraries
 3.1.3.3 Analysis in High-Throughput Format 745

Figure 5. Typical protocol for screening multiple metal-ligand complexes against

a certain target.

for secondary screening is still done on a computer and executed by a robot that
delivers the necessary chemicals from stock solutions, or even slurries in the
calculated amounts.

3.1.3.3 Analysis in High-Throughput Format

“Screen in a day, what you can analyze in a day” is one of the basic rules for HTS,
since in many cases the analysis of the screening runs is clearly the limiting step.
Analysis of primary screening reactions is certainly dependent on the transforma-
tion and the parameters that are of primary importance (just activity, or chemo-/
regio-/stereoselectivity as well). A parallel on-line monitoring of the reaction,
e. g. by infrared thermography [3] or thermistors [4], is certainly the fastest way
to obtain raw activity data. Post-reaction screening methods such as thin layer
chromatography, gas chromatography, gel permeation chromatography, capillary
electrophoresis, infrared spectroscopy, NMR, or thermal analysis (T,, T,) allow
the acquisition of more parameters than just activity. However, all these methods
are typically more time-consuming and may represent the rate-limiting step in the
high-throughput process. Significant efforts have been undertaken to develop new
methods and to speed up existing methods, e. g., by converting serial techniques to
parallel techniques [5, 61.
746 3.1 Development of Methods

3.1.3.4 Data Management and Software

The successful implementation of an HTS synthesis and screening program
requires the development of sophisticated software tools. The process begins
at the library design phase, where the source reagents (including diluents, con-
centrations, etc.), experimental protocols (orders of addition, reaction times,
etc.) and formulations within the library array have to be defined. Source reagent
information (such as molecular weight, density) is typically retrieved from a da-
tabase, enabling tedious calculations (stock solution concentrations, volumes,
molar quantities added to the array) to be performed by the software. Ideally,
this design tool will then allow the chemist to visualize and readily review the
design of the library. Subsequently, these library design instructions must be con-
verted into machine language to control the robots used for dispensing reagents
from the stock solutions to the library array. Additional tools are then necessary
to control and record the high-throughput screening experiments and the perfor-
mance characteristics of each catalyst formulation. Finally, a database and suit-
able interfaces must be created to record the library syntheses and screening ex-
periments in such a way as to allow for post-screen, high-level data analysis and
mining. The development of this software and database capability is one of the
more complicated and expensive aspects of creating a useful HTS capability, and
yet another reason why this technology requires a multidisciplinary team to be
effective.

Figure 6. Discovery screening workflow for new polyolefin catalysts.

 References 747

3.1.3.5 Discovery Screening Workflow for

New Polyolefin Catalysts
A fully integrated high-throughput screening workflow for the discovery of new
polyolefin catalysts has been implemented by Symyx Technologies. The work-
flow (Figure 6) employs many of the principles discussed in this section: design
of the libraries on a computer, automated delivery of metal precursors and ligands
into the reactors by a robot, primary screening at a level of more than 1000 reac-
tions per day, secondary screening with on-line monitoring of reaction rates, all
supported by the standard, but parallelized and highly automated characterization
tools.

References
[ l ] B. Jandeleit, D. J. Schafer, T.S. Powers, H. W. Turner, W. H. Weinberg, Angew. Chem.,
Int. Ed. 1999, 38, 2494.
[2] For examples of different approaches, see: (a) J.P. Stambuli, S.R. Stauffer, K.H.
Shaughnessy, J.F. Hartwig, J. Am. Chem. SOC. 2001, 123, 2677; (b) X. Gao, H.B.
Kagan, Chirality 1998, 10, 120; (c) A.M. Porte, J. Reibenspies, K . Burgess, J. Am.
Chem. SOC. 1998, 120, 9180; (d) K.D. Shimizu, M.L. Snapper, A.H. Hoveyda,
Chem. Eul: J. 1998, 4, 1885; (e) M.S. Sigman, E.N. Jacobsen, J. Am. Chem. SOC.
1998, 120, 4901; (f) M. B. Francis, E. N. Jacobsen, Angew. Chem., Int. Ed. 1999,
38, 937; (g) S.R. Gilbertson, S.E. Collibee, A. Agarkov, J. Am. Chem. SOC. 2000,
122, 6522; (h) J. Tian, G. W. Coates, Angew. Chem., Int. Ed. 2000, 39, 3626; (i) A.
Berkessel, D.A. Herault, Angew. Chem., Znt. Ed. 1999, 38, 102: 0 ) E M . Menger,
A.V. Eliseev, V.A. Migulin, J. Org. Chem. 1995, 60, 6666; (k) M.T. Reetz, A.
Zonta, K. Schimossek, K. Liebeton, K.-E. Jager, Angew. Chem., Int. Ed. Engl. 1997,
36, 2830.
[3] (a) F. C. Moates, M. Somani, J. Annamalai, J. T. Richardson, D. Luss, R. C. Wilson, Ind.
Eng. Chem. Res. 1996, 35, 4801: (b) A. Holzwart, H.-W. Schmidt, W. F. Maier, Angew.
Chem., Int. Ed. 1998, 37, 2644; (c) S. J. Taylor, J. P. Morken, Science 1998, 280, 267.
[4] A. R. Connolly, J. D. Sutherland, Angew. Chem., Int. Ed. 2000, 39, 4268.
[5] (a) T. R. Boussie, C. Coutard, H. Turner, V. Murphy, T. S. Powers, Angew. Chem.,
Int. Ed. 1998, 37, 3272: (b) K.H. Shaughnessy, P. Kim, J.F. Hartwig, J. Am.
Chem. SOC. 1999, 121, 2131; (c) C. Hinderling, P. Chen, Angew. Chem., Int. Ed.
1999, 38, 2253.
[6] For enantioselective catalysts, see: (a) M.T. Reetz, Angew. Chem., Znt. Ed. 2001, 40,
284; (b) G. A. Korbel, G. Lalic, M. D. Shair, J. Am. Chem. SOC.2001, 123, 361.
 Applied Homogeneous Catalysis with Organometallic Compounds
Edited by B. Cornils and W. A. Herrmann
Copyright 0 Wiley-VCH Verlag GmbH, D-69469 Weinheim, 2002

748 3.1 Development of Methods

3.1.4 Chemical Reaction Engineering Aspects

of Homogeneously Catalyzed Processes
Manfred Baerns, Peter Claus

Liquid-phase homogeneous catalytic reactions which are carried out in the ab-
sence of a second or even third phase, i.e., a gas or an immiscible liquid, can
be treated from a chemical reaction engineering point of view in analogy to
other homogenous reactions. If the chemical kinetics of such homogeneous cata-
lytic reactions are known, the reactor performance can easily be predicted with
respect to conversion and selectivity. The required procedures have been exten-
sively described in various textbooks, e. g., [ 1-31.
In two-phase systems in which the catalytic reaction takes place in the liquid
phase between a liquid reactant and gaseous reactants, the latter have to be trans-
ferred over the gadliquid boundary layer into the liquid phase. In this situation the
reaction engineering prediction described above can be performed in an analogous
way as long as the rate of transfer of the gaseous reactants into the liquid phase is
fast compared with the intrinsic catalytic reaction. Under these circumstances it
can usually be assumed that the liquid-phase concentrations of the gaseous reac-
tants correspond to gashiquid thermodynamic equilibrium.
In the case where the assumption of the rate-limiting catalytic reaction is not
valid, reaction engineering modeling and prediction of the reactor performance
is not trivial any more. Depending on the magnitude of the rates of the catalytic
reaction and of the transfer rate of the gaseous reactants, severe concentration gra-
dients may exist near the gas/liquid interface. These phenomena are illustrated in
Figure 1. As can be easily derived from the concentration pattern, the reaction
takes place either mainly in the bulk of the liquid phase or in the liquid-phase
boundary layer. If the catalytic reaction is fast a “reaction surface” may develop
within the boundary layer which may even move into the interface itself. From
a chemical point of view it is obvious that the selectivity toward desired product
is affected by these phenomena if a complex reaction network exists. If concen-
tration gradients near the gashiquid interphase are detrimental to good selectivity,
they have to be avoided. This can be done by increasing the rate of transfer of the
reactants or by lowering the rate of the catalytic reaction; the former is achieved
by engineering means, such as increasing the interface area per unit volume or/and
increasing the rate of transfer per unit interface area by influencing the fluid
dynamics (e.g., by stirring). The rate of the catalytic reaction may be reduced
by decreasing the concentration of the catalyst, or by diluting the reactants, or
by lowering the temperature.
The situation may become even more complicated if a second liquid phase is
present; it may either serve as the reaction space containing the catalyst while
the product as well as a part of the reactants exist in the first liquid phase, or it
may act as a solvent into which a desired intermediate is extracted from the react-
ing liquid phase (cf. Section 3.1.1.1). To describe quantitatively the course of a
homogeneous catalytic reaction in a multiphase chemical reactor it is necessary
to combine the following information in a suitable reactor model:
 3.1.4 Chemical Reaction Engineering Aspects 749

(1) intrinsic kinetics of the homogeneous catalytic reaction,

(2) mass transfer between the phases,
(3) effect of the hydrodynamic conditions on mass transfer,
(4) hydrodynamics within the reactor affecting the residence
time distribution in continuous operation.

I “I :

(n)

, liquid
- ‘A2,l

Figure 1. Concentration profiles in gas and liquid for the chemical reaction, A,,g + A*,[ + PI
(eq. 7) influenced by mass transfer, in the liquid phase at differing ratios of the
reaction rate compared with the rate of mass transfer.
(I) Slow reaction: Ha < 0.3, E = 1;i.e., there are no steep concentration gradients of
the reactants and the reaction occurs mainly in the bulk of the liquid.
(11) Reaction of medium rate: 0.3 < Ha < 3 ; i.e., a significant proportion of the
reaction takes place in the boundary layer and the concentrations of the key
reactants A, and A2 are low in the bulk of the liquid.
(111) Rapid reaction: Ha > 3, E 2 Ha; i.e., the rate of consumption of A , is so fast
that its concentration drops to zero in the bulk of the liquid; thus, the reaction occurs
only in the boundary layer.
(IV) Instantaneous reaction in the phase boundary layer: Ha + 3; i.e., the rate of
reaction of A , is so fast that the concentrations of A , and A2 drop to zero within the
boundary layer, resulting in a “reaction surface”.
(V) Instantaneous reaction in the phase boundary surface: cz, = 0; i.e., the reaction
surface moves into the interface between the two fluid phases and the bulk of the
liquid as well as the liquid-phase boundary layer are not utilized for the reaction any
more.
750 3.1 Development of Methods

It is the intention of this contribution to give an overview of the procedures to

be applied to model a multiphase reactor and its performance for a homogeneous
catalytic reaction; for a detailed multiphase design the reader is referred to appro-
priate textbooks.

3.1.4.1 Kinetics in Homogeneous Catalysis

3.1.4.1.1 Kinetics of Liquid-Phase Reactions

Homogeneously catalyzed reactions are often carried out in bi- or multiphase re-
actors. Gaseous reactants (e. g., H,, CO, H,/CO, 0,) have to be transferred from
the gas phase to the organic-liquid phase where the reaction takes place. Despite
the fact that most of these reactions are industrially applied (e. g., hydroformyla-
tion, carbonylation, hydrogenation) and the reaction mechanisms have been stu-
died extensively, only limited information is available on the kinetics and mass
transfer processes required for reaction engineering purposes. Some intrinsic
rate equations of homogeneously catalyzed reactions are shown in Table 1. Details
with respect to the kinetic parameters and the experimental conditions are given in
the references cited. Rate equations of homogeneously catalyzed reactions often
refer to the liquid-phase concentrations. In most of the cases the rate equations
are nonlinear with respect to the concentrations of the reactants (organic educt,
hydrogen, carbon monoxide, catalyst). These relationships are often analogous
to those frequently encountered in heterogeneously catalyzed reactions.

Table 1. Kinetic rate equations of homogeneously catalyzed reactions.

Chemical reaction Catalyst Kinetic model”’ Ref.

Hydroformylation of HCo(C0)d r = -kcAcBccat [41

propen e (Section 2.1.1) cco
Hydroformylation of CO*(C0)8 r = ~ C A C B C ~ ~ I
diisobutene (Section 2.1.1) KACA+ cco
PI

Hydroformylation of
1-heptene

Hydrogenation of RhCl(PPh3)3 ~ C A C ccat

B
r =
cyclohexene (Section 2.2) 1 + KACA+ KBCB [71

Hydrogenation of RhCl(PPh3)3 kKcAccat

r =
cyclohexene (Section 2.2) KCA CL + [81

Hydrogenation of RhCl(PPh3)3
ally1 alcohol (Section 2.2)
 3.1.4.1 Kinetics in Homogeneous Catalysis 75 1
Table 1. (Continued).
Chemical reaction Catalyst Kinetic model') Ref.

Hydrogenation of RuCl(CO)(OCOPh)(PPh,)z y = -
k C A c B Ccat
[lo1
cis- 1,4-polybutadiene (Section 2.2) CPPhi

Carbonylation of RhClJHI
methanol (Section 2.1.2)

Oxidation of Mn(OAc)z
cyclohexane (Section 2.8)

Oxidation of PdC12/CuCl, kCACPdCl:-

r = 2 ~131
ethylene (Wacker) (Section 2.4.1) cc~-Cn+
Polymerization of [ C3H5NiL2]PFh
butadiene (L = ligands)

Oligomerization of Ni(ChH5)2PCHzCOOH r = - kKCACcat

ethylene (SHOP) (Section 2.3.1.3) 1 +
KCA
I151

')cA = concentration of the organic reactant; cB = concentration of hydrogen;

= concentration of the catalyst.
cCat

3.1.4.1.2 Overall Kinetics of GasLiquid-Phase Reactions

To derive the overall kinetics of a gadliquid-phase reaction it is required to con-
sider a volume element at the gadliquid interface and to set up mass balances
including the mass transport processes and the catalytic reaction. These balances
are either differential in time (batch reactor) or in location (continuous opera-
tion). By making suitable assumptions on the hydrodynamics and, hence, the in-
terfacial mass transfer rates, in both phases the concentration of the reactants and
products can be calculated by integration of the respective differential equations
either as a function of reaction time (batch reactor) or of location (continuously
operated reactor). In continuous operation, certain simplifications in setting up
the balances are possible if one or all of the phases are well mixed, as in con-
tinuously stirred tank reactor, hereby the mathematical treatment is significantly
simplified.
Therefore, it is necessary to determine the influence of mass transfer to or from
the above-mentioned interfaces on the conversion, which leads to expressions for
the flux of a reactant across the interface and for the overall reaction rate. After
balancing the disappearance of the components Al and A*, e. g., at the gadliquid
interface, by analogy with the treatment of the rate of chemical reaction and pore
diffusion in heterogeneous catalysis, the overall reaction rate is given by eq. (1)
[21:
152 3.1 Development of Methods

Ha
= a
tanh Ha

For analysis of such coupled fluid-fluid systems it is useful to distinguish

between three regimes of the reaction rate (see Figure 1) which are characterized
by different values of the Hatta number Ha (eqs. (2) and (3)) and the enhancement
factor E (see below):

Ha =
1
kl,l /= 2
knJmDAi,cCA1
n-I m
'A2

H a = L & (first-order reaction) (3)

kl. I

0 For Ha < 0.3, E = 1, f ' ) = 1 Regime 1 : slow reactions, controlled by

chemical kinetics
Rate of chemical reaction < mass transfer (phase equilibria)

j Rate of chemical reaction > mass transfer (cA,,l 0) -

For Ha < 0.3, E = 1 , f - 0 Regime 1: slow reactions, controlled by diffusion

0 For 0.3 < Ha < 3, E > l , f = 0 Regime 2: fast reactions

jRate of chemical reaction > mass transfer (c,,,l = 0, 1 < f )

a For Ha > 3, E = Ha, f = 0 Regime 3: instantaneous reactions

j Rate of chemical reaction > mass transfer ( c i , ,=~ ci2,1= 0; /E < sF)

The mass exchange rate between two phases during the course of the chemical
reaction is compared with that for purely physical absorption. The ratio of these
two rates (eq. (4)), is known as the enhancement factor E for mass transfer on
the liquid side during the occurrence of a chemical reaction:

For slow reactions (Ha < 0.3) the rate of mass exchange through the fluid fluid
interface is not enhanced by the chemical reaction which mainly takes place in the
bulk of the reaction (catalytic) phase, and E becomes approximately 1 [2].
 3.1.4. I Kinetics in Homogeneous Cutulysis 753

Under the conditions of 0.3 < Ha < 3 , the rate of mass exchange is enhanced
by the chemical reaction ( E > I ) , and in the last case (Ha > 3), A, and A2 react so
fast that the reaction proceeds only in the boundary layer ( E = Ha). Thus, eq. (1)
for the overall rate of reaction is reduced to eq. (5):

A theoretical analysis to evaluate quantitatively the mass transfer effects for a

hyperbolic form of the intrinsic kinetics of a homogeneous catalytic reaction has
been developed [16], assuming a gaseous reactant A, an organic liquid-phase
reactant B and a homogeneous catalyst C. Two cases have to be considered:

(a) The reaction is assumed to occur in the bulk of the liquid.

(b) The reaction of A occurs completely in thefilm.

For case (b) a concept of a generalized Hatta number is used to obtain an ap-
proximate analytical solution for the enhancement factor. Plots of E vs. Ha at dif-
ferent values of parameters are given [16]. In the former case a transition in the
regimes of absorption with change in Ha is indicated, which, with respect to
the homogeneously catalyzed reaction, reflects a change in the concentration of
the catalyst. This approach [ 161, covering all the regimes of homogeneous cataly-
tic gas-liquid reaction, allows a quantitative prediction of mass transfer effects on
the kinetics of this operation mode.

3.1.4.1.3 Overall Kinetics of GasLiquidLiquid-Phase

Reactions
In the case of the above mentioned gas-liquid reactions the liquid phase contains
the homogeneous catalyst together with the liquid reactant and the dissolved gase-
ous reactant. To perform gas-liquid-liquid reactions in the biphasic (liquid/liquid)
mode it is essential that the solubility of the homogeneous catalyst in one of the
two liquid phases is negligible. On the one hand, by using water-soluble ligands,
homogeneous metal complex catalysts can be kept in the aqueous phase where the
catalytic reaction takes place. In these biphasic liquid systems different situations
are possible which would have to be considered in any quantitative treatment. For
instance, the following situations may occur:

(1) The gaseous reactants are dissolved in the catalyst-containing phase where
they react to an immiscible product which is only soluble in one of the two
liquid phases, i.e., in the product phase. The gaseous reactants are transferred
into the catalyst-containing phase either (a) directly from the gas phase and/or
(b) from the liquid phase in which they may be soluble too.
(2) The gaseous reactants are only soluble in one liquid phase. This requires that
the catalytic reaction takes place at the liquid/liquid interface only, i.e., the
754 3.1 Development of Methods

products, again soluble only in one of the two phases, are formed in the
boundary layer or in the phase boundary interface for the case of an instanta-
neous reaction (see Section 3.1.4.1.2).

These processes are still not fully understood and need further elucidation. For
example, in the gas/liquid/liquid, homogeneously catalyzed hydroformylation of
olefins according to the RuhrchemieEhBne-Poulenc process, the reaction prod-
ucts are nearly insoluble in the aqueous catalytic phase. Several water-soluble
catalysts, e. g., HRh(CO)(TPPTS), (see Section 3.1.1. l), have been used for
hydrogenation and hydroformylation reactions [ 17-19]. On the other hand, if
the homogeneous catalyst is not soluble in water, but in an organic liquid, the bi-
phasic homogeneously catalyzed reaction may also occur in the organic phase. For
instance, in the case of biphasic hydroformylation of ally1 alcohol (eq. (6)), the
educt and the reaction products are water-soluble but the catalyst is present in
the organic phase [20]. In some cases the second liquid phase is formed during
the catalytic reaction (e. g., in Shell’s SHOP process).

( n-heptanoVH20)

To determine the mode of operation (see below) it is useful to group these

homogeneous catalysts into “aqueous biphasic systems” (see Section 3.1.1.1)
and “nonaqueous biphasic systems” (see Section 3.1.1.2). Gas-liquid-liquid reac-
tions are also involved in organometallic phase transfer catalysis, e. g., in biphasic
carbonylation of benzyl chloride to phenylacetic acid by the catalyst system
NaCo(C0)J3u4NBr/NaOH [21]. Here, the biphasic system consists of an organic
solvent and aqueous alkali.
In all the above mentioned cases conversion can only take place when the com-
ponents are transferred to the catalytic phase or at least to the interface in which
the reaction proceeds. Transport from one phase to the other(s) requires a driving
force, i.e., the existence of concentration gradients. Figure 2 shows schematically
the principal steps of a homogeneously catalyzed gas-liquid-liquid reaction
(eq.(7)), where the reaction product PI is formed by the reaction between a gas-
eous reactant A, and reactant A2 in the liquid phase 1 in presence of a second
liquid phase which contains the catalyst. Both liquid phases are immiscible and
A l is only soluble in liquid phase 1.

homogeneous catalyst
+ A2’1 aaueous biDhase * PI (7)
(or nonaqu’eous)

Several steps influencing the overall rate of the reaction and the selectivity of
a desired product have to be considered; these are shown in Table 2 for an
aqueous biphasic reaction. It is important to note that steps (e) and (f) cannot
be separated from each other in both cases because, in general, the transport
 3.1.4. I Kinetics in Homogeneous Catalysis 755

gas phase
A1A

A1 ,I1 A2,Il P1,H liquid phase 1

A1,12

+
+ A2,12 -
homogeneous catalyst
p1,12 liquid phase 2

Figure 2. Principal steps of mass transfer and chemical reaction during the homogeneously
catalyzed gasfiiquidliquid reaction (eq. (13)).
A , = gaseous reactant; A2 = liquid reactant; PI = reaction product. A gas phase and
two immiscible liquid phases are present; A, is only soluble in liquid phase 1.

Table 2. Dependence of the steps in an aqueous biphasic catalytic reaction on the mode of
operation.
Step Case I Case I1
Aqueous droplets containing the Organic liquid phase is dispersed
dissolved catalyst are dispersed in a continuous aqueous phase which
in a continuous organic liquid phase contains the catalyst

(a) Transport of a gaseous reactant (A,) Transport of a gaseous reactant (A,)

from the bulk of the gas phase to the from the bulk of the gas phase to the
gaslorganic liquid interface gadaqueous catalyst interface

(b) Transport of A, through the Transport of A , through the

gaslorganic liquid interface gaslaqueous catalyst interface

(c) Transport of A, into the bulk of the Transport of A , into the bulk of the
organic liquid aqueous catalyst phase

(d) Transport of both dissolved A, and Transport of liquid reactant (A2)

liquid reactant (A2) from the organic from organic droplets to the
phase to the organic/aqueous interface organiclaqueous interface

(e) Transport of A, and A2 from the Transport of A2 from the

organiclaqueous interface to the
aqueous catalyst phase
(f) Homogeneously catalyzed reaction of
dissolved A , and A2 to products (P) in
the aqueous phase
organiclaqueous interface to the
aqueous catalyst phase
Homogeneously catalyzed reaction of
dissolved A, and A2 to products (P) in
the aqueous phase

(8) Transport of water-immiscible P from Transport of water-immiscible P from

the aqueous to the organic phase the aqueous to the organic liquid phase
156 3.1 Development of Methods

from the interfaces occurs simultaneously with the catalytic reaction. From the
above qualitative discussion it can be clearly derived that at least four important
factors, namely

- interphase mass transfer,

- solubility,
- thermodynamic phase equilibria, and
- intrinsic kinetics.

must be considered during quantitative analysis of gas-liquid-liquid reactions

(Figure 3).
For the reaction given above according to eq. (7) between A,,g and A2,[in a
homogeneous catalyst-containing aqueous phase, the enhancement of gas to
water mass transfer rates by a dispersed organic phase can be described, for in-
stance, with a new mass transfer theory without any additional parameter adjust-
ment, thefilm variable hold-up (FVH) model [22]. This model takes into account
the distribution of organic (e. g., 1-octene) and continuous aqueous phase near the
gadliquid interface and explains quantitatively the influence of hold-up, droplet
diameter, and permeability of the organic phase on the observed enhancement.

r -liquid-liquid
- of gaseous reactants
in the aqueous phase
(in the presence of - of organic reactants
a dispersed gas phase) in the catalytic phase
-gas-liquid - dependence on pressure
(in the Dresence of a dis-
persed'second liquid phase) - influence of co-solvent

mass transfer solubility

Overall reaction rate

of homogeneously catalyzed gas-liquid reactions

thermodynamic
phase equilibria
-t T intrinsic kinetics

L- determination of
reactant and product
- influence of concentration
(reactant, metal, ligand) /
concentrations in the partial and total pressure;
aqueous and liquid phase temperature

- determination of reaction
network

Figure 3. Factors controlling biphase hydrogenations.

 3.1.4.1 Kinetics in Homogeneous Catulysis 157

Experimental data have been presented on the enhancement of mass transfer into
an aqueous sulfite solution in a stirred cell, due to the presence of a dispersed
liquid l-octene phase. Also, the experimental data for O2 mass transfer enhance-
ment to hexadecane and for CO, mass transfer enhancement due to toluene drop-
lets can be reasonably well described, which indicates that in different liquid-
liquid systems the dispersed-phase distribution is similar for different organic
droplets in water.
The very low solubility of organic reactants in the catalytic phase often gives
rise to a drastic decrease of the effective reaction rate. This drawback of gas-
liquid-liquid reactions has been overcome by adding solvents or co-solvents. In
the case of 1-octene hydrogenation, which was performed in semi-batch operation
and by using [RhCl(COD),] TPPTS as water-soluble catalyst, the waterll-octene
co-solvent equilibria were estimated by a combination of the UNIFAC group dis-
tribution method and the UNIQUAC equation in order to select a convenient co-
solvent [23]. Ethanol, n-propylamine, or ethylene glycol considerably enhance the
1-octene concentration in the aqueous phase without losing catalyst in the organic
phase. Furthermore, it was shown that the hydrogen solubility in the aqueous cata-
lytic phase increases according to Henry's law (eq. (8)) (cf. Section 3.1.1.1)
* *
pi = HiCi

with increasing hydrogen pressures up to 10 MPa. Then, initial kinetics, derived

without any gas-liquid and liquid-liquid mass transfer limitations, showed first-
order reaction rates with respect to dissolved hydrogen and l-octene in the aque-
ous phase. Finally, by measuring time-dependent concentrations, and by use of the
thermodynamic liquid-liquid model, which makes it possible to calculate the con-
centrations of reactants and products in the aqueous catalytic and organic phases,
complete kinetics of parallel hydrogenation and isomerization were analyzed [23].
Several of the factors of Figure 3 controlling the activity and selectivity of the bi-
phasic selective hydrogenation of @unsaturated aldehydes to allylic alcohols,
for instance 3-methyl-2-butenal to 3-methyl-2-buten-1-01 (eq. (9)), with ruthe-
niudsulfonated phosphine catalysts were investigated [ 191, such as the effect
of agitation speed and the influence of aldehyde, ligand, and metal concentration.

H2 + & ' 0
RuCIgPPTS
(9)

Under optimized reaction conditions, where gas-liquid mass transfer was not
rate-determining, the kinetic eq. (10) was found to apply.
r = kCRuC"* (10)

A zero-order dependence with respect to the concentration of the aJ-unsatu-

rated aldehyde was found.
758 3.1 Development of Methods

GasAiquidAiquid reaction engineering was studied by Purwanto and Delmas

[24] during hydroformylation of 1-octene by [Rh(COD)Cl] TPPTS catalyst in a
batch reactor at pressures between 1.5 and 2.5 X lo3 kPa and temperatures of
333 and 343 K. As also shown for olefin hydrogenation [23], the concentration
of 1-octene in the aqueous phase was increased using a co-solvent (e. g., ethanol)
which gave rise to an enhancement of the reaction rate of hydroformylation [24,
251. The effect of co-solvent addition on gas-liquid and liquid-liquid equilibria
was studied both experimentally and theoretically by UNIFAC simulations.
Kinetic studies showed that the reaction is first order with respect to 1-octene
and catalyst concentrations. The reaction rate was enhanced by an increase in hy-
drogen partial pressure and at low CO partial pressures, while an inhibition was
observed at high CO pressures. This dependence on CO partial pressure was ty-
pical of hydroformylation kinetics in homogeneously catalyzed reactions with Rh
complex catalysts. A semi-empirical kinetic model (eq. (1 1)) based on initial
reaction rates obtained during this study was used to describe the overall rate of
the hydroformylation of 1-octene:

The parameter values obtained by means of an optimization routine are given in

Table 3. Furthermore, it was observed that, if PPh3 was added to the organic liquid
phase (toluene) during hydroformylation, the rate was increased by a factor of up
to 50 [25].
The kinetics of the above-mentioned biphasic hydroformy lation of ally1 alcohol
(see eq. (6)) were described by the rate eq. (12) [20]

which shows the inhibition of the reaction rate by the partial pressure of carbon
monoxide. An increase of the 1iquidAiquid interfacial area and therefore of the
overall reaction rate in the biphasic system was also observed by the use of
surfactants [26].
If the homogeneously catalyzed reaction is performed in the phase-transfer cat-
alyzed mode (e. g., [27, 39]), mass transfer rates of ionic intermediates between
the organic and aqueous phases, their phase and partition equilibria as well as

Table 3. Parameters of eq. (11) obtained for the kinetics of hydroformylation of 1-octene at
two temperatures [24].
Parameter T = 333 K T = 343 K
k, X [m9 k m ~ l -s-’1
~ 1.571 7.441
KE,> X lo-* [m’ kmol-’1 1.967 2.185
&I X lo-’ [m3 kmol-’1 1.133 1.886
 3.1.4.2 Aspects of Catalyst Recycling 759

the reaction rate in the organic phase have to be analyzed to model the overall re-
action rate. Finally, to describe the dynamics of liquid-liquid phase transfer reac-
tions a new phase-plane model was developed [28], based on the two-film theory.

3.1.4.1.4 Further Examples of Multiphase Reaction

Engineering
To simulate the effects of reaction kinetics, mass transfer, and flow pattern
on homogeneously catalyzed gas-liquid reactions, a bubble column model is
described [29, 301. Numerical solutions for the description of mass transfer
accompanied by single or parallel reversible chemical reactions are known [3 11.
Engineering aspects of dispersion, mass transfer, and chemical reaction in multi-
phase contactors [32], and detailed analyses of the reaction kinetics of some new
homogeneously catalyzed reactions have been recently presented, for instance, for
polybutadiene functionalization by hydroformylation in the liquid phase [33], car-
bonylation of 1,4-butanediol diacetate [34] and hydrogenation of cis- 1,4-polybu-
tadiene and acrylonitrile-butadiene copolymers, respectively [ 101, which can be
used to develop design equations for different reactors.
Nevertheless, in future a complete quantitative analysis on the basis of chemical
reaction engineering principles of homogeneously catalyzed reactions, especially
for the gas/liquid/liquid mode, has to be performed, considering all the factors
(Figure 3) that influence the overall reaction rate.

3.1.4.2 Aspects of Catalyst Recycling

As outlined in Section 3.1.1.1, the use of a liquid-liquid biphasic system, where
the reactants are in an organic phase and the homogeneous catalyst is in water,
has great advantages in product isolation and catalyst recycling. Results obtained
for three consecutive runs with the same aqueous phase during the selective
hydrogenation of 3-methyl-2-butenal to 3-methyl-2-buten- 1-01 (eq. (9)) using
RuCI, and TPPTS in the biphasic mode [I91 are shown in Table 4. Besides the
high chemoselectivity and conversion, the results show that the selectivity to
allylic alcohol remained unaffected throughout catalyst recycling. Furthermore,
no leaching of ruthenium and TPPTS in the organic phase was observed [19].

Table 4. Conversion of 3-methyl-2-buten- 1 -a1 and selectivity to 3-methyl-2-buten- 1-01 after

Ru catalyst recycling [19].
Run Time [h] Conversion [%] Selectivity [%)
1.o 100 96
0.5 99 97
0.5 99 97
760 3.1 Development of Methods

The immobilization of homogeneous catalysts offers advantages in catalyst

recycling. If the hydrogenation of a,p-unsaturated aldehydes such as 3-methyl-2-
buten- I-a1 (eq. (9)) or retinal was performed with supported aqueous-phase cata-
lysts (SAPCs), namely R u C ~ ~ ( T P P T S ) ~ /and
S~ORuH~(TPPTS)~/S~O~,
~ a dissolu-
tion of much of the ruthenium was observed in polar solvents [35]. These catalysts
were difficult to recycle because of poisonous adsorption of organic compounds at
the catalyst surface as detected by IR spectroscopy. Thus, the concept of SAPCs
seems to be limited to nonpolar media.
Silica-supported homogeneous catalysts, especially phosphino-iridium com-
pounds, appear more promising in the hydrogenation of a$-unsaturated alde-
hydes, provided that their productivity can be improved and catalyst deactivation
is avoided so that recycling of these materials could be meaningful [35].
Finally, the problems of product isolation and catalyst recycling were avoided
when heterogeneous catalysts were used for the selective hydrogenation of a&
unsaturated aldehydes in the gas phase. These were true bimetallic catalysts
which were prepared by the application of surface organometallic chemistry
(e. g., by controlled surface reaction of (n-C4H&3n with supported Group VIII
metals [36, 371 followed by reduction in hydrogen at 623 K or via immobilized
organobimetallic alkoxides [38]). These catalysts were able to control the intramo-
lecular selectivity by favoring hydrogenation of the C=O bond compared with
their C=C double bond, with high turnover frequencies and without any stress
of catalyst recycling.

Explanation of Symbols
interfacial area per unit volume
concentration of species i
concentration of species i at phase equilibrium
binary diffusion coefficient
enhancement factor
Henry coefficient
Hatta number
diffusion flow density
rate constant (dimension depends on kinetics)
mass transfer coefficient
reaction orders
partial pressure
reaction rate
reff effective reaction rate
 References 76 1

R gas constant [8.314 J mol-' K-'1

T temperature [KI
ai equilibrium coefficient [-I
6 film thickness Iml
1 distance of reaction plane from interface Lml
F fluid
gas
component (e.g., i = 1, 2 or A, B ...)
liquid

References
[ l ] K. R. Westerterp, W. P. M. van Swaaij, A. A. C. M. Beenackers, Chemical Reactor
Design and Operation, John Wiley, New York, 1984.
[2] M. Baerns, H. Hofmann, A. Renken, Chemische Reaktionstechnik, Lehrbuch der Tech-
nischen Chemie I, Georg Thieme, Stuttgart, 1987.
[3] 0. Levenspiel, Chemical Reaction Engineering, 2nd ed., John Wiley, New York, 1972.
[4] G. Natta, R. Ercoli, S. Castellano, F. H. Barbieri, J. Am. Chem. Soc. 1954, 76, 4049.
[ 5 ] A. R. Martin, Chem. Ind. (London) 1954, 11, 1536.
[6] G. Csontos, B. Heil, L. Mark6, Ann. N.E Acad. Sci. 1974, 239, 47.
[7] J. A. Osborn, F. H. Jardine, J. F. Young, G. Wilkinson, J. Chem. Soc. A 1966, 1711.
[8] J. Halpem, Inorg. Chim. Acta 1981, 50, 11 ;J. Alpem, C. S. Wong, J. Chem. Soc., Chem.
Commun. 1973, 629.
[9] J. G. Wadkar, R. V. Chaudari, J. Mol. Catal. 1983, 22, 105.
[lo] X. Guo, G. L. Rempel in Progress in Catalysis (Eds.: K. J. Smith, E. C. Sanford),
Elsevier, Amsterdam, 1992, p. 13.5.
[ I l l J. F. Roth, J. M. Craddock, A. Hershman, F. E. Paulik, Chem. Technol. 1971, 600.
[I21 Y. Kamiya, M. Kotake, Bull. Chem. Soc. Jpn. 1973, 46, 2780.
[I31 P. M. Henry, Adv. Organomet. Chem. 1975, 13, 363.
[14] R. Taube in Homogene Katalyse, Akademie-Verlag, Berlin, 1988, p. 243.
[15] W. Keim, F. H. Kowaldt, R. Goddard, C. Kriiger, Angew. Chem. 1978, 90, 493; Angew.
Chem., Int. Ed. Engl. 1978, 17, 466; M. Peukert, W. Keim, Organometallics 1983,
2, 594.
[16] R. V. Chaudhari in Frontiers in Chemical Reaction Engineering: Proc. Int. Chem.
React. Eng. Con$, New Delhi (Ed: L. K. Doraiswamy), 1984, I , 291.
[17] E. G. Kuntz, FP 2.314.910 (1975); CHEMTECH 1987, 17, 570.
[IS] E. Wiebus, B. Cornils, Chem.-1ng.-Tech.1994, 66, 916; B. Cornils, E. G. Kuntz, J. Or-
ganomet. Chem. 1995, 502, 177; W. A. Henmann, C. W. Kohlpaintner, Angew. Chem.
1993, 105, 1588; Angew. Chem., Znt. Ed. Engl. 1993, 32, 1524; B. Comils, E. Wiebus,
CHEMTECH 1995, 2.5, 33 and Hydrocarb. Proc. 1996, March, 63.
[I91 J. M. Grosselin, C. Mercier, G. Allmang, F. Grass, Organometallics 1991, 10, 2126.
[20] R. M. Deshpande, S. S. Divekar, B. M. Bhanage, R. V. Chaudhari, J. Mol. Cat. 1992,
75, L19.
162 3.1 Development of Methods

[21] L. Cassar, M. Foa, DE 2.801.886 (1978); J. Organomet. Chem. 1977, 134, C15.
[22] C. J. van Ede, R. van Houten, A. A. C. M. Beenackers, Chem. Eng. Sci. 1995, SO, 2911.
[23] I. Hablot, J. Jenck, G. Casamatta, H. Delmas, Chern. Eng. Sci. 1992, 47, 2689.
[24] P. Purwanto, H. Delmas, Catal. Today 1995, 24, 135.
[25] R. V. Chaudhari, B. M. Bhanage, R. M. Deshpande, J. Jenck, H. Delmas, P. Purwanto in
Proc. Int. Symp. Chem. React. Eng. (ISCRE-13), Baltimore, 1994, see [24]: Ref. [8].
[26] C. Larpent, F. Brise LeMenn, H. Patin, New. J. Chem. 1991, IS, 361.
[27] Y. Lee, M. Yeh, Y. Shih, Ind. Eng. Chem. Res. 1995, 34, 1572.
[28] H. Wu, Ind. Eng. Chem. Res. 1993, 32, 1323.
[29] J. J. Romanainen, T. Salmi, Chem. Eng. Sci. 1992, 47, 2493.
[30] W.-D. Deckwer, Reaktionstechnik in Blasensuulen, 1 st ed., Otto Salle Verlag, Frankfurt/
Main, and Verlag Sauerlander, Aarau, 1985.
[31] G. F. Versteeg, J. A. M. Kuipers, F. P. H. van Beckum, W. P. M. van Swaaij, Chem. Eng.
Sci. 1989, 44, 2295; Chem. Eng. Sci. 1990, 45, 183.
[32] T. A. Hatton, E. N. Lightfoot, AICHe J. 1984, 30, 235, 243.
[33] S. J. Tremont, E. E. Remsen, Chem. Eng. Sci. 1990, 45, 2801.
[34] S. B. Dake, R. V. Gholap, R. V. Chaudhari, Ind. Eng. Chem. Res. 1987, 26, 1513.
[35] E. Fache, C. Mercier, N. Pagnier, B. Despeyroux, P. Panster, J. Mol. Cat. 1993, 79, 117.
[36] P. Claus, D. Honicke in Catalysis of Organic Reactions (15th Conf. on Catalysis of
Organic Reactions, May, 1994, Phoenix, AZ), Marcel Dekker, New York, 1995, p. 431.
[37] P. Claus, Chem.-Ing.-Tech. 1995, 67, 1340.
[38] D. Delent, P. Claus, Int. Symp. Relat. Hom. Her. Cat. (8th SHHC), Balatonfured,
Hungary, September 10- 14, 1995, Poster 45.
[39] E. V. Dehmlow, S. S. Dehmlow, Phase-Transfer Catalysis, 3rd ed., VCH, Weinheim,
1993.

3.1.5 Introduction to Selected Multicomponent

and Multifunctional Catalysts
Diethard Hesse

3.1.5.1 Introduction
In order to synthesize a desired chemical compound, it is often necessary to pass
through a sequence of different reaction steps because side reactions can occur,
making the composition of the medium more and more complex and, thus, open-
ing additional undesired reaction pathways. The presence of a large number of dif-
ferent compounds decreases the concentration of the desired intermediates by di-
lution processes, leading to lower reaction rates of the necessary reactions. In most
of these cases, the consequence is an extremely low yield of the final product in
question, a result which cannot be accepted from a practical point of view.
Thus, in order to obtain a product in high yield, normally it is not synthesized in
a one-pot reaction, starting from a certain number of raw materials, but it is pro-
duced by buying the necessary intermediates from the chemical market and using
them in a one-step reaction.
 3.1.5.1 Introduction 763

Alternatively, a microorganism, for example, produces a large number of differ-

ent complex structured compounds, such as proteins, within a very restricted vo-
lume, starting from a small number of relatively simple compounds, e. g., glucose
and inorganic salts. It is now widely accepted that this capability of a living cell is
due to the action of highly organized multienzyme systems, and thus multicompo-
nent and multifinctional catalytic systems, which create special reaction condi-
tions that make possible synergetic effects like the channeling of metabolites
[ l ] and coordinated allosteric behavior [2]. In order to stabilize them, these sys-
tems appear as, for example, multienzyme complexes or as membrane-bound en-
zyme arrays. The structure of these enzyme clusters not only permits effective use
of the educt components by the extremely high selectivity of the biocatalysts, but
it also generates a reaction space wherein dilution processes are minimized. A
living cell can therefore be considered as the most efficiently working chemical
reactor known (cf. Sections 3.2.1 and 3.2.3).
In contrast, for a long time the chemical industry has been widely applying cata-
lysts to increase the rate as well as the selectivity of chemical reactions. Although
most of these catalysts have a complex chemical composition, the main aim of the
development was to obtain an optimal catalyst for a given one-pot reaction. These
catalysts are therefore monofunctional. In particular, such a situation often occurs
in the field of homogeneous catalysis since it is possible to adjust, to a certain ex-
tent, the characteristics of a complex catalyst for a given reaction by an appropri-
ate choice of its ligands. Instructive examples are the ligand-stabilized plati-
num(I1) chloride/tin(II) chloride complexes catalyzing olefin hydroformylation
reactions (see, e. g., [3]). Besides these Pt/Sn complexes, a relatively large number
of other multimetallic systems catalyzing the same reaction have been studied.
Some examples are given in Table 1. The investigations performed with this
type of catalyst demonstrate that not only multimetallic complexes can show

Table 1. Examples of multimetallic catalyst systems used to catalyze olefin hydroformylation

reactions.
Multimetallic catalyst system Ref.
764 3.1 Development of Methods

synergistic behavior but also they can generate a more effective reaction space in
comparison with monometallic systems, e. g., making hydrogen transfer processes
much faster. The use of these complex-structured homogeneous catalysts, how-
ever, can be very difficult or even impractical since the recovery of the different
components of the catalysts in question can lead to severe problems.

3.1.5.2 Advantages in the Use of Multicomponent

or Multifunctional Catalysts
Even though monofunctional “contacts” work very sucessfully in the chemical in-
dustry (see, e. g., [4]), this type of catalyst shows a general disadvantage since it
cannot shift a thermodynamic equilibrium state to obtain a higher yield. As a con-
sequence, in a thermodynamically controlled reaction the educt utilization can be
relatively low, even if an active catalyst is used.
Discussing this problem and taking the synthesis of methanol and of subse-
quent steps as an example for a monofunctional catalyst, this species is produced
from a mixture of CO and H2 at about 250 “C and about 10 MPa, using a mixture
of CuO, ZnO, and A1203 sintered together as the catalyst. Since the maximum
yield obtained under these conditions is limited by the value of the chemical equi-
librium constant, the educt gas content in the effluent gas is relatively high. To
obtain sufficient utilization of the syngas, H2 and CO must be recycled after the
separation process. Since such a procedure is not only cumbersome but also ex-
pensive, different techniques have been proposed in the open literature to avoid
this disadvantage [5-81.
If methanol can be considered to be the intermediate in a multistep reaction to
form a final species, e.g., gasoline as in the Mobil MTG process [4], then a bi-
functional catalyst ought markedly to increase the utilization of the syngas.
Since in the MTG process dimethyl ether (DME) is a key intermediate, Sofianos
et al. [9] proposed for this purpose a bifunctional catalyst, prepared by intimate
mixing of finely milled samples of the methanol catalyst and of y-alumina, the
acid catalyst which dehydrates methanol to DME. The results obtained show
that the CO conversion using the bifunctional catalyst is nearly four times higher
than that obtained with the monofunctional catalyst.
In order to avoid problems as with diffusion control [lo] a criterion for an op-
timal use of both catalysts is useful. As was shown by Weisz in his pioneering
paper on polyfunctional heterogeneous catalysts [ 111, diffusional transport inhibi-
tion does not influence the formation of the final product if the intimacy criterion
(eq. (1)) holds.

In this equation, r is the reaction rate of DME formation, denotes the

equilibrium concentration of methanol, DMeoH is the methanol diffusion coeffi-
cient, and R is the mean distance between different catalytic sites. If the rate con-
 3.1.5.2 Advantages in the Use of Multicomponent or Multifunctional Catalysts 765

stant of the second reaction is high, as in the given example, the intimacy of the
different sites according to eq. (1) must be high in order to guarantee their co-
operative action, i.e., the nonlinear superposition of the single actions. To be
sure that this behavior is obtained in a given reaction system, it is necessary to
link the two sites together. The resulting catalyst is called a multifunctional
catalyst. In those cases where both sites only have loose contact, as in a simple
mixture of the different catalysts, we speak of a multicomponent catalyst.
These definitions, similar to those given by Kirschner and Bisswanger [12] to
classify the different types of enzyme systems, were already used by Weisz [I13
and by Bowes [13], while Schuit and Gates [14] are of the opinion that, ultimately,
each catalyst of practical importance must be multifunctional.
In this discussion, it has been tacitly assumed that the reaction rates in question
follow first-order kinetics. To have cooperative action in this case, it is sufficient
that the intermediate passes fast enough from one site to the other. The situation,
however, becomes much more complicated for reactions proceeding according to
bimolecular kinetics. In that case, the concentrations of the two educt components
have to be kept high in the vicinity of a catalyticallyactive site. Following nature
(see [ l]), this possibility can be achieved by an optimal microenvironment of the
active sites in question.
Realizations of such microcompartments are obtained in normal heterogeneous
catalysis by using zeolite crystals as support material, e. g., in the formation of are-
nes from cycloparaffins by use of Y-zeolite crystals as catalysts [ 151 or the hydro-
isomerization of light paraffins by Pt-doped Y-zeolite [ 161. Concentration effects,
resembling channeling in enzyme-catalyzed reactions, are caused by the hindrance
of the transport of larger molecules through the apertures between the cavities
which form the three-dimensional pore texture of zeolite crystals.
This transport restriction by configurational diffusion, however, has additional
consequences. On one hand, it is one of the bases for shape-selective catalysis,
while a second is provided by the steric restrictions which operate during the for-
mation of the transition-state complex within the zeolite cages. On the other hand,
a slow release of the products from the reaction space can favor possible undesired
side reactions [ 151. Similar problems have already been discussed in the investi-
gations of Slaugh et al. [ 171 on batch hydroisomerization of benzene to phenylcy-
clohexane using different transition metals as hydrogenation sites and different
supports as the acid component of a dual-site catalyst. In order to maximize the
yield of the target product (phenylcyclohexane) the authors proposed limiting
the conversion of benzene since, as may be expected, the yield of the side prod-
ucts increases with increasing reaction time.
As a result of this discussion it has to be concluded that the preparation of use-
ful multicomponentas well as multifunctional catalysts requires, first of all, highly
selective catalytic sites which reach their optimal activity at nearly the same tem-
peratures. Since, already, this requirement can hardly to be met with the usual het-
erogeneous contacts, multifunctional catalysts are best prepared as homogeneous
catalysts, e. g., with transition metal complexes. Being well-defined chemical spe-
cies, they can be tailor-made for a given reaction. Experience shows that these
compounds accelerate the reaction by opening a relatively complex catalytic
766 3.1 Development of Methods

cycle wherein several intermediates exist in the medium as true molecules for a
certain lifetime. Since these intermediates can react with other components present
in the reaction mixture, the catalytic properties (activity, selectivity, stability) of
the system can be changed by each additional component.
An example is the hydroformylation reaction of cyclohexene catalyzed by the
unsaturated compound HCo(CO), which is formed under reaction conditions from
the precursor HCO(CO)~. Following the usual mechanism (see, e. g., [ 18]), the
catalytic cycle is depicted in Scheme 1. Since the oxidative addition of H2 to
the acylcobalt complex is the rate-determining step in this case the rate equation
follows eq. (2) (cf. Section 2.1.1):
ri = ~ I L H ~ P H ~ * C ~ (2)

wherein k , is the rate constant, LH2denotes the solubility constant of hydrogen in

the reaction medium, pH,is the hydrogen partial pressure, and c3 stands for the
concentration of complex @ in Scheme 1. Assuming the remaining reaction
steps to be in chemical equilibrium the kinetic expression given in eq. (3) is valid.

In this equation the K parameters denote the equilibrium constants, c, is the

concentration of cyclohexene, and cg denotes the chosen precursor concentration.

HCO(CO)4

n
KO
i -CO

H2 K3

I
0

co
Scheme 1. Catalytic cycle of the cobalt-catalyzed cyclohexene hydroformylation reaction.
 3.1.5.2 Advantages in the Use of Multicomponent or Multifunctional Catalysts 161

Lco stands for the solubility constant of CO and pco is its partial pressure. In
deriving eq. (3) it can be assumed that the relation
c1 + c3 <<cp (4)

holds.
A similar rate expression was first obtained by Natta et al. [19]. The problem
with this system, however, is that the yield after 4 h reaction time is only 14%
at 110 "C with pH,= pco = 40 MPa and tetrahydrofuran as the solvent[20]. In
order to obtain a-higher yield, Hidai et al. [20] added a certain amount of
Ru3(CO), to the cobalt carbonyl-containing reaction system. Although the hydro-
formylation activity of this carbonyl compound is relatively low (cf. Section
2.1.1.2. l), about one-third of that with the cobalt complex, the authors observed
a marked increase of the initial reaction rate with increasing ruthenium content.
They suggested that the ruthenium species opens an additional route for forming
the final C-H bond. Thus, it is to be expected that there is a second reaction rate,
r2, which can be given by eq. ( 5 ) :
r2 = ~ Z L H ~ P H ~c3
CRU (5)

For the total rate rT of aldehyde formation eq. ( 6 ) is valid:

Plotting the value of the quotient r2/r1versus the number, nRu,of Ru atoms
added to the reaction medium (see Figure l), it is found that this relation is linear
only for small nRuvalues. It is supposed that for higher ruthenium concentrations
additional reactions between the Ru species and other components in the reaction
mixture take place. Detailed information is not available.
The synergistic effect described can also be used to increase the selectivity of
a catalytic system. Hydroformylating norbornene instead of cyclohexene, cataly-
tic cycles operate according to Scheme 2 [21]. In this case, besides the aldehyde,
a lactone is formed in a side reaction. Adding the Ru species Ru3(C0),*to the
system increases not only the norbornene conversion but also the selectivity of
the system to aldehydes. For a fixed number of cobalt atoms, the norbornene
conversion as well as the aldehyde selectivity of the system is plotted as a func-
tion of the quotient n R u / ~ cino Figure 2. In this case, too, the synergistic effect is
pronounced for the addition of small amounts of the bifunctional Ru species
only.
Another example for such a synergistic effect is described by Tucci [22],
showing that the reaction rate and the selectivity can be adjusted independently
by adding a co-catalyst. Tucci investigated the hydroformylation activity of car-
bonyls of Cr, Mo, and W, and found that both their activity and their selectivity
were too low for practical purposes (cf. Section 2.1.1.1). Since it is well known
(see, e.g., [18]) that the selectivity of 0x0 catalysts for linear products can be
768 3.1 Development of Methods

nRu brnol1

Figure 1. Enhancement of the reaction rate of the cobalt-catalyzed cyclohexene

hydroformylation by addition of R u ~ ( C O )(data
, ~ from [20]).

increased by using bulkier ligands than CO, Tucci displaced one CO molecule
by the trialkylphosphine group PBu3. Comparing the yield from hydroformyla-
ting 1-hexene with Mo(CO)~and with that using the catalyst MO(CO)~(PBU~)
under the same reaction conditions, the selectivity increased from 0.56 to
0.83, while the catalyst activity remained constantly low (olefin conversion:
0.53). If, however, a small amount (3.6 X mol) of the catalyst HCo-
(CO),(PBu,) was added which had a high hydroformylation activity but a low
selectivity for linear products, the selectivity of the system stayed unchanged
while the activity increased to give a yield of 0.84. In order to explain this
synergistic effect, Tucci assumed that the Co species functions as a hydrogen-
transfer catalyst for the Mo catalyst (eq. (7)).
+ 2 HCO(CO)~(PBU~)G==
2 Mo(CO)~(PBU~)
+ CO~(CO)~(PBU&+ 2 CO
2 HMo(CO)~(PBU~)
(7)

This reaction thus raises the concentration of the active hydroformy lation
catalyst HMo(CO)~(PBU~), which has a higher selectivity than the cobalt catalyst.
Although these examples demonstrate a positive interaction between different
mobile, catalytically active components in the reaction medium, it must be as-
sumed that the situation will not always be so optimal for more complex systems,
since catalysts are coordinatively unsaturated. This is one reason why investiga-
tions on one-pot reaction sequences nearly always deal with heterogenized homo-
 3.1.5.2 Advantages in the Use of Multicomponent or Multifunctional Catalysts 769

Scheme 2. Catalytic cycle of the hydroformylation of norbornene (according to [21]).

0,1 -
I I I I I

Figure 2. Conversion and selectivity of the norbornene hydroformylation as a

function of the Ru content of the system (data from [21]).
770 3.1 Development of Methods

(PPh3)3Ru(H)CI

ArCOCl
I - HCI

(PPh3)3Ru (PPh3)3Ru(CI)(COAr)(q2-H2)

ArCOOCH2Ar (PPh3)3Ru(H)COAr
ArCHO

(PPh3)3Ru(OCH2Ar)COAr

Scheme 3. Catalytic cycles for the complex-catalyzed sequential Rosenmund-Tishchenko

reactions.

geneous catalysts. One exception is the system described by Grushin and Alper
[23] concerning the performance of sequential Rosenmund-Tishchenko reactions.
In that case, a special situation makes possible the synthesis of esters from acid
chlorides and hydrogen in a one-pot reaction by using (Ph3P)3Ru(H)C1as the cata-
lyst. As can be seen by the catalytic cycles of the two different reactions depicted
in Scheme 3, this example is indeed an exception, since both cycles can work
together optimally.
The situation is much more complex, however, if it is desired to perform the
reaction sequence given in eqs. (8)-(10) in a one-pot reaction.
 3.1.5.2 Advantages in the Use of Multicomponent or Multijhnctional Catalysts 77 1

(10)

This so-called Aldox process, commercially performed by Shell as well as

by Exxon [4, 351, is realized in a one-pot reaction by adding Ni and KOH
as co-catalysts to the medium of the “Co”-catalyzed 0x0 reaction (cf. Section
2.1.1).
Since one of the requirements of homogeneous catalysts, especially those con-
taining rhodium, is an effective strategy for catalyst recovery, methods for the
heterogenization of homogeneous catalysts have been discussed for several
years (e. g., Section 3.1.1.3 [24-271). According to one technique, supported
solid-phase catalysts (SSPCs) are built from a polymer matrix as the support,
phosphine groups as spacers, and a multifunctional catalyst for the aforemen-
tioned reaction, by using Rh groups to accelerate the 0x0 reaction as well as
the hydrogenation reactions, and amine groups to catalyze the aldol condensation
[28]. In a number of batch experiments 2-ethylhexanal was, indeed, produced.
The final hydrogenation step, i.e., the production of 2-ethylhexanol, does not
take place with this catalyst system, however. Comparing the results obtained
with the multifunctional catalyst with those observed with a mixture of SSPCs
containing only one catalytically active component, Batchelder et al. found that
the rate constants of all the reactions were much higher (by a factor of 4.5 for
hydroformy lation, 15 for condensation, and 32 for hydrogenation) with the multi-
functional system. Obviously, transport effects supported by swelling effects in
the flexible structure of the polymer matrix cause these remarkable differences.
Since this structural change depends on the polar character of the reactants, the
alteration of the microenvironment of the co-immobilized active sites do not
necessarily lead to synergistic effects. Nevertheless, the observation that swelling
effects can influence the properties of SSPCs opens an additional possibility for
adjusting transport restrictions for selected reactants, a situation which is compar-
able with that in zeolites.
Another surprising result of these investigations is that practically no propene
hydrogenation was observed, although hydrogenation of the condensation prod-
uct, even if incomplete, took place. As an explanation of this finding, the authors
refer to the fact that under hydroformy lation conditions carbon-carbon double
bonds conjugated with carbonyl groups are much easier to hydrogenate than
those in unactivated olefins (see, e. g., [IS]).
Finally it must be pointed out that the aldol condensation reaction is reversible;
thus, in a one-pot reaction the yield for this reaction step is increased by perma-
nently removing the condensation product. Since the immobilized catalyst system
permits a continuous process, all advantages of a heterogenized multifunctional
catalyst system can be utilized with the catalyst described.
772 3.1 Development of Methods

3.1.5.3 Problems in the Use of Multifunctional

or Multicomponent Catalysts
Pittman et al. [29] described the simultaneous aldol condensation and the hydro-
genation of the condensation product in a one-pot process with a perfluorinated
aliphatic ether polymer with pendant sulfonic acid groups as the acid catalyst
and Pd as the hydrogenation catalyst. Talung acetone and hydrogen as the
educt components the aim was to obtain 4-methyl-2-pentanone for given reaction
conditions.
The results obtained, however, show that the selectivity was relatively poor
since the condensation of the acetone proceeds at practically the same rate as
its hydrogenation. To reduce this competitive reaction Pd was substituted by
RhCl(PPh& as the hydrogenation catalyst. Since this catalyst has a lower activity
in comparison with Pd, the selectivity of the system increased while the yield of
the product decreased by a factor of three. In addition, high-boiling products were
obtained with the less active Rh catalyst. Since the Rh complex is not able to re-
move the condensation product, mesityl oxide, sufficiently fast from the reaction
medium, this intermediate undergoes further condensations leading to the ob-
served species. Again, this example demonstrates that it is very important to adjust
the rates of the necessary reaction steps very carefully in order to obtain a useful
one-pot reaction system.
There are, however, additional problems, which became apparent when Pittman
et al. [30] discussed one-pot cyclooligomerization and hydrogenation using the
complexes (PPh&Ni(CO)* and (PPh&RhCI co-immobilized with a crosslinked
polymer. For example, taking butadiene and hydrogen as the educt components
gives the reaction sequence (eqs. (11) and (12)):

Besides this, other intermediates, e. g., 4-vinylcyclohexene, may be formed.

Although this is a disadvantage in this case, too, the main problem with this
system is that the Ni complex decomposes in the presence of hydrogen.
To circumvent this as well as other difficulties, Pittman et al. [30] proposed a
different technique. Accordingly the reactions should not take place simul-
taneously but sequentially. Since this concept loses the main advantages
connected with the use of multifunctional catalysts, Gronewold et al. [31-331
proposed a different strategy for avoiding the fast deactivation of one type of
catalytically active site of a multifunctional catalyst. This starts with the prepara-
tion of the heterogenized multifunctional homogeneous catalyst by using different
 3.1.5.4 Conclusions 773

heterogenization techniques. In order to explain this in more detail, the reactions

in eqs. (13) and (14) are assumed to proceed simultaneously in a one-pot reaction
system:

While the ethylene dimerization reaction can be catalyzed by RhC13, the

sequential hydroformy lation reaction can be accelerated by the Rh complex
(PPh,),RhH(CO). This reaction system was heterogenized on porous y-A1203.
The dimerization catalyst was directly bound to the alumina surface by adsorption
forces, but the Rh complex was dissolved first in dimethylglycol phthalate. This
solution was then used to impregnate the RhC13-loadedsupport material. The mul-
tifunctional catalyst obtained thus combines a supported solid-phase catalyst
(SSPC) and a supported liquid-phase contact (SLPC). Although the pure dimeri-
zation SSPC deactivates very rapidly in the presence of CO under the given reac-
tion conditions, it is able to work in the multifunctional catalyst which, after an
induction period, produced valeraldehyde for several hours. One reason for this
higher stability is that CO and H2 are both only slightly soluble in dimethylglycol
phthalate while ethylene, the educt for the dimerization reaction, is easily dis-
solved in the phthalate phase. Since, in addition, the hydroformylation reaction
consumes H2 and CO in this phase, the dimerization catalyst is indeed protected
from poisoning. If the temperature of the reaction system is decreased, the hydro-
formylation reaction rate decreases while the rate of the dimerization reaction is
only slightly influenced by the temperature change. In addition, investigations
performed by Richers [34] gave more insight.

3.1.5.4 Conclusions
Useful multicomponent catalyst systems as well as multifunctional catalysts both
offer new possibilities for the performance of catalytic processes; this potential,
however, can hardly be used as yet. One of the reasons for this difficulty stems
from the fact that the preparation of such catalytic systems requires highly selec-
tive as well as sufficiently active catalytic components which, in addition, all reach
their optimal catalytic properties for the same reaction conditions. This demand
can be fulfilled by the use of tailor-made, catalytically active, transition metal
complexes. The problem, however, is that these catalysts normally work via a re-
latively complex catalytic cycle. In a one-pot reaction system, therefore, a large
number of different chemical species must be expected. Such a complex structured
system can lead to several problems since it cannot be assumed that in a homoge-
neously catalyzed reaction system all components do not negatively interact. Even
if a sufficiently stable catalyst system can be found by applying one or more of the
different heterogenization techniques, this type of problem is hard to solve be-
114 3.1 Development of Methods

cause of a fundamental difficulty: in order to obtain an optimal catalytically active

species of the type in question, it must be coordinatively unsaturated and show a
certain mobility in order to optimize the catalytic cycle for all components.
Finally, in such a heterogenization procedure for homogeneous catalysts, it can
become necessary to synthesize special polymer matrices as support material in
order to help the system to amplify a synergistic effect by the channeling of inter-
mediates from one active site to another.
Since each of the demands mentioned here is relatively restrictive, it seems that
the practical use of multicomponent as well as multifunctional catalysts will be
more or less an exception, and not the rule, in the near future.

References
[ I ] P. Friedrich in Organized Multienzyme Systems: Catalytic Properties (Ed.: G. R. Welch),
Academic Press, New York, 1985, p. 141.
[2] J. Picard in Organized Multienzyme Systems: Catalytic Properties (Ed.: G. R. Welch),
Academic Press, New York, 1985, p. 177.
[3] (a) I. Schwager, J. F. Knifton, J. Catal. 1976, 45, 256; (b) Eastman Kodak Company,
(J. L. Cooper), US 4.388.477, (1983); (c) M. Hidai, H. Matsuzaka, Polyhedron 1988,
22/23, 2369; (d) R. K. Menon, Ph.D. Thesis, Rutgers University, The State University
of Jersey, New Brunswick, 1986; (e) H. Marakchi, M. Haimeur, P. Escalant, J. Lieto,
J. P. Aune, New J. Chem. 1986, 10, 159; (f) P. Kalck, Polyhedron 1988, 22/23, 2441;
(8) B. L. Moroz, I. L. Mudrakovskii, V. A. Rogov, V. A. Likholobov, 9th Int. Symp.
on Homogeneous Catalysis, Jerusalem, 1994, Abstracts, p. 346; (h) W. R. Jackson,
R. S. Dickson, T. De Simone, E. M. Campi, G. D. Fallon, ibid., p. 166; (i) A. M.
Trzeciak, J. J. Ziolkowski, ibid., p. 176.
[4] K. Weissermel, H.-J. Arpe, Industrial Organic Chemistry, VCH, Weinheim, 1993.
[5] D. W. Agar, W. Ruppel, Chem.-Ing. Techn. 1988, 60, 731.
[6] K. R. Westerterp, Chem. Eng. Sci. 1992, 47, 2195.
[7] K. R. Westerterp, M. Kuczynski, Chem. Eng. Sci. 1987,42, 1871.
[8] M. Kuczynski, M. H. Oyevaar, R. T. Pieters, K. R. Westerterp, Chem. Eng. Sci. 1987,
42, 1887.
[9] A. C. Sofianos, M. S. Scurell, Ind. Eng. Chem. Res. 1991, 30, 2372.
[lo] M. Gogate, S. Lee, C. J. Kulic, Fuel Sci. Technol. Int. 1991, 9, 653.
[ I l l P. B. Weisz, Catal. 1962, 13, 137.
[12] K. Kirschner, B. Bisswanger, Annu. Rev. Biochem. 1976, 45, 143.
[I31 E. Bowes in Catalyst Support and Supported Catalysts: Theoretical and Applied
Concepts (Ed.: A. B. Stiles), Butterworth, London, 1987, p. 249.
[I41 G. C. A. Schuit, B. C. Gates, CHEMTECH 1983, 536, 693.
[15] B. C. Gates, Catalytic Chemistry, John Wiley, New York, 1992.
[I61 F. Chevalier, M. Guisnet, R. Maurel, Proc. Int. Congr. Catal. (6th, 1976) 1977, 1, 478.
[I71 L. H. Slaugh, J. A. Leonard, J. Catal. 1969, 13, 385.
[I81 A. J. Pearson, Metallo-organic Chemistry, John Wiley, New York, 1985.
[I91 G. Natta, Brennst.-Chem. 1955, 36, 176.
[20] M. Hidai, A. Fukuoka, Y. Koyasu, Y. Ushida, J. Chem. Soc., Chem. Commun. 1984, 516.
[21] Y. Ishii, M. Sato, H. Matsuzaka, M. Hidai, J. Mol. Catal. 1989, 54, L13.
[22] E. R. Tucci, Ind. Eng. Chem., Prod. Res. Dev. 1985, 24, 38.
[23] V. V. Grushin, H. Alper, J. Org. Chem. 1991, 56, 5159.
 3.1.6.2 History 775

[24] L. L. Murrell in Advanced Material in Catalysis (Eds.: J. J. Burton, R. L. Garden),

Academic Press, London, 1977, p. 236.
[25] Y. Iwasawa (Ed.), Tailored Metal Catalysts, Reidel, Dordrecht, 1986.
[26] P. R. Rony, Chem. Eng. Sci. 1968, 23, 1021.
[27] M. Hoffmeister, D. Hesse, Chem. Eng. Sci. 1990, 45, 2575.
[28] R. F. Batchelder, B. C. Gates, F. P. J. Kuijpers, Proc. Int. Congr. Catul. (6th, 1976) 1977,
9, 499.
[29] C. U. Pittman, Y. F. Liang, J. Org. Chem. 1980, 45, 5048.
[30] C . U. Pittman, L. R. Smith, J. Am. Chern. Soc. 1975, 97, 1749.
[31] B. Gronewold, Ph. D. Thesis, Technical University of Hannover, Germany 1993.
[32] B. Gronewold, D. Hesse, Hung. J. Ind. Chem. 1991, 19, 259.
[33] B. Gronewold, D. Hesse, Chem.-@.-Tech. 1993, 65, 1239.
[34] U. Richers, Diploma Thesis, Technical University of Hannover, Germany 1988.
[35] B. Cornils in New Syntheses with Carbon Monoxide (Ed.: J. Falbe), Springer, Berlin
1980, p. 145f.

3.1.6 Catalytic Carbon-Carbon Coupling

by Palladium Complexes: Heck Reactions
Wolfgang A. Herrmann

3.1.6.1 Introduction
Palladium is one of the most versatile and efficient catalyst metals in organic
synthesis, be it in elemental forms (palladium black and palladium colloids in
heterogeneous hydrogenation) or as palladium salts and complexes (e.g., PdC12
in the Wacker-Hoechst synthesis of acetaldehyde; cf. Section 2.4.1) [ l ,21. Both
the renaissance of organometallic chemistry in the 1960s and the subsequent
breakthrough of homogeneous organometallic catalysis in laboratory-scale and
industrial syntheses have received a major stimulus from palladium coordination
chemistry. Smidt and Hafner [3,4], Heck [5], Stille [6], and Trost [7] represent the
large group of researchers who developed organopalladium catalysis since 1960
[8, 91. n-Ally1 complexes, cr-alkylpalladium(I1) complexes, and palladium(0)
phosphine complexes are, in short, the key intermediates in catalytic C-C-bond
forming reactions. In many cases, the reversible redox process Pdo G Pd" +
2e- is of pivotal mechanistic importance.

3.1.6.2 History
It had been known from the work of Heck and Tsuji that certain organopalla-
dium(I1) species convert olefins into vinylic C-C-coupling products, with the active
species being generated in situ from organomercurials and common palladium(I1)
salts [lo]. The need for stoichiometric reagents, however, did not attract much
interest from organic chemists. It was only the discovery that direct oxidative addi-
776 3.1 Development of Methods

tion of organic halides RX also yields compounds of type RPd[P(C6H5)&X (X =

halide), thus avoiding the use of (toxic) organomercurials or other transmetallation
reagents (e. g., RMgX) [ 111, that Pd-mediated C-C-coupling became common. The
final, important step of “going catalytic” was set by Mizoroki and Heck, who in-
dependently discovered that vinylations according to eqs. (1) and (2) - now called
“Heck olefination” or simply “Heck reaction” - work with catalytic amounts of
certain palladium complexes. The presence of a base (e. g., organic amine) is ne-
cessary to bind the hydrogen halide HX formed during C-C-coupling [12, 131.
X

aryl halides styrenes

P R +, B +!?!
‘ 4 +~ RR
-, + [HBIX (2)
vinyl halides dienes

X = I, Br, N2BF4,C(=O)CI, CF3SO3 B = base: NR3, K2CO3, NaOAc

[Pd] = Pdo-phosphinecomplexes (see text)

3.1.6.3 Definition
The term “Heck reaction” summarizes catalytic C-C-coupling processes, such that
a vinylic hydrogen is replaced by a vinyl, aryl, or benzyl group, with the latter
being introduced from a halide or related precursor compound (cf. eq. (3)) [9 a,
14-16]. Therefore, the final step of product formation is the elimination of a hy-
drogen halide, and a base is thus required to bind the acid. The olefinic (vinylic)
double bond is retained throughout the Heck reaction. Palladium is practically the
only catalyst metal used, in the form of certain Pdo and Pd” salts or complexes;
normally 1-5 mol % of catalyst is administered.

--
R-X
6+ 6-
+
H
)=< cat._
R
)=< + H-X (3)
vinylic component
Vinyl-
Avl-
Benzyl-
] component, x = anionic leaving group

RX also represents aryldiazonium salts [23 a, b], aryl triflates [25, 261, and
hypervalent iodo compounds [71]. 1,3-Dienes and styrenes are the common
constitutional types to result. In light of the enormous synthetic potential
[9 a, 161, the Heck reaction is not treated properly in current textbooks and mono-
graphs [9 d, el, in which occasionally it is even ignored [9 g-i].
 3.1.6.4 Catalysts and Reaction Conditions 177

3.1.6.4 Catalysts and Reaction Conditions

Typical catalysts are Pdo-phosphine complexes, e. g., Pd[P(C6Hs)3]4,or in situ
catalysts such as P d ( 0 A ~ ) ~ P(C6Hs)3,
ln with n = 2...4 (OAc = acetate). Heck
and Spencer noticed that phosphines are necessary to somehow “stabilize” the
catalysts. Amines (e.g., N(C,H,),) are the most common bases but K2C03,
NaHC03, and NaOAc are also applied. The most frequently used catalyst is an
in situ combination of Pd(OAc):, and P(C6H&.
Heck reactions are conducted in polar aprotic, c-donor-type solvents such as
acetonitrile, dimethyl sulfoxide, or dimethylacetamide. Reaction temperatures
and times largely depend on the nature of the organic halide to be activated
and on the catalyst’s stability limit. Iodo derivatives are much more reactive
(<lo0 “C), so auxiliary (phosphine) ligands are not necessary here. Polar
solvents such as DMF, DMAc, and N-methylpyrrolidone (NMP) in combi-
nation with NaOAc as base are specifically beneficial in all cases, and even
mild phase-transfer conditions in a solid/solution system employing P ~ ( O A C ) ~
(without phosphine co-ligands), [N(n-C,H&]X in DMF (X = C1, Br), and
K2C03 as base (“Jeffery conditions”) [17, 181.
Both polymer-supported (immobilized) catalysts [ 191 and two-phase reactions
(water-soluble phosphine co-ligands) were described for aryl iodides only [20].
However, aryl iodides are not attractive starting materials for large-scale industrial
applications.
The latest catalyst developments have been focused on the activation of aryl
bromides and aryl chlorides. This problem has been solved by the design of ther-
mally stable catalysts like palladacycles 1-3 [52, 53, 771 as well as N-heterocyclic
carbene complexes of Pd (cf. 4 6 ; cf. Section 3.1.10) [60-621. There has been
much research activity in this field [63-66, 841.

1 2 (dimeric) 3
R = eTol, Mes, t-Bu, Cy, eXylyl

f@NNcH3
I

4 5 6
778 3.1 Development of Methods

The latter catalyst motif was also used to prepare highly active immo-
bilized, recyclable catalysts for the Heck reactions [73]. In an alternative
approach, PdC12 and [PPh,]Cl were proven as thermally stable catalyst sys-
tems [74]. Sterically demanding phosphites were used as in situ ligands in
high excess over Pd for thermally stable systems [75]. Recently, sterically de-
manding alkylphosphines were identified as highly activating ligands in com-
bination with a Pdo source like Pd2(dba)3. In particular, tri-tert-butylphosphane
and ferrocenyldi-tert-butylphosphane are especially good examples of this type
~761.
The modification of the reaction conditions, rather than the design of novel cat-
alysts, was also shown to supply highly active and thermally stable systems for the
activation of aryl bromides and aryl chlorides [77]. Mechanistic investigations
clarified the details [78].

3.1.6.5 Scope and Limitations

Both intra- and (more commonly) intermolecular Heck reactions have been re-
ported. Note that organic halides with P-hydrogen atoms cannot be used because
they would form olefins at Pd”. Electron-poor, monosubstituted olefins are more
reactive than electron-rich, disubstituted or cyclic olefins. Many functional groups
are compatible with Heck conditions [16], providing a means of synthesizing
carbo- and heterocyclic compounds (e.q. (4), C-C-double bond isomerization
included) [21] comprising natural products [22].

(4)

Me Me

Although aryl and vinyl halides have found vast applications in Heck coupling,
aromatic diazonium salts, particularly the isolable tetrafluoroborates, proved
successful in the work of Kikukawa et al. [23 a, b] and a one-pot reaction with
the C-C-coupling step [23 c-el. Extensions of this “tandem diazotation Heck
reaction” technique were reported by Beller et al. (eq. ( 5 ) ) [23 fl, including hete-
rogeneous Pdkarbon catalysts [23 g].

1.1 equiv. t-BuONO

. .. - 3H2
0.05 equiv. Pd(OAc)z
(5)
20 - 30 “C
d’ CH3COzH I CHzClz R
64 - 72 Yo
R = CH3,OCH3, CI, F
 3.1.6.5 Scope and Limitations 779

Blaser and Spencer used aroyl halides in place of aryl halides, with aroyl
chlorides being of specific interest as ubiquitous, relatively cheap compounds
("Blaser reaction") [24]. This latter reaction is normally conducted in aromatic
solvents; phosphines are not used here as catalyst ligands since they fully inhibit
the reaction. In the same way, benzoic acid anhydrides can be used as the aryl
source in combination with PdC12 and catalytic amounts of NaBr [79]. In this
reaction, one of the arenes is used in the coupling reaction by elimination of
CO, whereas the other benzoate serves as the base. The benzoic acid thus
formed can easily be recycled into the anhydride. The use of aryl and vinyl
triflates according to Cacchi [25] and Stille [26] extends the scope of the
Heck coupling to carbonyl compounds; phenol derivatives act via triflate func-
tionalization as synthetic equivalents of the aryl halides. The arylation of cyclic
alkenes [27], electron-rich vinyl ethers [28], and allylic alcohols [29] is acces-
sible through Heck reactions. Allylic alcohols yield C-C-saturated carbonyl
compounds (aldehydes) for mechanistic reasons @-H elimination), as exem-
plified in eq. (6).
r

- IPhToHl
1

Ph-l + -OH
pdLz
NEt3 I-PdLp

I
H-PdLI J - "PdL2'
- [HNEt

Heitz et al. introduced the Heck methodology into polymer chemistry [30,
3 11. Thus poly( 1,4-phenylene vinylene), a polymeric material of low molecular
weight (M, = 5000-10 000) and with all-trans configuration, was made from
(optionally substituted, R') 1,4-dibromobenzene and ethylene (eq. (7); cf. Sec-
tion 3.3.10.1).

Pd(0Ac)p
P(C-TOI)~
NEtB / DMF
R.
(7)

(subst.) poly(l,4-phenylene vinylene)

The excellent regio- and stereoselectivity of the Heck C-C-coupling has

the potential of enantioselective reactions [32]. Hayashi and Ozawa reported
the first case of decent optical induction (eq. (8)): (R)-2-aryl-2,3-dihydro-
furanes were thus obtained from the triflate precursors in 96% ee at
42-66% conversion in benzene when (R)-BINAP was used as chiral auxili-
ary [33]. C-C double bond migration occurs under the given reaction condi-
tions.
780 3.1 Development of Methods

3 mol-% Pd(0Acb

0 0(+
6 mol-% (R):BINiP
"proton sponge" (*)
ArOTf + * Ar A r S ' " 8 )
0 0 (8)
(*) 1,8-bis(dimethyIamino)naphthalene (R)-1 (q-2

Intramolecular Heck coupling of good enantioselectivity is also known [34].

Products exhibiting quaternary benzylic centers of asymmetry give particularly
good enantiomeric enrichment (eq. (9)).
,OR

OR Pd(0)-(S)-BINAP Me0
PMB I DMAc, 100 "C
0 (9)
conv. 95 %
I I
Me Me

Heck reactions are compatible with water (see Chapter 3.2.4) [35], which
increases the speed of reaction in the presence of quaternary ammonium salts
136 a]. It is not surprising, then, that aqueous solvents (e.g. CH3CN/H20) and
water-soluble catalysts such as Pd(TPPTS), where TPPTS = P(C,H,-m-SO,Na),
[35, 671 can be employed successfully (eq. (10)). However, only aryl and vinyl
iodides and aromatic diazonium salts (generated in situ from arylamines in
aqueous media) are, up to the present, accessible to this method [36 b-h].
! 2.5 rnol-% Pd(OAc)*

h 5 rnol-% TPPTS
NEt3 I CH3CN I H20
(10)
H2N 98%

Aryl and vinyl chlorides are most reluctant to undergo Pd-catalyzed activation.
Heck reactivity - as expected from the C-X bond dissociation energies (Figure 1)
- increases in the order C1 < < Br < I, with fluorides being completely unreac-
tive with any of the known catalysts [37].
The activation of chlorohydrocarbons is of major industrial interest 11, 9 h,
38 b]. Bozell et al. [68] tried it with NiPd catalysts. Milstein and co-workers
optimized the phosphine ligands [411: chelating trialkylphosphines, specifically
bis(diisopropy1phosphino)-propane (dippp) and -butane (dippb), were successful,
with the details depending on a number of factors (base, addition of zinc).
However, good results were only reported for styrenes (eq. (1 I)), while
electron-poor olefins such as acrylates suffer from nucleophilic attack by these
pronouncedly basic phosphines (leading to dimers of the olefins), and the air-
sensitivity of the latter constitutes a further drawback. Basic phosphines
yield dimers and oligomers of olefins, without any metal necessarily present
(cf. Section 3.1.6.8).
 3.1.6.5 Scope and Limitations 781

D (Ar-X) 140
kcalimol
at 298 K 126
I

96

01

65

40

20

I O F -CI -Br -I

Figure 1. Homolytic C-X bond dissociation energies (X = F, C1, Br, I) of aryl halides
(data taken from Ref. [38 b]). 1 kcal mol-' = 4184 kJ mol-'.

1 rnol-% Pd(OAc)2
2 rnol-% dippb

@, +
NaOAc I DMF I 1 5 0 C
",

The concept of electron-rich Pdo catalysts is based on the analogy between nu-
cleophilic aromatic substitution (eq. (12a)) and Pdoinsertion (cf. eq. (12b)) [42 c, d].
It had previously been applied in the carbonylation of aryl chlorides [38 a, b]. Re-
lated work by Milstein [42] and Basset [43] should be consulted. High-pressure
conditions seem to enhance the aryl chloride reactivity, too [44]. Meanwhile, var-
ious other methods have been developed for the selective activation of aryl chlor-
ides with defined Pd complexes as well as in situ systems (cf. Section 3.1.6.4).
182 3.1 Development of Methods

The intramolecular version has become a useful method of constructing hetero-

cyclic compounds, especially as the mild “Jeffery conditions” which suffice to
achieve such coupling reactions of some aryl and vinyl bromides or iodides
(eq. (13); L = P(C6H&) [16 cl.

Additional reactions may occur in constitutionally favourable cases (“domino

reactions”): for example, 2-quinolones result from an ordinary Heck coupling,
followed by a cyclization step due to nucleophilic attack of the amine at a car-
boxylic group (eq. (14)) [ 14el. Bicyclic nitrogen heterocycles were reported by
Buchwald [45]. For a comprehensive review of applications, the reader is referred
to the article by de Meijere and Meyer [ 16 a].

3.1.6.6 Mechanism
Generally accepted and taken for granted by all textbooks [9, 15, 16, 461, the me-
chanism of the Heck C-C-coupling according to Figure 2 starts from PdOspecies
that oxidatively add the aryl (vinyl) halide to give Pd” intermediates (step 1, rate-
determining in the case of aryl chlorides). These latter insert the olefin regioselec-
tively in a syn stereochemistry (step 2), followed by C-C-coupling (step 3) and
syn elimination (step 4, with concomitant B-H migration, C -+Pd) of the final ole-
fink C-C-coupling product. These normally exhibit a trans geometry. The cata-
lyst reactivation follows in step 5 via HX-elimination by the base, thus closing
the catalytic cycle. The syn insertionlsyn elimination sequence yields an inverted
olefin geometry if 1,2-disubstituted alkenes are used. Note that a rotation around
the C-C-bond is necessary after the olefin insertion step to bring the B-H atom in
close enough proximity to the metal center.
B-Elimination occurs from alkylpalladium(I1) intermediates prior to olefin in-
sertion, for which reason alkyl halides are not suitable starting materials for the
Heck coupling. The stereochemistry is lost in the case of vinyl derivatives as start-
ing compounds since they isomerize via 7t-allylpalladium intermediates.
It is steric effects that govern the regiochemistry. C-C-coupling prevails at the
least substituted carbon atom [47]. The predominant additon of the aryl group to
 3.1.6.6 Mechanism 783

ArX
I
Ar -Pd-X Ar -Pd-X

7R
I
1
-L -L +2L
PdL4- PdLB=PdL?+ PdX2
Ti +L Red.

B
[ I

L = phosphine ligand
B = base
ArX = aryl halide
Ar

Figure 2. Textbook mechanism of the Heck C-C-coupling.

the least-substituted carbon, regardless of the polarization of the olefin (at least in
the intermolecular version), is seen in Table 1. If the olefin bears a good leaving
group, such as a halide or an acetate, elimination of this group in preference to the
p-hydride may occur.

Table 1. Regioselectivity effects in the Heck arylation: typical examples [47].

H
\
,C=CH-C02Me
H
\
C=CH-CN H\
C=CH
Q
' 0
t H't t
> 99 Yo 1 99 Yo 60 % 40 Yo

H H H Me H
\ \ / \ /

to
C=CH-C02Me ,c=c
Me; t
96 Yo 4 Yo 93 %
" t Yo
79 21 Yo
184 3.1 Development of Methods

The commonly used mechanism presents several problems :

(1) Not all Heck reactions depend on PdO catalysts. There are plenty of cases in
which Pd" salts are efficient. Furthermore, the catalytic species of the system
Pd(OAc)2/N(C2H5)3is undefined until now. Suggestions that the amine
reduces the palladium, to be converted into an immonium salt, seem not to
have a reliable experimental basis [48]. A mechanism which is based on the
oxidation states +I1 and +IV of Pd has been proposed by Shaw to account
for the possibility of using palladium(I1) catalysts without previous reduction
to palladium(0) [81].
(2) The reduction step Pd" -+Pdo is mechanistically not well-defined, although
phosphines seem to be most effective, with their P-oxides thus being formed.
Nevertheless, cyclovoltametric studies have given insight into possible reduc-
tion routes [82].
(3) Even in the case of Pdo catalysts, it is not clear how different types of ligands
(phosphines, phosphine oxides, amines) stabilize the active metal center in the
various steps of the reactions, whether they form distinct metal complexes or
whether they rather stabilize metal colloids [49].

The pivotal mechanistic role of zerovalent palladium results from the known
activity seen for well-defined catalysts of the type Pd[P(a~-yl)~],(n = 2 4 ) . The
dissociation equilibria regarding n determine the catalytic performance, with ex-
cess phosphine, as expected, suppressing the reaction rate according to r =
[P(aryl),]-' [50].A sixfold excess of phosphine over palladium practically kills
catalysis [50 a].
In light of the enormous versatility of Heck reactions, one should ask why no
commercial application has been seen as yet:

(a) The conventional catalysts decompose with formation of palladium above

ca. 140 "C.
(b) Relatively high amounts of catalysts are necessary (low TONS).
(c) Expensive starting compounds (iodides, triflates) are required although it is
now possible to employ aryl chlorides with the most active catalyst systems
(cf. Section 3.1.6.4).
(d) No efficient method of catalyst recycling is at hand.
(e) The salt waste problem is inherent in this reaction sequence.
(f) Chloroaromatics are not converted by the standard Pd/phosphine catalyst into
Heck-type products.

3.1.6.7 Catalyst Deactivation

Detailed kinetic studies revealed an intrinsic deactivation process of the standard
phosphine-palladium catalyst [50, 5 11: both the system P ~ ( O A C ) ~ / P ( C and
~H~)~
isolated Pd[P(C6H5)3]4,employed in the reference reaction of eq. (1 5 ) , suffer
from P-C-bond cleavage, the extent of which seems to increase with temperature.
 3.1.6.7 Catalyst Deactivation 185

0 1 2 3 4
reaction time [h] - 5 6 7

Figure 3. Arylation of n-butyl acrylate with 4-bromoanisole: concentration vs. time diagram
at T = 140 "C, Pd(OAc)J4 P(C6H&. c,(Pd) = 2 mol% (taken from Ref. [50, 511).

It becomes clear from the kinetics of Figure 3 that even deactivated bromoarenes
pose this problem, not to speak of aryl chlorides.

2 mob% Pd(OAc)2
8 mol-% P(CBH&
C H 3 0 0 B r + @ c ~ ~ B+ ~
NaOAc 6
DMAc

Up to two phenyl groups per phosphine are incorporated into the unwanted side
product, n-butyl (0-cinnamate, and the phosphine oxide forms at the very begin-
ning (reduction Pd" + PdO; Scheme 1). The side products are due to differing
stabilities of intermediates of type rr~ns-Pd[P(C~H~)~]~(aryl)X,
with donor-substi-
tuted derivatives undergoing particularly facile aryl-aryl exchange between the
Pd" centers and coordinated phosphines [40 a-c]. This isomerization proceeds
at temperatures far below Heck conditions (2120 "C), and a mechanism has
been proposed [40 a, c]. The detrimental consequence of P-C-bond cleavage is
the loss of Pdo-stabilizing phosphines with formation of palladium black, a noto-
rious disadvantage of Pd-phosphine catalysts in general.
It is to be stressed that aryl chlorides do react with Pdo complexes such as
Pd[P(C,H,),],(dba) or Pd[(C,H,),], at 140 "C; cf. typical Heck conditions [40a].
786 3.1 Development of Methods

Pd(OAc)2 I n PPh3

1. reduction
2. oxidative
I
addition
I (X = Br, CI)

PPh3
I
I -
.Pd-X
I
PPh3
- 60"c
isomerization
-
11 Pd -1
I
PPhj

vinyk
substitution

Heck product side product

Scheme 1. Formation of side products via isomerization of arylpalladium(I1) intermediates

through P-C-bond cleavage (taken from Ref. [50, 5 11).

It is P-C-bond cleavage and subsequent isomerizations that are responsible for the
deactivation in the case of aryl chlorides and not a missing reactivity for oxidative
addition as previously suggested! Furthermore, the nature of the anion seems to
dominate the subsequent steps in the catalytic cycle. Recently, these problems
have been solved by the application of defined catalyst systems such as pallacycles.

3.1.6.8 Industrial Applications and Perspectives

The coupling of ethylene with 6-methoxy-2-bromonaphthalene (eq. (16)) is effi-
ciently catalyzed by palladacycles 4. The ethylene reacts only once, thus yielding
6-methoxy-2-vinylnaphthalenein excellent selectivity and yield [57].This elegant
reaction is being developed as an industrial process by the former Hoechst AG,
possibly the first industrial Heck coupling after the 30 years during which this
type of reaction has been in existence.
Since a new generation of structurally defined catalysts was discovered, Heck
reactions offer an excellent opportunity for industrial applications, even for the
 References 787

Palladacycles
(0.01 mol-Oh)
+ H?C=CH1 *
Me0 DMAc,NaOAc Me0
< 20 atm, < 130 "C

less reactive aryl chlorides. Nevertheless, further challenges are seen in the im-
provement of these catalysts in terms of their performance (especially lifetimes)
for the activation of aryl chlorides. Any such improvement must rely on a further
improvement of the thermal stability of the co-ligand-metal bonds throughout the
catalytic cycle. The design of chiral ligands for the purpose of stereoselective
Heck coupling is another major demand in this area. Above all, the basic features
of the reaction mechanism(s) warrant renewed studies in detail, in which context
the electrochemistry within the series Pdo Pd2+ Pd4+needs to be explored
[69]. Regarding the commercialization of Heck reactions, the running costs for
the now well-developed palladium catalysts should not be considered a problem.
Rather the expensive iodo- and bromo starting compounds will govern the process
economy - another reason to improve the efficiency of Heck coupling reactions of
chloroaromatics.
An alternative to the coupling of olefins with aryl halides is C-H activation of
benzenes and addition to alkynes. A Pd" catalyst was shown to catalyze this reac-
tion in an acidic medium such as CF,COOH, even at room temperature (eq. (17))
~331.
% + w0
OEt
Pd(O A C ) ~

TFA, r.t. * 3yE( (17)

This reaction is highly atom-economical as it co-generates no by products.

References
[ 11 K. Weissermel, H.-J. Arpe, Industriul Organic Chemistry, 3rd ed., VCH, Weinheim,
1988.
[2] W. A. Herrmann, Kontakte (Darmstadt, Merck), 1991, 1, 22 and 1991, 3, 29.
[3] (a) J. Smidt, W. Hafner, Angew. Chem. 1959, 71, 284; (b) E. 0. Fischer, H. Werner,
Z. Chem. 1962, 2, 174: (c) I. I. Moiseev, E. Fedoroskaya, Y. K. Syrkin, Russ. J.
Znorg. Chern. 1959, 4, 1218; (d) P. E. Slade, H. B. Jonassen, J. Am. Chem. Soc. 1957,
79, 1277; (e) B. L. Shaw, Chem. Ind. (London) 1962, 1190.
[4] (a)R. Jira, W. Freiesleben, in: OrganometallicReuctions (Eds.: E. I. Becker, M. Tsutsui), Vol.
3, pp. 1 ff., Wiley, New York, 1972; (b) A. Aguilo, Adv. Orgunomet. Chem. 1967, 5, 321.
[5] R. F. Heck, Palludium Reugents in Organic Synthesis, Academic Press, London, 1985:
see also Ref. [15].
[6] J. K. Stille, Angew. Chem. 1986, 98, 504: Angew. Chem. Int. Ed. Engl. 1986, 25, 508.
[7] B. M. Trost, R. R. Verhoeven, Organopalladium Compounds in Organic Synthesis and
Catalysis, in: Comprehensive Organometullic Chemistry (Eds.: F. G. A. Stone, G. Wil-
kinson, E. W. Abel), Vol. 8, Chapter 57, Pergamon Press, Oxford, 1992.
[8] Further leading references: (a) J. Tsuji, Organic Synthesis with Palladium Compounds,
Springer, Berlin 1980: (b) A. Suzuki, Pure Appl. Chem. 1991, 63, 419; A. Suzuki, ibid.
788 3.1 Development of Methods

1985, 57, 1749; A. Suzuki, Acc. Chem. Res. 1982, 15, 178; (c) D. Seebach, Angew.
Chem. 1990, 102, 1363; Angew. Chem. Int. Ed. Engl. 1990, 29, 1320; (d) E. Negishi,
Acc. Chem. Res. 1982, 15, 340; E. Negishi, Pure Appl. Chem. 1981, 53, 2333; (e)
E. Drent, Pure Appl. Chem. 1990, 62, 661; EP 121.965 (1984), Chem. Abstr. 1985,
102, 46423, EP 229.408 (1986), Chem. Abstr: 1988, 108, 6617.
[9] Recent monographs and textbooks: (a) J. Mulzer, H.-J. Altenbach, M. Braun, K. Krohn,
H.-U. Ressig, Organic Synthesis Highlights, VCH, Weinheim, 1991, pp. 174 ff.; (b) J. P.
Collman, L. S. Hegedus, J. R. Norton, R. G. Finke, Principles and Applications of
Organotransition Metal Chemistry, University Science Books, Mill Valley, CA, 1987;
(c) Ch. Elschenbroich, A. Salzer, Organometallics - A Concise Introduction, VCH,
Weinheim, 1989; (d) R. H. Crabtree, The Organometallic Chemistry of the Transition
Metals, John Wiley, New York, 1988; (e) Ch. M. Lukehart, Fundamental Transition
Metal Organometallic Chemistry, BrooksICole Publishing Co., Monterey, CA, 1985;
(f) A. Yamamoto, Organotransition Metal Chemistry, John Wiley, New York, 1986;
(8) P. Powell, Organometallic Chemistry, 2nd ed., Chapman and Hall, London, 1988,
p. 229; (h) G. W. Parshall, S. D. Ittel, Homogeneous Catalysis, 2nd ed., John Wiley,
New York, 1992; (i) J. A. Moulijn, P. W. N. M. van Leeuwen, R. A. van Santen
(Eds.), Catalysis - An Integrated Approach to Homogeneous, Heterogeneous and
Industrial Catalysis, Elsevier, Amsterdam, 1993; (k) B. C. Gates, Catalytic Chemistry,
John Wiley, New York, 1992.
[lo] (a) R. F. Heck, J. Am. Chem. SOC.1968, 90, 5518; (b) R. F. Heck, ibid. 1971, 93, 6896;
(c) J. Tsuji, Acc. Chem. Res. 1969, 2, 151.
[ 111 (a) P. Fitton, M. P. Johnson, J. E. McKeon, J. Chem. SOC. Chem. Commun. 1968, 6 ; (b)
D. R. Coulson, J. Chem. SOC.,Chem. Commun. 1968, 1530; (c) P. Fitton, E. A. Rick,
J. Organomet. Chem. 1971, 28, 287.
[12] R. F. Heck, J. P. Nolley, J. Org. Chem. 1972, 37, 2320.
[13] T. Mizoroki, K. Mori, A. Ozaki, Bull. Chem. SOC.Jpn. 1971, 44, 581.
[I41 (a) H. A. Dieck, R. F. Heck, J. Am. Chem. SOC. 1974, 96, 1133; (b) A. Schoenberg, R. F.
Heck, J. Org. Chem. 1974,39, 3327; (c) H. A. Dieck, R. F. Heck, J. Organomet. Chem.
1975, 93, 259; (d) H. A. Dieck, R. F. Heck, J. Org. Chem. 1975, 40, 1083; (e) J. Mel-
polder, R. F. Heck, ibid. 1976,41, 265; (0 B. A. Patel, C. B. Ziegler, N. A. Cortese, J. E.
Plevyak, T. C. Zebovitz, M. Terpko, R. F. Heck, ibid. 1977, 42, 3903; (g) T. C. Zebovitz,
R. F. Heck, ibid. 1977, 42, 3907; (h) J. E. Plevyak, R. F. Heck, ibid. 1978, 43, 2454; (i)
C. B. Ziegler, R. F. Heck, ibid. 1978, 43, 2941; (j)W. C. Frank, Y. C. Kim, R. F. Heck,
ibid. 1978, 43, 2947; (k) C. B. Ziegler, R. F. Heck, ibid. 1978, 43, 2949; (1) N. A. Cor-
tese, C. B. Ziegler, B. J. Hrnjez, R. F. Heck, ibid. 1978, 43, 2952; (m) B. A. Patel, R. F.
Heck, ibid. 1978, 43, 3898; (n) B. A. Patel, J. E. Dickerson, R. F. Heck, ibid. 1978, 43,
5018; (0)J. E. Plevyak, J. E. Dickerson, R. F. Heck, ibid. 1979, 44, 4078; (p) L. Kao,
F. G. Stakem,B. Patel, R. F. Heck, ibid. 1982, 47, 1267; (9) W. Fischetti, K. Mak,
F. G. Stakem, J. Kim, A. L. Rheingold, R. F. Heck, ibid. 1983, 48, 948; (r) T. Mitsudo,
W. Fischetti, R. F. Heck, ibid. 1984, 49, 1640.
[I51 (a) R. F. Heck, in Comprehensive Organic Synthesis (Eds.: B. M. Trost, I. Fleming, M. F.
Semmelhack), Vol. 4, Chapter 4.3, p. 833 ff, Pergamon Press, Oxford, 1991; (b) R. F.
Heck, Pure Appl. Chem. 1978,50, 691; (c) R. F. Heck, Acc. Chem. Res. 1979, 12, 146.
[ 161 Recent reviews: (a) A. de Meijere, F. E. Meyer, Angew. Chem. 1994, 106, 2473; Angew.
Chem., Int. Ed. Engl. 1994, 33, 2379; (b) W. Cabri, I. Candiani, Acc. Chem. Res. 1995,
28, 2; (c) L. S. Hegedus, Transition Metals in the Synthesis of Complex Organic Mole-
cules, University Science Books, Mill Valley, CA, 1994 (L. s. Hegedus, Organische
Synthese mit Ubergangsmetallen, VCH Weinheim, 1995); (d) J. Tsuji, Palladium
Reagents and Catalysts: Innovations in Organic Synthesis, John Wiley, Chichester,
1995.
 References 789

[17] (a) T. Jeffery, Tetrahedron Lett. 1985, 26, 2667; (b) T. Jeffery, J. Chem. SOC.,Chem.
Cornmun. 1984, 1287; (c) T. Jeffery, Synthesis 1987, 70; (d) T. Jeffery, J. Chem.
Soc., Chem. Cornmun. 1991, 324; (e) T. Jeffery, Tetrahedron Lett. 1991, 32, 2121; (f)
T. Jeffery, ibid. 1992, 33, 1989.
[I81 Selected reports: (a) S. K. Meegalla, N. J. Taylor, R. Rodrigo, J. Org. Chem. 1992, 57,
2422; (b) A. Lansky, 0. Reiser, A. de Meijere, Synlett 1990, 405; (c) A.-S. Carlstrom,
T. Frejd, Acta Chem. Scand. 1992,46, 163; (d) M. Miura, H. Hashimoto, K. Itoh, M. No-
mura, J. Chem. Soc. Perkin Trans. I 1990, 2207; (e) A. Amorese, A. Arcadi, E. Bernoc-
chi, S. Cacchi, S. Cemni, W. Fedeli, G. Ortar, Tetrahedron 1989,45, 813; (f) A. Lansky,
Ph. D. Thesis, Gottingen (Germany), 1992; (8) 0. Reiser, S. Reichow, A. de Meijere,
Angew. Chem. 1987, 99, 1285; Angew. Chem., Int. Ed. Engl. 1987, 26, 1277.
[19] (a) L. Hong, E. Ruckenstein, J. Mol. Catal. 1992, 77, 273; (b) P. Yi, Z. Zhuangyu,
H. Hongwen, J. Mol. Catal. 1990,62, 297; (c) Z. Zhuangyu, P. Yi, H. Hongwen, K. Tsi-
yu, Synth. Commun. 1990, 20, 3563; (d) Y. Wang, H. Lui, J. Mol. Catal. 1988, 45,
127; (e) C.-M. Anderson, K. Karabelas, A. Hallberg, J. Org. Chem. 1985, 50, 3891.
[20] (a) J. P. Genet, E. Blart, M. Savignac, Synlett 1992, 715; (b) M. Safi, D. Sinou, Tetrahe-
dron Lett. 1991, 32, 2025; (c) A. L. Casalnuovo, J. C. Calabrese, J. Am. Chem. Soc.
1990, 112, 4324; (d) H.-C. Zhang, G. D. Doyle, Organometallics 1993, 12, 1499; (e)
T. I. Wallow, B. M. Novak, J. Am. Chem. Soc. 1991, 113, 7411; (f) N. A. Bumagin,
P. G. More, I. P. Beletskaya, J. Organomet. Chem. 1989, 371, 397; (8) S. Sengupta,
S. Bhattacharya, J. Chem. Soc., Perkin Trans. 1993, 1943.
[21] Selected reports: (a) J.-M. Gaudin, Tetrahedron Lett. 1991, 32, 6113; (b) R. C. Larock,
S. Babu, ibid. 1987,28,5291; (c) M. Mori, K. Chiba, Y. Ban, ibid. 1977,18, 1037; (d) L. S.
Hegedus, Angew. Chem. 1988,100, 1147; Angew. Chem., Int. Ed. Engl. 1988,27, 1113;
(e) R. Grigg, P. Stevenson, T. Worakun, Tetrahedron 1988, 44, 2033; (f) E. Negishi,
Y. Zhang, B. O’Connor, ibid. 1988, 29, 2915; (g) R. C. Larock, H. Song, B. E. Baker,
W. H. Gong, Tetrahedron Lett. 1988, 29, 2919.
[22] Selected reports: (a) H. Naora, T. Ohnuki, A. Nakamura, Bull. Chem. Soc. Jpn. 1988,61,
2859; (b) R. J. Sundberg, R. J. Cherney, J. Org. Chem. 1990, 55, 6028; (c) S. Cacchi,
P. G. Ciattini, E. Morera, G. Ortar, Tetrahedron Lett. 1988, 29, 3117; (d) V. H. Rawal,
C. Michoud, J. Org. Chem. 1993, 58, 5583; (e) W. Oppolzer, R. J. DeVita, J. Org.
Chem. 1991, 56, 6256; (QA.-S. Carlstrom, T. Frejd, ibid. 1991,56, 1289; (g) A.-S. Carl-
strom, T. Frejd, J. Chem. Soc., Chem. Commun. 1991, 1216; (h) J. J. Bozell, C. E. Vogt,
J. Gozum, J. Org. Chem. 1991, 56, 2584; (i) S. G. Davies, D. Pyatt, Heterocycles 1989,
28, 163.
[23] (a) K. Kikukawa, K. Nagira, F. Wada, T. Matsuda, Tetrahedron 1981, 37, 31; (b)
K. Kikukawa, K. Nagira, N. Terao, F. Wada, T. Matsuda, Bull. Chem. SOC. Jpn.
1979, 52, 2609; (c) S. Sengupta, S. Bhattacharya, J. Chem. SOC., Perkin Trans 1993,
I , 1943; (d) K. Kikukawa, K. Maemura, Y. Kiseki, F. Wada, T. Matsudo, C. Giam,
J. Org. Chem. 1981, 46, 4885; (e) F. Akiyama, H. Miyazaki, K. Kaneda, S. Teranishi,
Y. Fujiwara, M. Abe, H. Taniguchi, ibid. 1980, 45, 2359; (f) M. Beller, H. Fischer,
K. Kiihlein, Tetrahedron Lett. 1994, 35, 8773; (g) M. Beller, K. Kiihlein, Synlett
1995, 441.
[24] (a) H.-U. Blaser, A. Spencer, J. Organornet. Chem. 1982,233, 267; (b) A. Spencer, ibid.
1982, 240, 209; (c) A. Spencer, ibid. 1983, 247, 117; (d) A. Spencer, ibid. 1984, 265,
323. (e) A. Spencer, ibid. 1983, 258, 101; (f) A. Spencer, ibid. 1984, 265, 323; (g)
Ciba-Geigy AG (A. Spencer), EP 78.768 (1982); (h) R. A. DeVries, A. Mendoza, Orga-
nometallics 1994, 13, 2405; (i) Dow Chem. Corp. (R. A. DeVries, G. F. Schmidt, H. R.
Frick, A. Mendoza), EP 0.506.314 (1992).
[25] (a) S. Cacchi, E. Morera, G. Ortar, Tetrahedron Lett. 1984, 25, 2271; (b) S. Cacchi, Syn-
thesis 1986, 320; (c) S. Cacchi, P. G. Ciattini, E. Morera, G. Ortar, Tetrahedron Lett.
790 3.1 Development of Methods

1987, 28, 3039; (d) P. G. Ciattini, E. Morera, G. Ortar, ibid. 1991, 32, 1579; (e) S. Cac-
chi, Pure Appl. Chem. 1990, 62, 713; (f) Q. Chen, Z. Yang, Tetrahedron Lett. 1986, 27,
1171; (8) Q.-Y. Chen, Y. B. He, Synthesis 1988, 896.
[26] (a) W. J. Scott, M. R. Pena, K. Sward, S. J. Stoessel, J. K. Stille, J. Org. Chem. 1985,50,
2302; (b) W. Cabri, I. Candiani, A. Bedechi, ibid. 1992, 57, 3.558; (c) W. Cabri, I. Can-
diani, A. Bedeschi, R. Santi, Synlett 1992, 871; (d) W. Cabri, I. Candiani, s. DeBarna-
dinis, F. Francalanci, S. Penco, J. Org. Chem. 1991, 56, 5796; (e) W. Cabri, I. Candiani,
A. Bedeschi, R. Santi, ibid. 1990, 55, 36.54.
[27] (a) R. C. Larock, Pure Appl. Chem. 1990,62,653; (b) R. C. Larock, W. H. Gong, J. Org.
Chem. 1989, 54, 2047; (c) R. C. Larock, B. E. Baker, Tetrahedron Lett. 1988, 29, 905;
(d) M. Prashad, J. C. Tomesch, J. R. Wareing, H. C. Smith, S. H. Cheon, ibid. 1989, 30,
2877; (e) A. Arcadi, F. Marinelli, E. Bernocchi, S. Cacchi, G. Ortar, J. Organomet.
Chem. 1989, 368, 249.
[28] (a) C.-M. Anderson, J. Larsson, A. Hallberg, J. Org. Chem. 1990, 55,5757; (b) G. D.
Daves, A. Hallberg, Chem. Rev. 1989, 89, 1433; (c) C.-M. Anderson, A. Hallberg,
J. Org. Chem. 1988, 53, 235; (d) C.-M. Anderson, A. Hallberg, ibid. 1987, 52, 3529;
(e) K. Karabelas, C. Westerlund, A. Hallberg, ibid. 1985, 50, 3896; (f) K. Karabelas,
A. Hallberg, Tetrahedron Lett. 1985, 26, 3131.
[29] (a) R. Benhaddou, S. Czernecki, G. Ville, A. Zegar, Organometallics 1988, 7, 243.5;
(b) W. Smadja, S. Czernecki, G. Ville, C. Georgoulis, ibid. 1987, 6, 166; (c) W. Smadja,
G. Ville, G. Cahiez, Tetrahedron Lett. 1984, 25, 1793; A. Chalk, S. Magennis,
J. Org. Chem. 1976, 41, 1206.
[30] (a) A. Greiner, W. Heitz, Makromol. Chem., Rapid Commun. 1988, 9, 581 ; (b) W. Heitz,
W. Briigging, L. Freund, M. Gailberger, A. Greiner, H. Jung, U. Kampschulte,
N. NieBner, F. Osan, H.-W. Schmidt, M. Wicker, Makromol. Chem. 1988, 189, 119;
(c) U. Scherf, K. Mullen, Synthesis 1992, 23.
[31] (a) M. Brenda, A. Greiner, W. Heitz, Makromol. Chem. 1990, 191, 1083; (b) H.-P.
Weitzel, K. Miillen, ibid. 1990, 191, 2837; (c) H. Martelock, A. Greiner, W. Heitz,
ibid. 1991, 192, 967; (d) W. Heitz, A. Knebelkamp, Makromol. Chem., Rapid Com-
mun. 1991, 12, 69; (e) M. Suzuki, K. Sho, J.-C. Lim, T. Saegusa, Polymer Bull.
1989, 21, 415.
[32] Short review: H.-G. Schmalz, Nachr Chem. Tech. Lab. 1994, 42, 270.
[33] (a) F. Ozawa, A. Kubo, Y. Matsumoto, T. Hayashi, Organometallics 1993, 12, 4188;
(b) F. Ozawa, A. Kubo, T. Hayashi, J. Am. Chem. SOC. 1991, 113, 1417; (c) T. Hayashi,
A. Kubo, F. Ozawa, Pure Appl. Chem. 1992,64,421; (d) F. Ozawa, T. Hayashi, J. Orga-
nomet. Chem. 1992, 428, 267; (e) F. Ozawa, A. Kubo, T. Hayashi, Chem. Lett. 1992,
2177; (f) F. Ozawa, A. Kubo, T. Hayashi, Tetrahedron Lett. 1992, 33, 1485; (8) T. Ha-
yashi, in Organic Synthesis in Japan (Ed.: R. Noyori), Tokyo Kagaku Dozin, 1992,
p. 10.5; (h) F. Ozawa, Y . Kobatake, T. Hayashi, Tetrahedron Lett. 1993, 34, 250.5;
(i) 0. Loiseleur, P. Meier, A. Pfaltz, Angew. Chem. 1996, 108, 218; Angew. Chem.,
Int. Ed. Engl. 1996, 35, 200.
[34] (a) T. Takemoto, M. Sodeoka, H. Sasai, M. Shibasaki, J. Am. Chem. Soc. 1993, 115,
8477; (b) K. Kondo, M. Sodeoka, M. Mori, M. Shibasaki, Tetrahedron Lett. 1993, 34,
4219; (c) K. Kondo, M. Sodeoka, M. Mori, M. Shibasaki, Synthesis 1993, 920; (d)
Y. Sato, T. Honda, M. Shibasaki, Tetrahedron Lett. 1993, 33, 2593; (e) Y. Sato, S. Wata-
nabe, M. Shibasaki, ibid. 1992, 33, 2589; (f) Y. Sato, M. Sodeoka, M. Shibasaki,
Chem. Lett. 1990, 1953; (8) Y. Sato, M. Sodeoka, M. Shibasaki, J. Org. Chem. 1989,
54,4738; (h) K. Kagechika, M. Shibasaki, ibid. 1991,56,4093;(i) A. Ashimori, T. Mat-
suura, L. E. Overman, D. J. Poon, ibid. 1993,58,6949; (j)A. Ashimori, L. E. Overman,
D. J. Poon, ibid. 1992, 57,4571; (k) N. E. Carpenter, D. J. Kucera, L. E. Overman, ibid.
1989, 54, 5846.
 Rejerences 79 1

[35] Recent review on Water-soluble Metal Complexes and Catalysts: W. A. Henmann,

Ch. W. Kohlpaintner, Angew. Chem. 1993, 105, 1667; Angew. Chem., Int. Ed. Engl.
1993, 32, 1524; cf. Section 3.1.1.1. See also J. P. GenCt, M. Savignac, J. Organomet.
Chem., 1999, 576, 305.
[36] (a) J. Jeffery, Tetrahedron Lett. 1994, 35, 3051; (b) J. P. Genet, E. Plart, M. Savignac,
Synlett 1992, 715; (c) M. Safi, D. Sinou, Tetrahedron Lett. 1991, 32, 2025; (d) A. L. Ca-
salnuovo, J. C. Calabrese, J. Am. Chem. Soc. 1990, 112, 4324; (e) H.-C. Zhang, G. D.
Doyle, Organometallics 1993, 12, 1499; (f) T. I. Wallow, B. M. Novak, J. Am. Chem.
Soc. 1991, 113, 7411; (g) N. A. Bumagin, P. G. More, I. P. Beletskaya, J. Organomet.
Chem. 1989, 371, 397; (h) S . Sengupta, S. Bhattacharya, J. Chem. Soc., Perkin Trans
I 1993, 1943.
[37] (a) M. Julia, M. Duteil, C. Grard, E. Kuntz, Bull. Soc. Chim. FK 1973, 279 1; (b) A. Spen-
cer, J. Organomet. Chem. 1984, 270, 115; (c) J. B. Davison, N. M. Simon, S. A. Sojka,
J. Mol. Cat. 1984, 22, 349; (d) Ciba-Geigy AG (A. Spencer), EP 103.544 (1984).
[38] (a) M. Huser, M.-T. Youinou, J. A. Osbom, Angew. Chem. 1989, 101, 1427; Angew.
Chem., Int. Ed. Engl. 1989, 28, 1386; (b) V. V. Grushin, H. Alper, Chem. Rev. 1994,
94, 1047; (c) V. V. Grushin, H. Alper, Organometullics 1993, 12, 1890; (d) V. V.
Grushin, H. Alper, J. Chem. Soc., Chem. Commun. 1992, 611.
[39] (a) Synthesis: Y. Takahashi, T. Ito, S. Sakai, Y. Ishii, J. Chem. SOC., Chem. Commun.
1970, 1065; (b) T. Ukai, H. Kawazurd, Y. Ishii, J. Organomet. Chem. 1974, 65, 253;
(b) Equilibria with phosphines: C. Amatore, A. Jutand, F. Khalil, M. A. M’Barki, L. Mot-
tier, Organometallics 1993, 12, 3168.
[40] Recent reports: (a) W. A. Henmann, Ch. BroRmer, Th. Priermeier, K. Ofele, J. Organo-
met. Chem. 1994, 481, 97; (b) W. A. Henmann, W. R. Thiel, Ch. BroBmer, K. Ofele,
Th. Priermeier, W. Scherer, ibid. 1993, 461, 51; (c) K.-C. Kong, C.-H. Cheng, J. Am.
Chem. SOC. 1991, 113, 6313.
(a) Y. Ben-David, M. Portnoy, M. Gozin, D. Milstein, Orgunometallics 1992, 11, 1995;
(b) M. Portnoy, Y. Ben-David, D. Milstein, ibid. 1993, 12, 4734; (c) M. Portnoy, D. Mil-
stein, ibid. 1994, 13, 600.
(a) Y. Ben-David, M. Portnoy, D. Milstein, J. Am. Chem. Soc. 1989, 111, 8742; (b)
Y. Ben-David, M. Portnoy, D. Milstein, J. Chem. Soc., Chem. Commun. 1989, 1816;
(c) M. Portnoy, D. Milstein, Organometallics 1993, 12, 1655; (d) M. Portnoy, D. Mil-
stein, ibid. 1993, 12, 1665.
[43] (a) J. F. Carpentier, F. Petit, A. Mortreux, V. Dufaud, J.-M. Basset, J. Thivolle- Cazat,
J. Mol. Cutul. 1993, 81, 1 ; (b) V. Dufaud, J. Thivolle-Cazat, J.-M. Basset, R. Matthieu,
J. Jaud, J. Waissermann, Organometullics 1991, 10, 4005; (c) V. Dufaud, J. Thivolle-
Cazat, J.-M. Basset, J. Chem. Soc., Chem. Commun. 1990, 426; (d) F. Dany, R. Mutin,
C. Lucas, V. Dufaud, J. Thivolle-Cazat, J.-M. Basset, J. Mol. Cutul. 1989, 51, L15; (e)
R. Mutin, C. Lucas, J. Thivolle-Cazat, V. Dufaud, F. Dany, J.-M. Basset, J. Chem. SOC.,
Chem. Commun. 1988, 896; (f) J. F. Carpentier, Y. Castanet, J. Brocard, A. Mortreux,
F. Petit, Tetrahedron Lett. 1991, 32, 4705; (g) J. F. Carpentier, Y. Castanet, J. Brocard,
A. Mortreux, F. Petit, ibid. 1992, 33, 2001.
[44] K. Voigt, U. Schick, F. E. Meyer, A. de Meijere, Synlett 1994, 189.
[45] A. S. Guram, R. A. Rennels, S. L. Buchwald, Angew. Chem. 1995, 107, 1456; Angew.
Chem., Int. Ed. Engl. 1995, 34, 1348.
[46] R. F. Heck, Org. React. 1982, 27, 345.
[47] Ref. [9 b], p. 724.
[48] R. McCrindle, G. Ferguson, G. J. Arsenault, A. J. McAlees, D. K. Stephenson, J. Chem.
Res. Synop. 1984, 360.
[49] M. Beller, H. Fischer, K. Kiihlein, C.-P. Reisinger, W. A. Henmann, J. Organomet.
Chem. 1996, 520, 257.
792 3.1 Development of Methods

[50] (a) W. A. Herrmann, Ch. BroBmer, K. Ofele, M. Beller, H. Fischer, J. Organomet.

Chem., 1995, 491, C I ; (b) W. A. Herrmann, Ch. BroBmer, K. Ofele, M. Beller,
H. Fischer, J. Mol. Cat. 1995, 103, 133.
[51] Ch. BroBmer, Ph. D. Thesis, Technische Universitat Miinchen, Germany, 1994.
[52] Hoechst AG (W. A. Herrmann, Ch. BroBmer, M. Beller, H. Fischer), DE 4.421.730 and
DE 4.421.753 (1994).
[53] (a) W. A. Herrmann, C. BroSmer, K. Ofele, C.-P. Reisinger, T. Priermeier, M. Beller,
H. Fischer, Angew. Chem. 1995, 107, 1989; Angew. Chem., Int. Ed. Engl. 1995, 34,
1844; (b) W.A. Herrmann, C. BroBmer, C.-P. Reisinger, T.H. Riermeier, K. Ofele,
M. Beller, Chem. Eur: J. 1997, 3, 1357.
[54] (a) M. Beller, H. Fischer, W. A. Herrmann, C. BroBmer, K. Ofele, Angew. Chon., Int.
Ed. Engl. 1995, 34, 1848; (b) Hoechst AG (M. Beller, H. Fischer, W. A. Herrmann,
C. BroRmer), DE 4.423.061 (1994).
[55] Hoechst AG (W. A. Herrmann, C.-P. Reisinger, M. Beller, H. Fischer), DE 4.421.753.6
(1995).
[56] W. A. Herrmann, C.-P. Reisinger, C. BroBmer, M. Beller, H. Fischer, J. Mol. Catal. 1996,
108, 51.
[57] W. A. Herrmann, C.-P. Reisinger, M. Beller, unpublished results, 1995.
[58] (a) W. A. Herrmann, C.-P. Reisinger, unpublished results, 1994/95; (b) S. Iyer, J. Orga-
nomet. Chem. 1995, 490, C27.
[59] (a) Review: A. J. Canty, Acc. Chem. Res. 1992,25, 83; (b) P. K. Byers, A. J. Canty, B. W.
Skelton, H. White, J. Chem. Soc., Chem. Commun. 1986, 1722; (c) A. J. Canty, Palla-
dium-Carbon a-Bonded Complexes, in: Comprehensive Organometallic Chemistry I1
(Eds.: E. W. Abel, F. G. A. Stone, G. Wilkinson), Vol. 9, Chapter 5 , Pergamon Press,
Oxford, 1995; (d) B. M. Trost, M. K. Trost, J. Am. Chern. Soc. 1991, 113, 1850.
(a) Hoechst AG (W. A. Herrmann, M. Elison, J. Fischer, C. Kocher, K. Ofele), DE
4.447.066 (1994); (b) W.A. Herrmann, M. Elison, J. Fischer, C. Kocher, G.R. J.
Artus, Chem. Eur: J. 1996, 2, 772.
Hoechst AG (W. A. Herrmann, M. Elison, J. Fischer, C. Kocher, K. Ofele), DE 4.447.068
(1994).
W. A. Herrmann, M. Elison, J. Fischer, C. Kocher, G. J. R. Artus, Angew. Chem. 1995,
107, 2602; Angew. Chem., Int. Ed. Engl., 1995, 34, 2371.
[63] H. W. Wanzlick, H. J. Schonherr, Angew. Chem. 1968,80, 154; Angew. Chem., Int. Ed.
Engl. 1968, 7, 141.
[64] K. Ofele, J. Organomet. Chem. 1968, 12, P42.
[65] (a) W. A. Herrmann, K. Ofele, M. Elison, F. E. Kuhn, P. W. Roesky, J. Organomet.
Chem. 1994, 480, C 7 ; (b) K. Ofele, W. A. Herrmann, D. Mihalios, M. Elison, E. Herdt-
weck, W. Scherer, J. Mink, ibid. 1993, 459, 177.
[66] (a) A. J. Arduengo 111, R. L. Harlow, M. Kline, J. Am. Chem. Soc. 1991, 113, 361; (b)
A. J. Arduengo 111, M. Tamm, S. J. McLain, J. C. Calabrese, F. Davidson, M. J. Marshall,
ibid. 1994, 116, 7927, and references cited therein.
[67] Hoechst AG (W. Konkol, H. Bahrmann, W. A. Herrmann, J. Kulpe), DE 3.942.789
(1992); YP 5.051.522 (1991); W. Konkol, H. Bahrmann, W. A. Herrmann, J. Kulpe,
J. Organomet. Chem. 1990, 389, 85.
[68] J. J. Bozell, C. E. Vogt, J. Am. Chem. SOC.1988, 110, 2655.
[69] (a) T. A. Stephenson, S. M. Morehouse, A. R. Powell, J. P. Heffer, G. Wilkinson, J. Chem.
Soc. 1965, 3632; (b) C. W. Lee, J. S. Lee, N. S. Cho, K. D. Kim, S. M. Lee, J. S. Oh,
J. Mol. Catal. 1993, 80, 31; (c) J. A. Goodfellow, T. A. Stephenson, M. C. Cornock,
J. Chem. Soc., Dalton Trans. 1978, 1195; (d) Ref. [51], p. 116 ff; (e) C. Amatore,
A. Jutand, M. A. M’Barki, Organometallics 1992, 11, 3009.
[70] T. Mitsudo, W. Fischetti, R. F. Heck, J. Org. Chem. 1984, 49, 1640.
 3.1.7.1 Introduction 793

[71] R. M. Moriarty, W. R. Epa, A. K. Awasthi, J. Am. Chem. SOC. 1991, 113, 6315.
[72] (a) W. A. Herrmann, V. P. W. Bohm, C.-P. Reisinger, J. Organomet. Chem. 1999,576, 23;
(b) M. Ohff, A. Ohff, M.E. van der Boom, D. Milstein, J. Am. Chem. SOC.1997, 119,
11687; (c) B.L. Shaw, S. D. Perera, E.A. Staley, Chem. Commun. 1998, 1361.
[73] J. Schwarz, V. P. W. Bohm, M. G. Gardiner, M. Grosche, W. A. Herrmann, W. Hieringer,
G. Raudaschl-Sieber, Chem. Eul: J. 2000, 6, 1773.
[74] M. T. Reetz, G. Lohmer, R. Schwickardi, Angew. Chem. 1998,110,492;Angew. Chem.,
Int. Ed. 1998, 37, 481.
[75] (a) D.A. Albison, R.B. Bedford, P.N . Scully, Tetrahedron Lett. 1998, 39, 9793; (b)
M. Beller, A. Zapf, Synlett 1998, 792.
[76] (a) A. F. Littke, G.C. Fu, J. Org. Chem. 1999, 64, 10; (b) K. H. Shaughnessy, P. Kim,
J.F. Hartwig, J. Am. Chem. Soc. 1999, 121, 2123.
[77] (a) D. E. Kaufmann, M. Nouroozian, H. Henze, Synlett 1996, 1091; (b) W. A. Herrmann,
V. P. W. Bohm, J. Organomet. Chem. 1999, 572, 141; (c) V. P. W. Bohm, W. A. Herr-
mann, Chem. Eur: J. 2000, 6, 1017.
[78] V. P. W. Bohm, PhD thesis, Technische Universitat Miinchen, 2000.
[79] M. S. Stephan, A. J. J. M. Teunissen, G. K. M. Verzijl, J. G. de Vries, Angew. Chem. 1998,
110, 688;Angew. Chern. Int. Ed. 1998, 37, 662.
[80] J. P. GenEt, M. Savignac, J. Organomet. Chem. 1999, 576, 305.
[81] B.L. Shaw, New J. Chem. 1998, 77.
[82] (a) C. Amatore, A. Jutand, M. A. M’Barki, Organometallics 1992, 11, 3009; (b) C. Ama-
tore, E. Carr6, A. Jutand, M. A. M’Barki, Organometallics 1995, 14, 1818; (c) 0. V. Tyu-
kalova, G. V. Ratovskii, L. B. Belykh, F. K. Shmidt, Russ. J. Gen. Chem. 1997, 67, 53.
[83] C. Jia, D. Piao, J. Oyamada, W. Lu, T. Kitamura, Y. Fujiwara, Science 2000, 287, 1992.
[84] Reviews: (a) W. A. Herrmann, Ch. Kocher, Angew. Chem. 1997, 109, 2256; Angew.
Chem., Int. Ed. Engl. 1997, 36, 2162; (b) W. A. Herrmann, Angew. Chem., Int. Ed.
2002, in press; (c) U. P. W. Bohm, W. A. Herrmann, Angew. Chem., Int. Ed. 2000,
39, 4036.

3.1.7 Catalytic Cyclopropanation

Alfred I? Noels, Albert Demonceau

3.1.7.1 Introduction
The birth of small-ring chemistry was painstaking and difficult. It is sufficient to
recall that the great chemists of the time, V. Meyer, A. von Baeyer, and E. Fischer,
were persuaded that cycles with fewer than six carbon atoms in a ring were not
capable of existence!
Nowadays, three-membered carbocyclic rings hold a prominent position in or-
ganic chemistry. The cyclopropane bonds are weaker than normal u-bonds and
under the influence of a variety of chemical reagents (e. g., electrophiles, nucleo-
philes, radicals, transition metals) or external physical forces (e. g., heat, light), cy-
clopropanes undergo a variety of ring-opening reactions. In contrast to normal par-
affins, the chemistry of the cyclopropane C-C single bond resembles that of a
C=C double bond and a cyclopropyl unit has often been compared with a vinyl
substituent. Progress in understanding the bonding in cyclopropane was first
794 3.1 Development of Methods

made in the late 1940s by Walsh [l] and by Coulson and Moffitt [2]. More re-
cently, Dewar no longer considered a-bonds as localized entities and introduced
the concept of a-aromaticity (a-conjugation): the three C-C a-bonds of cyclopro-
pane provide an array of six electrons and cyclopropane, accordingly, is aromatic
[ 3 ] .A modification of this approach utilizes the Walsh basis set and a-aromaticity
is then postulated to result from a three-center, two-electron bond [4]. These mod-
els, invoking a-aromaticity, have the merit of rationalizing the apparent anoma-
lous chemical and physical properties of cyclopropanes, such as the relatively
low ring strain (27.5 kcal mol-’; 115 kJ mol-’), NMR characteristics and high
reactivity towards electrophiles.
Cyclopropanes have in fact been utilized in virtually every synthetic sense that
befits the utility of alkenes in synthesis. Relief of ring strain provides a thermo-
dynamic driving force for most processes. Accordingly, it comes as no surprise
that cyclopropanes, besides being an interest in their own right, have served
extensively as synthons in molecular construction and as probes of reactivity.
Cyclopropane-based industrial applications remain limited however, and are
mostly restricted to the synthesis of some rather elaborate molecules utilized as
pharmaceuticals or insecticides.
Cyclopropane synthesis provides a significant challenge to chemists due to the
difficulty in controlling the relative and absolute chemistry around the cyclopro-
pane ring. Numerous methodologies have been developed for the construction of
three-membered carbocycles. Among them, catalytic cyclopropanation, which can
be regarded as a cycloaddition of a carbene fragment to a double bond, has
emerged as a most versatile synthetic reaction pathway. This strategy, which
amounts to a simple catalyzed cycloaddition with loss of nitrogen, is interesting
in terms of atom economy as well [5].
The synthetic use of organic diazo compounds, and especially of diazocarbonyl
compounds as carbene precursors in carbenoid transformations, has undergone a
renaissance in the last 20 years as a result of the discovery of new transition metal
based catalysts. The term “carbenoid” was coined to indicate that metal-bound
carbene intermediates behave differently from the free carbenes generated ther-
mally or photochemically. Recent advances in the understanding of the mechan-
isms of transition metal catalyzed reactions have led (and this process is still
going on) to a careful molecular engineering of thecatalysts, resulting in signifi-
cant improvements of the selectivities and permitting ultimately the achievement
of highly enantioselective cyclopropanations.

3.1.7.2 Transition Metal Catalyzed Cyclopropanations

3.1.7.2.1 Diazo Compounds as Carbene Precursors

Historically, copper-based catalysts have played a prominent role in the in situ
generation of metal carbenes (or carbenoids) from diazo compounds. In the
1970s, new transition metal complexes were discovered that widened the range
 3.1.7.2 Transition Metal Catalyzed Cyclopropanations 195

of catalyzed diazo compound applications while proceeding under much milder

reaction conditions. Among those, palladium derivatives and copper(1) complexes
of poorly coordinating ligands such as the triflate anion generated renewed interest
in catalyzed carbene reactions because of higher yields and increased selectivities.
These early results were soon extended to the first asymmetric cyclopropanations
mediated by copper-based catalysts [6]. A better insight into the possible reaction
mechanisms promoted further investigations on the catalytic behavior of transition
metal complexes that culminated in the discovery of dirhodium(I1) tetracarbo-
xylates [7] and later of the corresponding carboxamides [8]. These complexes are
the first really efficient and “polyvalent”, air-stable complexes that can be tailored
practically at will. For instance, rhodium(I1) carboxamides incorporating the chiral
oxazolidinone and pyrrolidinone ligands have become extremely important in en-
antioselective cyclopropanations (see below). Besides mediating carbene cycload-
ditions to carbon-carbon double and triple bonds to give respectively cyclopro-
panes and cyclopropenes, rhodium(I1) carbenoids undergo a broad spectrum of
chemical transformations that include carbene cycloaddition to aromatic rings
and insertion into a variety of activated X-H bonds (X = 0, S, N, etc.) and
into paraffinic C-H bonds. It has to be pointed out, however, that very few direct
experimental data bear on the mechanism of the reactions of diazo compounds
mediated by rhodium complexes or the intermediates, such as metal carbenes.
No rhodium carbene species involved in a catalytic cycle has, as yet, been spectro-
scopically observed, let alone fully characterized, or isolated. Reactions of dirho-
dium(I1) carbenes are supposed to be charge- or frontier orbital-controlled (or
both). Conformational and steric effects may also play a dominant role in product
formation with certain substrates.
Rhodium(I1)-mediated reactions have found many applications. The literature
up to 1985 in intramolecular and intermolecular cyclopropanations, including
choice of catalysts and mechanistic aspects, has been thoroughly reviewed by
Maas [9]. More recent reviews are available that focus on the ligand effects and
mechanism [lo], and on their utilization in fine organic synthesis as well as in nat-
ural product synthesis [ll]. All of these reviews, and in particular McKervey’s
comprehensive review [ 11 a] on organic synthesis with a-diazocarbonyl com-
pounds, deal with the utilization of functionalized diazo compounds as carbenoid
precursors. Henmann et al. surveyed the organometallic chemistry of diazo-
alkanes [I 1 c, 11 d].

3.1.7.2.2 Diazomethane as a Carbene Precursor

In contrast to the wealth of chemistry reported for catalyzed reactions of diazocar-
bony1 compounds, there are fewer applications of diazomethane as a carbenoid
precursor. Catalytic decomposition of diazomethane, CH2N2,has been reported
as a general method for the methylenation of chemical compounds [12]. The ef-
ficacy of rhodium catalysts for mediating carbene transfer from diazoalkanes is
poor. The preparative use of diazomethane in the synthesis of cyclopropane deri-
vatives from olefins is mostly associated with the employment of palladium cat-
196 3.1 Development of Methods

alysts. The disadvantages and limitations linked with the preparation and transport
of diazomethane, an explosive and toxic molecule, can now be circumvented, at
least to some extent, by a direct in-situ generation of diazomethane by alkaline
hydrolysis of N-methyl-N-nitrosourea in the presence of the olefin and palladium
catalyst [ 121.
The available literature data support the assertion that the outcome of the
methylene cycloadditions depends to a large extent on the ability of the olefin
to be coordinated to the palladium center. In that respect, the mechanism of pal-
ladium-catalyzed cyclopropanation appears to differ significantly from that of rho-
dium(I1)-catalyzedcyclopropanations. One advantage of using palladium catalysts
with diazomethane is associated with the possibility of synthesizing polycyclopro-
pane adducts, a topic of current interest (vide infra) which has no general satisfac-
tory solution with other diazo compound/catalyst combinations. This point is ex-
emplified below for the cyclopropanation of the esters of trans-polyunsaturated
acids. Moreover, the reactivity of the double bonds depends both on their position
in the linear hydrocarbon chain and on their configuration (eq. (1)).

R - _. gC02Me
1

- C02Me

90 Yo

While the only double bond cyclopropanated in the arachidonic ester 1 is that
next to the ester group, both trans double bonds of the unsaturated ester 2 are
cyclopropanated in good yield (eq. (2)) [12].

80-90 Yo

Palladium acetate was also recently used as catalyst in a multistep stereospecific

synthesis of enantiomeric rigid tryptamine derivatives [ 131. The chiral auxillary is
Oppolzer's sultam (e.q. (3)).

\ \
Ts Ts
 3.1.7.2 Transition Metal Catalyzed Cyclopropanations 797

3.1.7.2.3 a-Diazocarbonyl Derivatives as Carbene Precursors

a-Diazocarbonyl derivatives and especially a-diazoesters remain, however, the
most extensively studied carbenoid precursors. A drawback with these diazo
compounds is that the cyclopropanation is usually only moderately diastereose-
lective. Moreover, the use of the rhodium catalysts for targeted outcomes in com-
plex molecules containing several potential reaction sites also suffers from a re-
lative lack of chemoselectivity. This chemoselectivity can be modulated to some
extent by varying the stereoelectronic properties of the ligands but there remains
a paucity of information on carbenoid chemoselectivity. The recent finding that
cyclopropanations with vinyldiazomethane catalyzed by rhodium(I1) carbox-
ylates can be highly diastereoselective opens new perspectives for the control
of both relative and absolute stereochemistry [ 141. The resulting vinyl cycload-
ducts play an important role as precursors for cyclopentenes en route to cyclo-
pentanoid natural products. Vinyldiazomethane has to be employed with quite
active catalysts, however, in order to compete effectively with electrocyclization
to 3H-pyrazoles.
As already mentioned for rhodium carbene complexes, proof of the existence
of electrophilic metal carbenoids relies on indirect evidence, and insight into
the nature of intermediates is obtained mostly through reactivity-selectivity re-
lationships and/or comparison with stable Fischer-type metal carbene com-
plexes. A particularly puzzling point is the relevance of metallacyclobutanes
as intermediates in cyclopropane formation. The subject is still a matter of
debate in the literature. Even if some metallacyclobutanes have been shown
to yield cyclopropanes by reductive elimination [ 151, the intermediacy of
metallacyclobutanes in carbene transfer reactions is in most cases borne out
neither by direct observation nor by clear-cut mechanistic studies and such a
reaction pathway is probably not a general one. Formation of a metallacyclobu-
tane requires coordination both of the olefin and of the carbene to the metal
center. In many cases, all available evidence points to direct reaction of the
metal carbenes with alkenes without prior olefin coordination. Further, it has
been proposed that, at least in the context of rhodium carbenoid insertions
into C-H bonds, partial release of free carbenes from metal carbene complexes
occurs [16]. Of course this does not exclude the possibility that metallacyclo-
butanes play a pivotal role in some catalyst systems, especially in copper-
and palladium-catalyzed reactions.
There is thus to date no single general mechanism model for olefin cyclopro-
panation. The basic mode of ring closure in metal-catalyzed carbene transfer
reactions must still be regarded as hypothetical in most cases.
798 3.1 Development of Methods

3.1.7.3 Recent Developments and Applications

3.1.7.3.1 Enantioselective Cyclopropanations:

The Ultimate Goal
Copper-Based Catalysts

It is worth recalling that the asymmetric cyclopropanation of styrene with ethyl

diazoacetate, reported in 1966 by Noyori and co-workers, appears to be the
first example of transition metal catalyzed enantioselective reaction in homoge-
neous phase. This reaction remains a landmark in asymmetric cyclopropanation.
On a general standpoint, catalytic asymmetric cyclopropanation continues to at-
tract much attention, due in part to the marked trends toward marketing more
and more optically active molecules as the optically pure eutomer. This topic
has been much studied in connection, inter a h , with the synthesis of valuable
intermediates such as chrysanthemic acid derivatives and cilastatin. The subject
has been recently reviewed [17].
The cyclopropanations were initially carried out with copper(I1) chiral Schiff
base and later with semicorrin Cu" complexes. The actual catalysts are however
Cu' species, which suggested the direct use of Cu' complexes as catalyst precur-
sors. More recently, substituted chiral oxazolines (molecules possessing C, sym-
metry) proved to be extremely attractive ligands as a consequence of their topo-
graphy and ease of synthesis from readily available amino alcohols. In combina-
tion with Cut complexes of poorly coordinating ligands, typically Cur- OTf, they
form highly effective cyclopropanation catalysts. The reaction proceeds at 25 "C.
CU"(OT~)~ and other Cu" complexes do not catalyze the reaction unless they are
heated or preactivated with phenylhydrazine. Excellent diastereo- and enantio-
selectivity were achieved in the cyclopropanation of a variety of monosubstituted,
trans-disubstituted and terminally disubstituted olefins. Chiral semicorrin-copper
complexes are efficient enantiomeric catalysts for intramolecular cyclopropana-
tion reactions of diazomethyl alkenyl ketones leading to bicyclo[3.1 .O]hexan-2-
ones with up to 85 % ee and to bicyclo[4.l.0]heptan-2-oneswith up to 95 % ee
[ 181. Chelating chiral diamines have recently been successfully used in styrene cy-
clopropanation. Although the chemical yield is modest, the diastereoselectivity is
high (truns:cis = 93:7) with excellent enantioselectivity (up to 96% ee for the
trans isomer) [ 19 a]. Chiral derivatives of 2,2'-bipyridine, of 2,2':6,6'-terpyridine,
of phenanthroline and of aminopyridine were, however, reported to be much less
efficient in the same cyclopropanation reaction [19 b].
Practical applications include the synthesis of trans-2-phenylcyclopropanamine
(trade name tranylcypromine), an antidepressant acting as a monoamine oxidase
inhibitor [ 20 a], of 2,2-dimethylcyclopropane carboxylate from isobutene [20 b],
a key step in the commercial production of cilastatin, 3 (eq. (4)), and of esters of
chrysanthemic acid 4 (using the methylene bis(diphenyloxazo1ine) 5 ) [ 17, 211 (eq.
(5)). Cilastatin is a dehydropeptidase which acts as an in vivo stabilizer of the car-
bapenem antibiotic imipenem with achiral diazoesters.
 3.1.7.3 Recent Developments and Applications 799

+ N2CHC02Et " p..,

--
0.1 70 kO2Et
91 YOyield, 99 % ee

(4)
0 C02Na

)=/=< + N2CHCOzDCM 1 mol % (5)

tramcis = 95:5
4 trans 94 % ee

[CU]* = CdOTf + .
Ph" Ph
5
DCM = dicyclohexylmethyl

As chrysanthemic acid derivatives suffer from rapid photo-stimulated oxidative

degradation, no agricultural application could be considered until structural mod-
ification provided sufficient chemical stability. This led to the discovery of pyre-
throids. Pyrethroids constitute a family of photostable analogs of the chrysan-
themic acid esters, which they outperform as insecticides by order of magnitude.
They are today the most important class of environmentally friendly insecticides.
One possible straightforward approach to the synthesis of pyrethroids is a direct
catalytic asymmetric cyclopropanation of a suitable conjugated olefin. The reac-
tion requires full regio-, stereo- and enantiocontrol of carbenoid additions, as ex-
emplified here for cis-(+)deltamethrin 6, a compound marketed as the optically
pure ester of the cyanohydrin (eq. (6)). The required configuration of the cyclo-
propane stereogenic centers are (2R,3S).Amazingly, one stereocenter is inverted
compared with the natural model. The esterification step introduces a third stereo-
genic carbon (a-C). A crystallization-induced asymmetric transformation of the
racemate finally yields the eutomer with the appropriate S configuration at the
a-C [17].
800 3.1 Development of Methods

transesterferication /

6, X = Br, deltamethrin 2R, 3s

7 , X = CI, cypermethrin

Related insecticides include cypermethrin 7 (the corresponding dichloro deri-

vative) and permethrin (where a-C is an unsubstituted CH2 group). Many other
natural products containing the cyclopropyl group have been synthesized through
related reactions of a carbenoid of copper or of rhodium with a carbon-carbon
double bond; see [ 111 for further examples.

Rhodium-Based Catalysts

The dimeric rhodium(I1) complexes become enantioselective catalysts if they con-

tain optically active ligands. Use of optically active carboxylates results, however,
in small enantiomeric excesses (ee), probably for symmetry reasons and because
the asymmetric centers are too far away from the reaction sites. One recent
remarkable exception is the dirhodium tetra"-(arenesulfonyl)prolinate]. This
catalyst induces high ee with diazoesters [22]. The reason for this seems to be
an arrangement of the ligands resulting in complexes with D2 symmetry, a con-
figuration in which one face of the carbenoid is blocked. The cyclopropane
illustrated in eq. (7) is an intermediate in the synthesis of sertraline, a major
pharmaceutical agent for the treatment of depression [23].

yield 79 %, 94 % ee

Chiral substituents at the N atoms of carboxamide anions of dirhodium(I1)

complexes are closer to the reaction center and, as expected, such catalysts usually
 3.1.7.3 Recent Developments and Applications 801

deliver high levels of enantioselection in the cyclopropanation. The problem with

many rhodium carboxamides is that they frequently fail to decompose diazo-
carbonyl compounds. Rhodium complexes that possess four chiral pyrrolidone
or oxazolidone ligands have been prepared by ligand substitution of acetate
from dirhodium(I1) tetraacetate. The former complexes are usually more efficient
catalysts than the latter.
The methyl esters of (R)-or (S)-pyrrolidone-5-carboxylic acid (acronym: mepy)
respectively form [Rh*(5R-me~y)~] or [Rh2(5S-mepy)4]complexes (see Structure
8). The catalyst is thus available in both configurations, 5R or 5s. Such catalysts
deliver often more than 90% ee and conformational energy minima (extended
Huckel) of the carbene-styrene complex predict the observed enantiomer pre-
ference [24 a].
Catalysis with [Rh,(SS-mepy),] was extended from styrene to other olefins, for
which excellent results were also obtained. By using this chiral catalyst, it has
recently been possible to fix the three stereocenters in the cyclopropane ring of
(+)-(lR,2R,3R)presqualene diphosphate (Structure 9), an intermediate in the bio-
synthesis of squalene from farnesyl diphosphate [25].

ih'-Rh The two amide ligands which are directed to the front and

H
1' N'I
to the rear of the lantern structure are incompletely drawn
to provide better overview.

presqualene diphosphate 9

On the other hand, the exceptional capabilities of these catalysts for enantiocon-
trol are evident in results obtained in intramolecular cyclopropanations, which
usually occur with greater enantioselectivity than they do with copper catalysts.
The example shown in eq. (8) illustrates the synthesis of a strained bicyclic lac-
tone from a readily available ally1 diazoacetate [24]. Similarly, high enantioselec-
tivities for intramolecular cyclopropanations of homoallylic diazoacetates and
homoallylic diazoacetamides have been reported [24 b]. A comparative evaluation
of enantiocontrol for cyclopropanation of allylic diazoacetates with chiral Cu',
Rh", and Ru" catalysts showed the superiority of Rh-based catalysts in these in-
tramolecular reactions [24 c], an observation that cannot however be extrapolated
to different substrates [24 d].
802 3.1 Development of Methods

Rh2(5Smepy)4,82 %, 98 % ee
[Rh] =
Rh2(5R-r11epy)~,
83 %, 98 % ee

Dirhodium(I1) catalysts that possess chiral 2-pyrrolidone-5-carboxylate ester

ligands (mepy) are the most effective among those of dirhodium or copper for
highly diastereoselective and enantioselective intermolecular cyclopropenation
reactions between 1-alkynes and diazoesters (eq. (9)). Product yields are
moderate, and enantiomeric excesses range from 40 to 98 %. Interestingly, the
(R) or (S) catalyst produces the cyclopropene- 1-carboxylate respectively with
the (R) or (S) configuration [26].

R-C=CH + N2C,
’cox
R = CH(OEt)2, CH20Me, Bun, But
H

-xx
RMmepyh
R H
(9)

X = OMe, But, NMe2

So far, while there is a relative abundance of synthetically useful cyclopropana-

tion catalysts, all of them provide a mixture of diastereomers with the anti product
predominating. Thus, a catalyst able to provide optically active syn cyclopropyl
esters would constitute a useful complement to existing methodology. Rhodium
complexes of bulky porphyrins (“chiral fortress” porphyrins) have been developed
for this purpose [27]. The porphyrin ligands bear chiralbinaphthyl groups ap-
pended directly to the meso positions. Their rhodium(II1) complexes provide pre-
dominantly the syn cyclopropane with diazoesters, with very good stereoselectiv-
ity in some cases. However, the enantioselectivities observed are modest.
An alternative strategy for achieving asymmetric control may be by covalent
attachment of a chiral auxiliary to the carbenoid. This strategy has so far met
with rather limited success in cyclopropanation reactions (see eq. ( 3 ) for a similar
palladium-catalyzed reaction). However, the use of a-hydroxy esters as chiral aux-
iliaries with stabilized rhodium(I1) vinylcarbenoids allowed entry into both series
of enantiomeric vinylcyclopropanes with predictable stereochemistry. Optical
yields are fair to excellent [14] and the outcome of the reaction was rationalized
on the basis of interactions between the carbonyl oxygen of the chiral auxiliary
and the carbenoid carbon. The strategy led to an efficient synthesis of optically
active hydroxyvitamin D3 ring A [28].
Cyclopropane amino acids are extremely interesting compounds, which have
been found in nature. They present tremendous interest because of their biological
activity and potential use in conformationally restricted peptides (peptide mimics)
 3.I . 7.3 Recent Developments and Applications 803

and as biosynthetic and mechanistic probes. Since the mid-l980s, many synthetic
efforts have been directed toward this unique class of compounds [29]. Partially
enantioselective syntheses of the cyclopropane ring by catalyzed metal (mostly
rhodium) carbene addition to the properly substituted alkenes have been reported
but so far with only limited success. The subject has been reviewed [30 a].
Optimal catalysts for the key cyclopropanation step in a synthesis of 3-phenyl-
2,3-methanophenylalanine were identified by screening libraries of metal
complex-chiral ligand combinations. Rhodium(I1)-based catalysts proved to be
superior to the Ag-, Cu-, Ru-, Sc- and Pd-based complexes tested [30 b]. So
far, this constitutes one of the very rare applications of combinatorial chemistry
in catalyzed cyclopropanation reactions.
Efforts to recover and to reuse the catalyst have rarely been made and there
have so far been few attempts at heterogenizing soluble rhodium catalysts. Attach-
ment of dirhodium(I1) carboxylate groups to terminally substituted polyethylene
carboxylic ligands gave effective and reusable catalysts for olefin cyclopropana-
tion [311. Initial results of similar investigations with chiral dirhodium(I1) com-
plexes are not decisive. Although a high level (98 % ee) was attained in the intra-
molecular cyclopropanation of 3-methyl-2-buten-l-yl diazoacetate, enantioselec-
tion decreased after a few runs [32 a]. On the other hand, a comparative study
of the cyclopropanation of styrene and 1,2-dihydropyrane with diazoacetates cat-
alyzed by Cu and Rh complexes supported on a modified USY-zeolite indicated
no significant deviation of the reactivityhelectivity pattern from that obtained with
the corresponding complexes in solution, the Cu catalysts being remarkably more
active than the Rh ones. The supported catalysts could be used without loss of
cyclopropanation activity and metal leaching in at least five successive runs [32 b].
Another strategy to recover the catalyst is suggested by the concept of “fluorous
biphasic systems”. An application of this strategy to cyclopropanation with methyl
diazoacetate using as catalyst rhodium(I1) carboxylates featuring a long perfluoro-
alkyl chain showed that the catalyst could be reused several times without
significant loss of activity [32 c].

Simmons-Smith Reactions

Asymmetric cyclopropanation of olefins can also be achieved by the Simmons-

Smith reaction. This stoichiometric reaction, first investigated at the Du Pont com-
pany, involves an (iodoa1kyl)zinc iodide complex (eq. (10)) or, as reported more
recently, diiodomethane and trialkylaluminum [33].

RCH12 + Zn(Cu) -ether I-CHR-Znl -

>=( (10)

The organozinc intermediate is electrophilic but sterically rather hindered. The

reaction is characterized by broad generality, olefin stereospecificity, regioselec-
tivity, and chemoselectivity [34]. In the presence of a catalytic amount of a non-
804 3.1 Development of Methods

covalently bound chiral auxiliary, optically active cyclopropanes are formed [3S].
This is the so-called catalytic Simmons-Smith reaction (catalytic in ligand but not
in metal). The reaction shows some promise but the turnover number TON (based
on chiral ligand) and enantiomeric excesses are in most cases insufficient. Use of
C2-symmetrical chiral auxiliaries attached to achiral unsaturated aldehydes and
ketones by the formation of acetals or ketals appears most promising. For
instance, high yields and high enantiomeric excess (> 90 %) were reported [36]
with the readily available diisopropyl tartrate auxiliary (eq. (1 1)).

Despite the fact that zine carbenoids have been studied quite extensively, little
work has been done to modify the nature of the R group of the zinc reagent
“RZnCH,X”. A recent finding that phenoxide derivatives “ArOZnCHJ’ are
very reactive species for the cyclopropanation of unfunctionalized olefins consti-
tutes a first and promising step toward the development of an enantioselective
cyclopropanation method for unfunctionalized olefins [36 c].
Strategies based on the Simmons-Smith reaction are presently developed for
the synthesis of polycyclopropanes of defined absolute and relative stereochemis-
try in relation with natural product 10, a fascinating natural fatty-acid amide
nucleoside that shows promise as an antifungal drug [3S, 371.

O d

10

3.1.7.3.2 Non-Enantioselective Cyclopropanations

Styrene cyclopropanation continues to attract much interest. Cationic complex
CpFe(C0)2(THF)+BF4-mediates carbene transfer from ethyl diazoacetate with
high cis selectivity (cis:truns = 8S:lS) [38]. On the other hand, Tp’Cu(C2H4),
where Tp’ is hydrotris(3,S-dimethyl-1-pyrazolyl)borate, is one of the rare catalysts
to promote carbene transfer from ethyl diazoacetate to alkenes and also to alkynes.
While cyclopropanes are formed in high yield, cyclopropenes are obtained only in
moderate yield [39]. The same complex also catalyzes nitrene transfer from
PhI=NTs to alkenes to produce aziridines in high yields.
 3.1.7.4 Conclusion: In Search of New Catalysts 805

Another application of rhodium carbenoid chemistry relates to the synthesis of

strained-ring nitro compounds as high energy-density materials. Nitrocyclo-
propanes are the simplest members of this class of compounds and catalyzed
additions of a nitrocarbene to an olefin have only been described recently [40].
Detailed studies have shown that the success of the reaction is, as expected,
dependent on both the alkene and the nitrodiazo precursor. Consistently with
the electrophilic character of rhodium carbenoids, only electron-rich alkenes are
cyclopropanated. The reaction has been extended to the synthesis of nitrocyclo-
propenes but the yields are good for terminal acetylenes only [41].

3.1.7.4 Conclusion: In Search of New Catalysts

Rhodium-based catalysis suffers from the high cost of the metal and quite often
from a lack of stereoselectivity. This justifies the search for alternative catalysts.
In this context, ruthenium-based catalysts look rather attractive nowadays,
although still poorly documented. Recently, diruthenium(I1,II) tetracarboxylates
[42], polymeric and dimeric diruthenium(1,I) dicarboxylates [43], ruthenacarbor-
ane clusters [44], and hydride and silyl ruthenium complexes [45 a] and Ru por-
phyrins [45 b] have been introduced as efficient cyclopropanation catalysts,
superior to the Ru(I1,III) complex Ru,(OAc)4C1 investigated earlier [7]. In terms
of efficiency, electrophilicity, regio- and (partly) stereoselectivity, the most
efficient ruthenium-based catalysts compare rather well with the rhodium(I1)
carboxylates. The ruthenium systems tested so far seem to display a slightly
lower level of activity but are somewhat more discriminating in competitive
reactions, which apparently could be due to the formation of less electrophilic
carbenoid species. This point is probably related to the observation that some
ruthenium complexes competitively catalyze both olefin cyclopropanation and
olefin metathesis [46], which is at variance with what is observed with the
rhodium catalysts.
The first ruthenium-catalyzed asymmetric cyclopropanation has been reported
recently. The catalyst, prepared from [Ru"Cl,(p-cymene)], and the chiral bis(ox-
azolidiny1)pyridine ligand [47], cyclopropanates styrene with high stereoselectiv-
ity (trans:cis > 95:5) and enantioselectivity (> 95 % ee). Interestingly the same
ruthenium complex, [Ru"Cl2(p-cyrnene)],, in combination with tricyclohexylpho-
sphine is one of the most potent catalyst precursors for the metathesis of functio-
nalized cycloolefins [48]. A resin-bound arene-ruthenium(I1) complex has been
used as catalyst in cyclopropanation reactions and gave the desired products in
yields comparable with those from the corresponding soluble catalyst. No leach-
ing from the polymer support was observed [49]. Ruthenium complexes are thus
versatile derivatives that can promote either olefin metathesis or olefin cyclopro-
panation when reacted with diazo compounds. Their recent emergence as cyclo-
propanation catalysts is particularly worthy of interest. Because of the low cost
of the metal, ruthenium-based catalysts could advantageously replace the more ex-
pensive rhodium derivatives in the future. The reactions of ruthenium complexes
seem of broad generality and are characterized by an excellent tolerance of
806 3. I Development of Methods

organic functionalities. More detailed studies are now needed to assess fully their
place in the ever-expanding sphere of homogeneous catalysis.

References
[ l ] (a) A. D. Walsh, Trans. Faraday Soc. 1949,45, 179; (b) A. D. Walsh, Nature (London)
1947, 165, 712.
[2] (a) C. A. Coulson, W. E. Moffitt, Philos. Mag. 1949, 40, 1; (b) C. A. Coulson, W. E.
Moffitt, J. Chem. Phys. 1947, 15, 151.
[3] M. J. S. Dewar, J. Am. Chem. Soc. 1984, 106, 669.
[4] D. Cremer, J. Gauss, J. Am. Chem. Soc. 1986, 108, 7467.
[5] B. M. Trost, Angew. Chem., lnt. Ed. Engl. 1995, 34, 259.
[6] (a) T. Aratani, Pure Appl. Chem. 1985, 57, 1839; (b) A. Nakamura, ibid. 1978, 50, 37,
and references cited therein.
[7] A. J. Anciaux, A. J. Hubert, A. F. Noels, N. Petiniot, P. TeyssiC, J. Org. Chem. 1980,
45, 695.
[8] M. P. Doyle, B. D. Brandes, A. P. Kazala, R. J. Pieters, M. B. Jarstfer, L. M. Watkins,
C. T. Eagle, Tetrahedron Lett. 1990, 31, 6613.
[9] G. Maas, Top. Curx Chem. 1987, 137, 75.
[lo] (a) M. P. Doyle, Chem. Rev. 1986, 86, 919; Acc. Chem. Res. 1986, 19, 348; (b)
A. Padwa, D. J. Austin, Angew. Chem., Int. Ed. Engl. 1994,33, 1797; (c) A. Demonceau,
A. J. Hubert, A. F. Noels in Metal Promoted Selectivity in Organic Synthesis (Eds.: A. F.
Noels, M. Graziani, A. J. Hubert), Kluwer Academic Publishers, Dordrecht, 1991, p. 237;
(d) J. Adams, D. M. Spero, Tetrahedron 1991, 47, 1765.
[ l l ] (a) T. Ye, M. A. McKervey, Chem. Rev. 1994, 94, 1091; (b) A. Demonceau, A. F.
Noels, A. J. Hubert in Aspects of Homogeneous Catalysis, Vol. 6 (Ed.: R. Ugo),
D. Reidel, Dordrecht, 1987, p. 199; (c) W. A. Henmann, Angew. Chem. 1978, 90,
855; Angew. Chem., Int. Ed. Engl. 1978, 17, 800; (d) W. A. Henmann, Pure Appl.
Chem. 1982, 54,65.
[12] (a) Y. V. Tomilov, V. A. Dokichev, U. M. Dzhemilev, 0. M. Nefedov, Russ. Chem. Rev.
1993, 62, 799; (b) S. Denmark, R. Stavenger, A.-M. Faucher, J. Edwards, J. Org. Chem.
1997, 62, 3375.
[I31 S. Vangveravong, D. E. Nichols, J. Org. Chem. 1995, 60, 3409.
[I41 H. M. L. Davies, N. J. S. Huby, W. R. Cantrell Jr., J. L. Olive, J. Am. Chem. Soc. 1993,
115, 9468.
[15] (a) P. W. Jennings, L. L. Johnson, Chem. Rev. 1994, 94, 2241; (b) M. Brookhart, W. B.
Studabaker, ibid. 1987, 87, 41 1.
[16] (a) M. C. Pirmng, A. T. Morehead Jr., J. Am. Chem. SOC.1994, 116, 8991; (b) A.
Demonceau, A. F. Noels, J.-L. Costa, A. J. Hubert, J. Mol. Catal. 1990, 58, 21.
[17] Reviews: (a) R. Noyori, Asymmetric Catalysis in Organic Synthesis, John Wiley and
Sons, New York, 1994, p. 199; (b) S. Kotha, Tetrahedron 1994, 50, 3639; (c) R. A. Shel-
don, Chirotechnology: Industrial Synthesis of Optically Active Compounds, M. Dekker,
New York, 1993, p. 311.
[18] C. PiquC, B. Fiihndrich, A. Pfaltz, Synlett 1995, 491.
[19] (a) S. K Kanemasa, S. Hamura, H. Yamamoto, Tetrahedron Lett. 1994, 35, 7985; (b)
G. Cheluchi, M. A. Cabras, A. Saba, J. Mol. Catal. 1995, 95, 7.
[20] (a) F.-C. Shu, Q.-L. Zhou, Synth. Commun. 1992,29,567; (b) D. A. Evans, K. A. Woer-
pel, M. M. Hinman, M. M. Faul, J. Am. Chem. SOC. 1991, 113, 726.
[21] R. E. Lowenthal, S. Masamune, Tetrahedron Lett. 1991, 32, 7373.
 References 807

(221 M. A. McKervey, T. Ye, J. Chem. Soc., Chem. Commun. 1992, 823.

1231 E. J. Corey, T. G. Gant, Tetrahedron Lett. 1994, 35, 5373.
[24] (a) M. P. Doyle, W. R. Winchester, J. A. A. A. Horn, V. Lynch, S. H. Simonsen,
R. Ghosh, J. Am. Chem. Soc. 1993, 115, 9968 and references cited therein; (b) M. P.
Doyle, M. Y. Eismont, M. N. Protopopova, M. M. Y. Kwan, Tetrahedron 1994, 50,
1674; (c) M. P. Doyle et al., J. Chem. Soc., Chem. Commun. 1997, 211; (d) M. P.
Doyle et al., J. Chem. Soc., Chem. Commun. 1997, 983.
[25] D. H. Rogers, E. C. Yi, C. D. Poulter, J. Org. Chem. 1995, 60, 941.
1261 (a) M. N. Protopopova, E. A. Shapiro, Russ. Chem. Rev. 1989,58, 667; (b) M. P. Doyle,
M. N. Protopopova, P. Miiller, D. Ene, E. A. Shapiro, J. Am. Chem. Soc. 1994, 116, 8492
and references cited therein.
1271 (a) J. L. Maxwell, S. O’Malley, K. C. Brown, T. Kodadek, Organornetallics 1992, 11,
695; (b) S. O’Malley, T. Kodadek, ihid. 1992, 11, 2299; (c) D. W. Baetley, T. Kodadek,
J. Am. Chem. Soc. 1993, 115, 1656.
1281 W. G. Dauben, R. T. Hendricks, B. Pandy, S. C. Wu, X. Zhang, M. J. Luzzio, Tetra-
hedron Lett. 1995, 36, 2385.
1291 (a) R. Pelliciari, B. Natalini, M. Marinozzi, J. B. Monahan, J. P. Snyder, Tetrahedron
Lett. 1990, 31, 139; (b) K. Schimamoto, Y. Ohfune, ibid. 1990, 31, 4049; (c) S. F.
Martin, C. J. Oalman, S. Liras, Tetrahedron 1993, 49, 3521; (d) S. F. Martin, C. J. Oal-
man, S. Liras, ibid. 1993 49, 3521; review: J. Salaiin in Topics Current Chem. 2000,
207, 1.
[30] (a) C. H. Stammer, Tetrahedron 1990, 46, 2231; (b) 0. Moye-Sherman, M. B. Welch,
J. Reibenspies, K. Burgess, J. Chem. Soc., Chem. Commun. 1998, 2377.
1311 D.E. Bergbreiter, M. Morvant, B. Chen, Tetrahedron Lett. 1991, 32, 2731.
[32] (a) M. P. Doyle, M. Y. Eismont, D. E. Bergbreiter, H. N. Gray, J. Org. Chem. 1992, 57,
6103; (b) M. J. Alcon, A. Coma, et al., J. Mol. Catal. A: 1999, 147, 337; (c) A. Endres,
G. Maas, Tetrahedron Lett. 1999, 40, 6365.
[33] K. Maruoka, Y. Fukutani, H. Yamamoto, I. Org. Chem. 1985 50, 4412.
[34] K. P. Zeller, H. Gugel in Methoden Org. Chem. (Houben-Weyl)1989, Vol. EXIXb, p. 195.
[35] (a) C. R. Theberge, C. K. Zercher, Tetrahedron Lett. 1994, 35, 9181; (b) R. W. Arm-
strong, K. W. Maurer, ibid. 1995,36, 357 and references cited therein; (c) A. B. Charette,
H. Juteau, J. Am. Chem. SOC. 1994, 116, 2651; (d) A. G. M. Barrett, W. W. Doubleday,
K. Kasdorf, G. J. Tustin, A. P. J. White, J. Chem. Soc., Chem. Commun. 1995, 407 and
1143.
[36] (a) E. A. Mash, S. B. Hemperly, K. A. Nelson, P. C. Heidt, S. Van Deusen, J. Org. Chem.
1990,55, 2045; (b) A. Mori, I. Arai, H. Yamamoto, H. Nakai, Y. Arai, Tetrahedron 1986,
42, 6447, A. B. Charrette et al., Angew. Chem., In/. Engl., 2000, 39, 4539.
1371 S. Stinson, Chem. Eng. News 1995 (April 17), 22.
1381 W. J. Seitz, A. K. Saha, Tetrahedron Lett. 1992, 33, 7755.
1391 P. J. PCres, M. Brookhart, J. L. Templeton, Organometallics 1993, 12, 261.
[40] P. E. O’Bannon, W. P. Dailey, Tetrahedron 1990, 21, 7341.
[41] P. E. O’Bannon, W. P. Dailey, J. Org. Chem. 1991, 56, 2258.
1421 A. Demonceau, A. F. Noels, E. Saive, A. J. Hubert, J. Mol. Catal. 1992, 76, 123.
1431 G. Mass, T. Werle, M. Alt, D. Mayer, Tetrahedron 1993, 49, 881.
1441 A. Demonceau, E. Saive, A. F. Noels, I. T. Chizhevsky, I. A. Lobanova, V. I. Bregadze,
Tetrahedron Lett. 1992, 33, 2009.
1451 (a) A. Demonceau, E. Abreu Dias, C. A. Lemoine, A. W. Stumpf, A. F. Noels, C. Pie-
traszuk, J. Gulinski, B. Marciniec, Tetrahedron Lett. 1995, 36, 3519; (b) M. Frauenkorn,
A. Berkessel, Tetrahedron Lett. 1997, 38, 7175.
1461 A. F. Noels, A. Demonceau, E. Carlier, A. J. Hubert, R. Sanchez Delgado, J. Chem. Soc.,
Chem. Commun. 1988, 783.
808 3.1 Development of Methods

[47] (a) S. B. Park, H. Nishiyama, K. Itoh, J. Chem. Soc., Chem. Commun. 1994, 1315; (b)
H. Nishiyama, Y. Itoh, H. Matsumoto, S. B. Park, K. Itoh, J. Am. Chem. Soc. 1994,
116, 2223.
[48] A. W. Stumpf, E. Saive, A. Demonceau, A. F. Noels, J. Chem. Soc., Chem. Commun.
1995, 1127.
[49] N. E. Leadbeater, K. A. Scott, L. J. Scott, J. Org. Chem. 2000, 65, 3231.

3.1.8 The Fischer-Tropsch Synthesis -

Molecular Models for Homogeneous Catalysis?
Wolfgang A. Herrmann

3.1.8.1 Introduction
The Fischer-Tropsch (FT) synthesis comprises a group of reactions that convert
syngas (carbon monoxide and hydrogen) into liquid hydrocarbons for broad appli-
cations as motor fuels and chemical feedstocks. The original process was discov-
ered in 1925 by the German chemists Franz Fischer and Hans Tropsch in the
Kaiser-Wilhelm-Institut at MulheimRuhr (Germany), nowadays called the
Max-Planck-Institut fur Kohlenforschung [ 1-31. Equation (1) summarizes in a
most formalistic manner the rather complex chemistry of a process which stands
as a prototype of heterogeneous catalysis.

n CO + 2 n Hz 2 +cl-l2k + n H 2 0 + 165 kJ/mol (1)

Numerous patents, monographs [4], and review articles [5] appeared ever since
the Fischer-Tropsch synthesis was developed as an industrial process at Ruhr-
chemie AG in Oberhausen (Germany) by Otto Roelen and his group [6a]. With
a broad product spectrum being a typical feature of carbon monoxide reduction
according to eq. (l), it is no surprise that both the nature of the catalysts and
the reaction parameters determine the final product patterns, thus demonstrating
the enormous scope of what is called “the” Fischer-Tropsch synthesis. For
example, the related Kolbel-Engelhardt variant according to eq. (2) yields up to
60 % of hydrocarbons and 40 % of “oxygenates”, e. g., alcohols, aldehydes, and
other oxygen-containing products (iron-based catalysts, 180-280 OC, medium
pressure, CO-containing gas mixtures).
The role of water also comes to the fore in the “classical” Synthol and Kogasin
processes (Koks + Gas + Benzin; i.e., carbon + gaseous products + gasoline)
of Fischer and Tropsch, not least by virtue of the ubiquitous water-gas shift reac-
tion following eq. (3), (cf. Section 3.2.11). It is obvious that the reducing action of
water leads to a corresponding amount of carbon dioxide which is in equilibrium
under the standard process conditions.
 3.1.8.2 Historical and Economic Background 809

3nC0 + nH20 - ( c H ~+ ~2 n C 0 2 (2)

cat.
CO + H20 G= C02 + H2 + 40kJ/mol (3)

3.1.8.2 Historical and Economic Background

Although the Fischer-Tropsch synthesis is a textbook example of heterogeneous
catalysis, its treatment in this book is justified for a number of reasons.
First, the gradual but dramatic shift of the feedstock situation in the (normally
catalytic) synthesis of organic basic and fine chemicals has to be kept inmind.
Just to consider the German chemical industry (Figure l),the year 1960 landmarked
the crossover from coal- to petrochemical-based organic chemistry. In Germany,
from that time, an exponential shrinkage of the carbon feedstock occurred while
oil refineries became the dominating feature, even in a country which has no
such resources at all. In 1990, the share of feedstock carbon to make organic
base chemicals was down to 3.5 %. We note that 1960 also landmarked the accel-
eration of development of homogeneous catalysis processes, e. g., the manufacture
of acetaldehyde from ethylene rather than (as before) from coal-based acetylene, the
production of which has meanwhile descended to almost zero; yet acetylene repre-
sented the main foundation of organic chemistry in the first half of our century.
It is clear that for a number of political and economic reasons the FT-synthesis,
as the only large-volume carbon-based process having survived on the industrial
scene, can only compete in countries where coal is both abundant and cheap and
where the political situation favors or requires a domestic base of chemical feed-
stock. It seems that South Africa was the only place to meet these requirements.

v (lo3to)
Igvt I i chemicals
based on oil k
based on coal

50/50%

year - I
1960 1970
I I *
1980

Figure 1. Development of the feedstock scenario for organic chemicals in Germany.

8 10 3.1 Development of Methods

Otherwise, only significantly increased product selectivities (e. g., to value-added

chemical feedstocks such as ethylene and propene) could make Fischer-Tropsch
chemistry attractive in other countries, too [4 h, i].
Second, the original Fischer-Tropsch research was the wet-nurse in the cradle
of homogeneous catalysis. Otto Roelen had been in charge of Franz Fischer’s pilot
plant ( 1924-1934), as the successor of Hans Tropsch, before he joined Ruhrche-
mie AG where he invented the hydroformylation process (1938) as a spin off from
his work related to the commercialization of the Fischer-Tropsch synthesis [6 a,
b]. However, it only became evident in the early 1950s that a molecularly defined,
homogeneous catalyst - Hieber’s hydridocobalt tetracarbonyl, HCo(CO), - was
responsible for the “restricted C-C coupling” (by only one step) from ethylene
to propanal and from propene to butanal, respectively [6 a]. The “Verfahren zur
Gewinnung mehrgliedriger Paraffinkohlenwasserstoffe aus Kohlenoxid und
Wasserstoff auf katalytischem Wege” (“Process to obtain multi-unit paraffin hydro-
carbons from carbon monoxide and hydrogen in a catalytic way”) was filed as a
patent by Fischer and Tropsch on July 21, 1925 [ l a]. The first catalyst, an iron/
zinc oxide mixture, producing small amounts of higher hydrocarbons, had been
made for the first time on May 25, 1925, by Otto Roelen, then 28 years old!
Third, and not least, the mechanistic features of the Fischer-Tropsch hydrocar-
bon synthesis mirror a plethora of organometallic chemistry. More precisely: Mo-
lecular models have been invoked that could eventually lead to more product se-
lectivity for eq. (1). Although plausible mechanistic schemes have been consid-
ered, there is no way to define precisely the reaction path(s), simply because
the catalyst surface reactions escape detection under real process conditions
(see Section 3.1.1.4). Nevertheless, the mechanism(s) of reductive hydrocarbon
formation from carbon monoxide have strongly driven the organometallic chem-
istry of species that had previously been unheard of methylene (CH,) [7-91 and
formyl (CHO) [ 101 ligands were discovered as stable metal complexes (Structures
1-3) only in the 1970s [7, 81. Their chemistry soon explained a number of typical
Fischer-Tropsch features [ 11, 121. At the same time, it became clear to the cata-
lysis community that molecular models of surface-catalyzed reactions cannot be

-,.. 1
M=C
/ A
M-M M-C,
0
4
\
dimetallacyclopropane H
alkylidene (p-alkylidene) forrnyl

1 2 3
 3.1.8.4 Mechanistic Considerations 8 11

taken for granted in terms of a penultimate mechanism, simply because the real
reaction conditions are normally more severe than organometallic catalysts
would tolerate.

3.1.8.3 Technological Features

The largest application of the Fischer-Tropsch synthesis is centered in South
Africa: Sasol I in Sasolburg (since 1955) and Sasol II/III in Secunda (since
1980/1982) produce approx. 40-50 % of the entire South African supply of gaso-
line. There are estimates that South Africa converts ca. 22 million tons of coal an-
nually to at least 4.5 million tons of gasoline. By virtue of Ruhrchemiekurgi
technology, mostly higher-boiling hydrocarbons are manufactured (dieseloil,
waxes) with iron-based precipitation catalysts at 2 10-250 “C. Low-boiling prod-
ucts arise from the “Kellogg-Synthol process”, again with iron catalysts but at
higher temperatures (300-340 “C). More detailed information about the commer-
cial-scale FT synthesis is given in Ref. [4 d-f, h-k].
The product spectrum is generally poor in branched hydrocarbons and is domi-
nated by aliphatics and a-olefins. However, the specific nature of the catalysts
greatly influences the result. For example, ruthenium catalysts under very high
pressure yield polymethylene with molecular weights up to 240 000. By way of
contrast, nickel favors the methanization of carbon monoxide.
Both activity and selectivity respond in a very sensitive manner to the extent of
catalyst alkalization (normally doping by means of K,O). It appears that the
chemisorption of the reactants and the speed of all CO-consuming reactions
(CO reduction, water-gas shift reaction, surface-carbide formation, etc.) are
increased. While in former times the “liquefaction” result (amount of liquid gaso-
lines) was the quality measure of a Fischer-Tropsch catalyst, nowadays it is narrow
product distributions into which research puts its efforts. To this end, the mecha-
nistic question has maintained focal importance. The oil crisis in the 1970s initiated
intensive work in order to narrow down the Fischer-Tropsch product spectrum.

3.1.8.4 Mechanistic Considerations

Any mechanistic proposal must comply with the following observations. (1) The
Fischer-Tropsch hydrocarbon synthesis follows the formalism of polymerization
kinetics with a Schulz-Flory distribution of the molecular weights. (2) a-Olefins
and alcohols occur as the primary products. (3) The aliphatic final products are
formed consecutively by hydrogenation of the olefins according to I4C-labeling
experiments [4 f, 30 b]. (4) Chain termination processes do not deactivate the
catalyst centers because the chain-growth velocity stays constant for weeks.
The original inventors anticipated that their CO hydrogenation is basically a
“polymerization of methylene groups” [2 a]. However, alternative and additional
mechanisms must be invoked in light of organometallic chemistry and the fact that
certain oxygen-containing by-products are to be explained.
812 3.1 Development of Methods

3.1.8.4.1 The Carbidemethylene Mechanism

There is little doubt that both the carbon monoxide and the hydrogen molecule
undergo chemisorption on the catalyst surface resulting in bond dissociation to
give carbide, 0x0, and (monoatomic) hydrido species (Scheme 1).

f Fischer-Tropsch

. c.
0.
ylj

I I
I
I
I

Scheme 1
 3.I .8.4 Mechanistic Considerations 8 13

Subsequent hydrogenation of the surface-attached carbon atoms is anticipated

to yield methylidyne (CH), methylene (CH,), and methyl (CH,) fragments; the
oxygen is taken off the surface as water, again by hydrogenation. It is reason-
able to assume that a surface methylene group inserts in a CH3-Fe, bond (Fe,:
cluster ensemble of surface-iron atoms) to furnish the first C-C bond. Conse-
cutive methylene insertions carry the hydrocarbon chain growth to a point
where the standard termination reactions - b-hydrogen elimination or hydroge-
nation - come in operation. The “methylene polymerization” in the mechanism
suggested by Fischer and Tropsch 0 thus corresponds to a succession of inser-
tion steps. Methylene groups were detected spectroscopically on nickel surfaces
during the methanation of carbon monoxide [13, 21 b]. A number of experi-
mental facts and organometallic models give support to the mechanistic
Scheme 1:

(a) Sterically exposed carbon atoms in oligonuclear iron cluster structures like 4
undergo easy, reversible hydrogenation in terms of intramolecular hydrogen
migration (fast exchange of Ha and Hb, eq. (4)). This result indicates the
high mobility of hydrogen atoms on carbidic metal surfaces. The FeCH
three-center bonding, precisely detected for the cluster species 4 by neutron-
diffraction [ 141, underlines the importance of M-H-C interactions in catalytic
processes.

4
M = Fe(C0)3
Ha= Hb

(b) Metal-bridging methylene (CH,) undergoes interconversion into methyl (CH,)

and methylidyne (CH) groups. The well-explored chemistry of the dirhodacyc-
lopropane 5 yields, with H2/CH4 elimination, the (cationic) CH complex 6
upon treatment with protic reagents (eq. ( 5 ) ) [15]. On the other hand, equili-
bria of the type M-CH3 G HM=CH, have been invoked by Green et al. [16]
for the Ziegler olefin polymerization via “a-agostic interactions”.

H l+

1
6
8 14 3.1 Development of Methods

(c) The pivotal methylene/methyl coupling has a molecular precedent in the radi-
cal-initiated formation of the n-ethylene hydrido complex 7; intermediate
methylene/methyl vs. ethyl species seem to unequivocally describe the (iso-
lated) final product 7 [17] (eq. (6)).

(d) Surface-carbide formation is evident from labeling experiments exploiting the

Boudouard equilibrium of I3CO (Scheme 2a). Subsequent treatment of a I3C-
carbidized Fischer-Tropsch catalyst with ' *Corn2mixtures yields 13C-labeled
Cl+ hydrocarbons [ 181. In a chemically different approach [ 111, radiolabeled
ketene was passed over a catalyst surface. The 14CH2groups thus generated
(by CO elimination) transform into growing hydrocarbon chains upon treat-
ment with syngas under Fischer-Tropsch conditions (Scheme 2b).
(e) A most convincing support of the carbide/methylene mechanism comes from
a detailed study of the decomposition of gaseous diazomethane on Fischer-
Tropsch catalysts [ 191. Normally, only ethylene and nitrogen are formed be-
tween 25 and 200 "C under normal pressure on Ni, Pd, Fe, Co, Ru, and Cu
surfaces. Polymerization of the methylene groups thus generated only occurs
on Co, Fe, and Ru catalysts when CH2N2/H2 mixtures are being used.
Strikingly, both the product distribution (relative amounts of C, hydrocarbons,
see Figure 2), and the isomer pattern (e.g., the relative composition of C4
hydrocarbons, see Figure 3) are identical.
If dissociative hydrogen chemisorption does not occur, for example on copper
surfaces, then no CH2 + CH3 hydrogenation is possible and the methylene
groups can only dimerize to ethylene (Figure 2). Methyl groups are therefore ne-
cessary to induce the chain growth by consecutive C-C insertion; see Scheme 2.

A slightly modified proposal [20, 211 invokes surjiace vinyl species to arise
from methylidyne/methylene coupling (Scheme 2). Subsequent methylene inser-

a 2 1 3 ~ 0 - 13c02

Boudouard equilibrium
+ W.
..
V
a 1 4 ~ ~ ~ -
-=co~ =

"CO /
-I
~
1

H2
4

I\
~ ~ 2

14C-labeledhydrocarbons

Scheme 2
 3.1.8.4 Mechanistic Considerations 8 15

1 (bar) 68 (bar:
HzICHZN, HJCO
Co 200% Fe 2 7 5 " ~Ru 125°C Cu 1 5 0 " ~Pd 1 2 5 " ~Ni looocNi 200°C
100-

i.
80 - 1

60-

401LL
10
I- c,c3-c,1 3 5
3 5 ' h

Figure 2. Molecular-weight distribution of hydrocarbon fractions as generated on Fischer-

Tropsch catalysts from either H2/C0 or H2/CH2N2.Alkanes and olefins are plotted
together according to their chain lengths as indicated. The share of C2-hydrocarbons
is plotted as black columns. The results shown here originate from R. Pettit and co-
workers [19 a]; pressures up to 6.8 MPa (68 bar).

H,/CH,N,-gas feedl H,/CO-gas feed

100%- u u
90%- -
A/'
2

\
w
80%-

N N
70%-

60%- --<
N N
50%-
2% % 2 *
Figure 3. A Fischer-Tropsch catalyst containing 39 wt % cobalt on kieselguhr was heated at
210 "C at normal pressure with H2/CH2N2(left) and HJCO (right). The C,-fraction
was separated according to the isomers (see text). The data are reported in [19 a]
relating to the study of R. Pettit and co-workers.
8 16 3.1 Development of Methods

tion once again carries the chain-growth mechanism, with an allylic isomerization
taking care of the vinylic C-C unsaturation staying at the surface- metal “anchors”
(eq. (7)). This model explains the formation not only of a-olefins as the primary
Fischer-Tropsch products but also of some branched (a-)methyl hydrocarbons in
addition to the straight-chain hydrocarbons (eq. (8)). In addition, the often anom-
alously high proportion of C2 products would be in line with this mechanism.

Vinyl species have not been detected on metal surfaces but there is kinetic
evidence in the context of the dehydrogenation of (*H-labeled) ethylene to
chemisorbed ethylidyne on Pt( 111) sufaces, cf. eq. (9) [22].
Molecular models are available for all the reactions and intermediates invoked
in these mechanisms. For example, diazoalkanes have been known to generate
metal-carbene complexes, with the “cyclopropanation” of metal-metal “double”
bonds under smooth conditions (compare Section 3.1.7) being of particular
relevance to the chemistry of metal surfaces, cf. eq. (10) [8 a, 231.

The bisb-methy1ene)rhodium complex (Structure 8) undergoes thermal decom-

position at 300-350 “C to yield mainly propene and methane; 2H-labeling experi-
ments showed that the propene originates rather selectively (>75 %) from two
CH2 groups and one CH3 unit; a p-methylidene (CH) intermediate 9 (from H ab-
straction) with consecutive isomerizations is assumed to yield the propene
(Scheme 3).
The degradation can be followed under mild conditions in solution starting
from related cationic derivatives [20, 2 11. Model compounds of bond-labilized
 3.1.8.4 Mechanistic Considerations 8 17

8 9 4
M = (C5Me5)Rh

Scheme 3

carbon monoxide are in the meantime legion. It is common knowledge that 0-

coordination greatly weakens the C-0 bond, with the most spectacular example
still being the niobium cluster complex (Structure lo), with its unique p 3 , y2-co-
ordination mode of carbon monoxide [24]: the bond length is 130 pm in this
case (normally the length is 115-120 pm in C-coordinated CO), and the CO vibra-
tion occurs at 1330 cm-' in the infrared spectra (it is normally at 1600-1650 cm-'
for p,-CO, 1700-1850 cm-' for p2-C0, and > 1900 cm-' for terminal CO). Ther-
molysis of the cluster 10 yields carbidic niobium.
It appears reasonable from organometallic chemistry that Fischer-Tropsch
catalysts containing electropositive metals (e. g., potassium, lanthanoids) activate
carbon monoxide better than do pure metals. For example, the structurally
characterized complex 11 [25] exhibits quite a long C-0 bond (155.0 pm;
K O = 1667 cm-I).
130.3 pm

155.0 pm

An alternative route to surface-methylene groups involves stepwise reduction of

carbon monoxide rather than dissociative chemisorption. Scheme 4 describes a
number of plausible intermediates, all of which have been seen as isolable, well-
characterized molecular compounds [ 111: carbonyl (a), formyl (b), hydroxycarbene
(c), hydroxymethyl (d), and methylene (e). They are summarized in Ref. [8-121.
8 18 3.I Development of Methods

carbonyl (a) formyl (b) hydroxycarbene (c)

rnethylene (e) hydroxymethyl (d)

Scheme 4. Stepwise formal reduction of carbon monoxide. The figures 0 , 0 ,and 0 relate to
the numbers of the mechanistic models in Schemes 1 and 5.

It is of particular relevance here that reduction of O S ~ ( C O )by

, ~ a hydridobo-
ranate reagent yielded the methylene complex Os3(CO)I ICH2,with the hydrogen
atoms originating from the hydridic reductant [26]. Other intermediates along
the reduction path of Scheme 4 were first described in the classical review article
tackling molecular aspects of the Fischer-Tropsch reaction [ 111. Hydrogen does
not suffice, however, to perform the stepwise transformation (a) -++(e) in
Scheme 4. To our knowledge, not even the first step - formation of formyl from
carbon monoxide - has a molecular precedent established by elemental hydrogen.

3.1.8.4.2 The Hydroxycarbene Mechanism

To explain the incorporation of alcohols and aldehydes in Fischer-Tropsch prod-
ucts, hydroxycarbene species M=C(H)OH were invoked by several authors
although not on firm organometallic grounds (Scheme 5 , mechanism 0 ) .We
note particularly that metal-attached hydroxycarbene readily eliminates acetal-
dehyde [27] while condensation steps have not yet been seen in stoichiometric
reactions. However, the first C-C bond-making step of this Anderson-Emmett-
Kolbel mechanism [28] corresponds to a hydroxyacetylene HC =C-OH species,
of which metal complexes were recently isolated [29].

3.1.8.4.3 The Alkyl Migration Mechanism

Closely related to well-known organometallic chemistry is the third mechanistic
proposal, the Pichler-Schulz mechanism ( 1970), which proposes the migration
 3.1.8.5 Assessment and Perspectives 8 19

Anderson- Pichler-Schulz
Emmett-Kolbel

via =CH2

an
u
H, ,OH H, ,OH

II

of alkyl (methyl) groups from a surface position to coordinated carbon monoxide

(Scheme 5 , mechanism 0 ) .Problems are detected in the intermediacy of acyl spe-
cies which, according to common knowledge, do not hydrogenate to the desired
hydrocarbon. This proposal [30] would at least account for the observed formation
of oxygen-containing products, as does the Anderson-Emmett-Kolbel mecha-
nism.

3.1.8.5 Assessment and Perspectives

Far more than 5000 patents have been filed on the subject of the Fischer-Tropsch
hydrocarbon synthesis since it was discovered 75 years ago. A quite reliable
mechanistic picture is now available but a one-by-one transfer from heterogeneous
to homogeneous catalysis seems not to be feasible [21 b]. A key problem is the
820 3.1 Development of Methods

inertness of carbon monoxide toward hydrogen reduction (8, eq. (11)) in the
usual modes of coordination. Not even the organic-type Clemmensen @ and
Wolff-Kishner reductions @ have ever been observed for metal-coordinated
carbon monoxide. Furthermore, formyl groups - formed in the first step of CO
reduction - do not arise under “homogeneous” (i.e., molecular, organometallic)
Fischer-Tropsch conditions although, on the other hand, numerous well-defined
metal-formyl complexes are known.

0 I

If methylene and methyl groups were formed, their further C-C coupling trans-
formations could very well work in a molecular environment because there is
ample evidence in stoichiometric reactions [31]. This bonds back to the
“evergreen” topic of carbon monoxide activation: whoever is the first to find
molecular ensembles (probably di- or oligometallic) splitting the CO molecule
(e. g., with activity surpassing models like 10 and ll), will win the competition
for a homogeneous, possibly more selective, Fischer-Tropsch synthesis! It is
obvious, then, that the chemistry of di- and oligocomplexation at electronically
different sites (e. g., C o h , Fe/K) needs to be investigated. This last-named
feature is clearly the secret of Fischer-Tropsch catalysts. One has to be reminded
that typical Fischer-Tropsch conditions (180-220 “C) are not very far from the
organometallic limits.
It should also be noted that hydrocarbon activation is a possible alternative
entry to “methylene polymerization”: methane, for example, may activate at
metal sites to yield surface-methyl species adjacent to each other (eq. (12)).
There is a molecular precedent of binuclear, intramolecular methane elimination
from such structures (osmium) to yield p-methylene complexes [311.

Under these perspectives, the chemistry of methylidyne and methylene groups

in a bimetallic environment including electronically different metals (e. g., iron
and lanthanum) merits future efforts to obtain a more precise understanding of
the fundamental hydrocarbon coupling/isomerization processes. One should not
naively believe, however, that organometallic studies can provide us with a
fully detailed catalytic cycle (only a single one?) - they are good enough to
demonstrate the feasibility of isolated mechanistic steps!
 References 821

References
[ l ] (a) F. Fischer, H. Tropsch, DE 484.337 (1925/1929); (b) F. Fischer, H. Tropsch, DE
524.468 (1926/1931).
[2] (a) F. Fischer, H. Tropsch, Brennst.-Chem. 1926, 7, 97; (b) F. Fischer, H. Tropsch,
Ber: Dtsch. Chem. Ges. 1926, 59, 830.
[3] G. Wilke, Festschrifi zum 75jahrigen Bestehen des Max-Planck-lnstituts fur Kohlen-
forschung, Miilheim/Ruhr, 1989.
[4] (a) H . H. Storch, N. Golumbic, R. B. Anderson, The Fischer-Tropsch and Related Syn-
theses, John Wiley, New York, 1951; (b) G. c. Bond, Catalysis by Metals, Academic
Press, New York, 1962; (c) C. D. Frohning, H. Kolbel, M. Ralek, W. Rottig, F. Schnur,
H. Schulz, in Chemierohstoffe aus Kohle (Ed.: J. Falbe), Thieme-Verlag, Stuttgart, 1977,
Chapter 8 , pp. 219-299; (d) C. D. Frohning, in New Syntheses with Carbon Monoxide,
Springer, Berlin, 1980; (e) M. E. Dry in Catalysis-Science and Technology (Eds.: J. R.
Anderson, M. Boudart), Springer, Berlin, 1981, Vol. 1, pp. 159-255; (f) R. B. Anderson,
The Fischer-Tropsch Synthesis, Academic Press, London, 1984; (8) R. A. Sheldon, Che-
micals from Synthesis Gas, D. Reidel, Dordrecht, 1983; (h) C. D. Frohning, B. Cornils,
Hydrocarb. Proc. 1974, ( l l ) , 143; (i) B. Biissemeier, C. D. Frohning, B. Cornils, Hydro-
curb. Proc. 1976, (1 l), 105; (k) G. Ertl, H. Knozinger, J. Weitkamp (Eds.), Handbook of
Heterogeneous Catalysis, VCH, Weinheim, 1997.
[S] (a) C. Masters, Adv. Organomet. Chem. 1979, 17, 61 ; (b) G. Henrici-Olive, S. OlivC, The
Chemistry of the Catalyzed Hydrogenation of Carbon Monoxide, Springer, Berlin, 1984;
(c) M. Roper in Catalysis in C, Chemistry (Ed.: W. Keim), D. Reidel, Dordrecht, 1983,
pp. 41-88; (d) G. Henrici-OlivC, Angew. Chem. 1976, 88, 144; Angew. Chem., Znt. Ed.
Engl. 1976, 15, 136; (e) G. Henrici-OlivC, J. Mol. Catal. 1978, 3, 443 and 1978, 4, 379;
(f) C. K. Rofer-dePoorter, Chem. Rev. 1981, 81, 447.
[6] (a) Historical review: B. Cornils, W. A. Henmann, M. Rasch, Angew. Chem. 1994, 106,
2219; Angew. Chem., Int. Ed. Engl. 1994, 33, 2144; (b) G. Plumpe, Die I.G. Farben-
industrie AG, Duncker & Humblot, Berlin, 1990.
[7] (a) W. A. Henmann, B. Reiter, H. Biersack, J. Organomet. Chem. 1975, 97, 245; (b)
Review: W. A. Henmann, Angew. Chem. 1978, 90, 855; Angew. Chem., Int. Ed.
Engl. 1978, 17, 800.
[8] (a) R. R. Schrock, J . Am. Chem. SOC.1975, 97, 6577; (b) L. J. Guggenberger, R. R.
Schrock, ibid. 1975, 97, 6578.
[9] Reviews: (a) W. A. Henmann, Adv. Organomet. Chem. 1982, 20, 159; (b) W. A. Herr-
mann, Pure Appl. Chem. 1982,54, 65; (c) R. R. Schrock, Acc. Chem. Res. 1979,12, 98;
(d) R. R. Schrock in Transition Metal Carbene Complexes (Eds.: F. R. Kreil3l et al.),
VCH, Weinheim, 1983.
[lo] (a) J. P. Collman, S. R. Winter, J. Am. Chem. Soc. 1973, 95, 4089; (b) C. P. Casey, M. A.
Andrews, D. R. McAlister, J. E. Rinz, ibid., 1980, 102, 1927; (c) C. P. Casey, S. M. Neu-
mann, M. A. Andrews, D. R. McAlister, Pure Appl. Chem. 1980, 52, 625.
[ l l ] W. A. Henmann,Angew. Chem. 1982,94, 118;Angew.Chem., Int. Ed. Engl. 1982,21, 117.
[I21 W. A. Henmann, Kontakte, No. 3, Merck, Darmstadt, 1991, pp. 29-52.
[13] M. C. Kaminsky, N. Winograd, G. L. Geoffroy, A. Vannice, J. Am. Chem. Soc. 1986,
108, 1315.
[14] (a) E. L. Muetterties, J. Organomet. Chem. 1980, 200, 177; (b) M. Tachikawa, E. L.
Muetterties, J. Am. Chem. Soc. 1980, 102, 4541; (c) M. A. Beno, J. M. Williams,
M. Tachikawa, E. L. Muetterties, ibid. 1981, 103, 1485.
[15] (a) W. A. Henmann, J. Plank, M. L. Ziegler, K. Weidenhammer, J. Am. Chem. Soc. 1979,
101, 3133; (b) W. A. Henmann, J. Plank, D. Riedel, M. L. Ziegler, K. Weidenhammer,
E. Guggolz, B. Balbach, ibid. 1981, 103, 63.
822 3.1 Development of Methods

[I61 Review: M. Brookhart, M. L. H. Green, J. Organomet. Chem. 1983, 250, 395.

1171 J. C. Hayes, G. D. N. Pearson, N. J. Cooper, J. Am. Chem. SOC.1981, 103, 4648.
[I81 P. Biloen, J. N. Helle, W. M. H. Sachtler, J. Catal. 1979, 58, 95.
[I91 (a) R. C. Brady, R. Pettit, J. Am. Chem. SOC.1980, 102, 6181 and 1981, 103, 1297; (b)
P. Biloen, J. Roy. Neth. Chem. SOC. 1980, 99, 33; (c) P. Biloen, W. M. H. Sachtler,
Adv. Catal. 1981, 30, 165.
[20] M. L. Turner, H. C. Long, A. Shenton, P. K. Byers, P. M. Maitlis, Chem. Eur: J. 1995, I, 549.
1211 (a) P. M. Maitlis, F. Ma, J. Martinez, P. K. Byers, I. Saez, G. J. Sunley in Homogeneous
Transition Metal Catalyzed Reactions (Eds.: W. R. Moser, D. W. Slocum), Adv. Chem.
Ser., Vol. 230, American Chemical Society, Washington DC, 1992, Chapter 39, p. 565;
(b) P. M. Maitlis, H. C. Long, R. Quyoum, M. L. Turner, Z.-Q. Wang, Chem. Commun.
1966, p. 1.
1221 F. Zaera, J. Am. Chem. Soc. 1989, I l l , 4240.
[23] (a) W. A. Henmann, Ch. Bauer, J. Plank, W. Kalcher, D. Speth, M. L. Ziegler, Angew.
Chem. 1981,93, 212;Angew. Chem., Int. Ed. Engl. 1981,20, 193; (b) W. A. Henmann,
J. Plank, M. L. Ziegler, P. Wulknitz, Chem. Ber: 1981, 114, 716.
[24] W. A. Henmann, H. Biersack, M. L. Ziegler, K. Weidenhammer, R. Siegel, D. Rehder,
J. Am. Chem. Soc. 1981, 103, 1692.
[25] S. W. Kluser, P. M. Skarstad, J. M. Burlitch, R. E. Hughes, J. Am. Chem. Soc. 1973,
95, 4469.
[26] G. R. Steinmetz, G. L. Geoffroy, J. Am. Chem. SOC.1981, 103, 1278.
[27] E. 0. Fischer, G. Kreis, F. R. KreiRI, J. Organomet. Chem. 1973, 56, C 37.
1281 (a) R. B. Anderson, L. J. Hofer, H. H. Storch, Chem.-Ing.-Tech. 1958, 30, 560; (b)
H. Kolbel, J. Trapper, Angew. Chem. 1966, 78, 908; Angew. Chem., Int. Ed. Engl.
1966, 5, 843.
1291 A. C. Filippou, W. Griinleitner, C. Volkl, P. Kiprof, Angew. Chem. 1991, 103, 1188;
Angew. Chem., Int. Ed. Engl. 1991, 30, 1167.
[30] (a) H. Pichler, Adv. C a d . 1952, 4, 271; (b) H. Pichler, H. Schulz, C1zem.-1ng.-Tech.
1970, 42, 1162.
[31] K. M. Motyl, J. R. Norton, C. K. Schauer, 0. P. Anderson, J. Am. Chem. SOC.1982,
104, 7325.

3.1.9 Arene Coupling Reactions

Wolfgang A. Herrmann

3.1.9.1 Introduction
Aromatic compounds, especially benzene and its derivatives, form c-and n-com-
plexes with a number of transition metal ions. Of particular importance in organic
synthesis is the electrophilic reaction of palladium(I1) with arenes, leading to
hydrogen substitution and further functionalization via a metallation step (eq. (1)).
The palladium ion behaves like a “giant proton”, as can be seen from the para-
specificity of metallation. The palladium-aryl bond allows numerous consecutive
reactions, for example CO insertion, Grignard coupling, and ary-aryl coupling.
The Heck-type C-C-coupling was described in Section 3.1.6. Palladium is one
 Applied Homogeneous Catalysis with Organometallic Compounds
Edited by B. Cornils and W. A. Herrmann
Copyright 0 Wiley-VCH Verlag GmbH, D-69469 Weinheim, 2002

3.1.10.2 Ligand Design for 829

3.1.10 Tailoring of Catalysts: N-Heterocyclic Carbenes

as an Example of Catalyst Design
Wolfgang A. Herrmann, Karin Denk, Christian W K. Gstottmayr

3.1.10.1 Introduction
The tailoring of homogeneous catalysts has made special progress by virtue of N -
heterocyclic carbenes (NHCs). Since the first studies by Ofele [I], Wanzlick [2],
and later Arduengo [ 3 ] ,a broad field of applications for NHCs has been explored
[4-1 I]. Especially as ligands in transition metal complexes, they resemble the
ubiquitous phosphines [ 12, 131. However, theoretical and experimental studies
show that NHC exhibit a much higher ligand dissociation energy from the metal
(Structure 1) [14, 151.
-electronic properties
- lmmobillzatlon

- steric properties
-solubility

This effect has become particularly beneficial in homogeneous catalysis, espe-

cially if low-coordination complex fragments have to be stabilized, asymmetric in-
duction of a chiral ligand is needed, or the ligand is immobilized on a solid phase
and metal leaching has to be suppressed. As a drawback NHC complexes often
show a reduced activity compared with their phosphine analogues since the active
undercoordinated species is formed in lower quantities [ 16, 171. Nevertheless there
are recent examples where complexes bearing NHC ligands proved to be even
more active than their phosphine analogues [18]. In contrast to phosphines, elec-
tronic and steric properties of NHC ligands can be modified separately.

3.1.10.2 Ligand Design for N-Heterocyclic Carbenes (NHC)

While the substituents at the nitrogen atoms influence the steric surroundings of
the metal, the electronic interaction is dependent on the substitiuents at C4 and C5
and the type of heterocycle (imidazole, imidazoline, benzimidazole, etc.).

3.1.10.2.1 Design of Steric Properties

The steric bulk of the substituents at the nitrogen atom ranges from the small
methyl groups as in Ofele’s first chromium NHC complex (2) [l] to the very
bulky adamantyl groups that were introduced by Arduengo in the first isolated
NHC (3) [3].
830 3.1 Development of Methods

-v
CH3

2 3

These substituents also determine the thermal and kinetic stability of the ligands
and their complexes: as a rule, the bulkier the substituents, the more stable are the
free carbenes. Due to the geometry of the heterocycle these substituents are point-
ing towards the metal center, in contrast to phosphines, where the three substitu-
ents point in the opposite direction. Besides the higher ligand dissociation energy,
this difference makes NHC more suitable for chiral induction by using asymmetric
substituents [19-241. For example, ee values of up to 70% could be reached in
hydrosilylation (cf. Section 2.6) using a Rh catalyst with a chiral NHC ligand
1251 (eq. (1)).
F! m R’

H H

The strong metal-carbene bond can also be utilized to immobilize transition

metal complexes on the solid phase (cf. Section 3.1.1.3). Leaching effects are sup-
pressed, especially if the metal is coordinated by an immobilized chelating NHC
ligand. While the activity of such immobilized complexes is reduced compared
with the homogeneous analogues, it was shown that chelating does not necessarily
have a negative effect on the activity [26]. This principle has been demonstrated
with an immobilized chelated NHC catalyst of palladium for the Heck and Suzuki
reactions (4) [27, 281.
 3.1.10.2 Lignnd Design,for 831

Besides chelating bridged di-N-heterocyclic carbene ligands there are also ex-
amples of bidentate NHCs with the second coordination site in the N-substituent.
Recently a Pd complex bearing an NHC with pyridinyl substituents was de-
scribed. Besides the strong metal-carbene bond this ligand is also able to establish
hemilabile nitrogen-metal bonds, if there are no other free ligands available [29].
This combination of a strongly and a weakly bonded ligand has proven to be very
effective for homogeneous catalysis in the past (eq. (2)) [27, 30, 311.
!+ '+

2 PFi -+- PPh3

PPh3
A
2 PFe

(2)

3.1.10.2.2 Design of Electronic Properties

In their binding properties NHC resemble basic alkylphosphines. However, their
a-donor ability is more pronounced than observed with phosphines, and they
show almost no n-acceptor property. The basicity and @-donor ability of the
metal-coordinating carbon atom is strongly dependent on the type of hetero-
cycle on which the NHC is based.
A simple way to evaluate the basicity of a carbene ligand is to compare the IR
data of carbon monoxide ligands in corresponding carbene(carbony1) complexes.
The wavenumber of the CO-stretching frequencies are directly proportional to the
back-donation from the metal center. A very basic ligand should result in a rela-
tively low wavenumber induced by a strong a-donation of the carbene C to the
metal and little n-back-donation from the metal center to the ligand [13, 321. Ex-
tensive studies have shown that CC-unsaturated 1,3-di-R-imidazolin-2-ylidenes
( 5 ) induce less electron density to the metal center than their CC-saturated analo-
gues, the 1,3-Di-R-imidazolidin-2-ylidenes (6). Recently Henmann et al. found
Alder's acyclic bis(diisopropy1amino)carbene (7) [6] to be the most basic free
isolable carbene ligand known to date [33].
rn n P S
R"yN\R R"yNxR R"yN\R

1,3-Di-R-imidazolin-2-ylidene 1,3-Di-R-imidazolidin-2-ylidene Bis(di-R-amino)carbene

5 6 7

An even broader variety of electronic purposes is accessible, if the imidazole

backbone is changed, for example, by introducing more heteroatoms like nitrogen
or sulfur [7, 34, 351.
832 3.1 Development of Methods

3.1.10.3 Catalytic Applications

As homogeneous catalysts for olefin metathesis (see Section 2.3.3) Ru-phosphine
complexes have unfolded dramatic progress, since they tolerate polar functional
groups and work at room temperature at the same time [36-41]. The most famous
example is the Ru-alkylidene system developed by Grubbs and co-workers [39].
Replacing both phosphine ligands by NHC ligands results in a slightly less active
catalyst for olefin metathesis (cf. eq. (3)) 1161.

This loss of activity is due to the very strong metal-carbon bond (ca. 42 kcal/
mol [30]) that reduces the formation of a coordinatively unsaturated Ru fragment
which is postulated as the catalytically active species [42, 431. By combining a
labile ligand with an NHC ligand the catalyst can be optimized: the labile ligand
dissociates to form the coordinatively unsaturated active species that is stabilized
by the electron-donating NHC ligands. With support from DFT calculations, dif-
ferent phosphines and metal fragments were examined as potential labile ligands
(8, 9) P O , 441.

CI, I CI, I
,RU=CH-Ph
CI I CI/Y=CHPh

The activity of the catalyst systems increases as the dissociation energy of the
labile ligand is reduced. The catalytic performance of these systems is comparable
with Schrock’s highly active yet very sensitive molybdenum system [45]. So even
tetrasubstituted olefins are accessible by ring-closing metathesis using these opti-
mized air- and moisture-stable ruthenium systems [46, 471.
Pd-catalyzed C-C-coupling reactions of the Heck type, e. g., Suzuki [48c] and
Stille [49c] cross-coupling, are excellent tools for the preparation of biaryls (see
also Section 3.1.9). The activity and stability of the catalyst is highly dependent
on the steric and electronic properties of the ligands. Sterically demanding
basic alkylphosphines e. g., tri(t-butyl)phosphine, have proven to be very effective
ligands in the Heck reaction [50] as well as in the Suzuki cross-coupling [51].
NHCs resemble those basic phosphines (see above) and therefore were tested
 3.1.10.3 Cutulytic Applications 833

(NHC)Pd(P&)I,

A (NHC),Pdl,

A
A

Figure 1
0 50 100 150

t/min - 200 250 300

as ligands in these C-C-coupling reactions. For Pd" complexes the same effect
can be observed in the Suzuki and the Stille cross-coupling as with the Ru metath-
esis catalysts: a mixed NHC-phosphine Pd" complex combines the high activity
of a bis(phosphine) compound with the high stability of a bis(NHC) complex, re-
sulting in the highest turnover number (TON) of these three types (cf. Figure 1)
[31, 521.
In contrast to the other examples, a Pd" bis (NHC) complex (10) reveals
the highest activity known to date in the Suzuki cross-coupling of chloroarenes
P31.
tBu tBu\

[$-Pd+N] N

\tBu feu'
I0

However, the problem of catalyst decomposition that was known previously

only for phosphine complexes prevents quantitative yields with these catalysts.
This means that in the coupling of p-chlorotoluene with phenylboronic acid
with 3 % 1,3-di(t-butylimidazolin-2-ylidenePd' a conversion of 55 9% is observed
after only 10 min. Yet no more than 68 % yields are reached due to catalyst
decomposition.
For Pd" the strong electron-donor effect of the NHC seems to have a desta-
bilizing effect on the metal center that is "oversaturated" with electron density.
However, this high electron density facilitates the oxidative addition of the
834 3.1 Development of Methods

chloroarene which is believed to be the rate-determining step in C-C-coupling

reactions [54]. A recent review article [136] summarizes the entire literature
up to December 2001. The field is growing rapidly.

References
[I] K. Ofele, J. Organomet. Chem. 1968, 12, P42.
[2] H. W. Wanzlick, H. J. Schonherr, Angew. Chem. 1968, 80, 154; Angew. Chem., Int. Ed.
Engl. 1968, 7, 141.
[3] A. J. Arduengo 111, R.L. Harlow, M. Kline, J. Am. Chem. Soc. 1991, 113, 361.
[4] D. Enders, K. Breuer, G. Raabe, J. Runsink, J. H. Teles, J. P. Melder, K. Ebel, S . Brode,
Angew. Chem., Int. Ed. Engl. 1995, 34, 1021; Angew. Chem. 1995, 107, 1119.
[5] A. J. Arduengo 111, J. R. Goerlich, W. J. Marshall, A. J. Am. Chem. SOC. 1995, 11 7,
11027.
[6] R. W. Alder, P.R. Allen, M. Murray, A.G. Orpen, Angew. Chem. 1996, 108, 1211;
Angew. Chem., Int. Ed. Engl. 1996, 35, 1121.
[7] G. A. McGibbon, J. HruSak, D. J. Lavorato, H. Schwarz, J. K. Terlouw, Chem. Eur: J.
1997, 3, 232.
[8] R. W. Alder, C. P. Butts, A. G. Orpen, J. Am. Chem. SOC. 1998, 120, 11526.
[9] G. Maier, J. Endres, Chem. Eur: J. 1999, 5, 1590.
[lo] F. E. Hahn, L. Wittenbecher, R. Boese, D. Blaser, Chem. Eur: J. 1999, 5, 1931.
[ 1I] R. W. Alder, M. E. Blake, C. Bortolotti, A. Bufali, C. P. Butts, E. Linehan, J. M. Oliva,
A.G. Orpen, M.A. Quale, Chem. Commun. 1999, 241.
[12] M. Regitz, Angew. Chem. 1991, 105, 691; Angew. Chem., Int. Ed. Engl. 1991, 30, 674.
[I31 (a) W. A. Herrmann, C. Kocher, Angew. Chem. 1997,109,2256;Angew. Chem., Int. Ed.
Engl. 1997,36, 2162: (b) Recent review: W. A. Herrmann, Angew. Chem., 2002, in press:
Angew. Chem., Int. Ed. Engl. 2002, in press.
[ 141 C. Kocher, Dissertation, Technische Universitat Munchen (1997).
[ 151 R. Schmid, Dissertation, Technische Universitat Munchen (1997).
[ 161 T. Weskamp, W. C. Schattenmann, M. Spiegler, W. A. Herrmann, Angew. Chem. 1998,
110, 2631; Angew. Chem., Int. Ed. 1998, 37, 2490.
[I71 T. Weskamp, V. P. W. Bohm, W. A. Herrmann, J. Organomet. Chem. 1999, 585, 348.
[18] V. P. W. Bohm, C. W. K. Gstottmayr, T. Weskamp, W. A. Herrmann, J. Organomet.
Chem. 2000, 595, 186.
[ 191 L. J. GooBen, Dissertation, Technische Universitat Munchen ( 1 997).
[20] W. A. Herrmann, L. J. GooBen, M. Spiegler, Organometallics 1998, 17, 2162.
[21] W.A. Herrmann, L.J. GooBen, C. Kocher, G.R.J. Artus, Angew. Chem. 1996, 108,
2980; Angew. Chem., Int. Ed. Engl. 1996, 3.5, 2805.
[22] D. Enders, H. Gielen, G. Raabe, J. Runsink, J. H. Teles, Chem. Ber: 1996, 129, 1483.
[23] D. Enders, H. Gielen, G. Raabe, J. Runsink, J. H. Teles, Chem. Ber: 1997, 130, 1253.
[24] D. Enders, H. Gielen, G. Raabe, J. Runsink, J. H. Teles, Eur: J. Inorg. Chem. 1998, 9 13.
[25] M. Steinbeck, Dissertation, Technische Universitat Miinchen ( 1 998).
[26] C. P. Reisinger, Dissertation, Technische Universitat Munchen (1997).
[27] J. Schwarz, Dissertation, Technische Universitat Munchen (2000).
[28] J. Schwarz, V. P. W. Bohm, M. G. Gardiner, M. Grosche, W. A. Herrmann, W. Hieringer,
G. Raudaschl-Sieber, Chem. Eur: J. 2000, 6, 1773.
[29] J. C. C. Chen, I. J. B. Lin, Organornetallics 2000, 19(24), 51 13.
[30] T. Weskamp, F. J. Kohl, W. Hieringer, D. Gleich, W. A. Herrmann, Angew. Chem. 1999,
111, 1573;Angew. Chem., Int. Ed. 1999, 38, 2416.
 3.1.11.1 Introduction 835

[31] W.A. Henmann, V. P. W. Bohm, C. W. K. Gstottmayr, M. Grosche, C.-P. Reisinger,

T. Weskamp, J. Organomet. Chem. 2001, 617-618, 616.
1321 M. Elison, Dissertation, Technische Universitat Munchen (1995).
1331 K. Denk, P. Sirsch, W. A. Herrmann, J. Organomet. Chem. 2002, in press.
1341 G. Maier, J. Endres, H. P. Reisenauer, Angew. Chem. 1997, 109, 1788; Angew. Chem.,
Int. Ed. Engl. 1997, 36, 1709.
[35] W.A. Henmann, L. J. GooBen, G.R. J. Artus, C. Kocher, Organornetallics 1997,
16, 2472.
[36] S.T. Nguyen, L. K. Johnson, R. H. Grubbs, J. Am. Chem. Soc. 1992, 114, 3974.
[37] S.T. Nguyen, R. H. Grubbs, J. W. Ziller, J. Am. Chem. Soc. 1993, 115, 9858.
1381 A. W. Stumpf, E. Saive, A. Deonceau, A. F. Noels, Chem. Commun. 1995, 1127.
[39] P. Schwab, M.B. France, J.W. Ziller, R.H. Grubbs, Angew. Chem. 1995, 107, 2179;
Angew. Chem., Int. Ed. Engl. 1995, 34, 2039.
[40] W.A. Henmann, W.C. Schattenmann, 0. Nuyken, S.C. Glander, Angew. Chem. 1996,
108, 1169; Angew. Chem., Int. Ed. Engl. 1996, 35, 1087.
[41] A. Demonceau, A. W. Stumpf, A. Saive, A.F. Noels, Macromolecules 1997, 30, 3127.
[42] J. L. Herisson, Y. Chauvin, Makromol. Chem. 1970, 141, 161.
1431 E.L. Dias, S. T. Nguyen, R. H. Grubbs, J. Am. Chem. SOC. 1997, 119, 3887.
1441 J. Huang, E.D. Stevens, S.P. Nolan, J.L. Petersen, J. Am Chem. Soc. 1999, 121, 2647.
14.51 R. R. Schrock, J. Feldman, L. F. Cannizzo, R. H. Grubbs, Macromolecules 1987,
20, 1169.
[46] T.A. Kirkland, R. H. Grubbs, J. Org. Chem. 1997, 62, 3942.
[47] L. Ackermann, A. Fiirstner, T. Weskamp, F. J. Kohl, W. A. Herrmann, Tetrahedron Lett.
1999, 40, 4787.
1481 (a) N. Miyaura, A. Suzuki, Chem. Rev. 1995, 95, 2457; (b) A.R. Martin, Y. H. Yang,
Acta Chem. Scand. 1993, 47, 221; (c) A. Suzuki, Pure Appl. Chem. 1991, 63, 419.
[49] (a) V. Farina, V. Krishnamurthy, W. J. Scott, Org. React. 1997, 50, 1 ; (b) T. N. Mitchell,
Synthesis 1992, 803; (c) J. K. Stille, Angew. Chem. 1986, 98, 504; Angew. Chem., Int.
Ed. Engl. 1986, 25, 508.
[SO] A. F. Littke, G.C. Fu, J. Org. Chem. 1999, 64, 10.
1.511 A.F. Littke, G.C. Fu, Angew. Chem. 1998, 110, 3586; Angew. Chem., Int. Ed. 1998, 37,
3387.
[52] T. Weskamp, V. P. W. Bohm, W. A. Herrmann, J. Organomet. Chem. 1999, 585, 348.
1.531 V.P. W. Bohm, C. W.K. Gstottmayr, T. Weskamp, W.A. Herrmann, J. Organomet.
Chem. 2000, 595, 186.
[54] V. V. Grushin, H. Alper, Chem. Rev. 1994, 94, 1047.

3.1.11 Micellar Catalysis

Giinther Oehme

3.1.11.1 Introduction
Amphiphilic compounds with surface-active properties, such as surfactants or ten-
sides, assemble in water to form spherical aggregates. The size and shape of these
aggregates depends on the structure of the amphiphile. As a general rule amphi-
philes with one polar head group and one nonpolar alkyl chain form micelles,
836 3.1 Development of Methods

monolayer spherical micelle reverse micelle

(idealized) (more realistic)

bilayer multilamellar vesicle unilamellar vesicle

Figure 1. Principle of the association of amphiphiles.

whereas amphiphiles with two alkyl chains per head group preferentially form
vesicles (Figure 1) [l].
Aqueous micelles are thermodynamically stable and kinetically labile aggre-
gates. Their formation begins above a characteristic concentration, the critical mi-
celle concentration (CMC) and above a certain temperature (Kraffts temperature).
With increasing concentration the associate morphology can change from spherical
to rod-like or hexagonal structures. The aggregation of amphiphiles in an aqueous
medium is controlled entropically due to the dehydration of the alkyl chains [2].
The association-dissociation process in micelles is very rapid, often occurring
within milliseconds, faster than most chemical reactions [3]. Micelles are relatively
small, with radii between 1.5 and 3 nm and aggregation numbers <100, in contrast
to vesicles, which have diameters of 20 nm or more. The polar head group of an
amphiphile can be either charged (anionic, cationic, zwitterionic) or neutral with
polyether or polyalcohol groups; the hydrophobic chain can contain alkyl or a
combination of alkyl and aryl groups. Table 1 displays a selection of very common
amphiphiles with their critical aggregation concentration in aqueous medium.
Due to the high polarity gradient between a hydrophilic surface and a hydro-
phobic core the micelle can solubilize polar and nonpolar reactants from the sur-
rounding water phase and thereby enhance or inhibit the rate of a reaction [4]. Any
enhancement is often designated micellar catalysis. The rate enhancement can be
due to a combination of the following effects [ 5 ] :(1) a medium effect caused by a
lower dielectric constant in the interior in water; (2) a stabilization of the transition
state owing to an interaction with the polar head group, and (3) concentration of
the reactants at the surface or by incorporation into the micelle. Other typical
effects of organized surfactants on reactants are the alteration of chemical and
photophysical pathways, alteration of quantum efficiency and ionization poten-
tials, change of oxidation and reduction properties, and finally separation of prod-
ucts and charges.
 3.1.11.2 Examples of Micellar-Promoted Reactions 837

-
Table 1. Typical micelle-forming surfactants and their CMC values.
Surfactant CMC [molh-']

0
II
0 -sII -0- Na+ (SW 8.1 x
0

I
LN4 Br- (CTABr) 9.2 X lo4
I

I (DDAPs) 1.2 x

CH3(CHz)q&OO- CHz
I
CH~(CHZ)~&OO-CH 0
I II + 4.7 x lo-'"
H2C- O-P-OCHzCHzN(CH3)3
I
0-

Reactions in micelles and in the double layers of vesicles are analogous to nat-
ural membrane systems and in special cases are comparable with the function of
an enzyme (cf. Section 3.2.1). In contrast to macromolecular enzymes, amphiphile
aggregates with linked catalytic centers have a less rigid supramolecular structure.
The preorganization of an enzyme is highly selective and as a consequence en-
zyme catalysis is much more effective than micellar catalysis, a type of artifical
mimic [6].
Micellar catalysis enables water to be employed as a reaction medium, to gain
not only an enhancement in the rate of reaction but also improvements in selec-
tivity and sometimes even to allow the catalyst to be recycled in a simple manner
(cf. Section 3.1.1.1). A micellar system is a multiphase system in a colloidal
dimension and allows the microheterogenization of a catalyst under special con-
ditions [7].

3.1.11.2 Examples of Micellar-Promoted Reactions

Typically reported topics are solvolytic reactions, oxidations, reductions, and C-C
coupling reactions. The saponification of activated esters in aqueous micelles is a
typical model for an enzyme mimetic reaction. The influence of the micellar
medium on the reaction rate has been investigated, as well as the alteration of
the stereoselectivity. Models of metalloenzymes were developed with the ligands
1-3 [8].
Typical metal ions for complexation are Ni", Cu", Zn" and Co". The amphiphi-
lic ligands which were embedded in micelles or vesicles enhanced the reaction
838 3.1 Development of Methods

rates in comparison with a dispersion in pure water. The use of optically active
ligands led to a moderate kinetic resolution of a-aminoesters.

NR &R

RNH OH R'-O,) NOR'

1
OH

1 2 3

R =CH3,CnHln+, n =8,12,13,16

As an example of micelle-promoted oxidation reactions Rabion et al. [9] de-

scribed a methane oxygenase model with the iron complexes [Fe20(r'-H20)(r'-
OAC)(TPA),]~'and [Fe20(q1-H20)(r'-OAc)(BPIA)2]3' in the presence of cetyltri-
methylammonium hydrogensulfate (TPA = tris[(2-pyridyl)methyl]amine; BPIA
= bis[(2-pyridyl)methy1]-[2-( 1-methylimidazolyl)methyl]amine).In this example
cyclohexanol and cyclohexanone were formed from cyclohexane and t-butylhy-
droperoxide. The reaction does not occur in a biphasic aqueous system in the ab-
sence of a surfactant. Reductive processes involving transition metal complexes as
catalysts have been well investigated in aqueous biphasic systems [lo]; especially
in asymmetric hydrogenations a loss of activity and enantioselectivity was ob-
served [ 111. Surprisingly, in the Rh-catalyzed enantioselective hydrogenation of
amino acid precursors in water, the addition of a small amount of a micelle-form-
ing surfactant leads to a significant increase in the reaction rate and the enantio-
selectivity [12, 131.
All types of surfactants promote the reaction but only the hydrogensulfate was
successful in the case of cationic amphiphiles. Sometimes the enantioselectivity
surpassed the values observed when methanol was used as a solvent. This method
was even used successfully for the enantioselective hydrogenation of a-aminopho-
sphonic [ 141 and a-aminophosphinic acid precursors [ 151. The concentration of
the surfactant leads to an efficient reaction only above the CMC.
Yonehara et al. [ 161 recently extended the scope of surfactant-promoted enan-
tioselective hydrogenation on simple enamides. With respect to other reductive
processes conducted in the presence of surfactants, it is noteworthy that the
efficiency of an artifical nitrogenase model was selectively very enhanced by
the addition of phospholipids [17].
One of the most important goals in organic chemistry is the formation of C-C
bonds. This field has advanced rapidly due to the introduction of transition metal
catalysts. Engberts and co-workers [ 181 observed an extraordinary rate enhance-
ment (up to 1.8 . lo6 fold) in the Diels-Alder reaction between 3-(puru-substituted
pheny1)-1-(2-pyridyl)-2-propen- 1-ones and cyclopentadiene in presence of cop-
per(I1) or zinc(I1) dodecylsulfate micelles. The lanthanide-catalyzed aldol reaction
described by Kobayashi and Manabe [ 191 is also important as a typical method in
 3.1.11.3 Reactions in Reverse Micelles 839

"green chemistry". The authors obtained good results using Sc"' or YII1triflates in
the presence of SDS or Triton X-100 as surfactants and were able to improve these
results further by using scandium tris(dodecylsu1fate) or scandium tris(dodecane-
sulfonate) ("Lewis acid-surfactant combined catalysts" or LASCs).
All C-C-coupling reactions utilizing carbon monoxide are of industrial
significance. Especially in the hydroformylation of long-chain olefins (e. g., 1-do-
decene) a phase-transfer reagent (cf. Section 3.2.4) or a micellar system is required
when aqueous conditions are employed. Early experiments were submitted by
Dror and Manassen [20] and by Matsui and Orchin [21]. Fell and Papadogianakis
[22] synthesized surface-active phosphines starting from tris(2-pyridyl) phosphine
and different long chain /?-sultones. Application of these ligands to the hydrofor-
mylation of n-tetradec- 1-ene gave approximately 80 % of n-aldehyde selectivity.
Recently, Hanson 1231 and van Leeuwen used new types of amphiphilic phos-
phine ligands with high activities and satisfying regioselectivities. The best results
with respect to the normalliso ratio (-50) were described by an amphiphilic
xanthene-derived diphosphine [24].

A systematic investigation of surfactants during the hydroformylation of higher

olefins catalyzed by water-soluble Rh/TPPTS complexes (cf. Section 3.1.1. l), was
conducted by Chen et al. [25]. The authors found that only cationic amphiphiles
gave a significant effect on the yield and a moderate influence on the d i ratio.
The telomerization of I ,3-butadiene to octadienol (cf. Section 2.3.5) catalyzed
by palladium phosphine complexes was realized in an aqueous micellar medium
1261. The micellar effects depend strongly on the type of surfactant and on the
water solubility of the palladium complexes.
Suzuki-type C-C-coupling reactions (cf. Section 2.11) with Pd phosphine com-
plexes as catalysts can also be promoted by amphiphiles in an aqueous biphasic
system (toluene/water). The amphiphile should have a phase-transfer function,
with the best effect being observed with micelle-forming amphiphiles 1271.

3.1.11.3 Reactions in Reverse Micelles [28]

Reverse micelles are formed by the interaction of the polar head group of an
amphiphile with colloidal water drops in an apolar medium. This represents an
840 3.1 Development of Methods

enthalpy stabilization, in contrast to the case with aqueous micelles. AOT (bis(2-
ethylhexyl) sodium sulfosuccinate) is a favored surfactant for reverse micelles due
to the geometry of its structure, although SDS and tetraalkylammonium salts are
suitable as well. The water core of a reverse micelle can act as a microreactor for
chemical, photochemical, and enzymatic reactions.
The first example is an asymmetric reduction of different phenyl alkyl ketones
with sodium tetrahydroborate in an ephedrine-derived chiral reverse micelle [29].
The combination of R = n-C,2H25in the ephedrinium salt and R'= Ph, R2= t-Bu
in the ketone gave the best results with 84 % yield and 24 % ee.
Elsevier and co-workers [30] reported an example of a selective C-H band
activation with sodium tetrachloroplatinate in inverse micelles. A solution of
the catalyst in D 2 0 was dispersed in the presence of AOT in either n-heptane
or methylcyclohexane. CH/CD exchange was observed under mild conditions
in the CH3 groups with high selectivity.
Finally, it should be mentioned that a series of enzymes have been trapped in
reverse micelles as a method of dispersing the hydrophilic biocatalysts in a
very unpolar organic medium [31].

3.11.1.4 Limits and New Developments

Aggregates of amphiphiles in aqueous and organic media enable the solubilization
of reactants with very different polarities. Catalytic reactions sometimes occur
with high activity and high selectivity (even stereoselectivity). Practical problems
in micellar catalysis include the separation of the product and surfactant and the
recycling of catalysts. A solution could be the use of polymeric amphiphiles
[32], polymerized micelles [33], or amphiphilized polymers [34]. It is possible
to embed or to link the catalyst to the macromolecular amphiphile. The recycling
of the catalyst could be achieved by retention in a membrane reactor [35] or by
filtration or sedimentation of the immobilized insoluble polymer. An important
condition for this would be that all macromolecular amphiphiles fulfill the same
function as the associated monomers. Examples are given with the triphase cata-
lysts [36] in phase-transfer systems [37] and even in pseudo-micellar systems
[38]. Immobilized cationic amphiphiles are analogous to immobilized ionic
liquids [39].

References
[ 11 J. H. Clint, SLirjiuctant Aggregation, Blackie, Glasgow, 1992.
[2] Y. Moroi, Micelles. Theoretical and Applied Aspects, Plenum, New York, 1992.
[3] S. Hamid, D. Shemngton, J. Chem. Soc., Chem. Commun. 1986, 937.
[4] C. A. Bunton, in Kinetics and Catalysis in Microheterogeneous Systems (Eds.: M. Grat-
zel, K. Kalyanasundaram), Dekker, New York, 1991, p. 13.
1.51 J.M. Brown, S.K. Baker, A. Colens, J.R. Darwent, in Enzymic and Non-enzymic
Catalysis (Eds.: P. Dunnil, A. Wiseman, N. Blakebrough), Horwood, Chichester, 1980,
p. 111.
 References 84 1

[6] J. H. Fendler, Membrane Mimetic Chemistry, Wiley, New York, 1982.

[7] P. Scrimin, in Supramoleculur Control of Structure and Reactivity (Ed.: A. D. Hamilton),
Wiley, Chichester, 1996, Vol. 3, p. 101.
[8] P. Scrimin, U. Tonellato, in Surjiactants in Solution (Eds.: K.L. Mittal, D.D. Shah),
Plenum, New York, 1991, Vol. 11, p. 349.
[9] A. Rabion, R.M. Buchanan, J.-L. Seris, R.H. Fish, J. Mol. Catal. A: 1997, 116, 43.
[lo] (a) D. Sinou, Bull. Soc. Chim. Fr. 1987, 480; (b) D. Sinou, Trends Orgunomet. Chem.
1994, I , 15.
[ l l ] L. Lecomte, D. Sinou, J. Bakos, I. Toth, B. Heil, J. Organomet. Chem. 1989, 370, 277.
[12] G. Oehme, E. Paetzold, R. Selke, J. Mol. Cutul. 1992, 71, L1.
[13] 1. Grassert, E. Paetzold, G. Oehme, Tetrahedron 1993, 49, 6605.
[ 141 I. Grassert, U. Schmidt, S. Ziegler, C. Fischer, G. Oehme, Tetrahedron: Asymmetry 1998,
Y, 4193.
[15] T. Dwars, U. Schmidt, C. Fischer, I. Grassert, R. Kempe, R. Frohlich, K. Drauz,
G. Oehme, Angew. Chem. 1998, 37, 2853; Angew. Chem., Int. Ed. Engl. 1998, 37,2853.
[I61 K. Yonehara, K. Ohe, S . Uemura, J. Org. Chem. 1999, 64, 9381.
[ 171 L. P. Dikenko, V. D. Makhaev, A. K. Shilova, A. E. Shilov, Prepl: 4th Int. Symp. Homo-
gen. Catal. Leningrad 1984, Vol. 11, p. 102.
[18] S. Otto, J. B. F. N. Engberts, J. C. T. Kwak, J. Am. Chem. SOC.1998, 120, 9517.
[19] S. Kobayashi, K. Manabe, Pure Appl. Chem. 2000, 72, 1373.
[20] Y. Dror, J. Manassen, Stud. Surf Sci. Catal. 1981, 7, 887.
[21] Y. Matsui, M. Orchin, J. Organomet. Chem. 1983, 244, 369.
[22] B. Fell, G. Papadogianakis, J. Mol. Catal. 1991, 66, 143.
[23] B. Hanson, Coord. Chem. Rev. 1999, 185-186, 795.
[24] J. N. H. Reek, P. C. J. Kamer, P. W. N. M. van Leeuwen, in Rhodium Catalyzed Hydrofor-
rnylation (Eds.: P. W. N. M. van Leeuwen, C. Claver), Kluwer, Dordrecht, 2000, pp. 253,
259.
[25] H. Chen, Y. Li, J. Chen, P. Cheng, Y. He, X. Li, J. Mol. Catal. A: 1999, 149, 1.
[26] E. Monflier, P. Bourdauducq, J.-L. Courturier, J. Kervennal, A. Mortreux, Appl. Catal.
A.: 1995, 131, 167.
[27] E. Paetzold, G. Oehme, J. Mol. Catal. A.: 2000, 152, 69.
[28] P. L. Luisi, in Kinetics and Catalysis in Microheterogeneous Systems (Eds.: M. Gratzel,
K. Kalyanasundaram), Dekker, New York, 1991, p. 115.
[29] Y. Zhang, P. Sun, Tetrahedron: Asymmetry 1996, 7, 3055.
[30] S. Gaemer, K. Keune, A.M. Kluwer, C. J. Elsevier, EUKJ. Znorg. Chem. 2000, 1139.
[31] P.L. Luisi, M. Giomini, M.P. Pileni, B.H. Robinson, Biochim. Biophys. Acta 1988,
947, 209.
[32] Nonionic Surjiactants: Polyoxyalblene Block Copolymers (Ed.: V. M. Nace), Dekker,
New York, 1996.
[33] B. Boutevin, J.-J. Robin, B. Boyer, G. Lamaty, A. Leydet, J.-P. Roque, 0. Senhaji, New
J. Chem. 1996, 20, 137.
[34] H.N. Flach, I. Grassert, G. Oehme, M. Capka, Colloid Polym. Sci. 1996, 274, 261.
[35] T. Dwars, J. Haberland, I. Grassert, G. Oehme, U. Kragl, J. Mol. Catal. A: 2001, 168, 81.
[36] B. Comils, W.A. Henmann, R. Schlogl, H.-C. Wong (Eds.), Catalysis from A to Z,
Wiley-VCH, Weinheim, 2000.
1371 S . L. Regen, Angew. Chem. 1979, 91, 464; Angew. Chem., Int. Ed. Engl. 1979, 18, 421.
[38] I. Rico-Lattes, A. Schmitzer, E. Perez, A. Lattes, Chirality 2001, 13, 24.
[39] M. J. Earle, K. R. Seddon, Pure Appl. Chem. 2000, 112, 3927.
 Applied Homogeneous Catalysis with Organometallic Compounds
Edited by B. Cornils and W. A. Herrmann
Copyright 0 Wiley-VCH Verlag GmbH, D-69469 Weinheim, 2002

842 3.1 Development of Methods

3.1.12 Sulfur in Homogeneous Catalysis

Philippe Kalck, Philippe Serp

3.1.12.1 Introduction
Metalloproteins play an important role in many biological reactions. However, but
not so surprisingly, many systems contain sulfur and act efficiently in biological
processes. For instance, proteins which contain iron-sulfur clusters not only occur
in the electron-transfer processes in living cells, but also act directly as powerful
catalysts in binding, activating substrates, and synthesizing molecules [I]. In the
past few years, the role of these metalloproteins has been investigated and under-
stood: delivering sulfur to form iron-sulfur clusters, but also producing biotin,
molybdopterin, thiamine, and some other similar entities [2]. Recently, model
compounds have been synthesized in which the pterin ligand is replaced by pro-
ligands which contain a dithiolene moiety attached to a dihydropyran ring fused to
a partially reduced pyrazine [3]. Thus, a cyclopentadienylcobalt moiety (1) has
been coordinated to the sulfur atoms of such a proligand.

1
A second model compound is provided by a stable Fe"-porphyrin alkanethio-
late complex in which the sulfur atom is protected from reactive molecules such as
0, or NO by a sterically crowded group. In this way NO can bind directly to the
metal center simulating the role played by heme proteins in the biosynthesis of
NO and in signal transduction mediated by NO [4].
However, if sulfur-containing ligands exert a determinant role in enzymatic cat-
alysis and in numerous biological processes, the opposite situation exists in het-
erogeneous catalysis. Indeed, sulfur has the disastrous, but established, reputation
of poisoning, and thus killing definitively, numerous catalysts. For instance, in the
synthesis of methanol from CO and HZ,the Cu/Zn/Al oxide-based catalysts were
known very early, but were used only after the 1970s when the technology
allowed less than 1 ppm of sulfur in synthesis gas [ 5 ] . Medium pressures can
be used (5-10 MPa and 240-260 "C). Previously, methanol was produced during
the period 1923-1970 by the BASF process operating at 320-380 "C and 34 MPa
using a Zn chromite which is resistant to sulfur at low concentrations and allows a
service life of several years. The modern trend is to reduce sulfur further in
petrochemicals, not only to preserve the lifetime of the most efficient catalysts
which have been developed, but also to respect the worldwide regulations to re-
duce the sulfur levels in transportation fuels. A contrario, the main heterogeneous
 3.1.12.2 Sulfur in Curbonylution Reactions 843

catalysts which tolerate high contents of sulfur are used in desulfurization cataly-
sis. Development of highly active and selective hydrotreating catalysts in hydro-
desulfurization (HDS) processes has led the petroleum industry to develop
sulfided Co-Mo- and Ni-Mo-based materials, which consist of small clusters of
molybdenum disulfide doped with cobalt or nickel (cf. Section 3.2.13) [6]. The
active phase has been proven to form exclusively along certain types of MoS2
crystal edges [7].
Curiously, chemists have tackled homogeneous catalysis with the preconceived
idea that sulfur would also exert a strong poisonous effect. Some early studies
have nevertheless shown that Rh [8] and Pt [9] complexes containing thioethers
are active in the hydrogenation of C-C double bonds. In the low-pressure hydro-
formylation reaction, the reaction of COS - present with H2S in the syngas -
with [Rh(H)(PPh,),] affords the [Rh(SH)(CO)(PPh,),] thiol complex [ 101.
Among thiolato-bridged dirhodium complexes, the derivative [Rh2@-S’Bu)2(C0)2
{P(OMe),},], which not only contains the S’Bu bridging ligands but also the unu-
sual phosphite P(OMe)3 ligand, is an active precursor in hydroformylation [ 111.
The reaction is performed under mild conditions, mainly at 80°C, so that no
thermal stress is encountered by the catalyst. Thus, it is necessary to conclude
that the sulfur-containing ligands act as classical ancillary ligands with their
own electronic and steric properties in the coordination sphere of the metal. But
what about long-duration catalytic tests? Particularly in commercial processes,
for instance in an exothermic reaction like hydroformylation, hot spots in the reac-
tor can lead the sulfur ligand to have a poisonous effect. Experience of more than
16 years has been gained by Celanese in the Ruhrchemie plant of Ober-
hausen where the RCH/RP 0x0 process brings into operation the complex
[RhH(CO)(TPPTS),]; this tris(m-sulfophenyl)phosphine, or TPPTS, ligand con-
tains three sulfonato groups which exhibit good stability under the operating
conditions [12]. Similarly Union Carbide Corporation is said to use a rhodium-
monosulfonated triphenylphosphane complex to hydroformylate long-chain ole-
fins [131.
Numerous catalyst precursors containing sulfur ligands have been described in
the literature. They were reviewed in detail in 1999 [14], so this Section focuses
on the most important conclusions from the various catalytic reactions which have
been explored and on the more recent results reported.

3.1.12.2 Sulfur in Carbonylation Reactions

Since the development of the so-called Monsanto process of methanol carbon-
ylation to acetic acid where the active species is [RhI,(CO),]- [15], many
studies have been devoted to the improvement of the catalyst [16]. In particular,
phosphinophosphine sulfides or phosphines containing a thiol termination have
shown a higher level of activity [17, 181. For instance, the complex [RhI
(CO){Ph,PCH,P(S)Ph,}] is eight times more active than the anionic [Rh12(CO),]-
[ 171, whereas [Rh@-SCH2CH2PPh2)(C0)l2 is four times as active [ 181. Mechan-
istic studies performed by Haynes and co-workers revealed that the ligand pro-
844 3.1 Development of Methods

Scheme 1

motes both methyl iodide oxidative addition and migratory insertion of CO

(Scheme 1) [19].
The first step is quite usual and the rate is improved by the electronic effects of
the phosphine ligand, whereas the dramatic increase in the rate of the second step
is due to steric effects of the phenyl groups, for which the acyl species is less hin-
dered than the methyl group in the hexacoordinated species. Similarly, y5-cyclo-
pentadienyl Co (or Rh) thioether carbonyl complexes, in which one carbon
chain of the thioether ligand is eventually bonded to the Cp ligand, have been
patented [20].
For the low-pressure hydroformylation of alkenes to the corresponding alde-
hydes, many studies have been carried out on dinuclear thiolato-bridged Rh com-
plexes since the discovery of the high activity of [Rh2@-SR)2(CO)2(PR'3)2][ 11,
211. Diphosphine and dithiolato ligands can be introduced including mixed brid-
ging groups or chiral dithiolate ligands for asymmetric catalysis [14]. The com-
plex can be grafted to silica or alumina (cf. Section 3.1.1.3), or even to an ion-ex-
change resin for catalyst recovery [14], but the most interesting way to immobilize
the complex in another phase is to use the water-soluble TPPTS ligand (cf. Section
3.1.1.1) [12, 22, 231. The reaction can be extended to heavy alkenes, provided a
phase transfer agent like P-cyclodextrin is present or a supported aqueous phase
on an hydrophilic support (SAPC) is used [24]. The mechanism of this reaction
has been investigated deeply. Whereas in the early studies, a mechanism was pro-
posed [25] in which all the intermediate species of the catalytic cycle remained
dinuclear, more especially as addition of thiol to the hydrido mononuclear rho-
dium complex [Rh(H)(CO)(PPh,),] provides the dinuclear complex [Rh,@-
SR,)(CO),(PPh,),] under hydroformylation conditions [26], more recent studies
propose a mononuclear active species. Cross-over experiments [27] and infrared
observations under pressure [28] suggest [Rh(H)(CO)(PPh,),] as active species.
However, the mechanism could actually be more intricate and we are at present
exploring combined catalytic cycles involving dinuclear and mononuclear species
to explain the kinetic curves [29]. Dithiolato bridging ligands have also been
introduced between two Rh atoms and their low-pressure activity has been inves-
tigated in the hydroformylation reaction [30, 3 11. Here also, high-pressure
infrared studies show the presence of the hydrido mononuclear complex
[Rh(H)(CO),(PPh,)], which is formed under H2/C0 with the dithiol being
expelled from the coordination sphere.
The main interest of such a chemistry is to avail oneself of chiral dithiols, like
1,l '-binaphtalene-2,2-dithiol, in order to perform asymmetric hydroformylation
 3.1.12.3 Sulfur in Hydrogenation, Isomerization, and Related Reactions 845

reactions [14, 321. Infrared and NMR investigations under a pressure of syngas
prove the addition of (2S,4S)-(-)-2,4-bis(diphenylphosphino)pentane to a Rh
cyclooctadiene precursor with formation of the species 2 in equilibrium with
the predominant hydrido mononuclear complex [Rh(H)(CO),(diphos*)] and the
dirhodium(0) carbonyl-bridged complex [Rh,(j~-CO)~(CO)~(diphos*)~].

2
Very recently the [ { CpFe( 1,2-(PPh2),-4-%u)}Rh(S-%u)(CO)] complex contain-
ing a terminal tert-butylthiolato ligand has been shown to be active in the hydro-
formylation of 1-octene at 1 MPa, but with a mediocre selectivity in linear alde-
hyde (52 %); however, the complex was recovered unchanged after catalysis [33].
A few studies have been carried out on alkoxycarbonylation, but the catalytic
activities are relatively low [14, 331.

3.1.12.3 Sulfur in Hydrogenation, Isomerization,

and Related Reactions
Various complexes of platinum group metals have been synthesized with
thioether, dithioether, sulfido, sulfoxide, thiolato, dithiolato, phosphine sulfide,
and dithiocarbamato ligands. Their activity in hydrogenation of various substrates
has been investigated. The general trend is that these ligands behave as classical
ones to tune the coordination sphere of the metallic centre, except maybe the high
catalytic activity of [Rh,(CO),,(SMe,),] which has been suspected to be due to
colloidal metal formed during the hydrogenation of 1-hexene [34].
A salient feature is the partial hydrogenation of conjugated dienes to monoenes
catalyzed by [PtC12(SPh)2]/SnC12,although an extensive isomerization of the
terminal alkene occurs to internal olefins [9], or the hydrogenation of alkene/
alkyne mixtures catalyzed by [RuCI,(SEt,),] to remove the acetylenic components
[35]. Pd or Pt complexes coordinated by a ferrocene ligand bearing a thioether and
an amine in a cis position have been shown to be active in this reaction of con-
jugated dienes, presumably because the thiother ligand decoordinates to open a
vacant position [36].
Of course, many efforts have been devoted to the design of chiral sulfur-
containing complexes in order to achieve asymmetric hydrogenation including
hydrogen transfer, mainly from isopropanol [14]. The good activity of the
[Ir(1,5-COD)(dithioether)]+ complexes is interesting; they achieve the hydro-
846 3.1 Development of Methods

genation of itaconic acid under ambient conditions with an ee of 68 % [37], or 96 %

ee obtained in the hydrogenation of Z-methyl a-acetamidocinnamate in the pre-
sence of the complexes [Rh,@i-Cl)(p-SR)(CO), { PPh,(+)neomenthyl)} ,], where
R = 'Bu or CH,CH,Si(OEt), under more drastic conditions (120 "C, 7 MPa) [38].
These mixed bridged-dinuclear Rh complexes [Rh2(p-C1)(p-SR)(CO)2(PR',),I
also catalyze the transformation of epoxides or unsaturated alcohols into the
corresponding ketones [39].
Several Co, Rh, Ni, and Pd complexes containing dimethyl sulfoxide, thio-
cyanato, and thio- or dithioketonato ligands are able to catalyze efficiently the iso-
rnerization of terminal alkenes [ 141. Interestingly, a cyclopentadienyldithiophena-
tocobalt derivative isomerizes a quadricyclane into norbornadiene through C-C
bond splitting and further rearrangement: such a cyclic reaction could convert
solar energy [40].
For hydrosilylation, numerous platinum group metals containing thio ligands
have been inspected [14], and generally high reactivities can be achieved. Great
attention has especially been paid to the asymmetric hydrosilylation of ketones
and imines [41]. Although more or less sophisticated ligands have been designed,
including a chiral macrocyclic thioether, deceptive ee values ranging from 50 to
60 % have been observed [ 141. Rh complexes containing pyridinethiazolidine li-
gands have led to ee values of 80 % [ 141. Thiofuryl derivatives such as bis(a1ken-
y1)dihydrosilane can be transformed by a double intramolecular hydrosilylation
reaction into a spirosilane with 98 % selectivity and 99 % ee (see eq. (1)) [42].

Finally, it is important to mention that hydrodesulfurization occurs with catalyts

which present a low sensitivity to substrates containing sulfur in the backbone
(cf. Section 3.2.13).

3.1.12.4 Sulfur in Carbon-Carbon Coupling Reactions

The Heck reaction [43] has also been explored using sulfur-containing ligands
coordinated to Pd [14]. The catalytic system, grafted onto a polymer, is only
affected when the molar S/Pd ratio is too high.
Pd-catalyzed allylic substitutions such as the Tsuji-Trost reaction have been in-
vestigated widely, essentially in their asymmetric version [44]. This represents a
valuable tool in organic synthesis since the catalyst can accommodate various
functionalities on the substrate and it is possible to tune the coordination sphere
through the electronic and steric effects of the ligands. Those which contain a sul-
fur atom are based on an oxazoline backbone, and an ee as high as 96 % has been
 3.1.12.5 Miscellaneous Reactions 841

obtained with an aromatic thioether substituent [45]. Chelating ligands have also
been designed with one phosphorus atom and a thioether group to coordinate Pd':
an X-ray and NOESY NMR spectra have shown that the PS ligand exerts a
disymmetric influence on the allylic substrate and thus on its reactivity. In order
to gain regioselectivity and enantioselectivity simultaneously, it is essential that
in addition to the electronic effects, adjusted steric effects allow a good structural
control [14, 44, 461. As the nucleophilic incoming reactant provides an external
attack on the allylic moiety, the chiral ligand should have steric groups far from
the coordination centers which differentiate strongly the two sites of attack.
Cross-coupling of an organomagnesium compound with an organic halide can
also be catalyzed by Ni, Pd, or Cu complexes containing either a macrocyclic
thioether or thioether-alkylamino ligand [ 141. Copper(1) catalyzes also the addi-
tion of an organocuprate to an a$-unsaturated ketone or ester. The enantioselec-
tivity of these cross-coupling reactions remains at a modest level for the sulfur-
containing complexes [47].
The oligomerization and polymerization of alkenes can also be catalyzed by
complexes which contain sulfur in the coordination sphere. For instance,
[Rh2(11-SRF)2(C8H12)2] catalyzes the trimerization of CF3C=CH and CF3C=CCF3
under ambient conditions [48]. [Rh { K'-O~S(O)CF~ } (PiPr,),] promotes the cyclo-
tetramerization of butadiene, and an intermediate species in which the triflate
ligand is Icl-bonded to a rhodium bis(a1lylic) C8 moiety has been intercepted
[49]. Ti and Zr complexes containing a cyclopentadienyl ligand with a
methylthio-functionalized amido side chain have shown a moderate activity in
the polymerization of ethylene, when activated with methylaluminoxane [30].
The X-ray crystal structures reveal that besides the cyclopentadienyl- and
amido-coordinated ligands, sulfur is bound to Zr, but not to Ti. However, in
this latter case, when B(C,F,), is added, the cationic Ti part of the ion-pair is pre-
sumably stabilized by coordination of the sulfur atom. Rhodium, and platinum
complexes containing crown thioethers, or dithiocarbamate and xanthate nickel
complexes, also catalyze the polymerization of ethylene [5 1, 521.

3.1.12.5 Miscellaneous Reactions

Addition of alcohol to an internal alkyne can occur in the presence of a diiri-
dium-palladium or -platinum sulfido cluster and gives rise to the corresponding
acetal [53].
The complex [($-C5Me,),Rh,(11-S)2][BPh4]2 catalyzes the electrochemical
reduction of C 0 2 to HCOO- when [Bu,N][BF,] is present, the [Bu4N]' cation
being the proton source; in the presence of LiBF, the reaction produces oxalate
[S4]. The Co and Ir analogue clusters give rise to the same oxalate production
from CO, [55].
The dithiolate complex [ 1,S-bis(mercaptoethy1)-1,5-diazacyclooctane]NiT' or
-Pd" reacts with SO, to produce sulfur-site SO, adducts and then with O2 to
form sulfato complexes. Exogenous thiolates used as an electron source allow
SO, oxygenation to ions [56]. The complex ci~-[pt(SH)~(PPh~)~] catalyzes
848 3.1 Development of Methods

in homogeneous phase the classical heterogeneous Claus reaction [57] which

transforms SO, into elemental sulfur by reaction with H2S. A search for models
of this reaction has shown that a formal 1,2-insertion of SO2 into the S-Si
bond (to mimic S-H) of [CpRuLL'SSiR3] occurs to give [CpRuLL'SS(O)OSiR,]
and thus to support the formation of a hydrosulfite complex [58].
Dithioacetals react with [Cp,Ti{P(OEt),},] to produce [Cp2Ti(SR),] and an
alkylidene species [Cp2Ti=C(R')(R2)] which is an excellent entry to the Wittig-
type reactions from carbonyl, alkene, and alkyne substrates [59].
D2/H+ exchange between D2 and ethanol can be catalyzed by
[RhH(CO)("b"S,")] or the PCy, analogue, "buS4)'being the 1,2-bis(2-mercapto-
3,5-di-tert-butylphenyIthio)ethaneligand, and should model the reaction at the
metal-sulfur sites of hydrogenases [60], Ally lamines can be efficiently depro-
tected by 2-mercaptobenzoic acid in the presence of catalytic amounts of a Pdo
complex [61].
Homogeneous oxidation of CO by oxygen to CO, can be easily achieved by
using Ni complexes coordinated by alkyldithiocarbamate ligands. Actually, the
oxygen transfer reaction proceeds through the [Ni(NO,)]-[Ni(NO)] sequence [62].
Many catalytic reactions are not sensitive to the presence of a sulfur atom on
the substrate. Two examples can be quoted: the Nozaki-Hiyama-Kishi reaction
where a chlorosilane-mediated Cr-Mn-catalyzed C-C coupling occurs between
a halogenoalkene and an aldehyde [63], and the [IrC1(C0)3]-catalyzed intramole-
cular ally1 transfer in functionalized 1,3-thiozanes [64].
The catalytic macrocyclization of thietanes [65] appears to be described parti-
cularly conclusively, since (1) it results from stoichiometric preliminary studies of
reactivity on clusters; (2) the activation of the first building block occurs through
the coordination of the sulfur atom to two metal centers; (3) the reaction is slow
enough to intercept most of the intermediates and to characterize them, including
X-ray crystal structure determination; (4) the selectivity of the reaction originates
from the cluster template, whose nuclearity seems to be maintained along the cata-
lytic cycle; and ( 5 ) sulfur is particularly well adapted to the catalytic system.
For instance, thiacyclobutane, or thietane, can be trimerized into 1,5,9-trithia-
cyclododecane in the presence of [Re3(p-H)3(p-SCH2CH2CH2)(CO)10] which
itself results from the reaction of thietane with [Re,(p-H)3CO)10(NCMe)2].A
simplified catalytic cycle is shown in Scheme 2, where the vertex represents
rhenium atoms (bridging hydrides and terminal CO ligands have been omitted
for clarity).

3.1.12.6 Conclusions
Numerous catalytic systems have been described in the literature which involve
sulfur-containing ligands or which are not sensitive to the presence of sulfur
atoms in the reactants. In several cases, these sulfur ligands play a spectator
role. However, it is important to consider that these ancillary ligands participate,
like any other more classical ligands such as phosphanes, to the coordination
sphere of the metal center. Due to their electronic properties, their bulkiness,
 References 849

Q
us
A\

Scheme 2

and their ability to modulate them along the catalytic cycle (by retro-donation, and
due to the presence of doublets), they contribute to the capacity of the complex to
ensure all the steps of the catalytic cycle.
As in enzymes, sulfur ligands often have beneficial effects. Owing to their co-
ordination properties and their flexibility [66], they take part in the chemo-, regio-,
and even enantioselectivity of the reaction, which is the major criterion required
in modern catalysis.

References
[ l ] C. Krebs, T. E Henshaw, J. Cheek, B. H. Huynh, J. B. Broderick, J. Am. Chem. Soc.
2000, 122, 12497 and references therein.
[2] R.L. Rawls, Chem. Ing. News 2000, Nov. 20, 43.
[3] B. Bradshaw, D. Collison, C.D. Gamer, J.A. Joule, Chem. Commun. 2001, 123.
[4] N. Suzuki, T. Higuchi, Y. Urano, K. Kikuchi, T. Uchida, M. Mukai, T. Kitagawa,
T. Nagano, J. Am. Chem. Soc. 2000, 122, 12059.
[5] K. Weissermel, H.-J. Arpe, Industrial Organic Chemistry, 3rd ed., Wiley-VCH,
Weinheim, New York, 1997.
850 3. I Development of Methods

161 H. Topscle, B. S. Clausen, F. E. Massoth, Hydrotreating Catalysis: Science and Tech-

nology, in Catalysis, Science and Technology (Eds.: J. R. Anderson, M. Boudart),
Springer-Verlag, Berlin, 1996, 11.
171 J.V Lauritsen, S. Helveg, E. Laegsgaard, I. Stensgaard, B.S. Clausen, H. Topscle,
F. Besenbacher, J. Catal. 2001, 197, 1.
IS] B. R. James, F. T. T. Ng, G. L. Rempel, Inorg. Nucl. Chem. Lett. 1968, 4, 197.
[9] H. A. Tayin, J. C. Bailar Jr., J. Am. Chem. Soc. 1967, 89, 4330.
[lo] T. R. Gaffney, J. A. Ibers, Inorg. Chem. 1982, 21, 2860.
[ l l ] Ph. Kalck, J.-M. Frances, P.-M. Pfister, T. G. Southern, A. Thorez, J. Chem. Soc., Chem.
Commun. 1983, 510.
[12] B. Cornils, E. G. Kuntz, in Aqueous-Phase Organometallic Catalysis, Concepts and
Applications (Eds.: B. Cornils, W. A. Henmann), Wiley-VCH, Weinheim, 1998, p. 27 1 .
[ 131 H. Bahrmann, S. Bogdanovic in Aqueous-Phase Organometallic Catalysis, Concepts and
Applications (Eds.: B. Cornils, W. A. Henmann) Wiley-VCH, Weinheim 1998, p. 306.
[14] J.C. Bayon, C. Claver, A.M. Masdeu-Bultb, Coord. Chem. Rev. 1999, 193-195, 73.
[ 151 cf. Section 2.1.2.1.
[16] J. H. Jones in Platinum Metals Rev. 2000, 44(3), 94.
[17] M. J. Baker, M. F. Giles, A. G. Orpen, M. J. Taylor, R. J. Watt, J. Chem. Soc., Chem.
Commun. 1995, 197.
[ 181 J. R. Dilworth, J. R. Miller, N. Wheatley, M. J. Baker, J. G. Sunley, J. Chem. Soc., Chem.
Commun. 1995, 1579.
[19] L. Gonsalvi, H. Adams, G. J. Sunley, E. Ditzel, A. Haynes, J. Am. Chem. Soc. 1999, 121,
11233.
[20] E. J. Ditzel, A. D. Poole, D. J. Cole-Hamilton, A. C. Marr (BP Chemicals), EP 1.043.300
and EP 1.043.301 (1999).
[21] Ph. Kalck, in Organornetallics in Organic Synthesis. Aspects of a Modern Interdisciplin-
ary Field (Eds.: A. de Meijere, H. tom Dieck), Springer-Verlag, Berlin, 1987, p. 297.
[22] P. Escaffre, A. Thorez, Ph. Kalck, Nouv. J. Chim., 1987, 11, 601.
[23] Ph. Kalck, P. Escaffre, F. Serein-Spirau, A. Thorez, B. Besson, Y. Colleuille, R. Perron,
New J. Chem. 1988, 12, 687.
[24] Ph. Kalck, M. Dessoudeix, Coord. Chem. Rev. 1999, 190, 1185.
[25] A. Dedieu, P. Escaffre, J.-M. Frances, Ph. Kalck, Nouv. J. Chim. 1986, 10, 631.
[26] P. Escaffre, A. Thorez, Ph. Kalck, B. Besson, R. Perron, Y. Colleuille, J. Organomet.
Chem. 1986,302, C17.
[27] R. Davis, J. W. Epton, T.G. Southern, J. Mol. Catal. 1992, 77, 159.
[28] M. DiCguez, C. Claver, A.M. Masdeu-Bult6, A. Ruiz, P. W. N. M. van Leeuwen, G. C.
Schoemaker, Organometallics 1999, 18, 2 107.
[29] R. Giordano, Ph. Serp, Ph. Kalck, unpublished results.
[30] A.M. Masdeu, A. Ruiz, S. Castillon, C. Claver, P. J. Hitchcock, P. Chaloner, C. Bo, J. M.
Poblet, P. Sarasa, J. Chem. Soc., Dalton Trans. 1993, 2689.
[31] A. Aaliti, A.M. Masdeu-Bult6, C. Claver, J. Organomet. Chem. 1995, 101, 489.
[32] A. Castellanos-PAez, S. Castillon, C. Claver, P. W. N. M. van Leeuwen, W. G. J. de Lange,
Organometallics 1998, 17, 2543.
[33] R. Broussier, E. Bentabet, M. Laly, Ph. Richard, L. G. Kuz’mina, Ph. Serp, N. Wheatley,
Ph. Kalck, B. Gautheron, J. Organomet. Chem. 2000, 613, 77.
[34] S. Rossi, K. Kallinen, J. Pursiainen, T. T. Pakkanen, T. A. Pakkanen, J. Organomet.
Chem. 1991,419, 219.
[35] Institut FranGais du PCtrole, FR 1.538.700 (Chem. Abstl: 1969, 71, 317).
[36] C.K. Lai, A.A. Naiimi, C.H. Brubaker Jr., Inorg. Chim. Acta. 1989, 164, 205; A.A.
Naiimi, M.O. Okoroafor, C.H. Brubaker Jr., J. Mol. Catal. 1989, 54, L 27; see also:
C.H. Wang, C.H. Brubaker Jr., J. Mol. Catal., 1992, 75, 221.
 References 85 1

[37] M. DiCguez, A. Ruiz, C. Claver, M. M. Pereira, A.M. d’A. Rocha Gonsalves, J. Chem.
Soc. Dalton Trans. 1988, 3517.
[38] M. Eisen, J. Blum, H. Schumann, B. Gorella, J. Mol. Catal. 1989, 56, 329.
[39] H. Schumann, S. Jurgis, H. Stanislaw, P. Ekkehardt, J. Blum, M. Eisen, Chem. Ber. 1985,
118, 2738.
[40] M. Kajitani, T. Fujita, T. Okumachi, M. Yokoyama, H. Hatano, H. Ushijima,
T. Akayama, A. Sugimori, J. Mol. Catal 1992, 77, LI.
[41] H. Nishiyama, K. Itoch, in Catalytic Asymmetric Synthesis, 2nd ed. (Ed.: I. Ojima),
Wiley-VCH, New York, 2000, p. 111.
[42] K. Tamao, K Nakamura, H. Ishi, S. Yamaguchi, M. Shiro, J. Am. Chem. Soc. 1996,118,
12469.
[43] R.F. Heck, in Comprehensive Organic Synthesis (Eds.: B. Trost, I. Fleming, M.F.
Semmelhack), Pergamon Press, Oxford, 1991, p. 833.
[44] A. Pfaltz, M. Lautens, in Comprehensive Asymmetric Catalysis (Eds.: E. N. Jacobsen,
A. Pfaltz, H. Yamanato), Springer-Verlag, Berlin, 1999, p. 833
[45] J. V. Allen, J. F. Bower, J. M. J. Williams, Tetrahedron: Asymmetry 1994, 5, 1895.
[46] K. Selvakumar, M. Valentini, P. S. Pregosin, A. Albinati, Oragnometallics 1999, 18,
459 1, and references therein.
[47] T. Hayashi, in Comprehensive Asymmetric Catalysis (Eds.: E. N. Jacobsen, A. Pfaltz,
H. Yamanoto), Springer-Verlag, Berlin, 1999, p. 887.
[48] J. J. Garcia, C. Sierra, H. Torrens, Tetrahedron Lett. 1996, 37, 6097.
[49] M. Bosch, M. S. Brookhart, K. Ilg, H. Werner, Angew. Chem., Int. Ed. 2000, 39, 2304.
[50] J. Okuda, T. Eberle, T. P. Spaniol, V. Piquet-FaurC, J. Organomet. Chem. 1999, 591, 127,
and references therein.
[51] S. Timonen, T.T. Pakkanen, T. A. Pakkanen, J. Mol. Catal. 1996, 11, 267.
[52] A.M. A. Bennett, G. A. Foulds, D. A. Thornton, Polyhedron 1990, 9, 2823.
[53] D. Masui, T. Kochi, Z. Tang, Y. Ishii, Y. Mizobe, M. Hidai, J. Organomet. Chem. 2001,
620, 69.
[54] Y. Kushi, H. Nagao, T. Nishioka, K Isobe, K. Tanaka, Chem. Lett. 1994, 2175.
[55] Y. Kushi, H. Nagao, T. Nishioka, K. Isobe, K. Tanaka, J. Chem. Soc., Chem. Commun.
1995, 1223.
[56] M. Y. Darensbourg, T. Tuntulani, J. H. Reibenspies, Inorg. Chem. 1995, 34, 6287.
[57] A. Shaver, M. El-Khateeb, A.-M. Lebuis, Angew. Chem., lnt. Ed. Engl. 1996, 35, 2362.
[58] I. Kovacs, C. Pearson, A. Shaver, J. Organomet. Chem. 2000, 596, 193.
[59] Y. Horikawa, M. Watanabe, T. Fujiwara, T. Takeda, J. Am. Chem. Soc. 1997,119, 1127;
see also: B. Breit, Angew. Chem., Int. Ed. 1998, 37, 453.
[60] D. Sellmann, G.H. Rackelmann, F. W. Heinemann, Chem. Eur: J. 1997, 3, 2071.
[61] S . Lemaire-Audoire, M. Savignac, J.-P. GenEt, J.-M. Bernard, Tetrahedron Lett. 1995,
36, 1267.
[62] C. A. Tsipis, D. P. Kessissoglou, G. E. Manoussakis, Inorg. Chim. Acta 1982, 65, L 137.
[63] A. Furstner, Chem. Eur: J . 1998, 4, 567, and references therein.
[64] H. Alper, C. Crudden, K. Khumtaveeporn, .I. Chem. Soc., Chem. Cornmun. 1995, 1199.
[65] R. D. Adams, in Catalysis by Di- and Polynuclear Metal Cluster Complexes (Eds.: R. D.
Adams, F. A. Cotton), Wiley-VCH, New York, 1998, p. 283.
[66] M. Rakowski DuBois, in Catalysis by Di- and Polynuclear Metal Cluster Complexes
(Eds.: R. D. Adams, F. A. Cotton), Wiley-VCH, New York, 1998, p. 127.
Applied Homogeneous Catalysis with Organometallic Compounds
Edited by B. Cornils and W. A. Herrmann
Copyright 0 Wiley-VCH Verlag GmbH, D-69469 Weinheim, 2002
 3.1.13.1 Introduction 853

It is further characterized by rapid diffusion, low viscosity, and practically no

surface tension. On the other hand, the supercritical phase still acts as a solvent
for the solid metal complex, and both its heat capacity and its density can reach
typical liquid-like values.
The density of an SCF at the critical point (d,) is the mean value of the density
of the liquid and gaseous phase just before entering the supercritical region. It
must be noted, however, that the local density of an SCF is subject to large fluc-
tuations and may differ considerably from the bulk density, especially around
solute molecules [6]. Furthermore, the high compressibility in the near-critical
region allows the bulk density to be varied continuously from gas-like to
liquid-like values with relatively small variations in temperature and/or pressure.
At 37°C the density of scCOz is only 0.33 g m I ? at 8 MPa, but it rises to
0.80 g mL-' at 15 MPa [7]. A number of solvent properties of the fluid phase
are directly related to or change in parallel with bulk density. Accordingly, such
properties can be "tuned" very precisely in SCFs with small changes of the reac-
tion conditions. For example, the dielectric constant of an SCF varies in parallel
with density, and this change may directly influence homogeneously catalyzed
reactions [8]. The changes in polarity are very pronounced for polar SCFs such
as HCF3 or water, but less dramatic for nonpolar scC0, (1.0 < E < 1.6).
Just like other solvents, SCFs can influence a chemical reaction not only
through their physical properties, but also by chemical interactions with all reac-
tive species. Carbon dioxide has a well established reactivity toward organometal-
lic compounds which plays an important role for the choice of suitable catalysts
(vide infra). A typical chemical interaction of CO, with substrates is the formation
of carbamic acids or carbamates in the presence of secondary or primary amines.
This effect can be exploited systematically by using compressed CO, as a protec-
tive reaction medium, as demonstrated by the effective ring-closing metathesis of
secondary amines using Grubbs' catalyst (see eq. (3)) [9]. In conventional sol-
vents, substrates containing free NH groups lead to irreversible deactivation of
the carbene catalyst and two additional synthetic steps of protectioddeprotection
are required to achieve the same transformation. Another striking example is the
switch of chemoselectivity during cyclization of allylic amines under hydro-
formylation conditions in scC0, (Scheme 1) [ 101. The reduced nucleophilicity
of the NH group in CO, as compared with conventional solvents shuts down
the direct ring-closing reaction and forces the reaction through the complete
hydroformylation/reductive amination sequence.
The phase behavior of mixtures is much more complex than that shown in Fig-
ure 1 for pure CO, [2b]. It is therefore not sufficient to work at a temperature and
pressure above the critical values of the pure solvent to achieve single-phase con-
ditions in the presence of other components. Although a large body of data on the
phase behavior of C 0 2 with various other substances is available, much less is
known about systems which are directly related to synthetic procedures. A full
mapping of the phase behavior is still rather challenging for multicomponent sys-
tems with varying concentrations as encountered in typical reaction mixtures [ 111.
The use of high-pressure equipment allowing for visual control of the phase be-
havior of reaction mixtures is therefore mandatory when exploring organometallic
854 3.1 Development of Methods

COJHZ
Rh-cat.
b

I dioxane I
I co2
CO/H,
major product

Rh-cat.
b
\
major product

Scheme 1. ScC02 as a protective medium: changing chemoselectivity by in situ conversion

of a secondary amine to its carbamic acid during catalysis in scC02.

catalysis in SCFs. The installation and use of such equipment on a laboratory scale
requires appropriate safety considerations, but is far less demanding than often an-
ticipated. Some guidelines are available in the literature [ 11 and from commercial
suppliers of high-pressure equipment.

3.1.13.2 Single-Phase Catalysis Using SCFs as Solvents

3.1.13.2.1 Choosing a Promising Catalyst

In order to operate under single-phase conditions, the solubility of the organome-
tallic catalyst and all relevant active species must be sufficiently high in the SCF
to allow reasonably fast turnover rates for practical applications. The threshold for
the minimum catalyst solubility depends critically on the activity of the intermedi-
ates, and even extremely low solubilities may be sufficient for highly active cata-
lysts. Furthermore, it is important to note that the substrate(s) and product(s) can
affect the solvent properties of the reaction mixture quite substantially : the pre-
sence of organic substrates will usually increase the solubility of organometallic
catalysts, whereas added reaction gases will generally lead to a decrease in solu-
bility by reducing the density.
The solubility of solid materials such as coordination compounds in scC0, is
governed largely by their vapor pressure and their polarity, relating again to the
Janus-faced gadliquid character of SCFs [ 121. Accordingly, fairly volatile metal
compounds such as carbonyl complexes and clusters, cp* complexes, or 1,3-dike-
tonates have generally significant solubilities in compressed CO,. Added ligands
will usually suppress the solubility, but very nonpolar ligands such as trialkyl
phosphines or phosphites may allow for solubilities that are still sufficient for
catalytic applications in many cases. The large class of arylphosphorus ligands
is generally not available for direct use in SCCO,, but the addition of “CO,-philic”
side groups can lead to highly soluble species. Similar groups are required to dis-
 3.1.13.2 Single-Phase Cutulysis Using SCFs as Solvents 855

solve charged complexes in nonpolar carbon dioxide. For cationic species, the
groups can be introduced in the ligand attached to the catalytically active metal
center or, more conveniently, in the respective counterion. The sections below
exemplify successful applications of each of the above approaches.
In addition to the design of the solubility properties, the reactivity of organome-
tallic species toward C 0 2 [ 131 (and many other potential supercritical reaction
media) must be considered as important criteria for the choice of the catalyst.
For example, the bisallyl ruthenium complex shown in Table 1 cannot be utilized
as a precursor for ring-opening metathesis polymerization (ROMP) in scC02, be-
cause the insertion of CO, into the Ru-ally1 bond prevents the initiation mecha-
nism [14]. Metal-mediated oxygen transfer to form CO and phosphine oxide was
found to lead to deactivation of the [Ni(~od)~]/PMe~ (cod = 1,5-cis-cycloocta-
diene) catalyst system [15]. On the other hand, the reactivity of C 0 2 with metal

Table 1. Reactivity of some organometallic catalysts toward compressed COz and implications
for catalvsis in scCO? (see text for details).
Reactivity Catalysis
toward COz in scCOz

Insertion in Inactive
Ru-ally1 bond

Oxygen Limited catalyst

transfer lifetime
H

Insertion in Hydrogenation
Rh-H bond of co:

No reaction Hydroformy lation

and hydrogenation
of C=C bonds
856 3.1 Development of Methods

complexes may also be beneficial, especially in cases where carbon dioxide is

used not only as solvent, but also as a reactant. For example, the insertion of
C 0 2 into metal hydride bonds, as in complex [(dpp~)~RhH] (dppp = 1,3-bis(di-
phenylphosphino)propane), is a key step in the hydrogenation of COz to formic
acid and its derivatives [ 161. With related ruthenium catalysts this reaction occurs
very effectively in scCOz and leads to outstanding catalytic turnovers [17]. In
contrast, the isoelectronic rhodium hydride complex [(3-H2F6-BINAPH0S)Rh
(CO),H] (BINAPHOS = 2-(dipheny1phosphino)-1,l '-binaphthalene-2'-~1-1,l '-bi-
naphthalene-2,2'-diylphosphite) was recently identified as a stable species by
NMR spectroscopy in scCOz solution and has no measurable tendency to insert
C 0 2 into the Rh-H bond [ 181. The BINAPHOS-based hydride is a direct precursor
for highly efficient Rh-catalyzed asymmetric hydroformylation in scC02. Simi-
larly, the mechanism of the hydrogen transfer during asymmetric hydrogenation
in scC02 is not altered by the presence of carbon dioxide [ 191. As a conclusion,
the reactivity of catalytic active intermediates with the solvent C 0 2 can play an im-
portant role for homogeneous catalysis in this medium, but the factors controlling
the possible chemical interactions are fairly subtle and predictions remain difficult.

3.1.13.2.2 Catalysis in SCFs Using Established Catalysts

The high solubility of carbonyl complexes in scC02 was utilized in a pioneering
study on the hydroformylation of 1-propene using [Co,(CO),] as a catalyst precur-
sor (cf. Section 2.1.1; eq. (1)) [20]. The main focus of this investigation was the
NMR spectroscopic characterization of catalytically active intermediates exploit-
ing the reduced linewidths of quadrupolar nuclei such as 59C0 under supercritical
conditions [21]. An increased ratio of the linear to branched aldehyde at similar
reaction rates was noted in the original work and investigated in detail recently
[22]. The same catalyst precursor is active for Pauson-Khand cyclizations (cf.
Section 3.3.7) in scC02 [23] and in scC2H4 [24]. Cyclopentadienyl complexes
of cobalt are active and stable mediators for the cyclotrimerization of alkynes
even under the extreme conditions of supercritical water (T, = 374OC, p , =
22.1 MPa) [2S].
T = 80°C
p"(tot) = 180 bar
A + H2 + CO (1)
[C0,(C0)81
scco*

Mo hexacarbonyl was used as oxidation catalyst in scC02 with 'BuOOH as

oxidant by several groups [lS, 26, 271. Depending on the water content and the
reaction temperature, epoxides or vicinal trans-diols are obtained in good yields.
The epoxidation (cf. also Section 2.4.3) of allylic and homoallylic alcohols with
'BuOOH also occurs smoothly in liquid COz with [VO(OiPr)3] or [Ti(O'Pr),] as
a catalyst [27]. Using di(isopropy1) tartrate (DIPT) as a chiral ligand for the Ti
catalyst yields up to 87% ee at 0°C (eq. (2)). The isopropyl groups in the
 3.1.13.2 Single-Phase Catalysis Using SCFs as Solvents 857

metal components and in the ligand are crucial for sufficient solubility and hence
catalytic efficiency.

,, [Ti(O’Pr)4]/DIPT
0

(2)
liqCO2, 0°C
ee = 87%

Unmodified Rh catalysts are highly active in scC02 for hydroformylation of

various olefinic substrates [28]. The catalytically active and highly soluble car-
bonyl species can be formed readily from commercially available precursors
such as [(cod)Rh(acac)]. In contrast to the Co-catalyzed reaction discussed
above, significantly higher reaction rates were observed for the hydroformylation
of internal olefins in scC02 as compared with conventional solvents. Furthermore,
an increased selectivity for the branched isomer was noted in several cases. Trial-
kylphosphines can be used as co-catalysts if terminal alkenes are hydroformylated
to linear aldehydes as the target products, but over-reduction to the corresponding
alcohols becomes a significant side reaction with this type of ligand [29].
The Pd-catalyzed carbonylation of aryl halides (cf. Section 2.1.2) occurs with
high turnover numbers and reaction rates in scC02 as the solvent using standard
precursor complexes and commercially available phosphine or phosphite ligands
[30]. The generally better performance of the phosphite-based catalysts was attrib-
uted to their better solubility in the reaction mixture, but the formation of Pd car-
bonyl complexes was also mentioned as a possibility. The [Ni(cod),]/dppb system
(dppb = 1,4-bis(diphenylphosphino)butane) was investigated in an early study as
a catalyst for the synthesis of pyrones from alkynes and CO, under conditions
beyond the critical data of carbon dioxide [3 I]. Replacing dppb with PMe3 results
in a system with better solubility and catalytic performance, albeit catalyst de-
activation remains a problem [3 c, 151.
The hydrogenation of scC02 to yield formic acid is catalyzed very efficiently
by ~ ~ S - [ R U ( H ) , ( P Mand
~ ~ related
) ~ ] alkylphosphine Ru complexes in the presence
of triethylamine [17, 321. The solubility of the catalyst precursor in the reaction
mixture was verified experimentally. The reaction is initially homogeneous and
turns heterogeneous later due to the precipitation of the liquid HCOOWNEt,
product. However, if too much NEt, is present the reaction mixture is heteroge-
neous from the start, leading to a dramatic decrease in rate. Homogeneous condi-
tions can also be achieved in the presence of methanol, leading to formation of
methyl formate as the product [33]. In contrast, the synthesis of formamides via
hydrogenation of CO, in the presence of secondary amines occurs most efficiently
in biphasic mixtures, as discussed in more detail below [33-361.
Grubbs’ catalysts ~ ~ U ~ S - [ ( C ~ ~ P ) ~ C I , R ~ =
are
C active
( H ) R for
] olefin metathesis
(cf. Section 2.3.3) in scC0, 19, 371. The solubility of the catalyst precursor in the
reaction mixture is, however, very low and most of the charged bulk material
remains undissolved. Nevertheless, ring-opening metathesis polymerization
(ROMP) is initiated efficiently and solvent-free polymeric material is obtained
directly from the reaction mixture. The reaction occurs as precipitation poly-
merization, whereby the excellent mass transfer properties of scC0, lead to
858 3.1 Development of Methods

rapid diffusion of the monomers into the precipitate and ensure high polymer-
ization rates.
Ring-closing metathesis (RCM) is also possible in scC02, leading to interesting
procedures for the synthesis of macrocyclic compounds such as the 16-membered
lactone shown in eq. (3). The strong influence of the C 0 2 density on the competi-
tion between intramolecular ring closure and intermolecular oligomerization can
be attributed mainly to two synergistic effects [9b, 381: Increasing density
leads to a decrease in the molar fraction of substrate, and hence to an effective
dilution at constant volume; this situation favors cyclization over oligomerization.
At low densities, local concentrations of substrate are significantly increased over
the bulk values due to solute/solute clustering; this favors the intermolecular
pathway over the intramolecular cyclization reaction [39].

Ru-cat.:
“7
/[=
CI.. Ph d = 0.83 g mL-1 88% yield
___
CI d = 0.55 g rnL-1 70% yield
CY3

3.1.13.2.3 Catalysis Using “CO,-philic” Catalysts

Neutral Catalysts or Catalyst Precursors

The design of materials with high affinity for scC0, is an area of paramount im-
portance for a broader application of this solvent [40]. Whereas solubility is the
only design parameter in many potential applications [4 11, the structural modifi-
cations required to render an insoluble organometallic catalyst “C02-philic” can
affect also its catalytic performance. Such changes are kept to a minimum in
the general approach depicted schematically in Figure 2 [42]. The “C0,-philic”
side group is connected to the catalyst in the periphery of the ligand sphere
using a linker that allows control of electronic effects at the metal center. At pre-
sent perfluoroalkyl groups have been used to provide high affinity to C 0 2 for
metal catalysts almost exclusively. Just one or two CF3 groups per aryl ring can
be sufficient for catalytically relevant solubilities [43, 441, and direct fluorination
of aryl rings may also be efficient [45]. These modifications result in greatly
reduced electron densities at the metal centers as compared with the parent un-
modified catalysts [46]. The introduction of two methylene units is known to
block the electron-withdrawing effect of long perfluoroalkyl chains [47] and the
 3.1.13.2 Single-Phase Catalysis Using SCFs as Solvents 859

- 0
scco,
= C0,-philic

=
side group, e.0. -(CF,),F
linker, e.g. -(CHZ)*-

Figure 2. “C0,-philic” catalysts can be obtained by connecting suitable solubilizers in the

periphery of the ligand framework.

(CH2)2(CF2)6Fside group can be introduced into aryl phosphorus ligands via a

very flexible synthetic route [18, 19, 42, 48, 491. Spectroscopic data suggest
that this group (referred to in the following sections as H2F6) exhibits a slightly
electron-donating effect, similarly to a methyl substituent [42].
Although alkane groups are expected to increase the lipophilicity of aryl phos-
phorous ligands, their introduction does not usually increase the solubility of the
corresponding organometallic catalysts sufficiently without the addition of co-sol-
vents [50, 511. It is again important to note that solubility in scCOz is controlled
by a more complex set of parameters than just polarity alone. In contrast to the
fluoroalkyl congeners, the addition of long alkane chains usually decreases the
vapor pressure of a given complex, exhibiting a negative effect on COz solubility.
Additional positive interactions between fluorinated groups and COz are also
discussed, which are not available for the respective alkane chains [52].
Neutral catalysts or catalyst precursors based on fluorinated ligand systems
have been applied in compressed C 0 2 to a broad range of transformations
such as Zn- and Cr-catalyzed copolymerization of epoxides and C 0 2 [53, 541,
Mo-catalyzed olefin metathesis [9], Pd-catalyzed coupling reactions [43, 55, 561
and Pd-catalyzed hydrogen peroxide synthesis [57]. Rhodium complexes with
peffluoroalkyl-substituted P ligands proved successful in hydroformylation of
terminal alkenes [28, 42, 44, 581, enantioselective hydroformylation [ 18, 59, 601,
hydrogenation [6I], hydroboration [62], and polymerization of phenylacetylene
~31.
The enantioselective hydroformylation using BINAPHOS-based ligand sys-
tems provides a particularly illustrative example. The original catalytic system
[64] gives preparatively unsatisfactory results in scC0, as the ee values are always
lower than in conventional solvent systems or in neat substrate [65, 661. Further-
more, the ee values show a strong dependence on the C 0 2 density, with significant
asymmetric induction only at values close to or below the critical density of pure
COz [65]. At low densities, the solvent power of C 0 2 is not sufficient to dissolve
860 3.I Development of Methods

the substrate styrene and the corresponding aldehydes completely, so small

amounts of liquid phases are present at various stages of the reaction. Rh com-
plexes of BINAPHOS are practically insoluble in scC02 and can therefore contri-
bute to catalytic turnover only in the presence of such liquid phases. Unmodified
Rh carbonyls, which are in equilibrium with BINAPHOS-containing species
under hydroformylation conditions [64], are highly soluble and active in the
supercritical phase, leading to formation of racemic product. The perfluoro-
alkyl-substituted derivative 3-H2F6-BINAPHOS ameliorates all these problems
and gives excellent ee values independently of the phase behavior [59]. Most
rewardingly, a significant increase in the regioselectivity toward the desired
branched aldehyde is obtained with this new system for a broad range of sub-
strates (eq. (4)) [ 181. Control experiments demonstrated unambiguously, that the
higher regioselectivity is due to the ligand substitution pattern. It is interesting
to note that the selectivity increase is fully consistent with an electron donating
effect of the side chain within current models for the hydroformylation mechanism
~671.
T = 40 - 60°C
p”(tot) = 150 - 205 bar
/== + C O +H2 k C H 0 + R/cHo
R 3-H2F6-BINAPHOSI*
[cod)Rh(hfacac)] R
scCO2 (4)
R = Ph, cv = 98% 93 [92% (R)] 7
R = ~ - ‘ B I J C ~ cv
H ~>, 99% 96 [go% (R)] 4
R = 2-naphthy1, cv > 99% 92 [78% (-)I : 8
R = OCOCH3, cv > 99% 92 [91% (S)] : 8

Cationic Catalysts or Catalyst Precursors

The examples discussed in the previous section comprise neutral organometallic

species as catalysts and catalyst precursors. Although the metal centers are present
in various oxidation states that may change during the catalytic cycle, a corre-
sponding number of anionic ligands compensate the resulting positive charge.
There is, however, a large class of catalysts in which the active center is part of
a complex cation. The application of such species in nonpolar carbon dioxide
appears difficult at first sight.
The use of “CO2-philic” ligands can help to increase the solubility of ionic
compounds also, but the most important target to influence the performance of
such catalysts in scC02 is the anion. Firstly, the synthetic effort necessary to in-
troduce “C0,-philic” groups in the anion is generally smaller than for the ligand
and one anion can be applied to various cationic complexes. Secondly, there is a
strong tendency for ionic compounds to form ion pairs and even higher aggregates
in the nonpolar medium C 0 2 [68], and the association or dissociation of these
units can exhibit a strong influence on the reactivity and selectivity of the metal
center.
 3.1.13.2 Single-Phase Catalysis Using SCFs as Solvents 861

100
90 I X=BARF I
80
70
-
2
s
v
60
50
a,
a, 40
30
20
10
0
la Ib la Ib la Ib
catalyst

Figure 3. Enantioselectivities of cationic Ir catalysts in eq. ( 5 ) .

The systematic series of cationic Ir catalysts 1 illustrates the importance of the

choice of the anion [69]. Only the complexes with the BARF anion (BARF =
tetrakis[3,5-bis(trifluoromethyl)phenyl]borate) give excellent enantioselectivities
in the asymmetric hydrogenation of imines (eq. ( 5 ) ; Figure 3 ) , matching those
obtained in conventional solvents such as CH2C12.Interestingly, the ee is indepen-
dent of the anion in the conventional solvent. A 20-fold increase of catalyst effi-
ciency is observed if the same catalyst precursor is used in C 0 2 as compared with
CH2C12.The improved performance in SCCO,? is related to a change in the reaction
profile rather than a simple increase in reaction rate.

la,R=H
1b, R = H2F6

H2 (30bar)
N/Ph
T = 40"C, po = 200 bar
t

PhACH, Ir-cat.
scco2

Chiral cationic Rh catalysts for the hydrogenation of prochiral C-C double

bonds require the use of BARF or related anions even with potentially C02-soh-
ble ligands such as Et-DuPHOS (DuPHOS = 1,2-bis(2,5-dialkylphospholano)-
benzene) [70] or a peffluoroalkyl-substituted aryl phosphonite [ 191. The ligand
862 3.1 Development of Methods

3-H2F6-BINPAHOSallows high rates and enantioselectivities with simple BF4-

as counterion, but at least partly under multiphase conditions [18]. Remarkably,
the excellent performance of the BINAPHOS skeleton for asymmetric hydro-
genation was discovered for the first time as part of the studies toward its use
in scC02.
Cationic Pd diimine complexes initiate polymerization of terminal olefins in
scC02 as the solvent [71]. Again, BARF is the anion of choice both for solubility
and reactivity reasons. Similarly to the ROMP experiments described above, high
turnover rates are observed even after precipitation of the polymer. The solubility
of the catalyst was estimated to be in the order of 10" mol L-'.
The choice of the anion is also crucial in systems where the active cationic spe-
cies is formed from a neutral precursor, as in the case of the nickel ally1 chloride
catalyst used for asymmetric hydrovinylation (eq. (6); cf. also Section 3.3.3). The
previously optimized conditions for this reaction involved the use of highly flam-
mable Al2Et3Cl3as chloride-abstracting agent and required the use of CH2C12at
-78°C. Using NaBARF in compressed C02, the C-C bond coupling occurs
around room temperature with excellent chemo-, stereo-, and enantioselectivity
[73]. This example demonstrates nicely that the application of C 0 2 can have en-
vironmental benefits for catalytic processes far beyond the solvent replacement.

f Y=
0 + C2H4
T = 040°C

Ni-cat./activator
compressed C 0 2

A12Et3C13 92%, 70% (R)

NaOTf ---
<I%,

NaBARF 88%, 86% (R)

3.1.13.3 Multiphase Catalysis Using SCFs as Solvents

3.1.13.3.1 Catalytic Reactions Under Multiphase Conditions

Involving SCFs
In general, the potential benefits of using scC02 or other SCFs in homogeneous
catalysis can be exploited best under single-phase conditions. For many of the ex-
amples discussed in the previous sections, control experiments demonstrate that
the presence of a single homogeneous reaction phase is a necessary prerequisite
 3.I . 13.3 Multiphase Catalysis Using SCFs as Solvents 863

for efficient catalysis. A number of examples are known, however, where catalytic
reactions occur also when more than just one phase is present. In favorable cases,
some of the benefits of the supercritical state can still be retained without the need
to adjust the catalyst to the solvent properties of the SCF.
A classical example is the hydrogenation of C 0 2 in the presence of secondary
amines to yield formamides (eq. (7)). The formation of carbamates from the amine
and CO, leads to the presence of a liquid phase that cannot be dissolved in CO,
even at temperatures and pressures way beyond the critical data of pure C02.
Nevertheless, the reaction occurs with extraordinarily high turnover numbers
and reaction rates [17, 341, even with catalysts that have no solubility in scC0,
[35,72]. Most likely, the reaction occurs in the liquid phase, but the "supercritical"
C 0 2 phase ensures rapid mass transfer of the reactants (CO,, H2) and the product
(DMF) between the two phases. It has been shown recently that the addition of
ionic liquids (vide infru) can help to control the distribution of reactants, inter-
mediates, and products between the two reaction phases. Additional control
over the chemoselectivity of the transformation is thus possible by judicious
segregation of various components of the reaction mixture [36, 741.
T = 100°C 0
p"(tot) > 200 bar
CO2/HZ + [Me2NC0,][MezNHz] + H2O
Ru-cat.
* Me2N NMe2
"supercritical" "dimcarb", liquid sc-phase I-phase

(7)
The rapid mass transfer between the liquid and the supercritical phase in such
systems is not just a result of the presence of the SCF, but largely due to the
swelling of the liquid phase by dissolved CO,. Many organic liquids are able to
dissolve large quantities of CO,, leading to significant expansion of their volumes
associated with reduced densities and viscosities. Such expanded solvent systems
are already formed under pressures below the critical pressure of CO, and have
recently received attention especially for catalytic oxidation reactions [75]. CO,
is also soluble to a large extent in organic solids, leading to considerable melting
point depression in many cases [76]. Thus, "solventless" syntheses become
possible in liquefied substrates at temperatures way below their conventional
melting points. Again, both subcritical [77] and supercritical [ 181 pressures can
be applied.

3.1.13.3.2 Catalysis and Extraction Using Supercritical

Solutions (CESS)
The strongest impetus to break down the homogeneous single-phase situation of
an SCF reaction comes from the possibility of separating catalyst and products,
leading to new and highly efficient processes for catalyst immobilization. The
basic principle of this concept is to combine the molecular design of homogeneous
864 3. I Development of Methods

Table 2. Principles of catalyst immobilization exemplified for hydroformylation.

Immobilizing principle Rh catalyst Ref.
~~~ ~

Supercritical/solid Silica-bound XantphosRh complex [go1

SupercriticaVliquid RNTPPDS in ionic liquid [881
Phase behavior Rh/4-H2F6-TPP [281

organometallic catalysis with the process design of supercritical fluid extraction.

As exemplified in Table 2 for the Rh-catalyzed hydroformylation of terminal
olefins (eq. (8)), there are three distinct approaches to the utilization of SCFs in
such systems.
In a first approximation, the new methods correspond to the conventional sol-
vent techniques of supported catalysts (cf. Section 3.1.1.3), liquid biphasic cata-
lysis (cf. Section 3.1.1. l), and thermomorphic (“smart”) catalysts. One major dif-
ference relates to the number of reaction phases and the mass transfer between
them. Owing to their miscibility with reaction gases, the use of an SCF will reduce
the number of phases and potential mass transfer barriers in processes such as hy-
drogenation, carbonylations, oxidation, etc. For example, hydroformylation in a
conventional liquid “biphasic” system is in fact a three-phase reaction (g/M),
whereas it is a two-phase process (sc/l) if an SCF is used. The resulting elimina-
tion of mass transfer limitations can lead to increased reaction rates and selectiv-
ities and can also facilitate continuous flow processes. Most importantly, however,
the techniques summarized in Table 2 can provide entirely new solutions to
catalyst immobilization which are not available with the established set of liquid
solvents.
The use of organometallic catalysts that are immobilized on organic or in-
organic supports can benefit from the use of an SCF as the mobile phase in a
way similar to classical heterogeneous catalysts [78]. Polyvinylpyrrolidone proved
effective as a support for recyclable Rh catalysts used in methanol carbonylation
[79]. Highly active catalysts for the hydrogenation of COz to DMF have been pre-
pared by anchoring Ru complexes to silica gels of various pore sizes [72]. Macro-
porous catalysts proved considerably more active than microporous materials,
probably reflecting the fact that this reaction occurs in a three-phase system (sc/Vs).
Under sc/l conditions such silica-supported systems can be readily implemented
for continuous-flow operation as demonstrated recently for the hydroformy lation
of long-chain olefins (eq. (8)) [80]. The organometallic catalyst was supported
using classical sol-gel techniques and the specific ligand structure gives very
high selectivities for the linear aldehyde. In a flow-type reactor, scC0, is then
used to transport the reactants and products along the catalyst bed, allowing
continuous operation with no detectable catalyst leaching.
CHO

H9C.4- \
COIH2

immobilzed Rh-cat.
* H9C4-CHo + H9C44-
(8)

scco2 n-aldehyde iso-aldehyde

866 3.1 Development of Methods

90 I

Figure 4. The nickel catalyst for asymmetric hydrovinylation (see eq. (6)) is activated, tuned,
and immobilized in an IL/C02 continuous-flow system.

phase. Selective extraction of the products with an SCF of low solvent power
yields the product in solvent-free form, leaving behind the catalyst for further
use. This sequence has been referred to as catalysis and extraction using super-
critical solutions (CESS), but the expression may be applied in a more general
sense to all techniques described in this section.
Many of the above-mentioned reactions can be successfully coupled with an
extraction step in the CESS procedure. In the hydrogenation of imines, the con-
version of the substrate to the product is sufficient to change the solubility of
the Ir catalyst in the medium [69]. The transformation and subsequent extraction
can thus be carried out without changes in pressure and temperature, effectively
immobilizing the catalyst for at least four subsequent cycles. The low solubility
of the Grubbs metathesis catalyst allows for a similar sequence in RCM [9].
The highly “CO2-philic” fluoroalkyl-substituted catalysts are particularly useful
for this immobilization technique, as demonstrated for the hydroformylation of
various alkenes (cf. Section 3.1.1.2.1). Figure 5 shows the results of batchwise
recycling experiments using the 4-H2F6-TPPRh catalyst for 1-octene hydrofor-
mylation (eq. (8)) [28]. A pressure swing is most effective for switching from
single-phase reaction to selective extraction in this case. Rhodium contamination
of the product as low as 1 ppm is possible even under nonoptimized laboratory
conditions. Similar values are achieved in the asymmetric hydroformylation of
vinyl arenes using 3-H2F6-BINAPHOS[18]. In this case, there is also a potential
for product purification by selective extraction of the desired branched aldehyde
 3.1.13.4 Conclusions and Outlook 867

100

80

20

0
1 2 3 4 5
cycle

Figure 5. Product isolation and catalyst recycling via the CESS approach in the
hydroformylation of l-octene (eq. (8)) using the C02-philic in situ catalyst
4-H2F6-TPP/[(cod)Rh(hfacacj] (4: 1).

during the separation sequence. It is important to note that no satisfactory method

for product isolation and catalyst recycling is available for the unmodified parent
catalysts in either reaction under conventional conditions.

3.1.13.4 Conclusions and Outlook

The unique solvent properties of supercritical fluids hold many opportunities for
new and innovative applications in homogeneous catalysis. The favorable proper-
ties of carbon dioxide in terms of acute toxicology, environmental hazard, process
safety, and material costs make this particular solvent especially attractive for
“green” and sustainable synthetic processes. The investment and operating costs
associated with high-pressure techniques are clearly a major issue for potential
technical applications. This balance is certainly unfavorable for linear extrapola-
tions of batchwise laboratory experiments. There is, however, rapidly growing en-
gineering know-how resulting from an increasing number of applications of
scC0, as a solvent in other chemistry-related industries [2]. This is also expected
to influence the process design of synthetic applications and may help to stimulate
the acceptance of this technology in chemical production. The development of
continuous-flow processes and catalyst immobilization techniques will be crucial
for synthetic applications on any scale.
Extensive research efforts are still required to provide the scientific basis for
such potential applications. Homogeneous catalysis in SCFs has been flourishing
since it started to receive more general attention in the mid-1990s. Some rules and
general patterns become apparent for catalyst design, but new generations of
cheap and readily available “C0,-philic” catalysts are urgently required. En-
868 3.1 Development of Methods

hanced reaction rates and selectivities have been observed in a variety of reac-
tions, but their detailed understanding on a molecular basis is still limited. Highly
promising areas like oxidation or the use of C 0 2 as a solvent and feedstock have
only been touched. It is important to note, however, that the basic catalyst devel-
opment is still in its infancy in many of these areas, even in conventional solvents.
The challenge for homogeneous catalysis in SCFs is the combination of molecular
design, reaction engineering, and process development. Progress in this exciting
field of organometallic chemistry is therefore expected to originate particularly
from interdisciplinary efforts between synthetic chemists, physico-chemists, and
engineers.

References
[ l ] Chemical Synthesis Using Supercritical Fluids (Eds.: P. G. Jessop, W. Leitner), Wiley-
VCH, Weinheim, 1999.
(a) K. Zosel, Angew. Chem., Int. Ed. Engl. 1978, 17, 702; (b) M. McHugh, V. J. Kruko-
nis, Supercriticul Fluid Extraction, Buttenvorth-Heinemann, Boston, 1994; (c) S. Wells,
J. M. DeSimone, Angew. Chem., Int. Ed. Engl. 2001, 40, 5 18.
For some early reviews see: (a) P. G. Jessop, T. Ikariya, R. Noyori, Science 1995, 269,
1065; (b) D.A. Morgenstern, R.M. LeLacheur, D.K. Morita, S.L. Borkowsky,
S. Feng, G. H. Brown, L. Luan, M. F. Gross, M. J. Burk, W. Tumas, in Green Chemistry
(Eds.: P. T. Anastas, T. C. Williamson), ACS Symp. Ser: 626, American Chemical Society,
Washington DC, 1996, p. 132; (c) E. Dinjus, R. Fomika, M. Scholz, in Chemistry under
Extreme or Non-Classical Conditions (Eds.: R. van Eldik, C. D. Hubbard), Wiley, New
York, 1996, p. 219.
[4] (a) P.G. Jessop, T. Ikariya, R. Noyori, Chem. Rev. 1999, 99, 475; (b) D. Walther,
M. Ruben, S. Rau, Coord. Chem. Rev. 1999, 182, 67; (c) R. S. Oakes, A. A. Clifford,
C. M. Rayner, J. Chem. Soc., Perkin Trans I 2001, 917.
[5] W. Leitner, Top Curr: Chem. 1999, 206, 107.
[6] S.C. Tucker, M. W. Maddox, J. Phys. Chem. B 1998, 102, 2437.
[7] R. Span, W. Wagner, J. Phys. Chem. Ret Data 1996, 2.5, 1509.
[8] D.C. Wynne, M.M. Olmstead, P.G. Jessop, J. Am. Chem. Soc. 2000, 122, 7638.
[9] (a) A. Furstner, D. Koch, K. Langemann, W. Leitner, C. Six, Angew. Chem., Int. Ed.
Engl. 1997, 36, 2466; (b) A. Furstner, L. Ackermann, K. Beck, H. Hori, D. Koch,
K. Langemann, M. Liebl, C. Six, W. Leitner, J. Am. Chem. Soc. 2001, 123, 9000.
[ 101 K. Wittmann, W. Wisniewski, R. Mynott, W. Leitner, C. L. Kranemann, T. Rische, P. Eil-
bracht, S. Kluwer, J. M. Emsting, C. J. Elsevier, Chem. Eur: J. 2001, 7, 4584.
[ I l l J. Ke, B. Han, M. W. George, H. Yan, M. Poliakoff, J. Am. Chem. Soc. 2001, 123, 3661.
[12] Mass separation using SCFs was referred to as Destruktion by Zosel [2a] to emphasize
the contribution of vapor pressure (distillation = Desrillation) and polaritykolvation
(extraction = Extraktion).
[13] (a) A. Behr, Carbon Dioxide Activation by Metal Complexes, VCH, Weinheim, 1988;
(b) W. Leitner, Coord. Chem. Rev. 1996, 153, 257.
[14] C. Six, A. Wegner, W. Leitner, Organometallics 2000, 19, 4639.
[lS] U. Kreher, S. Schebesta, D. Walther, Z. Anorg. Allg. Chem. 1998, 624, 602.
[ 161 For reviews see: (a) P. G. Jessop, T. Ikariya, R. Noyori, Chem. Rev. 1995, 95, 259;
(b) W. Leitner, Angew. Chem., Int. Ed. Engl. 1995, 34, 2207.
[17] P. G. Jessop, Y. Hsiao, T. Ikariya, R. Noyori, J. Am. Chem. Soc. 1996, 118, 344.
 References 869

[18] G. Francih, K. Wittmann, W. Leitner, J. Orgunomet. Chem. 2001, 621, 130.

[19] S. Lange, A. Brinkmann, P. Trautner, K. Woelk, J. Bargon, W. Leitner, Chirality 2000,
12, 450.
[20] J. W. Rathke, R. J. Klingler, T. R. Krause, Organometallics 1991, 10, 1350,
1211 J. W. Rathke, R. J. Klingler, R. E. Gerald 11, D. Fremgen, K. Woelk, S. Gaemers, C. J.
Elsevier, in Ref. [l], Section 3.2, p. 165.
[22] (a) Y. Guo, A. Akgerman, Ind. Eng. Chem. Res. 1997, 36, 4581; (b) Y. Guo, A. Akger-
man, J. Supercrit. Fluids 1999, 15, 63; (c) B. Lin, A. Akgennan, Ind. Eng. Chem. Res.
2001, 40, 1113.
[23] N. Jeong, S.H. Hwang, Y. Woo, Lee, J. S. Lim, J. Am. Chem. Soc. 1997, 119, 10549.
[24] N. Jeong, S.H. Hwang, Angew. Chem., Int. Ed. Engl. 2000, 39, 636.
[25] (a) K.S. Jerome, E.J. Parsons, Organometallics 1993 12, 2991; (b) H. Borwieck,
0. Walter, E. Dinjus, J. Rebizant, J. Organomet. Chem. 1998, 570, 121.
[26] (a) G. R. Haas, J. W. Kolis, Tetrahedron Lett. 1998, 39, 5923; (b) G. R. Haas, J. W. Kolis,
Organometallics 1998, 17, 4454.
1271 D.R. Pesiri, D.K. Morita, W. Glaze, W. Tumas, Chem. Commun. 1998, 1015.
[28] D. Koch, W. Leitner, J. Am. Chem. SOC.1998, 120, 13398.
1291 I. Bach, D. J. Cole-Hamilton, Chem. Commun. 1998, 1463.
Y. Kayaki, Y. Noguchi, S. Iwasa, T. Ikariya, R. Noyori, Chem. Commun. 2000, 1235.
M.T. Reetz, W. Konen, T. Strack, Chimia 1993, 47, 493.
P. G. Jessop, T. Ikariya, R. Noyori, Nature (London) 1994, 368, 23 1.
P. G. Jessop, Y. Hsiao, T. Ikariya, R. Noyori, J. Chem. Soc., Chem. Commun. 1995, 707.
P.G. Jessop, Y. Hsiao, T. Ikariya, R. Noyori, J. Am. Chem. Soc. 1994, 116, 8851.
0. Krocher, R. A. Koppel, A. Baiker, Chem Commun. 1997, 453.
F. Liu, M. B. Abrams, R.T. Baker, W. Tumas, Chem. Commun. 2001, 433.
For use of less defined Ru catalysts in ROMP: (a) C. D. Mistele, H. H. Thorp, J. M. De-
simone, Polym. Prepl: 1995, 36, 507; (b) C. D. Mistele, H. H. Thorp, J. M. Desimone,
J. Mucromol. Sci., Pure. Appl. Chem. 1996, A33, 953.
The discussion is restricted here to kinetic effects, although a thermodynamic contribu-
tion cannot be excluded.
S. Panday, M . A . Kane, G.A. Baker, F.V. Bright, A. Furstner, G. Seidel, W. Leitner,
J. Phys. Chem. B 2002, in press.
For a mini-review see: W. Leitner, Nature (London), 2000, 405, 129.
For applications in metal ion extraction see: N. G. Smart, T. Carleson, T. Kast, A. A. Clif-
ford, M. D. Burford, C. M. Wai, Talantu 1997, 44, 137.
S. Kainz, D. Koch, W. Baumann, W. Leitner, Angew. Chem., Int. Ed. Engl. 1997,
36, 1628.
D. K. Morita, D. R. Pesiri, S. A. David, W. H. Glaze, W. Tumas, Chem. Commun. 1998,
1397.
(a) D. R. Palo, C. Erkey, Ind. Eng. Chem. Res. 1998,37,4203; (b) D. R. Palo, C. Erkey,
Ind. Eng. Chem. Res. 1999, 38, 3786; (c) D. R. Palo, C. Erkey, Organometallics 2000,
19, 81.
K.-D. Wagner, N. Dahmen, E. Dinjus, J. Chem. Eng. Data 1999, 45, 672.
C. A. Tolman, Chem. Rev. 1977, 77, 312.
(a) I. T. Horvgth, J. RBbai, Science 1994, 266, 72; (b) I. T. HorvBth, G. Kiss, R. A. Cook,
J. E. Bond, P. A. Stevens, J. Rabai, et al., J. Am. Chem. Soc. 1998, 120, 3133.
S. Kainz, Z. Luo, D. P. Curran, W. Leitner, Synthesis 1998, 1425.
For a general review on the syntheses of perfluoroalkyl-substituted ligands see: L. P.
Barthel-Rosa, J.A Gladysz, Coord. Chem. Rev. 1999, 190-192, 587.
J. Xiao, S.C.A. Nefkens, P.G. Jessop, T. Ikariya, R. Noyori, Tetrahedron Lett. 1996,
37, 2813.
870 3.1 Development of Methods

[51] M. F. Sellin, D. J. Cole-Hamilton, J. Chem. Soc., Dalton Trans. 2000, 1681.

[52] A. Dardin, J. DeSimone, E.T. Samulski, J. Phys. Chem. B 1998, 102, 1775.
[53] (a) M. Super, E. Berluche, C. Costello, E. Beckman, Macromolecules 1997, 30, 368;
(b) for insoluble Zn catalysts see: D. J. Darensbourg, N. W. Stafford, T. Katsurao,
J. Mol. Catal. A: Chemical 1995, 104, L1.
[54] S. Mang, A.I. Cooper, M.E. Coclough, N. Cauhan, A.B. Holmes, Macromolecules
2000, 33, 303.
1551 N. Shezad, R. S. Oakes, A. A. Clifford, C. M. Rayner, Tetrahedron Lett. 1999,40, 2221.
[56] M.A. Carrol, A.B. Holmes, Chem. Commun. 1998, 1395.
[57] D. Hsncu, E. J. Beckman, Green Chem. 2001, 3, 80.
[58] A. Banet, D.R. Paige, A.M. Stuard, I. R. Chadbond, E. G. Hope, J. Xiao, 11th Znt. Symp.
Homogeneous Catalysis, St. Andrews, 1998, p. 252.
[59] G. Francio, W. Leitner, Chem. Commun. 1999, 1663.
[60] D. Bonafoux, B. Wang, I. Ojima, Abstracts of the ACS Spring Meeting, Sun Diego,
2001, ORGN-442, American Chemical Society, Washington DC, 2001.
[61] S. Kainz, D. Koch, W. Leitner, in Selective Reactions of Metal-Activated Molecules
(Eds.: H. Werner, W. Schreier), Vieweg, Wiesbaden, 1998, p. 151.
[62] C. A. G. Carter, R. T. Baker, S. P. Nolan, W. Tumas, Chem. Commun. 2000, 347.
[63] H. Hori, C. Six, W. Leitner, Macromolecules 1999, 32, 3178.
[64] (a) K. Nozaki, N. Sakai, S. Mano, T. Higashijima, T. Horiuchi, H. Takaya, J. Am. Chem.
Soc. 1997, 119, 4413; (b) K. Nozaki, H. Takaya, T. Hiayama, Top. Card 1997, 4, 175.
[65] S. Kainz, W. Leitner, Catal. Lett. 1998, 55, 223.
[66] I. Ojima, M. Tzamarioudaki, C. Y. Chuang, D. M. Iula, Z. Li, Catalytic Carbonylations in
Supercritical Carbon Dioxide, in Catalysis of Organic Reactions (Ed.: F. E. Herkes),
Marcel Dekker, New York, 1998, p. 333.
[67] C. P. Casey, E. L. Paulsen, E. W. Beutenmuller, B. R. Proft, B. A. Matter, D. R. Powell,
J. Am. Chem. Soc. 1999, 121, 63.
[68] (a) A. P. Abbott, G. A. Griffith, J. C. Harper, J. Chem. Soc., Faraday Trans. 1997, 93,
577; (b) A. P. Abbott, J.C. Harper, Phys. Chem. Chem. Phys. 1999, 1 , 839.
[69] S. Kainz, A. Brinkmann, W. Leitner, A. Pfaltz, J. Am. Chem. Soc. 1999, 121, 6421.
[70] M. J. Burk, S. Feng, M. F. Gross, W. Tumas, J. Am. Chem. Soc. 1995, 117, 8277.
[71] T. J. de Vries, R. Duchateau, M. A. G. Vorstman, J. T. F. Keurentjes, Chem. Commun.
2000, 263.
[72] (a) 0. Krocher, R. A. Koppel, A. Baiker, Chem. Commun. 1996, 1497; (b) 0. Krocher,
R. A. Koppel, M. Froba, A. Baiker, J. Catal. 1998, 178, 284; (c) L. Schmid, M. Rohr, A.
Baiker, Chem. Commun. 1999, 2303.
[73] A. Wegner, W. Leitner, Chem. Commun. 1999, 1583.
[74] For a related discussion with an organic/scC02 biphasic system see: Y. Kayaki, Y.
Noguchi, T. Ikariya, Chem. Commun. 2000, 2245.
[75] G. Musie, M. Wei, B. Subramaniam, D.H. Busch, Coord. Chem. Rev. 2001, 219-221
789.
1761 This effect also forms the basis of various crystallization techniques. See A. Bertucco,
in Ref. [l], Section 2.3, p. 109.
1771 P. Jessop, D. C. Wynne, S. DeHaai, D. Nakawatase, Chem. Commun. 2000, 693.
[78] (a) A. Baiker, Chem. Rev. 1999, 99,453; (b) W. K. Gray, F. R. Smail, M. G. Hitzler, S. K.
Ross, M. Poliakoff, J. Am. Chem. Soc. 1999, 121, 10711.
[79] R. J. Sowden, M. F. Sellin, N. De Blasio, D. J. Cole-Hamilton, Chem. Commun. 1999,
2511.
[80] N.J. Meehan, A.J. Sandee, J.N.H. Reek, P.C.J. Kramer, P.W.N.M. van Leeuwen,
M. Poliakoff, Chem. Commun. 2000, 1497.
[81] B.M. Bhanage, Y. Ikushima, M. Shirai, M. Arai, Chem. Commun. 1999, 1277.
 References 87 1

[82] B. M. Bhanage, Y. Ikushima, M. Shirai, M. Arai, Tetrahedron Lett. 1999, 40, 6427.
[83] K. P. Johnston, K. L. Harrison, M. J. Clarke, S. M. Howdle, M. P. Heitz, F. V. Bright,
et al., Science, 1996, 271, 624.
[84] G. B. Jacobsen, C.T. Lee, Jr., K. P. Johnston, W. Tumas, J. Am. Chem. Soc. 1999, 121,
11902.
[85] (a) P. Wasserscheid, W. Keim, Angew. Chem., Int. Ed. 2000, 39, 3772; (b) T. Welton,
Chem. Rev. 1999, 99, 2071; (c) J.D. Holbrey, K.R. Seddon, Clean Products and
Processes 1999, I, 223.
[86] L. A. Blanchard, D. Hbncu, E. J. Beckman, J. F. Brennecke, Nature (London) 1999,
399, 28.
[87] R. A. Brown, P. Pollett, E. McKoon, C. A. Eckert, C. L. Liotta, P. G. Jessop, J. Am. Chem.
SOC.2001, 123, 1254.
[88] M. F. Sellin, P. B. Webb, D. J. Cole-Hamilton, Chem. Commun. 2001, 781.
[89] A. Bosmann, G. Francib E. Janssen, M. Solinas, W. Leitner, P. Wasserscheid, Angew.
Chem., Int. Ed. Engl. 2001, 40, 2691.
 Applied Homogeneous Catalysis with Organometallic Compounds
Edited by B. Cornils and W. A. Herrmann
Copyright 0 Wiley-VCH Verlag GmbH, D-69469 Weinheim, 2002

872 3.2 Special Catulysts and Processes

3.2 Special Catalysts and Processes

3.2.1 Biocatalysis and Enzyme-Analogous Processes

Carsten Schultz, Harald Grogel; Carlo Dinkel,
Karlheinz Drauz, Herbert Waldmann

3.2.1.1 Introduction
A modem survey of homogeneous catalysis would not be complete without a
discussion of enzyme-catalyzed transformations. The fact that enzymes represent
the first chiral catalysts should ensure them a place next to the most sophisticated
man-made catalysts. Although it seems odd that the catalyst has to be isolated
from cells, tissue, or organs and that sometimes whole organisms are employed
to do the work, the rapid development and success of biocatalytic processes
[ 1-1 51 for the synthesis of natural products, pharmaceuticals, and agrochemicals
[ 161 has immensely increased their acceptance among chemists. They have in part
found industrial applications, especially since many technical problems entailed -
such as enzyme stabilization, enzyme immobilization, and cofactor regeneration -
have been solved. Also, the availability of enzymes has been largely improved: of
the more than 3000 enzymes known, several hundred are commercially accessible
or can be obtained in sufficient purity through easy, well-developed procedures.
Moreover, enzymes can in principle be produced in large quantities by recom-
binant DNA techniques and their properties can be manipulated in favor of a
desired performance by directed evolution or DNA shuffling [17, 181. When en-
zyme techniques are combined with high-throughput screening systems [ 171 to
test for improved efficacy, scientists now have very powerful tools on hand to
overcome some of the classic caveats for using enzymes and thrive on their
advantages.
Due to the characteristic properties of enzymes compared with the chemical
reactions usually employed, enzymatic transformations are exceptional in several
respects.
(1) They operate under mild conditions within a pH range of 5 to 8 at tempera-
tures around 2 0 4 0 ° C in aqueous media.
(2) Many of them tolerate organic solvents [5, 12, 191.
(3) Enzymes are highly efficient catalysts, accelerating reactions by factors of
105-101*compared to the corresponding uncatalyzed reactions.
(4) Enzymes often combine a high selectivity for the reactions they promote and
the structures they recognize with a broad substrate tolerance.
( 5 ) Besides their chemoselectivity many enzymes exhibit a high degree of
diastereo-, regio-, andor enantioselectivity.
As a result of the increasing desire for complex, biologically relevant
substances and the problems connected with their efficient preparation, it is
 3.2.1.2 Examples of Enzymatic Conversions 813

mainly the enantio-discriminating properties of enzymes that have led to the ex-
ponential development of the use of such complex molecules in organic synthesis.
In this revised section, some recent examples have been selected emphasizing
applications of enzymes to generation of natural products and derivatives and pre-
cursors combined with some of the latest technical developments.

3.2.1.2 Examples of Enzymatic Conversions

3.2.1.2.1 Syntheses by Means of Hydrolases

Due to their ready availability and the ease with which they can be handled,
hydrolytic enzymes have been widely applied in organic synthesis. They do not
require coenzymes, are reasonably stable, and often tolerate organic solvents.
Their potential for regioselective and especially for enantioselective synthesis
makes them valuable tools [lo, 14, 16, 191.

Acylation

Regioselective acylations of polyhydroxylated compounds such as carbohydrates,

glycerols, steroids, or alkaloids have been carried out with lipases, esterases, and
proteases [13, 201. One example is the Candida antartica lipase (immobilized on
acrylic resin) catalyzed monoacylation of the signalling steroid ectysone (1) giv-
ing selectively the 2-0-acetate 2 (eq. (1)). Using vinyl acetate for this transesteri-
fication the reaction was irreversibly pushed to the product side, since the
liberated enol instantaneously isomerizes to acetaldehyde [2 11. The sometimes
unfavorable aldehyde is avoided when 1-ethoxyvinyl acetates [22], trichloro- or
-fluoroethyl esters [23 a, b], oxime esters [23 c] or thioesters [23 d] are employed
for the “quasi-irreversible’’ reaction courses.

Novozyrn 435@

HO \ O h

0 f-AmOH, 10% pyridine,

45°C.7d
1 2
95%
Deacylation

In the synthesis of highly phosphorylated phosphoinositide derivatives regioselec-

tive hydrolysis of one out of three butyrates by a lipase in pH 7.8 buffer containing
814 3.2 Special Catalysts and Processes

OTBDMS
lipase
P
buffer

H7C3 HO C3H7

0
0

Scheme 1

5 % methanol gave the key intermediate 3, unfortunately without yielding an

enantiomeric excess (Scheme 1) [24].

Enantioseparation

An intensively utilized strategy is the kinetic resolution of racemic mixtures [ 191,

either by stereoselective (trans)-esterification or -amidation reactions in organic
solvents or hydrolysis in aqueous media. This approach is particularly attractive
when the unreacted enantiomer is racemized in the process and re-reacted. In
the example shown in Scheme 2 ethyl acetate was used as the acylating agent

H3C\/ Ph
H3cYPh
NH2
+
H3C\/
-
-
-
Ph acylation
immobilized lipase,* H3CYPh
NH2
-
- +

NH2 ethyl acetate

O Y N H
CH3

(S)-4 (R)-4 G3-4 5

t racernization
PdIC

Scheme 2
 3.2.1.2 Examples of Enzymatic Conversions 875

PPL in PPL in
MeOAc buffer

OAc OAc

OH OAc
R
OAc OH

(R)-7 (s)-7
98% 91%
92% ee ~95%ee

Scheme 3

and triethylamine was the solvent [25]. The enzyme was again the immobilized
lipase Cundidu anturctica (Novozym SP 435@).Racemization of the unreacted
enantiomer (S)-4 was achieved with Pd on charcoal. Isolated yields of 5 were
64 % with an ee of 99 %.
Another advantageous use of hydrolytic enzymes consists in the enantioselec-
tive hydrolysis of prochiral substrates, making use of the ability of these biocata-
lysts to discriminate between enantiotopic groups. An elegant way to obtain both
enantiomers (R)-7 and (S)-7 from the prochiral diol 6 is the combination of por-
cine pancreatic lipase (PPL)-mediated hydrolysis and esterification as shown in
Scheme 3 [26].
Pig liver esterase (PLE) has found extensive use for the hydrolytic cleavage of
methyl or ethyl esters of prochiral carboxylic acids.
The usefulness of hydrolases like the immobilized lipase LIP to provide chiral
substances for elaborated synthetic strategies is demonstrated in the example
represented by Scheme 4. rneso-Diol8 was quantitatively acetylated to the mono-
acetate 9, an important intermediate in the preparation of synthon 10 used for
prostaglandin syntheses [27].

_OH OAc

LIP on Celite

- OAc
* ~ -
6H
O..l,IO
,%Ao
6H THF, 10% TEA, 3 h, 25°C
a 9 10
100%
>99% ee
Scheme 4
876 3.2 Special Catalysts and Processes

As can be deduced from the examples above, availability and use of immo-
bilized enzymes (cf. also Section 3.1.1.3) has increased significantly over the
past years. When used in organic solvents immobilized enzymes often show a
greatly augmented catalytic activity due to an increased surface area and reduced
denaturation [ 19 b]. Three techniques are frequently employed to immobilize en-
zymes: simple absorption, entrapment, and covalent immobilization. Especially,
lipases with their need for an aqueous-lipid interface proved to be favorably al-
tered in their activities. Lipases entrapped in hydrophobic sol-gels made from
alkylsilanes and Si(OMe)4 showed up to 100-fold increased activity in organic
solvents [28]. Their use in water has also been demonstrated [29]. Covalent fixa-
tion of enzymes to a matrix is often achieved by cross-linking an absorbed bio-
catalyst with glutaraldehyde [30]. Surprisingly, this methodology is particularly
powerful when small cross-linked enzyme crystals (CL E O) are formed
[31, 321.
Several hydrolytic enzymes other than esterases have been applied for synthetic
purposes. One important subject is the chemoenzymatic preparation of amino
acids. An industrial method for the synthesis of unnatural D- or L-amino acids em-
ploys the enzymatic hydrolysis of hydantoins, prepared by Bucherer-Bergs con-
densation using either D- or L-hydantoinase (cf. Section 3.2.1.4) [33]. Another
efficient method of preparing natural and unnatural amino acids is the two-step
synthesis which features a Pd-catalyzed amidocarbonylation (eq. (2); cf. Section
2.1.2.4) to afford racemic N-acyl amino acids followed by enantioselective hydro-
lysis using various acylases [34].
1) co 0 0
R N +~ O Y H
I H ~ PdBr,/LiBrlH+ b R’V’&oH + H 2 N- G o H
II
0
R2
I 2) amino hydrolases 6 2 R2

The enzymatic hydrolysis of a broad range of nitriles to the corresponding

amides and acids is documented [35]. These conversions are effected directly
by nitrilases or by successive action of a nitrile hydratase and an amidase. Most
of these enzymes are usually unstable and whole-cell preparations are preferred.
However, recently a purified nitrile hydratase preparation without amidase activity
was shown to convert several 2-arylpropionitriles enantioselectively to the cor-
responding optically active amides (eq. (3)) [36].

-
nitrile hydratase R = H, COPh:
up to 90% ee (3)
at 30% turnover

The important use of penicillin acylases is discussed in Section 3.2.1.4.

 3.2.1.2 Examples of Enzymatic Conversions 877

3.2.1.2.2 Reduction of C=O and C=C Bonds

Carbonyl reductases utilizing NADH or NADPH as cofactor have been success-
fully applied for the asymmetric reduction of carbonyl groups. These enzymes
deliver a hydride from the reduced cofactor in accordance with Prelog’s rule to
the re face or in rare cases to the si face of the carbonyl group. The most
commonly used alcohol dehydrogenase for this purpose is the one from horse
liver (HLADH), which preferentially reduces cyclic carbonyl compounds [37].
The completely regioselective reduction of the 3,5-dioxocarboxylate 11 using
the alcohol dehydrogenase from kctobacillus brevis and employing substrate-
coupled recycling of the cofactor gave the alcohol 12 (Scheme 5 ) [38], in excellent
enantiomeric excess and good yields.
Lactate dehydrogenases represent another important subgroup of carbonyl
reductases. They reduce a-0x0 acids enantiospecifically to a-hydroxy acids.
Both the D- and the L-selective enzymes are available, giving access to both
enantiomers of various a-hydroxy acids [39].
The use of purified nicotinamide cofactor-dependent dehydrogenases in pre-
parative reduction reactions requires an efficient regeneration of the expensive
and unstable NADPH cosubstrate. For the recycling of NADH the formate/for-
mate dehydrogenase system is well established, which combines the use of an in-
expensive substrate (HCOONa) with the formation of the volatile coproduct C 0 2
[40]. The use of cofactor-bound CLECs is an elegant way to avoid the instabilities
of enzyme and cofactor [32]. An example of an alternative single-enzyme system
is shown in Scheme 5. Through oxidation of the added propan-2-01 the dehydro-
genase, which also catalyzes the reduction of the carbonyl compound, regenerates
NADPH [411. To avoid troublesome and often problematic cofactor regeneration,
whole cell mediated reductions are currently utilized extensively. By this means
the necessary cofactors and their regeneration is provided by immanent pathways.
As demonstrated in Scheme 6, baker’s yeast catalyzed reduction of the ketone 13
was a key step for the preparation of phorocantholide 1 (14) [42].
Baker’s yeast has also been used for the highly stereoselective reduction of the
prochiral 2,2-dimethyl- 1,3-~yclohexanedione [43]. The resulting S-configured
hydroxycyclohexanone served as a versatile starting material for the synthesis
of various natural products [ 10, 441.

0 0 0 OH 0

-Ornu
11 ?=?
NADPH NADP+
d o 12

77%,
m u

99.4% ee

recLBADH

Scheme 5
818 3.2 Special Catalysts and Processes

13 14

Scheme 6

NADH-dependent enoate reductases are also interesting tools for synthetic appli-
cations. They stereoselectively reduce conjugated carbonyl double bonds and those
activated by electron-withdrawing substituents, as shown in eqs. (4) and ( 5 ) [45].
R = -CH2-CH=C(CH3)2
baker's yeast - -CH2-CH(CH& (4)
R R
-CH2Ph2
95-98% ee
-
Beauveria
/\/\/OH >95%ee

3.2.1.2.3 Oxidation of Alcohols and Oxygenation

of C-H and C=C Bonds
Horse liver alcohol dehydrogenase has been used for the enantiotopic oxidation of
meso-diols, preferably applying an ammonium a-ketoglutaratelglutamate
dehydrogenase recycling system to regenerate NAD+. The initially produced
asymmetric hydroxy aldehyde cyclizes to the hemiacetal, which is further
oxidized to the lactone 15 [46]. Scheme 7 presents an illustrative reaction with
an alternative NAD' regeneration path [47].

xH
0
NAD' 15

FMNHZ FMN

Scheme 7
 3.2.1.2 Examples of Enzymatic Conversions 879

0
Pseudomonas
putida 39-D

HO
99% ee

Scheme 8

Mutants of Pseudomonas putida were found to exhibit an arene dioxygenase

activity, which has been exploited in whole-cell reactions for the regio- and
enantioselective preparation of cis-dihydrodiols starting from benzene, substituted
benzenes, and polycyclic or heteroaromatic compounds [48]. The products are
invaluable precursors for natural product synthesis, as exemplified in Scheme 8
WI.
The enzymatic counterpart of the Baeyer-Villiger reaction is catalyzed by a fla-
vine containing monooxygenase (cyclooxygenase) in the presence of oxygen and
NAD(P)H. Using whole cells, racemic mixtures of cyclic ketones were kinetically
resolved or enantio- and regioselectively oxidized [50].Recently, a cell-free sys-
tem with the cyclohexanone monooxygenase and recombinant NADP+-dependent
formate dehydrogenase for cofactor regeneration was successfully introduced to
prepare the chiral a-lactone 17 from prochiral 4-methylhexanone 16 (Scheme 9)

+
1511.

O > q 0 @
NADPH + H' NADP'
16 (S)-17

COZ HCOOH
Scheme 9 FDH

Regio- and stereospecific monohydroxylations of elaborated molecules have

been achieved with monooxygenases that are in most cases membrane-bound
cytochrome P450 enzymes. Because these are coupled with a complex redox sys-
tem for electron transport from NADPH, the reactions are preferably carried out
with whole cells [52]. The same is true for enantioselective enzymatic epoxida-
tions. An impressive example documented in eq. (6) is the preparation of 18 in
78 % yield and high ee [53].
880 3.2 Special Catalysts and Processes

chloroperoxidase from ::<0

Caldariomyces fumago
H202,citrate buffer, acetone
25"C,2h

(2R,3S)-18
100%
95% ee

3.2.1.2.4 Carbon-Carbon Coupling

A wide range of natural and unnatural monosaccharides has been generated by
exploiting the catalytic capacity of aldolases which perform reactions equivalent
to nonenzymatic aldol additions [54]. More than 20 aldolases have been identified
so far and can be divided into three main groups, accepting either dihydroxyace-
tone phosphate (DHAP), acetaldehyde, or pyruvic acid, and phosphoenolpyruvate
as nucleophilic methylene component. A common feature is their high stereocon-
trol in the formation of the new C-C bond. As presented in Scheme 10 all four
possible vicinal diols are accessible by selection of the appropriate DHAP-aldo-
lase [2, 551, all of which show a distinct preference for the two stereocenters
and a broad substrate tolerance for the aldehyde component.

I OH

OH

&OP
OH
- E3

OH OH
OP
E' = D-fructose-l,6-bisphosphate-aldolase
E' = D-tagatose-l,6-bisphosphate-aldolase
E3 = L-fuculose-1-phosphate-aldolase
E4 = L-rharnnulose-1-phosphate-aldolase

-
P = Po-:
x = -CH*-OP (for E ' , E ~ )
E4 +OP X = -CH3 (for E3, E4)
--
OH OH

Scheme 10
 3.2.1.2 Examples of Enzymatic Conversions 88 1

one-pot-synthesis ? &OH

lr HzP2072.
OH
19
phytase 29% (from glycerol)

HZPOL phytase

*
pH4 L H z P O L

-4
glycerol phosphate fructose 1,6-bis-
OH oxidase 0 phosphate aldolase

HO&OPO~H- 0
P
0
3
H
,-,J
.H
0
. pH 7s OP03H-
+ -0
112 0 2 OH
-
OH
-
HO&OPO~H’
catalase

Scheme 11

A particularly elegant example is shown in Scheme 11: 5-deoxy-5-ethyl-~-xy-

lulose (19) was prepared from glycerol by a four step, one-pot chemoenzymatic
reaction sequence. The key step was the aldol reaction catalyzed by fructose-
1,6-bisphosphate aldolase (FruA) from Staphylococcus curnosus [56].
Other C-C coupling reactions have been published [l, 21. A prominent
example is the enzymatic Diels-Alder reaction which affords (-)-solanapyrone

- :XH
A (20) (eq. (7)). The enzyme solanapyrone synthase from extracts of the
phytopathogenic fungus Alternuria solunu has hence been named “Diels-

Ho
Alderase” [57].

0 ”Diels-Alderase”

20
>98% ee, 51%

(7)

3.2.1.2.5 Formation of Glycosidic Bonds

The most frequently applied concepts for the enzymatic formation of oligosac-
charides and glycoproteins involve the utilization of glycosyl transferases or
exo- and endo-glycosyl hydrolases (glycosidases) [58]. Glycosyl transferases re-
quire expensive and often unstable sugar nucleotides as activated donor substrates,
a major problem besides the poor availability of the enzymes. However, trans-
882 3.2 Special Catalysts and Processes

ferase-catalyzed glycoside synthesis leads to regio- and stereochemically pure

products in high yields. Glycosidases, on the other hand, are inexpensive and
easy to handle. The reactions are mostly carried out under kinetic control using
simple glycosides as donors. Generally one or more regiomers are obtained in
moderate yields, all of them having the same anomeric configuration of the
newly formed glycosidic linkage.
For instance a-fucosides and a-sialosides, which are both difficult to produce
by means of classical carbohydrate chemistry, have been synthesized using the
corresponding nitrophenyl glycoside donors by applying pig liver a-fucosidase
[59] and the sialidase from Vibrio cholerue [60], respectively.
Starting from lactose as donor and N-acetylglucose as acceptor substrate the
&ylactosidase from Bacillus circuluns gives exclusively N-acetyl-lactosamine
21 [6I], which has been subjected to sialyltransferase-catalyzed conversion to
the trisaccharide Neu5Ac-a(2-3)Gal-/3( 14)GlcNAc 22 (Scheme 12). By combi-
nation of these two enzymatic steps the reaction is pushed toward the product
and the problem of low yields related with the galactosidase-mediated reaction
could be overcome [62].
To avoid problems connected with transferase-catalyzed reactions, i. e., the
high price of the sugar nucleotides and possible inhibition through the released

p-galactosidase
from Bacillus circulans
I

HO OH
HO

lc
HO &o&OH OH Ho NHAc ' HO
OH

21

sialyltransferase
a-(2-3)- c M p ~ ~ ~

OH
HO
HO OH NHAc

Scheme 12 22
884 3.2 Special Catalysts and Processes

3.2.1.2.6 Enzymatic Protecting Group Techniques

Often, not only highly selective but also extremely mild methods of introducing
and removing protecting groups are needed. This applies in particular for the con-
struction of complex, polyfunctional molecules, e. g., oligosaccharides, peptides,
and nucleotides and their conjugates, as well as for the synthesis of alkaloids,
macrolides, and further natural products. In this respect enzymes offer valuable
opportunities complementing the already elaborate classical techniques. Their
chemo-, regio-, and stereoselectivity allow enzymes to establish otherwise unat-
tainable “quasi-orthogonal’’ protecting group arrangements.
The already mentioned hydrolase-catalyzed regioselective acylations and
deacylations of a wide array of polyhydroxylated compounds has been addressed
in numerous cases [13].
In a recent advanced application of enzymatic protecting group techniques
for the construction of complex multifunctional and sensitive targets, the syn-
thesis of the characteristic S-palmitoylated and S-farnesylated lipohexapeptide
of the human N-Ras protein (26) was built up. The product 26 which would
not withstand standard procedures under basic or acidic conditions could be ob-
tained by following two different routes both employing enzyme-labile protect-
ing groups. On the one hand the choline ester group was employed for C-term-
inal chain elongation [66]. On the other hand the p-acetoxybenzyloxycarbonyl
(AcOZ) urethane group served well in an N-terminal coupling strategy [67]
(Scheme 14).
The spectrum of enzymatic deprotecting tools (Figure 1) was further broadened
by the introduction of the p-phenylacetoxybenzyloxycarbonyl(PhAcOZ) group
for N-terminal protection [68] and the p-phenylacetoxybenzyl ester (PAOB)
group for C-terminal protection of peptides [69], respectively. Both groups are
readily cleavable by penicillin G acylase and have been used successfully in lipo-
peptide and glycophosphopeptide synthesis [69, 701. The glucosyloxycarbonyl
(Gloc) group is a suitable substrate for glycosidases [71].
penicillin

PAOB Q PhAcOZ

glucosidase

H O G 0 t
Ho OH )fN,R
Q
Figure 1 Gloc
 I
s

w
0
- -
Aloc -C ys Met - Gly 0

Pal
-
+
NMe3
Br-
3.2.1.2 Examples of Enzymatic Conversions

- choline
esterase
Aloc- Cys- Met -Gly -OH
I
s\

1
Pal

H-Leu- Pro-Cys-
5,
I
OMe

Far
885

26

Aloc -7ys-OH t
H - Met - GIy -Leu- Pro-?ys -OMe
s, Far
1) AcOZ-Met-Gly-OH
carbodiirnide
2) lipase
1
H -Leu- Pro-Cys -OMe
I
s, Far

lipase
~ o ~ O y ~ - L e u - P r Io - C y s - O M e

I
0 S 4 y - y\ - y \

Y
Scheme 14 Far
886 3.2 Special Catalysts und Processes

3.2.1.3 Enzyme-Analogous Catalysts

The capabilities of enzymes to transform organic substrates smoothly, in good
yields, and highly selectively, have stimulated the desire of organic chemists to
tailor catalysts with similar features for specific reactions.
In this respect, reactions catalyzed by monoclonal antibodies have been the
focus of much interest [72]. One of the first antibody-supported syntheses on a
gram scale and with an enantiomeric excess of up to 99 % was the kinetic resolu-
tion of aldol adducts. The products resulting from the retro-aldol reaction served
as precursors in the synthesis of epothilones A and B [73].
For the production of an effective monoclonal antibody it is crucial to raise it
from a well-designed transition state analogue. Besides not resembling the product
too much in order to avoid product inhibition, this hapten should mimic the tran-
sition state as closely as possible to maximize its stabilization by the antibody gen-
erated. Utilizing the extraordinary specificity of the immune system by this means,
the combining site of the antibody is programmed to exhibit a specific catalytic
activity. This technique has been directed toward the development of selective
reactions which are chemically difficult to achieve, for example "disfavored",
and for which no suitable enzyme is available.
Therefore several reactions were subjected to various antibody catalyses, e. g.,
ester and enol ether cleavage, transesterification, ketone reduction, Cope rearran-
gement, ring closure via epoxide opening, or Diels-Alder cycloaddition [74, 751.
An exceptional reaction is the antibody-catalyzed Robinson annulation of trike-
tone 28 to the Wieland-Miescher ketone 29 on a preparative scale. Surprisingly,
even the alkylation of diketone 27 with methyl vinyl ketone was catalyzed by
the same antibody, but at moderate rates (Scheme 15) [76].

+oh antibody 38C2,O antibody 38C2

H20 I MeCN,
23°C 10d *od
27 28 (S)-29
94% (from 28)
Scheme 15 96% ee

Ribonucleic acids (RNAs) were employed as catalysts in the synthesis of

amides and esters, peptide bond formation and Diels-Alder reactions. The ap-
proach suffers from the fact that it requires the reactants to be either RNA itself
or a compound covalently tethered to RNA. Indeed, there is one prominent exam-
ple where RNA acts as a true catalyst in a bimolecular Diels-Alder cycloaddition
without tethering the substrates [77].
The chemical modeling of active sites of enzymes can help to gain deeper in-
sight into their catalytic mechanisms and might also lead to enzyme substitutes
which are reliable and easy-to-handle tools for organic synthesis. Recently, it
 3.2.1.4 Commercial Applications 887

was discovered that a single proline can mimic the active site of an aldolase. High
ee values were obtained with either acetone or hydroxyacetone, generating one or
two new stereocenters in fair to excellent yields, respectively (eqs. (8) and (9)).
This reaction seems to be well suited to industrial application, because of its sim-
plicity and low costs [78].

@)-Proline

/k
(20 VOI %)
+ H
I
b
(30-40rnol%)
DMSO,25"C,2d
~

I
97%
96% ee
(8)

(R)-30

4 OH
+ H q
(L)-Proline
(20-30 mol%)
DMSO,25"C, 1-3;
62%
20:l dr
99% ee
(9)

(20 vol %) (3S,4S)-31

A very recent topic has so far received little attention, but will most probably
develop to great importance in bioorganic chemistry: the use of enzymes for ligat-
ing peptides [79]. Peptide cyclization to form the antibiotics tyrocidine A and gra-
micidin S was achieved with the thioesterase domain of tyrocidine synthetase
[79 a]. a-Chymotrypsin catalyzed the condensation of larger peptide fragments
to form an active sequence of the human thyroid anchoring protein Ht31 [79 b].
The synthetic peptide was able to abolish forskolin-induced outward chloride
currents in guinea pig ventricular myocytes.

3.2.1.4 Commercial Applications

3.2.1.4.1 General
Since the mid- 1970s biotransformations have become a very well-established
tool in the fine chemicals industry. Biocatalytic systems, including crude and
purified enzymes as well as whole-cell systems performing highly selective
reactions under mild conditions, are widely used, especially in synthesis and
production of biologically active compounds in the agrochemical and pharma-
ceutical sectors.
Biocatalysis has already been proven in many cases to overcome specific
synthetic problems. Thus, the need for hazardous reagents or the formation
of specific impurities or by-products can be avoided. Furthermore, biocatalysis
can provide excellent regio- and stereoselectivity, and much higher turnover
numbers compared with chemical catalysts are possible. Therefore, it is not sur-
prising that biocatalysis has also found an important place among industrial
932 3.2 Special Catalysts and Processes

In 1995 Menger et al. [60] again delivered evidence for an alternative mecha-
nism for Rebek’s self-replicating system. The aminolysis of simple naphthoyl and
benzoyl esters, both without any hydrogen-bonding sites, is catalyzed by Rebek’s
“template” 44. In Menger’s non-self-replicative mechanism the catalysis arises
from the fact that the amide group can stabilize a zwitterionic tetrahedral inter-
mediate and does not invoke a termolecular complex. Catalysis is predicted
upon an amide group functioning with the bimolecular complex. The new me-
chanism accommodates a trivial autocatalysis, but is not self-replicative.
The “self-assembling’’ principle has begun to be exploited by chemists in the
design of synthetic molecular receptors. Hunter and co-workers [611 describe
the use of metalloporphyrin coordination chemistry to build up the self-association
of a very stable cyclic porphyrin dimer 45 which recognizes derivatives of
terephthalic acid (46, 47) through hydrogen-bonding interactions (Scheme 15).
A further interesting application of self-assembly is the synthesis of a chromo-
phore containing five porphyrin units [62]. Acting as a model for light-collecting
porphyrin adducts, it is important for the understanding of energy and electron
transfer in natural photosynthetic active centers. If meso-tetra(4-pyridy1)porphyrin

I R
46 R = R * = pentyl
47 R = H, R‘ = pentyl

The 4-pentylphenylsubstituents on the

meso positions of the porphyrin are
omitted for clarity.

45

Scheme 15. Hunter’s stable cyclic porphyrin dimer 45, which is able to recognize derivatives
of terephthalic acid 46, 47 through hydrogen-bonding interactions.
 3.2.2.7 Self-Organization 933

48
Zn4 - tetramer

50 (48 + 49)

(H2-Py,P, 49) is added to a solution of the cyclic tetrameric Zn4-48, it leads to the
formation of a strong 1: l-complex 50.
Stoddart and co-workers developed the efficient template-directed one-pot syn-
thesis of the [2]catenane from a bipyridinium salt, bis(bromomethyl)benzene, and
a paracyclophane crown ether [63]. The dominant, noncovalent interactions in-
volved are based on electrostatic and dispersive forces brought about by the reci-
934 3.2 Special Catalysts and Processes

51

procal formation of a sandwich (a) of a hydroquinone ether unit between parallel

bipyridinium units and (b) of a bipyridinium unit between parallel hydroquinone
ether units. The n-donorh-acceptor stacking of the electron-rich and electron-
poor arene groups leads to an orthogonal arrangement of the building blocks,
the logical consequence of which is the formation of [2]catenanes.
Stoddart and co-workers transferred the strategy of template-directed synthesis
to the formation of the first molecular system consisting of five interlocked rings
in a linear array (Structure 51). They suggested that this [5]catenane should be
called olympiadane [64]. Recently they reported the self-assembly of a new
type of rotaxane, in which three side chains are linked directly to a single central
core, producing a dendritic-type structure [65].
Leigh and co-workers [66] introduced the smallest [2]catenane on the basis of
amide linkage. The condensation of eight molecules in one “step” leads to the
[2]catenane 52 (eq. (2)).

1 Et3N / CHC13

{ 0

52
 3.2.2.8 Further Developments and Applications 935

OMe

.OMe
o=.s

W
53b

Recently Vogtle and co-workers synthesized the first catenanes (Structure 53)
and rotaxanes containing sulfonamide units. The sulfonamide catenanes 53a,
53b have a topologically chiral structure [67].

3.2.2.8 Further Developments and Applications

Kool and co-workers [68] have reported on the construction of a cyclic hybrid mo-
lecule which contains two oligonucleotide sections bridged by two oligo (ethylene
glycol) chains. An oligomer is employed as (guest) template in the cyclization, in
order to bring the reactive phosphate and hydroxy end groups into the appropriate
orientation for intramolecular esterification in the presence of BrCN, imidazole,
and NiC12.
The sequence-specific binding of synthetic oligonucleotides and analogs to
RNA and DNA is studied intensively in the examination of natural polynucleo-
tides and for the development of potential therapeutics [69].
Natural proteins undergo a folding process that leads to a spatially defined ter-
tiary structure. With synthetic polypeptides, folding to a globular structure is not a
matter of course. The situation in vivo is not always comparable with that in a test
tube. A concept introduced by Mutter et al. [70] represents a step toward achiev-
936 3.2 Special Catalysts and Processes

ing the folding of artificial proteins. According to this concept, peptide blocks
leading to formation of secondary structure are covalently attached to a topologi-
cally tailor-made template. The template serves to direct the peptide chains into a
characteristic three-dimensional structure, as in proteins. The resulting macromo-
lecules are described by Mutter et al., in accord with the method used in their for-
mation, as “template-associated synthetic proteins” (TASPs). In contrast with the
other template molecules discussed here, in this case the template results in the
stabilization of a specific conformation rather than in supporting the formation
of a covalent link.
The remarkable specificity of a monoclonal antibody has been used by Schultz
and co-workers [7 13 to control the selective reduction of the carbonyl compound
54 with NaBH3CN (eq. (3)). The observed enantiomeric excess of 96% (S)-55
cannot be obtained with conventional chemical methods.

54

1NaBH3CN
antibody
(3)

55 ( S ) : 9 6 . 3 % e e

Use of polymers in place of discrete metal ions or neutral molecules gave rise to
the template polymers [72] of Bystrom et al. If the term “template” is taken in its
original meaning borrowed from photography, the template polymers are actually
templates in the true sense. In a process similar to that used in photography, im-
pressions (macromolecular niches) are initially generated on the surface (or in the
interior) of the polymer by so-called “imprint molecules”. If the molecular imprint
contains appropriate functional groups, molecules can be adsorbed and chemically
converted with regio- and stereoselectivity (Figure 4).
The selective reduction of steroid ketones by means of LiAlH,-activated tem-
plate polymers can be carried out following the principle of an ion exchanger.
Although the application of polymers in template syntheses is currently limited,
and the reactions do not always run satisfactorily, this method appears to be a
landmark for future rational syntheses. Microporous phases with three-dimen-
sional lattice networks and defined pore structures and sizes can be obtained by
the use of molecules or hydrated ions of alkali metals or alkaline earth metals
as templates [73]. A concept developed by the Mobil Oil Company for the syn-
thesis of porous materials employs a regular arrangement of molecules formed
 3.2.2.9 Conclusions and Outlook 937

Figure 4. Niches, which allow regio- and stereoselective conversion of the substrate, are
produced on the surface of the polymer by “imprint” molecules. For the steroidal
ketone selected here only a specific polymerhbstrate binding leads to chiral
transfer of the hydride from the concave template to the carbonyl group of the guest
(a). All other polymerhbstrate bindings are unsuitable for steric reasons (b) and do
not lead to the desired reaction (at the carbonyl group).

by self-assembly rather than a single, solvated, organic molecule or metal ion as

template. Three-dimensional porous media can be used in their turn for molecular
recognition and as templates. Defined cavity structures could lead to “inclusion
chemistry on the nanoscale” and are termed “reaction vessels of nanometer
dimensions”.

3.2.2.9 Conclusions and Outlook

Tailor-made template units (guest ions and molecules) allow acceleration and con-
trol of reactions in a defined direction, and frequently even the preparation of
products that otherwise would be difficult to obtain. The discovery and develop-
ment of new template-controlled reactions and the clarification of the basic me-
chanisms involved in intermediate and permanent host-guest interactions are
worthy targets of research aimed at effective syntheses, replication, and catalysis.
It has already been indicated in the text that quite striking analogies between
template syntheses and homogeneously catalyzed reactions exist (see especially
Sections 3.2.2.2, 3.2.2.3 and 3.2.2.7). The “guest” (see Figure 1) - like a homo-
geneous catalyst - brings the reactants in proximity and in a suitable position to
react in a specific way to the desired (often cyclic) product (see, e. g., cyclooligo-
merization, enyne isomerization [74]). This is frequently accompanied by a selec-
tive substrate recognition (see, e. g., Section 3.2.1). After the reaction is completed
the separation of both the “guest” and the catalyst in some cases may be difficult.
Special techniques in the course of immobilization and heterogenization (see Sec-
tion 3.1.1) of the catalyst could be transferred to find more effective cyclic reac-
tion paths in various template reactions. On the other hand, the template syntheses
show that - besides the preferred metallic catalysts - neutral organic molecules
can sometimes be charged as well to accelerate special reactions. Supramolecular
938 3.2 Special Catalysts and Processes

interactions and molecular recognition most often play a key role in these cases.
Such a “supramolecular catalysis” [75] is not only of interest in building up, for
example, analagous enzyme or antibody catalytic systems, but could also achieve
technical importance. Thus it is a worthwhile subject for basic as well as industrial
scientists, especially as far as the perspectives of homogeneous catalysis are con-
cerned.

References
[la] N. V. Gerbeleu, V. B. Anon, J. Burgess, Template Synthesis of Macrocyclic Compounds,
Wiley-VCH, Weinheim 1999; T. J. Hubin, A. G. Kolchinski, A. L. Vance, D. H. Busch,
Template Control of Supramolecular Architectures, in: Advances in Supramolecular
Chemistry, Vol. 5 , p. 237, JAI Press, 1999; F. Diederich, P. J. Stang, Template Directed
Synthesis, Wiley-VCH, Weinheim 2000.
[lb] N. F. Curtis, J. Chem. Soc. 1960, 4409; M. M. Jones, Ligand Reactivity and Catalysis,
Academic Press, New York, 1968; P. A. Chaloner, Handbook of Coordination Catalysis
in Organic Chemistry, Buttenvorths, London, 1986. Overviews: F. Vogtle, R. Hoss,
Angew. Chem. 1994, 106, 389; Angew. Chem., Int. Ed. Engl. 1994, 33, 37.5; S. Ander-
son, H. L. Anderson, J. K. M. Sanders, Acc. Chem. Res. 1993, 26, 469.
[2] M. Lahav, Het. Chem. Rev. 1994, 1(2), 159.
[3] G. A. Melson (Ed.), Coordination Chemistry of Macrocyclic Compounds, Plenum, New
York, 1979; S. M. Nelson, F. S. Esho, M. G. B. Drew, J. Chem. Soc., Dalton Trans.
1982, 407; D. K. Mitchell, J.-P. Sauvage, Angew. Chem. 1988, 100, 98.5; Angew.
Chem., Znt. Ed. Engl. 1988, 27, 930; C. 0. Dietrich-Buchecker, J.-P. Sauvage, Chem.
Rev. 1987, 87, 795.
[4] M. C. Thompson, D. H. Busch, J. Am. Chem. SOC.1962, 84, 1762.
[5] Critical considerations of the “cesium-effect” in macrocyclization, which is not generally
regarded as a template effect: C. Galli, Org. Prep. Proced. Int. 1992, 24, 285. The term
“cesium-effect’’is thus misleading, as the cesium atom itself is not responsible for the rate
acceleration, the higher yield, or the cyclooligomer selectivity. The effect seems to be
caused, for example, by aggregation of cesium carbonate (often added as auxiliary
base), which sets up a specific basicity/nucleophilicity of the reaction medium, see
also: A. Ostrowicki, E. Koepp, F. Vogtle, Top. Curr: Chem. 1991, 161, 37.
[6] D. Wohrle, G. Meyer, Kontukte (Darmstadt) 1985, 3, 38.
[7] F. Vogtle, Supramolekulare Chemie, 2nd ed., Teubner, Stuttgart, 1992, Chapter 2.2 (Eng-
lish translation: Supramolecular Chemistry, Wiley, Chichester, 1991, 1993); J.-M. Lehn,
Supramolecular Chemistry, VCH, Weinheim, 1995.
[8] [4]- and [Slcatenanes: D. B. Amabilini, P. R. Ashton, A. S. Reder, N. Spencer, J. F. Stod-
dardt, Angew. Chem. 1994, 106, 450; Angew. Chem., Int. Ed. Engl. 1994, 33, 433.
191 J.-P. Sauvage, C. 0. Dietrich-Buchecker, J. Guilhem, C. Pascard, Angew. Chem. 1990,
102, 1202; Angew. Chem., Int. Ed. Engl. 1990, 29, 1154; J.-C. Chambron, V. Heitz,
J.-P. Sauvage, J. Chem. Soc., Chem. Commun. 1992, 1131.
[lo] J.-F. Nierengarten, C. 0. Dietrich-Buchecker, J.-P. Sauvage, J. Am. Chem. Soc. 1994,
116, 375.
[ l l ] J.-P. Sauvage, Nature’s 3rd Int. Con$ in Europe, Paris, April 27-28, 1995, J.-C. Cham-
bron, C. 0. Dietrich-Buchecker, V. Heitz, J.-F. Nierengarten, J.-P. Sauvage, C. Pascard,
J. Guilhem, Pure Appl. Chem. 1995, 67(2), 233; J.-C. Chambron, C. 0. Dietrich-Buch-
ecker, J.-F. Nierengarten, J.-P. Sauvage, Pure Appl. Chem. 1994, 66(7), 1543.
 References 939

[I21 S. Shinkai, Adv. Supramol. Chem. 1993, 3, 97.

[13] K. Maruoka, N. Murase, H. Yamamoto, J. Org. Chem. 1993, 58, 2938.
[I41 (a) A. Shanzer, J. Libman, J. Chem. Soc., Chem. Commun. 1983, 846; (b) A. Shanzer,
J. Libman, F. Frolow, J. Am. Chem. Soc. 1981, 103, 7339.
[15] M. Buhner, W. Geuder, W.-K. Gries, S. Hunig, M. Koch, T. Poll, Angew. Chem. 1988,
100, 1611;Angew.Chem., Int. Ed. Engl. 1988, 27, 1553.
[16] K. Saigo, R.-J. Lin, M. Kubo, A. Youda, M. Hasegawa, J. Am. Chem. Soc. 1986, 108,
1996.
[17] C. A. Hunter, J. Am. Chem. Soc. 1992, 114, 5303.
[I81 F. Vogtle, S. Meier, R. Hoss, Angew. Chem. 1992, 104, 1628; Angew. Chem., Int. Ed.
Engl. 1992, 31, 1619.
[19] S.Ottens-Hildebrandt, S.Meier, W. Schmidt, F. Vogtle, Angew. Chem. 1994, 106, 1818;
Angew. Chem., Int. Ed. Engl. 1994, 33, 1767.
[20] S. Ottens-Hildebrandt, M. Nieger, K. Rissanen, J. Rouvinen, S. Meier, G. Harder,
F. Vogtle, J. Chem. Soc., Chem. Commun. 1995, 777.
[21] F. Vogtle, M. Handel, S. Meier, S. Ottens-Hildebrandt, F. Ott, T. Schmidt, Liebigs Ann.
1995, 739; see L. F. Lindoy, Nature (London) 1995, 376, 293.
[22] T.R. Kelly, C. Zhao, G. J. Bridger, J. Am. Chem. Soc. 1989, 111, 3744.
[23] W. H. Chapman, Jr., R. Breslow, J. Am. Chem. SOC. 1995, 117, 5462.
[24] R. J. Pieters, I. Huc, J. Rebek, Jr., Chem. Eur: J. 1995, 1, 183.
[25] (a) G. von Kiedrowski, Angew. Chem. 1986, 98, 932; Angew. Chem., Int. Ed. Engl.
1986, 25, 932; (b) G. von Kiedrowski, B. Wlotzka, J. Helbing, M. Matzen, S. Jordan,
ibid. 1991, 103, 456 and 1991, 30, 423; D. Sievers, G. v. Kiedrowski, Nature (London)
1994, 369, 221: J. Burmeister, D. Sievers, B. Wlotzka, G. v. Kiedrowski, COST-
Chemistry-Action - D7, Molecular Recognition Chemistry Workshop, Sintra, Portugal,
June 7-10, 1995.
[26] M. W. Gobel, J. W. Bats, K. G. Diirner, Angew. Chem. 1992, 104, 217; Angew. Chem.,
Int. Ed. Engl. 1992, 31, 207.
[27] B. Dietrich, V. Viout, J.-M. Lehn, Macrocyclic Chemistry, VCH, Weinheim, 1993,
Chapter 3.3.
[28] (a) J. E.McMurry, G. J. Harley, J. R. Matz, J. C. Clardy, J. Mitchell, J. Am. Chem. Soc.
1986, 108, 515; (b) R. Friederich, M. Nieger, F. Vogtle, Chem. Ber: 1993, 126, 1723.
[29] L. Collazo, F. S. Guziee, Jr., J. Org. Chem. 1993, 58, 43.
[30] F. Vogtle, L. Rossa, Angew. Chem. 1979, 91, 534; Angew. Chem., Int. Ed. Engl. 1979,
18, 514; A. Dohm, F. Vogtle, Top. Cum Chem. 1991, 161, 69.
[31] J. Breitenbach, F. Ott, F. Vogtle, Angew. Chem. 1992, 104, 360; Angew. Chem., Int. Ed.
Engl. 1992, 31, 307.
[32] F. Ott, J. Breitenbach, M. Nieger, F. Vogtle, Chem. Ber: 1993, 126, 97.
[33] R. Breslow, Ace. Chem. Res. 1980, 13, 170; see also R. Breslow, D. Wiedenfeld, Tetra-
hedron Leu. 1993, 34, 1107.
[34] S. Sun, P. Harrison, Tetrahedron Lett. 1991, 33, 7715.
[35] U.Kramer, A. Guggisberg, M. Hesse, H. Schmidt, Angew. Chem. 1977, 89, 899; Angew.
Chem., Int. Ed. Engl. 1977, 16, 861; A. Guggisberg, B. Dabrowski, U. Kramer, C. Hei-
delberger, M. Hesse, H. Schmidt, Helv. Chim. Acta 1978, 61, 1039. See also: M.Hesse,
Ring Enlargement in Organic Chemistry, VCH, Weinheim, 1991.
[36] N. J. Leonhard, S. Swann, Jr., J. Figueras, Jr., J. Am. Chem. Soc. 1952, 74, 4620;
N. J. Leonhard, S. Swann, Jr., E. H. Mottus, ibid. 1952, 74, 6251.
[37] H.Stetter, H. Spangenberger, Chem. Ber: 1958, 91, 1982.
[38] V. Bhat, R. C. Cookson, J. Chem. Soc., Chem. Commun. 1981, 1123: R. C.Cookson,
P. S. Ray, Tetrahedron Lett. 1982, 23, 3521.
[39] J. R. Mahajan, H. C. Araujo, Synthesis 1976, 54, 111.
940 3.2 Special Catalysts and Processes

[40] Y. Kobuke, Y. Sumida, M. Hayashi, H. Ogoshi, Angew. Chem. 1991,103, 1513; Angew.
Chem., lnt. Ed. Engl. 1991, 30, 1496.
[41] A. C. Benniston, A. Harriman, Synlett 1993, 223.
1421 D. H. Busch, N. A. Stephenson, Coord. Chem. Rev. 1990, 100, 119.
[43] M. C. Thompson, D. H. Busch, J. Am. Chem. SOC. 1962, 84, 3744.
1441 A. Eschenmoser, Pure Appl. Chem. 1963, 7, 297.
[4S] E. K. Barefield, Inorg. Chem. 1972, 11, 2273.
[46] S. R. Cooper (Ed.), Crown Compounds, VCH, Weinheim, 1992.
[47] S. Anderson, H. L. Anderson, J. K. L. Sanders, Angew. Chem. 1992, 104, 921; Angew.
Chem., Int. Ed. Engl. 1992, 31, 907; see also S. Anderson, H. L. Anderson, J. K. L.
Sanders, Ace. Chem. Res. 1993, 26, 469.
[48] D. Philp, J. F. Stoddart, Synlett 1991, 445.
[49] N. Nishino, H. Mihara, H. Koyota, K. Kobata, T. Fujimoto, J. Chem. Soc., Chem. Com-
mun. 1993, 162.
[50] J.-L. Mascarenas, K. C. Hayashibara, G. L. Verdine, J. Am. Chern. Soc. 1993, 115,
373.
[51] Y. Jenkins, J. Barton, J. Am. Chem. Soc. 1992, 114, 8736.
[S2] R. Rubin, T. L. McKee, E. T. Kool, J. Am. Chem. Soc. 1993, 115, 360.
[S3] P. N. W. Baxter, J.-M. Lehn, J. Fischer, M.-T. Youinou, Angew. Chem. 1994, 106, 2432;
Angew. Chern., Int. Ed. Engl. 1994, 33, 2284; see M. Fujita, Y. J. Kwon, 0. Sasaki,
K. Yamdguchi, K. Ogura, J. Am. Chem. Soc. 1995, 117, 7287.
[54] G. S. Hanan, C. R. Arana, J.-M. Lehn, D. Fenske, Angew. Chem. 1995, 107, 1191;
Angew. Chem., Int. Ed. Engl. 1995, 34, 1122.
[S5] C. A. Hunter, Angew. Chem. 1995, 107, 1180; Angew. Chem., Int. Ed. Engl. 1995,
34, 1079.
[S6] M. Fujita, F. Ibukuro, K. Yamaguchi, K. Ogura, J. Am. Chem. SOC. 1995, 117, 4175.
[57] M. M. Conn, E. A. Wintner, J. Rebek, Jr., J. Am. Chern. SOC. 1994, 116, 8823.
[%I F. M. Menger, A. V. Eliseev, N. A. Khanjin, J. Am. Chem. Soc. 1994, 116, 3613.
[S9] R. J. Pieters, I. Huc, J. Rebek, Jr., Tetrahedron 1995, 51(2), 485; E. A. Wintner, M. M.
Conn, J. Rebek, Jr., J. Am. Chem. SOC. 1994, 116, 8877.
1601 F. M. Menger, A. V. Eliseev, N. A. Khanjin, M. J. Sherrod, J. Org. Chern. 1995,
60, 2870.
[61] C. A. Hunter, L. D. Sarson, Angew. Chem. 1994, 106, 2424; Angew. Chem., lnt. Ed.
Engl. 1994, 33, 2313.
[62] S. Anderson, H. L. Anderson, A. Bashall, M. McPartlin, J. K. M. Sanders, Angew. Chem.
1995, 107, 1196; Angew. Chem., Int. Ed. Engl. 1995, 34, 1096; see D. W. J. McCallien,
J. K. M. Sanders, J. Am. Chem. Soc. 1995, 117, 6611.
[63] (a) C. L. Brown, D. Philp, J. F. Stoddart, Synlett 1991, 462; (b) B. Odell, M. V. Redding-
ton, A. M. Z. Slawin, N. Spencer, J. F. Stoddart, D. J. Williams, Angew. Chem. 1988,
100, 160S;Angew. Chem., lnt. Ed. Engl. 1988, 27, 1547.
[64] D. B. Amabilino, P. R. Ashton, A. S. Reder, N. Spencer, J. F. Stoddart, Angew. Chem.
1994, 106, 1316; Angew. Chem., Int. Ed. Engl. 1994, 33, 1286.
[6S] D. B. Amabilino, P. R. Ashton, M. Belohradsky, F. M. Raymo, J. F. Stoddart, J. Chem.
SOC., Chem. Commun. 1995, 751.
A. G. Johnston, D. A. Leigh, R. J. Pritchard, M. D. Deegan, Angew. Chem. 1995, 107,
1324, 1327;Angew. Chem., Int. Ed. Engl. 1995, 34, 1209, 1212.
S. Ottens-Hildebrandt, T. Schmidt, J. Harren, F. Vogtle, Liebigs Ann. 1995, 1855;
F. Vogtle, R. Jager, M. Handel, S. Ottens-Hildebrandt, W. Schmidt, Synthesis 1996,
in press.
S. Rumney IV, E. T. Kool, Angew. Chem. 1992,104, 1686; Angew. Chem., lnt. Ed. Engl.
1992, 31, 1617.
 3.2.3.1 Introduction 94 1

1691 J. S. Cohen, Oligodeoxynucleotides: Antisense Inhibitors of Gene Expression, CRC,

Boca Raton, FL, 1989.
1701 M. Mutter, S. Vuilleumier, Angew. Chem. 1989, 101, 551; Angew. Chem., Int. Ed. Engl.
1989, 28, 535; I. Ernest, J. Kalvoda, C. Sigel, G. Rihs, H. Fritz, M. J. J. Blommers,
F. Raschdorf, E. Francotte, M. Mutter, Helv. Chim. Acta 1993, 76, 1539.
1711 L. C. Hsieh, S. Yonkovich, L. Kochersperger, P. G. Schultz, Science 1993, 260, 337.
(721 S. E. Bystrom, A. Borje, B. Akermark, J. Am. Chem. Soc. 1993, 115, 2081.
1731 P. Behrens, G. D. Stucky, Angew. Chem. 1993,105, 1729; Angew. Chem., Int. Ed. Engl.
1993, 32, 696.
[74] L. S. Hegedus, Organische Synthese mit Ubergangsmetallen, VCH, Weinheim, 1995,
Chapters 4.3 and 8.4 and references therein.
1751 See J.-M. Lehn, Supramolecular Chemistty, VCH, Weinheim, 1995, Chapter 5.

3.2.3 Membrane Reactors in Homogeneous Catalysis

Udo Kragl, Claw Dreisbach

3.2.3.1 Introduction
Decoupling the residence time of a homogeneous catalyst and reactants in a reac-
tor is an important aspect of process development. The aim is to achieve high total
turnover numbers (TTNs) for the catalyst in order to reduce the product-specific
catalyst costs, to obtain easy recovery of the catalyst for its repeated use, and to
facilitate downstream processing. In continuously operated reactors reaction con-
ditions such as reactant concentrations can be controlled more accurately than in
batch processes, resulting in (for example) higher selectivities (cf. Section 3.1.4).
To address these problems, anchoring of homogeneous catalysts to insoluble sup-
ports (inorganic materials or organic polymers) has been used most often (cf. Sec-
tion 3.1.1.3). The main problems related to this approach are the nonuniform and
partly unknown structures of the resulting heterogeneous catalysts, mass transport
limitations due to hindered diffusion, leaching, and a low catalytic activity. Since
the 1970s there have been several attempts to recover homogeneously soluble
catalysts using membranes. An inherent advantage of this approach is the possi-
bility of adding fresh catalyst even in continuously operated reactors, which is im-
possible in the case of fixed-bed reactors (cf. Section 3.1.1.6). Until now, however,
no data for industrial processes using this approach have been published. In con-
trast, in biotechnology, enzyme membrane reactors, in which the soluble enzyme
is retained behind an ultrafiltration membrane, are used on a multi-100 ton scale
for industrial synthesis of fine chemicals. The application of such reactors has
been reviewed quite recently [ 1-41.
In this section, after a classification of the different types of membrane reac-
tors, selected examples including some of the most recent developments in asym-
metric synthesis, highlight the potential of this approach (cf. Sections 2.9 and
3.3.1).
942 3.2 Special Catalysts and Processes

3.2.3.2 Classification and Examples of Membrane Reactors

According to IUPAC a membrane reactor is a “device for simultaneously carrying
out a reaction and membrane-based separation in the same physical enclosure”.
This type of reactor has been studied intensively by many groups, resulting in
more than 1400 publications since 1994 [ 5 ] . The membrane may act in several
ways. A rough classification is illustrated in Figure 1. Examples of each type
are listed in Table 1.
Figure I(a) shows the principle of a catalytically active membrane, where the
educt is converted while passing the membrane. The membrane material itself
may have catalytic activity or the catalyst may be immobilized within the mem-
brane or on its surface. This type of reactor is often called a catalytic membrane
reactor (CMR) [6]. Figure l(b) shows an example in which the product is selec-
tively removed through the membrane in order to increase conversion. Controlled
dosing of a substrate may also be possible, thus increasing the selectivity by
avoiding high concentrations of one reactant. The immobilized catalyst is loca-
) homogeneously soluble cata-
lized in a fixed or fluidized bed. In Figure l ( ~ the
lyst is retained by an appropriate membrane, whereas educt and product molecules
can pass through it.
In practice, quite often a combination of the types described above is found. For
example, palladium membranes act as permselective membranes for H2 and as
catalysts for hydrogenation reactions at the same time, so the descriptions of
types (a) and (b) both apply.

Figure 1. Examples of membrane reactors in which the membrane acts in different ways:
(a) Catalytically active membrane, where the membrane material itself is
catalytically active or the catalyst is immobilized within the membrane.
(b) Selective removal of product by a selective membrane - the immobilized
catalyst is present in a fixed or fluidized bed.
(c) The soluble catalyst is retained by a membrane, through which educts and
products can pass.
E = educt; P = product; C = catalyst; sC = soluble catalyst.
Table 1. Examples of the use of membrane reactors.")
Reactor typeb' Membrane material Reaction Catalyst Ref.
AI2O3impregnated with catalyst Claus reaction PA1203
A1203impregnated with catalyst Reduction of NO, v205

Polypropylene Hydrolysis of butter oil Lipase

Organic polymer containing Enantioselective hydrolysis of Lipase
the enzyme racemic methyl glycidate
Polydimethylsiloxane Epoxidation S,S-Salen complex
Pt on V Decomposition of H2S Pt (thermolysis)
Pd-Ag Dehydrogenation of Noble metal
(methy1)cyclohexene
Pd Hydrogenation of ethylene Pd (membrane)
Alumina Methane steam reforming Ni/A1203
MgO Oxidative coupling of methane PbO
Ag Oxidation of ethanol Ag
Polypropylene Oxidation of ethylene PdCI,/CuClJCu(OAc),
in water
PTFE Oxidation of benzyl alcohol NBH4HS04 as phase-
transfer catalyst
l(b)-removal of ester Mod. poly(viny1 alcohol) Esterification
~ ______

a) From several examples given in the literature only a representive one is taken.
') RO = reverse osmosis; UF = ultrafiltration.
Table 1. (Continued)
Reactor typeb) Membrane material Reaction Catalyst Ref.
1(b) Polymer Regeneration of cofactors in Oxidoreductase ~ 7 1
enzymic reductions
1(c)-UF Organic polymer Enantioselective hydrolysis of Aminoacylase [4, 281
ruc-N-acylmethionine
1(c)-UF Organic polymer C-C bond formation Aldolase
1(c)-UF Pol yamide Hydrogenation, hydroformylation Rh complex; phosphane
bound to polystyrol
1(c)-RO Polyimide Hydrogenation Ru-phosphane complex
I(c)-RO, UF Cellulose acetate, silicone rubber Hydroformylation Rh-carbonyl complex
1 (c)-RO Silicone rubber Hydroformylation Coxarbonyl complex
1(c)-RO Polyimide Hydroformylation Rh-phosphane complex
or Co-carbonyl complex
1(c)-UF Alumindgraphite Epoxidation W-phosphate complex
1(c)-UF Organic polymer Reduction of NAD(P)' Rh complex, bipyridyl
bound to PEG
1(c)-UF Polyaramide Hydroformylation Rh catalyst with long-
chain amines
1(c)-UF Polyaramide Enantioselective addition of Ligand bound to soluble
dialkvlzinc to aldehvdes methacrylate
RO = reverse osmosis; UF = ultrafiltration.
Table 1. (Continued)
Reactor typeb’ Membrane material Reaction Catalyst Ref.
1(c)-NF Polyphenylene oxide Enantiomeric ketone reduction Oxaborolidine/soluble 158, 671
polystyrene
1(c)-NF Polyphenylene oxide Acylation Pyridine/dendrimers 1711
1(c)-NF Polyphenylene oxide Kharasch addition Dendritic Ni catalyst [591
1(c)-NF Polyphenylene oxide Allylic substitution Dendritic Pdlphosphine 1601
1(c)-NF Polyphenylene oxide Hydrovinylation Dendritic Pdphosphine 1751
1(c)-NF Polyphenylene oxide Allylic alkylation Dendritic Pdphosphine [76]
1(c)-NF Polydimeethy lsiloxane Hydroformylation Rhlorganophosphite I781
1(c)-NF Regenerated cellulose Asymmetric hydrogenation RhBPPM in micelles [61]
b, RO = reverse osmosis: UF = ultrafiltration

B
R
F
a
 3.2.3.3 Membrane Reactors for Homogeneously Soluble Catalysts 947

the total turnover number, which would result in a cost reduction. The older litera-
ture deals with the application of different membrane types in organic solvents.
More recently, water-soluble catalysts have become important as they can be
recovered simply by extraction [40]. However, membrane processes for phase
separation have also been reported [41] (cf. Section 3.1.1.6). Over the years,
the number of companies selling more stable and better-defined membranes has
been increasing significantly. Surveys of available membranes [42, 44, 55, 631
have been published. Supported liquid membranes have been used for cleavage
of racemates [46].

3.2.3.3 Membrane Reactors for Homogeneously

Soluble Catalysts
Especially for chiral ligands, which are often more expensive than the noble
metals with which they coordinate, easy recovery and repeated use in order to
increase the total turnover number are highly desirable [45, 641. Attempts to
couple chiral ligands to insoluble polymers often result in a decrease in the
enantiomeric excess of the product, as described for the addition of diorganozinc
to aldehydes (eq. (1)) [47, 481.

-
0 i) hexane, 4
HO H
ii) H30+
) + ZnEt2
Ph Ph
1 2 3

Figure 3 is a schematic representation of the concepts to generate a homoge-

neously soluble catalyst retainable in a membrane reactor, either bound to a poly-
meric backbone (cf. Section 3.1.1.3), or a dendrimer (cf. Section 3.2.2), or
embedded in a micelle (cf. Section 3.1.11).

dialkylzinc addition, cat: prolinol

ketone reduction, cat: oxazaborolidine
allylic substitution, cat: Pd-phosphine complex

hydrogenation, cat: Rh-phosphine complex

Figure 3. Retention of a homogenously soluble catalyst in a membrane reactor.

948 3.2 Special Catalysts and Processes

For the example of the addition of diethylzinc 2 to benzaldehyde 1 (eq. (I)),

a continuous asymmetric synthesis in a membrane reactor using a homogeneously
soluble catalyst [38, 391 has been developed for the first time. a,a-Diphenyl-.c-pro-
linol, which is used as the chiral ligand, has been coupled to a copolymer made
from 2-hydroxyethyl methacrylate and octadecyl methacrylate [49] (molecular
weight 96000 g mol-'), resulting in the polymer-enlarged chiral ligand 4 [50].

HO
@ = soluble support
Ph

The reaction chosen is very suitable for process development as it occurs only
in the presence of the catalyst. A leakage from the reactor would cause a decrease
in conversion due to a lowered volumetric activity, yet no change in the enantio-
meric excess (ee) of the product. The membrane used is a solvent-stable poly-
aramide membrane NadirTMUF PA20, cut off 20000 g mol-', having a retention
of more than 99.8% for the polymer-enlarged ligand 4. The ee which can be
reached with 4 is somewhat lower than with the noncoupled ligand (80 % com-
pared with 97 %), but still higher than for ligands immobilized on insoluble sup-
ports [47]. In the continuously operated reactor an ee of the same order of mag-
nitude can be reached. Based on the ratio of concentrations and the time for which
the reactor has been operated, the total turnover number for the chiral ligand has
been raised 10-fold, from 50 to 500.
The use of membrane reactors is favorable not only with respect to an increase
in the total turnover number. In certain cases the selectivity can also be increased
by applying high concentrations of the soluble catalyst together with making use
of the behavior of a continuously operated stirred-tank reactor. Basically, this is
also possible with a catalyst coupled to an insoluble support, but here the maxi-
mum volumetric activity is limited by the number of active sites per mass unit
of the catalyst. This has been shown for the enantioselective reduction of ketones
(eq. (2)) such as acetophenone 5 with borane 6 in the presence of polymer-
enlarged oxazaborolidines 8 and 9 [65-671.

+BH38w2 MeOH
i) THF,
ii) 8 or 9
t
3 (2)

5 6 w 7
 3.2.3.3 Membrane Reactors for Homogeneously Soluble Catalysts 949

8 9 (cf. Figure 3)

Besides the fast catalyzed reaction leading to the desired enantiomer, the
slower, non-catalyzed reduction leading to the racemate also takes place. The lat-
ter may be suppressed by high catalyst concentrations and low substrate concen-
trations. Typically 5 to 10 mol % of the oxazaborolidine is used, and the ketone is
slowly added to a solution of the catalyst and the borane. This reaction is used on
a kilogram-scale for the production of chiral intermediates [68, 691. On the basis
of the kinetic parameters, the operating conditions for the continuously operated
membrane reactor were estimated [.52, 53, 671. An increasing catalyst concentra-
tion corresponding to an increasing Damkohler number (the product of catalyst
concentration, residence time, and rate constant; it can be regarded as the product
of probability of reaction and residence in the reactor [5 I]) leads to higher enan-
tioselectivities. This behavior is more pronounced at higher substrate concen-
trations. Results for a typical experiment for the reduction of acetophenone to
(R)-1-phenylethanol, (R)-7, are given in the following. Under these conditions
published, a space-time yield of 290 g L-' d-' and a TTN of 120 have been
achieved. For this combination of substrate and catalyst the maximum ee is
94 %. For the catalyst 9 and tetralone ee > 99 % has been achieved [67]. Increas-
ing the substrate concentration to 2.50 mmol L-' and decreasing the catalyst con-
centration and residence time increased the space-time yield to 1400 g L-' d-' and
the TTN up to 560 [67]. In a batch reactor without recovery of the catalyst, that
would correspond to a catalyst concentration of only 0.18 mol %. A similar ap-
proach has been published recently with an increase of the TTN to 1400 [%I.
In this case a polymer-enlarged oxazaborolidine based on hydroxyproline has
been used.
Besides the use of homogeneously soluble polymethacrylates or poylstyrene, as
for the examples described above, other soluble supports may be used in order to
yield a catalyst which can be retained by ultra- or nanofiltration membranes. Sev-
eral groups have introduced catalysts (chiral and nonchiral) coupled to dendrimers
and dendrimer-like structures [54, 59-76]. Compared with catalysts coupled to
polymers, such complexes offer the advantage of a more defined structure.
Thus, the number of active sites can be controlled more accurately. As these
will be present at the surface of a globular structure they will be easily accessible.
 References 95 1

the other hand, the catalyst has already been removed from the product solution by
the filtration step, thus simplifying downstream processing. Currently nanofiltra-
tion membranes do not in every case fulfill the demand for stability and repro-
ducibility. This, in general, seems to be less of a problem for ultrafiltration
membranes, making them the better choice if the polymer is large enough.
Nevertheless, there is a need for further studies, e. g., on possible interaction of
membrane materials with the catalyst.

References
[ l ] U. Kragl, D. Vasic-Racki, C. Wandrey, Chem.-Ing.-Tech. 1992, 64, 499; U. Kragl,
D. Vasic-Racki, C. Wandrey, Indian J. Chem. 1993, 32B, 103.
[2] A. S. Bommarius in Biotechnology, Vol. 3, Bioprocessing (Eds.: H.-J. Rehm, G. Reed,
A. Puhler, P. Stadler, G. Stephanopoulos), VCH, Weinheim, 1993, pp. 4 2 7 4 6 6 .
[3] D. M. F. Prazeres, J. M. S. Cabral, Enzyme Microb. Technol. 1994, 16, 738.
[4] U. Kragl in Industrial Enzymology (Eds.: T. Godfrey, S. West), 2nd ed., MacMillan,
Hampshire, 1996.
[S] Search in the Science Citation Index database from 1994 until spring 2001 using the
search term “membrane and reactor”. For a more thorough search details on the
membrane processes such as ultrafiltration have to be included in the term as well.
[6] T. T. Tsotsis, A. M. Champagnie, S. P. Vasileiadis, Z. D. Ziaka, R. G. Minet, Sep. Sci.
Technol. 1993, 28, 397.
[7] V. M. Gryaznov, Platinum Met. Rev. 1986, 30, 68.
[8] J. Shu, B. P. A. Grandjean, A. van Neste, S. Kaliaguine, Can. J. Chem. Eng. 1991,
69, 1036.
[9] H. P. Hsieh, Catal. Rev.-Sci. Eng. 1991, 33, 1 .
[lo] K. Keizer, V. T. Zaspalis, T. J. Burggraaf, Muter: Sci. Monogl: 1991, 660, 2511.
[ l l ] G. Saracco, V. Specchia, Catal. Rev.-Sci. Eng. 1994, 36, 305.
[ 121 E. Drioli, A. Basile in Prepr: Aachener Membrane Colloquium, GVC.VD1, Diisseldorf,
1995, pp. 105-120.
[13] J.-A. Dalmon in Handbook of Heterogeneous Catalysis (Eds.: G. Ertl, H. Knozinger,
J. Weitkamp), VCH, Weinheim, 1997.
[14] H. J. Sloot, G. F. Versteeg, W. P. M. van Swaaij, Chem. Eng. Sci. 1990, 45, 2415.
[15] V. T. Zaspalis, W. van Praag, K. Keizer, J. G. van Ommen, J. R. H. Ross, A. J. Burggraaf,
Appl. Catal. 1991, 74, 249.
[I61 F. X. Malcata, C. G. Hill jr., C. H. Amundsen, Biotechnol. Bioeng. 1992, 39, 984.
[17] Sepracor Inc. (J. L. Lopez, S. L. Mattson), WO 9.006.996 (1990); Sepracor Inc. (S. L.
Matson, S. A. Wald, C. M. Zepp, D. R. Dodds) US 5.077.217 (1991).
[18] J. L. Lopez, S. A. Wald, S. L. Matson, J. A. Quinn, Ann. N.I.: Acad. Sci. 1990, 613, 155.
[19] D. J. Edlund, W. A. Pledger, J . Membl: Sci. 1993, 77, 255.
[20] J. K. Ali, E. J. Newson, D. W. T. Rippin, Chem. Eng. Sci. 1994, 49, 2129.
[21] N. Itoh, AlChE J. 1987, 33, 1576.
[22] J. N. Armor, Chemtech 1992, 557.
[23] K. Omata, S. Hashimoto, H. Tominaga, K. Fujimoto, Appl. Cat. 1989, 52, L1.
[24] V. M. Gryaznov, V. I. Vedernikov, S. G. Gul’yanova, Kinet. Catal. 1986, 26, 129.
[25] S. Chen, H. Fan, Y.-K. Kao, Chem. Eng. J. 1992, 49, 35.
[26] R. Waldburger, F. Widmer, W. Heinzelmann, Chon.-Ing.-Tech. 1994, 66, 850.
[27] Bend Research Inc. (P. van Eikeren), EP 349.204 (1989).
[28] A. S. Bommarius, K. Drauz, H. Klenk, C. Wandrey, Ann. N.Y Acad. Sci. 1992,672, 126.
952 3.2 Special Catalysts and Processes

[29] E. Bayer, V. Schurig, Angew. Chem. 1975, 87, 484; Angew. Chem., Int. Ed. Engl. 1975,
14, 493.
[30] L. W. Gosser, W. H. Knoth, G. W. Parshall, J. Mol. Catal. 1977, 2, 253.
[31] BP Chemicals Ltd. (J. E. Ellis), GB 1.312.076 (1973).
[32] Imperial Chemical Industries Ltd. (W. Featherstone, T. Cox), GB 1.432.561 (1976).
[33] Enichem S.p.A. (N. Andriollo, G. Cassani, P. D’Olimpio, B. Donno, M. Ricci), EP
0.586.009 (1994).
[34] E. Steckhan, S. Henmann, R. Ruppert, J. Thommes, C. Wandrey, Angew. Chem. 1990,
102, 445; Angew. Chem., Int. Ed. Engl. 1990, 29, 388.
[35] U. Meyer-Blumenroth, J. Schneider in Prepr: Aachener Membrane Colloquium,
GVC.VD1, Dusseldorf, 1991, pp. 329-352.
[36] Hoechst AG (H. Bahrmann, M. Haubs, W. Kreuder, T. Muller), DE 3.842.819 (1990).
[37] U. Kragl, B. Bossow-Berke, J. Danzig, C. Wandrey, Dechema Monographs 1993,
129, 223.
[38] C. Dreisbach, Ph. D. Thesis, University of Bonn (Germany), 1994.
[39] U. Kragl, C. Dreisbach, Angew. Chem. 1996, 108, 684; Angew. Chem., Int. Ed. Engl.
1996, 35, 642.
[40] W. A. Henmann, C. W. Kohlpaintner, Angew. Chem. 1993, 105, 1588; Angew. Chern.,
Int. Ed. Engl. 1993, 32, 1524.
[41] Exxon Chemical Patents Inc. (J. R. Livingston, E. J. Mozeleski, G. Sartori), WO 93/
04029 (1993).
[42] R. Reidy, Profile of the International Filtration and Separation Industry, Elsevier,
Oxford, 1993.
[43] Prepr: Aachener Membrane Colloquium, GVC.VD1, Dusseldorf, 1995, pp. 525-548.
[44] R. Rautenbach, A. Groschl, Desalination 1990, 77, 73.
[45] J. T. F. Keurentjes, L. J. W. M. Nabuurs, E. A. Vegter, Proc. Chiral ’94 USA,Reston,
Virginia, USA, 1994, pp. 39-40.
[46] R. A. Sheldon, Chirotechnology: Industrial Synthesis of Optically Active Compounds,
Marcel Decker, New York, 1993.
[47] S. Itsuno, J. M. J. Frechet, J. Org. Chem. 1987, 52, 4140.
[48] K. Soai, S. Niwa, Chem. Rev. 1992, 92, 833.
[49] The copolymer was a gift of Bayer AG, Leverkusen, Germany; it contains 0.75 mmol of
hydroxy groups per g of polymer.
[50] C. Dreisbach, G. Wischnewski, U. Kragl, C. Wandrey, J. Chem. Soc. Perkin Trans. 1
1995, 875.
[5 11 For a more detailed treatment refer to textbooks about chemical reaction engineering,
such as: M. Baerns, H. Hofmann, A. Renken, Chemische Reaktionstechnik, 2nd ed.,
Thieme, Stuttgart, 1992; K. R. Westerterp, R. J. Wijngaarden, Ullmann’s Encycl. Ind.
Chem. 5th ed. 1992, Vol. B4, pp. 5-83 and following chapters.
[52] M. Biselli, U. Kragl, C. Wandrey in Enzyme Catalysis in Organic Synthesis (Eds.:
K. Drauz, H. Waldmann), VCH, Weinheim, 1995, pp. 371-397.
[53] U. Kragl, U. Niedermeyer, M.-R. Kula, C. Wandrey, Ann. N.K Acad. Sci. 1990, 613, 167.
[54] J. W. J. Knapen, A. W. van der Made, J. C. de Wilde, P. W. N. M. van Leeuwen,
P. Wijkens, D. M. Grove, G. van Koten, Nature (London) 1994, 372, 659.
[55] L. P. Raman, M. Cheryan, N. Rajagopalan, M. S. Ray, Chem. Eng. Prog. March 1994,68.
[56] A. Tavolaro, E. Drioli, Adv. Muter: 1999, l I , 975.
[57] A. Julbe, D. Farusseng, C. Guizard, J . Membrane Sci. 2001, 181, 3.
[58] J. Woltinger, A.S. Bommarius, K. Drauz, C. Wandrey, Org. Proc. Res. Dev., 2001,
5, 241.
[59] A. W. Kleij, R. A. Gossage, R. J.M. Klein Gebbink, N. Brinkmann, E.J. Reijerse,
U. Kragl, M. Lutz, A. L Spek, G. van Koten, J. Am. Chem. Soc. 2000, 122, 12112.
 3.2.4.1 Introduction 953

[60] N. Brinkmann, D. Giebel, G. Lohmer, M.T. Reetz, U. Kragl, J. Catal. 1999, 183, 163.
[61] T. Dwars, J. Haberland, I. Grassert et al. J. Mol. Catal. A - Chem. 2001, 168, 81.
[62] G. Grigoropoulou, J. H. Clark, D. W. Hall, K. Scott, Chem. Commun. 2001, 547.
[63] M. Mulder, Basic Principles of Membrane Technology, Kluwer Academic Publishers,
Dordrecht, 1996.
[64] Chiral Catalyst Immobilisation and Recycling (Eds.: D. E. DeVos, I. F. J. Vankelecom,
P. A. Jacobs), Wiley-VCH, Weinheim, 2000.
[65] E. J. Corey, R. K. Bakshi, S. Shibata, C.-P. Chen, V. K. Singh, J. Am. Chem. Soc. 1987,
109, 7925.
[66] L. Deloux, M. Srebnik, Chem. Rev. 1993, 93, 763.
[67] G. Giffels, J. Beliczey, M. Felder, U. Kragl, Tetrahedron: Asymmetry 1998, 9, 691.
[68] S. Wallbaum, J. Martens, Tetrahedron: Asymmetr?,1992, 3, 1475.
[69] H.-U. Blaser, B. Pugin, F. Spindler, Enantioselective Synthesis in Applied Homogeneous
Catalysis with Organometallic Compounds (Eds.; B. Comils, W. A. Henmann) VCH,
Weinheim, 1996, pp. 992-1009.
[70] C. Salagnad, A. Godde, B. Emst, U. Kragl, Biotechnol. Prog. 1997, 13, 810.
[71] T. Marquardt, U. Luning, Chem. Commun. 1997, 1681.
1721 C. Bolm, N. Denien, A. Seger, Chem. Commun. 1999, 2087.
1731 M.T. Reetz, G. Lohmer, R. Schickardi, Angew. Chem., Int. Ed. Engl. 1997, 36, 1526.
1741 H. Bmnner, S. Altmann, Chem. Bel: 1994, 127, 2285.
[75] N. J. Hovestad, E. B. Eggeling, H. J. Heidbuchel, J. T. B. H. Jastrzebski, U. Kragl,
W. Keim, D. Vogt, G. van Koten, Angew. Chem. Int. Ed. 1999, 38, 1655.
[76] D. de Groot, E. B. Eggeling, J. C. de Wilde, H. Kooijman, R. J. van Haaren, A. W. van der
Made, A.L. Spek, D. Vogt, J.N.H. Reek, P.C.J. Kamer, P.W.N.M. van Leeuwen,
Chem. Commun. 1999, 1623.
[77] I. F. J. Vankelecom, P. A. Jacobs, Catal. Today 2000, 56, 147.
[78] Union Carbide Chemicals & Plastics Technology Corporation (J. F. Miller, D. R. Bryant,
K. L. Hoy, N. E. Kinkade, R. H. Zanapalidou), US 5.681.473 (1997).

3.2.4 Phase-Transfer Catalysis and Related Systems

Yuri Goldberg, Howard Alper

3.2.4.1 Introduction
Phase-transfer catalysis (PTC) is the most widely used method for solving the pro-
blem of the mutual insolubility of nonpolar and ionic compounds. Basic princi-
ples, synthetic uses, industrial applications of PTC, and its advantages over con-
ventional methods are well documented [l-31. PTC has become a powerful and
widely accepted tool for organic chemists due to its efficiency, simplicity, and
cost effectiveness. The main merit of the method is its universality. It may be ap-
plied to many types of reactions involving diverse classes of compounds. An im-
portant feature of PTC is its compatability with other methods for the intensifica-
tion of biphasic reactions (sonolysis, photolysis, microwaving, etc.) as well as
with other types of catalysis, in particular, with transition-metal-complex catalysis.
Homogeneous metal-complex catalysis under PTC conditions involves the simul-
954 3.2 Special Catalysts and Processes

taneous use of a PT agent (quaternary ammonium salt, crown ether, poly(ethy1ene

glycol) (PEG), etc., in general Q X - ) and a transition metal complex to carry out
organic reactions in two-phase systems. The role of the PT agent consists as a rule,
of transporting the reagent anion or the anionic metal complex (preformed or gen-
erated in situ) to a low-polarity medium where the catalytic or stoichiometric
reaction occurs.
The problems of metal-complex catalysis under PTC conditions have been dis-
cussed previously in a number of reviews [4-71 and monographs [l-31. In this
section, biphasic reactions in the presence of a PT agent and a transition-metal
complex are considered with the emphasis on the most recent results.

3.2.4.2 Homogeneous Transition-Metal Catalyzed

Reactions Under Phase-Transfer Conditions

3.2.4.2.1 Reduction, Hydrogenation, and Hydrogenolysis

Nitro Compounds

The biphasic reduction of nitroarenes with stoichiometric Fe,(CO),, under

nitrogen is one of the first examples of the use of metal complexes in PTC
reactions [%lo]. The reaction occurs quickly under mild conditions to give
the corresponding anilines in high yield. [HFe3(CO),,I-, generated in situ at
the interface, is the key intermediate. The latter can be transferred to the or-
ganic phase in the form of an ion-pair with a quaternary ammonium cation
[lo]. The reduction also occurs under triphase catalysis conditions using a
polymer-bound PT agent [ll]. It is possible to use catalytic R u ~ ( C O ) under
,~
a CO atmosphere instead of Fe3(C0)12[12]. The PTC reduction of nitro com-
pounds is also effectively catalyzed by PhCCo3(C0)9 in a CO atmosphere [13]
as well as by Ru(PPh3)$212 with CO-H2 (1:l) [14]. Nitroarenes can also be
reduced ina benzenehq. NaOH system containing two complexes (Co,(CO),
and [Rh(1,5-hexadiene)C12])and a PT agent (Me3N+C,2H25C1-)[ 15, 161. More
recently, the biphasic reduction of nitroaromatics with [CpVH(CO),]- generated
from CPV(CO)~ was camed out [ 171. Nitroarenes, including sterically
hindered ones, were reduced to the corresponding amines quickly and in high
yield.

Alkynes, Alkenes, a,p-Unsaturated Carbonyl Compounds,

Aromatics, and Heteroaromatics

Palladium(I1) chloride in conjuction with PEG400 smoothly catalyzes the bipha-

sic reduction of arylalkynes with sodium borohydride [18]. The reaction does not
occur in the absence of PdC12. In contrast to LiA1H4 (a well-known reagent for the
 3.2.4.2 Homogeneous Transition-Metal Catalyzed Reactions 955

reduction of alkynes to trans-alkenes), NaBH4 with PdCl,/PEG gives cis-alkenes

selectively.
The catalytic pair PdCI,/TDA-1 readily catalyzes the reduction of alkenes and
alkynes with hydrogen [19]. The reduction of chalcone and some other enones
with formate ion, solubilized in the organic solvent by a PT agent, is effectively
catalyzed by a Ru" complex to give the corresponding saturated ketone in quan-
titative yield [20]. Iron pentacarbonyl in a benzene/aq. alkyl amine system reduces
the C=C bond in enones at room temperature (r.t.) in the presence of a stoichio-
metric amount of a crown ether. This system is a source of OH-, solubilized in the
organic phase, which generates active anionic species from Fe(C0)5 [21]. A num-
ber of two-phase cationic reactions catalyzed by ionic compounds with a lipophi-
lic anion and hydrophilic cation (i.e., formal antipodes of typical PT agents) have
been described [22], including reduction processes [23, 241. 1,1-Diarylethylenes
and 9,9'-bifluorenylidene were quantitatively reduced upon treatment with
CO,(CO)~in the presence p-C,2H2sC6H4S03-Na+in a benzene/48 % aq. HBF4
system. Sodium dodecylsulfate was shown to enhance Ru" catalyzed hydrogen
transfer reduction (HTR) of 4-phenyl-3-buten-2-one to the corresponding satu-
rated ketone [25].
The anionic, water-soluble cobalt complex K3[Co(CN)S]H,under PTC condi-
tions, effectively catalyzes the hydrogenation of dienes to monoenes [26-281.
In most cases 1,4-addition prevails, producing trans-alkenes in high yield. The
catalytic pair Co'/Q'X- also accelerates the biphasic hydrogenation of styrene to
ethylbenzene [29].
In a series of papers [30-351, Blum and co-workers reported the hydro-
genation of alkenes, alkynes, and arenes in the presence of a hydrated ion-pair
[Oct3NMe]+[RhCl4(H20),1-.The quaternary ammonium tetrachlororhodate also
catalyzes HTR of alkynes, alkenes and a,B-unsaturated carbonyl compounds
with polymethylhydrosiloxane [36, 371. Recently, heterogenized and therefore
recyclable quaternary ammonium halometallates, namely glass-encapsulated
catalysts [38] and polymer-bound tetrachlororhodate [39], have been described.
Both types of the insoluble catalysts effectively promote various processes in-
cluding the hydrogenation of alkenes and the HTR of a$-unsaturated carbonyl
compounds [40].
A remarkably mild biphasic hydrogenation of aromatics to cyclohexanes has
been carried out using a Rh' complex and a PT agent (eq. (l)), [41]. 2-Ethylfuran,
2-methylpyridine, and quinoline are also easily reduced, the latter only undergoing
hydrogenation of the heterocyclic ring [42].

H$hexane/aq. buffer (pH 7.6)

[Rh(l ,5-hexadiene)Cl]2/QCX-

The hydrogenation of alkenes, dienes, trienes and enones in the above system
does not require a PT agent; therefore the reaction is biphasic but not PTC [42].
Similarly, no PT catalyst is needed for the chemospecific hydrogenation of a$-
956 3.2 Special Catalysts and Processes

unsaturated aldehydes and ketones at the C=C bond in the presence of

(Cy3P),Rh(H)C1, in a biphasic aqueous/organic system under mild conditions
[431.
Some hydrogenations can be also carried out under so-called inverse PTC
(IPTC) conditions where the function of a PT agent (e.g, cyclodextrin, CD) com-
prises the transfer of an organic substrate into aqueous phase [44]. Conjugated
dienes are reduced with hydrogen to monoolefins in the presence of p-CD and
hydridopentacyanocobaltate anion, generated in situ, in alkaline aqueous solution
[45]. The same catalytic system is also highly effective for the IPTC reduction of
the C=C bond in a$-unsaturated carbonyl compounds [46].

Organohalides

Hydrodehalogenation of aryl halides is of interest from an environmental (detox-

ification of haloaromatics) and synthetic point of view [47]. Recent studies re-
vealed the significant potential of using PTC in conjunction with metal catalysts
for the reductive dehalogenation of aryl halides. Rh"' complexes, L2Rh(H)CI2(L =
Cy3P or (i-Pr),P), were shown to be excellent catalysts for the PTC hydrogenoly-
sis of aryl chlorides (eq. (2)) [48]. The reaction occurs under mild conditions and
affords arenes in good yield. The catalytic system is tolerant of many functional
groups.
Ar-CI
H2/L2Rh(H)C12/[Et3NCH2Ph]+Cl-
toluenei40 % aq. KOH
- Ar-H
67-99 %

Polychlorobenzenes in the presence of a Pd/C catalysts can be dehalogenated

with sodium hypophosphite [49] or hydrogen [SO, 511 in a multiphase system
(eq. (3)). 1,2,4,5-Tetrachlorobenzenegives a quantitative yield of benzene using
H2 or NaH2P02 as reductant.

CI
4"
CI
isooctaneA0 % KOH

Q+X-/H2or NaH2P02
~

CI
-0
(3)

Pd/C also catalyzes the PTC reduction of aryl and heteroaryl halides with
sodium formate [52]. The reductive dehalogenation of ally1 and benzyl halides
with HCOOK can be carried out in a heptane/water system in the presence of
water-soluble complexes of type PdC12(sulfonated phosphine)2 and a PT agent
[S3]. Isomeric bromoanisoles are dehalogenated with HCOONa in fair yield
under mild conditions using Pd/C and CD as catalysts. CD in this case functions
as an inverse PT agent which transports the substrate into the organic phase
[541.
 3.2.4.2 Homogeneous Transition-Metul Cutulyzed Reactions 957

Ketones and Imines

Iron carbonyls catalyze the HTR of ketones to secondary alcohols in the presence
of a PT agent (Et,N+CH2PhC1-, 18-crown-6) [ S S , 561. The disadvantage of this
system is the relatively low product yield and quite high concentration of the
metal catalyst. More recently, the HTR of alkyl aryl(heteroary1) ketones was
shown to occur readily in a solid/liquid system using i-PrOH as hydrogen
donor, KF/A1203 as a base, [Ir(COD)Cl], as the metal catalyst and 18-crown-6
as the PT agent (eq. (4)) [57]. The function of a FT agent is the transfer of alkoxide
anions generated at the interface to the bulk of the organic phase providing these
species for the metal catalyzed HTR.

Ar 1 R
i-PrOH/[ Ir(cod)Cl]z/18-crown-6

KF/AI203
*
Ar
il”
R
(4)

The cationic Rh’ complex effectively catalyzes the hydrogenation of imines

under mild conditions using a nonionic surfactant, Triton X-100, as the PT
agent [%I.

3.2.4.2.2 Oxidation
Alkenes, Alkynes, and Allenes

The first examples of metal (Os, Mo, W, or V)- and PT-catalyzed biphasic oxida-
tions of alkenes with H202 have been described by Starks [59]. The PT agent
probably transports H202 molecules into the organic phase and prevents the
decomposition of the peroxide. The direction of the reaction depends on the nature
of the transition metal.
The oxidation of styrene in a dichloroethane/aq. H202system, in the presence
of RuC13 and Me2N+(dodecyl)2Br- at 80 “C affords benzaldehyde (64 %), benzoic
acid (6 %), and phenyloxirane (4 %). The quaternary ammonium salt extracts both
H202 and RuC13 into the organic phase [60].
Biphasic epoxidation of alkenes with aqueous H202is smoothly catalyzed by a
PT agent and a two-component mixture of tungstate and phosphate (or arsenate)
ions (eq. ( 5 ) ) [61]. Alkenes (1-octene, cyclohexene, styrene, etc.) are transformed
to the corresponding oxiranes. Quaternary ammonium tetrakis(diperoxotungst0)-
phosphates generated in situ are catalytically active intermediates [62]. They
were obtained by reacting H2W04, H3P04, H202, and quarternary ammonium
halide and used for preparing vic-diols from various alkenes [63].The epoxidation
of olefinic polymers [64] and (meth)acrylic esters [65] has also been carried
out using a similar catalytic system.

8 Yo H202 (PH 1.6-4.5)/DCE

[WO~]”/[PO~]”lAliquat336
958 3.2 Special Catalysts and Processes

The PTC oxidation of terminal alkynes to the corresponding a-ketoaldehydes

with aq. H202 along with a PT agent and molybdate or tungstate ion occurs
only in the presence of Hg" salts [66]. The epoxidation of alkenes, allylic alco-
hols, and allenes in a CHClJaq. H202 system can be carried out in the presence
of Mo- or W-based heteropolyacids, H3PM12040(M = Mo or W), and cetylpyri-
dinium chloride [67-721. Quaternary phosphonium pertungstate, [Ph,P+CH,Ph],-
[W201,I2-, catalyzes the epoxidation of isolated double bonds under mild condi-
tions and gives oxiranes in acceptable yield [73].
Besides hydrogen peroxide, sodium hypochlorite in combination with a por-
phyrin metal complex and PT agent is also used for the biphasic epoxidation of
alkenes [74]. (meso-Tetraphenylporphyrinato)manganese(III) acetate, for exam-
ple, catalyzes the epoxidation of styrene in a PT system. Under optimum condi-
tions, phenyloxirane is obtained in 90 % yield [75]. The presence of a PT agent
(solubilizing the C10- ion in the organic phase) is essential, otherwise the conver-
sion of styrene does not exceed 5 %. The oxidative system described, highly eff-
cient in the case of styrene, is unsuitable for nonactivated alkenes. This system
was modified by introducing pyridine as a sixth (axial) ligand in the porphyrin
complex [75, 761 and was shown to be very effective for the epoxidation of
many olefins. The factors controlling the catalytic activity of Mn"' porphyrins
have been extensively investigated [77]. The epoxidation of alkenes with aq.
NaClO is smoothly catalyzed by iron(II1) tetraarylporphyrin/Me2N+CH2Ph(tetra-
decyl)Cl-. In this case, unlike Mn"'-porphyrin-catalyzed reactions, it is not neces-
sary to add an axial ligand [78].
Potassium peroxomonosulfate (Oxone') is also an effective oxidizing agent for
the epoxidation of various alkenes in the presence of Mn"' porphyrin and a PT
catalyst [79]. The biphasic epoxidation of various olefins is readily catalyzed
by Co" and Ni" phthalocyanines with NaClO as the oxygen donor and
Bu,N+Br- as the PT agent [80]. The PTC oxidation of alkenes with NaClO is
also catalyzed by square-planar Ni" complexes [81-83].
The oxidation of terminal alkenes to the corresponding 2-alkanones (Wacker
reaction; cf. Section 2.4.1) has also been carried out under PTC conditions.
This process is catalyzed by a PT agent and PdC12 in the presence of CuC12
(reoxidant; eq. (6)) [84]. The reaction is very sensitive to the nature of the
PT catalyst: only quaternary salts of type Me," (CI2-Cl4-alkyl)Br- are effec-
tive.
0
O2 (1-3 atm.)/PdCI2/CuCl2/Q+X-
P R * AR
CcH,j/H20
40-73 Yo

For the oxidation of terminal alkenes to methyl alkyl ketones, RhC13 and RuC13
as well as their complexes may be used instead of PdC12. In these cases, symme-
trical quaternary ammonium salts are also effective. However, under these condi-
tions, the isomerization of alkenes occurs simultaneously with the oxidation [85].
The biphasic Wacker reaction can also be carried out under IPTC conditions using
a-or p-CD as the PT agent [86, 871.
 3.2.4.2 Homogeneous Transition-Metal Catalyzed Reactions 959

Alcohols

The synergism of the catalytic action of (tetraphenylpophyrinato)manganese(III)

chloride [Mn"'(TTP)Cl] and methyltrioctylammonium chloride was demonstrated
by their joint appication for the PTC oxidation of benzyl alcohol with NaClO [88].
Benzaldehyde is formed within several minutes in almost quantitative yield. The
reaction proceeds much more slowly when only one of these catalysts is used.
The addition of a PT agent accelerates the RuC1,-catalyzed biphasic oxidation
of alcohols by NaBr0, [89, 901. Secondary alcohols are transformed to the corre-
sponding ketones in excellent yield. In the absence of a PT catalyst, the reaction
proceeds much more slowly, even at elevated temperatures [89]. RuC& in combi-
nation with a PT agent also catalyzes the selective oxidation of benzylic alcohols
to benzaldehydes in the presence of a solid base using CC1,[91]. A lipophilic qua-
ternary ammonium salt easily solubilizes the ruthenium salt in CC1, to give a
catalyst which effectively promotes the formation of aldehydes in quantitative
yield. Potassium ruthenate is highly effective for the facile oxidation of allylic
and benzylic alcohols under PTC conditions. In the presence of K2Ru04 and
K2S208(reoxidant), the alcohols are transformed to the corresponding carbonyl
compounds at r.t. Saturated alcohols are not oxidized under these conditions.
This permits the selective oxidation of benzylic hydroxy groups of polyhydroxy
compounds to yield hydroxyketones [92].
Aqueous H202in conjunction with RhC1, and didecyldimethylammonium bro-
mide provides a synthetically useful system for the oxidation of primary aliphatic
alcohols to carboxylic acids [93]. The oxidation of alcohols in a dichloroethanel
aq. H202 system is catalyzed by tungstate or molybdate anions in the presence
of a PT agent [94]. In this reaction, as in the epoxidation of alkenes (see
above), the pH of the aqueous phase is very important. The oxidation of cyclohex-
anol, menthol, borneol, 2-octanol, and benzyl alcohol under optimum conditions
gives the corresponding ketones and PhCHO in good yield. Another method for
the PTC synthesis of carbonyl compounds is the dehydration of alcohols using
metal complexes. Secondary alcohols are transformed to ketones in liquidlliquid
systems containing a PT agent and a Rh' complex [95]. The dehydration of alco-
hols in a solidliquid system is also catalyzed by Pd(OAc)2 and Bu,N+Cl- [96].
The oxidation of ethyl mandelate with t-BuOOH is promoted by CuC12 and
Bu,N+Br-. The presence of both catalysts is essential [97].

Sulfides

There are some examples of the biphasic oxidation of sulfides using metal cata-
lysts and PT agents simultaneously. An oxidative system H202-H+/W042- (or
MOO:-), containing neutral lipophilic ligands has been used for the oxidation
of methyl p-chlorophenyl sulfide. This method results in the fast and, as a rule,
highly selective transformation of the thioether to the corresponding sulfoxide
1981. Sulfides are also smoothly oxidized at r.t. to sulfoxides in a nitromethane/
aq. HN03 system containing tetrabutylammonium aurate [99]. More recently,
960 3.2 Special Catalysts and Processes

[Bu4N][AuBr4]was shown to be an even more efficient catalyst for the oxidation

of sulfides to sulfoxides in the same biphasic system [loo].

Saturated and Aromatic Hydrocarbons

The oxidative functionalization of hydrocarbons is a fundamental problem in or-

ganic synthesis. Metal-complex catalysis plays an important role in the solution of
this problem. In this connection, the elaboration of simple, convenient, and indus-
trially applicable catalytic methods using cheap and easily available oxidants is
very important. One of the possible routes for the creation of such methods is
the joint use of metal-complex catalysis and PTC.
It has already been mentioned that Mn"'(TPP)Cl and Oct,N+MeCl- act syner-
gistically in the oxidation of benzyl alcohol with C10- in a CH2C12/H20system.
The oxidation of adamantane (Ad-H) has been investigated by Tabushi [88] and
Meunier [ 1011, who studied the oxidation of Ad-H with aqueous hypohalites
(NaClO, NaBrO; pH 12-13) in the presence of a PT catalyst [Me2N+CH2Ph(n-
C 14H29)]C1-and Mn"' porphyrin complexes of various structures. The reaction
of cyclohexane with NaClO or KHS05 in the presence of MnIII porphyrin com-
plexes and PT agents also leads to the conversion of the hydrocarbon. However,
the yield of the main products (cyclohexyl chloride in the case of NaClO or
cyclohexanol in the case of KHS05) does not exceed 15 % [ 101, 1021. In 1990,
magnesium monoperoxyphthalate [ 1031 and sodium chlorite (NaC10J [ 1041
were shown to be efficient oxidants for the hydroxylation of adamantane, cyclo-
hexane, and some other hydrocarbons catalyzed by Mn"' porphyrins and PT
agents in two-phase systems.
The industrially important oxidation of alicyclic ketones to dicarboxylic acids
(e. g., cyclohexanone to adipic acid) with oxygen has been successfully carried
out. A solid/liquid system was used in the presence of catalytic amounts of
PEG-400 and rhenium carbonyl 11051. The absence of one of the catalysts
drastically decreases the yield.
The oxidation of aromatic hydrocarbons to oxygen-containing derivatives is of
the same theoretical and practical interest as the oxidation of saturated hydrocar-
bons. The application of transition-metal compounds in combination with PT cata-
lysts leads to rather interesting results. The hydroxylation of benzene with aqu-
eous Hz02 is catalyzed by an Fe"'/catechol pair [ 1061. Hydrophobic 4-substituted
catechols are the most effective. Using this method, one can obtain phenol under
mild conditions. No reaction occurs in the absence of the one of the catalysts.
An effective method for the hydroxylation of benzene is its reaction with H202
in the presence of a transition-metal salt [Fe", Fe"', Cu", etc.] and a PT catalyst
11071. Systems containing iron compounds and Bu4N+C1-are the most effective.
Under optimum conditions, the yield of phenol is 65-80 %.
The joint use of PT catalyst and RuC1, substantially improves the oxidation of
methylarenes with C10- in a biphasic system [108]. Toluene and some of its
derivatives are quickly and almost quantitatively oxidized to carboxylic acids
under exceptionally mild conditions.
 3.2.4.2 Homogeneous Transition-Metal Catalyzed Reactions 96 1

The same catalytic pair is also used for the oxidation of cumene with hydrogen
peroxide (eq. (7)) [ 1091 yielding 2-phenylpropan-2-01 and acetophenone. The
function of the PT catalyst is three-fold: extraction of H202 to the organic
phase, solubilization of RuC13, and protection of the ruthenium salt against reduc-
tion [ 1091.

3.2.4.2.3 Carbonylation
Organohalides

The possibility of the carbonylation of organic halides under PTC conditions was
demonstrated for the first time in 1976 [ l lo]. Benzyl chloride was transformed to
phenylacetic acid in a xylenehq. NaOH system containing a Pdo complex and a
PT catalyst. Metal carbonyls are the most frequently used carbonylation catalysts.
The effectiveness of C O ~ ( C Ofor
) ~ the PTC carbonylation of benzyl halides was
discovered independently by two research groups [ 111, 1121. Under mild condi-
tions, benzyl halides are converted into carboxylic acids (eq. (8)).

CO (1 atrn.)/Cop(CO)$[Et3NCH2Ph]’CI-
Ar - X CsHd5 N NaOH, r. t. * A~”COOH (8)

It has been suggested that the reaction occurs in the following way. Tetra-
carbonylcobaltate anion, generated from C O ~ ( C O ) migrates ~, to the organic
phase in the form of an ion-pair [R,N]+[Co(CO)J, where the latter ion reacts
with ArCH2X to give ArCH,Co(CO),. Reaction with CO leads to the formation
of ArCH,COCo(CO), and the C-Co bond is cleaved by OH- [ 11I]. Subsequent
kinetic studies confirmed that the function of the PT catalyst is the transport of
[Co(CO),]- to the nonpolar medium. The cleavage of the acylcobalt carbonyl
complex at the interface is the rate-limiting step of the process [113, 1141.
The PTC carbonylation of substituted benzyl chlorides with C O ~ ( C Ogives )~ a
mixture of products [ l l l , 1151. In all cases, arylacetic acids prevail. These are the
sole products when R = H, CF3. Double carbonylation with subsequent alkylation
producing ketoacids is observed in the case of methyl-substituted benzyl chlo-
rides. 2,4,6-Trimethylbenzyl chloride yields mesitylacetic and mesitylpyruvic
acid in equal amounts [115].
The carbonylation of secondary benzylic halides PhCH(Br)Me, catalyzed by
C O ~ ( C Oin
) ~ two-phase systems yields coupled products PhCH(Me)CH(Me)Ph
or carboxylic and ketoacids PhCH(Me)COOH and PhCH(Me)COCOOH, depend-
962 3.2 Special Catalysts and Processes

ing on the experimental conditions [ 1161. The carbonylation of benzyl halides in a

benzene/5M NaOH system is effectively catalyzed by the mononuclear cobalt
complex [Co(CO),NO] in the presence of a PT agent [117]. The corresponding
arylacetic acids are the major reaction products. The PTC carbonylation of benzal
bromides is readily catalyzed by Co2(C0)&t3N+CH2Ph C1- and gives arylacetic
acids in high yields [ 1181.
Aryl and vinyl halides do not react with CO/CO~(CO)~/PT agent systems under
conditions similar to those described above for benzyl halides. These reactions can
be successfully carried out under UV irradiation [119-1211. During the photo-
stimulated carbonylation, benzyl-containing PT catalysts should not be used
since these conditions convert quaternary salts of type R3N+CH2C6H4RX-to
RC6H4CH2COOH[ 120, 1211. Tetrabutylammonium bromide, stable with respect
to UV irradiation, effectively catalyzes the PTC reaction of aryl bromides with CO
in the presence of C O ~ ( C O ) ~ .
One of the most interesting photostimulated PTC carbonylations is the prepara-
tion of benzolactams and benzolactones from the appropriately substituted aryl
bromides (eq. (9)) [119].

0
n = 2, X = NH; n = 1, X = 0 72-95 Yo

Tetracarbonylcobaltate anion, generated under PTC conditions, catalyzes the

reaction of aryl halides with excess methyl iodide under a CO atmosphere
[122]. The reaction produces aryl methyl ketones and carboxylic acids as the
main products. Stoichiometric or catalytic iron pentacarbonyl can also be used
for the carbonylation of organohalides under PTC conditions [ 123-1281. For
example, reactions of alkyl and arylalkyl halides with CO in aqueous-organic
systems using catalytic amounts of Fe(CO)S and a PT agent afford alkyl- and
arylacetic acids as the main products [127].
In the first work on the PTC carbonylation of organohalides, Pd(PPhJ4 was
used as a metal catalyst [110]. There are a number of other examples of the use
of Pdo complexes in two-phase carbonylations. The selective formation of one
of four possible products, including esters, depends mainly on the composition
of the metal complex (e. g., Pd(PPh,k vs. Pd(dba),) [129]. Radical intermediates
may be involved in the formation of several of the products. Esters (e. g., benzyl
phenylacetate from benzyl bromide) are the major products of the carbonylation of
benzyl bromides using a zwitterionic rhodium catalyst [ 1301.
The carbonylation of benzyl halides in t-BuOH, catalyzed by Pd(PPh,),Cl, and
Et,N+CH,PhCl-, is a mild, efficient, one-pot route to t-butyl esters of arylacetic
acids [ 1311. Similar reactions using benzyl halides, ethanol, CO, Bu4N+I-, and
polymer-bound palladium chloride produce ethyl arylacetates [ 1321.
 3.2.4.2 Homogeneous Transition-Metal Catalyzed Reactions 963

Aryl, vinyl, and benzyl halides are catalytically carbonylated by CO gener-

ated in situ from chloroform and aqueous alkali, in the presence of phos-
phine-palladium complexes such as PdCI2(PPh3),. The biphasic reactions do
not require a PT agent, they occur at r.t., and they afford the corresponding
carboxylic acids in up to 92% yield. Labeling experiments with I3CHC1,
showed that the source of the C1 unit in the carbonylation is chloroform
[133]. It should also be noted that less-reactive chloroarenes can be carbonylated
under biphasic conditions using bis(tricyclohexy1phosphine)palladium dichloride
as the metal catalyst. Again, the presence of a PT agent does not affect the reaction
[134].
PdO- and PT-catalyzed carbonylation of gerninal vinylic dibromides gives
diynes or dicarboxylic acids using benzene or t-amyl alcohol as a solvent, respec-
tively (eq. (10)) [ I 351.
CO (1 atm.)/PdL,/Q+X
I C6Hd5 N NaOH, 55-70 "C - Ar = =
30-70 Yo
Ar

Ar -CBr2
~ COOH
(10)
CO (1 atm.)/Pd(dipho~)~/[Et~NCH~Ph]+CI-
'AmOH/5 N NaOH Ar ACOOH
07-93 Yo

The palladium-catalyzed carbonylation of propargyl halides under PTC condi-

tions affords allenic acids and olefinic diacids in good yields [ 1361. The carbon-
ylation of allyl halides under PTC conditions is best catalyzed by nickel complexes.
Ally1 chlorides react with CO in the presence of Ni(C0)4 and a quaternary ammo-
nium salt to afford mixtures of butenoic acids, of unknown stereochemistry [137].
The reaction of allyl halides with CO in a PT system is catalyzed by Ni" com-
plexes, viz. K,[Ni(CN),] and [Ni(CN),] [138]. A similar catalytic system was
used successfully for the direct carbonylation of aryl iodides under nonphotolytic
conditions [139]. This is a genuine PTC reaction since the iodoarene is recovered
unchanged in the absence of a PT agent. It is proposed that the reaction proceeds
by the interaction with ArI of cyanotricarbonylnickelate anion, generated in situ,
to give [ArNi(CO),CN]- the carbonylation of which gives the corresponding acyl-
metal complex. Cleavage of the C-Ni bond with base affords the acid. This
method is exceptionally simple in execution and workup of the reaction, and it
avoids the use of highly toxic Ni(CO)+ The nickel-cyanide-catalyzed biphasic car-
bonylation of benzylic chlorides is promoted by lanthanide salts (CeCl,, LaC1,)
[140].
Nickel cyanide catalyzes the PTC carbonylation of vinyl halides to a,D-unsat-
urated acids [ 1411. A similar reaction involving 2-bromo- l-phenyl-l,3-butadiene
gives the a-ketolactone (60 %) and dienoic acid (15 %); (the former results from
the double carbonylation reaction (eq. (1 1)) [ 142]), possibly proceeding via a
nickel metallacycle [ 1431.
964 3.2 Special Catalysts und Processes

Ph A CO/Ni(CN)2/[Me3N(C~~H33)]fBr-
toluene/6.25 N NaOH *
0
COOH

Si02

XPh
0

The catalytic pair Ni(CN),/Bu,N+Br- readily catalyzes the biphasic carbonyla-

tion of a-haloalkynes [ 144, 1451 and allenyl halides [ 1451. The first reaction results
in a mixture of allenic monoacids and unsaturated diacids, whereas allenyl halides
transform to allenic acids with high regioselectivity. The carbonylation of gem-
dibromocyclopropanes under PTC conditions is catalyzed by Ni" and Co" salts.
The reaction gives the corresponding cyclopropanecarboxylic acids in fair yields
[ 1461.
In conclusion, it should be mentioned that aryl and alkyl iodides can be car-
bonylated to the corresponding carboxylic acids using Co" salts, KCN, aqueous
alkali and PEG-400 in a two-phase system. The reaction is promoted by BF3
Et,O with FeC12 as a copromoter [147].

Alkynes, Dienes, Trienes, and Allenes

Treatment of [Co(CO),]- under PT conditions with a mixture of alkyne and Me1

(excess) in a CO atmosphere gives hydroxybut-2-enolides (eq. (12)) [ 1481. When
benzyl bromide is used instead of MeI, the but-2-enolides are not formed due to
the fast hydrolysis of the acylcobalt carbonyl intermediate [PhCH,COCo(CO),]
before the alkyne complex is formed. This obstacle has been overcome by carry-
ing out the reaction in the absence of water, using solidAiquid PTC [ 1491. The di-
rection of the PTC carbonylation of alkynes in the presence of Me1 changes again
when cobalt and ruthenium carbonyls are used simultaneously (1 : 1) [ 1501. In this
case, y-ketoacids are obtained.

-R + Me1
CO (1 atrn.)/C02(CO)$[Me~N(C,~H~~)lfBr-
CsH& N NaOH, r. t. * 0 hOH
18-68 Yo
(12)

The PTC reaction of phenylacetylene with CO in the presence of nickel cyanide

affords atropic acid [ 1511. A similar reaction involving alkynols gives unsaturated
diacids. The stereoselectivity of the reaction is sensitive to the nature of the
quaternary ammonium salt (eq. (13)) [152].
 3.2.4.2 Homogeneous Transition-Metal Catalyzed Reactions 965

CO (1 atrn.)/Ni(CN)2/QtX-

HO
toluene/5 N NaOH (13)
83-95 Yo

The cobalt and PTC carbonylation of dienes and trienes give acylated products
[ 1471. Cyclohexa-l,3-diene is transformed to 1-acetylcyclohexa-1,3-diene and a
mixture of isomeric diacylated cyclohexadienes. 1-Vinylcyclohexene and other
substituted dienes are acylated at the dienic moiety to give the trans-isomers of
the corresponding dienones [ 1531. Carbonylation of a-vinylcinnamic acid in the
presence of nickel cyanide gives a-ketolactone, resulting from a decarboxyla-
tion-double carbonylation reaction [ 1541.
The PTC reaction of fulvenes with CO/MeI gives monoacylated derivatives as
the major products [ 1551. Metal-carbonyl catalyzed reactions of allenes have also
been affected under PTC conditions (eq. (14)). Nickel cyanide catalyzes the re-
giospecific carbonylation of allenes to p,?-unsaturated acids [ 1561 while hydroxy-
ketones are usually the main products when CO*(CO)~ and Me1 are used 11571.
The PTC reaction of allenes with CO in the presence of Mn2(CO)loand Me1
afford (a-a$-unsaturated ketones [ 1581.
R

The PTC carbonylation of Schiff bases affords ketoamides [ 1591. Azadienes

[ 1601 and azobenzenes [ 1611 undergo reductive mono- or diacylation, respec-
tively, with stoichiometric C O ~ ( C Oand
) ~ excess Me1 under PTC conditions.

Oxiranes, Thiiranes, and Azirines

The biphasic double carbonylation of phenyloxirdnes under PT conditions affords

4,5-dihydro-4-phenylfuran-2,3-diones[ 1621. A similar reaction involving 2-
phenylthiirane gives the b-mercapto-substituted acid [ 1631. The PTC reaction
of vinyl epoxides with CO and Me1 in the presence of catalytic amounts
of C O ~ ( C Oand
) ~ TDA-1 affords p-hydroxy acids [ 1641.
966 3.2 Special Catalysts and Processes

The same catalytic pair affects the novel conversion of epoxy alcohols to 2-C-
(2,5-dihydro-2-oxofur-5-yl)lactic acids in moderate yields. This transformation
constitutes the first example of a net triple carbonylation reaction [165]. 2,5-
Dihydro-2-oxo-3-arylfurans(the single carbonylation products) are also formed
as by-products (eq. (15)).

* ' d o ,
0
TDA-l/toluene/l N NaOH, r. t.*
CO/Co2(CO)$Mel
Ar

0q H

COOH
+oAB
(15)
The carbonylation of 2-phenylaziridine under PTC conditions catalyzed by Pdo
complexes affords 2-styrylindole [ 1661.

3.2.4.2.4 Vinylation, Ethynylation, and Allylation

Palladium-catalyzed reactions of organohalides with alkenes have been consid-
erably improved with the application of PTC. This method for C-C bond forma-
tion at an unsubstituted vinylic position (Heck reaction) is based on the cis
addition of an organopalladium complex to the double bond followed by the
cis-elimination of palladium hydride [ 1671. Homogeneous methods for these
reactions have a number of disadvantages such as high temperature, a large
amount of catalyst, etc. Various aryl iodides can be vinylated by a$-unsaturated
esters, ketones and aldehydes under mild conditions using solid/liquid PTC in
the presence of palladium(I1) acetate (eq. (16)) [168]. The reactions occur
regio- and stereoselectively to give mainly P-trans-products. Without a PT
catalyst, the vinylation does not occur at all. Similar reactions involving aryl
iodides and 2-amidoacrylates give rise to aromatic (2)-didehydroamino acid
derivatives (cf. also Section 3.1.6) [169, 1701.

The reaction of vinyl iodides with methyl acrylate, methyl vinyl ketone, and
acrolein affords the corresponding dienoates, dienones, and dienals in excellent
yields (90-97 %) with high stereoselectivity (95-99 %). Trans- and cis-vinyl
halides produce trans,truns- and cis,trans-dienes, respectively [ 17I]. The
described method has also been applied to acetylenic iodides. Practically valuable
enynoates and enynones, having the trans configuration, have been prepared in
fair yield by reacting 1-iodoalkynes with methyl acrylate or methyl vinyl ketone
(eq. (17)) [172]. Recently, the importance of the presence of water for the
efficiency of quaternary ammonium salts in Pd-catalyzed vinylations of organo-
halides has been demonstrated [173].
 3.2.4.2 Homogeneous Transition-Metal Catalyzed Reactions 967

40-60Yo

The coupling of 1-alkynes or w-functionally substituted 1-alkynes with alkenyl

halides in a benzene/aq. NaOH system in the presence of Pd(PPh3)4,CuI, and PT
agent produces the corresponding enynes stereospecifically [ 174, 1751. The PTC
vinylation of alkynes was also used for the preparation of heterocyclic enynes
[176, 1771.
The allylation of terminals alkynes catalyzed by Cu’ salts proceeds smoothly
under solidhquid PTC conditions [178]. More recently, it was shown that the
allylation of alkynes can be effectively carried out under “classical” IiquidAiquid
PTC conditions in the presence of CuCl and quaternary ammonium salt [179].
Palladium catalyzed coupling of arylsulfonyl chlorides with alkyl acrylates,
accompanied by desulfonylation, under solidhquid PTC conditions, gives the cor-
responding (E)-3-aryl-2-propenoates [ 180, 18I]. The cross-coupling of diethyl-
(pyridy1)boranes with vinyl bromides in the presence of a Pdo complex and a
PT catalyst gives alkenylpyridines stereospecifically and with high regioselec-
tivity. Similar reactions involving phenylacetylene afford phenylethynylpyridines
[182].

3.2.4.2.5 Miscellaneous
Isomerization

The isomerization of allylic alcohols to carbonyl compounds is usually carried out

in the presence of transition-metal complexes under rather drastic conditions. The
joint use of PTC and metal-complex catalysis creates a simple, mild, and efficient
method for the isomerization of unsaturated alcohols [ 1831. Allylic alcohols
are converted to ketones in a PT system with a Rh’ complex. An ion-pair
[R4N]+[RhC1J (see Section 3.2.4.2.1) is also effective for the isomerization of
allylic alcohols as well as allylarenes [ 1841. Another example of PTC isomeriza-
tion is the transformation of allylic alcohols, RCH(OH)CH=CH2, to ketones,
RCOCHZCH3 [ 1851.
IrCI3-catalyzed isomerization of 4-allylanisole in a two-phase aqueous/organic
system is accelerated by ,O-CD; the latter enhances the accessibility of the organic
substrate to the aqueous catalyst via inclusion-complex formation [ 1861.

Cyanation of Vinyl and Aryl Halides

The application of PTC in metal catalyzed reactions of vinyl and aryl halides with
alkali-metal cyanides is a convenient and efficient method for the preparation of
968 3.2 Special Catalysts and Processes

the corresponding nitriles. Vinyl halides react with KCN in a solidAiquid system
in the presence of 18-crown-6 and a Pd' complex to give vinyl nitriles in a stereo-
selective manner (eq. (18)) [187]. Without the crown ether, the nitriles are not
formed even under more drastic conditions.

[Rh(C0)2C1]2/Et3N/Pd(PPh&
18-crown-G/KCN/benzene

84-98 %

The PTC synthesis of aryl nitriles by the reaction of aryl halides with NaCN is
effectively catalyzed by a Nio complex [ 1881.

Desulfurization

The possibility of performing metal-catalyzed desulfurization under PTC condi-

tions was first demonstrated for thiobenzophenones. These compounds were
reacted with cyclopentadienylmetal carbonyls in a benzenehq. NaOH system
containing a PT agent [189]. Fulvenes and disulfides are formed in the presence
of iron complexes (cf. Section 3.2.13).
Iron and cobalt carbonyls react with mercaptans under PTC conditions to give
the corresponding hydrocarbons in good yields [ 1901. A benzenehq. HBF, system
has been proposed for the desulfurization of benzylmercaptans with the aid of iron
carbonyl [ 19 I]. Mercaptans ArCH2SH are transformed to methylarenes ArCH3
and sulfides (ArCH,),S upon treatment with Fe3(C0)12.Disulfides (ArCH,S),
and coupling products ArCH2CH2Arare also formed in small amounts. Anionic
hydridocarbonyliron complexes generated in situ are suggested to be responsible
for the desulfurization.

3.2.4.3 Transition-Metal Containing Phase-Transfer

Agents and Their Use in Synthesis
The idea that transition-metal complexes can act as PT agents was presented in
some early studies of metal-complex-catalyzed reactions under PTC conditions.
Lately, several approaches to the design of bifunctional catalysts have been
made. Organometallic complexes capable of effecting phase transfer reactions
were prepared for the first time in 1982 [192, 1931. Tertiary phosphines containing
polyether substituents react with Pd(PhCN),CI2 to afford complexes capable of
catalyzing the reduction of bromobenzene with NaH suspended in toluene.
Phosphine-containing crown ethers, combined with [Rh( 1,5-cycloocta-
diene)C1I2,promote hydrogenation of alkali-metal cinnamates [ 1941. It has been
also demonstrated that (7t-C3H5PdC1)2,in the presence of such crown ethers, cat-
alyzes the reaction of ally1 bromide with powdered NaI or KI in benzene [194].
 3.2.4.4 Conclusions 969

Some porphyrin Mn'" complexes also display bifunctional catalytic properties.

The system consisting of two liquid phases (nonactivated hydrocarbon in organic
solvent and salt NaY (Y = N3, I, Br, C1) aqueous solution) containing oxidant
(Phl=O) and Mn"' tetraphenylporphyrinate (Mn'"(TPP)X, X = C1, OAc) affects
the conversion of a C-H bond in the hydrocarbon to a C-X bond [195]. Alkanes
R-H are transformed to R-X and R-OH catalytically and in fair yield. In a
CH2C12/H20system, Mn"' tetraarylporphyrin, containing a quaternary ammonium
moiety on one of the aromatic rings, in the presence of 4'-(imidazol-l-yl)aceto-
phenone (axial ligand), readily catalyzes the epoxidation of styrene and cyclo-
hexene by NaClO, producing the corresponding oxiranes [ 1961.
Another approach to the design of bifunctional catalysts is based on the as-
sumption that ionic complexes of transition metals can possess unique properties
due to the metal atom, which provides activity in metal-complex catalysis, and the
ionic structure, which is a prerequisite for catalysis of PTC reactions. In fact, cat-
ionic complexes of rhodium, iridium, or iron catalyze typical PTC reactions such
as the exchange of halide in alkyl halides for thiocyanate [197]. The bifunctional
nature of cationic metal complexes was tested in various consecutive reactions
giving high yields. The first reaction was metal-catalyzed and the second PTC-
catalyzed. The reactions were carried out in one pot without isolation of the
first product. The cationic complexes catalyze: the homogeneous hydrogenation
of phenylacetylene to styrene followed by dichlorocarbene addition under PTC
conditions, the homogeneous hydrogenation of cinnamaldehyde to hydrocinna-
maldehyde with subsequent trichloromethyl anion addition to yield P-phenylethyl-
trichloromethylcarbinol, and the hydrosilylation of phenylacetylene with triethyl-
silane followed by PTC reaction of a- and P-silylstyrenes with dichlorocarbene.
The products of both the homogeneous and biphasic reactions are obtained in
high yields. It should be noted however that these complexes are less effective
in PTC reactions than commonly used onium salts since the metal-complex cat-
ions are not lipophilic enough.
Systems containing a transition-metal anion, with a quaternary onium ion as
the cation (e. g., [R,N],+[IrCl,]"), should possess an advantage [ 198-2001. The
bifunctional catalytic properties of such systems were demonstrated in the hydro-
silylation of PhC =CH and subsequent PTC reaction with dichlorocarbene
generated in situ.

3.2.4.4 Conclusions
Scrutiny of the literature data shows that numerous transformations of diverse
organic molecules are readily catalyzed by homogeneous metal complexes in
two-phase systems. The joint use of transition metals and phase-transfer agents
considerably expands the synthetic possibilities of both metal-complex catalysis
and PTC. The combination of these two different types of catalysts in many
cases leads to higher reaction rates, higher product yields, milder conditions,
higher selectivities, and simpler reaction execution and product isolation. Biphasic
reactions in the presence of transition-metal complexes and PT agents have been
970 3.2 Special Catalysts and Processes

intensively studied by a number of research groups. Also, various transformations

of organometallic complexes under PTC conditions have been examined. The
combination of these two fields, in our opinion, can result in further improvement
of known catalytic processes as well as the development of new, highly effective,
catalytic systems for organic synthesis.

References
[l] C. M. Starks, C. L. Liotta, M. Halpern, Phase Transfer Catalysis. Fundamentals,
Applications, and Industrial Perspectives, Chapman and Hall, New York, 1994.
[2] E. V. Dehmlow, S. S. Dehmlow, Phase Transfer Catalysis, 3rd ed., VCH, Weinheim,
1993.
[3] Yu. Goldberg, Phase Transfer Catalysis. Selected Problems and Applications, Gordon
and Breach, Philadelphia, 1992.
[4] H. Alper, Aldrichim. Acta 1991, 24, 3.
[5] J.-F. Petrignani in The Chemistry of the Metal-Carbon Bond, Vol. 5 (Ed.: F. R. Hartley),
John Wiley, New York, 1989, p. 63.
[6] E. S. Core, Platinum Metal Rev. 1990, 34, 2.
[7] T. G. Southern, Polyhedron 1989, 8, 407.
[8] H. Alper, H.-N. Paik, Nouv. J. Chem. 1978, 2, 245.
[9] H. Alper, D. Des Roches, H. Des Abbayes, Angew. Chem., Znt. Ed. Engl. 1977, 16, 41.
[lo] H. Des Abbayes, H. Alper, J. Am. Chem. SOC.1977, 99, 98.
[ l l ] K. Jothimony, S. Vancheesan, J. C. Kuriacose, J. Mol. Catal. 1989, 52, 297.
[12] H. Alper, S. Amaratunga, Tetrahedron Lett. 1980, 21, 2603.
[I31 K. Januszkiewicz, H. Alper, J. Mol. Catal. 1983, 19, 139.
[14] M. Miura, M. Shinohara, M. Nomura, J. Mol. Catal. 1988, 45, 151.
[I51 K. E. Hashem, J.-F. Petrignani, H. Alper, J. Mol. Catal. 1984, 26, 285.
[16] F. Joo, H. Alper, Can. J. Chem. 1985, 63, 1157.
[17] S. Falicki, H. Alper, Organometallics 1988, 7, 2548.
[I81 N. Suzuki, Y. Kaneko, T. Tsukanaka, T. Nomoto, Y. Ayaguchi, Y. Irawa, Tetrahedron
1985, 41, 2387.
[19] D. Villemin, M. Letulle, Synth. Commun. 1989, 19, 283.
[20] R. Bar, Y. Sasson, Tetrahedron Lett. 1981, 22, 1709.
[21] F. Wada, R. Ishihara, Y. Kamohara, T. Matsuda, Bull. Chem. SOC.Jpn. 1979, 52, 2959.
[22] See [3], Chapter 7, pp. 343-354.
[23] H. Alper, J. Heveling, J. Chem. SOC., Chem. Commun. 1983, 365.
[24] V. Galamb, S. C. Shim, F. Sibtain, H. Alper, Isl: J. Chem. 1985, 26, 216.
[25] K. Nozaki, M. Yoshida, H. Takaya, J. Organomet. Chem. 1994, 473, 253.
[26] D. L. Reger, M. M. Habib, Tetrahedron Lett. 1979, 115.
[27] D. L. Reger, M. M. Habib, D. J. Fauth, J. Org. Chem. 1980, 45, 3860.
[28] D. L. Reger, M. M. Habib, J. Mol. Catal. 1980, 7, 365.
[29] K. Yamashita, K. Ohkubo, Nippon Kaguku Kaishi 1984, 505.
[30] J. Blum, I. Amer, A. Zoran, Y. Sasson, Tetrahedron Lett. 1983, 24, 4139.
[31] I. Amer, H. Amer, J. Blum, J. Mol. Catal. 1986, 34, 221.
[32] I. Amer, H. Amer, R. Ascher, J. Blum, Y. Sasson, K. P. C. Vollhardt, J. Mol. Catal. 1987,
39, 185.
[33] J. Azran, 0. Buchman, I. Amer, J. Blum, J. Mol. Catal. 1986, 34, 229.
[34] I. Amer, T. Bravdo, J. Blum, K. P. C. Vollhardt, Tetrahedron Lett. 1987, 28, 1321.
 References 97 1

[35] J. Blum, I. Amer, K. P. C. Vollhardt, H. Schwartz, G. Hohne, J. Org. Chem. 1987,

52, 2804.
[36] J. Blum, I. Pri-Bar, H. Alper, J. Mol. Catal. 1986, 37, 359.
[37] J. Blum, G. Bitan, S. Marx, K. P. C. Vollhardt, J. Mol. Catal. 1991, 66, 313.
[38] A. Rosenfeld, D. Avnir, J. Blum, J. Chem. SOC.,Chem. Commun. 1993, 583.
[39] 0. Arrad, Y. Sasson, J. Org. Chem. 1989, 54, 4993.
[40] J. Blum, Izv. Akad. Nauk., Ser Khim. 1993, 1697.
[41] K. R. Januszkiewicz, H. Alper, Organometallics 1983, 2, 1055.
[42] K. R. Januszkiewicz, H. Alper, Can. J. Chem. 1984, 62, 1031.
[43] V. V. Grushin, H. Alper, Organometallics 1991, 10, 831.
[44] See [3], Chapter 7, Section 7.2, p. 359.
[45] J.-T. Lee, H. Alper, J. Org. Chem. 1990, 55, 1854.
[46] J.-T. Lee, H. Alper, Tetrahedron Lett. 1990, 31, 1941.
[47] V. V. Grushin, H. Alper, Chem. Rev. 1994, 94, 1047.
[48] V. V. Grushin, H. Alper, Orgunometallics 1991, 10, 1620.
[49] C. A. Marques, M. Selva, P. Tundo, J. Org. Chem. 1993, 58, 5256.
[50] C. A. Marques, M. Selva, P. Tundo, J. Chem. SOC.,Perkin Trans. I , 1993, 529.
[51] C. A. Marques, M. Selva, P. Tundo, J. Org. Chem. 1994, 59, 3830.
[52] P. Barnfield, P. M. Quan, GB 1.458.633 (1976); Chem. Abstx 1976, 84, 1643711.
[53] E. Paetzold, G. Oehme, J. Prakt. Chem. 1993, 335, 181.
[54] S . Shimizu, Y. Sasaki, C. Hirai, Bull. Chem. SOC.Jpn. 1990, 63, 176.
[55] K. Jothimony, S. Vancheesan, J. C. Kuriacose, J. Mol. Catal. 1985, 32, 11.
[56] K. Jothimony, S. Vancheesan, J. Mol. Catal. 1989, 52, 301.
[57] Yu. Goldberg, H. Alper, J. Mol. Catal. 1994, 92, 149.
[58] C. J. Longley, T. J. Goodwin, G. Wilkinson, Polyhedron 1986, 34, 221.
[59] Continental Oil Co (C. M. Starks), SA 7U01.495 (1971); GB 1.324.763 (1973); Chem.
Abstl: 1972, 76, 1531918.
[60] G. Barak, Y. Sasson, J. Chem. SOC., Chem. Commun. 1987, 1266.
[61] C. Venturello, E. Alneri, M. Ricci, J. Org. Chem. 1983, 48, 3831.
[62] C. Venturello, R. D’Aloisio, J. Org. Chem. 1988, 53, 1553.
[63] C. Venturello, M. Gambaro, Synthesis 1989, 295.
[64] X. Jian, A. S. Hay, J. Polym. Sci. Part C, Polym. Lett. 1990, 28, 285.
[65] Y. Fort, A. Olszewski-Ortar, P. Caubere, Tetrahedron 1992, 48, 5099.
[66] F. P. Ballisteri, S. Failla, G. A. Tomaselli, J. Org. Chem. 1988, 53, 830.
[67] Y. Matoba, H. Inoue, J. Akagi, T. Okabayashi, Y. Ishii, M. Ogawa, Synth. Commun.
1984, 15, 865.
[68] Y. Ishii, K. Yamawaki, T. Ura, H. Yamada, T. Yoshida, M. Ogawa, J. Org. Chem. 1988,
53, 3587.
[69] Y. Ishii, K. Yamawaki, T. Yoshida, T. Ura, M. Ogawa, J. Org. Chem. 1987, 52, 1868.
[70] F. P. Ballisteri, S. Failla, E. Spina, G. A. Tomaselli, J. Org. Chem. 1989, 54, 947.
[71] Y. Ishii, Y. Sakata, J. Org. Chem. 1990, 55, 5545.
[72] S. Sakaguchi, S. Watase, Y. Katayama, Y. Sakata, Y. Nishiyama, Y. Ishii, J. Org. Chem.
1994, 59, 5681.
[73] J. Prandi, H. B. Kagan, H. Mimoun, Tetruhedron Lett. 1986, 27, 2617.
[74] D. Mansuy, Pure Appl. Chem. 1990, 62, 741.
[75] B. Meunier, E. Guilmet, M.-E. De Carvalho, R. Roiblanc, J. Am. Chem. SOC.1984, 106,
6668.
[76] E. Guilmet, B. Meunier, Tetrahedron Lett. 1982, 23, 2449.
[77] S. Banfi, F. Montanari, S. Quici, J. Org. Chem. 1989, 54, 1850.
[78] S. Takagi, E. Takahashi, T. K. Miaymoto, Y. Sasaki, Chem. Lett. 1986, 1275.
[79] B. Meunier, M.-E. De Carvalho, A. Robert, J. Mol. Catal. 1987, 41, 185.
972 3.2 Special Catalysts and Processes

[80] E. Larsen, K. A. Jorgensen, Acta Chem. Scand. 1989, 43, 259.

[81] H. Yoon, C. J. Burrows, J. Am. Chem. Soc. 1988, 110, 4087.
[82] T. R. Wagler, C. J. Burrows, Tetrahedron Lett. 1988, 29, 5091.
[83] H. Yoon, T. R. Wagler, K. J. O’Connor, C. J. Burrows, J. Am. Chem. Soc. 1990,
112, 4568.
[84] K. Januszkiewicz, H. Apler, Tetrahedron Lett. 1983, 24, 5159.
[85] K. Januszkiewicz, H. Alper, Tetrahedron Lett. 1983, 24, 5163.
[86] A. Harada, Y. Hu, S. Takahashi, Chem. Lett. 1986, 2083.
[87] H. A. Zahalka, K. Januszkiewicz, H. Alper, J. Mol. Catal. 1986, 35, 249.
[88] I. Tabushi, N. Koga, Tetrahedron Lett. 1979, 3681.
[89] S. Kanemoto, H. Tomioka, K. Oshima, H. Nozaki, Bull. Chem. Soc. Jpn. 1986,59, 105.
[90] Y. Yamamoto, H. Suzuki, Y. Moro-oka, Tetrahedron Lett. 1985, 26, 2107.
[91] Y. Sasson, H. Wiener, S. Bashir, J. Chem. Soc., Chem. Commun. 1987, 1574.
[92] K. S. Kim, S. J. Kim, Y. H. Song, C. S. Hahn, Synthesis 1987, 1017.
[93] G. Barak, J. Dakka, Y. Sasson, J. Org. Chem. 1988, 53, 3553.
[94] 0. Bortolini, V. Conte, F. Di Furia, G. Modena, J. Org. Chem. 1986, 51, 2661.
[95] H. Alper, K. Hashem, S. Gambarotta, Can. J. Chem. 1980, 58, 1599.
[96] B. M. Choudary, N. P. Reddy, M. L. Kantam, Z. Jamil, Tetrahedron Lett. 1985,26,6257.
[97] L. Feldberg, Y. Sasson, J. Chem. Soc., Chem. Commun. 1994, 1807.
[98] 0. Bortolini, F. Di Furia, G. Modena, R. Seraglia, J. Org. Chem. 1985, 50, 2688.
[99] F. Gasparini, M. Giovannoli, D. Misiti, Tetrahedron 1983, 39, 3181.
[I001 F. Gasparini, M. Giovannoli, D. Misiti, G. Natile, G. Palmieri, J. Org. Chem. 1990,
55, 1323.
[ l o l l B. De Poorter, M. Ricci, 0. Bortolini, B. Meunier, J. Mol. Catal. 1985, 31, 221.
[I021 B. De Poorter, M. Ricci, B. Meunier, Tetrahedron Lett. 1985, 26, 4459.
[lo31 C. Querci, M. Ricci, Tetrahedron Lett. 1990, 31, 1779.
[I041 J. P. Collman, H. Tanaka, R. T. Hembre, J. I. Brauman, J. Am. Chem. Soc. 1990, 112,
3689.
[lo51 K. Osowska,-Pacewicka, H. Alper, J. Org. Chem. 1988, 53, 808.
[lo61 K. Hotta, S. Tamagaki, Y. Suzuki, W. Tagaki, Chem. Lett. 1981, 789.
[107] E. A. Karakhanov, S. Yu. Narin, T. Yu. Filippova, A. G. Dedov, Dokl. Akad. NaukSSSR
1987, 292, 1387.
[108] Y. Sasson, G. D. Zappi, R. Neumann, J. Org. Chem. 1986, 51, 2880.
[lo91 G. Barak, Y. Sasson, J. Chem. Soc. Chem. Commun. 1988, 637.
[I101 L. Cassar, M. Foa, A. Gardano, J. Organomet. Chem. 1976, 121, C55.
[ 1111 H. Alper, H. Des Abbayes, J. Organomet. Chem. 1977, 134, C1 1.
[ 1121 L. Cassar, M. Foa, J. Organomet. Chem. 1977, 134, C15.
[I131 H. Des Abbayes, A. Buloup, J. Organomet. Chem. 1980, 198, C36.
[114] H. Des Abbayes, A. Buloup, G. Tanguy, Organometallics 1983, 2, 1730.
[I151 H. Des Abbayes, A. Buloup, J. Chem. Soc., Chem. Commun. 1978, 1090.
[116] F. Francalanci, M. Foa, J. Organomet. Chem. 1982, 232, 59.
[117] S . Gambarotta, H. Alper, J. Organomet. Chem. 1981, 212, C23.
[I181 S . C. Shim, C. H. Doh, W. H. Park, Y. G. Kwon, J. Organomet. Chem. 1990,382,419.
[I191 J.-J. Brunet, C. Sidot, P. Caubere, J. Org. Chem. 1983, 48, 1166.
[120] J.-J. Brunet, C. Sidot, P. Caubere, J. Org. Chem. 1983, 48, 1919.
[I211 P. Caubere, Pure Appl. Chem. 1985, 57, 1875.
[122] M. Miura, F. Akase, M. Shinohara, M. Nomura, J. Chem. Soc., Perkin Trans. I 1987,
1021.
I1231 Y. Kimura, Y. Tomita, S. Nakanishi, Y. Otsuji, Chem. Lett. 1979, 321.
[I241 G. Tanguy, B. Weinberger, H. Des Abbayes, Tetrahedron Lett. 1984, 25, 5529.
[I251 P. Laurent, G. Tanguy, H. Des Abbayes, J. Chem. Soc., Chem. Commun. 1986, 1754.
 References 973

[126] G. C. Tustin, R. T. Hembre, J. Org. Chem. 1984, 49, 1761.

[127] H. Des Abbayes, J.-C. Clement, P. Laurent, G. Tanguy, N. Thilmont, Organornetallics
1988, 7, 2293.
[128] J.-J. Brunet, M. Taillefer, J. Organomet. Chem. 1990, 384, 193.
[129] H. Alper, K. Hachem, J. Heveling, Organornetallics 1982, I , 775.
[I301 S. Amaratunga, H. Alper, J. Organomet. Chem. 1995, 488, 25.
[131] S. R. Adapa, C. S. Prasad, J. Chem. Soc., Chern. Commun. 1989, 1706.
[132] N. P. Reddy, M. L. Kantam, B. M. Choudry, Indian J. Chem. 1989, 28B, 105.
[133] V. V. Grushin, H. Alper, Organometallics 1993, 12, 3846.
[134] V. V. Grushin, H. Alper, J. Chern. SOC.Chem. Commun. 1992, 611.
[135] V. Galamb, M. Gopal, H. Alper, Organometallics 1983, 2, 801.
[136] H. Arzoumanian, M. Choukrad, D. Nuel, J. Mol. Catal. 1993, 85, 287.
[137] M. Foa, L. Cassar, Gazz. Chim. Ital. 1979, 109, 619.
[138] F. Joo, H. Alper, Organometallics 1985, 4, 1775.
[139] I. Amer, H. Alper, J. Org. Chem. 1988, 53, 5147.
[140] I. Amer, H. Alper, J. Am. Chem. Soc. 1989, 111, 927.
[141] H. Alper, I. Amer, G. Vasapollo, Tetrahedron Lett. 1989, 30, 2615.
[142] H. Alper, G. Vasapollo, Tetrahedron Lett. 1989, 30, 2617.
[143] K. Younis, I. Amer, Organornetallics 1994, 13, 3120.
[144] H. Arzoumanian, F. Cochini, D. Nuel, J. F. Petrignani, N. Rosas, Organometallics 1992,
11, 493.
[145] H. Arzoumanian, F. Conchini, D. Nuel, N. Rosas, Organornetallics 1993, 12, 870.
[146] V. V. Grushin, H. Alper, Tetrahedron Lett. 1991, 32, 3349.
[147] J.-T. Lee, H. Alper, Organornetallics 1990, 9, 3064.
[148] H. Alper, J. K. Currie, H. Des Abbayes, J. Chem. Soc. Chern. Commun., 1978, 311.
[ 1491 H. Arzoumanian, J.-F. Petrignani, Tetrahedron Lett. 1986, 27, 5979.
[150] H. Alper, J.-F. Petrignani, J. Chem. SOC., Chem. Commun. 1983, 1154.
[151] I. Amer, H. Alper, J. Organornet. Chem. 1990, 383, 573.
[ 1521 N. Satyanarayana, H. Alper, Organometallics 1991, 10, 804.
[153] H. Alper, J. K. Currie, Tetrahedron. Lett. 1979, 2665.
[154] I. Amer, H. Alper, J. Mol. Catal. 1993, 85, L117.
[155] H. Alper, D. E. Laycock, Tetrahedron Lett. 1981, 22, 33.
[ 1561 N. Satyanarayana, H. Alper, Organometallics 1990, 9, 284.
[157] S. Gambarotta, H. Alper, J. Org. Chem. 1981, 46, 2142.
[158] N. Satyanarayana, H. Alper, J. Chem. SOC., Chem. Cornmun. 1991, 8.
[159] G. Vasapollo, H. Alper, Tetrahedron Lett. 1988, 29, 5113.
[ 1601 H. Alper, S. Amaratunga, Can. J. Chem. 1983, 61, 1309.
[I611 D. Roberto, H. Alper, Organometallics 1990, 9, 1245.
[ 1621 H. Alper, H. Arzoumanian, J.-F. Petrignani, M. Saldana-Maldonado, J. Chern. SOC.,
Chem. Commun. 1985, 340.
[I631 S. Calet, H. Alper, J.-F. Petrignani, H. Arzoumanian, Organometallics 1987, 6, 1625.
[164] H. Alper, S. Calet, Tetrahedron Lett. 1988, 29, 1763.
[I651 H. Alper, A. Eisenstat, N. Satyanarayana, J. Am. Chem. SOC.1990, 112, 7060.
[I661 H. Alper, C. P. Mahatantila, Heterocycles 1983, 20, 2025.
[167] R. F. Heck, Palladium Reagents in Organic Synthesis, Academic Press, New York,
1985.
[168] T. Jeffery, J. Chem. Soc., Chem. Commun. 1984, 1287.
[169] A.-S. Carlstrom, T. Frejd, Synthesis 1989, 414.
[170] A.-S. Carlstrom, T. Frejd, Acta Chem. Scand. 1992, 46, 163.
[171] T. Jeffery, Tetrahedron Lett. 1985, 26, 2667.
[172] T. Jeffery, Synthesis 1987, 70.
974 3.2 Special Catalysts and Processes

[173] T. Jeffery, Tetrahedron Lett. 1994, 35, 3051.

[174] R. Rossi, A. Carpita, Tetrahedron 1983, 39, 287.
[175] R. Rossi, A. Carpita, M. G. Quirici, M. L. Gaudenzi, Tetrahedron 1982, 38, 631.
[I761 A. Carpita, A. Lezzi, R. Rossi, F. Marchetti, S. Merlino, Tetrahedron 1985, 41, 621.
[177] M. D’Auria, A. De Mico, F. D’Onofrio, G. Piancatelli, Gazz. Chim. Ztal. 1986,
116, 747.
[178] T. Jeffery, Tetrahedron Lett. 1989, 30, 2225.
[I791 V. V. Gmshin, H. Alper, J. Org. Chem. 1992, 57, 2188.
[180] M. Miura, H. Hashimoto, K. Itoh, M. Nomura, Tetrahedron Lett. 1989, 30, 975.
[ 1811 M. Miura, H. Hashimoto, K. Itoh, M. Nomura, J. Chem. SOC., Perkin Trans. I 1990,
2207.
[I821 M. Ishikura, M. Kamada, T. Ohta, M. Terashima, Heterocycles 1984, 22, 2475.
[183] H. Alper, K. Hashem, J. Org. Chem. 1980, 45, 2269.
[184] Y. Sasson, A. Zoran, J. Blum, J. Mol. Catal. 1981, 45, 2269.
[185] Y. Sasson, A. Zoran, J. Blum, J. Mol. Catal. 1979, 6 , 289.
[186] G. Barak, Y. Sasson, Bull. Chem. SOC. FI: 1988, 584.
[ 1871 K. Yamamura, S.-I. Murahashi, Tetrahedron Lett. 1977, 4429.
[I881 L. Cassar, M. Foa, F. Montanari, G. P. Marinelli, J. Organomet. Chem. 1979, 173, 335.
[189] H. Alper, H.-N. Paik, J. Am. Chem. SOC.1978, 100, 508.
[I901 H. Alper, F. Sibtain, J. Heveling, Tetrahedron Lett. 1983, 24, 5329.
[191] H. Alper, F. Sibtain, J. Organomet. Chem. 1985, 285, 225.
[192] T. Okano, M. Yamamoto, T. Noguchi, H. Konishi, J. Kiji, Chem. Lett. 1982, 977.
[193] T. Okano, M. Iwahara, T. Suzuki, H. Konishi, J. Kiji, Chem. Lett. 1986, 1467.
I1941 T. Okano, M. Iwahara, H. Konishi, J. Kiji, J. Organomet. Chem. 1988, 346, 267.
[195] C. L. Hill, J. A. Smegal, T. J. Henly, J. Org. Chem. 1983, 48, 3277.
[I961 S. Takagi, T. K. Miyamoto, Y. Sasaki, Bull. Chem. SOC.Jpn. 1986, 59, 2371.
[197] Yu. Goldberg, I. Iovel, M. Shymanska, J. Chem. SOC.,Chem. Commun. 1986, 286.
[198] I. Iovel, Yu. Goldberg, M. Shymanska, E. Lukevics, J. Chem. SOC.,Chem. Commun.
1987, 31.
[I991 I. Iovel, Yu. Goldberg, M. Shymanska, E. Lukevics, Organometallics 1987, 6, 1410.
[200] E. Liepinsh, Yu. Goldberg, I. Iovel, E. Lukevics, J. Organomet. Chem. 1987, 335, 301.

3.2.5 Rare Earth Metals in Homogeneous Catalysis

Reiner Anwander

3.2.5.1 Introduction
Catalytic activity of rare earth elements (i.e., lanthanides, symbol Ln) in homoge-
neous catalysis was mentioned as early as 1922 when CeCI, was tested as a “true
catalyst” for the preparation of diethylacetal from ethanol and acetaldehyde [ 11.
Solutions of inorganic Ln”’ salts were subsequently reported to catalyze the hydro-
lysis of carbon and phosphorous acid esters [2], the decarboxylation of acids [ 3 ] ,
and the formation of 4-substituted 2,6-dimethylpyrimidines from acetonitrile and
secondary amines [4]. In the meantime, the efficiency of rare earth metals in
heterogeneous catalysis, e. g., as promoters in lanthanide (element mixtures)-
 3.2.5.1 Introduction 975

exchanged Y-zeolites for catalytic fluid cracking, or their addition to ceramic

post-combustion catalysts for automobiles, became well established [5].
Significant research activities on organometallic reagents containing lantha-
nides developed in the early 1960s, since the rare earth market allowed their
abundant availability in high purity and at an affordable price [6]. During this
period, the rare earth elements were explored as multicomponent coordination
catalysts in the stereospecific polymerization of conjugated dienes [7]. Pathfind-
ing with respect to the utilization of organolanthanides in homogeneous catalysis
proved the activity of “Cp,LnR’- and ‘‘Er2(C6Hlo)s”-type complexes in ethylene
polymerization [8] and in the hydrogenation of alkynes and olefins [9], respec-
tively. The discovery that lanthanide shift reagents derived from fluorinated B-
diketonates effect the Lewis acid-catalyzed Diels-Alder dimerization was an-
other milestone [ 101.
Meanwhile, organolanthanide complexes boosted the field of organic synthesis
as highly selective catalysts, especially with respect to fine chemicals [ 11-14]. Re-
ports accumulate where organic substrates seem to discriminate not only between
ligand environments but also between single lanthanide elements. Successful ex-
planations of these phenomena are based on the systematic investigation and char-
acterization of organolanthanide compounds which reveal significant changes in
structural and reactive chemistry by passing the “17-series’’ [ 151. This review
will focus on the topic “stereoselective catalysis by single-component Ln“’ sys-
tems” as outlined in Figure 1. Recently, complexes derived from weakly coordi-
nated anions (“superacids”) which, so to speak, “link” the groups of inorganic [ 161
and organometallic reagents attracted considerable attention as reusable catalysts
in many carbon-carbon bond-forming reactions [ 171. Patent literature is not cited
here.

Lanthanide Precatalysts

,------------
L _ _ _ _ _ _ _ _ _ _ _ _

strict I extendef extended strict

I1
r--------

with carbon no Ln-C linkage with Ln-C linkage

with C-C linkage with C-C linkage
e.g. LnCp3
e.g. Ln(CN)3 e.g. L ~ ( O A C ) ~ L~CP*~
Ln(OTf)3 Ln(f~d)~ Cp2LnR
Ln(OPf)3 Ln(hf~)~ (R = H, CH(SiMe3)*
Ln(NTf2)3 Ln(OR)3 NRz, CI)
Ln(BNP)3 Ln12(0R) [CpLn(OAr)(H)Iz
Ln(NR2)3 LiLn(C3H&
RLnl

Figure 1. Classification of homogeneous single-component catalysts of the lanthanides.

976 3.2 Special Catalysts and Processes

3.2.5.2 Catalytic Potential

Rare earth cations appear to be an “extended playground of Lewis acidity, electro-
philicity, oxophilicity and redox stability” to organic substrates. The element
series represents the largest subgroup in the periodic table and offers a unique,
gradual variation of those properties which provide the driving force for various
catalytic processes (Figure 2) [IS-221. The cation size determines both the
complex geometry and availability of flexiblehdditional coordination sites.
Lanthanide cations are considered as hard acids in the HSAB classification of
Pearson, being located between Sf’ and Ti’”. Sc”’, as by far the smallest Ln”’
cation, is located in a “pole position” with respect to various factors. The catalytic
reactivity is further directed by the kinetic lability of the Ln-X bond which
even for the thermodynamically very stable Ln-O(0R) bond reaches a high
level as proven, e. g., in alcohol exchange reactions [23]. Lanthanide elements
in their “hot oxidations states” [24] also initiate substrate transformations,
however, which as a rule implies switching to the more stable, catalytically acting
Ln”’ species [25]. Therefore, due to the inaccessibility of oxidative addition/
reductive elimination sequences, catalysis via unconventional electrophilic path-
ways mainly contributes to the difference in behavior between the f-elements
and d-elements.

Ln4+[Eo (M4+/M3+),V] - 1.74 3.2

Ln3+[I 81

Ln2+[Eo(M2+/M3’), V] - -1.55 -0.36 -2.1 -1.15

Cation Size (A)”) pol 0 . 7 4 5 a1.0321.01 7 10 . 9 3 8 7 0.861

Lewis Acidity
( ~ n ~relative)
+,
r]
Oxophilicity [21]
[D,(LnO), (k5 kcalmol-’)I
Electronegativity[22)
(Pauling)
II 165 170 190 188

1.3 1.2 1.1 1.1

D 167 - 136 112 170 144 122 95 159

1 .I

Figure 2. Trends within intrinsic properties of Ln”’ cations.

a) Effective ionic radii for six-coordination.
 3.2.5.3 Precatalysts 977

Organolanthanide chemistry means ligand-dependent chemistry. The reactivity

of the considerably ionic organolanthanide complexes is closely related to the
nature (type, size, basicity, capability of ligand functionalities (hardkoft)) of the
ligand, which directly affects properties such as cation size and Lewis acidity.
A fruitful Ln-metavligand synergism implies applications in ligand-directed
and -enhanced selective catalysis [26]. In addition, interaction of the oxophilic
lanthanide center with the substrate can be an important factor to govern
chemo-, regio-, and stereoselectivities.
As a result of these intrinsic properties of the lanthanide elements and the
specific metal/ligand interplay, ligand exchange and insertion reactions rule the
mechanistic scenarios of lanthanide(II1)-catalyzed transformations.

3.2.5.3 Precatalysts
Ligand design for lanthanide precatalysts gradually attains the high level of vari-
ety and sophistication evidenced by d-transition metals [27]. Adaptation of the
prevailing precatalyst types (cyclopentadienyl-, alkoxide-, p-diketonate-based)
to the requirements of highly enantioselective catalysis is represented by Struc-
tures 1-3.

1 t

‘El*

(+)momenthy1 (a) (-)-menthy1 (b)

1, [Me2Si(CSMe,)(C~HpR’)1LnN(SiMe3)2 2, Na3La[(S)-BINOL)lp6THF.H20 3,Eu(hfc)p

Bulky ligands accomplish the desired, well-defined monolanthanide precatalyst

species and their fine tuning directly affects the reactivity, as impressively demon-
strated by tied-back cyclopentadienyl complexes and even water-stable BINOL
systems. Simultaneously, strongly chelating ligands provide a sterically rigid
ligand frame (“spectator area”) which is a prerequisite for induction of asymmetry
at the lanthanide center.
978 3.2 Special Catalysts and Processes

3.2.5.4 Carbon-Carbon Bond-Forming Reactions

3.2.5.4.1 Polymerization Reactions

Since the first reports on the property of alkyl-bridged cyclopentadienyl com-
plexes of type [L~(CPR’)~R’’]~ (R’ = H, Me, Et, SiMe,; R” = Me, n-Bu,
A1Me4) to act as initiators for olefin polymerization [8] and the fact that such a
single-component system can afford “polymerization at an astonishing rate”
((Cp*,LuMe),: > 115 g mmol-’ min-’ (kg/cm2 of C2H4)-’,50-80 “C in cyclohex-
ane) [28,29], the field of olefin transformation has experienced an immense boom
(vide infru). The suitability of this class of organometallic compounds has been
proved as excellent models for clarifying the active sites of a Ziegler-Natta
catalyst by emulation of the major initiation, propagation, and termination steps
which revealed key features such as insertion, P-hydrogen elimination, and /3-
alkyl elimination [28, 291. Detailed studies on the polymerizationbehavior also
provided the first hints to “Ln-C(-H)”-induced CH activation reactions of olefins
(termination by CH activation [28, 291, a-bond metathesis [30]), arenes, and even
alkanes. Moreover, investigations exploiting deuterium isotopic perturbation of
the stereochemistry propose that a-C-H agostic interactions assist chain pro-
pagation (transition state) [30], while p-C-H interactions retard ethylene insertion
(ground state) [3 13. Although “agostic bonding”, which was originally proposed
for the formation of two-electron three-center bonds of type C-H+M [32], is
weak and usually not observed in solution [33], it can have significant impli-
cations for the molecular and electronic structure and hence reactivity of the
molecule. Y1“ pentenyl chelate complexes serve as excellent models for the
proposed do metal-alkyl-alkene intermediate in Ziegler-Natta polymerization
reactions, e. g., for Cp*,Y [q1,q2-CH2CH2C(CH3)2CH=CH2] an upper limit of
the intermolecular alkene binding energy was estimated as 10.4 kcal mol-’ on
the basis of low-temperature NMR spectroscopy [34].
Various sterically unsaturated lanthanide complexes are active olefin polymer-
ization precatalysts and it is far beyond the scope of this section to name every
precatalyst. Rather, the exceptional features of a group of structurally character-
ized precatalysts which were originally designed for ethylene and propylene
polymerization are emphasized (Structures 4-19; e. g., 4(Nd;H)/THF means
Cp,*NdH(THF) [29, 351. Monomers such as CO, CO,, and RC=N usually
“deactivate” this type of precatalyst by formation of strong Ln-O(N) linkages.

a-Olefin Polymerization (Oligomerization)

Hydride-based precatalysts (R = H) showed the highest initiation rates in a-ole-

fin polymerization (Table 1, see p. 980) and this efficiency was later often
assigned to the in situ formation of terminal “Ln-H” moieties. For ~ ( S Cit)
was shown that the order of decreasing rate of ethylene insertion is Sc-H 9
Sc-CH2(CH2),CH3 (n 2 2) 2 Sc-CH2CH2CH3 > Sc-CH3 > Sc-CH2CH3 >
 3.2.5.4 Curbon-Curbon Bond-Forming Reactions 979

Ln-R

Me3Si
4 5 6 7

9 10 11

12 13 14 15

I
R’ DO
g
0
RE

16 17 18 19

Sc-C6H5 [3 I]. Appropriate metavligand constellation enhanced the initially

reported activities (3 g mmol-’ bar-’ min-I; M , < 14000; polydispersity, PDI
(= MJM,) = 1.5-2.5) as high as 3040 g mmol-’ bar-’ min-’ [36, 371. The
most striking feature of the “best” ethylene polymerization catalysts is the for-
mation of high-molecular-weight polymers (up to M , = 676 X lo3) along with
extremely narrow polydispersities (PDI = 1.3-1.9).
A major disadvantage of the highly reactive ethylene polymerization catalyst 4
was the decreased turnover number and decreased efficiency at prolonged reaction
Table 1. Ethylene versus propylene polymerization by selected organolanthanide(II1) initiators (compare with Structures 4-19).")
Type Ethylene polymerization Propylene polymerization (oligomerization) Ref.
(R = H)
TOF = 1800 S-', M , = 676 000,PDI = 2.03 Formation of Cp*,La(q3-C3H5)"
TOF = 95 S-I, M, = 361 000,PDI = 1.68 Formation of Cp*,Lu(y3-C3H5)"
True living polymerization system Formation of C ~ * , S C ( C ~ H , ) ~
TOF = 1.6 S-' (dl Complex product mixture at 66 "C with up to C2,-oligomersg'
Rapid formation of polyethylene Catalytic dimerization (head-to-tail) at 80 "C
Rapid formation of polyethylene Iso-specific polymerization (97.0 % mmmm), M , = 4200,
PDI = 2.32, T,,, = 157°C
Formation of Ln(p-Et2SiCpCp*),(lr-H)(p-CH2CH3)LnFormation of Ln(lr-Et2SiCpCp*),(lr-H)(lr-C3H7)Ln'
Rapid formation of polyethylene Atactic polymerization (head-to-tail), M , = 9600, PDI = 1.8
1.3 X 10-~3
g polyethylene mmol-' bar-' min-' -

M , = 39 350, PDI = 5.7, T,,, = 127.6"C Formation of trans- [Cp*Y (OAr)],(LI-H)(LI-C3H7)

Formation of [DADMB1Y(C2Hs)(THF)",o -

a) At ambient temperature.
b, R' = t-Bu, Do = PMe3.
R' = t-Bu, DO = THE
dl Precatalyst solubility problems; Ln = Nd.
DADMB = 2,2'-bis((terr-butyldimethylsilyl)amido)-6,6'-dimethylbiphenyl.
See Section 3.2.5.6.
Ln = Lu.
 3.2.5.4 Carbon-Carbon Bond-Forming Reactions 98 1

times. Longer catalyst lifetimes, although with only one-tenth of the reactivity,
were reported for neodymium catalysts prepared by the simple addition of mag-
nesium alkyls to Cp*,NdCl,Li(OEt,), [38].
Oligomerization of propene is sufficiently slowed down to allow even the quan-
titative study of stepwise insertion of the olefin [31]. The formation of stable r3-
bonded allyl complexes, e. g., Cp*,Nd($-C3HS) [36], counteracts the polymeriza-
tion of propene. Examination of various ansa-scandocene and ansa-yttrocene allyl
complexes provided mechanistic details of their fluxional behavior [39]. The
barriers of (r3-C3Hs)e ($-C3H5) interconversion, which depend on metal size
and ligand type, act as an indicator of the olefin binding energy to do metallocenes.
Utilizing 4(Lu;Me) as a precatalyst provided the first oligomerizations (60 psi pro-
pene in cyclohexane) with oligomers up to at least CZ4[40]. rac-7(H) yields a high
degree of isotacticity for polypropene [4 11. Brintzinger-type, C,-symmetric in-
denyl-derived ansa-lanthanidocene complexes such as rac-lO(N(SiHMe,),)
were obtained according to a novel silylamine elimination reaction utilizing
complexes Ln[N(SiHMe,),I3(THF). as synthetic precursors [42]. In contrast to
routinely employed salt metathesis transformations, this synthetic route excludes
ate complex formation and alkali metal salt contamination, which are known to
markedly affect the stereoselectivity of polymerization reactions. In the presence
of small ligands R, e. g., hydride, “chelating” ansa-lanthanidocene complexes are
often unstable with respect to ligand redistribution, affording “flyover” dimers of
type 8. These complexes can lead to stable monoinsertion products with ethylene
(Table 1) [43].
Amide (16) and alkoxide (17) co-ligands formed a “next-generation” ligand set
which should render the metal more Lewis acidic and more electron-deficient. The
linked cyclopentadienyl amide ligand additionally increases the bite angles by
approximately 20 O compared with the classic 4-type. 16 (Sc; H)/PMe3 exhibits
a single-component catalyst capable of oligomerization of a-olefins such as
propene, 1-butene, and 1-pentene [44]. However, chain propagation occurs rather
slowly with > 99 % “head-to-tail” coupling to afford linear atactic polymers. The
16(Y,H)/THF derivative polymerizes ethylene with moderate activity, while its
1-hexene monoinsertion product initiates the polymerization of styrene to give
atactic polystyrenes with low polydispersities (PDI = 1.10-1.23) and microstruc-
tures enriched in syndiotacticity (IT = 70 %) [45]. Lanthanidocene complexes
[(t-BuCp),Ln(p-Me)], initiate the polymerization of styrene at 70 “C according
to a radical initiation mechanism [46]. Complexes Sm[N(SiMe3)2]2(THF)2,
Srn[CH(SiMe3),l3, and Cp*La[CH(SiMe,),],(THF) also produce atactic polysty-
rene at 50 “C ( M , = (1.5-1.8) X lo4, PDI = 1.5-1.8) [47]. Under high pressure
(750 MPa) divalent organolanthanide complexes of type 18(ER = OC6H2t-Bu2-
2,6-Me-4) produce high-molecular-weight polystyrene ( M , = 23 X lo4, PDI =
2.92) even at ambient temperature [48]. For comparison, samarocene 13 forms
a stable oxidation product with styrene (eq. (1)) [49].
982 3.2 Special Catalysts and Processes

Complex 17(H) does not polymerize propene; instead, polymerization of higher

a-olefins and cyclopolymerization of 1,5-hexadiene were achieved [50]. Type
7(H) and 16(Sc;H)/PMe3also initiate polymerization of higher a-olefins. N-ligated
"post-metallocene" hydride complexes derived from bis(trimethy1)benzamidinate
[5 11 and tris(3,5-dimethyl-l -pyrazolyl)borohydride ligands [52] display catalyti-
cally active systems for ethylene polymerization whilst complex 19(Y;H)/THF
gives a monoinsertion product with ethylene or 1-hexene [53]. SmCp*, (12) poly-
merizes ethylene at 344 kPa in toluene to high-molecular-weight polyethylene
[54]. The catalytic activity of this sterically crowded molecule was unexpected
since it contains none of the usual hydride, alkyl, or Sm"-initiating sites (vide
infra).The most likely route is via the q'-C5Me5intermediate shown in Scheme 1.

\
12

Scheme 1. Proposed initiation mechanism for ethylene polymerization by complex 12.

Divalent samarocene complexes also show unique reactivity toward a-olefins

[55]. Bis-Cp* complexes of type 13 display high polymerization activity toward
ethylene, but yield rather low molecular weights (M, < 25 000) [56]. The poly-
merization mechanism was investigated using field desorption mass spectroscopy
(FD-MS) and proposed as outlined in Scheme 2. A 2: 1 complex of 13 with ethyl-

13

Scheme 2. Proposed a-olefin polymerization mechanism for divalent samarocene complexes.

 3.2.5.4 Carbon-Carbon Bond-Forming Reactions 983

ene is the initiating step, followed by electron transfer and formation of a dialkyl
complex, acting as a bifunctional initiator (Scheme 2). rne~o-lS/(THF)~ displays
a polymerization activity as high as 8330 g mmol-’ bar-’ min-’. In addition
to the production of high-molecular-weight polyethylene (M,, F= 1.45 X lo6;
PDI = 1.89), ra~-14/(THF)~ polymerizes a-olefins such as 1-pentene, giving
highly isotactic polymers, and copolymerizes 1,S-hexadiene to poly(methy1ene-
1,3-~yclopentane)[57].
Studies on homogeneous, single-component catalysis of butadiene poly-
merization have been concentrated on allyl-type complexes such as
[Li(C4H802)’ . 5 ] [ L ~ ( v ~ - C ~and
H ~[N~(V~-C,H,>C~(THF),]
)~] [B(C6Hs)4]to elucidate
the catalytic structure-reactivity relationship [58]. Unlike type 4 metallocene com-
plexes, which produce stable q3-crotyl complexes [ 3 11, such ally1 complexes poly-
merize butadiene to trans- 1,4-poIybutadiene. Stereospecific butadiene and iso-
prene polymerization ought to be the domain of multicomponent catalyst systems
[7]. The selective cis-l ,4-polymerization of 1,3-butadiene by catalyst systems
such as Nd(OR)3/t-BuCl/Al(i-Bu)3 is the only industrially applied process
using homogeneous rare earth catalysts (see Section 2.3.2.2). Divalent 13(Sm)/
(THF)* induced rapid polymerization of butadiene in the presence of MMAO
(MMAO = modified methylaluminoxane containing isobutyl-aluminoxane;
S d A 1 = 1:200; 98.8 % 1,4-~is;M , = 400 900; PDI = 1.82) [S9].

Polymerization of Functionalized Olefins

Modern polymer chemistry aims at the synthesis of highly syndiotactic or isotactic

polymers exhibiting high molecular weight (M,, > SO0 000) and extremely
narrow molecular weight distribution (PDI = 1.05) [35]. Even more challenging
is this theme when it comes to the synthesis of biodegradable products. The
“multipurpose” precatalyst 4 meets this demand, e.g., in the ideal living poly-
merization of MMA (methyl methacrylate) - a highlight in recent polymerization
catalysis (eq. (2); Table 2) [60-631.

Precatalyst 4(Sm) was utilized as a standard system [60]. The mechanism

follows a coordination anionic polymerization via an eight-membered transition
state (Scheme 3, see p. 985). Formation of a metal enolate turned out to be essen-
tial for the initiation of the MMA polymerization and was confirmed by the
initiation activity of the enolate complex [(C5H4SiMe3)2Y (OCH=CH2)],. The
rate of polymerization is directed by steric factors depending on the metal (Sm
> Y > Yb > Lu) and the auxiliary ligand (Cp > Cp”). Ethyl, isopropyl and
t-butyl methacrylates are also stereospecifically polymerized, but the rate of poly-
984 3.2 Special Catalysts and Processes

Table 2. Trends for highly efficient precatalyst in the polymerization of MMA and related
monomers.
Precatalyst Monomer”)Temp. M , X lo3 PDI rr Conversion [%] Ref.
[OCIb) [%I” (reaction period)

4(Sm;H) MMA 0 58 1.02 82.4 99 (1 h) [601

4(Sm;H) MMA -78 82 1.04 93.1 97 (18 h) [601
4(Lu;Me)/(THF), MMA 0 61 1.04 83.7 98 (2 h) [601
4(Yb ;AIMe4) MMA 0 55 1.04 84.3 93 (2 h) [601
Yb(indenyl),(THF) MMA -78 2270 - 93.8 [601
R-la(La;N(SiMe,),) MMA -35 896 6.7 94 (mm) 99 (160 h) [621
R-lb(Lu;N(SiMe,),) MMA 25 1645 3.2 73 24 (20 h) [621
ll(Er;N(SiMe,),) MMA -78 h) h) 82
99 (0.5 h) ~631
Yb(SPh),(HMPA), MMA 0 25 1.34 82 80 (24 h) ~ 4 1
Yb[C(SiMe,),l, MMA - 500 1.1 97 (mm) - ~ 9 1
[L]Yb(THF):’ MMA 0 - - 89 (mm) 82 (2 h) ~701
4(Sm;Me)/THF MeA“) 0 55 1.04 - 99 [601
4(Sm;Me)/THF EtAO 0 63 1.03 - 96 [601
4(Sm;Me)/THF BuAg’ 0 78 1.02 - 99 (601
~~ ~ ~ ~~

a)0.2 mol %. b, Polymerization temperature. Syndiotacticity. dl SiMe2(2-pyridylphenyl-

methyl); bimodal molecular weight distribution (37.2 %: M , = 255 000, PDI = 2.01 ; 62.8 %:
M , = 16 800, PDI = 1.93). e , MeA = methyl acrylate. EtA = ethyl acrylate. g, BuA = butyl
acrylate. h, Bimodal molecular weight distribution (> lo6, > 10’; narrow PDI).

merization and syndiotacticity decrease with an increase in the bulkiness of the

alkyl group (Table 2). Polymerization of acrylic esters such as methyl acrylate,
although surprisingly proceeding in a living manner using 4(Sm;Me)/THF, yields
completely atactic products reflecting the stereoregulating effect of the olefinic
methyl group of MMA (Scheme 3).
The efficiency of chiral 1-type precatalysts in controlling the stereochemistry
of the polymerization could be demonstrated [62]. Group R (H, CH(SiMe3)2),
N(SiMe&) has no effect on stereoregulation, but affects the kinetics of the initia-
tion process. It was proposed that the stereospecificity is controlled by rates of
stereoselective conjugate addition and template-mediated enolate isomerization.
C,-symmetric ansa-lanthanidocene complexes, e. g., ll(Er;N(SiMe&) [63], and
thiolate complexes Ln(SPh)3(HMPA)3[64] are also efficient precatalytsts for the
syndio-rich polymerization of MMA. The process of racerno-rneso interconver-
sion [65] seems to significantly affect the stereospecific formation of PMMA
by C2-symmetric ansa-lanthanidocene complexes of type 11 which, at low tem-
perature and depending on the size of the metal, produce iso-rich polymer [66].
 3.2.5.4 Curbon-Curbon Bond-Forming Reactions 985

q2R
t

o /

OMe
X-ray analysis (R= H)

Scheme 3. Proposed initiation mechanism for syndiotactic polymerization of MMA.

Living polymerization of methyl acrylates also occurs via lanthanide(I1) initiators

[67-701. This polymerization is initiated by one-electron transfer from 13/(THF)*
to form MMA radical anions and proceeds via bimetallic samarium(II1)bisenolate
complexes as shown in Scheme 4 [67]. The "link-functionalized" polymers
formed this way feature molecular weights twice those predicted from monome-
tallic polymerization, and the initiator appears to be 5 50 % efficient. Highly iso-
tactic (97 %), monodisperse, high-molecular-weight PMMA was obtained in the
presence of the divalent organolanthanide complexes Yb[C(SiMe3)3]2(Table 2)
[69] and [SiMe2(2-pyridylphenylmethyl)]Yb(THF)2[70].

13
2n-2 M M A Me0
___)

"link-functionalized polymers

Scheme 4. Proposed initiation mechanism for the polymerization of MMA by Ln" complexes.
986 3.2 Special Catalysts and Processes

“Constrained-geometry” complexes 16(Y;H or CH2SiMe3)not only polymerize

tert-butyl acrylate, but in contrast to lanthanidocene hydride and alkyl complexes,
they produce yellow, atactic poly(acrylonitri1e) via a keteneiminato complex [($-
CsMe4SiMe2NR’)Y(N=C=CHCH2R) formed through 1,44nsertion [7I]. Gener-
ally, monocyclopentadienyl complexes are ascribed a promising catalytic potential
in acrylonitrile polymerization [69]. Isocyanates are polymerized by various
metalorganic rare earth reagents, including type 4 metallocene complexes [72],
alkoxy-functionalized phenyl complexes, e. g., Sm[C6H3(0i-Pr)2-2,6]3[73], and
lanthanide isopropoxides [74]. For example, LaS0(0i-Pr)13produced high-mole-
cular-weight ( M , > lo6) poly(hexy1isocyanate) under appropriate conditions
[74]. Type 4 yttrium and lanthanum hydrides are active catalysts for the oligomer-
ization of 2-cycloalken-1-ones (P, 5 15) [75].

Ring-Opening Polymerization

Precatalyst 4(Sm;Me)/THF also initiates the living polymerization of lactones

such as 8-valerolactone and e-caprolactone (eq. (3); Table 3) [60]. In the proposed
initiation step a metal alkyl species attacks a coordinated ester group to provide
an acetal without ring cleavage. Propagation proceeds via attack of e-caprolactone
on the acetal by ring-opening and Ln-alkoxide bond formation [76]. The presence
of an alkoxide moiety in the active species is supported by the initiation of
the same process by 4(Sm;OMe)/OEt2 [76], Li[Y(ys:$-CsMe4SiMe2NCH2-
CH,OMe),] [77], YS0(0i-Pr)13,and “Y(OCH2CH20Et),” [78]. LaSO(Oi-Pr)13

Table 3. Ring-opening polymerization of e-caprolactone promoted by various precatalysts.“’

Precatalyst M, X 10’ PDI Conversion [%I Ref.
(reaction period)
4(Sm ;Me)/THF 83.4 1.06 95 ( 5 h)
4(Sm ;H) 142.2 1.05 65 (5 h)
4(Sm;OEt)/OEt2b) 108 1.09 92 (10 h)
Li[Y (C5Me4SiMe2NC2H40Me)2] 51 1.5 92 (1.5 h)
Y”(SiMeJ213 524 2.9 65 (1.5 h)
Y,O(Oi-Pr) 13 37.3 1.07 97 ( 5 min)
Nd(Oi-Pr)3(1,lO-phenanthroline) 17.7 1.04 99 (0.5 h)
“Y(OCH2CH2OEt),” 47.3 1.10 91 (5 min)
13/(THF)2 63 1.4 99 (1 h)
SmlN(SiMe,)212(THF)2 48 2.6“ 99 (5 min)
a) 0.2 mol %, at ambient temperature. b , At 0 “C. Stimng problems due to speed of
reaction.
 3.2.5.4 Curbon-Curbon Bond-Forming Reactions 987

causes rapid polymerization even at -64°C. The kinetics and mechanism of

s-caprolactone polymerization was studied in detail. For the initiating system
Y (OC6H3t-Bu2-2,6)3/HOi-Pr,polymerization is first order in monomer and initia-
tor [79]. (EA),LnOi-Pr (EA = diethyl acetoacetate) and Y(Oi-Pr)3L (e.g., L =
1,10-phenanthroline, 18-crown-6 ether) initiators showed that sterically bulky
ligands favor the screening of linear polymer chains by kinetically suppressing
transesterification reactions [SO]. Various Sm" reagents were utilized and the
variation of reactivity as a function of the ligand environment was pointed out
(Table 3) [81].
0

e-caprolactone

Biodegradable poly(1actide) was obtained by living ring-opening poly-

merization of (L,L)-lactide [82-851, employing functionalized alkoxides
"Ln(OCH2CH2NMe2)3"as the effective catalyst (eq. (4)) [82] and other com-
plexes [86]. The reaction is zero order in monomer and the turnover frequency
for Y(OCH2CH2NMe2)3in CH2C12 at ambient temperature was estimated as
TOF (NJ = 30 min-I. Again, the lanthanum derivative is even more reactive.
For comparison, the fastest aluminum alkoxide initiator Al(Oi-Pr), is reported
at 0.78 min-' (70 "C, 1.3 M lactide).

Y(OCH2CH2NMe2)3,0.2 mol%
$0
O+
0
-
toluene / CH2C12,20 "C, 15 min p o f n (4)

(I,l)-lactide 97%(Mw/M"= 1.15

Ring-opening polymerization of methylenecyclopropane in the presence of

4-type precatalyst proceeds to yield exo-methylene products in low yield [87] ;
4-type precatalysts do not polymerize oxiranes.

Copolymerization

Nonpolar-Nonpolar

For example, random copolymerization of 1-hexene with ethylene was initiated

by complex S(Lu;H) [37]. The ratio of ethylene/l-hexene in the polymer of 3:l
indicates the sensitivity of chain propagation toward steric bulk of the incoming
monomer. Precatalyst 4(Lu;H) effects the random copolymerization of ethylene
with methylenecyclopropane to achieve 65 exo-methylenes per 1000 CH2 units
[87]. C5Me5/ER-ligatedSm" complexes 18 can not only homopolymerize styrene
988 3.2 Special Catalysts and Processes

and ethylene (highest activity for ER = OC6H2t-Bu2-2,6-Me-4 and R =

N(SiMe&), but also produce block styrene-ethylene copolymers (PSE) [MI; at
25 “C and 1 atm ethylene, a typical polymer features 89 wt % PSE selectivity,
60 mol % PS, M,, > 146 000, and PDI = 1.66. The absence of activity for Yb” and
silylene-bridged cyclopentadienyl derivatives suggested that the polymerization
reaction is initiated by dissociation of neutral KCsMes from the Sm” center, fol-
lowed by one-electron transfer from Sm” to an incoming monomer (cf. Scheme 2).

Nonpolar-Polar

The dual function of the precatalysts 4 opened the way to well-controlled block
polymerization of ethylene and MMA (eq. ( 5 ) ) [89, 901. Homopolymerization
of ethylene ( M , = 10000) and subsequent copolymerization with MAA
(M,, = 20000) yielded the desired linear AB block copolymers. Mono and
bis(alkyl/silyl)-substituted “flyover” metallocene hydride complexes of type 8
gave the first well-controlled block copoymerization of higher a-olefins with
polar monomers such as MMA or CL [91]. In contast to the rapid formation of
polyethylene [92], the polymerization of 1-pentene and 1-hexene proceeded rather
slowly. For example, AB block copolymers featuring poly( 1-pentene) blocks
(M,, = 14000, PDI = 1.41) and polar PMMA blocks ( M , = 34000, PDI =
1.77) were obtained. Due to the bis-initiating action of samarocene(I1) complexes
(Scheme 4), type 13-15 precatalysts are capable of producing ABA block copoly-
mers of type poly(MMA-co-ethylene-co-MMA), poly(C1-co-ethylene-co-CL),
and poly(DTC-co-ethylene-co-DTC; DTC = 2,2-dimethyltrimethylene carbonate)
~901.

Polar-Polar

Random copolymerization of MMA with other polar monomers proceeds in a liv-

ing fashion with relative monomer reactivity ratios in the order BuA 9 MMA =
EtMA > i-PrMA when mediated by 4(Sm;Me)/THF [60, 891. Block polymeriza-
tion of MMA with other polar monomers as lactone yields ideal living copolymers
(PDI = 1.11-1.34) under these conditions. Similarly, ABA triblock copolymers
were obtained by sequential addition of MMA, BuA, and MMA [89]. AB
block copolymers could be obtained by sequential addition of (L,L)-lactide and
(D,D)-lactide (PDI = 1.38) as well as &-caprolactoneand (L,L)-lactide monomers
(PDI = 1.36) in the presence of “Y(OCH2CH2NMe2)”[82].
Up to 22% ethylene carbonate could be incorporated into rubbery caprolac-
tone polymers using Sm” catalysts such as 13/(THF)2 or Sm[N(SiMe,),],(THF),
[W.
 3.2.5.4 Curbon-Carbon Bond-Forming Reactions 989

3.2.5.4.2 Dimerization, Cyclization, and Isomerization

Steric restrictions at the metal center, which often prevent substrate polymeriza-
tion, can be profitably utilized, e. g., in dimerization reactions [94].

Alkyne Substrates

Despite a report that complex 4(Sc;Me) catalyzes the formation of oligo- and
polyacetylene [95], alkyne chemistry is characterized by ligand exchange and
dimerization reactions.
The catalytic oligomerization of terminal alkynes HC=CR by 4(Ln;
CH(SiMe,),) reveals that the regioselectivity and the extent of oligomerization
are dependent on the lanthanide metal applied, as well as on the alkyne substituent
R [30, 961. Furthermore, the extent of oligomerization was ascribed to the differ-
ences of activation energy for CH-bond activation and insertion. A monomeric
acetylide formed by dissociation of oligomeric [Cp*,Ln(C -CR)], is assumed
to be the catalytically active species. Selective dimerization was obtained for
Ln = Sc, Y and R = alkyl to yield head-to-tail dimers (gem-enynes), the yttrium
complex exhibiting turnover frequencies (TOF) of 5400 h-’ at 20 “C and 1 atm
propyne [96]. Phenylacetylene and (trimethylsily1)acetylene afforded mixtures
of two enynes, indicating electronic effects. The larger metals lanthanum and
cerium produced, besides dimers, higher oligomers (trimers, tetramers) of various
types (allenes, diynes). Utilizing bidentate N,N’-bis(trimethylsi1yl)benzamidinate
as a spectator ligand in { [C6H5C(NSiMe3)2]2Y (p-H)] allowed discrimination
between phenylacetylene and (trimethylsily1)acetylene [5 11. While the former
afforded the head-to-tail coupled product, the latter exclusively yielded the
head-to-head product trans- R(H)C=C(H)-CsCR (R = SiMe3).
Cyclodimerization of disubstituted alkynes R’C =CR” mediated by this type of
precatalyst (Ln = La, Ce; Y is unreactive) seems to be limited to alkynes bearing
at least one a-methyl group (R’) and a small second alkyl group (eq. (6)) [97].
Already use of R” = Et, n-Pr results in formation of two isomers. For example,
formation of 1,2-dimethyl-3-ethylidenecyclobutene from excess 1- butyne is com-
plete in ca. 10 h at 80 “C, giving a TOF of 2 h-’. Unprecedented propargylic
metalation/alkyne insertion are the key steps of the proposed mechanistic cycle.

-
Cp*2CeCH(SiMe3)2,5 mot%
2 - * (6)
benzene, 80 “C, TOF = 2 h-‘

z 99 Yo

Olefinic Substrates

Highly regiospecific head-to-tail dimers were obtained from a-olefins employing

5(Sc;H)/PMe3 as precatalyst. This dimerization reaction was subsequently
990 3.2 Special Catalysts and Processes

applied to the catalytic cyclization of a,w-dienes [29, 981. Methylenecycloalk-

anes containing five- to nine-membered rings were obtained this way. In the
course of these studies, reversible branching of 1,4-pentadienes and catalytic
opening of methylenecyclopropane and methylenecyclobutane were observed.
The highly electrophilic Sc system tolerated amine and thioether functionalities
within the olefinic substrate, while diallyl ether underwent only a single insertion
to afford a very stable chelated product. The dinuclear hydride complex derived
from 9 catalyzes the regio- and stereoselective homodimerization of a range of
a-olefins at 80°C as well as the head-to-head codimerization of styrene with
other olefins [99].
Functionalities such as ether and acetals have been tolerated in an organo-
yttrium-catalyzed cyclization of 1,5- and 1,6-dienes [loo]. The precatalyst
4(Y;Me)/THF could be easily prepared by a one-pot reaction. The enormous effect
of bulky groups R in the 3-position of an 1,5-diene on the regio- and diastereos-
electivites is in agreement with the debated mechanism (eq. (7)). Under the pre-
vailing reaction conditions (H2!) cyclization of 1,6-dienes is complicated by hy-
drogenation reactions.
OCPh3
Cp*2YMe(THF),5 mol%
7 OCPh3
benzene, 20 "C, 45 min *
- .(1-2 atm)
Hs
99 % yield regioselectivity > 99 % not formed
diastereoselectivity 21 :I

3.2.5.4.3 Other Reactions

The oxophilicity and coordination ability of the lanthanide elements turned out to
be crucial for the attraction and activation of oxygenated functions which display
pivotal components in important condensation and addition reactions [ 1011. Orga-
nometallic systems such as fluorinated /3-diketonate and alkoxide complexes
which contain highly polarized Ln-0-C linkages and are soluble in non-oxy-
gen-containing solvents seem to be predestined for this type of homogeneous
transformation (Structures 20-24). It must be assumed that other precatalysts
(Ln"-derivatives or Ln"'-alkyls) underlie in situ formation of catalytically active
Ln-O(a1koxide) moieties such as enolates when substrates such as ketones or
aldehydes are involved.

Diels-Alder Reactions

The more or less accidental discovery that fluorinated /3-diketonates of europium

both effect the Lewis acid catalysis of Diels-Alder reactions [ 101 and interact with
carbonyl functionalities of the substrates [lo21 emerged in a very prolific research.
Despite the ready feasibility of homo-Diels-Alder reactions [ 1031, hetero-Diels-
Alder cycloadditions are preferentially mediated [l 041. The endo selectivities
 3.2.5.4 Carbon-Carbon Bond-Forming Reactions 99 1

1Eu

20, E~(f0d)3 21, Eu(dppmh 22, (S)-LnMB

%;%
00
00
3

23 24, Ln-PEG-Li

which are generally observed are reasonably explained by a preceding metal-

dienophile complexation.
Trace amounts of complexes 3 and 20 promote the synthesis of optically pure,
multiply functionalized, versatile intermediates such as pyrones or lactones from
activated, acid-labile siloxydienes with aldehydes. The reagents typically work
under mild conditions and therefore promote the survival of valuable functionality
in the dienophile, the diene, and cycloadduct [ 105-1071. As a consequence this
procedure is applied in the total synthesis of various natural products, often re-
quiring an intramolecular Diels-Alder approach [ 1061. “Specific interactivity”
of the chiral precatalyst Eu(hfc)? (hfc = 3-(heptafluorpropy1hydroxymethylene)-
D-camphorate with “Danishefsky’s diene” bearing a chiral auxiliary resulted in
cycloaddition products of high diastereofacial excess (95 %; eq. (8)) [105].
OR* H
(+)-Eu(hfc)s, 5 mol%
+ PhCHO *
hexane, -20 “C,60 h
R3SiO
R3Si0 ph R3Si0 H
OR’ = 8-phenmenthyl, R3Si = ‘BuMepSi 25 1

Immobilized Y(fod)3 precatalysts were obtained according to surface organo-

metallic chemistry (SOMC; cf. Section 3.1.1.4) utilizing a heterogeneously per-
formed silylamide route on periodic mesoporous silica (PMS) [ 108aI. Such species
show highly selective reaction behavior in the Danishefsky transformation to form
product A exclusively, as shown in Scheme 5 (TOF = 70 h-’: Ln = Y, 50 “C). This
was ascribed to an in situ silylation ensuring the complete “end-capping” of all of
992 3.2 Special Catalysts and Processes

' Je n

2 mol% Sc, hexane, 10 h, 97 % yield

Ph
OMe T Me3Si0 A

Me3Si0 A HKPh
2 mol% Y, hexane, 20 h, 90 %yield

Scheme 5. Control of product selectivity by different immobilization procedures.

the Brgnsted acidic surface silanol groups and hence the handling and isolation of
sensitive substrate molecules and reaction intermediates. For comparison, a hybrid
material which was obtained by contacting a dehydrated MCM-41 sample directly
with Y(fod), initiated conversion of product A into B from the beginning.
Moreover, the long-term stability of the surface- and pore-confined Y (fad),-cat-
alyst could be demonstrated. The homogeneous catalyst Y (fod), was more active
at the beginning of the reaction, but the conversion came to a halt after approxi-
mately 1 h (80 %) and no further activity could be observed upon addition of an-
other equivalent of the substrates. In contrast, although the initial activity of the
PMS-confined catalyst was slightly decreased compared to its molecular congener
due to diffusion limitation, almost 95 % conversion was obtained after 50 h (Ln =
Y), and new substrates were converted as quickly as the first time, revealing no
marked decrease in activity toward the end of the reaction. Asymmetric screening
of the mesoporous catalysts via surface-mediated ligand exchange using different
chiral ligands produced the highest diastereomeric and enantiomeric excesses
[67 % de, 37 % ee (-35 "C); cf. Er[(-)-hfc],: 68 % de, 55 % ee) for the L-(-)-3-
(peffluorobutyry1)camphor derivative [MCM-4l]Y((-)-hfc),(THF), [ 108bI.
Cationic lanthanidocene complexes, [Cp*,Ln][BPh,], also act as effective
Lewis acid catalysts for the Danishefsky transformation shown in Scheme 5 ,
tolerating nitro- and pyridyl-functionalized aldehydes [ 1091.
 3.2.5.4 Curbon-Curbon Bond-Forming Reactions 993

A chelation-controlled mechanism was discussed in the asymmetric hetero-

Diels-Alder reaction of a-alkoxy aldehydes and N-protected amino aldehydes
with “Brassard’s diene” mediated by Eu(hfc)s (eq. (9); BOC = t-butoxycarbonyl)
[107].

Me0 fiMe3 OMe + ‘PrycHo

NHBOC
(+)-Eu(hfc)3, 5 mol%
CH&I*, 20 “C,
80 % yield
ipr

NHBOC
OMe (9)

95 % de

Heterobimetallic complexes 2 and 22 catalyze asymmetric Diels-Alder reac-

tions of some dienophiles with cyclopentadiene [ 1101. Use of 6,6’-dibromo-
substituted BINOL ligands led to significantly improved yield, endo:exo ratio,
and enantioselectivity.

Aldol and Michael Reactions

The basic character of lanthanide alkoxides such as Ln,(Ot-Bu), seem to effect

aldol, cyanosilylation, aldol, and Michael reactions [ 11I]. Complexes 2 and 22,
abbreviated as LnMB (Ln = lanthanide, M = alkali metal, B = BINOL) [112]
were thoroughly studied in the catalytic, asymmetric nitroaldol reaction (Henry re-
action; eq. (10)) [113].

m: + CHBNO~
(S)-PP(LaLiB; LiCI) 10 mol%
THF, -40 “C, 18 h
91 % vield
(10)
90 O h ee
The presence of LiCl and H 2 0 in specific ratios (e. g. 1: 5 ) is essential for both
acceleration of the reaction rate and enhancement of the enantiomeric selectivity.
Nitroaldols obtained from sodium-derived complexes such as 2 were mostly race-
mic. Larger lanthanide elements gave both higher chemical and optical yields.
Interestingly, retro-nitroaldol reactions were not observed in LnLB-catalyzed
(L=Li) nitroaldol reactions which were efficiently applied in the multistep syn-
thesis of optically active P-blockers, e. g., (-)-pindolo1 [ 114 a], and of (2S,3S)-
3-amino-2-hydroxy-4-phenylbutanoicacid, a component of the HIV-protease in-
hibitors KNI-227 and KNI-272 [ 114 b]. Efficient diastereoselective and enantio-
selective nitroaldol reactions were achieved from both optically active a-amino
aldehydes and prochiral materials by using 6,6’-bis((trialkylsily1)ethynyl)-sub-
stituted LnLB precatalysts [ 1151. “Second-generation’’ heterobimetallic catalysts,
LnLB-11, prepared from LnLB/H20/n-BuLi, promote the nitroaldol reaction at
considerably lower catalyst concentration (1 mol %) [ 1161. LnMB systems were
also screened (Yb:K:BINOL = 1: 1:3) to catalyze efficiently the first enantioselec-
tive nitro-Mannich-type reaction [ 1171. Moreover, the first direct catalytic asym-
994 3.2 Special Catalysts and Processes

metric aldol reaction using aldehydes and unmodified ketones (i.e., no ketone
conversion to more reactive species such as enol silyl ethers is required) was
accessible via LnMB complexes [ 1181. Development of a heteropolymetallic
asymmetric catalyst from (R)-LnLB, KOH, and H 2 0 greatly improved this asym-
metric reaction by decreasing the LnLB catalyst concentration from 20 mol % to
3-8 mol%.
Complex Na,La[(S)-BINOL], . 6THF . H 2 0 (2) seems to accommodate a uni-
que metaVligand constellation which makes this complex the first heterobimetal-
lic, multifunctional, asymmetric catalyst. Michael adducts in enantiomeric ex-
cesses as high as 92% were obtained in high yield even at room temperature
(eq. (11)) [1191.

OBn
THF, 20"C, 12
96 % yield
h:
benzyl methylrnalonate
0
90 % ee

It was proposed that a Lewis acid lanthanum center controls the direction of the
carbonyl function and activates the enone while the "sodium alkoxide" forms
enolate intermediates and regenerates the catalyst by hydrogen abstraction
(Scheme 6). Other Lnhlkali metal combinations, including La/Li, show negligible
asymmetric induction, yet give almost racemic products in excellent yield. In con-
trast, alkali-metal free BINOL ester enolate complexes catalyze Michael reactions
with high enantioselectivities, albeit at lower temperatures.

Scheme 6. Bifunctional asymmetric catalysis of Michael reactions.

 3.2.5.4 Carbon-Carbon Bond-Forming Reactions 995

La-linked-BINOL complex 23 was introduced as a stable, storable, and reuse-

able asymmetric catalyst for the Michael reaction [120]. Optimization of the reac-
tion between dibenzyl malonate and 2-cyclohexene- 1-one in DME afforded the
Michael adduct in 94 % yield and > 99 % ee. The extraordinary versatility of
LnLB catalyts is also documented in the highly efficient Michael addition of thiols
to a$-unsaturated carbonyl compounds [ 12I] and tandem Michael-aldol reac-
tions [ 1221.
Another highly fluorinated rare earth p-diketonate, 21 (Ln = Pr, Eu, Ho; dppm
= di(perfluoro-2-propoxypropionyl)methanate),showed itself to be a delicate re-
agent, not only for accomplishing high chemoselectivity in Mukaijama aldol reac-
tions with aldehydes and ketene silyl acetals (KSA) [123], for it was attributed

1
with a mode of "stereomodulating" catalysis in the aldol reaction of alkoxy alde-
hydes with KSA (eqs. (12) and (13)).

(dppm)3Eur::-OEt
B"0&0siMe3

H
Mde'' H

(12)
0 Me3Si0 0
OEt Eu(dppm)3,2 mol% dOE
4H
6Bn
+ AOSiMe3 CHzClp, -4O"C, 3 h r bBn
72 % yield
3,4-syn (99 %)

0 OMe (13)
Eu(dppm)3, 2 mol%
dH + 40SiMe3 CH2CI2, -40 "C, 6 h r
OSiMe2But (85"/.) 80 % yield OSiMe2But
3,4-anti (95Yo)
2,3-syn : anti = 94 : 1

The geometry of the aldol transition state was interpreted in terms of the
variation in mode of the aldehydekatalyst complexation [Felkin-Ahn (nonchelat-
ing) model versus chelating model] and size of KSA. The same complex
efficiently catalyzes the Michael reaction of a,p-unsaturated ketones with KSA
[124].
The stereochemical outcome of a Mukaijama aldol reaction effected by
( [Cp(SiMe3)2]2YbC1}was rationalized by the formation of a six-membered tran-
sition state involving the metal and both substrates [125]. A Ln triflate complex
996 3.2 Special Catalysts and Processes

supported by a chiral sulfonamide ligand was also utilized in asymmetric Mukai-

jama aldol reactions [ 1261. Preliminary catalytic investigations revealed that Sm”
menthoxide and 0-1-adamantoxide are stable under aldol reaction conditions and
catalyze the Mukaijama reaction with better diastereoselectivity compared with
the corresponding reactions with trivalent lanthanide alkoxides [ 1271. Cerium
enolate complexes of the Cl,Ce(OCR=CHR) type achieve higher yields in stoi-
chiometric cross-aldol reactions of sterically crowded substrates than the cor-
responding lithium enolates [128]. The larger cerium atom is assumed to be
more effective in the inital aldol chelate formation. Lanthanide(II1) isopropoxides
catalyze the cyclodimerization of a$-unsaturated ketones [ 1291 and the Michael-
type addition of hydroxyl compounds to unsaturated carboxylic acids [ 1301. The
resulting ether carboxylates can be used as metal sequestrants and are in general
readily biodegradable. Higher-order heterobimetallic alkoxide complexes of type
24 were prepared from lanthanide triflate, 6 equivalents n-BuLi, and 6 equivalents
of poly(ethy1ene glycol) (PEG) [ 1311. These Ln-PEG-Li complexes are water-
tolerant catalysts and promote Robinson-type reactions in the presence of water
best for Ln = Tb and a PEG with an average molecular weight of ca. 200. A
1: 1 mixture of Yb(fod)3 and glacial acetic acid efficiently promotes an ene-like
reaction of inexpensive vinyl ethers such as 2-methoxypropene with aldehydes
[132].

Diverse Carbon-Carbon Bond-Forming Reactions

Lanthanide isopropoxides were introduced as the first-generation alkoxide-type

precatalysts (Structures 1-3) [133]. They proved to be more effective in the
catalytic ring-opening of epoxides and aziridines than Et,N [134]. The acetone
cyanohydrin reaction provided P-hydroxynitriles and p-aminonitriles. Strong basi-
city of the lanthanide isopropoxides is considered to catalyze the transhydrocya-
nation effectively from acetone cyanohydrin to several aldehydes and ketones
[ 1351. “YbBu,” exhibited similar catalytic activity in this reaction.
Silylated nucleophiles such as trimethylsilyl cyanide are assumed to preferen-
tially attack on the less hindered side of styrene oxide, due to the bulky t-butoxide
group of a mixed SmI,(Ot-Bu) precatalyst (eq. (14)) [136]. Unique stereocontrol
(chelation versus nonchelation) in the Eu(fod),-catalyzed cyanosilylation (fod =
6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanedionate) of chiral alkoxy and
a-amino aldehydes could be explained by lanthanide-induced shift NMR analysis
[ 1371. A catalytic amount of La50(0i-Pr)13produced dinitrile derivatives in
excellent yield by the reaction of oxime esters or acid aldehydes with Me3SiCN
[138].

OSiMen CN

‘0 ylelu
77 1 23
 3.2.5.5 Carbon-Heteroelement Bond-Forming Reactions 997

Cerium isopropoxide catalyzes the highly diastereoselective pinacol coupling

of aliphatic and aromatic aldehydes (eq. (15)) [139].

Ce(OiPr)3,3 mol%, MeBSiO MeoSiO

0
ZnEtp,TMSCI PhLph : + ph+ Ph (15)
PhAH THFIhexane, 25 "C,15 h,)
84 % yield OSiMe3 O S ~ M ~ ~

97 3

3.2.5.5 Carbon-Heteroelement Bond-Forming Reactions

3.2.5.5.1 Hydrogenation and Related Processes

The following catalytic olefin transformations are another domain of metallocene
complexes [ 1401, and hence are closely related to those described in the preceding
sections, e. g., with respect to type of catalyst and mechanistic steps.

Hydrogenation

This topic (cf. Section 2.2) was pioneered by Evans et al., who found that lantha-
nide complexes prepared by metal vapor synthesis quantitatively convert 3-hexyne
to cis-3-hexene (96 % cis) [141], and also utilized complexes of type 4 for the cat-
alytic hydrogenation of alkynes and alkenes at room temperature and 1 bar hydro-
gen [ 142, 1431. Detailed kinetic and mechanistic studies on the hydrogenation of 1-
hexenes, cyclohexene, and 3-hexyne involving screening of the ligand environment
revealed that for a-olefins the olefin insertion is very fast and the Ln-C bond hy-
drogenolysis is rate-determining [ 1441. The smaller lanthanide metals better match
the high chargehadius ratio demands in the four-centered transition state and
accelerate the hydrolytic activation of H2. For example, 4(Lu;H) exhibits activities
of TOF = 120 000 h-' for the transformation of 1-hexene to n-hexane. For bulkier
olefins, the insertion becomes rate-determining and a more open metal center, as
in 5, is more reactive. C1- symmetric 1 (hydride) accomplished enantioselective
hydrogenations of 2-phenyl- 1- butene with enantiomeric excesses as high as
64 % (96 % at -80 "C) and high turnover frequencies [145]. Selective hydrogena-
tion of substituted dienes and functional-group compatibility were examined to
develop the process of hydrogenation into a useful, general technique. Complex
4(Y,Me)/THF can achieve site selectivity in the monoreduction of a,w-olefins
which are differentiated only by allylic substitution of one of the olefins [146].
Type 4 and 5 alkyl complexes also catalyze the regioselective hydrogenation of
acyclic imines (190 psi of H2, 90 O C , TOF = 0.40 h-') [ 1471. The stoichiometric
reaction of N-benzylidene(trimethylsily1)imine with 4(Sm;CH(SiMe3),) yielded a
desilylated Cp*,Sm-imine-amido complex with a four-membered Sm(NSi-
Me,)(CPh)N=CHPh chelate ring which converts further to &-symmetric
998 3.2 Special Catalysts and Processes

Hp (20 psi), 25 "C

":Me3 benzene h0
N
C ~ * ~ s r n c H ( S i M e+~ ) ~
\
*
-CHZ(S~M~~)~
- HSiMe3
JI
Ph'

Scheme 7. Reaction of N-benzylidene(trimethylsily1)imine with 4(Sm;CH(SiMe3),) and

H2 to structurally identified products.

(Cp*,SmCN)6 featuring an unusual chairlike 18-membered (SmCN)6 ring

(Scheme 7).

Hydrosilylation

Organolanthanide complexes of types 1, 4, 5, and 19 effect a diverse variety of

regio- and enantioselective catalytic olefin hydrosilylation reactions of a- and
styrenic olefins by PhSiH3 [ 148-15 13 (cf. Section 2.6). Kinetic investigations sug-
gest an autocatalytic mechanism involving a reactive hydride complex (Scheme 8)
[149, 1521. Rapid olefin insertion into the Ln-H bond via Si-mu-C transposi-
tion, as the turnover-limiting step, does not require complex dissociation into
monomeric species 11531. In accord with this mechanistic scenario is the action
of silanes in a new "drop-in" chain transfer process for metallocene-catalyzed
olefin polymerization to produce silyl-terminated polyolefins [ 1541. Styrenic
substrates show a remarkable 2,l-regioselectivity and a rate enhancement by
para-electron-releasing substituents (eq. (16)), while for (sterically encumbered)
a-olefins, predominantly 1,2-addition is observed.

Me0
CH /
II
+ PhSiH3
5 (Sm;CH(SiMe&), 0.5 mol%
benzene, 23 "C, ti2(!)
Me0
\ .SiH9Ph

TOF = 50 h-', 98 % yield

99 % 2,l-addition

Asymmetric hydrosilylation of 2-phenyl- 1-butene yields enantiomeric excess

(ee) values as high as 68 % [ 1491. Products obtained by sequential cyclization/
silylation reactions of 1S-dienes and 1,6-dienes feature in the suggested mechanis-
tic scenario (Scheme 8) [ 149, 1551. Furthermore, hydrosilylation of terminal ole-
fins achieved both excellent chemoselectivity in the presence of any internal ole-
fin, and functional-group compatibility with halides, ethers, and acetals [ 1551.
 3.2.5.5 Carbon-Heteroelement Bond-Forming Reactions 999

Cp*2Ln-N(SiMe3)2
Cp*zLn-R

R&+H (!) HN(SiMe&

H "Cp*2Ln-H"
,A.-,SiR3
R )(HydrosiIyla;~

RBSi-H

Scheme 8. Mechanistic scheme for organolanthanide-catalyzed hydrosilylation and

hydroamination.

Although terminal alkynes are metallated by 4(Sm;Me)/THF, internal alkynes do

undergo effective hydrosilylation [ 1561.

Dehydrogenative Coupling of Silanes

The observation that type-4 complexes effect the dehydropolymerization (oligo-

merization) of silanes to polysilanes supports the u-bond metathesis polymeriza-
tion mechanism, proposed for the comparatively much more effective zirconium
systems [ 1571. Kinetic and mechanistic features imply a four-centered heterolytic
bond-breakinghond-forming pattern [ 1581 and, when hydrocarbyl precatalysts are
employed, autocatalytic formation of the reactive Ln-H bond precedes [ 1571.
Complex 4(Lu;H) (0.009 mol %) affects the initial dehydrogenation of phenylsi-
lane coupling at TOF = 5200 h-' in toluene [158]. At room temperature the degree
of oligomerization is in the order of 5-9, while an increase of temperature drasti-
cally promotes the formation of higher oligomers. For example, 0.01 mol
4(Nd;CH(SiMe,),) affords at 130 "C after 2 d a solid polymerization product
(M, = 1600; PDI = 1.91) [159]. The conversion of high-molecular-weight
poly-(methylsilane) to P-SiC by crosslinking through the loss of methylsilane,
subsequential transformation to polycarbosilane, and final ceramization with the
loss of methane and hydrogen (eq. (17)) was considered [160].

Cp*2NdCH(SiMe3)2,0.2 mol% pyrolysis, 900 "C

p-Sic
MeSiH3 ,- MeSiH3, -H2, -CHI *
-H2 (17)
68 %
M, = 7340; PDI = 5.0
Me/SiH = 1.O
1000 3.2 Special Catalysts and Processes

Hydroamination

Organolanthanide-catalyzed hydroaminationkyclization (cf. Section 2.7) of

N-unprotected amino olefins is not restricted to primary amines and produces
2-methyl heterocycles (five-, six-, or seven-membered) with > 99 % regioselectiv-
ity and a new asymmetric center adjacent to the heterocyclic nitrogen atom (eq.
(18)) [145, 1611. The turnover frequencies are dependent on the type of substrate
and correlate with the coordinative unsaturation at the metal center. TOFs of chiral
precatalysts 1 (max. 93 h-’) are about 10 times those of the 4-catalyzed reaction,
obviously reflecting the steric situation. The importance of steric effects was again
demonstrated by using “constrained-geometry” catalysts, e. g., 16(Nd;N(SiMel),)/
R’ = t-Bu, which doubled the TOFs for a given reaction [162], or by using
less bulky lanthanidocene complexes such as { [C,H,(SiMe,)],Nd(-Me)}
for the hydroamination of hindered alkenes [ 1631. TOFs are indistinguishable
for H-, CH(SiMe3)2- and N(SiMe,),-type precatalysts, which favors the more
easily synthesized amide derivative. The overall high enantioselectivities afforded
by C,-symmetric 1 are increased at lower temperatures and can attain up to
74% ee.

HIN & l b (Sm;N(SiMe&, 0 5-2 mol %

pentane, - 30 “C,
> 99 % yield - ,\,p
> 95 % regioselectivity
74 % ee (+)
(18)

Kinetic studies suggest essentially zero-order dependence on the substrate con-

centration, but also indicate a competitive inhibitor function of the product hetero-
cycles. The rapidly formed amine-amide adducts of type Cp2Ln(HNR)(H2NR)
are assumed to be the active catalyst [161]. The turnover-limiting process is the
intramolecular olefin insertion into the Ln-N bond which proceeds via a chairlike,
seven-membered transition state (see Scheme 8). As expected, the chiral precata-
lysts also initiate diastereoselective processes (>95 % de).
The same type of precatalysts catalyze the regiospecific hydroaminatiordcycli-
zation of aliphatic and aromatic aminoalkynes RC =C(CH2)nNH2[ 1641. The me-
chanistic scenario parallels that of the corresponding amino olefin cyclization.
However, the cyclization of the aminoalkynes is 10-100 times more rapid and
a rather contrary effect of the cyclopentadienyl substitution on the TOF was
observed.
Type 4 metallocene complexes catalyze the regioselective intermolecular
addition of primary amines to acetylenic, olefinic, and diene substrates at rates
which are = 1/1000 those of the most rapid intramolecular analogues [165].
Variants such as the intramolecular hydroamination/cyclization of aminoallenes
[166] and the intra- and intermolecular tandem C-N and C-C bond-forming
processes of aminodialkenes, aminodialkynes, aminoallenynes, and amino-
alkynes [ 1671 were applied as new regio- and stereoselective approaches to
naturally occurring alkaloids. For example, bicyclic pyrrolizidine intermediate E
 3.2.5.5 Carbon-Heteroelement Bond-Forming Reactions 1001

H
4(La;CH(SiMe&),
benzene, 23 “C, 1-5
85 % yield
< 15rnol
rnin,
% -
nC5H11
p:H\
I

19(Srn;N(SiMe3)2),5 rnol %

benzene, 45 “C, 18 h,
80 % yield

Pd(OH),/C, MeOH

97 % yield

F, (+)-xenovenine

Scheme 9. Synthesis of pyrrolizidine (+)-xenovenine using organolanthanide precatalysts.

is formed via a stereoselective tandem bicyclization of the acyclic precursor C

in the presence of a “constrained-geometry’’ catalyst, 16(Sm;(N(SiMe3),)/R’ = t-
Bu, under mild conditions (Scheme 9). In contrast, precatalyst 4(La;CH(SiMe3),)-
yields exclusively the corresponding monocyclic pyrrolidine D via a regio-
selective insertion-cyclization of the allene group into the Ln-N bond.
Pyrrolizidine (+)-xenovenine F ((3S,5R,8S)-3-heptyl-5-methylpyrrolizidine) is
found in the venom of ants and was first isolated from Solenopsis xenoveneum
in 1980 [168].

Hydrophosphination and Hydrophosphonylation

Lanthanidocene complexes and “constrained-geometry’’ organolanthanides are

also competent catalysts for the intramolecular hydrophosphinatiodcyclization
of primary and secondary alkenyl and alkynyl phosphines [169]. Kinetic studies
implicate the same turnover-limiting catalytic step observed for organolantha-
nide-mediated hydroamination, that is, insertion of the carbon-carbon unsatura-
tion into the Ln-heteroatom bond. For analogous substrates and catalysts, hydro-
phosphination is = 5-1 0 times slower than the corresponding hydroamination
process. The formation of six-membered phosphorinanes via a noncatalytic
intramolecular 1,2-addition of secondary phosphinino alkenes displays a notable
competing side reaction.
1002 3.2 Special Catulysts and Processes

0
II
H-P(OMe)z

Scheme 10. LnPB-catalyzed asymmetric hydrophosphonylation of imines.

Heterobimetallic catalysis mediated by LnMB complexes (Structures 2 and 22)

represents the first highly efficient asymmetric catalytic approach to both a-hydro
and a-amino phosphonates [ 1121. The highly enantioselective hydrophosphonyla-
tion of aldehydes [170] and acyclic and cyclic imines [171] has been achieved.
The proposed catalytic cycle for the hydrophosphonylation of acyclic imines is
shown representatively in Scheme 10. Potassium dimethyl phosphite is initially
generated by the deprotonation of dimethyl phosphite with LnPB and immediately
coordinates to the rare earth metal center via the oxygen. This adduct then
produces with the incoming imine an optically active potassium salt of the
a-amino phosphonate, which leads via proton-exchange reaction to an a-amino
phosphonate and LnPB.
2,2,5,5-Tetramethyl-3-thiazoline was used as a model compound to study the
hydrophosphonylation of cyclic imines for the production of pharmaceutically
interesting a-amino phosphonates (eq. (19)) [ 1721. The resulting thiazolidinyl-
phosphonate can be regarded as an N,S-protected phosphonic acid analogue of
the a-amino acid D-penicillamine which functions, e. g., as an HIV-protease
inhibitor.
0
//
(Me0)2F?.
(R)-22(LnPB; Ln = Yb, P = K), 5 mol %

THFholuene (1:7),50 "C,48 h,

> 90 % yield
* &k (19)

96%ee(S)
 3.2.5.5 Carbon-Heteroelement Bond-Forming Reactions 1003

Hydroboration

Complexes of the 4 type catalyze the hydroboration of various olefins with

catecholborane at ambient temperature [ 1731. The proposed mechanism of the
hydroboration reaction - although not within the scope of this book - parallels
that of the hydrogenation and hydrosilylation reactions. The architecture of
both olefins (terminal L terminal disubstituted > internal disubstituted >
trisubstituted) and organolanthanides (TOF(La) = 10 TOF(Sm); TOF(5)
TOF(4) affects the rate of hydroboration, which for 4(La;CH(SiMe3),) and
- 4

l-hexene is TOF = 200 h-', for example. The observed high regioselectivities
are exclusively anti-Markovnikov. For smaller metal centers (Y, Zr, Ti) and
other ligand systems (bis(cyclopentadienyl), bis(benzamidinat0)) inactivation
of the catalyst by catecholborane or Lewis base-metal complex induced dispro-
portionation of catecholborane appeared to compete effectively with the catalytic
conversion [ 1741.
Members of the above class of lanthanide complexes also effect the hydro-
stannylation of olefins [175].

3.2.5.5.2 Functional Group Transformation,

Rearrangement and Exchange Reactions
Functional group transformations such as oxidations and reductions mediated
by Ln" and Ce'" complexes are well established in organic synthesis [13, 1761.
However, these processes usually involve stoichiometric and excess amounts
of metal reagent.
Ln50(i-Pr),,-mediated Oppenauer oxidations and Meerwein-Ponndorf-Verley
(MPV) reductions have been studied in detail [177, 1821. The gadolinium deri-
vative, employed in situ without elimination of LiC1, was reported to be ten
times more reactive in the MPV reduction of cyclohexanone than the standard
reagent Al(Oi-Pr)3 [ 1771. MPV-type reductive acetylation of carbonyl com-
pounds to acetates was successfully carried out in the presence of isopropenyl
acetate and catalytic amounts of Ln(Oi-Pr)3 [ 1791. Heteroleptic iodoalkoxides,
LnI,(OR), also revealed promising activity in MPV-Oppenauer reactions
[ 1SO]. Lanthanide alkoxide moieties have been immobilized on mesoporous si-
lica MCM-41 by direct alkoxide grafting and via a heterogeneously performed
silylamide route (cf. Scheme 5 ) [ 1811. The latter procedure accomplishes
"mononuclear" Ln alkoxide sites independently of the size of the ligand. Such
rare earth alkoxide surface complexes display subtly differentiated catalytic
behavior in the MPV reduction of tert-butylcyclohexanone. A chiral alkoxide
ligand was employed in enantioselective samarium-catalyzed MPV reductions
of aryl methyl ketones (eq. (20)) [182].
1004 3.2 Special Catalysts and Processes

Bn

f i-\rPh
Phr,,.

0-Sm-0
I CI OH
I
5 mol %
THF, 20 "C, 24 h
- b-
96 YO yield
97 % ee

A cooperative effect of the basic alkoxide oxygen, the soft nucleophile I- and
the Lewis acidic Ln3+center was responsible for the selectively catalyzed rearran-
gement of terminal epoxides to methyl ketones by LnI,(Ot-Bu) (eq. (2 1)) [ 1831.
0
0 'BuOSm12, 10 %
n-CeH17ij
THF, 20 "C,20
90 Yo

The catalytic asymmetric epoxidation of a,b-unsaturated ketones with hydro-

peroxides such as tert-butyl hydroperoxide (TBHP) and cumene hydroperoxide
(CMHP) can be carried out at ambient temperature by using alkali-metal free
Ln-BINOL complexes (eq. (22)) [184]. The oligomeric structure of the catalyst
is assumed to play a key role: that is, the Ln alkoxide moiety acts as a Brgnsted
base, activating a hydroperoxide molecule, while another Ln metal ion acts as a
Lewis acid, both activating and controlling the orientation of the enone.

\
La

@&O'

5 mot%

MS 4A, THF, r.t., 48 h * 'Pr

> 95 % yield

La(Oi-Pr)3-mediated transesterification and the ester exchange reactions are

sensitive to steric constraints of the substrates and to metal ion size [185]. For
example, transesterification is best applied to primary alcohols. Eu(fod)3, 20,
catalyzes the stereospecific rearrangement reactions of allylic methoxyacetates
under exceptionally mild conditions (eq. (23)) [ 1861. NMR spectroscopy rein-
forced the idea that the Eu(fod)3-reagent exerts its catalytic activity for the rearran-
gement through chelate formation with the oxygen atoms of the methoxy and ester
carbonyl groups, contrary to late transition metal catalysis which proceeds via
coordination to the potentially congested olefin. The synthesis of enediynes was
accomplished similarly [ 1871.
 3.2.5.6 Catalyst Structure 1005

81 %

The iodoalkoxide SmI,(Ot-Bu) promotes the intramolecular Tishchenko reac-

tion via a metal-chelate intermediate to form perfectly stereocontrolled lactones
(eq. (24)) [189]. Ethyllanthanide iodide complexes, “EtLnI” (Ln = Pr, Nd, Sm)
etc. [25 b, 1861, also serve as catalyst precursors for the Tishchenko condensation
reaction [190].
OBn OBn
CHO ‘BuOSm12, cat.
THF, 20 “C

single stereoisomet
89 Yo

Ytterbium triisopropoxide (10-20 mol %) catalyzes the ring-opening of epox-

ides with trimethylsilyl azide at ambient temperature to yield vicinal azide al-
cohols (eq. (25)) [ 19l]. Complexatiodchelation interactivity of functionalized
substrates affects the regioselectivity in the product.
OSiMes

Me0
do
+ Me3SiN3
“Yb(OPr’)$, 10 mol%
THF, 20 “C,12 h,
75 % yield
- M e o A N 3
> 99:l regioselectivity
(25)

LnCp, and Cp,LnCI complexes initiate the dehalogenation of aryl and vinyl
halides by NaH. Chemoselectivity is observed in the reduction of m-bromochloro-
benzene and p-iodochlorobenzene to chlorobenzene [ 1921. The asymmetric re-
duction of methylphenyl glyoxylate to methyl mandelate by NADH models is
catalyzed by chiral lanthanide P-diketonates [ 1931.

3.2.5.6 Catalyst Structure

What is the composition of the “true catalyst”? What are the intermediates in a
catalytic cycle? Confrontation with these questions is of fundamental importance
for understanding the catalyst reactivity and for developing more efficient cata-
lysts, e. g., by tuning of the ligand environment. Application of various spectro-
scopic methods helps to shed light on this topic. An ultimate approach is the
“freezing out” of a precatalyst-substrate interaction by controlling the stoichiome-
try and subsequent structural elucidation of this species. Table 4 gives examples
Table 4. Precatalysthbstrate interactivity detected by X-ray analysis. -
0
0
Process Substrate Precatalyst Interactivity Ref. a
Olefin polymerization Ethylene 4(Sc;H)
10
16(Sc ;H)
19(Y,H)/THF
Propylene 4(Sm;H)
16(Sc;H)
MMA 4(Sm;H)
Acrylonitrile 16(Y,H)/R = t-Bu [(y5-CSMe4SiMe2NR')Y
(N=C=CHCH2R) [711 A
-0
Isocyanate (MeC5H4)2YNi-Pr2 (MeCSH&Y [OCN(i-Pr),NPh](THF) [721
Alkyne oligomerization Acetylene 4(Sc;Me) Cp"2Sc-c =C-ScCp"2
L',YI&-H)~'' [L'ZYb-C CH)]*
HCECMe 4(Ce;CH(SiMe3)2) (Cp*2Ce)2(lc-q2:r2-MeC=C=C=CMe)
HC-Ct-Bu (Cp,ErMe), [Cp,Er(C -Ct-Bu)IZ
4( Sm ;H) [C~*,S~(C=C~-BU)~~,, U961
Cp*,Sm(t-BuCCH=CCt-Bu=CH,)
4(Ce;CH(SiMe3)2) (Cp*,Ce)&-rz:r2-t-BuC=C=C=Cf-Bu) P61
HC-CPh 4(Ln;N(SiMe3),) (Cp*,Ln),@-y2:q2-PhC=C=C=CPh)
(Ln = La, Nd) [ 196,1971
Aldol reaction Acetone 4(Ce;CH(SiMe3),) Cp*,CeO[CMe,CH,C(=O)Me] [I981
Hydroamination H2NMe 4(La;CH(SiMe3),) Cp*,La(NHMe)(H2NMe) [161 b]
Silane coupling H2Si(SiMe3)2 4(Sm;CH(SiMe3),) [Cp*,SmSiH(SiMe,),], [ 157 b]
~~ ~~ ~ ~ ~~

L= (v5-C5Me4)SiMe2(r]'-Nt-Bu). DADMB = 2,2'-bis((tert-butyldimethylsiIyl)amido)-6,6'-dimethylbiphenyl. c, L' = C6HSC(NSiMeJ2.

 References 1007

which involve Ln"' precatalysts [ 194-1 991, simultaneously mentioning important

catalytic applications in review.

3.2.5.7 Perspectives
Organometallic compounds of the rare earth metals are often misunderstood as
highly moisture-sensitive species. However, it is just these highly reactive com-
pounds that have been developed into important model systems, e. g., for olefinic
polymerization. Future investigations will be directed toward balancing the intrin-
sic properties of the elements on the one hand, and the hydrolysis rates on the
other. The first easily tractable, highly selective organometallic catalysts have
been successfully applied, and the availability of new ligand environments will
cope better with the high standards required by enantioselective catalysis. The in-
tellectual acrobatics which are performed in ligand architecture of main group and
d-transition metal catalytic systems await transfer and adaptation to the organo-
lanthanide competitors. Asymmetric catalysis is challenged by the first well-
defined monolanthanide complexes featuring catalytically relevant chiral counter-
ligands such as salen [200], sulfonamide [201], and bis(oxazo1ine) ligands [202].
Rare earth complexes that have been applied so far have often revealed to be
superior to traditional reagents for the solution of specific problems in organic
synthesis and therefore appear promising in many homogeneously catalyzed in-
dustrial processes, including medicinal applications such as catalytic RNA clea-
vage [203]. Moreover, exceptional reactivity of sterically unsaturated surface-
grafted organolanthanide species accessible via surface organometallic chemistry
can be foreseen [204]. Apart from specific rare earth metal properties, there is no
group of elements in the Periodic Table that can better be tuned stereoelectroni-
cally. This is a unique chance in the development of new homogeneous catalysts.

References
[l] H. Adkins, B. H. Nissen, J. Am. Chem. Soc. 1922, 44, 2749.
[2] (a) E. Bamann, M. Steber, H. Trapmann, I. Braun-Krasny, Naturwiss. 1957, 44, 328;
(b) E. Bamann, H. Trapmann, A. Schuegraf, Chem. Ber: 1955, 88, 1726.
[3] E. Gelles, K. S. Pitzer, J. Am. Chem. Soc. 1955, 77, 1974.
[4] J. H. Forsberg, T. Balasubramanian, V. T. Spazino, J. Chem. Soc., Chem. Commun. 1976,
1060.
[5] (a) M. P. Rosynek, Cutal. Rev. 1977, 16, I1 1 ; (b) G. N. Sauvion, P. Durcros, J. Less-
Common. Met. 1985, 111, 23.
[6] E. Greinacher in Industrial Applications of Rare Earth Elements (Ed.: K. A. Gscheidner,
Jr.), American Chemical Society, Washington, DC, 1981, Chapter 1.
[7] Z. Shen, J. Ouyang in Handbook on the Physics and Chemistry of Rare Earths (Eds.;
K. A. Gschneidner, Jr., L. Eyring), North-Holland, Amsterdam, 1987, Chapter 61;
(b) Z. Shen, Inorg. Chim. Acta 1987, 140, 7.
[8] D. G. H. Ballard, A. Courtis, J. Holton, J. McMeeking, R. Pearce, J. Chem. SOC., Chem.
Commun. 1978. 994.
1008 3.2 Special Catalysts and Processes

[9] W. J. Evans, S. C. Engerer, P. A. Piliero, A. L. Wayda, J. Chem. Soc., Chem. Commun.

1979, 1007.
[lo] T. C. Morrill, R. A. Clark, D. Bilobran, D. S. Youngs, Tetrahedron Lett. 1975, 6, 397.
[ l l ] J. R. Long in Handbook on the Physics and Chemistry of Rare Earths (Eds.: K. A.
Gschneidner, Jr., L. Eyring), North-Holland, Amsterdam, 1986, Chapter 57.
[12] (a) H. B. Kagan, J. L. Namy, Tetrahedron 1986, 42, 6573; (b) H. B. Kagan in Funda-
mental and Technological Aspects of Organo-j-Element Chemistry (Eds.: T. J. Marks,
I. L. FragalB), D. Reidel, Dordrecht, 1985, pp. 49-76.
[13] G. A. Molander, Chem. Rev. 1992, 92, 29.
[ 141 T. Imamoto, Lanthanides in Organic Synthesis, Academic Press, London, 1994.
[ 151 See review: C. Schaverien, Adv. Organomet. Chem. 1994, 36, 283.
[16] H. Imamura, K. Kitajima, S. Tsuchiya, J. Chem. Soc., Faruday Trans. I 1989, 85, 1647.
[17] S. Kobayashi, Synlett 1994, 689; (b) J. Inanaga, Y. Sugimoto, T. Hanamoto, New J.
Chem. 1995, 19, 707.
[18] L. R. Morss, Chem. Rev. 1976, 76, 827.
[19] (a) S. P. Nolan, D. Stem, T. J. Marks, J. Am. Chem. SOC.1989, 111, 7844; (b) W. A. King,
T. J. Marks, Inorg. Chim. Acta 1995, 229, 343.
[20] R. D. Shannon, Acta Crystallogr: Sect. A 1976, 32, 751.
[21] (a) E. Murad, D. L. Hildenbrand, J. Chem. Phys. 1980, 73, 4005; (b) M. B. Liu, P. G.
Wahlbeck, High Temp. Sci. 1974, 6,179; (c) G. V. Samsonov, The Oxide Handbook,
2nd ed., IFUPlenum, New York, 1982, pp. 86-105.
[22] M. Husain, A. Batra, K. S. Srivastava, Polyhedron 1989, 8, 1233.
[23] L. G. Hubert-Pfalzgraf, New J. Chem. 1995, 19, 727.
[24] D. A. Johnson, Adv. Inorg. Chem. Radiochem. 1977, 20, 1.
[25] See for examples: (a) D. A. Evans, A. H. Hoveyda, J. Am. Chem. Soc. 1990,112, 6447;
(b) K. Yokoo, N. Mine, H. Taniguchi, Y. Fujiwara, .I. Organomet. Chem. 1985,279, C19.
[26] Leading references: (a) M. T. Reetz, Angew. Chem. 1984, 96, 542; Angew. Chem., Int.
Ed. Engl. 1984, 23, 556; (b) A. H. Hoveyda, D. A. Evans, G. G. Fu, Chem. Rev.
1993, 93, 1307; (c) D. J. Berrisford, C. Bolm, K. B. Sharpless, Angew. Chem. 1995,
107, 1159; Angew. Chem., Int. Ed. Engl. 1995, 34, 1059.
[27] Reviews: (a) R. Noyori, M. Kitamura, Angew. Chem. 1991, 103, 34; Angew. Chem., Int.
Ed. Engl. 1991, 30, 49; (b) R. 0. Duthaler, A. Hafner, Chem. Rev. 1992, 92, 807;
(c) R. L. Halterman, Chem. Rev. 1992, 92, 965.
[28] P. L. Watson, G. W. Parshall, Acc. Chem. Res. 1985, 18, 51 and references therein.
[29] M. E. Thompson, J. E. Bercaw, Pure Appl. Chem. 1984, 56, 1 .
[30] (a) M. E. Thompson, S. M. Baxter, A. R. Bulls, B. J. Burger, M. C. Nolan, B. D.
Santarsiero, W. P. Schaefer, J. E. Bercaw, J. Am. Chem. SOC. 1987, 109, 203;
(b) W. E. Piers, J. E. Bercaw, J. Am. Chem. Soc. 1990, 112, 9406.
[31] B. J. Burger, M. E. Thompson, W. D. Cotter, J. E. Bercaw, J. Am. Chem. Soc. 1990, 112,
1566.
[32] (a) M. Brookhart, M. L. H. Green, J. Organomet. Chem. 1983, 250, 395; (b) M. Brook-
hart, M.L.H. Green, L.-L. Wong, Prog. Inorg. Chem. 1988, 36, 1.
[33] C. J. Schaverien, G. J. Nesbitt, J. Chem. Soc., Dalton Trans. 1992, 157.
[34] C.P. Casey, S.L. Hallenbeck, J.M. Wright, C.R. Landis, J. Am. Chem. SOC.1997, 119,
9680.
[35] H. Yasuda, H. Tamai, Prog. Polym. Sci. 1993, 18, 1097.
[36] G. Jeske, H. Lauke, H. Mauermann, P.N. Swepston, H. Schumann, T.J. Marks, J. Am.
Chem. Soc. 1985, 107, 8091.
[37] G. Jeske, L.E. Schock, P.N. Swepston, H. Schumann, T.J. Marks, J. Am. Chem. SOC.
1985, 107, 8103.
[38] X. Olonde, A. Mortreux, F. Petit, K. Bujadoux, J. Mol. Catal. 1993, 82, 75.
 References 1009

[39] M. B. Abrams, J. C. Yoder, C. Loeber, M. W. Day, J. E. Bercaw, Organometallics 1999,

18, 1389.
[40] P. L. Watson, T. Herskovitz, ACS Symp. Sex 1983, 212, 459.
[41] E.B. Coughlin, J.E. Bercaw, J. Am. Chem. SOC.1992, 114, 7606.
[42] J. Eppinger, M. Spiegler, W. Hieringer, W. A. Henmann, R. Anwander, J. Am. Chem.
Soc. 2000, 122, 3080.
[43] D. Stem, M. Sabat, T. J. Marks, J. Am. Chem. Soc. 1990, 112, 9558.
[44] P. J. Shapiro, W. D. Cotter, W. P. Schaefer, J. A. Labinger, J. E. Bercaw, J. Am. Chem. Soc.
1994, 116, 4623.
[45] (a) K. C. Hultzsch, P. Voth, K. Beckerle, T. P. Spaniol, J. Okuda, Organometallics 2000,
19, 228; (b) S. Amdt, P. Voth, T. P. Spaniol, J. Okuda, Organometallics 2000, 19, 4690.
[46] N. Ishihara, M. Kuramoto, M. Uoi, Macromolecules 1988, 21, 3356.
[47] H. Yasuda, E. Ihara, Bull. Chem. Soc. Jpn. 1997, 70, 1745.
[48] Y. Zhang, Z. Hou, Y. Wakatsuki, Macromolecules 1999, 32, 939.
[49] W. J. Evans, T. A. Ulibam, J. W. Ziller, J. Am. Chem. Soc. 1990, 112, 219.
[50] (a) C. J. Schaverien, Organometallics 1994, 13, 69; (b) W. E. Piers, E. E. Bunel, J. E.
Bercaw, J. Orgunornet. Chem. 1991, 407, 5 1.
[51] (a) R. Duchateau, C. T. van Wee, J. H. Teuben, J. Am. Chem. Soc. 1993, 115, 4931;
(b) R. Duchateau, C. T. van Wee, J. H. Teuben, Orgunometallics 1996, 15, 2291.
[52] D. P. Long, P.A. Bianconi, J. Am. Chem. SOC. 1996, 118, 12453.
[53] T. I. Gountchev, T. D. Tilley, Organometallics 1999, 18, 2896.
[54] (a) W. J. Evans, S.L. Gonzales, J. W. Ziller, J. Am. Chem. Soc. 1991, 113, 7423; (b) W. J.
Evans, K. J. Forrestal, J. W. Ziller, Angew. Chem. 1997, 109, 798; Angew. Chem. Int. Ed.
1997, 36, 774; (c) W. J. Evans, K. J. Forrestal, J. W. Ziller, J. Am. Chem. SOC.1998, 120,
9273.
[55] (a) W. J. Evans, I. Bloom, W. E. Hunter, J.L. Atwood, J. Am. Chem. Soc. 1981, 103,
6507; (b) W. J. Evans, L. A. Hughes, T. P. Hanusa, J. Am. Chem. Soc. 1984, 106, 4270.
[56] W. J. Evans, D. M. DeCoster, J. Greaves, Macromolecules 1995, 28, 7929.
[57] E. Ihara, M. Nodono, K. Katsura, Y. Adachi, H. Yasuda, M. Yamagashira, H. Hashimoto,
N. Kanehisa, Y. Kai, Organometallics 1998, 17, 3945.
[58] (a) R. Taube, H. Windisch, J. Organomet. Chem. 1994, 472, 71; (b) R. Taube, S. Mai-
wald, J. Sieler, J. Organomet. Chem. 2001, 621, 327.
[59] S. Kaita, Z. Hou, Y. Wakatsuki, Macromolecules 1999, 32, 9078.
[60] (a) H. Yasuda, H. Yamamoto, K. Yokota, S. Miyake, A. Nakamura, J. Am. Chem. SOC.
1994, 114, 4908; (b) H. Yasuda, H. Yamamoto, M. Yamashita, K. Yokota, A. Nakamura,
S. Miyake, Y. Kai, N. Kanehisa, J. Am. Chem. Soc. 1993, 26, 7134.
[61] (a) T. Jiang, Q. Shen, Lin Y, S. Jin, J. Organomet. Chem. 1993, 450, 121. (b) L. Mao,
Q. Shen, J. Polym. Sci., Part A: Polym. Chem. 1998, 36, 1593.
[62] M. A. Giardello, Y. Yamamoto, L. Brard, T. J. Marks, J. Am. Chem. Soc. 1995,117,3276.
[63] (a) M. H. Lee, K.-W. Hwang, Y. Kim, J. Kim, Y. Han, Y. Do, Organometallics 1999, 18,
5124; (b) C. Qian, W. Nie, J. Sun, Organornetallics 2000, 19, 4134.
[64] Y. Nakayama, T. Shibahara, H. Fukumoto, A. Nakamura, K. Mashima, Macromolecules
1996, 29, 8014.
[65] J. C. Yoder, C. Loeber, M. W. Day, J. E. Bercaw, Organometallics 1998, 17, 4946.
[66] H. W. Gorlitzer, Ph. D. Thesis, Technische Universitit Munchen, 2000.
[67] L. S. Boffa, B. M. Novak, Macromolecules 1994, 27, 6993.
[68] S.Ya. Knjazhanski, L. Elizalde, G. Cadenas, B. M. Bulychev, J. Organornet. Chem. 1998,
568, 33.
[69] H. Yasuda, J. Polym. Sci., Part A: Polym. Chem. 2001, 39, 11955.
[70] E. Ihara, K. Koyama, H. Yasuda, N. Kanehisa, Y. Kai, J. Organomet. Chem. 1999,
574. 40.
1010 3.2 Special Catalysts and Processes

1711 K. C. Hultzsch, T.P. Spaniol, J. Okuda, Angew. Chem. 1999, 111, 163; Angew. Chem.
Int. Ed. 1999, 38, 227.
[72] L. Mao, Q. Shen, M. Xue, J. Sun, Organometallics 1997, 16, 3711.
[73] E. Ihara, Y. Adachi, H. Yasuda, H. Hashimoto, N. Kanahisa, Y. Kai, J. Organomet.
Chem. 1998, 569, 147.
[74] N. Fukuwatari, H. Sugimoto, S. Inoue, Macromol. Rapid Commun. 1996, 17, 1.
[75] B.-J. Deelman, E. A. Bijpost, J. H. Teuben, J. Chem. Soc., Chem. Commun. 1995, 1741.
[76] M. Yamashita, Y. Takemoto, E. Ihara, H. Yasuda, Macromolecules 1996, 29, 1798.
[77] K. C. Hultzsch, J. Okuda, Macromol. Rapid Commun. 1997, 18, 809.
[78] S. J. McLain, N. E. Drysdale, Am. Chem. Soc., Div. Polym. Chern. 1992, 33, 174.
[79] W. M. Stevels, M. J. K. AnkonC, P. J. Dijkstra, J. Feijen, Macromolecules 1996,
29, 8296.
[80] Y. Shen, Z. Shen, Y. Zhang, K. Yao, Macromolecules 1996, 29, 8289.
[81] W. J. Evans, H. Katsumata, Macromelecules 1994, 27, 2330.
[82] S. J. McLain, T. M. Ford, N. E. Drysdale, Am .Chem. Soc., Div. Polym. Chem. 1992,
33, 463.
[83] W. M. Stevels, M. J. K. AnkonC, P. J. Dijkstra, J. Feijen, Macromolecules 1996,
29, 6132.
[84] B. M. Chamberlain, Y. Sun, J. R. Hagadorn, E. W. Hemmesch, V. G. Young, Jr., M. Pink,
M. A. Hillmyer, W. B. Toman, Macromolecules 1999, 32, 2400.
[85]X. Deng, M. Yuan, X. Li, C. Xiong, EUKPolym. J. 2000, 36, 1151.
[86] K. Beckerle, K.C. Hultzsch, J. Okuda, Macromol. Chem. Phys. 1999, 200, 1702.
[87] X. Yang, A.M. Seyam, P.-F. Fu, T.J. Marks, Macromolecules 1994, 27, 4625.
[88] Z. Hou, Y. Zhang, H. Tezuka, P. Xie, 0.Tardif, T. Koizumi, H. Yamazaki, Y. Wakatsuki,
J. Am. Chem. Soc. 2000, 122, 10533.
1891 (a) H. Yasuda, M. Furo, H. Yamamoto, A. Nakamura, S. Miyake, N. Kibino, Macromo-
lecules 1992, 25, 5 115. (b) E. Ihara, M. Morimoto, H. Yasuda, Macromolecules 1995,
28, 7886.
[90] G. Desurmont, M. Tanaka, Y. Li, H. Yasuda, T. Tokimitsu, S. Tone, A. Yanagase,
J. Polym. Sci., Part A: Polym. Chem. 2000, 38, 4095.
[91] G. Desurmont, T. Tokimitsu, H. Yasuda, Macromolecules 2000, 33, 7679.
[92] G. Desurmont, Y. Li, H. Yasuda, T. Maruo, N. Kanehisa, Y. Kai, Organometallics 2000,
19, 1811.
[93] W. J. Evans, H. Katsumata, Macromelecules 1994, 27, 4011.
[94] S. M. Pillai, M. Ravindranathan, S. Sivaram, Chem. Rev. 1986, 86, 353.
[95] M.St. Clair, W. P. Schaefer, J. E. Bercaw, Organometallics 1991, 10, 525.
[96] (a) K. H. den Haan, Y. Wielstra, J. H. Teuben, Organometallics 1987, 6, 2053;
(b) H. J. Heeres, J. H. Teuben, Organometallics 1991, 10, 1980; (c) H. J. Heeres,
J. Nijhoff, J. H. Teuben, R. D. Rogers, Organometallics 1993, 12, 2609.
1971 H. J. Heeres, A. Heeres, J. H. Teuben, Organometallics 1990, 9, 1508.
1981 (a) E. Bunel, B. J. Burger, J. E. Bercaw, J. Am. Chem. SOC.1988, 110, 976; (b) S. Hajela,
J. E. Bercaw, Organometallics 1994, 13, 1147.
[99] W. P. Kretschmer, S. I. Troyanov, A. Meetsma, B. Hessen, J. H. Teuben, Organometal-
lics 1998, 17, 284.
[loo] G. A. Molander, J.O. Hoberg, J. Am. Chem. SOC.1992, 114, 3123.
[ l o l l R. Anwander, Top. Cum Chem. 1996, 179, 149.
[lo21 E. Dunkelblum, H. Hart, J. Org. Chem. 1977, 42, 3958.
[lo31 For examples, see: (a) S. Danishefsky, M. Bednarski, Tetrahedron Lett. 1985, 26,
2507; (b) R.P. Gandhi, M.P.S. Ishar, A. Wali, J. Chem. Soc., Chem. Commun.
1988, 1074; (c) M. P. S. Ishar, A. Wali, R.P. Gandhi, J. Chem. Soc., Perkin Trans.
1990, 2185; (d) A.E. Vougioukas, H.B. Kagan, Tetrahedron Lett. 1987, 28, 5513;
 References 1011

(e) C.-K. Sha, C.-Y. Shen, R.-S. Lee, S.-R. Lee, S.-L. Wang, Tetrahedron Lett. 1995,
36, 1283.
[lo41 H. Waldmann, Synthesis 1994, 535.
[lo51 M. Bednarski, S. Danishefsky, J. Am. Chem. Soc. 1986, 108, 7060 and references
therein.
[lo61 (a) S. J. Danishefsky, M. P. DeNinno, Angew. Chem. 1987, 99, 15; Angew. Chem., Int.
Ed. Engl. 1987, 26, 15; (b) S.J. Danishefsky, W.H. Pearson, D.F. Harvey, J. Am.
Chem. Soc. 1984, 106, 2455; (c) M.M. Midland, R.S. Graham, J. Am. Chem. Soc.
1984, 106, 4294. (d) K. Takeda, Y. Igarashi, K. Okazaki, E. Yoshii, K. Yamaguchi,
J. Org. Chem. 1990, 55, 3431; (e) T. Bauer, J. Kozak, C. Chapuis, J. Jurczak,
J. Chem. Soc., Chem. Commun. 1990, 1178; (0C. Spino, G. Liu, J. Org. Chem.
1993, 58, 817.
[lo71 (a) M.M. Midland, M.M. Alfonso, J. Am. Chem. Soc. 1989, 111, 4368; (b) M.M.
Midland, R. W. Koops, J. Org. Chem. 1990, 55, 5058.
[lo81 (a) G. Gerstberger, C. Palm, R. Anwander, Chem. EUKJ. 1999, 5, 997; (b) G. Gerst-
berger, R. Anwander, Microporous Mesoporous Muter. 2001, 44, 303.
[lo91 G. A. Molander, R. M. Rzasa, J. Org. Chem. 2000, 65, 1215.
[110] T. Morita, T. Arai, H. Sasai, M. Shibasaki, Tetrahedron: Asymmetry 1998, 9, 1445.
[ l l l ] (a) H. Sasai, T. Suzuki, S. Arai, T. Arai, M. Shibasaki, J. Am. Chem. Soc. 1992, 114,
441; (b) T. Okano, Y. Satou, M. Tamura, J. Kiji, Bull. Chem. Soc. Jpn. 1997, 70, 1879.
[112] For reviews, see: (a) M. Shibasaki, H. Sasai, Pure Appl. Chem. 1996, 68, 523; (b)
M. Shibasaki, H. Sasai, T. Arai, Angew. Chem. 1997, 109, 1290; Angew. Chem. Int.
Ed. 1997,36, 1237. (c) M. Shibasaki, H. Groger, Top. Organomet. Chem. 1999, 2, 199.
[113] H. Sasai, T. Suzuki, N. Itoh, K. Tanaka, T. Date, K. Okamura, M. Shibasaki, J. Am.
Chem. Soc. 1993, 115, 10372.
[114] (a) H. Sasai, Y.M.A. Yamada, T. Suzuki, M. Shibasaki, Tetrahedron 1994, 50, 12313;
(b) H. Sasai, W.-S. Kim, T. Suzuki, M. Shibasaki, Tetrahedron Lett. 1994, 35, 6123.
[115] H. Sasai, T. Tokunaga, S. Watanabe, T. Suzuki, N. Itoh, M. Shibasaki, J. Org. Chem.
1995, 60, 7388.
[116] T. Arai, Y. M. A. Yamada, N. Yamamoto, H. Sasai, M. Shibasaki, Chem. EUKJ. 1996,
2, 1368.
[117] K. Yamada, S. J. Hanvood, H. Groger, M. Shibasaki, Angew. Chem. 1999, 111, 3713;
Angew. Chem. Int. Ed. 1999, 38, 3504.
[118] (a) Y. M. A. Yamada, N. Yoshikawa, H. Sasai, M. Shibasaki, Angew. Chem. 1997, 109,
1942; Angew. Chem. Int. Ed. 1997, 36, 1871; (b) N. Yoshikawa, Y.M. A. Yamada,
J. Das, H. Sasai, M. Shibasaki, J. Am. Chem. Soc. 1999, 121, 4168.
[119] (a) H. Sasai, T. Arai, M. Shibasaki, J. Am. Chem. Soc. 1994, 116, 1571; (b) H. Sasai,
T. Arai, Y. Satow, K.N. Houk, M. Shibasaki, J. Am. Chem. Soc. 1995, 117, 6194.
[120] Y. S. Kim, S. Matsunaga, J. Das, A. Sekine, T. Ohshima, M. Shibasaki, J . Am. Chem.
Soc. 2000, 122, 6506.
[121] E. Emori, T. Arai, H. Sasai, M. Shibasaki, J. Am. Chem. Soc. 1998, 120, 4043.
[122] T. Arai, H. Sasai, K. Aoe, K. Okamura, T. Date, M. Shibasaki, Angew. Chem. 1996,
108, 103; Angew. Chem., Int. Ed. Engl. 1996, 35, 104.
[123] (a) K. Mikami, M. Terada, T. Nakai, J. Org. Chem. 1991, 56, 5456; (b) K. Mikami,
M. Terada, T. Nakai, J. Chem. Soc., Chem. Commun. 1993, 343.
[124] M. Terada, T. Nakai, K. Mikami, Inorg. Chim. Actu 1994, 222, 377.
[125] L. Gong, A. Streitwieser, J. Org. Chem. 1990, 55, 6235.
[126] K. Uotsu, H. Sasai, M. Shibasaki, Tetrahedron: Asymmetry 1995, 6, 71.
[I271 Y. Makioka, I. Nakagawa, Y. Taniguchi, K. Takaki, Y. Fujiwara, J. Org. Chem. 1993,
58, 4771.
[128] T. Imamoto, T. Kusumeto, M. Yokoyama, Tetrahedron Lett. 1983, 24, 5233.
1012 3.2 Special Catalysts and Processes

[129] T. Okano, K. Ohno, J. Kiji, Chem. Lert. 1996, 1041.

[130] J. Huskens, J. A. Peters, H. van Bekkum, G. R. Choppin, Inorg. Chem. 1995, 34, 1756.
[131] M. Kamaura, K. Daikai, T. Hanamoto, J. Inanaga, Chem. Lett. 1998, 697.
[ 1321 M. A. Ciufolini, M. V. Deaton, S. Zhu, M. Chen, Tetrahedron 1997, 53, 16299.
[133] K. S. Kirshenbaum, New J. Chem. 1983, 7, 699.
[134] H. Ohno, A. Mori, S. Inoue, Chem. Lett. 1993, 975.
[135] H. Ohno, A. Mori, S. Inoue, Chem. Left. 1993, 375.
[136] P. van de Weghe, J. Collin, Tetrahedron Lett. 1995, 36, 1649.
[137] J.-H. Gu, M. Okamoto, M. Terada, K. Mikami, T. Nakai, Chem. Lett. 1992, 1169.
[138] A. Fujii, S. Sakaguchi, Y. Ishii, J. Org. Chem. 2000, 65, 6209.
[ 1391 E. Groth, M. Jeske, Angew. Chem. 2000,112,586;Angew. Chem. lnt. Ed. 2000,39,574.
[ 1401 (a) F. T. Edelmann, Top. Curr: Chem. 1996, 179, 247; (b) G. A. Molander, Chemtracts -
Org. Chem. 1998, 11, 237; (b) G. A. Molander, E. D. Dowdy, Top. Organomet. Chem.
1999, 2, 119.
[141] W. J. Evans, I. Bloom, S. C. Engerer, J. Catal. 1983, 84, 468.
[142] W. J. Evans, I. Bloom, W. E. Hunter, J. L. Atwood, J. Am. Chem. SOC. 1983,105, 1401.
[143] See also: C. Ye, C. Qian, X. Yang, J. Orgunomet. Chem. 1991,407, 329 and references
therein.
[144] G. Jeske, H. Lauke, H. Mauermann, H. Schumann, T. J. Marks, J. Am. Chem. Soc.
1985, 107, 8111.
[145] M. A. Giardello, V. P. Conticelli, L. Brard, M. R. Gagne, T. J. Marks, J. Am. Chem. Soc.
1994, 116, 10241.
[146] (a) G. A. Molander, J. 0. Hoberg, J. Org. Chem. 1992, 57, 3266; (b) G. A. Molander,
J. Winterfeld, J. Organomet. Chem. 1996, 524, 275.
[147] Y. Obora, T. Ohta, C. L. Stem, T. J. Marks, J. Am. Chem. SOC. 1997, 119, 3735.
[148] (a) T. Sakakura, H.-J. Lautenschlager, M. Tanaka, J. Chem. Soc., Chem. Commun.
1991, 40; (b) S. Onozawa, T. Sakakura, M. Tanaka, Tetrahedron Lett. 1994, 35, 8177.
[149] P.-F. Fu, L. Brard, Y. Li, T. J. Marks, J. Am. Chem. Soc. 1995, 117, 7157.
[150] A. R. Muci, J.E. Bercaw, Tetrahedron Lett. 2000, 41, 7609.
[ 15 11 T. I. Gountchev, T. D. Tilley, Organometallics 1999, 18, 5661.
[152] N. S. Radu, T.D. Tilley, J. Am. Chem. SOC. 1995, 117, 5863.
[ 1531 A. Z. Voskoboynikov, A. K. Shestakova, I. P. Beletskaya, Organometallics 2001,
20, 2794.
[154] (a) P.-F. Fu, T. J. Marks, J. Am. Chem. Soc. 1995, 117, 10747; (b) K. Koo, T. J. Marks,
J. Am. Chem. Soc. 1998, 120, 4019; (c) P.-F. Fu, K. Koo, T. J. Marks, Macromolecules
1999, 32, 981.
[155] (a) G. A. Molander, M. Julius, J. Org. Chem. 1992, 57, 6347; (b) G. A. Molander,
P. J. Nichols, J. Am. Chem. SOC. 1995, 117, 4415; (c) G. A. Molander, P. J. Nichols,
J. Org. Chem. 1996, 61, 6040; (d) G.A. Molander, C.P. Corrette, J. Org. Chem.
1999, 62, 9697.
[ 1561 G. A. Molander, W. H. Retsch, Organometallics 1995, 14, 4570.
[157] (a) T. D. Tilley, Acc. Chem. Res. 1993,26,22; (b) N. S. Radu, T. D. Tilley, J. Am. Chem.
SOC. 1992,114, 8293; (c) N.S. Radu, T.D. Tilley, J. Am. Chem. SOC.1995,117, 5863;
(d) I. Castillo, T. D. Tilley, Organometallics 2000, 19, 4733.
[158] C.M. Forsyth, S.P. Nolan, T.J. Marks, Organometallics 1991, 10, 2543.
[159] T. Sakakura, H.-J. Lautenschlager, M. Nakajima, M. Tanaka, Chem. Lett. 1991, 913.
[ 1601 T. Kobayashi, T. Sakakura, T. Hayashi, M. Yumura, M. Tanaka, Chem. Lett. 1992, 1157.
[161] (a) M. R. Gagne, T. J. Marks, J. Am. Chem. SOC. 1989,111,4108; (b) M. R. Gagne, C. L.
Stem, T. J. Marks, J. Am. Chem. Soc. 1992, 114, 275; (c) M. A. Giardello, V. P. Conti-
celli, L. Brard, M. Sabat, A. L. Rheingold, C. L. Stem, T. J. Marks, J. Am. Chem. Soc.
1994, 116, 10212.
 References 1013

[162] S. Tian, V. M. Arrendondo, C. L. Stern, T. J. Marks, Organometallics 1999, 18, 2568.

[163] (a) G.A. Molander, E. D. Dowdy, J. Org. Chem. 1998, 63, 8983; (b) G. A. Molander,
E. D. Dowdy, J. Org. Chem. 1999, 64, 6515.
[164] (a) Y. Li, P. F. Fu, T. J. Marks, Organometallics 1994,13, 439; (b) Y. Li, T. J. Marks,
J. Am. Chem. Soc. 1996, 118, 9295.
[165] Y. Li, T. J. Marks, Organometallics 1996, 15, 3770.
[166] (a) V. M. Arrendondo, F. E. McDonald, T. J. Marks, J. Am. Chem. Soc. 1998,120,4871;
(b) V. M. Arrendondo, S. Tian, F.E. McDonald, T. J. Marks, J. Am. Chem. Soc. 1999,
121, 3633; (c) V. M. Arrendondo, F. E. McDonald, T. J. Marks, Organometallics 1999,
18, 1949.
[167] (a) Y. Li, T. J. Marks, J. Am. Chem. Soc. 1996, 118, 707; (b) Y. Li, T. J. Marks, J. Am.
Chem. Soc. 1998, 120, 1757.
[168] T. H. Jones, M. S. Blum, H. M. Fales, C. R. Thompson, J. Org. Chem. 1980, 45, 4778.
[169] M. R. Douglass, T. J. Marks, J. Am. Chem. Soc. 2000, 122, 1824.
[170] (a) T. Yokomatsu, T. Yamagishi, S. Shibuya, Tetrahedron: Asymmetry 1993, 4, 1783;
(b) N. P. Rath, C. D. Spilling, Tetrahedron Lett. 1994, 35, 227; (c) H. Sasai, M. Bou-
gauchi, T. Arai, M. Shibasaki, Tetrahedron Lett. 1997, 38, 2717.
[171] H. Sasai, S. Arai, Y. Tahara, M. Shibasaki, J. Org. Chem. 1995, 60, 6656.
[172] H. Groger, Y. Saida, H. Sasai, K. Yamaguchi, J. Martens, M. Shibasaki, J. Am. Chem.
Soc. 1998, 120, 3089.
[173] K. N. Harrison, T. J. Marks, J. Am. Chem. Soc. 1992, 114, 9220.
[174] E.A. Bijpost, R. Duchateau, J. H. Teuben, J. Mol. Catal. 1995, 95, 121.
[ 1751 A. Z. Voskoboynikov, I. P. Beletskaya, New J. Chem. 1995, 19, 723.
[176] (a) T.-L. Ho, Synthesis 1973, 34; (b) H. B. Kagan, J. L. Namy, in Handbook on the
Physics and Chemistry of the Rare Earths (Eds.: K.A. Gscheidner, L. Eyring),
North-Holland, Amsterdam, 1984, Chapter 50; (c) J. A. Soderquist, Aldrichim Actu
1991, 24, 15; (d) for a recent review, see: H.B. Kagan, J.L. Namy, Top. Organomet.
Chem. 1999, 2, 155.
[177] T. Okano, M. Matsuoka, H. Konishi H, J. Kiji, Chem. Lett. 1987, 181.
[ 1781 C. F. de Graauw, J. A. Peters, H. van Bekkum, J. Huskens, Synthesis 1994, 1007.
[179] Y. Nakano, S. Sakaguchi, Y. Ishii, Tetrahedron Lett. 2000, 41, 1565.
[180] J. L. Namy, J. Souppe, J. Collin, H. B. Kagan, J. Org. Chem. 1984, 49, 2045.
[181] R. Anwander, C. Palm, Stud. Su$ Sci. Cutal. 1998, 117, 413.
[182] D.A. Evans, S.G. Nelson, M.R. Gagne, A.R. Muci, J. Am. Chem. Soc. 1993, 115,
9800.
[183] J. Prandi, J. L. Namy, G. Menoret, H. B. Kagan, J. Organomet. Chem. 1985, 285,
449.
[184] M. Bougauchi, S. Watanabe, T. Arai, H. Sasai, M . Shibasaki, J. Am. Chem. Soc. 1997,
119, 2339.
[185] (a) T. Okano, K. Miyamota, J. Kiji, Chem. Lett. 1995, 246; (b) T. Okano, Y. Hayashi-
zaki, J. Kiji, Bull. Chem. Soc. Jpn. 1993, 66, 1863.
[186] B.K. Shull, T. Sakai, M. Koreeda, J. Am. Chem. Soc. 1996, 118, 11690.
[187] (a) W.-M. Dai, M. Y. H. Lee, Tetrahedron Lett. 1999, 40, 2397; (b) W.-M. Dai, W. L.
Mak, A. Wu, Tetrahedron Lett. 2000, 41, 7101.
[188] J. Uenishi, S. Masuda, S. Wakabayashi, Tetrahedron Lett. 1991, 32, 5097.
[189] S. Onozawa, T. Sakakura, M. Tanaka, M. Shiro, Tetrahedron 1996, 52, 4291.
[I901 H. Berberich, P. W. Roesky, Angew. Chem. 1998, 37, 1569; Angew. Chem. Int. Ed.
1998, 110, 1618.
[191] M. Meguro, N. Asao, Y. Yamamoto, J. Chem. Soc., Chem. Cornmun. 1995, 1021.
[192] C. Qian, D. Zhu, Y. Gu, J. Mol. Cutal. 1990, 63, L1.
[193] S. Zehani, G. Gelbard, J. Chem. Soc., Chem. Cornmun. 1985, 1162.
1014 3.2 Special Catalysts and Processes

[194] W. J. Evans, T. A. Ulibam, J. W. Ziller, J. Am. Chem. Soc. 1990, 112, 2314.
[195] J. L. Atwood, W. E. Hunter, A.L. Wayda, W. J. Evans, Inorg. Chem. 1981, 20, 4115.
[196] (a) W.J. Evans, R.A. Keyer, J. W. Ziller, Organometallics 1990, 9, 2628; (b) W. J.
Evans, R. A. Keyer, J. W. Ziller, Organometallics 1993, 12, 2618.
[I971 C. M. Forsyth, S. P. Nolan, C. L. Stem, T. J. Marks, A. L. Rheingold, Organometallics
1993, 12, 3618.
[ 1981 H. J. Heeres, M. Maters, J. H. Teuben, G. Helgesson, S. Jagner, Organometallics 1992,
11, 350.
[ 1991 W. J. Evans, D. K. Drummond, T. P. Hanusa, R. J. Doedens, Organometallics 1987,
6, 2279.
[200] 0. Runte, T. Priermeier, R. Anwander, Chem. Commun. 1996, 1385.
[201] H. W. Gorlitzer, M. Spiegler, R. Anwander, Eur: J. Inorg. Chem. 1998, 1009.
[202] H. W. Gorlitzer, M. Spiegler, R. Anwander, J. Chem. SOC., Dalton Trans. 1999,
4287.
[203] S. Amin, J.R. Morrow, C.H. Lake, M.R. Churchill, Angew. Chem. 1994, 106, 824;
Angew. Chem., Int. Ed. Engl. 1994, 33, 173.
[204] R. Anwander, Chem. Mat. 2001, 13, 4419.

3.2.6 Recent Progress in Special Phosphorus-Containing

Auxiliaries for Homogeneous Enantioselective
Catalysis
Francine Agbossou-Niedercorn

3.2.6.1 Introduction
An elegant way of reducing the generation of waste and talung into account the
depletion of raw materials while producing chemicals is to use very efficient,
productive, and environmentally friendly catalytic processes [ 11. Many complex
organic derivatives possess a stereogenic center, which can be efficiently intro-
duced in an enantioselective catalytic step during their synthesis. With that objec-
tive, the design of chiral ligands for transition metal catalyzed asymmetric reac-
tions has been intensively followed with the aim of obtaining very efficient enan-
tioselective catalysts (cf. Section 2.9) [2]. The latter must address high synthetic
efficiency in terms of chemo-, regio-, diastereo-, and enantio-selectivity. For
these processes, the key parameter is generally the design of the most satisfactory
chiral auxiliary. Recent reviews provide examples of the incredibly fertile area of
chiral ligand design for enantioselective catalysis [3].
Chiral diphosphanes (diphosphines) occupy a special place among the chiral
auxiliaries described so far because of their efficiency and for historical reasons.
Typically, diphosphines are involved industrially in the enantioselective hydroge-
nation of C=C, C=O, and C=N bonds, and in the isomerization of an allylamine
[4]. The design of the ligand is intimately connected to the catalytic process in
which the ligand will be involved. In addition, the combination of the metallic
 3.2.6.2 Monophosphines 1015

centers and the diversity of organic precursors offer an enormous potential for new
catalytic systems. Ligand modifications allow the electronic and steric character-
istics in the vicinity of the P atoms to be varied. A large family of auxiliaries is
constituted by heteroatom-containing phosphine ligands in which the heteroatom
is either directly connected to the phosphorus making it possible thus to vary
intimately the properties of the auxiliaries, or present as a second coordination
end-group providing chelating ligands with specific features. This review
describes some recent progress in the setting up of special new ligands. Several
ligands will be preserved in order to indicate the scope of these auxiliaries. In
addition, the examples are selected deliberately from recent reports including
the accompanying catalytic reactions (cf. Section 3.1.1.7).

3.2.6.2 Monophosphines

3.2.6.2.1 Monodentate Monophosphines

Although most of the research is often concerned with setting up chelating
auxiliaries [5], monodentate monophosphorus ligands have been investigated
with some success [6]. In the context of this section, these feature heteroatoms
bound to the P atom, which may be chiral as well. The vicinal heteroatoms
allow the subtle control exerted by the ligands on the metallic center to be varied.
In order to induce enantiodifferentiation in the catalytic process, the monopho-
sphine ligands have to present a very high level of conformational rigidity. To ful-
fil this requirement, the best auxiliaries have been based on binaphthol, TADDOL,
and hindered diamines. These ligands participate efficiently in C-C bond-forming
reactions, those mostly studied being 1,4-addition to unsaturated compounds and
allylic substitution. For example, phosphoramidite (Structure 1) [7] was used with
success in Cu-catalyzed dialkylzinc addition to cyclohexanediones [S] and nitro-
olefins [9] leading to selectivities as high as 99 % and 92 % ee respectively for the
substrates. Binaphthol-based ligands [lo], TADDOL derivatives 2 [ 11, 121 and
others [I31 were used in diethylzinc addition to enones (up to 89% ee). Bi-
naphthol based auxiliaries [ 14, 151 were used in Ir- [ 161 and Pd-catalyzed allylic
substitution (up to 96 % ee), and in Rh-catalyzed hydrogenation of itaconic acid
derivatives (99 % ee) [ 171.

Ph, ,Ph

T
‘’ IT Ph/ ‘Ph
X = NMe2
1016 3.2 Special Catalysts and Processes

Ligands of type 1 have also led to interesting results in kinetic resolutions

during Cu-catalyzed reactions of dialkylzinc with cycloalkene oxides (eq. (1))
[18] and cyclohexenones [19]. On the other hand, monophosphonites bearing a
fused 1,4-dioxane ring behave moderately in the Rh-catalyzed hydrosilylation
of ketones (up to ca. 56% ee) [20]; cf. Section 2.6 Finally, a phosphapallada-
cyclic complex has been reported as an exceptionally fast catalyst for the
hydroarylation of norbornene (TONS up to 10") but with low ees (<25%)

46% yield 37% yield

80% ee 99% ee

Thus, chiral monophosphine auxiliaries have a real potential for various cata-
lytic processes and certainly deserve further attention. In addition, their synthesis
allows a modular approach to a variety of structures. Due to the importance of
the binaphthol framework for efficient enantioselection, the latter has been the
most frequently used for the construction of monophosphine monodentate auxi-
liaries.

3.2.6.2.2 Bidentate Monophosphine Ligands

Since the first synthesis of the chiral chelating diphosphine DIOP (Structure 3)
described by Kagan and Dang [22] and the breakthrough of Noyori and Takaya
with the axially chiral BINAP ligand 4 [23] including its exceptionally wide use
in enantioselective catalysis, a huge amount of effort has been devoted to the
synthesis of C,-symmetric diphosphines [2, 51. In fact, the C, symmetry concept
has led to remarkable results in the field of asymmetric catalysis. In addition,
even if the phenyl-substituted phosphine-based auxiliaries have been the most
used for a long time, the emergence of ligands containing phosphorus atoms
exhibiting modular acido-basic features, as is the case for Me-DuPHOS 5 [24]
for example, has gained general acceptance. Nonsymmetrical bidentate dipho-
sphine ligands have also had their own active promoters [25, 261. Due to the suc-
cess of phosphorus ligands, the other chiral nitrogen containing compounds such
as bis(oxazo1ines) 6 have appeared in the literature only since 1990. One of the
first reactions related to the use of these new C,-symmetric ligands has been
described by Masamune et al. [27], namely the cylopropanation of olefins
using Cu catalysts (90% ee).
Subsequently, the modification of the centrosymmetric group [(X) in Structure
61 joining the two oxazoline moieties as well as of the substituents on the oxazo-
 3.2.6.2 Monophosphines 1017

3 4 5 6

line part has led to numerous new ligands that have been applied in cyclopropana-
tion, Diels-Alder, hydrosilylation, aldol addition, glyoxylate-ene, and many other
reactions [28].

Bidentate Heterofunctionalized Phosphines

The synthesis and application of auxiliaries bearing different potentially coordi-

nating moieties, so-called bitopic ligands, has likewise appeared to be a promising
research area [5]. Nevertheless, species exhibiting a P and either a weakly coor-
dinating hemilabile function (0 or S) or a hard nitrogen moiety as the second
coordinating site have appeared only lately. As a P,O bidentate auxiliary, the
binaphtyl based MOP ligand 7 [29] has been the most frequently investigated
for hydrovinylation (62 % ee) [30] and imine arylation (96 % ee) [3 I]. Other
P,O- and P,S-type bidentates have also appeared. For example, the SEMI-
ESPHOS S [32] , acid-based [33, 341 and sulfur-containing derivatives 9 [35,
361 were all devoted to allylic alkylation or amination either in the standard test
reaction (up to 99% ee) [32, 34, 36, 371 or for the synthesis of natural product
intermediates [33, 36, 381. A BINAP hemioxide has also been described in
platinum-catalyzed hydroformylation of styrene, but with only moderate enantio-
selectivities (30 % ee) [39].

7 8 9 10

As final examples of potentially P,O bitopic ligands, amidophosphines have

been applied with success to various enantioselective transformations, e. g., addi-
tion of arylboronic acids, Grignard reagents, and organocuprates to enones in the
presence of Rh and Cu catalysts (10) (> 96 % ee) [40].
The chiral nitrogen-phosphine ligands represent the most flourishing bitopic
auxiliaries. They can be divided into five classes closely related to their skelet-
ons, which are binaphtyl-, pyridine-, metallocene-, amine-, or oxazoline-based.
Much attention has been given to the last class, which has led to a spectacular
1018 3.2 Special Catalysts and Processes

recent development. These ligands constitute perfect examples in which the C2

symmetry concept (which a priori favors a restricted number of diastereomeric
intermediates) is abandoned in favor of an electronic control of these diastereo-
meric species responsible - from the thermodynamic or kinetic points of view
- for the asymmetric induction. For the binaphtyl-based P,N ligands, one naph-
thy1 residue bears the phosphorus end while the other carries the diversely sub-
stituted nitrogen site. As such, their structure is closely related to the previously
reported MOP ligand [29]. These auxiliaries have been developed for various
reactions, e.g., allylic substitution (up to 71 % ee) [41], conjugate addition to
enones (up to 98% ee) [42], and Suzuki coupling (up to 87% ee) [43] (see
also Section 2.11).
Pyridine and related aromatic (quinoline, quinazoline) P,N derivatives (11, 12)
have been created for Rh-catalyzed hydroboration-oxidation [44] or -amination
[45]. Other pyridine-related auxiliaries have been synthesized for Pd-assisted
allylic alkylation [46] in test conditions furnishing the substitution product in
up to 93 % ee. The QUIPHOS ligand 13 has been tested in Pd-assisted allylic
amination (up to 94 % ee) [47], allylic alkylation of b-ketoesters (up to 95 % ee)
[48], and Cu-catalyzed Diels-Alder reaction between an acryloyl derivative and
cyclopentadiene [49].

11 12 13

Ferrocenyl-based ligands comprise a versatile class of auxiliaries because they

can be easily modified at the benzylic position with retention of configuration and
can incorporate both central and planar chiralities. The appropriate balance of
steric and electronic factors has provided ferrocenyl derivatives featuring chelat-
ing P,N properties that proved beneficial in numerous enantioselective transforma-
tions [50].Among more recent applications, they could be utilized very efficiently
in Pd-catalyzed hydrosilylation (14; > 99 % ee) [5 11 and hydroboration (> 94 %
ee) [52] of olefins, allylic amination (99 % ee) [53], Suzuki cross coupling reac-
tions (Section 2.11) [54], and enamide hydrogenation (>99 % ee) [55].

14
 3.2.6.2 Monophosphines 1019

Other aminophosphines have also been sought and applied in different enantio-
selective transformations, e. g., allylic substitution [56] (up to 95 % ee), and
Ir-based imine hydrogenation (88 % ee) [57]. Chiral aminophosphines have also
been investigated in the asymmetric transfer hydrogenation of ketones (up to
84 % ee for the reduction of aryl ketones) [58].

Chiral Phosphine Oxazoline Auxiliaries

A large class of P,N ligands is composed of the phosphine oxazoline deriva-

tives (phosphines and phosphites). Abundant structural variations and broad
catalytic applications summarize the properties of these auxiliaries. Indeed,
the setting up of such derivatives enjoys considerable current popularity.
Their use has been reviewed recently [59-611. The modular approach to
such ligands is very powerful and several chiral centers can be introduced.
In addition, as the oxazoline ring originates from amino alcohols and amino
acids, the syntheses can benefit from the potential of the chiral pool source.
As mentioned, the structural array provided by such ligands is very attractive
and diverse. Among these compounds some phenyl-based ones were reported
roughly at the same time by Helmchen [62], Pfaltz [63], and Williams [64].
There followed many examples of heterofunctionalized oxazoline P,N ligands
based on aryls (15) [65-671, ferrocenes (16) [68, 691, carbohydrates (17)
[70, 711, amines [72, 73 a], binaphthol [74, 751, and TADDOL (18) [72, 761
providing phosphine and phosphite oxazolines. The common key is proper
adjustment of the stereoelectronic properties of the ligands in order to induce
the greatest discrimination of the prochiral site of the substrates to be trans-
formed. The principal effect foreseen is the different trans influences of the
phosphorus and nitrogen atoms.

M;:
15 16 17

R = t-BU
CPr
18
1020 3.2 Special Catalysts and Processes

The potential of such ligands is very significant [S9] as they operate an efficient
enantiocontrol in many reactions. As recent examples, they proved to be effective
in Ir-catalyzed hydrogenation of simple olefins (eq. (2)) (up to 98 % ee) [77] and
imine [78], and standard allylic substitution with C- and N-nucleophiles catalyzed
by Pd (up to 99 % ee) [38, 68 b, 70, 71, 74, 791 and Pt (up to 90 % ee) [go], but
also in alkylation of nonsymmetric allylic acetates (up to 99% ee) [38, 66, 72,
73 a, el, hydrosilylation of ketones (up to 86 % ee) (Rh-based) [76, 811 and imines
(Ir-catalyzed, up to 96% ee) [69, 81 a], Heck reaction (eq. (3); cf. Section 3.1.6)
[67, 68 a, 73 b, c], Ru-mediated olefin cyclopropanation (up to 75 % ee; cf. Sec-
tion 3.1.7) [6S], Ru-mediated transfer hydrogenation of ketones (up to 94% ee)

&%
[82], copper-catalyzed 1,4-addition of organometallic reagents to enones [7S],
and other [S9].

@ /
+ H2 [K*(COD)]BAR; @ \ P

Me0 50bar 'y'b / /--

3-Bu
239: Me0 97% ee /
BARF: (tetrakis[3,5bis(tifluoromethyl)phenyl]b --- (2)

[Pd2(dba)3.dba](4 ml%)
L: P,N based oxazoline ligand
bervlene
r.t., 5 days
* fl
91% yield
98% ee
(3)

The applications of the chiral chelating heterofunctionalized monophosphine

ligands described in this section prove that they present attractive features and
are excellent auxiliaries for a large variety of reactions. As such, they constitute
an impressive and large library of ligands for which the full potential is perceived
but still unknown. It is thus expected that these families of ligands will be further
developed in the future. Libraries of phosphino oxazolines have been constituted
using a combinatorial approach [83]. Up to now, these ligands have often been
applied in standard test reactions and are expected to find use in the synthesis
of fine chemicals.

3.2.6.3 Bi(di,bis)phosphines
Likewise, in the continuing research aimed at the discovery of new chiral bipho-
sphines, specific attention is also being devoted to the design of biphosphines pos-
sessing heteroatoms bound to the phosphorus moieties. The main purpose is to
access structures with stereoelectronic properties that can be fine-tuned and
hence, intrinsically, to control the regio- and stereoselectivity of a catalytic reac-
tion. These auxiliaries present a variety of structures and are based on symmetrical
or nonsymmetrical skeletons supplying a diversity of phosphines possessing P-0
 3.2.6.3 Bi(di,bis)phosphines 1021

bonds, e. g., di(bi)phosphinites, diphosphites, phosphine phosphonites, phosphine

phosphites; P-N bonds, e. g., phosphine phosphoramidite, bisaminophosphines;
or both, e. g., aminophosphine phosphinite and related ligands. The organic pre-
cursors are symmetrical or nonsymmetrical diols or diamines, sugars, or amino
alcohols.

3.2.6.3.1 P(0)-Containing Chiral Bisphosphines

Although they are often considered as poorer ligands than diphosphines, they lead
also to very efficient and attractive enantioselective catalytic systems as exempli-
fied here. As recent examples, diphosphinites 19 and 20 have been involved suc-
cessfully in hydrogenation of olefins (mostly itaconate derivatives and enamides,
up to > 99.9 % ee) ([84-891 and functionalized ketones (21) (up to 86 % ee) [90],
hydrocyanation (19) [9 11, standard Pd-mediated allylic alkylation (20) [92] (up to
86% ee) [93], and Diels-Alder reaction between a,D-enals and dienes (eq. (4);
99% ee) [94].

catalyst
(5 mol%)
2,6di-te&-buiy@yidine
(5mol%) ~ &Br
+ A C H O CYCh CHO
-20T,
20 h exolendo = 10190
86% > 99% ee (4)

RajanBabu et al. has deeply explored the chemistry of carbohydrate phosphinite

complexes [84, 951. While the carbohydrate backbone provided the necessary
stereochemical diversity, substitution patterns around phosphorus were used to
vary the steric and electronic properties of the ligand.
1022 3.2 Special Catalysts and Processes

In parallel, bisphosphites have attracted much attention mainly as ligands for

rhodium-mediated hydroformylation (cf. also Sections 2.1.1, 2.9, and 3.3.1).
For that reaction, it has long been difficult to reach very high asymmetric induc-
tions with either Pt or Rh catalysts [96]. A high enantioselectivity was reported for
the hydroformylation of styrene using a bisphosphite ligand (90 % ee) [97], but
the selectivities observed for other olefinic substrates were unsatisfactory. Yet,
since the discovery of BINAPHOS by Nozaki and Takaya [98], a phosphine phos-
phite ligand based on binaphthyl, very high enantioselectivities have been ob-
tained for a large range of olefins (>94 % ee) [99]. Other ligands of that large
family also led to good enantioselectivities in olefin hydrogenation [I02 a, b,
1031 (> 99.5 % ee), enamine hydrogenation (up to 71 % ee) [104], hydroformyla-
tion [103, 1051 (up to 74% ee), Pd-assisted allylic alkylation [loo] and
Cu-mediated 1,4-additions [ 1011. Interestingly, all of the ligands described are
based on biphenyl or binaphthyl moieties.
Bisphosphites, some of them with C, symmetry, were applied with success in
organometallic addition to a,P-unsatured carbonyl compounds (22) (up to 92 % ee)
[ 106, 1071, hydrocyanation (up to 73 % ee) [ 1071, hydrogenation (up to 99 % ee)
[108, 1091, and Pt- and Rh-based asymmetric hydroformylation (22, 23) (up to
92% ee) [108, 1101.

23

22

Many efforts are devoted to the design of new P(0)-containing biphosphine

ligands. However, the most difficult task is still to reach very high enantioselec-
tivities in the hydroformylation reaction, as well as high turnover numbers.

3.2.6.3.2 P(N)-Containing Chiral Bisphosphines

Diamine-based auxiliaries have been less investigated than the P(0)-containing
derivatives, but bisaminophosphanes induced interesting enantioselectivities in
hydrogenation of enamides (24, up to 98% ee) [87] and ketones (up to 87%
ee) [ l l l ] , olefin hydroboration (up to 77 % ee) [112] as well as allylic substitu-
tion [ 1131. Diiminophosphoranes, which coordinate through their nitrogen
atoms, have been applied in the standard Pd-mediated allylic alkylation (25)
(up to 85 % ee) [I 141 and in Cu-assisted cyclopropanation of styrene (26)
(90% ee) [115].
 3.2.6.3 Bi(di,bis)phosphines 1023

24 25 26

3.2.6.3.3 P(N)- and P(0)-Containing Chiral Bisphosphines

Non-C2-symmetric organophosphorus ligands bearing both P(0) and P(N)
moieties, namely the aminophosphine phosphinites, have already been under
investigation for a long time [26]. The primary interest in such derivatives
relied on their easy and modular synthesis based on optically pure natural
precursors, e. g., amino acids and amino alcohols. They provided auxiliaries
with a great potential for ligand variation and tuning for a number of transition
metal catalyzed transformations. In addition to their nonsymmetrical skeletons,
they also provide phosphorus end with different electronic properties that can
be beneficial to a catalytic process. Thus, electron-rich or electron-deficient
groups can substitute on the P atoms, providing quite different ligand properties.
For example, it has been demonstrated that electron-rich AMPP ligands (e. g.,
Structure 27) were particularly well suited for hydrogenation of functionalized
ketones [ 1161. The ligand optimization furnished structures that induce over
99 % ee for the hydrogenation of several functionalized ketones. In addition,
such auxiliaries (27) were used very recently to hydrogenate simple fluorinated
ketones equally well with exceptionally high enantioselection (eq. ( 5 ) ) [ 1171.

Less electron-rich ligands could be applied efficiently in olefin hydrogenation

(28) [IlS-1221, Pd-catalyzed allylic alkylation (29) (up to 60% ee) [123], and
hydroformylation (up to 77 % ee) [124].

27 28 29
1024 3.2 Special Cutulysts and Processes

3.2.6.4 Heterofunctionalized Multidentate P-Containing

Chiral Auxiliaries
Multidentate ligands presenting more than two potentially coordinating sites have
been recognized as useful auxiliaries for creating an adequate chiral environment
in metal-catalyzed asymmetric reactions. Such ligands present features that are
able to accommodate several factors profitable to a catalytic process. In addition
to the parent ligand chelation, for example, a second functionality can temporarily
coordinate the metal during catalysis, producing a beneficial effect on the selec-
tivity of the transformation. Such behaviour is suspected to arise in Cu-catalyzed
conjugate addition to enones conducted in the presence of the P,N ligand 30 (up to
91 % ee) [125]. Another example is related to the use of a bisphosphine ligand
with an appending amino group 31 as reported by Achiwa et al. [126]. Ligand
32 has been used in Pd-mediated allylic alkylation (up to 99% ee). However, if
this secondary interaction happens to be too strong, the kinetics of the catalytic
reaction can be seriously affected.

30 31 32

Other profitable interactions (attractive or repulsive) are characterized by sec-

ondary contacts between a remote ligand functionality and a suitable group in
the substrate, e. g., by hydrogen bonding. Towards this end, Bomer and co-work-
ers studied the impact of the use of chiral hydroxy-based phosphines (32) [ 1281 on
the rate and selectivity of the enantioselective hydrogenation reaction, with a gen-
eral improvement of the selectivity [ 1291. However, a lowering of the reaction rate
is often observed due to the above mentioned possible coordination of a hydroxy
group onto the metal [130]. There are two other reports of phosphanes leading to
higher enantioselectivities than their oxygen-protected analogues in the hydroge-
nation of itaconic acid derivatives (up to 95 % ee) [ 1311 and dehydroamino acid
derivatives (up to > 99 % ee) [132]. The benefit observed can be related to either
the hemilabile potential of the additional function or secondary interactions with
the substrate, or a combination of both.
Another major contribution of polydentate ligands is the creation of a chiral
pocket around the catalytic center providing, an appropriate chiral environment.
The chiral pocket concept has been introduced by Trost for catalytic enantioselec-
tive allylic alkylation with the tetradentate aminophosphine ligand 33 [ 1331. The
nucleophile fits into the chiral environment created by the chiral ligand and the $-
ally1 Pd intermediate. As a result, the enantiocontrol of the newly formed chiral
center is very effective. In addition, the chiral control is likely to be efficient
even at positions remote from the chiral ligand. That auxiliary has been widely
 3.2.6.5 Immobilization and Recycling 1025

used for the Pd-catalyzed formation of the C-C bond of diverse chiral synthons.
Analogous ligands have been synthesized by varying the bridge between the two
amine skeletons [134-1391.

Ph2P

33
The resulting derivatives were applied with success in the standard asymmetric
allylic alkylation (up to 97 % ee) [ 134, 1361 or in transformations involving either
specific allylic substrates (2-cycloalkenyl derivatives, up to > 99 % ee) [135,
1371, unsymmetrical substrates (monosubstituted ally1 acetate, up to 83 % ee)
[ 1401, or especial nucleophiles (nitroalkanes [141], iminoesters [138 a], or dike-
tones [139, 140, 1421). Such ligands were also effective in the formation of qua-
ternary chiral carbon through allylic substitution (eq. (6)) [ 138, 1431, deracemiza-
tion of vinyl epoxides (up to 99 % ee) [ 1441, or alkylation of ketone enolates
[ 138 b], and deracemization of allylic derivatives [ 1451.

Ph
d.r. = 19:l
95% ee
91% yield

Hybrid P,N,N,N ligands have also being synthesized and used in the standard
Pd-catalyzed allylic substitution (up to 69 % ee) [146]. The polydentate ligands,
e. g., tetradentate oxazolinylphosphine for standard allylic substitution (up to
90 % ee) [ 1471 and tridentate N,P,N for transfer hydrogenation of ketones (up
to 79 % ee) [148], P,N,P for hydrosilylation of ketones (up to 66 % ee) [149 a]
and transfer hydrogenation of acetophenone (up to 45% ee) [149 b], P,S,P for
enamide hydrogenation (up to 5.5 % ee) [150 a] and transfer hydrogenation of
acetophenone (up to 65 % ee) [150 b], and the above-described P,N,N. Structure 15
[65] is representative of this class of polydentate ligands.

3.2.6.5 Immobilization and Recycling

The recycling of enantioselective catalysts has attracted less attention than achiral
catalytic processes. Nevertheless, several approaches have been investigated with
success in that direction. As such, chiral diphosphanes have been modified in
order to obtain congeners able to operate efficiently in water (Structure 34)
1026 3.2 Special Catalysts and Processes

[ 1491. These bisphosphinite auxiliaries were used in Rh-based hydrogenation of

dehydroamino acids in water (up to 59% ee; cf. Section 3.1.1.1). Nevertheless,
the corresponding catalyst operates more efficiently in an organic media (up to
70% ee in THF). In addition, the parent protected bisphosphinite induced the
highest enantioselection during reduction of the corresponding dehydroamino
acid derivatives (up to 92 % ee in THF). In order to obtain catalysts able to per-
form best in an aqueous medium, other routes have been explored. For example,
,&B-trehalose-based bisphosphinites 35 have also been used in either an aqueous
or an aqueous/organic biphasic medium for the hydrogenation of dehydroamino
acid derivatives [ 1521. In water alone, the enantioselectivity of the hydrogenation
of dehydroamino acid derivatives could reach 99.9 % ee in the presence of a sur-
factant. Very interestingly, a high level of enantioselection could also be obtained
in the H,O-MeOH/AcOEt biphasic system (up to 98 % ee). In that case, the cat-
alytic solution could be isolated by simple phase separation and reused with a
retention of the catalytic properties. Identical behavior was obtained when the
hydroxybisphosphine 36 was applied in the Rh-assisted hydrogenation of de-
hydroamino acids and derivatives in a surfactant-containing water medium (enan-
tioselectivity improvement Aee up to 70 %) rather than in pure water [ 153, 1541.
Other examples of phosphines providing water soluble Rh catalysts are the hy-
droxybisphospholane and sulfonated diphosphines (tetrasulfonated 1,2-bis(diphe-
nylphosphinomethy1)cyclobutaneis the best example) applied respectively in the
hydrogenation of 2-acetamidoacrylic acid (water, 99.6 % ee) [ 1551 and in styrene
hydroformylation (up to 17 % ee) [ 1561.
Ho ,OH

34 35 36

Liquid or supercritical carbon dioxide has also been used as a friendly medium
providing easy recycling of the catalyst. Enantioselective catalyses (hydro-
formylations, hydrogenations) have been described with different catalysts
[157-1.591.
Polymer-supported chiral catalysts have likewise been prepared in order to
obtain access to reusable systems (cf. Section 3.1.1, especially Section 3.1.1.3).
For example, copolymerized functionalized BINAP [ 160, 1611 could be applied
in the enantioselective hydrogenation of olefinic substrates (up to 94 % ee). Simi-
larly, the copolymerization of vinyl-BINAPHOS with styrene derivatives led to a
heterogenized auxiliary which made it possible to hydroformylate styrene and
vinyl acetate (Rh catalysis) with selectivities and enantioselectivities close to
those provided by the parent homogeneous catalytic system [ 1621.
Chiral auxiliaries have also been included in dendrimeric structures (cf. Section
3.2.2). Two general strategies are possible for that purpose. Thus, multiple auxi-
 References 1027

liaries can be located at the periphery or the ligand can be incorporated in the core
of the dendrimer. The properties of the corresponding catalysts are often close to
those of the monomeric congeners for the first type, while they can be quite dif-
ferent for the second because of the space-filling nature of the dendritic structure.
The two strategies have been explored and the recycling of the macromolecular
catalyst is done by nanofiltration. For example, core dendritic BINAP ligand
was applied and recycled in the Ru-catalyzed hydrogenation of 2-[p(2-methylpro-
pyl)phenyl]acrylic acid, providing the hydrogenated product (ibuprofen) in up to
92.6 % ee. Importantly, retention of the catalytic properties was observed after
several cycles [ 1631. Peripheral dentritic ferrocenyl chiral auxiliaries (based on
37) have been applied successfully in the Rh-mediated hydrogenation of dimethyl
itaconate (up to 98 % ee) [163].

3.2.6.6 Conclusions
The chiral phosphorus-based auxiliaries presented in this article attest the potential
of such ligands in many types of enantioselective transformations catalyzed by or-
ganometallic complexes. In addition, a wide range of chiral substances have been
produced with high enantiomeric purity by using the appropriate combination of
metal and chiral auxiliary for the targeted transformation. The diversity of struc-
tures prepared and the several strategies employed allow a modular approach to
the design of ligands and a fine-tuning of the properties of the most appropriate
auxiliaries. The field of ligand design for enantioselective catalysis is in constant
expansion. The full potential of these auxiliaries is enormous and their continuing
investigation promises well.

References
[ l ] (a) R. A. Sheldon, CHEMTECH, March 1994, 38; (b) H.-U. Blaser, M. Studer, Appl.
Catal. A: Gen. 1999, 189, 191; (c) H.-U. Blaser, M. Studer, Chirality 1999, 11, 4.59.
[2] (a) H. Brunner, W. Zettelmeir, Handbook of Enantioselective Catalysis with Transition
Metal Compounds, Vols. I and 11, VCH, Weinheim, 1993; (b) Comprehensive Asym-
metric Catalysis, Vols. 1-3 (Eds.: E. N. Jacobsen, A. Pfaltz, H. Yamamoto), Springer,
Berlin, 1999.
[3] (a) L. Tonks, J. M. J. Williams, Contemp. Org. Synth. 1996, 3, 259; (b) L. Tonks, J. M. J.
Williams, Contemp. Org. Synth. 1997, 4, 3.53; (c) A.C. Regan, J. Chem. SOC., Perkin
Trans. I 1998, 1151; (d) M. Wills, J. Chem. Soc., Perkin Trans. I 1998, 3101; (e)
M. Wills, H. Tye, J . Chem. Soc., Perkin Trans. 1 1999, 1109; (f) H. Tye, J. Chem.
Soc., Perkin Trans. I 2000, 274.
1028 3.2 Special Catalysts and Processes

[4] A. N. Collins, G. N. Sheldrake, J. Crosby (editors), Chirality in Industry, Vols. I and 11,
John Wiley, Chichester, 1992 and 1997; (b) H.-U. Blaser, F. Spindler, Top. Catal. 1997,
4, 275.
[5] (a) T. Noyori, in Asymmetric Catalysis in Organic Synthesis, Wiley, New York, 1994;
(b) Catalytic Asymmetric Synthesis (Ed.: I. Ojima), VCH, New York, 1993.
[6] (a) F. Lagasse, H.B. Kagan, Chem. Pharm. Bull. 2000, 48, 315; (b) I.V. Komarov,
A. Borner, Angew. Chem. Int. Ed. 2001, 40, 1197.
[7] (a) A. H. M. de Vries, A. Meetsma, B. L. Feringa, Angew. Chem., Int. Ed. Engl. 1996,35,
2374; (b) R.N. Naasz, L.A. Arnold, L.A. Pineschi, E. Keller, B.L. Feringa, J. Am.
Chem. SOC. 1999, 121, 1104.
[8] R. Imbos, M. H. G. Brilman, M. Pineschi, B. L. Feringa, Org. Lett. 1999, I , 623.
[9] (a) N. Sewald, V. Wendisch, Tetrahedron: Asymmetry 1998, 9, 1341 ; (b) J. P. G. Vers-
leijen, A.M. van Leusen, B. L. Feringa, Tetrahedron Lett. 1999, 40, 5803.
[lo] A. Alexakis, C. Benhai’m, X. Foumioux, A. van den Heuvel, J.-M. Leveque, S. March,
S. Rosset, Synlett 1999, 1811.
[ l l ] E. Keller, J. Maurer, R. Naasz, T. Schader, A. Meetsma, B.L. Feringa, Tetrahedron:
Asymmetry 1998, 9, 2409.
[12] A. Alexakis, J. Vastra, J. Burton, C. Benhaim, P. Mangeney, Tetrahedron Lett. 1998,
39, 7869.
[13] (a) F.-Y. Zhang, A. S. C. Chan, Tetrahedron: Asymmetry 1998, 9, 1179; (b) T. Mori,
K. Kosaka, Y. Nakagawa, Y. Nagaoka, K. Tomioka, Tetrahedron: Asymmetry 1998,
9, 3175; (c) M. Yan, Y. Zhou, A.S.C. Chan, Chem. Commun. 2000, 115.
[14] B. Bartels, G. Helmchen, Chem. Commun. 1999, 741.
[15] K. Fuji, N. Kinoshita, K. Tanaka, T. Kawabata, Chem. Commun. 1999, 2289.
[I61 H. Tye, D. Smyth, C. Eldred, M. Wills, Chem. Commun. 1997, 1053.
[17] M. T. Reetz, G. Mehler, Angew. Chem. Int. Ed. 2000, 39, 3889.
[18] (a) F. Bertozzi, P. Crotti, F. Macchia, M. Pineschi, A. Arnold, B. L. Feringa, Org. Lett.
2000, 2, 933; (b) F. Bertozzi, P. Crotti, F. Macchia, M. Pineschi, B. L. Feringa, Angew.
Chem. Int. Ed. 2001, 40, 930.
[19] R. Naasz, L. A. Arnold, A. J. Minnaard, B. L. Feringa, Angew. Chem. Int. Ed. 2001,
40, 927.
[20] D. Haag, J. Runsink, H.-D. Scharf, Organometallics 1998, 17, 398.
[21] J.-M. Brunel, M.-H. Hirlemann, A. Heumann, G. Buono, Chem. Commun. 2000, 1869.
[22] (a) T. P. Dang, H. B. Kagan, J. Chem. Soc., Chem. Commun. 1971,481; (b) H. B. Kagan,
C. R. Acad. Sci. Paris, Se‘rie II b 1996, 322, 131.
[23] (a) R. Noyori, H. Takaya, Acc. Chem. Res. 1990, 23, 345; (b) R. Noyori, T. Ohkuma,
Angew. Chem. Int. Ed. 2001, 40, 40.
[24] (a) M. J. Burk, J. Am. Chem. Soc. 1991, 113, 8518; (b) M. J. Burk, M. F. Gross, G. T.
Harper, C. S. Kalberg, J. R. Lee, J. P. Martinez, Pure Appl. Chem. 1996, 68, 37.
[25] (a) K. Inogushi, S. Sakuraba, K. Achiwa, Synlett 1992, 169; (b) T. V. RajanBabu, A. L.
Casanuovo, J. Am. Chem. SOC. 1996, 118, 6325.
[26] F. Agbossou, J.-F. Carpentier, F. Hapiot, I. Suisse, A. Mortreux, Coord. Chem Rev. 1998,
178-180, 1615.
[27] R. E. Lowenthal, A. Abido, S. Masamune, Tetrahedron Lett. 1990, 31, 6005.
[28] (a) A. Pfaltz, Acc. Chem. Res. 1993,26, 339; (b) A. K. Gosh, P. Mathivanan, J. Cappiello,
Tetrahedron: Asymmetry 1998, 9, 1.
[29] Y. Uozumi, T. Hayashi, J. Am. Chem. Soc. 1991, 113, 9887.
[30] (a) N. Nomura, J. Jin, H. Park, T. V. RajanBabu, J. Am. Chem. Soc. 1998, 120, 459;
(b) M.Nandi, J. Jin, T. V. RajanBabu, J. Am. Chem. Soc. 1999, 121, 9899.
[31] T. Hayashi, M. Ishigedani, J. Am. Chem. SOC. 2000, 122, 976.
[32] S. Breeden, M. Wills, J. Org. Chem. 1999, 64, 9735.
 References 1029

[33] (a) G. Knuhl, P. Sennhenn, G. Helmchen, J. Chem. Soc., Chem. Commun. 1995, 1845;
(b) E. J. Bergner, G. Helmchen, Eur: J. Org. Chem. 2000, 419.
[34] H. Kodama, T. Taiji, T. Ohta, I. Furukawa, Tetrahedron: Asymmetry 2000, 11, 4009.
[35] (a) K. Selvakumar, M. Valentini, P. S. Pregosin, Organometallics 1999, 18, 4591 ;
(b) H. Nakano, Y. Okuyama, H. Hongo, Tetrahedon Lett. 2000, 41, 4615.
[36] D. A. Evans, K. R. Campos, J. S. Tedrow, F. E. Michael, M.R. GagnC, J. Org. Chem.
1999, 64, 2994.
[37] K. Fuji, H. Ohnishi, S. Moriyama, K. Tanaka, T. Kawabata, K. Tsubaki, Synlett 2000,
351.
[38] S . Schleich, G. Helmchen, E m J. Org. Chem. 1999, 2515.
[39] S. Gladiali, E. Alberico, S. Pulacchini, L. Kollar, J. Mol. Catal. A: Chem. 1999, 143,
155.
[40] (a) M. Kuriyama, K. Tomioka, Tetrahedron Lett. 2001, 42, 921; (b) M. Kanai, Y. Na-
kagawa, K. Tomioka, Tetrahedron 1999, 55, 3843; (c) Y. Nakagawa, M. Kanai,
Y. Nagaoka, K. Tomioka, Tetrahedron 1998, 54, 10295.
[41] S. Vyskocil, M. Smrcina, V. Hanus, M. Polasek, P. Kocovsky, J. Org. Chem. 1998,
63, 7738.
[42] X. Hu, H. Chen, X. Zhang, Angew. Chem. Int. Ed. 1999, 38, 3518.
[43] (a) P. Kocovsky, S. Vyskocil, I. Cisarova, J. Sejbal, I. Tislerova, M. Smrcina,
G.C. Lloyd-Jones, S.C. Stephen, C.P. Butts, M. Muray, V. Langer, J. Am. Chem.
Soc. 1999, 121, 7714; (b) J. Yin, S.L. Buchwald, J. Am. Chem. Soc. 2000, 122,
12051.
[44] (a) S. U. Son, H.-Y. Jang, J. W. Han, I. S. Lee, Y. K. Chung, Tetrahedron: Asymmetry
1999, 10, 347; (b) M. McCarthy, M.W. Hooper, P.J. Guiry, Chem. Commun. 2000,
1333; (c) M. McCarthy, P.J. Guiry, Polyhedron 2000, 19, 541; (d) J.M. Valk, G.A.
Whitlock, T. P. Layzell, J. M. Brown, Tetrahedron: Asymmetry 1995, 6, 2593.
[45] E. Femandez, M. W. Hooper, F. I. Knight, J. M. Brown, Chem. Commun. 1997, 173.
[46] (a) J. W. Han, H.-Y. Jang, Y. K. Chung, Tetrahedron: Asymmetry 1999, 10, 2853;
(b) K. Ito, R. Kashiwagi, K. Iwasaki, T. Katsuki, Synlett 1999, 1563; (c) C.G. Arena,
D. Drommi, F. Faraone, Tetrahedron: Asymmetry 2000, 11, 4753; (d) X. Dai, S. Virgil,
Tetrahedron Lett. 1999, 40, 1245.
[47] T. Constantieux, J.-M. Brunel, A. Labande, G. Buono, Synlett 1998, 49.
[48] J.-M. Brunel, A. Tenaglia, G. Buono, Tetrahedron: Asymmetry 2000, 11, 3585.
[49] J.M. Brunel, B. Del Campo, G. Buono, Tetrahedron Lett. 1998, 39, 9663.
[50] (a) T. Hayashi, Ferrocenes (Eds.: A. Togni, T. Hayashi), VCH, Weinheim, 1995, p. 105;
(b) C. J. Richards, A. J. Locke, Tetrahedron: Asymmetry 1998, 9, 2377.
[51] G. Pioda, A.N. Togni, Tetrahedron: Asymmetry 1998, 9, 3903.
[52] H. C. L. Abbenhuis, U. Burckhardt, V. Gramlich, A. Martelletti, J. Spencer, I. Steiner,
A. Togni, Organometallics 1996, 15, 1614.
[53] A. Togni, U. Burckrhardt, V. Gramlich, P. S. Pregosin, R. Salzmann, J. Am. Chem. Soc.
1997, 118, 1031.
[54] A. N. Cammidge, K.V.L. CrCpy, Chem. Commun. 2000, 1723.
[55] J. L. Almera Perea, M. Lotz, P. Knochel, Tetrahedron: Asymmetry 1999, 10, 375.
[56] (a) J. P. Cahill, D. Cunneen, P. J. Guiry, Tetrahedron: Asymmetry 1999, 10, 4157; (b)
M.-J. Jin, J.-A. Jung, S.-H. Kim, Tetrahedron Lett. 1999, 40, 5197; (c) A. Saitoh,
K. Achiwa, K. Tanaka, T. Morimoto, J. Org. Chem. 2000, 65, 4227; (d) T. Kohara,
Y. Hashimoto, K. Saigo, Synlett 2000, 517; (e) I.C.F. Vasconcelos, N.P. Rath,
C.D. Spilling, Tetrahedron: Asymmetry 1998, 9, 937; (f) F. Robert, F. Delbecq,
C. Nguefack, D. Sinou, Eur: J. Inorg. Chem. 2000, 351; (g) J. C. Anderson, R. J. Cub-
bon, J.D. Harling, Tetrahedron: Asymmetry 1999, 10, 2829; (h) H.-Y. Jang, H. Seo,
J. W. Han, Y. K. Chung, Tetrahedron Lett. 2000, 41, 5083; (i) T. Kohara, Y. Hashimoto,
1030 3.2 Special Catalysts and Processes

K. Saigo, Synlett 2000, 517; (j)Y. Okuyama, H. Nakano, H. Hongo, Tetrahedron:

Asymmetry 2000, 11, 1193.
[S7] J. P. Cahill, A. P. Lightfoot, R. Goddard, J. Rust, P. J. Guiry, Tetrahedron: Asymmetry
1998, 9, 4307.
[58] A. Maj, M. Pietrusiewicz, I. Suisse, F. Agbossou, A. Mortreux, J. Organomet. Chem.
2001, 626, 157.
[59] (a) A. Pfaltz, J. Heterocyclic Chem. 1999, 36, 1437; (b) A. Pfaltz, Synlett 1999, 835;
(c) G. Helmchen, A. Pfaltz, Acc. Chem. Res. 2000, 33, 336.
1601 P. Braunstein, F. Naud, Angew. Chem., Int. Ed. 2001, 40, 680.
[61] M. Gomoez, G. Muller, M. Rocamora, Coord. Chem. Rev. 1999, 769.
1621 (a) J. Sprinz, G. Helmchen, Tetrahedron Lett. 1993,34, 1769; (b) G. Helmchen, S. Kudis,
P. Sennhenn, H. Steinhagen, Pure Appl. Chem. 1997, 69, 513.
[63] (a) P. von Matt, A. Pfaltz, Angew. Chem., Int. Ed. Engl. 1993,32, 566; (b) A. Pfaltz, Acta
Chem. Scand. B. 1996, 50, 189.
[64] (a) G. J. Dawson, C. G. Frost, J. M. J. Williams, S. J. Cote, Tetrahedron Lett. 1993, 34,
3149; (b) J. M. J. Williams, Synlett 1996, 705.
[65] S.-W. Park, J.-H. Son, S.-G. Kim, K. H. Ahn, Tetrahedron: Asymmetry 1999 10, 1903.
[66] P. A. Evans, T. A. Brandt, Org. Lett. 1999, I , 1563.
[67] Y. Hashimoto, Y. Horie, M. Hayashi, K. Saigo, Tetrahedron: Asymmetry2000, 11, 2205.
[68] (a) W.-P. Deng, X.-L. Hou, L.-X. Dai, X.-W. Dong, Chem. Commun. 2000, 1483; (b)
W.-P. Deng, X.-L. Hou, L.-X. Dai, Y.-H. Yu, W. Xia, Chem. Commun. 2000, 285.
[69] I. Takei, Y. Nishibayashi, Y. Arikawa, S. Uemura, M. Hidai, Organometallics 1999,
18, 2271.
[70] (a) K. Yonehara, T. Hashizume, K. Mori, K. Ohe, S. Uemura, Chem. Commun. 1999,
415; (b) K. Yonehara, T. Hashizume, K. Mori, S. Uemura, J. Org. Chem. 1999,64,9374.
[71] B. Glaser, H. Kunz, Synlett 1998, 53.
[72] R. Hilgraf, A. Pfaltz, Synlett, 1999, 1814.
[73] (a) Gilbertson, D. Xie, Angew. Chem. Int. Ed. 1999,38,2750; (b) S . R. Gilbertson, Z. Fu,
D. Xie, Tetrahedron Lett. 2001,42, 365; (c) S. R. Gilbertson, F. Zice, Org. Lett. 2001, 3,
161; (d) 0.Loiseleur, P. Meier, A. Pfaltz, Angew. Chem., Int. Ed. Engl. 1996,35, 200; (e)
0. Loiseleur, M. C. Elliott, P. von Matt, A. Pfaltz, Helv. Chim. Acta 2000, 83, 2287.
[74] (a) K. Selvakumar, M. Valentini, M. Worle, P. S. Pregosin, A. Albinati, Organometallics
1999, 18, 1207; (b) Y. Imai, W. Zhang, T. Kida, Y. Nakatsuli, I. Ikeda, Tetrahedron Lett.
1998, 39, 4343.
[75] (a) A. K. H. Knobel, I. H. Escher, A. Pfltz, Synlett 1997, 1429; (b) R. PrCtGt, A. Pfaltz,
Angew. Chem. Int. Ed. 1998, 37, 323; (c) I.H. Escher, A. Pfaltz, Tetrahedron 2000,
56, 2879.
[76] D. K. Heldmann, D. Seebach, Helv. Chim. Acta 1999, 82, 1096.
[77] (a) A. Lightfoot, P. Schnider, A. Pfaltz, Angew. Chem., Int. Ed. 1998, 37, 2897; (b) D. G.
Blackmond, A. Lightfoot, A. Pfaltz, T. Rosner, P. Schnider, N. Zimmermann, Chirality
2000, 12, 442.
1781 P. Schnider, G. Koch, R. PrCtGt, G. Wang, F. M. Bohnen, C. Krtiger, A. Pfaltz, Chem. Eul:
J. 1997, 3, 887.
[79] S. Kudis, G. Helmchen, Angew. Chem., Int. Ed. 1998, 37, 3047.
[80] (a) A. J. Blacker, M. L. Clark, M. S. Loft, J. M. J. William, Chem. Commun. 1999, 913;
(b) A.J. Blaker, M.L. Clarke, M.S. Loft, M.F. Mahon, M.e. Humphries, J.M.J.
Williams, Chem. Eul: J. 2000, 6, 353.
[81] (a) Y. Nishibayashi, K. Segawa, H. Takada, K. Ohe, S. Uemura, Chem. Commun. 1996,
847; (b) T. L. Langer, J. Janssen, G. Helmchen, Tetrahedron: Asymmetry 1996, 7, 1599;
(c) L. M. Newman, J. M. J. Williams, R. McCague, G. A. Potter, Tetrahedron: Asymmetry
1996, 7, 1597.
 References 1031

1821 (a) Y. Arikawa, M. Ueoka, K. Matoba, Y. Nishibayashi, P. Hidai, S. Uemura, J. Orga-

nomet. Chem. 1999, 572, 163; (b) T. Sammakia, E. L. Stangeland, J. Org. Chem. 1997,
62, 6104; (c) P. Braunstein, C. Graiff, F. Naud, A. Pfaltz, A. Tiripicchio, Znorg. Chem.
2000, 39, 4468.
[83] (a) S.R. Gilbertson, C.-W.T. Chang, J. Org. Chem. 1998, 63, 8424; (b) A.M. Porte,
J. Reibenspies, K. Burgess, J. Am. Chem. Soc. 1998, 120, 9180.
[84] T. V. RajanBabu, B. Radetich, K. K. You, T. A. Ayers, A. L. Casalnuovo, J. C., Cala-
brese, J. Org. Chem. 1999, 64, 3429.
[85] Y. Chen, X. Li, S.-k. Tong, M.C. K. Choi, A.S.C. Chan, Tetrahedron Lett. 1999,
40, 957.
[86] N. Demen, C. B. Dousson, S. M. Roberts, U. Berens, M. J. Burk, M. Ohff, Tetrahedron:
Asymmetry 1999, 10, 3341.
[87] A. Zhang, B. Jiang, Tetrahedron Lett. 2001, 42, 1761.
1881 (a) A.S.C. Chan, W. Hu, C.-C. Pai, C.-P. Lau, J. Am. Chem. Soc. 1997, 119, 9570;
(b) W. Hu, M. Yan, C.-P. Lau, A.S.C. Chan, Y. Jiang, A. Mi, Tetrahedron Lett.
1999, 40, 973.
[89] G. Zhu, X. Zhang, J. Org. Chem. 1998, 63, 3133.
[90] S. Naili, I. Suisse, A. Mortreux, F. Agbossou, M. Ait Ali, A. Karim, Tetrahedron Lett.
2000, 41, 2876.
1911 A. L. Casalnuovo, T. V. RajanBabu, T. A. Ayers, T. H. Warren, J. Am. Chem. Soc. 1994,
116, 9869.
1921 A. Zhang, Y. Feng, B. Jiang, Tetrahedron: Asymmetry 2000, 11, 3123.
[93] D. S. Clyne, Y. C. Mermet-Bouvier, N. Nomura, T. V. RajanBabu, J. Org. Chem. 1999,
64, 7601.
[94] M.E. Bruin, E. P. Kundig, Chem. Commun. 1998, 2635.
19.51 (a) T. V. RajanBabu, A. L. Casalnuovo, T. A. Ayers, Advances in Catalytic Processes,
Vol. 2, JAI Press, Greenwich, 1997, p. 1; (b) T. V. RajanBabu, T. A. Ayers, G. A. Halli-
day, K. K. You, J. C. Calabrese, J. Org. Chem. 1997, 62, 6012.
1961 (a) F. Agbossou, J.-F. Carpentier, A. Mortreux, Chem. Rev. 1995, 95, 2485; (b) S.
Gladiali, J. C. Bayon, C. Claver, Tetrahedron: Asymmetry 1995, 6, 1453.
1971 J. E. Babin, G. T. Whiteker, WO 93/03839, US 911.518 (1992); Chem. Abstr. 1993,119,
159872h.
1981 (a) N. Sakai, K. Nozaki, S. Mano, H. Takaya, J. Am. Chem. Soc. 1993, 115, 7033;
(b) N. Sakai, K. Nozaki, H. Takaya, J . Chem. Soc., Chem. Cornmun. 1994, 395.
1991 (a) K. Nozaki, N. Sakai, T. Nanno, T. Higashijima, S. Mano, T. Horiuchi, H. Takaya,
J. Am. Chem. Soc. 1997, 119, 4413; (b) T. Horiuchi, E. Shirakawa, K. Nozaki, H. Ta-
kaya, Organometallics 1997, 16, 298 1 .
[loo] S. Deerenberg, H. S. Streckker, G. P. F. van Strijdonck, P. C. J. Kamer, P. W. N. M. van
Leeuwen, J. Fraanje, K. Goubitz, J. Org. Chem. 2000, 65, 4810.
[I011 M. DiCguez, S. Deerenberg, 0. Pamies, C. Claver, P. W. N. M. van Leeuwen, P. Kamer,
Tetrahedron: Asymmetry 2000, 11, 3161.
[lo21 (a) M.T. Reetz, A. Gosberg, R. Goddard, S.-H. Kyung, Chem. Cornmun. 1998, 2077;
(b) M. T. Reetz, A. Gosberg, Tetrahedron: Asymmetry 1999, 10, 2129.
[I031 G. Francio, F. Faraone, W. Leitner, Angew. Chem. Znt. Ed. 2000, 39, 1428.
[ 1041 V. I. Tararov, R. Kadyrov, T. H. Riermeier, J. Holz, A. Bomer, Tetrahedron: Asymmetry
1999, 10, 4009.
[ 1051 A. Kless, J. Holz, D. Heller, R. Kadyrov, R. Selke, C. Fischer, A. Bomer, Tetrahedron:
Asymmetry 1996, 7, 33.
[ 1061 (a) 0. Pamies, M. DiCguez, G. Net, A. Ruiz, C. Claver, Tetrahedron: Asymmetry 2000,
11, 4377; (b) M. Yan, Z.-Y. Zhou, A. S. C. Chan, Chem. Commun 2000, 115.
[lo71 M. Yan, Q.-Y. Xu, A. S. C. Chan, Tetrahedron: Asymmetry 2000, 11, 845.
1032 3.2 Special Catalysts and Processes

[lo81 (a) 0 Pamies, G. Net, A. Ruiz, C. Claver, Tetrahedron: Asymmetry 2000, 11, 1097;
(b) 0. Pamies, M. Dieguez, G. Net, A. Ruiz, C. Claver, Chem. Commun. 2000, 2383.
[lo91 (a) M. T. Reetz, T. Neugebauer, Angew. Chem. Int. Ed. 1999, 38, 179; (b) 0. Pamies,
G. Net, A. Ruiz, C. Claver, Eul: J. Inorg. Chem. 2000, 1287.
[110] (a) S. CserCpi-Szucs, J. Bakos, Chem. Commun. 1997, 635; (b) S. Cserkpi-Szucs,
I. Toth, L. Parkanyi, J. Bakos, Tetrahedron: Asymmetry 1998, 9, 3135; (c) Y. Jiang,
S.Xue, Z. Li, J. Deng, A. Mi, A. S. C. Chan, Tetrahedron: Asymmetry 1998, 9, 3185;
(d) R. Kadyrov, D. Heller, R. Selke, Tetrahedron: Asymmetry 1998, 9, 329; (e)
G.J.H. Buisman, L.A. van der Veen, A. Klootwijk, W.G.J. de Lange, P.C.J.
Kamer, P. W. N. M. van Leeuwen, D. Vogt, Organometallics 1997, 16, 2929; (0C.
Botteghi, G. Delogu, M. Marchetti, S. Paganelli, B. Sechi, J. Mol. Catal. A: Chem.
1999, 143, 3 11.
[ill] A. Roucoux, I. Suisse, M. Devocelle, J.-F. Carpentier, F. Agbossou, A. Mortreux,
Tetrahedron: Asymmetry 1996, 7, 379.
[112] J.-M. Brunel, G. Buono, Tetrahedron Lett. 1999, 40, 3561.
[113] A. Zhang, Y. Feng, B. Jiang, Tetrahedron: Asymmetry 2000, 11, 3123.
[114] M. Sauthier, J. Fomes-Camer, L. Toupet, R. RCau, Organometallics 2000, 19, 553.
[115] M. T. Reetz, E. Bohres, R. Goddard, Chem. Commun. 1998, 935.
[116] (a) C. Pasquier, S. Naili, A. Morteux, F. Agbossou, L. PClinski, J. Brocard, J. Eilers,
I. Reiners, V. Peper, J. Martens, Organometallics 2000, 19, 5723; (b) C. Pasquier,
L. PClinski, J. Brocard, A. Mortreux, F. Agbossou-Niedercom, Tetrahedron Lett.
2001, 42, 2809.
[117] (a) Y. Kuroki, D. Asada, K. Iseki, Tetrahedron Lett. 2000, 41, 9853; (b) Y. Kuroki,
Y. Sakamaki, K. Iseki, Org. Lett. 2001, 3, 457.
[ 1181 E. A. Broger, W. Burkart, M. Hennig, M. Scalone, R. Schmid, Tetrahedron: Asymmetry
1998, 9, 4043.
[119] H.-J. Kreuzfeld, C. Dobler, J. Mol. Catal. A: Chem. 1998, 136, 105.
[120] (a) R. Lou, A. Mi, Y. Jiang, Y. Qin, Z. Li, F. Fu, A. S. C. Chan, Tetrahedron 2000, 56,
5857; (b) A. Mi, R. Lou, Y. Jiang, J. Deng, Y. Qin, F. Fu, Z. Li, W. Hu, A. S.C. Chan,
Synlett 1998, 847.
[121] X. Li, R. Lou, C.-H. Yeung, A.S.C. Chan, W. K. Wong, Tetrahedron: Asymmetry,
2000, 11, 2077.
[I221 D. Moulin, C. Darcel, S. JugC, Tetrahedron: Asymmetry 1999, 10, 4729.
[123] (a) Y. Xie, R. Lou, Z. Li, A. Mi, Y. Jiang, Tetrahedron: Asymmetry 2000, 11, 1487;
(b) L. Gong, G. Chen, A. Mi, Y. Jiang, F. Fu, X. Cui, A.S.C. Chan, Tetrahedron:
Asymmetry 2000, 11, 4297.
[I241 (a) R. Ewalds, E. B. Eggeling, A. C. Hewat, P. C. J. Kamer, P. W. N. M. van Leeuwen,
D. Vogt, Chem. Eul: J . 2000, 6 , 1496; (b) 0. Lot, I. Suisse, A. Mortreux, F. Agbossou,
J. Mol. Catal. A: Chem, 2000, 164, 125; (c) S. Naili, I. Suisse, A. Mortreux, F. Agbos-
sou-Niedercorn, G. Nowogrocki, J. Organomet. Chem. 2001, in press.
[125] T. Morimoto, Y. Yamaguchi, M. Suzuki, A. Saitoh, Tetrahedron Lett. 2000, 41, 10025.
[126] I. Achiwa, A. Yamazaki, K. Achiwa, Synlett 1998, 45.
[ 1271 S. Boms, R. Kadyrov, D. Heller, W. Baumann, J. Holz, A. Bomer, Tetrahedron: Asym-
metry 1999, 10, 1425.
[128] J. Holz, M. Quirmbach, U. Schmidt, D. Heller, R. Stunner, A. Bomer, J. Org. Chem.
1998, 63, 803 1.
[I291 (a) J. Holz, M. Quirmbach, A. Bomer, Synthesis 1997, 983; (b) S. Boms, R. Kadyrov,
D. Heller, W. Baumann, A. Spannenberg, R. Kempe, J. Holz, A. Bomer, Eul: J. Inorg.
Chem. 1998, 1291.
[ 1301 (a) J. Holz, R. Kadyrov, S. Boms, D. Heller, A. Bomer, J. Organomet. Chem. 2000,603,
61 ; (b) M. Quirmbach, J. Holz, V. I. Tararov, A. Bomer, Tetrahedron 2000, 56, 775.
 References 1033

[131] D. Carmichael, H. Doucet, J. M. Brown, Chem. Commun. 1999, 261.

[132] W. Li, Z. Zhang, D. Xiao, X. Zhang, Tetrahedron Lett. 1999, 40, 6701.
[I331 (a) B.M. Trost, D. L. Van Vranken, C. Bongel, J. Am. Chem. SOC.1992, 114, 9327;
(b) B. M. Trost, Acc. Chem. Res. 1996, 50, 189; (c) B. M. Trost, D. L. Van Vranken,
Chem. Rev. 1996, 96, 395.
[134] A. Saitoh, T. Uda, T. Morimoto, Tetrahedron: Asymmetry 2000, 11, 4049.
[135] A. Saitoh, T. Uda, T. Morimoto, Tetrahedron: Asymmetry 1999, 10, 4501.
[136] S.-G. Lee, S. H. Lee, C. E. Song, Tetrahedron: Asymmetry 1999, 10, 1795.
[ 1371 J. M. Longmire, B. Wang, X. Zhang, Tetrahedron Lett. 2000, 41, 5435.
[138] (a) S.-L. You, X.-L. Hou, L.-X. Dai, B.-X. Cao, J. Sun, Chem. Commun. 2000, 1933;
(b) S.-L. You, X.-L. Hou, L.-X. Dai, X.-Z. Zhu, Org. Lett. 2001, 3, 149.
[139] B. M. Trost, G. M. Schroeder, J. Am. Chem. Soc. 2000, 122, 3785.
[I401 B. M. Trost, F. D. Toste, J. Am. Chem. SOC.1999, 121, 4545.
[I411 B.M. Trost, J.P. Survivet, J. Am. Chem. Soc. 2000, 122, 6291.
[142] B. Trost, D. E. Patterson, E. J. Hembre, J. Am. Chem. SOC.1999, 121, 10834.
[I431 (a) B. M. Trost, X. Ariza, Angew. Chem., Int. Ed. Engl. 1997,36,2635; (b) B. M. Trost,
X. Ariza, J. Am. Chetn. SOC.1999,121, 10727; (c) B. M. Trost, C. B. Lee, J. Am. Chem.
SOC.1998, 120, 6818; (d) B. M. Trost, R. Radinov, E. M. Grenzer, J. Am. Chem. Soc.
1997, 119, 7879.
[144] B. M. Trost, W. Tang, J. L. Schulte, Org. Lett. 2000, 2, 4013.
[145] (a) A. Bohme, H.-J. Gais, Tetrahedron: Asymmetry 1999, 10, 2511; (b) B.M. Trost,
H. C. Tsuji, F. D. Toste, J. Am. Chem. SOC.2000, 122, 3534.
[146] Y. K. Kim, S. J. Lee, K. H. Ahn, J. Org. Chem. 2000, 65, 7807.
[I471 M. Gomez, S. Jansat, G. Muller, D. Panyella, P. W. N. M. van Leeuwen, P. C. J. Kamer,
K. Goubitz, J. Fraanje, Organometallics 1999, 18, 4970.
[148] Y. Jiang, Q. Jiang, G. Zu, X. Zhang, Tetrahedron Lrtt. 1997, 38, 6565.
[I491 (a) G. Zhu, M. Terry, X. Zhang, J. Organomet. Chem. 1997,547, 97; (b) P. Braunstein,
F. Naud, A. Pfaltz, S. J. Rettig, Organometallics 2000, 19, 2676.
[150] (a) E. Hauptman, R. Shapiro, W. Marshall, Organometallics 1998, 17, 4976; (b) P. Bar-
baro, C. Bianchini, A. Togni, Organornetallics 1997, 16, 3004.
[I511 (a) S. Shin, T. V. RajanBabu, Org. Let. 1999, 1, 1229.
[152] K. Yonehara, T. Hashizume, K. Mori, K. Ohe, S. Uemura, J. Org. Chem. 1999,
64, 9381.
[153] R. Selke, J. Holz, A. Riepe, A. Bomer, Chem. Eur: J. 1998, 4, 769.
[154] F. Robert, D. Sinou, J. Organomet. Chem. 2000, 604, 99.
[I551 J. Holz, D. Heller, R. Stiirmer, A. Bomer, Tetrahedron Lett. 1999, 40, 7059.
[ 1561 M. D. Miquel-Serrano, A.M. Masdeu-Bulto, C. Claver, D. Sinou, J. Mol. Catal. A:
Chem. 1999, 143, 49.
[I571 G. Francio, W. Leitner, Chem. Commun. 1999, 1663.
[I581 A. Wegner, W. Leitner, Chem. Commun. 1999, 1583.
[159] J. A. J. Breuzard, M. L. Tommasino, M. C. Bonnet, M. Lemaire, J. Organomet. Chem.
2000, 616, 37.
[160] Q.-H. Fan, C.-Y. Ren, C.-H. Yeug, W.-H. Hu, A. S. C. Chan, J. Am. Chem. Soc. 1999,
121, 7407.
[161] R. ter Halle, E. Schulz, M. Spagnol, M. Lemaire, Tetrahedron Lett. 2000, 41, 3323.
[161] K. Nozaki, Y. Itoi, F, Shibahara, E. Shirakawa, T. Ohta, H. Takaya, T. Hiyama, J. Am.
Chem. SOC. 1998, 120, 4051.
[ 1621 Q.-H. Fan, Y.-M. Chen, X.-M. Chen, D.-Z. Jiang, F. Xi, A. S. C. Chan, Chem. Commun.
2000, 789.
[163] (a) C. Kollner, B. Pugin, A. Togni, J. Am. Chem. Soc. 1998, 120, 10274; (b) R. Schnei-
der, C. Kollner, I. Weber, A. Togni, Chem. Commun. 1999, 2415.
 Applied Homogeneous Catalysis with Organometallic Compounds
Edited by B. Cornils and W. A. Herrmann
Copyright 0 Wiley-VCH Verlag GmbH, D-69469 Weinheim, 2002

1034 3.2 Special Catalysts and Processes

3.2.7 Homologation
Helmut Bahrrnann

3.2.7.1 Historical Background

The energy and oil supply crisis of 1973 focused the interest of the West and Japan
primarily on the production of large-volume commodity chemicals on the basis of
domestic raw materials such as coal, with syngas as the chemical building block.
It was thought that syngas facilitates the transition from oil- to coal-based
products. Regardless of what it is made from, it is an identical chemical species
and it fits in with existing equipment and technology. It was reckoned that in
the syngas building block the carbon itself would cost only half as much as in
the ethylene building block [l]. The highest efficiency in the use of syngas is
reached if the oxygen content of the carbon monoxide remains in the end-product.
This is the case in the classical syntheses of methanol and in the Monsanto process
for the formation of acetic acid [2] (cf. Section 2.1.2.1). In this connection, homo-
logation of methanol to ethanol and subsequent dehydration could provide a new
route to ethylene. Later on, when the use of tetraethyllead as an octane booster
was scheduled to be discontinued for health reasons, a mixture of ethanol and
higher alcohols became of interest as an octane booster and cosolvent for metha-
nol in wet hydrocarbons, because methanol alone could separate from the hydro-
carbons at lower temperatures and attack various parts of the fuel distribution sys-
tem [3].
Originally, the homologation reaction, i.e., the enlargement (extension) of the
carbon chain of oxygen-containing molecules by a -CH2- group according to
eq. (l), e. g., was discovered by Wietzel, Eder, Vorbach, and Scheuermann during
the period 1941-1943 [4]. They converted aliphatic primary alcohols into the next
higher alcohols on reacting with syngas as a source for -CH2- at raised tempera-
tures and pressures (eq. (2)).

R'OH + fCH2f &

R'-CH1-OH (1)

metal carbonyls
ROH + CO + 2H2 RCH2OH + H20

The by-products consisted of higher acids, their esters, and hydroxy ethers. The
results of this experiments remained unnoticed so that work in 1949 by Wender et
al. [5J - after whom this reaction was named - was a kind of rediscovery. In 1952,
the essential conclusions of the work of Wietzel et al. were confirmed in a funda-
mental paper by Ziesecke [6].
In 1956 Berty [7] introduced a iodine activator to the basic catalyst cobalt car-
bony]; this made possible a noticeable increase in the reaction rate and represented
the transition from the high-pressure syntheses (40- 100 MPa) to the medium-
pressure syntheses (18-40 MPa), a state-of-the-art which lasted until 1988.
 3.2.7.2 Chemical Basics and Applications 1035

A further improvement to the selectivity of the reaction, especially in the period

1975-1985, could be reached in the field of catalyst development. This develop-
ment can be characterized by the transition of the original one-component catalyst
cobalt to complex multicomponent catalyst systems [8]. The added catalyst com-
pounds are activators, such as halogens or halogenides, and promoters, such as
donor ligands of the Group 5 elements, as well as additional co-catalysts, such
as ruthenium or nickel. In the homologation of methanol the transition metal
ruthenium is especially useful for an in-situ hydrogenation to ethanol of the pri-
mary product acetaldehyde, whereas nickel facilitates the formation of acetalde-
hyde dimethyl acetal [9]. Some attention was also dedicated to the development
of a process for the production of acetaldehyde [lo, 111. The state-of-the-art up
to 1982 has been reviewed in [12]. Later, most of the activity has still been
concentrated on the homologation of methanol. An ultimate breakthrough may
have been achieved in 1988 by Moloy and Wegman when they changed the
basic catalyst metal from cobalt to rhodium. They succeeded in the development
of a novel rhodium-ruthenium-diphosphine-methyl iodide catalyst which en-
abled a low-pressure, (relatively) low-temperature homologation of methanol
for the first time [47].
Table 1 includes new literature on catalyst systems and reaction conditions up
to 1994. As can be seen from this table, a large range of different catalyst combi-
nations, promoters, and solvents has been investigated. However, the overall con-
version and selectivity remain unsatisfactory. It seems to be impossible to achieve
both a high conversion of methanol and a high selectivity to ethanol at the same
time. Thus, the results of all the efforts have not justified a commercial realization
of the homologation process up to now.

3.2.7.2 Chemical Basics and Applications

Although the homologation reaction was originally restricted to aliphatic alcohols,
its scope has been extended to a broad range of basic organic chemicals (eq. (3)).
rCH20H
r CH2-CH20H

R
COOH
+ 2COlH2 - R
kCH2-CHO
I
CH2-COOH
+ H20 (3)

I
LCOOR LCH2-COOR

Within this scope, homologation reactions are all variants of enlarging the car-
bon chain in a oxygen-containing molecule by one C atom with the use of syngas.
Thus the homologation reaction can be used, for example, for the synthesis of
acetaldehyde from methanol [48], propionic acid from acetic acid [47], or ethyl
acetate from methyl acetate [50]. Styrene may be produced from toluene by oxi-
dation to benzyl alcohol [5 11 and homologation to 2-phenylethanol, which in turn
can be dehydrated to styrene. From the chemical point of view, the applications of
homologation reactions are broad and useful. But, as mentioned before, low selec-
 Y
Table 1. Homologation of methanol - current state in the development of catalysts. 0
w
Press. Temp. Catalyst Promoters Remarks Conversion Product/ By-product Ref. a
[bar1 ["CI [%I selectivity [%] selectivity [%]
80-170 Co 12/Br2,phosphine Addition of Acetaldehyde
chelate inert solvent
170-250 Co Halogen containing Ethanol
complex phosphine
chelate
170-250 Co Halogen containing Addition of Ethanol
complex phosphine water
chelate
350 260 co (CO~BLH? 9.5 Ethanol174 Methyl acetate/6.8
320 260 Co2(CO), NaI, Na,CO? C O and water 42 Ethanol129 Methyl acetate/l4
conversion 1, l-dimethoxy-
ethane17
400 185 Pretreatment 23 Ethanol156 Methyl acetate15.5
with C O Ethyl acetatel5.6
200 190 67 EthanoV36 Acetaldehydel9.6
Acetic acid/13.7
200 185 Co(OAc), 12, Br2, and AsR,, Addition of 55 Acetaldehyde/3 3 Ethanol/?.?
SbR3 or BiR3 inert solvent Acetic acidB.1
200 205 Co(OAc), 12,PBu3 Addition of 47 Ethanol/70 Methane/25.5
inert solvent Acetic acidl6.8
200 190 Co(OAc)? Iz, Br2, phosphine 50.6 Ethanol/65 Acetaldehyde1 1
chelate I , 1-Dimethoxy-
ethane/lO
Methane/l8.4
Table 1. (Continued)
Press. Temp. Catalyst Promoters Remarks Conversion Product/ By-product Ref.
[bar] ["C] [%I selectivity [%] selectivity [%]
200 185 CO(OA~)~ 43 EthanoV65
400 200 Co(OAc)> 50 EthanoU33.3 n-Propanoll3
Ethyl acetate/3
Acetaldehyde/2
275 180 Fe/Co 42 AcetaldehydeB4 Methyl acetate/l4

270 220 RulCo 54 Ethanol/80 Methane/l

Dimethyl ether/2
Methylethyl ether/3
Methyl acetate/:!
Diethyl ether/3
n-propanol/5
Ethyl acetate/3
276 175 Co(acac), 59 Ethanol160 Dimethyl ether/5
Methyl acetate/l5
Diethyl ether/l4
276 200 Co" rneso- 68 Acetaldehyde162 Dimethyl ethed9.3
tetraaromatic Ethanol/] 1.4
phosphine Methyl acetate/l2.9
280 200 [Co(CO),L12 71 Acetaldehyde153 Dimethyl ethed6.7
where Ethanol/ 18.1
L = AsR, Methyl acetate/l3
280 200 CO(CO)3L,12 44 Ethanol172 Dimethyl ethed3.5
where Diethyl ether13.0
1
L = PBu~ Methyl acetate/9.6
0
Others11 1.8 W
4
Table 1. (Continued) +

Press. Temp. Catalyst Promoters Remarks Conversion Product/ By-product Ref.

s
Go

[bar1 ["CI [%I selectivity [%] selectivity [%]

400 185 CO(OAC)~ 12,PPh3, 1,2-bis(di- Acetaldehyde/
phenylphosphin0)- 53.3
ethane
200 250 cos, c02s3 PR3 Addition of 36 EthanoV86.3 Acetaldehyde/2.1
nitrogen- Methyl acetate/3.2
containing Ethyl acetate/l
solvent
CHJ 80 EthanoV42 n-PropanoV4
n-ButanoV2
Acetaldehyde/:!
260 215 C02(CO)* Acetaldehyde

210 181 CO(OAC)~ 43 EthanolBO

245 190 CO(OAC), 100 EthanoV65.5 Acetaldehydeh .7

Methyl acetate/23.2
Ethyl acetdte/9.6
290 200 CO(OAC), HI, PPh, and 58 1,l -Dimethoxy- Acetaldehyde/8.6
Ni(OAc), ethane/80 Methyl acetate/5-8
300 200 CO(OAC)~ 1,1-Dimethoxy-
ethane
Addition of EthanoV80
ethers
Table 1. (Continued)
Press. Temp. Catalyst Promoters Remarks Conversion Product/ By-product Ref.
[bar1 ["CI [%I selectivity [ %] selectivity [%I
350 185 Halogen or halide 72 EthanoY69 Acetaldehyde and
add. of 1 ,Zbis(di- acetals/2
phenylphosphino- n-PropanoY4
ethane)
550 185 NaI, 0-containing 42 EthanoV76 Acetaldehyde and
phosphine chelate acetals/Esters/S
235 200 Halide, Bu,P+ Br- Ethanol
15 250 Heterocyclic amines Ethanol
270 220 MeI, PPh3 Variation of 58 EthanoV86
source of Ru
550 220 NaI, sulfonated and 56 EthanoV69 n-Propanow2
carboxy lated Hydrocarbond9
phosphines Etherdl7
Esters/3
32 EthanoY62
550 200 Iodide, amine or Amide
amide, heterocyclic
70 180 N-contg. compds., 1,4-Dioxane 82 EthanoV58 Acetaldehyde/7
1,1 '-bis(dipheny1- n-PropanoVl4
phosphino)ferrocene Methyl acetate/5
200 230 Bu,P C6HdOH- 28 EthanoK34
contg. compds
70 140 DiphosphineMeI EthanoV70-80
1040 3.2 Special Catalysts and Processes

tivities and/or activities of the existing catalyst systems have still prevented broad
research and development in this field. Most of the research is still restricted to the
laboratory scale and to reactions with methanol.

3.2.7.3 Mechanism of Reaction

Despite the quantity of informations available, the material does not allow clear
deductions to be made about the mechanism. However, it is obvious that the me-
chanism of the homologation reaction depends basically on the main catalyst
metal which is used.
Under the drastic reaction conditions and the acidic influence of the classical
cobalt catalyst [HCO(CO)~],acetaldehyde and subsequent acetals are formed,
which in turn may be hydrolyzed back to acetaldehyde or directly hydrogenated
to ethanol (cf. eq. (4)).

4'- -
t t
H20 I H2
CH3OH Co1H2* CHBCHO CH30H + C2H50H (4)
\

I 0-
t
In contrast, under the milder reaction conditions with rhodium, no acetals are
observed (cf. eq. ( 5 ) ) .

CH30H -% CH31 CO I H2
* CHsCHO -
H2
ClHsOH ( 51
Similarly to the reaction with cobalt, the acetaldehyde intermediate formed will
be further hydrogenated to ethanol. Overall, the Rh-catalized homologation me-
chanism resembles the Monsanto process with the exception that, as a result of
the presence of hydrogen, acetaldehyde is now the main product and acetic
acid definitely the only by-product. Some key catalyst components present at
the end of the homologation reaction, such as Rh(diphosphine)COMe)12 and
[Ru(CO)I3j4-have been isolated and identified by Moloy et al. [49]. It may be as-
sumed that the Ru complex is responsible for the intermediate in-situ hydrogena-
tion to the high ethanol selectivity obtained.
More data are available from the cobalt catalyst system. Under reaction condi-
tions the cobalt compounds will form the following equilibrium with syngas (eq.
(6)).
C02(C0)8 + H2 K== 2 HCo(C0)4 (6)
These cobalt carbonyl compounds may be involved in the primary step of the
homologation reaction, the formation of a metal-alkyl complex. For this, nine
different routes according to Scheme 1 are discussed in the literature [ 12~1.
 3.2.7.3 Mechanism of' Reaction 1041

[co(co)4l-

1 1
@ HPR31
CH3PR31
- H20 -HI, - PR3

@ HCo(C0)21 insertion OC,...X

.:;H3
I' 1 'OH

Scheme 1. Primary step of the homologation reaction: the formation of the

metal-alkyl bond.

Additionally, the situation will be further complicated by the fact that, under the
reaction conditions of the homologation reaction, Co2(C0)* with methanol,
halogen, halide, or phosphines may undergo various different disproportionation
reactions, from which some compounds were identified by IR spectroscopy, e. g.,
[CO(CH~OH)~]~' [CO(CO)~]~- [52], [Co(CO)J [53, 541, Cox2 + M'[Co(CO),]-,
[Co(CH,OH),(C0>,1,ln', [Co(C0>41,,~WI, [CO(CO)~(L-L)I', and [Co(CO),l-
mi.
Nevertheless, from the nine different routes to form the key intermediate of the
homologation reaction set out in Scheme 1, three remain the most convincing: the
insertion mechanism; the S,2 mechanism; and the phosphonium ion mechanism
(cf. Schemes 2 and 3 ) .
Scheme 2 outlines the insertion and the SN2 mechanisms. In both cycles cobalt
complexes are involved in the splitting-off of water. The key intermediate in the
insertion mechanism is HCO(CO)~Iand in the SN2 mechanism the anion
[Co(CO),]-, resulting from one of the previously mentioned disproportionation
reactions.
1042 3.2 Special Catalysts and Processes

HCo(C0)31

SN2-mechanism
mechanism

CH3Co(C0)4

co co
CH~COCO(CO)~I
H2 H2

Scheme 2. Insertion and SN2mechanism of the homologation reaction with methanol.

As proposed by Keister [57] and supported by own investigations [58], phos-

phines are partly quarternized, so in the reaction mixture from the homologation
of methanol in the presence of triphenylphosphine and hydroiodic acid methyltri-
phenylphosphonium iodide could be isolated and identified by IR spectroscopy,
which shows a quantitative methylation of the intermediate formed [HPPhJI-
with methanol. This fact suggests a phosphonium ion mechanism, which is pro-
posed by the author and outlined in Scheme 3.
Within this mechanisms the phosphonium ions function as a methyl-group
transfer agent and the critical step for the conversion of methanol - the splitting-
off of water - is facilitated by taking place outside the direct catalyst cycle.

3.2.7.4 Technical Applications

So far, the homologation reaction has reached only the pilot-plant scale [58, 611.
Little information is available about the reaction in continuous operation. The only
cobalt-catalyzed continuously conducted reaction led to a mixture of 20 different
products. The yield of ethanol is low (16 mol %) [59]. By activation with iodine
and variation of the space-velocity, the overall yield has been improved and the
ratio of acetaldehyde/ethanol could be varied between 13: 18 and 2: 17 [60]. BP
has described continuous homologation with the Co/I/PPh3 catalyst system. The
yield of ethanol reached only 25 mol % [ 111. Semicontinuous work on the homo-
logation reaction has been reported by the former Ruhrchemie AG [61].
Seven of the most convincing discontinuously developed catalyst systems were
recycled nine times and conversion and selectivity were noted (cf. Table 2). The
catalyst compounds were separated by a special distillation unit under CO/H2
 3.2.7.4 Technical Applications 1043

co
CH3CHO

Scheme 3. Phosphonium ions as methyl-group transfer agents in the homologation of

methanol.

pressure. The best results were reached with the system no. 1. During recycling,
conversion of methanol decreased by 7 points and the selectivity to ethanol by 18
points. In further recycling experiments, fresh catalyst was added in such an
amount that conversion and selectivity remained constant. It was found that
20-30 % fresh catalyst must be added in order to reach the steady state. The sta-
bility of the catalyst during the reaction and the recycling was too low for a tech-
nical application. Furthermore, owing to the insufficient methanol conversion,
high energy and investment costs for separation and recycling of unconverted
methanol would be required. Finally, the same is true for the separation of the dif-
ferent reaction products.
1044 3.2 Special Catalysts and Processes

Table 2. Recycling behavior of selected Ruhrchemie AG catalysts.

No. Catalyst system Conversion Selectivity
[mol %] [mol %]
of methanol to ethanol
Start End Start End
1 Co, Ru, N d , 1,3-bis(diphenylphosphino)propane 59 52 80 62
2 CO, Ru, NaI, ChHIIP(CH2CH2COOH)2 48 21 80 10
3 Co, Ru, NaI, PPh,/HPPh,'I 59 35 78 49
4 Co, Pt, NaI, 1,3-bis(diphenyIphosphino)propane 59 32 76 62
5 Co, Ru, NaI, methyl-2-pyrrolidone"' 49 <5 68
6 Co, Ru, NaI, high-boiling holvent (polyglycol 1000) 45 40 51 32
7 Co, Ru, HI, high-boiling solvent (polyglycol 1000) 78 52 65 55
Reaction conditions: 550 bar, 3 h, CO/H2 = 1 :2, CH30H/Co = 500, NaIM = 1 : 1,
promotorlM = 2 : 1, Ru/Co = 0.1.
.I) Only one recycle possible.

3.2.7.5 Future Prospects

Despite considerable improvements in the 1980s with respect to the conversion of
methanol and the selectivity to ethanol or acetaldehyde, both are still insufficient
and prevent a technical application. This is also true for the other homologation
reactions. It seems that the relatively severe reaction conditions of the classical co-
balt catalyst system are inherently connected with this fact. One could speculate
about whether the same effort and expenditure of research which was directed
to the cobalt system were to be concentrated into the new rhodium system,
with generally much milder reaction conditions and the potential for essentially
higher selectivity, the state-of-the-art of the homologation reaction could be
much brighter than it is. In this light, the homologation reaction is still waiting
to be reinvestigated.

References
[ I ] J. I. Ehrler, B. Juran, Hydrocarbon Proc. 1982, 2, 109.
[2] J. F. Roth, J. H. Craddock, A. Hershman, E. Paulik, CHEMTECH 1971, 10, 600;
D. Forster, Adv. Organomet. Chem. 1979, 17, 255.
[3] J. F. Knifton, J. J. Lin, D. A. Storm and S. F. Wong, Card Today 1993, 18, 355.
[4] BASF AG (G. Wietzel, 0. Vorbach, A. Scheuermann), DE 843.876, 867.849, 875.346
(1 941-1 943).
[ S ] 1. Wender, M. Orchin et al., I. Am. Chem. Soc. 1949, 71, 4160; I. Wender et al. ibid.
1951, 73, 2656; 1. Wender et al., Science 1951, 113, 206.
[6] K. H. Ziesecke, Brennstoff-Chem. 1952, 33, 385.
 Rejerences 1045

[7] J. Berty, L. Marko, D. Kallo, Chem. Tech. (Leipzig) 1956, 8, 260.

[8] Commercial Solvents Corporation (A. D. Miley, W. 0. Bell), US 3.248.432 (1961).
[9] Union Rheinische Braunkohlen Kraftstoff AG (J. Korff, M. Fremery, J. Zimmermann),
DE 0s 2.913.677 (1979).
[ 101 RhGne-Poulenc Industries (J. Gauthier-Lafaye), EP Appl. 22.735 and 22038 (1979).
[ I l l BP (W. J. Ball, D. G. Stewart) GB Appl. 2.053.915 (1980).
[I21 (a) H. Bahrmann, B. Comils, Chem.-Ztg. 1980, 104, 39; (b) H. Bahrmann, B. Cornils
in New Synthesis wirh Curbon Monoxide (Ed.: J. Falbe), Springer-Verlag, Berlin, 1980;
(c) H. Bahrmann, W. Lipps, B. Comils, Chem.-Ztg. 1982, 106, 249.
[I31 Agency of Ind. Sci. Tech., JA 56.020.536 (1979).
[ 141 Agency of Ind. Sci. Tech., JA 56.020.536 (1979).
[ 151 Agency of Ind. Sci. Tech., JA 56.02.5.122 (1 979).
[I61 Air Products and Chemicals Inc. (C. M. Bartish), US 4.171.461 (1978).
[I71 Allied Chemical Corp. (M. Novotny, L. R. Anderson), US 4.126.752 (1978).
[ 181 Allied Chemical Corp. (M. Novotny), US 4.283.582 (1978).
[ 191 BP (C. M. Thomas), EP Appl. 29.723 (1979).
[20] BP (B. R. Gane), EP 1.936 (1977).
[21] BP (B. R. Gane), EP 1.937 (1977), EPAppl. 3.876 (1978).
[22] BP (B. R. Gane, D. G. Stewart), EP Appl. 10.373 (1978).
[23] B. R. Gane and D. G. Stewart, GB 2.036.730 (1977).
[24] Commercial Solvents Corp. (G. N. Butter), US 3.285.948 (1965).
[25] Exxon (G. Doyle), EP Appl. 27.000 (1980).
[26] Exxon (G. Doyle), EP Appl. 30.434 (1980).
[27] Gulf (W. R. Pretzer, T. P. Kobylinski, J. E. Bozik), US 4.133.966 (1977).
[28] Gulf (W. R. Pretzer, T. P. Kobylinski, J. E. Bozik), US 4.151.208 (1977).
[29] Gulf (J. E. Bozik, T. P. Kobylinski, T. W. R. Pretzer), US 4.239.704 (1978), US
4.239.705.
[30] BP (B. R. Cane), EPAppl. 1.937 (1977), EP Appl. 3.876 (1978).
[311 Mitsubishi Gas Chemicals, JP 52.136.1 1 1 ( 1 976).
[32] Mitsubishi Gas Chemicals, DE-OS 3.016.715 (1979).
[33] Montedison (D. Paolo), IT Appl. 1.034.761 (1975).
[34] UCC (R. A. Fiato), US 4.233.466 (1979), US 4.253.987 (1980).
[35] UCC (W. E. Walker), US 4.277.634 (1980).
[36] Union Rheinische Braunkohlen Kraftstoff AG, BE 890.964 (1982).
[37] K. Kudo, Nippon Kagaku Kuishi 1982, 3, 462.
[38] Ruhrchemie AG (B. Cornils, C. D. Frohning, G. Diekhaus, E. Wiebus, H. Bahrmann),
EP Appl. 53.792 (1980).
[39] Ruhrchemie AG (B. Cornils, C. D. Frohning, H. Bahrmann, W. Lipps), DE-OS
3.042.434 ( 1 982).
[40] Texaco Development Corp. (J. F. Knifton, J. J. Lin), EP Appl. 56.679 (1982).
[41] Ethyl Corp. (D. C. Hargis, M. Dubeck), US 4.361.499 (1982).
[42] G. Doyle, J. Mol. Cutul. 1983, 18(2), 251.
[43] Ruhrchemie AG (H. Bahrmann, B. Comils, W. Lipps), EP 84.833 (1983).
[44] Ruhrchemie AG (H. Bahrmann, B. Cornils, W. Lipps), DE 0s 3.330.507 ( 1 983).
[45] Texaco Inc. (J. F. Knifton, J. J. Lin), US 4.476.326 (1984).
[46] Agency of Industrial Sciences and Technology (Y. Isogai), JP 62.242.636 (1987).
[47] UCC (W. R. Wegman, K. G. Moloy), US 4.727.200 (1988); K. G. Moloy and R. W. Weg-
man, J. Chem. Soc., Chem. Commun. 1988, 820.
[48] Rh6ne-Poulenc Industries (J. Gauthier-Lafaye), EP Appl. 1 1.042 (1978).
[49] J. F. Knifton, CHEMTECH 1981, 10, 609.
[SO] G. Braca, G. Branca, G. Valentini, Fundum. Res. Honzog. Cut. 1979, 3, 22 1 ; Imhausen-
Chemie-GmbH, DE-OS 2.73 1.962 (1979).
1046 3.2 Special Catalysts and Processes

[51] Anon., Chem. Eng. News July 4, 1977, 13.

[52] I. Wender, H. Sternberg, M. Orchin, J. Am. Chem. Soc. 1952, 74, 1216.
[53] W. R. Pretzer, T. P. Kobylinski, Ann. N . E: Acad. Sci. 1980, 333, 58.
[54] Y. Iwashita, F. Tamura, H. Wakamatsu, Bull. Chem. SOC.Jpn. 1970, 43, 1520;
F. Ungvary, A. Sisak, L. Marko, J. Organomet. Chem. 1980, 188, 373.
[55] P. S. Braterman, A. E. Leslie, J. Organomet. Chem. 1981, 214, C45.
[56] J. Ellermann, J. Organornet. Chem 1975, 94, 201; Andreetta et al., Now. J. Chim. Ital.
1978, 2, 436; A. Sacco, Gazz. Chim. Ital. 1963, 93, 698; D. J. Thornhill et al., J. Chem.
Soc. Dalton Trans. 1974, 6; R. L. Peterson et al., Inorg. Chem. 1973, 12, 3009.
[57] J. B. Keister, R. Gentile, J. Organomet. Chem. 1981, 222, 143.
[58] W. Lipps, H. Bahrmann, B. Cornils, Ruhrchemie AG, unpublished work.
[59] G. S. Koermer, W. S. Slinkard, Ind. Eng. Chem., Prod. Res. Dev. 1978, 17, 231.
[60] Mitsubishi Gas-Chem. Inc. (T. Asano, K. Ishida, T. Imai), JP 48.002.525 (1964).
[6 11 H. Bahrmann, W. Lipps, Ruhrchemie AG, Forschungsbericht T 85-054, Technologische
Forschung und Entwicklung, Bundesministerium fur Forschung und Entwicklung
(BMFT), 1985.

3.2.8 Homogeneous Electrocatalysis

Didier Astruc

3.2.8.1 Introduction
Redox processes have introduced powerful ways to activate substrates in inor-
ganic [ 11 and organic chemistry [2]. Painvise organometallic processes including
homogeneous catalysis have also become an extremely rich field [3]. The combi-
nation of these two worlds should have a considerable impact on the advancement
of catalysis [4]. In this chapter a summary of the catalytic aspects of redox pro-
cesses is given, restricting the scope to homogeneous reactions although the
heterogeneous aspects are also of great importance and can be well understood
by using a similar and global approach [5]. Pairwise redox changes (oxidative ad-
dition and reductive elimination) are not discussed since the focus is on single-
electron transfer processes. There are two major areas of homogeneous catalysis
involving single-electron transfer:
(1) Electrocatalysis, also named Electron-Transfer-Chain (ETC) catalysis, where-
by a reaction (mostly of non-redox type) is catalyzed by an electron (reduc-
tion) or by an electron hole (oxidation). Organotransition-metal complexes
can carry an electron or an electron hole and, if they achieve this function
without decomposition, they are electron-reservoir complexes [6].
(2) Redox mediation or catalysis whereby a redox reaction is mediated or cata-
lyzed by a redox reagent. This type includes and is inspired by biological cat-
alysis with metalloenzymes. Here again both states need to be stable in order
to insure this function. Thus the redox mediator used must also be an electron-
reservoir complex [7].
 Applied Homogeneous Catalysis with Organometallic Compounds
Edited by B. Cornils and W. A. Herrmann
Copyright 0 Wiley-VCH Verlag GmbH, D-69469 Weinheim, 2002

1046 3.2 Special Catalysts and Processes

[51] Anon., Chem. Eng. News July 4, 1977, 13.

[52] I. Wender, H. Sternberg, M. Orchin, J. Am. Chem. Soc. 1952, 74, 1216.
[53] W. R. Pretzer, T. P. Kobylinski, Ann. N . E: Acad. Sci. 1980, 333, 58.
[54] Y. Iwashita, F. Tamura, H. Wakamatsu, Bull. Chem. SOC.Jpn. 1970, 43, 1520;
F. Ungvary, A. Sisak, L. Marko, J. Organomet. Chem. 1980, 188, 373.
[55] P. S. Braterman, A. E. Leslie, J. Organomet. Chem. 1981, 214, C45.
[56] J. Ellermann, J. Organornet. Chem 1975, 94, 201; Andreetta et al., Now. J. Chim. Ital.
1978, 2, 436; A. Sacco, Gazz. Chim. Ital. 1963, 93, 698; D. J. Thornhill et al., J. Chem.
Soc. Dalton Trans. 1974, 6; R. L. Peterson et al., Inorg. Chem. 1973, 12, 3009.
[57] J. B. Keister, R. Gentile, J. Organomet. Chem. 1981, 222, 143.
[58] W. Lipps, H. Bahrmann, B. Cornils, Ruhrchemie AG, unpublished work.
[59] G. S. Koermer, W. S. Slinkard, Ind. Eng. Chem., Prod. Res. Dev. 1978, 17, 231.
[60] Mitsubishi Gas-Chem. Inc. (T. Asano, K. Ishida, T. Imai), JP 48.002.525 (1964).
[6 11 H. Bahrmann, W. Lipps, Ruhrchemie AG, Forschungsbericht T 85-054, Technologische
Forschung und Entwicklung, Bundesministerium fur Forschung und Entwicklung
(BMFT), 1985.

3.2.8 Homogeneous Electrocatalysis

Didier Astruc

3.2.8.1 Introduction
Redox processes have introduced powerful ways to activate substrates in inor-
ganic [ 11 and organic chemistry [2]. Painvise organometallic processes including
homogeneous catalysis have also become an extremely rich field [3]. The combi-
nation of these two worlds should have a considerable impact on the advancement
of catalysis [4]. In this chapter a summary of the catalytic aspects of redox pro-
cesses is given, restricting the scope to homogeneous reactions although the
heterogeneous aspects are also of great importance and can be well understood
by using a similar and global approach [5]. Pairwise redox changes (oxidative ad-
dition and reductive elimination) are not discussed since the focus is on single-
electron transfer processes. There are two major areas of homogeneous catalysis
involving single-electron transfer:
(1) Electrocatalysis, also named Electron-Transfer-Chain (ETC) catalysis, where-
by a reaction (mostly of non-redox type) is catalyzed by an electron (reduc-
tion) or by an electron hole (oxidation). Organotransition-metal complexes
can carry an electron or an electron hole and, if they achieve this function
without decomposition, they are electron-reservoir complexes [6].
(2) Redox mediation or catalysis whereby a redox reaction is mediated or cata-
lyzed by a redox reagent. This type includes and is inspired by biological cat-
alysis with metalloenzymes. Here again both states need to be stable in order
to insure this function. Thus the redox mediator used must also be an electron-
reservoir complex [7].
 3.2.8.2 Electron-Transfer-Chain (ETC) Catalyzed Reactions 1047

Each of these two areas can be further divided into two parts, depending on the
nature of the redox change during the catalytic cycle: electron transfer versus atom
transfer. The latter mode of redox change is necessarily an inner-sphere version of
the electron-transfer reaction, whereas the first mode is frequently of the outer-
sphere type [8].
Chain inorganic reactions have been reviewed several times [9-141 whereas
redox catalysis is an extremely large area dealing with metal-catalyzed oxidations
[15, 161 (cf. Section 2.4) and bioorganic catalysis [17, 181 (cf. Section 3.2.1). Many
important references concern electrochemistry (heterogeneous electron transfer)
and therefore are not cited here but interested readers can find them in [4].

3.2.8.2 Electron-Transfer-Chain (ETC) Catalyzed Reactions

3.2.8.2.1 Principles
Thermodynamically favorable reactions such as A +B which suffer from ki-
netic limitations can be catalyzed by an electron or by an electron hole using,
for instance, a redox carrier as an initiator. The reaction can be split into an initia-
tion step and a chain propagation cycle. The latter can be distinguished as a
“chemical” step and a cross redox step (Scheme 1).
overall: A iC + 6+ D
mechanism initiation: A + A*

propagation:

A* + C + B* + D (chemical step)
I I
B* + A + B iA* (cross ET step) initiation (ie)
Scheme 1

The reaction works best if (1) the electron-transfer initiation step is exergonic
i.e., the redox reagent is a good oxidant or a good reductant, depending on
which is required (vide infra); (2) both propagation steps are exergonic (or if
not, at least the overall propagation cycle must be exergonic, and side reactions
of the endergonic step must be avoided).
Catalysis is obtained because the rate of the chemical step is often considerably
more favorable at the odd-electron level than at the even-electron (closed-shell)
level. Indeed, most of the time inorganic radicals react about lo9 times faster
than their isostructural diamagnetic analogs. For organic radicals, the rate en-
hancement is even larger [9].

3.2.8.2.2 Initiation
The initiation can be oxidation or reduction, but usually only one of these two
possibilities is working. The reason is that the cross redox step should be exergo-
1048 3.2 Special Catalysts and Processes

nic to provide an efficient chain reaction. It is also easy to know if the redox step
is exergonic, whereas this is not the case for the "chemical" propagation step. If
the reaction product is more electron-rich than the starting material, the initiator
should be a reductant in order to have an exergonic cross redox step; whereas
it should be an oxidant if the reaction product is less electron-rich than the starting
material. More precisely, the ergonicity of an electron-transfer reaction is given by
the Rehm-Weller equation [ 191:

AGO (kcal mol-') = 23.06 (Fred

- I?),,) + 331.2 [(Z,, - Zred- l)(f/~d)] (1)

where:
I? = thermodynamic redox potential,
Z = charge,
f = ionic-strength factor,
E = dielectric c9nstant of the solvent,
d = r,, + rred (A) = sum of the radii r,, and ?-red of the
oxidant and reductant.

If the oxidant is a monocation (Z,, = 1) and the reductant a neutral species

(Zred= 0), the electrostatic term is nil and the ergonicity is simply deduced
from the respective values of the thermodynamic redox potentials. The electro-
static factor can be large, however, if the difference of charge is high, if the
radii are small, and if the solvent has a low dielectric constant, e.g., THF
( E = 7.5), Et,O ( E = 4.2) or hydrocarbons ( F < 3) [20].
These thermodynamic considerations can also be used for the cross redox step
of the propagation cycle. Thermodynamic redox potential values ?I for initiators
can be found in Table 1.

3.2.8.2.3 Examples
Ligand Substitution Reactions

The first example of recognized ETC catalysis was published by Taube in 1954
[25].Chlorine exchange in [Au"'CIJ was initiated by the reductant [Fe11(CN)6]4-
(eq. (2) and Scheme 2).

Footnotes to Table 1
a ) The redox potential of sandwich complexes can be finely tuned by modification of the
number of ring substituents. (Only approximate values are given for the redox potentials).
For a review of redox potential values, see [21]; for E? values of organometallic complexes,
see [22]; for NAr3, Z?' values range from 0.52 V to 1.72 V vs. SCE depending on the nature
of Ar, see [23]; for transition-metal sandwich compounds, see [24].
') Abbreviations: bipy, bipyridine; Tol, o-tolyl; Cp, r-C5H5; TTF, tetrathiafulvalene; TMPD,

tetramethylphenylenediamine; TCNQ, tetracyanoquinotdimethane; Cp, cyclopentadienyl;

Cp*, pentamethylcyclopentadienyl; TBA, tetrabutylammonium.
 3.2.8.2 Electron-Transfer-Chain (ETC) Catalyzed Reactions 1049

Table 1. Redox reagents suitable for initiation of electrocatalysis."'

Reagentb' Redox potential '?I Solvent
vs. SCE at 25 "C (V)

+ 1.32 MeCN
+ 1.06 DMF
+ 1.11 DMF
+ 1.27 DMF
+ 0.76 THF
+ 0.53 0.1 M HCI
+ 0.3 H20
+ 0.40 MeCN
+ 0.45 DMF
+ 0.30 MeCN
+ 0.21 DMF
+ 0.127 MeCN
- 0.12 MeCN
- 0.29 MeCN
- 0.82 MeCN
- 0.87 DMF

THF
DMF
MeCN
DMF
DMF
DMF
DMF
DMF
MeCN
[CoCp*l* - 0.89 DMF
Footnotes see p. 1048.
 3.2.8.2 Electron-Transfer-Chain (ETC) Catalyzed Reactions 1051

cat.
[Fe'Cp'(C&lee)]
2 PMe3
I - CO

*
Scheme 3. Note how the strength of the reductant is important to initiate the reaction. Also the
two metals are differentiated ("redox recognition"), which leads to regiospecific
reactions [28].

Ph
I
-. -.
/--l
Ph

Ph
I

x
. Ph . Ph

I
Ph

-.A
Ph
I
-. Ph
P
I
PEt3

I
Ph
I
- Ph
u
Scheme 4. Electrocatalytic exchange of CO by a P-donor in the bicapped cluster: the four
radical anions participating in the propagation cycle have been characterized by
EPR, by coupling with P ligand(s) in a stepwise sequence at low temperature [30].
1052 3.2 Special Catalysts and Processes

'L I I
Fe' G==== F;e'
18e

R = H or Me
L = PMe3, P(OMe)3, EtOH, 'BuCN
L3 = diphos + MeCN
(diphos = dppe or dppm)

x1
Scheme 5. The exchange of arene was first disclosed with solvent ligands [31]. Later, it was
found that 19-electron complex [Fe'Cp(arene)], generated from [Fe"Cp(arene)]'
and Na/Hg in THF, can catalyze the ligand exchange with P donors with turnover
numbers of about 100 [32, 331.

(4
- [M=CR21+
18 e [M-SO~V]'
19e

[M-so~v]+ [M=CR2r
18 e
+e
19 e + -R'

M = FeCp+(CO)?;R = H, R' = Ph

M = Fe(C0)2PR'3(R' = Me, Ph); R2C=CR2 = tetrathiafulvalene

Scheme 6. Electrocatalytic carbene transfer to organic substrates: cyclopropanation of olefins

(a) initiated by mild chemical reductants such as Zn powder [34], and carbene
dimerization (b) initiated by mild oxidants such as O2 from air [35].
 3.2.8.2 Electron-Transfer-Chain (ETC) Catalyzed Reactions 1053

/ Fe'
oc,\*+~.""
- dimer

co
18 e I 19 e
Na+[naphthyI]' 18 e

P p -l+*x-
- precipitation or CO exchange
with polar solvent

17 e
18 e

A
I
18 e
[ FeCp2]+X- t
Scheme 7
1054 3.2 Special Catalysts and Processes

CO Insertion

The classic CO migratory insertion into the Fe-CH3 bond can also be initiated
either by an oxidant or a reductant, although the external ligand is not the same
in the two cases. This difference of external ligand (CO versus PPh3) makes the
insertion reaction exergonic in both cases (eqs. (3) and (4); E: = anodic peak
potential; E i = cathodic peak potential; = ( E ; + Ei)/2).

El12 = 0.38 V VS.SCE El12 = 0.47 V vS. SCE

CH2C12,quasi-reversible CH2C12,quasi-reversible
turnover > 20; yield 85-90 %

oc,+" pCH3 PPh3

[cathode], -13 0 V vs. SCE
I h, 20 "C \
co PPh3 CH3 (4)
El12 = -1.90 V vS. SCE El12 = -1.95 V VS. SCE
irreversible irreversible
turnover 5-7; yield 85 YO

Other Reactions

Most other inorganic reactions have been carried out using ETC catalysis: iso-
merization of octahedral complexes [ 3 9 411, disproportionation [42], metal-
metal bond cleavage and formation [43, 441, CO extrusion in formyl complexes
[ 111. Although many studies involve electrochemical initiation, the use of a
chemical oxidant is also often shown to work. It is possible to use a photoexcited
state as the initiator given its enhanced redox power [45].

Coupling ETC Catalysis with Organometallic Catalysis

A major drawback in many catalytic reactions is the kinetic limitation to replace a

ligand in the available precatalyst by the substrate in the coordination sphere of the
transition metal. Heating or a long reaction time is required to overcome the in-
duction period. If a suitable ETC-catalyzed ligand substitution reaction between
the ligand and the substrate is coupled with the organometallic catalysis, it should
be possible to enhance reaction rates and selectivities greatly and to reduce reac-
tion temperatures and times. Such a system was designed for this purpose in the
case of the Wo-catalyzed terminal alkyne polymerization [46] whose mechanism
has been shown by Katz to proceed via metallacyclobutadiene intermediates [47].
Using [W(C0)3(NCMe)3]the polymerization requires either heating to 100 "C, or
one week of reaction at 20 "C. The replacement of an acetonitrile ligand by a less
 3.2.8.3 Atom-Transfer-Chain (ATC)Catalysis 1055

electron-donating alkyne ligand requires an oxidative initiation in order to provide

an exergonic cross redox step. Thus ferricinium salt was used in milligram
amounts in conjunction with Wo catalyst since it must be present only in a cata-
lytic amount with respect to the catalyst. Under these conditions, the reaction
is fast at 20 "C, as expected (eq. ( 5 ) and Scheme 8).

-R -
cat., init.
polyacetylenes K - 25000 (51
cat. = [W(C0)3(NCMe)3;
init. = [FeCp2]+[PF6]-(initiator);
R = alkyl, phenyl

MS2
M = W(CO),(NCMe)
propagation

)( S = NCMe
L = alkyne

MSL

CH H M-C
M -111 + M=C=C( ==== I I
4 t R
R C ~ H RCECH R,c=c\ H

Scheme 8

3.2.8.3 Atom-Transfer-Chain (ATC) Catalysis

3.2.8.3.1 Halogen-ATC Catalysis

The particle transferred in the chain reaction is now a hydrogen or a halogen atom
rather than simply one electron. The cross atom-transfer propagation step is exer-
1056 3.2 Special Catalysts and Processes

gonic if the bond formed is stronger than the bond broken. It was Taube again who
reported the first recognized example in transition-metal chemistry. Radioactive
36Cl was incorporated into [Pt1"Cl6l2-in water at 25 "C for a few minutes upon
irradiation with diffuse visible light [25]. Taube's recognition of the chain
mechanism for ligand substitution explained such reactions, which had in fact
been found 120 years earlier [48] (Scheme 9). The termination step is the dismu-
tation of the Pt"' intermediate to Pt" and Pt'".

Scheme 9

The important oxidative addition reaction was found in 1972 by Osborn and co-
workers to proceed according to an ATC mechanism in the case of the addition of
certain halides to Ir'. For instance, irradiation at 436 nm was proposed to induce
reduction of EtI from the photoexcited state of Ir', generating Et' and I$', a process
accelerated by addition of an electron-rich phosphine which produces a better re-
ductant (eq. (6) and Scheme 10) [49].

Etl + [Ir1(CI)(CO)(L2)] - [Ir1"(l)(CI)(CO)(L2)] (6)

Et

b
( ] hv or
L = PMe3, PMePhz

Scheme 10 Q' QI

Many classical reactions have been recognized to proceed according to this

halogen-ATC catalysis mechanism: examples are the dehydroiodination of
secondary iodides by Pt' [lo], the bromination of [Mn,(CO),,], and the exchange
of carbonyls by phosphines or isonitriles [50].
 3.2.8.4 Conclusions 1057

3.2.8.3.2 Hydrogen-ATC Catalysis

In 1975, Brown [51] found that the substitution of CO by a phosphine in
[Re(H)(CO),] proceeded according to a hydrogen-ATC mechanism. The reaction
can be initiated, for instance, by irradiation at 3 11 nm of the dimer [Re,(CO),,,]
which generates the [Re(CO),]’ radical and can be inhibited by O2 (eq. (7) and
Scheme 11).
-
H-M-CO

H-lMgiCO 1
+ PR H-M-PR3

[M;!eR3]’x
+ CO

CO
(7)

H-M-PRB [M-CO]’ PR3

18e 17e

Scheme 11
t hv
CO-M-M-CO

This mechanism is quite general for this substitution reaction in transition metal
hydride-carbonyl complexes [52]. It is also known for intramolecular oxidative
addition of a C-H bond [53], heterobimetallic elimination of methane [54], inser-
tion of olefins [55],silylenes [56], and CO [57] into M-H bonds, extrusion of CO
from metal-formyl complexes [ 111 and coenzyme B 12- dependent rearrangements
[58]. Likewise, the reduction of alkyl halides by metal hydrides often proceeds
according to the ATC mechanism with both H-atom and halogen-atom transfer
in the propagation steps [4, 531.
Finally, group-transfer chain catalysis involves the transfer of a group in the
cross-propagation step; a few examples are known with transfers of groups
such as ally1 [59], cyclopentadienyl [60], and rhodium octaethylporphyrin [57].

3.2.8.4 Conclusions
Electrocatalysis and redox catalysis both involve catalysis using redox processes.
Molecular engineering is a key feature in these areas of catalysis. It requires
precise thermodynamic data for the investigated systems as well as imaginative
designs, including the coupling of several types of catalysis in multicatalytic
systems. Homogeneous systems are all the more useful as devices are complex
because they are amenable to kinetic investigations, thus allowing a mechanistic
approach. The latter, in turn, is useful for improving multicomponent systems
which involve not only homogeneous processes but also heterogeneous ones
including semiconductors and colloids. At this stage, molecular electronics and
catalysis are clearly connected sciences. Such interdisciplinarity will spread
in the future for the improvement of “catalytic engineering” to mimic the
increasingly well-understood metalloenzymatic catalysis.
1058 3.2 Special Catalysts and Processes

References
[l] H. Taube, Electron-Transfer Reactions of Complex Ions in Solution, Academic Press,
New York, 1970.
[2] D. R. H. Barton, S. 1. Parekh, Halfa Century of Free-Radical Chemistry, Cambridge
University Press, Cambridge, 1993.
[3] F. A. Cotton, G. Wilkinson, Advanced Inorganic Chemistry, 5th ed., Wiley, New York,
1988.
141 D. Astruc, Electron Transfer and Radical Processes in Transition-Metal Chemistry,
VCH, New York, 1995.
[5] D. Astruc in 141, Chapters 2 and 6.
[6] D. Astruc, Angew. Chem. 1988, 100, 662; Angew. Chem., Int. Ed. Engl. 1988, 27, 643.
[7] D. Astruc, Acc. Chem. Res. 1991, 24, 36.
181 The distinction between inner-sphere and outer-sphere electron transfer was established
by Taube; see Ref 1 (and for instance, Ref. 4, Chapters 1 and 7).
191 M. Chanon, Acc. Chem. Res. 1987, 20, 214; M. Chanon, Bull. Soc. Chim. FI: 1982,
11-197 and 1985, 209; M. Chanon, Chem. Rev. 1983, 87, 425.
[lo] J. A. Osbom in Organotransition-Metal Chemistry (Eds.: Y. Ishii, M. Tsutsui), Plenum,
New York, 1978, p. 69.
[ l l ] J. K. Kochi, J. Organomet. Chem. 1986, 302, 389.
[I21 M. I. Bruce, Coord. Chem. Rev. 1987, 76, 1 .
[13] N. J. Coville in Radical Processes in Organometallic Chemistry, J. Organornet. Chem.
Library, Vol. 22 (Ed.: W. C. Trogler), Elsevier, New York, 1990, p. 108.
[ 141 M. Chanon, M. Julliard, J.-C. Poite (Eds.), Paramagnetic Species in Activation, Selec-
tivity, Catalysis, Kluwer, Dordrecht, 1988.
[15] R. A. Sheldon, J. K. Kochi, Metal-Catalyzed Oxidation of Organic Compounds, Aca-
demic Press, 1981, New York.
[16] J. P. Collman, P. S. Wagenknecht, J. E. Hutchinson, Angew. Chem. 1994, 106, 1620;
Angew. Chem., Int. Ed. Engl. 1994, 33, 1537.
1171 J. Reedjik (Ed.), Bioinorganic Catalysis, Dekker, New York, 1993.
[I81 L. Stryer, Biochemistry, 2nd ed., New York, Freeman, 1981.
[I91 D. Rehm, A. Weller, Is% J. Chem. 1970, 8, 259.
[20] L. Eberson, Electron Transfer in Organic Chemistry, Springer, Berlin, 1987, Chapter X.
1211 A. J. Bard (Ed.), Encyclopedia of Electrochemistry of the Elements, Vols. 1-14, Dekker,
New York, 1980.
[22] N. G. Connelly, W. E. Geiger, Adv. Organomet. Chem. 1989, 23, 1.
[23] E. Steckhan, Top. Cur% Chem. 1987, 142, 1.
[24] D. Astruc, Chem. Rev. 1988, 88, 1 1 89.
[25] R. L. Rich, H. Taube, J. Am. Chem. Soc. 1954, 76, 2608.
[26] See [4], Chapter 7. For a recent example see: Y. Koite, C. K. Schauer, Organometallics
1993, 12,4854; M. Hidai, Y. Misobe, Chem. Rev. 1995, 95, 1115; D. Sellmann, Angew.
Chem. 1993, 105, 67; Angew. Chem. Int. Ed. Engl. 1993, 32, 64.
1271 For an in-depth study of ETC catalyzed substitution chemistry in [Co,(CO)&(,-CR)]
clusters, see K. Hinckelmann, J. Heinze, H. Schacht, J. S. Field, H. J. Vahrenkamp,
J. Am. Chem. Soc. 1989, 111, 5078. Carbonyl substitution can also be autocatalytic
(self-initiated); see W. Kaim in Organometallic Radical Processes, J. Organomet.
Library, Vol. 22 (Ed.: W. C. Trogler), Elsevier, New York, 1990, p. 173.
1281 D. S. Brown, M.-H. Delville-Desbois, R. Boese, K. P. C. Vollhardt, D. Astruc, Angew.
Chem. 1994, 106, 715; Angew. Chem., Int. Engl. Ed. 1994, 33, 661.
1291 M. Tilset in Energetics of Organometallic Species (Ed.: J. A. M. Simoes), Kluwer,
Dordrecht, 1992, pp. 109-129.
 References 1059

[30] H. H. Ohst, J. K. Kochi, J. Chem. Soc., Chem. Cornmun. 1986, 121; H. H. Ost, J. K.
Kochi, Inorg. Chem. 1986, 25, 2066.
[31] C. Moinet, E. Roman, D. Astruc, J. Electroanal. Chem. Inter&acial Electrochem. 1981,
241, 121.
[32] J. Ruiz, M. Lacoste, D. Astruc, J. Am. Chem. Soc. 1990, 112, 5471.
[33] P. Boudeville, J.-L. Burgot, A. Darchen, New. J. Chem. 1995, 19, 179
[34] C. Roger, C. Lapinte, J. Chem. Soc., Chem. Commun. 1989, 1598.
[35] D. Touchard, J.-L. Fillaut, H. Le Bozec, C. Moinet, P. H. Dixneuf in [14], p. 311.
[36] J.-N. Verpeaux, M.-H. Desbois, A. Madonik, C. Amatore, D. Astruc, Organometallics
1990, 9, 630.
[37] M.-H. Desbois, D. Astruc, J. Chem. Soc., Chem. Commun. 1990, 943.
[38] D. Astruc, M.-H. Delville, J. Ruiz in Molecular Electrochemistry of Inorganic, Bioinor-
ganic and Organometallic Compounds, NATO AS1 Series, Vol. 385 (Eds.: A. J. L. Pom-
beiro, J. A. McCleverty), Kluwer, Dordrecht, 1993, p. 277.
[39] R. D. Rieke, H. Kojima, K. Ofele, J. Am. Chem. Soc. 1976, 98, 6735; Angew. Chem.
1980, 92, 550; Angew. Chem., Int. Ed. Engl. 1980, 19, 538.
[40] N. G. Connelly, S. J. Raven, G. A. Carriedo, V. Riera, J. Chem. Soc., Chem. Commun.
1986, 992.
[41] C. M. Arewgoda, B. H. Robinson, J. Simpson, J. Chem. Soc., Chem. Cornmun. 1982,
284.
[42] D. R. Tyler in Prog. Inorg. Chem., Vol. 36 (Ed.: S. J. Lippard), Wiley, New York 1988,
125.
[43] S. L. Yang, C. S. Li, C. H. Cheng, J. Chem. SOC., Chem. Cornmun. 1987, 1872.
[44] S. D. Jensen, B. H. Robinson, J. Simpson, Organornetallics 1986, 5, 1690.
[45] D. P. Summers, J. C. Luong, M. S. Wrighton, J. Am. Chem. Soc. 1981, 103, 5238.
[46] M.-H. Desbois, D. Astruc, J. Chem. Soc., Chem. Commun. 1988, 472; M.-H. De,bois,
D. Astruc, New J. Chem. 1989, 13, 595.
[47] T. C. Klarcke, C. S. Yannoni, T. J. Katz, J. Am. Chem. Soc. 1983, 105, 1787.
[48] J. Herschel, Philos. Mag. 1832, I , 58; M. Boll, Ann. Phys. (Paris) 2, 1914, 5, 226.
[49] J. S. Bradley, D. E. Connor, D. Dolphin, J. A. Labinger, J. A. Osborn, J. Am. Chem. Soc.
1972, 94, 4043; J. A. Labinger, A. V. Kramer, J. A. Osborn, ibid. 1973, 95, 7908.
[50] N. M. J. Brodie, A. J. Poe in [14], p. 345.
[Sl] B. H. Byers, T. L. Brown, J. Am. Chem. Soc. 1975, 97, 947; B. H. Byers, T. L. Brown,
ibid. 1977, 9Y, 2527.
[52] T. H. Whitesides, J. Shelly, J. Organomet. Chem. 1975, 92, 215.
[53] T. L. Brown in Organometallic Radical Processes, J. Organomet. Chem. Library, Vol 22
(Ed.: W. C. Trogler), Elsevier, New York, 1990, p. 67; N. J. Coville, ibid. p. 108.
[54] R. T. Edidin, J. R. Norton, J. Am. Chem. Soc. 1986, 108, 948.
[55] J. Halpern, J. Am. Chem. Soc. 1984, 106, 8319; J. Halpern in [14], p. 423.
[56] D. H. Berry, J. H. Mitstifer, J. Am. Chem. SOC. 1987, 109, 3777.
[57] B. B. Wayland, B. A. Woods, J. Chem. Soc., Chem. Cornmun. 1981, 700.
[58] J. Halpern, Science 1985, 227, 869.
[59] M. Rosenblum, P. S. Waterman, J. Organomet. Chem. 1980, 187, 267.
[60] B. D. Fabian, J. A. Labinger, J. Am. Chem. Soc. 1979, 101, 2239; B. D. Fabian, J. A.
Labinger, Organometallics 1983, 2, 659.
 Applied Homogeneous Catalysis with Organometallic Compounds
Edited by B. Cornils and W. A. Herrmann
Copyright 0 Wiley-VCH Verlag GmbH, D-69469 Weinheim, 2002

1060 3.2 Special Catalysts and Processes

3.2.9 Homogeneous Photocatalysis

Andreas Heumann, Michel Chanon

3.2.9.1 Definitions
The actual meaning of the word “photocatalysis is somewhat controversial
”

[ I , 21. The aim of the contribution is to show how organometallic complexes

have made it possible to invent novel chemical transformations without neces-
sarily disentangling all the kinetic subtleties associated with this field. The
definitions adopted will be the rather pragmatic ones proposed by Kirsch
to represent the set of transformations involving photochemistry and more
or less directly connected with catalysis [ 3 ] . However, other definitions are
used elsewhere, and therefore references are cited in which other definitions
have been adopted. Although stoichiometric transformations (e. g., [4]) are
obviously interesting, nothing in their molecular description connect them
with catalytic phenomena. If one thinks that the compulsory bottleneck of
passing through very small quantities of electronically excited states is remi-
niscent of the very small quantities of catalysts used in an efficient catalytic
transformation, one goes back to some old approaches of photochemistry
where light was considered as a catalyst just because it was inducing a trans-
formation.
Photocatalysis can be defined as “acceleration of a photoreaction by the pre-
sence of a catalyst” [3, 51. The catalytic dimension may originate either because
of the quantity of consumed photons or because of the quantity of one added
substance [6]. The most restrictive situation corresponds to a transformation,
photoinduced with a catalytic quantity of photons, provided that a catalytic
quantity of an exogenous substance is added to the reaction mixture. The two
other possibilities, where the catalytic dimension comes either from the number
of consumed photons or from the presence of an added substance in catalytic
quantities, are also well identified.
Several processes that are “catalytic” (a photon is not a substance) in photons
and involve a catalytic quantity of one compound have been reported. Different
labels were associated with such an overall situation: electron transfer induced
chain reactions [7], photoinduced catalytic reactions [8], or photogenerated
catalysis [9]. The main experimental observations which characterize such
processes are:
(1) the presence of quantum yields greater than 1 (exceptions to this statement are
known [lo, 111);
(2) the possible presence of an induction period;
(3) the possible continuation of catalysis after termination of the irradiation.
Salomon identified several types of generic situations among the transfor-
mations responding to these experimental criteria [9]. They are gathered in
Scheme 1.
 3.2.9.1 Definitions 1061

PC
pc + s I+S
PC
1
1 hv

1 1
x 1) II., u
C

'1
hv hv

P S
CP cs
u S P
P R

1.1 1.2 1.3 1.4 1.5

Scheme 1. Types of photocatalytic process (see also Scheme 4).

In this Scheme, pC stands for pro-catalyst, C for catalyst, CS for a complex

between catalyst and substrate, CP for a complex between catalyst and product,
I for an initiator, S' for a structural variation of the substrate, R for an added
reagent. In cases 1.1 and 1.2 the catalysis is based on a coordinative interaction
between catalyst and substrate; in case 1.1 the product is released to regenerate
C (for example by reductive elimination) whereas in case 1.2 the regeneration
of CS results from a substitution of the complexed product by S. It should
be clear that cases 1.1 and 1.2 do not exhaust the formal possibilities offered to
photogenerated catalysis. One may actually imagine a photogeneration of catalyst
from a selected pro-catalyst for any of the multiple catalytic cycles identified in
homogeneous catalysis centered on transition metal complexes [ 121.
In case 1.3 the pro-catalyst interacts with the substrate (for example by photo-
substitution) to generate the actual catalyst. Such a case is germane to photo-
induced electron transfer catalyzed reactions [7] shown in case 1.4. Here, an
excited state of a transition metal complex (designated as I) could interact with
the substrate by a positive or negative electron transfer. Because of the activation
induced by electron transfer [13] S would be transformed into S', whose fate is to
be regenerated one or several steps after yielding P.
In cases 1.1 to 1.4 the role of the photon is played outside the catalytic cycle,
which explains why the quantum yield of P is usually greater than 1. In stoichio-
metric photogenerated catalysis [9] (Scheme 13,also labeled photoassisted [S,
141, photoenhanced [15], or photouctivated [16], the role of the photon is inside
the catalytic cycle; therefore every S + P transformation consumes a photon and
the overall quantum yield for the production of P is smaller than 1. Scheme 1, case
1.5 should not be confused with sensitization because in the step S + C + P + pC
both the substrate and the catalyst are in their ground state, which is not the case
for photosensitization.
An example of case 1.1 is provided by the photosubstitution of CO ligands by L
(L = PBu3, PPh3) in HRe(CO)5 in the presence of catalytic quantities of Re2(CO),o
or Mn,(CO),, for which a possible mechanism is shown in Scheme 2. This me-
chanism is not the one proposed in the original report [17]: it illustrates the inter-
vention of uneven catalytic cycles (contrasted with the ones involving species
1062 3.2 Special Catalysts and Processes

(C0)5Re-Re(C0)5

1 hv

Re(C0)4L Re(CO)5L
17 e 19 e

co
Scheme 2. Photosubstitution in rhenium carbonyl complexes.

with an even number of valence electrons) and the importance of 19e species
[18, 191.
The double bond migration or cis-trans isomerization of linear pentenes
catalyzed by a variety of transition metal complexes (Fe(CO),, Fe3(C0)12,
R U ~ ( C O )in
~ ~the
) presence of irradiation illustrates the operation of case 1.3
[20, 211 (Scheme 3). Case 1.4, which covers photoinduced electron transfer

16 e
4

16 e

Scheme 3. Photoisomerization of linear pentene.

 3.2.9.1 Definitions 1063

catalysis, has been dealt with thoroughly in [7]. Electrochemical studies [22-261
suggest that the photochemical scope of this type of process involving organo-
metallics has been underexploited.
Case 1.5 would be illustrated by photoextrusion of a ligand from a 18e transi-
tion metal complex [27] creating an unsaturation, making possible the complex-
ation of the substrate S to be activated.
The terms used to describe the class of processes that are noncatalytic in
photons, depicted in Scheme 1, case 1.5, are rather confusing. Kutal proposed
to cover all situations by the term catalyzed photochemistry [28]. This includes
three cases:

(1) An excited state of the substrate S reacts with the transition metal complex,
whereas S in the ground state would not react. Such a situation was labeled
catalyzed photoreaction by Wubbels [l], Salomon [9], Mirbach [29], and
Hennig [8].
(2) Case 1.5 in Scheme 1.
(3) Photosensitized reactions.

This combination may be justified because it is experimentally not trivial to dis-

tinguish the situation where photocatalysis results from an interaction between the
excited state of the substrate and the catalyst, and the situation where photocata-
lysis results from a ground-state interaction between the catalyst and the substrate.
It is apparently easier to distinguish experimentally a process that is catalytic in
photons from a noncatalytic one, than to establish that the overall catalytic activity
originates from an interaction between the excited state of the substrate (S) and a
transition metal complex (C) and not from a ground-state interaction between S
and C [30].
The other great class of processes connected to photocatalysis is photosensiti-
zation. Here the processes are no longer “catalytic” in photons but may involve
catalytic quantities of sensitizer. Therefore the quantum yield of product formation
is generally smaller than 1. If one relies on the most general definition of a photo-
sensitized reactions as “a reaction in which a chemical species having absorbed
light undergoes no practical change but some other species undergo a certain
chemical reaction without absorption of photons” [311, then the sensitizer may
sensitize the formation of a catalyst or an initiator. In these specific cases the quan-
tum yield of product formation may obviously become greater than 1. The formal
criterion to distinguish between q5 < and 4 > 1 is to write the catalytic cycle and
to check if hv is operating inside or outside the catalytic cycle (see Scheme 1, cases
1.1-1.4 vs. 1.5). The difficulties in establishing experimentally the mechanism best
fitting the formal scheme prevent the attribution of an unambiguous label to many
of the identified transformations involving both light and transition metal com-
plexes.
Several illustrations are necessary to clarify sensitized photoreactions. If we
limit ourselves to the cases where the organometallic compound is the sensitizer,
most of the situations are gathered in Scheme 4. The extension to photosensitized
transformations of organometallics is straightforward [32].
 1064 3.2 Special Catalysts and Processes

P- I
t Sensf Sens* Sensf Sens'
, SensS Sens'

4.1 4.2 4.3 4.4

Scheme 4. Photocatalytic systems centered on sensitizers.

In Scheme 4, Sens stands for sensitizer, S for substrate, S' for transformed sub-
strate, Sac for sacrificial reagent (because 1 mol of Sac is consumed for 1 mol of
S -+ P transformation). Case 4.1 corresponds to an energy transfer induced trans-
formation of the substrate into product(s). Cases 4.2 and 4.3 correspond to a
transformation resulting from an electron transfer between the sensitizer in its
excited state and the substrate.
The difference between cases 4.2 and 4.3 is that in the first case the transforma-
tion of S into P is coupled with the regeneration of Sens (case 4.2), whereas in the
second case (case 4.3) this regeneration has to be performed by an oxidant or a
reducing agent purposely added to the reaction mixture. Finally, the excitation
of the sensitizer may lead to an associative activation of the substrate toward
the sensitizer and it is this substrate-sensitizer complex which evolves toward
product(s) with regeneration of the sensitizer.
These schemes have been thoroughly explored with inorganic transition metal
complexes, particularly with respect to the use of solar energy [33-351. Far less
has been explored in this direction using organometallic compounds as sensitizers
or substrates.
Some references of reviews besides the ones already cited are given [ 1, 3, 5-9,
19, 23-25, 28, 3 1, 331. Organometallic photochemistry [36] was excellently trea-
ted in [37] and may be compared with inorganic photochemistry to gain further
inspiration [38-40]. A recent multiauthored book strongly overlaps with the sub-
ject matter of the present section, and should certainly be consulted [41]. Electron
transfer reactions play a determinant role in many photocatalytic processes;
several recent reviews and books may be cited on this topic [42-44]. The photo-
chemistry of the M-CO bond [45] and the theme of photocatalysis by transition
metal complexes [46] have recently been reviewed. Covalently linked donor-ac-
ceptor systems for mimicry of photosynthetic energy transfer have been discussed
in [47]. Several special issues of Coordination Chemistry Reviews have been
devoted to the photochemistry and photophysics of coordination compounds
[48-501, and a special issue to photochemistry [51]. Further developments in
photochemistry were the subject of a special issue of Chemical Reviews [52].
Practical considerations useful for designing photochemical experiments may
be found in [53].
 Applied Homogeneous Catalysis with Organometallic Compounds
Edited by B. Cornils and W. A. Herrmann
Copyright 0 Wiley-VCH Verlag GmbH, D-69469 Weinheim, 2002

3.2.9.2 Synthesis and Activation - What hv Metal Catalysis Can Do Better? 1065

3.2.9.2 Synthesis and Activation -

What hv Metal Catalysis Can Do Better?
In a review devoted to transition metal complexes in photocatalysis numerous
examples of transformations [S4] and for the selective activation of small
molecules [ S S ] have already been gathered.

3.2.9.2.1 C-C Bond Formation

Alkylation and Carbonylation

Allyl-ally1 cross-coupling of allyl bromides (Structure 1) and allyl sulfides (2)

carrying homoallylic alcohol or ester functions takes place under irradiation
with hexamethylditin (see eq. (1)). The reaction cleanly leads to 2,6-dienes (3)
and no isomerization of allylic bromides is oberserved [S6].

RpBr + $OR’ (Me3Sn)2,

hv
, T o R ’
and isomers
(1)
34 - 57 Yo
1 2 3

An interesting result of control of acyclic stereochemistry is reported by

Nagano et al. [S7], who showed that efficient 1,2-asymmetric induction can
be achieved in radical-mediated allylation of diethyl (2S,3S)-3-bromo-2-0~0-
succinates stereoselectively. In the Eu(fod)3 ( 1.1 equivalent) photocatalyzed
reaction of bromohydroxy compound (4) diastereoselectivity is reversed with
respect to the simple photoreaction. On the other hand, substitution with silyl
groups tends to enhance diastereoselectivity up to 8.6: 1. The effect is still
operative to a lesser extent with catalytic amounts of the lanthanide reagent
(0.1 equivalents, threo/erythro [5/6] = 3 : 1) (eq. (2)) [S7].

threo 5 erythro 6

R=H 1 1.9
R=H Eu(fod)3 1.7 1
R = SiMe3 Eu(fod)3 8.6 1

Dimeric iron or manganese carbonyl complexes such as [CpFe(CO,)], and

Mn2(CO),o, respectively, upon irradiation photocatalytically cleave carbon-halo-
gen bonds. This leads to carbon-centered radicals which can be reduced to hydro-
1066 3.2 Special Catalysts and Processes

carbons or add to alkenes yielding saturated (8) and/or unsaturated (9) products
(eq. (3)). This transformation is also suitable for cyclization reactions (intramole-
cular radical-trapping) [58].

c
cp, / \ ,co
y cp +
oc’ Fe-Fe, R-x + d yhv_ Ry
- + R‘*=/y
(3)
7 8 9
6 X = halogen
FP2 Y = CN, Ph, C02Me

In the cobalt-catalyzed photochemical carbonylation of olefins, hydrofonnyla-

tion can be performed easily at ambient temperature (and high pressure) with
high primary aldehyde selectivities (cf. Section 2.1 .l) [59]. Under comparable
conditions allylic amines are carbonylated to 2-pyrrolidinone, N,N’-diallylurea,
and N-allyl-3-butenamide [60]. Photochemical methoxycarbonylation of olefins
is possible at ambient conditions, i.e., at room temperature and atmospheric
pressure [61].
In the photochemical activation of CO, the successful achievement of Ni cata-
lysis is considered a milestone [62]. For the first time, a nickel-phosphine cluster
can efficiently reduce C 0 2 to radical anion CO,*- capable of carbon-carbon
coupling reactions (cf. Section 3.3.4).

Photocyclization

In 1989 Curran and co-workers reported on a photocatalytically induced free-

radical cyclization leading to various cyclic, bi-, or polycyclic carbocycles (fused
and spiro) via isomerization of unsaturated iodides (alkenes, alkynes) [63]. This
corresponds to the nonreductive variant of the tin hydride method. Under sunlight
irradiation and in the presence of 10 mol % hexabutylditin, a-iodo esters, ketones,
and malonates are efficiently transformed via an iodide atom transfer chain
mechanism (eq. (4)).

G R Me3SnSnMe30.1
hv eq.

R=Ph 74 26 (68%)
(trans: cis 2.5: 1 : 2 : 1)

The y-iodo carbonyl compounds can either be isolated or transformed in situ

to deiodinated products or to lactones. Synthetic and mechanistic studies with
hex-5-ynyl iodides showed the generality of the method [64]. When tested
 3.2.9.2 Synthesis and Activation - What hv Metal Catalysis Can Do Better? 1067

and compared under three sets of conditions, the photolysis with catalytic
hexabutyltin showed the highest reactivity and selectivities. The tin additive
plays the role of an iodine trap in a two-step radical chain reaction. The
synthesis ofa capnellene (10) outlined in eq. (5) also shows the synthetic po-
tential of this highly controlled radical reaction (a cascade or domino reaction
[65, 661).

Bu3SnSnBu3
I (5)

t l1
10
I
Curran's procedure has been used for ring closure reactions of various methy-
lenecyclopropyl-substituted malonate iodides via 5-ex0, 7-endo, or 8-endo cycli-
zation [67].
The radical photoisomerization of iodoacetylenic esters (alkynes) represents a
route to iodoalkylidene lactones [68]. Zinc has been added to reduce side reac-
tions and to increase yields of the photolysis reaction. Bromoalkynyloxiranes
are photocatalytically (tri-n-butyltin) cyclized to allenylidene tetrahydrofurans
~691.
One may note that these radical reactions involve catalytic amounts of organo-
metallic and catalytic amounts of light (4 > 1) but, as is the case for some photo-
induced electron transfer catalyzed reactions (cf. Section 3.2.9. l), they could be
classified as chain processes rather as catalytic processes [70].
Photocyclization of methoxynaphthyl analogs of chalcone is reported to pro-
ceed via (unusual) electron transfer from excited vinyl arenes. Copper(I1) gives
an organocopper intermediate which evolves via a radical cation to a cyclized
radical and the final naphthofuran 12 (eq. (6)) [71].

hv
1068 3.2 Special Catalysts and Processes

Palladium-catalyzed cross-coupling of alkyl halides is a challenging problem

due to slow oxidative addition rates and rapid /3-elimination of palladium hydride
(Scheme 5 ) .

xFR
hv, P c ~ ( P P0.006
~ ~ ) eq
~
K3P04,benzene, r.t.
9-R-9-BBN
60 %
R = C8H17

I
Pd(0) - Pdl
t 9-R-9-BBN

Scheme 5. Palladium-catalyzed photocatalytic carbonylative coupling with boranes [73].

Photocatalytic carbonylative coupling with 9-alkyl-9-borabicyclo[3.3.1]-

nonanes (9-R-9-BBN), however, made it possible to transform alkyl halides to
ketones [72]. Iodoalkenes or iodoalkynes are thus cyclized to five-membered
rings [73]. The oxidative addition of iodoalkyl to palladium(0) proceeds via
radicals allowing the ring closure to take place prior to the dual coupling with
CO and the alkylboranes.

Photocycloaddition

Photodimerization and cross-cycloaddition of coumarins are improved by

Lewis acids [74]. Similarly, photochemical [2+2] cycloadditions [75] of 1- and
2-naphthols [76] with ethylene are promoted by aluminum halides yielding
the [2+2] adduct from the (complexed) enone form. According to the structure,
substitution (e.g., methyl) vicinal to the OH group in 1-naphthol gives rise to
ring-contracted indanone products. The formation of (ring-contracted) benzo-
bicyclo[3.1 .O]bicyclohexenone was already observed by irradiation (A1C13) of
1-naphthol without ethylene (Scheme 6) [77].
The [3+2] methylenecyclopentane annulation of [(trimethylsilyl)methylene]-
cyclopropane dicarboxylates with unactivated and electron-rich alkenes (vinyl
ether, vinyl thioether, or vinyl silyl ether) are efficiently photocatalyzed by
butyl disulfide or bis(tributy1tin) [78].
With the sequential [2+2] cycloaddition, em-ally lation, hydrohalogenation, and
ring expansion, cycloalkenes and dichloroketene are transformed to cis-fused
cycloheptanones. The photocatalytic step consists of radical alkylation (cycli-
 3.2.9.2 Synthesis and Activation - What hv Metal Catalysis Can Do Better? 1069

41 - 7 2 Yo
3a %

Scheme 6. [2+2] Photocycloaddition and ring contraction of 1- and 2-naphthols [76, 771.

zation) of the cyclobutanone and subsequent radical ring enlargement (Bu,SnH)

(eq. (7)) [791.

Curran's photocatalytically induced radical [4+11 annulation of phenyl

isocyanide (13) and bromopyridone (14) represents the key step of the campto-
thecin synthesis [80, 8 11. The remarkable one-step synthesis of the tetracyclic
heterocyclic system starts with photolytic cleavage of hexamethylditin to form
the Me,Sn radical, which then cleaves the C-Br bond in 14. This new radical
reacts with the isonitrile carbon to form 15 which yields the final 16 via
two subsequent radical intermediates (eq. (8)) (cascade or domino reaction
165, 661).
Me3SnSnMe3

13 14 15
1070 3.2 Special Catalysts and Processes

3.2.9.2.2 Photooxidation
The most important photocatalytical reactions are oxidation reactions which
include the oxygenation of unsaturated systems, but also oxidations of saturated
carbons with or without incorporation of oxygen (C-H activation). The photo-
oxygenation of olefins in the presence of Ti'", V'", or Mo"' catalysts leads
one-pot to epoxy alcohols (17) via singlet oxygen (eq. (9)) [82].

17

The advantage of this method lies in the fact that the peroxidic oxygen is gen-
erated in situ, does not accumulate, and transfers an oxygen atom to the allylic
alcohol. Chemical yields and diastereoselectivities are good; the important pattern
is the ene reactivity of the alkene with singlet oxygen. Chiral epoxides could be
obtained with diethyl tartrate in a good enantiomeric excess of 72 % ee. The reac-
tion has been successfully extended to vinylsilanes (oxyfunctionalization at the
allylic site) [83], halogen substituted alkenes [84], and hydroxyvinylstannones
which after TPP reduction predominantly yield erythro diols [85]. The same dia-
stereoselectivity is observed in the singlet-oxygen ene reaction with chiral allylic
acetates [86]. However, an allylic hydroxy group directs, via coordination of the
incoming electrophilic oxygen, to threo 1,2-dioxygen products. Application of
photocatalytic conditions to these hydroperoxy homoallylic alcohols leads to
epoxy alcohols with unusually high diastereoselectivities [87]. Besides its
synthetic interest, this transformation illustrates the difficulty of easily defining
a borderline between organometallic and inorganic photocatalysis.
Bergman [88] reported on the Mo"' 0x0 complex-catalyzed epoxidation of
olefins by alkyl hydroperoxides (e. g., t-butyl hydroperoxide, TBHP) (eq. (lo)).
The active Cp*Mo02C1 catalyst is generated by irradiation of Cp*Mo(C0)3Cl
in the presence of dioxygen.

CP* CP*

ofic'/
c c\\
I
Mo
:;\cl
02_
hv 04f\
0
-0'
CI
+ (CH3)3C-0H ('O)
I1
0 0

The combination of a (tetraary1porphyrinato)Fe''' photocatalyst and molecular

oxygen transforms strained alkenes to (preferentially) epoxides, whereas un-
strained olefins lead to allylic oxygenation products [89]. The use of water-soluble
metal porphyrin complexes (Mn"', Fe"') facilitates the separation of substrates and
products in aqueous solvent systems [90]. Copper(I1) chloride induces chemo- and
regioselectivity in the photooxyclorination of olefins (eq. (1 1)) [9 11.
 3.2.9.2 Synthesis and Activation - What hv Metal Catalysis Can Do Better? 1071

CuClp, hv, 0 2

R4 pyridine / C H z C l r
R

3.2.9.2.3 C-H Activation [92]

Organic substrates (alkanes alkenes, alcohols) are also photooxidized by trans-
dioxo Ru"' and 0s"' complexes [93]. The interest in these catalysts may lie in
the transformation of cyclohexane to cyclohexanone and cyclohexanol in rea-
sonable yields. The presence of alcohol, ester, and ketone functional groups is
tolerated in the catalytic functionalization [94] with polyoxometallates and Pt'
as co-catalyst [95].
Rh' catalyzes the photochemical dehydrogenation of alkanes with high
efficiency [96]. Cyclooctane was transformed with quantum yields up to 0.10
and turnover numbers as high as 5000 [97] (Scheme 7). tr~ns-Rh(PMe~)~(CO)Cl
was shown to be the only significant photoactive species in solution. The active
catalyst Rh(PMe3)2Cl is formed by photoextrusion of carbon monoxide from
the rhodium carbonyl complex, a process that delivers the energy needed for
the thermodynamically unfavored dehydrogenations.

Rh(PMe&(CO)CI

H2 + Rh(PMe3)2CI

Scheme 7. Photochemical dehydrogenation of cyclooctane [97].

The same photocatalyst system permits the observation of the insertion of

alkynes into C-H bonds [98]. Isonitrile insertion into aromatic C-H bonds with
(C5Me5)Rh(CNCH2CMe3)2gives aldimines in low yield [99]. Photoinduced
1072 3.2 Special Catalysts and Processes

electron transfer between pyridine derivatives and alkyltin reagents leads to alkyl-
ation in a and y positions of the pyridine [loo].
The asymmetric coupling of 2-naphthol to optically active 1,l ’-bis(2-naphthol)-
derivatives (18; eq. (12) [ 1011) has now been realized photocatalytically with
C3-symmetric ~l-[Ru(menbpy)~]~+ (menbpy = 4,4’-di-(lR,2S,SR)-(-)-menthoxy-
carbonyl-2,2’-bipyridine) as a photosenzitizer and [C~(acac)~] as an oxidant
(16.2% ee) [102].

(R)-18

Mercury photosensitized (3P1-excitedstate) dehydrodimerization of hydrocar-

bons [lo31 has been developed into a useful organic synthetic method by using
a simple reflux apparatus in which the radical reaction products are protected
from further transformation simply by condensation (vapor-pressure selectivity)
[ 1041. The selectivity of C-H cleavage increases from primary to tertiary carbons
(350:l) and the method permits the formation of highly substituted C-C bonds
(eq. (13)). One limitation for product formation is the appearance of four sets
of obligatory 1,3-syn methyl-methyl steric repulsions (e. g., 2,3,4,4,5,5,6,7-octa-
methyloctane).
H3C\ Hs(~P~) H3C\ /CH3
H3C-C-H H3C-C-C-CH3
hv / \ (13)
H3C’ H3C CH3

The reaction may proceed as homo- or cross-dehydrodimerization [ 1051 and

takes place with a wide range of substituted substrates such as higher alcohols,
ethers, silanes, and partially fluorinated alcohols and ethers, but also with ketones,
carboxylic acids, esters, amides, and amines [106]. Besides the formation of
1,2-diols from saturated alcohols, unsaturated substrates are also dimerized
under hydrogen to form 1,n-diols other than the 1,2-isomers [107]. The regio-
selectivity of the diols is controlled by the formation of the most stable radical,
which then dimerizes.

3.2.9.2.4 Photoreduction and Photocleavage

Photocatalytic reductions may concern organic unsaturations (C=O, C=C, etc.), or
inorganic C02,or bicarbonate. Even carbon tetrachloride is very efficiently photo-
reduced to chloroform by alcohols with rneso-tetra(2,6-dichlorophenyl)porphyrin
[ 1081. Intermolecular hydrogen transfer is catalyzed by cobalt-phosphine com-
plexes [ 1091. In this reaction photoirradiation generates the active hydride species
“COH[PP~(OE~),]~” for the reduction of ketones with secondary alcohols. The
 3.2.9.2 Synthesis and Activation - What hv Metal Catalysis Can Do Better? 1073

efficient (TON up to 59) and chemoselective reduction of aldehyde carbonyls has

been described with Rh(PMe,),(CO)Cl using cyclooctane as a hydrogen source
(eq. (14)) [1101.

The challenging photochemical reduction of carbon dioxide to formate is cata-

lyzed by Ru" 11111 (cf. Section 3.3.4). For example, with the 2,2'-bipyridine-
ruthenium(I1) complex the active species is formed by photolabilization. Water
renders the system more efficient with quantum yields up to 15 %. Methanol is
the photoproduct when C 0 2 is reduced with TiO, in propene carbonate/2-propanol
[ 1121. In a more sophisticated system, containing deazariboflavin (dRF1, 19) as
photosensitizer, N,Nr-dimethy1-4,4'-bipyridinium (MV2+)as primary electron ac-
ceptor, and sodium oxalate as sacrificial electron donor, in the presence of a Pd
colloid stabilized by P-cyclodextrin (Pd-P-CD), bicarbonate is reduced to formate
[ 1131 (Scheme 8).

Pd-P-CD 19 0

Scheme 8. Reduction of bicarbonate in the presence of a Pd colloid stabilized by

b-cyclodextrin [ 1 131

The mechanism of photocatalytic hydrogenation has been studied (by IR) with
norbornadiene (nbd) and Group 6 metal carbonyls with respect of the role of H2
[114] and the role of the diene [115]. In a subsequent study [116], mer-
[Cr(C0),(v4-norbornadiene)(v2-ethylene)] was found to be a key compound in
the understanding of the photocatalytic diene hydrogenation (eq. (15)).

nbd-Cr(C0)4

*up to 100 turnovers

nbd-Cr(C0)3(C2H4)'
* 4& 1 :
+

3.2
(15)
1074 3.2 Special Catalysts and Processes

Photocatalytic cleavage of 1,2-diols [ 1171 or 1,2-diphenylethane- 1,2-diols [ 1181

with Fe"' porphyrin (Fe"' (tmpyp)) leads to aldehydes and small quantities of the
corresponding acids (eq. (16)).
PhHC -CHPh
hv Ar
I I + 2 Fe"'(tmpyp) 2 PhCHO + 2 Fe"I(tmpyp) + 2 H+ (16)
OH OH

3.2.9.2.5 Isomerization
Iron carbonyl complexes are efficient in photoisomerizations of 2-alkenylphos-
phoramides to 1-alkenylphosphoramides [ 1191 and of unsaturated alcohols to
ketones (eq. (17)) or aldehydes, respectively [ 1201.

eoH Fe3(C0)12
hv, n-hexane
~

90 Yo

3.2.9.2.6 Polymerization
Photopolymerization with transition metals [ 1211 has been used for the formation
of homopolymers and block copolymers from norbornene (nbn) and phenylacety-
lene with W(CO)6 (eq. (18); cf. Sections 2.3.3 and 3.3.10.1) [122].

-
Ph

w(co)6 -Ph-H
I//-w(co)5
H
(CO),W=C=(
Ph

3.2.9.3 Conclusion: What Photochemical Techniques

Can Provide in Mechanistic Studies of
Transition Metal Catalysis
The highly elaborate equipment associated with some time-resolved photochemi-
cal studies makes it possible to observe directly and study quantitatively the reac-
tivity of transient species involved in a catalytic cycle. Time-resolved IR spectro-
scopy has allowed not only direct observations of "nonclassical" dihydrogen com-
plexes of v ~ - ( C ~ R ~ ) M ( CM ~ , a Group 5 metal, but also the kinetic study
O )being
of V ~ - ( C ~ R ~ ) M ( Cintermediates.
O)~ Photoacoustic calorimetry has provided
almost direct evidence that 16-electron species formed by photoejection of CO
from a metal carbonyl compound are solvated even in hydrocarbon solvents
[123]. Other examples are given in [6]. These types of in-depth studies will
certainly increase the understanding of thermal transition metal complex-induced
catalysis.
 References 1075

References
[ l ] G. G. Wubbels, Acc. Chem. Res. 1983, 16, 285.
121 (a) A. Albini, Acc. Chem. Res. 1984, 17, 234; (b) A. Albini, J. Chem. Educ. 1986,
63, 383.
131 H. Kisch in Photocatalysis, Fundamentals and Applications (Eds.: N. Serpone, E. Peliz-
zetti), Wiley New York, 1989, pp. 1-8.
[4] (a) S. Dumas, E. Lastra, L. S. Hegedus, J. Am. Chem. Soc. 1995, 117, 3368; (b) C.
Dubuisson, Y. Fukumoto, L. S. Hegedus, J. Am. Chem. Soc. 1995, 117, 3697.
[ 51 J. Plotnikov, Allgemeine Photochemie, Walter de Gruyter, Berlin, 1936, pp. 362-375.
[6] F. Chanon, M. Chanon in Photocatalysis, Fundamentals and Applications (Eds.: N.
Serpone, E. Pelizzetti), Wiley, New York, 1989, pp. 489-540.
171 M. Chanon, L. Eberson in Photoinduced Electron Transfer, Part A (Eds.: M. A. Fox,
M. Chanon), Elsevier, Amsterdam, 1988, pp. 409-797.
181 H. Hennig, D. Rehorek, R. D. Archer, Coord. Chem. Rev. 1985, 61, 1 .
191 R. G. Salomon, Tetrahedron 1983, 39, 485.
[lo] D. P. Summers, J. C. Luong, M. S. Wrighton, J. Am. Chem. Soc. 1981, 103, 5238.
[ l l ] S. Oishi, J. Mol. Catal. 1987, 40, 289.
[I21 J. P. Collman, L. S. Hegedus, J. R. Norton, R. G. Finke, Principles and Applications
of Organotransition Metal Chemistry, University Science Books, Mill Valley, CA,
1987.
[13] M. Chanon, M. Rajzmann, F. Chanon, Tetrahedron 1990, 46, 6193.
[14] L. Moggi, A. Juris, D. Sandini, M. F. Manfrin, Rev. Chem. Intermed. 1981, 5, 107.
[15] A. W. Adamson, Comments Inorg. Chem. 1981, 1, 33.
[16] W. Strohmeier, L. Weigelt, J. Organomet. Chem. 1977, 133, C43.
[17] B. H. Byers, T. L. Brown, J. Am. Chem. Soc. 1977, 99, 2527.
[18] D. Astruc, Chem. Rev., 1988, 88, 1189.
[19] (a) D. R. Tyler in Paramagnetic Organometallic Species in Activation, Selectivity, Cat-
alysis (Eds.: M. Chanon, M. Julliard, J. C. Poite), Reidel, Dordrecht, 1988, pp. 201-211;
(b) D. R. Tyler, Acc. Chem. Res. 1991, 24, 325.
[20] R. G. Austin, R. S. Paonessa, P. J. Giordano, M. S. Wrighton, ACSAdv. Chem. Sex 1978,
168, 189.
[21] M. A. Schroeder, M. S. Wrighton, J. Am. Chem. Soc. 1976, 98, 551.
[22] M. I. Bruce, Coord. Chem. Rev. 1987, 76, 1.
[23] N. G. Connelly, W. E. Geiger, Adv. Organomet. Chem. 1984, 23, 1; N. G. Connelly,
W. E. Geiger, ibid. 1985, 24, 87.
[24] J. C. Kotz in Topics in Organic Electrochemistry (Eds.: A. J. Fry, W. E. Britton), Plenum,
New York, 1986, p. 142.
[25] T. M. Bockman, J. K. Kochi, J. Am. Chem. Soc. 1987, 109, 7725.
[26] D. Astruc, Electron Transfer and Radical Processes in Transition Metal Chemistry,
VCH, Weinheim, 1995.
[27] (a) A. Davison, N. Martinez, J. Organomet. Chem. 1974, 74, C17; (b) T. G. Attig, R. G.
Teller, S.-M. Wu, R. Bau, A. Wojcicki, J. Am. Chem. Soc. 1979, 101, 619.
[28] C. Kutal, Coord. Chem. Rev. 1985, 64, 191.
[29] M. J. Mirbach, EPA New1 1984, 20, 16.
[30] See also [7], p. 421.
[31] M. Koizumi, S. Kato, N. Mataga, T. Matsuura, Y. Usui, Photosensitized Reactions,
Kagakudojin Publishing, Kyoto, Japan, 1978.
[32] A. Fox, A. Poe, R. Ruminski, J. Am. Chem. Soc. 1982, 104, 7327.
[33] M. Gratzel in Photoinduced Electron Transfer, Vol. D (Eds.: M. A. Fox, M. Chanon),
Elsevier, Amsterdam, 1988, p. 394.
1076 3.2 Special Catalysts and Processes

[34] New J. Chem. 1987, 11, (2) special issue devoted to the photochemical conversion and
storage of solar energy.
[35] A. Harriman, M. West (Eds.), Photogeneration of Hydrogen, Academic Press, London,
1982.
[36] Heterogeneous photocatalysis: M. A. Fox, M. T. Dulay, Chem. Rev. 1993, 93, 341.
[37] G. L. Geoffroy, M. S. Wrighton, Organometallic Photochemistry, Academic Press, New
York, 1970.
[38] G. J. Ferraudi, Elements in Inorganic Photochemistry, Wiley, New York, 1987.
[39] A. W. Adamson, P. D. Fleischauer, Concepts of Inorganic Chemistry, Wiley, New York,
1975.
[40] V. Balzani, V. Carassiti, Photochemistry of Coordination Compounds, Academic Press,
New York, 1970.
[41] K. Kalyanasundaram, M. Gratzel (Eds.), Photosensitization and Photocatalysis Using
Inorganic and Organometallic Compounds, Kluwer Academic, Amsterdam, 1993.
[42] G. J. Kavarnos, Fundamentals of Photoinduced Electron Transfer, VCH, Weinheim,
1993.
[43] J. Photochem. Photohiol. A. Chemistry, 1994, 82 (August), special issue.
[44] Chem. Rev., 1992, 92 (3), special issue devoted to electron transfer reactions.
[45] I. V. Spirina, V. P. Maslennikov, Russ. Chem. Rev. 1994, 63, 41.
[46] 0. V. Gerasimov, V. N. Parmon, Russ. Chem. Rev. 1992, 61, 154.
[47] Tetrahedron Symposia in Print No. 39, 1989, 45, special issue devoted to covalently
linked donor-acceptor species for mimicry of photosynthetic electron and energy transfer.
[48] J. Sykora, J. Sima, Coord. Chem. Rev. 1990, 107, special issue devoted to the photo-
chemistry of coordination compounds.
[49] Coord. Chem. Rev. 1991, 111, special issue devoted to the photochemistry and photo-
physics of coordination compounds.
[50] Coord. Chem. Rev. 1994, 132, special issue devoted to the photochemistry and photo-
physics of coordination compounds.
[51] Coord. Chem. Rev. 1993, 125, special issue devoted to perspectives in photochemistry.
[52] Chem. Rev. 1993, 93 (I), special issue devoted to photochemistry.
[53] J. Mattay, A. Griesbeck, (Eds.), Photochemical Key Steps in Organic Synthesis, VCH,
Weinheim, 1994.
1541 See 161. The following reaction types have been listed: (a) Geometric isomerization of
alkenes; (b) Allylic [ 1,3] hydrogen shift; (c) Cycloaddition of alkenes, Dimerization, Tri-
merization, Polymerization; (d) Skeletal rearrangments of alkenes and methathesis; (e)
Hydrogenation of alkenes; (f) Additions to alkenes; (8) Additions to C = X; (h) Aliphatic
substitutions; (i) Aromatic substitution; (j)Vinyl substitution; (k) Oxidation of alkenes;
(I) Oxidation of alcohols; (m) Oxidation of arenes; (n) Oxidative decarboxylation; (0)
Oxidation of amines; (p) Oxidation of vinylsilanes and sulfides; (9) Oxidation of benzal-
dehyde; (r) Dehydrogenations.
[55] P. C. Ford, A. F. Friedman in Photocatalysis, Fundamentals and Applications (Eds.:
N. Serpone, E. Pelizzetti), Wiley, New York, 1989, pp. 541-565.
1561 A. Yanagisawa, Y. Noritake, H. Yamamoto, Chem. Lett. 1988, 1899.
[57] H. Nagano, Y. Kuno, J. Chem. Soc., Chem. Comm. 1994, 987.
[58] B. Giese, G. Thoma, Helv. Chim. Acta 1991, 74, 1135.
[59] S. Mori, S. Tatsumi, M. Yasuda, K. Kudo, N. Sugita, Bull. Chem. Soc. Jpn. 1991, 64,
3017-3022.
[60] S. Mori, H. Matsuyoshi, K. Kudo, N. Sugita, Chem. Lett. 1991, 1397.
[61] Y.-T. Tao, T. J. Chow, J.-T. Lin, C.-C. Lin, M.-T. Chien, C.-C. Lin, Y. L. Chow, G. E.
Buono-Core, J. Chem. SOC.Perkin Trans. I 1989, 2509.
[62] W. Leitner, Angew. Chem., Int. Ed. Engl. 1994, 33, 173, and references therein.
 References 1077

1631 D. P. Curran, C.-T. Chang, J. Org. Chem. 1989, 54, 3140.

[64] D. P. Curran, M.-H. Chen, D. Kim, J. Am. Chem. Soc. 1989, I l l , 6265.
[65] L. F. Tietze, U. Beifuss, Angew. Chem., Int. Ed. Engl. 1993, 32, 131.
1661 A. de Meijere, F. E. Meyer, Angew. Chem., lnt. Ed. Engl. 1994, 33, 2379.
1671 C. Destabel, J. D. Kilbum, J. Knight, Tetrahedron 1994, 50, 11289.
[68] G. Haaima, L. R. Hanton, M.-J. Lynch, S. D. Mawson, A. Routledge, R. T. Weavers,
Tetrahedron 1994, 50, 2161.
[69] J.-P. Dulckre, E. Dumez, R. Faure, J. Chem. SOC., Chem. Cornrnun. 1995, 897.
1701 See 171, p. 415, for a discussion of this matter.
1711 S. Kar, S. Lahiri, J. Chem. SOC., Chem. Cornmun. 1995, 957.
[72] T. Ishiyama, N. Miyaura, A. Suzuki, Tetrahedron Lett. 1991, 32, 6923.
1731 T. Ishiyama, M. Murata, A. Suzuki, N. Miyaura, J. Chem. SOC., Chem. Commun. 1995,
295.
[74] F. D. Lewis, S. V. Barancyk, J. Am. Chem. SOC. 1989, 111, 8653.
[75] D. I. Schuster, G. Lem, N. A. Kaprinidis, Chem. Rev. 1993, 93, 3.
[76] K. Kakiuchi, B. Yamaguchi, M. Kinugawa, M. Ue, Y. Tobe, Y. Odaira, J. Org. Chem.
1993, 58, 2797.
[77] K. Kakiuchi, B. Yamaguchi, Y. Tobe, J. Org. Chem. 1991, 56, 5745.
[78] C. C. Huval, D. A. Singleton, J. Org. Chem. 1994, 59, 2020.
1791 W. Zhang, Y. Hua, G. Hoge, P. Dowd, Tetrahedron Lett. 1994, 35, 3865.
[80] D. P. Curran, H. Liu, J. Am. Chem. SOC. 1992, 114, 5863.
[81] Asymmetric approach: D. P. Curran, S.-B. KO, J. Org. Chem. 1994, 59, 6139.
[82] W. Adam, M. Braun, A. Griesbeck, V. Luccini, E. Staab, B. Will, J. Am. Chem. SOC.
1989, 111, 203.
[83] W. Adam, M. Richter, Tetrahedron Lett. 1992, 33, 3461; W. Adam, M. J. Richter,
J. Org. Chem. 1994, 59, 3341.
[84] W. Adam, S. Kommerling, E.-M. Peters, K. Peters, H. G. von Schnering, M. Schwarm,
E. Staab, A. Zahn, Chem. Bel: 1988, 121, 2151.
[85] W. Adam, 0. Gevert, P. Klug, Tetrahedron Lett. 1994, 35, 1981.
1861 W. Adam, B. Nestler, J. Am. Chem. Soc. 1992, 114, 6549; W. Adam, B. Nestler, ibid.
1993, 115, 5041.
[87] W. Adam, B. Nestler, J. Am. Chem. Soc. 1993, 115, 7226.
[88] M. K. Trost, R. G. Bergman, Organometallics 1991, 10, 1172.
[89] L. Weber, R. Hommel, J. Behling, G. Haufe, H. Hennig, J. Am. Chem. SOC. 1994, 116,
2400.
1901 H. Hennig, J. Behling, R. Meusinger, L. Weber, Chem. Bel: 1995, 128, 229.
[91] T. Sato, S. Yonemochi, Tetrahedron 1994, 50, 7375.
[92] The biomimetic approach: D. Mansuy, Coord. Chem. Rev. 1993, 125, 129.
[93] V. W.-W. Yam, C.-M. Che, New J. Chem. 1989, 13, 707.
1941 C. L. Hill, R. F. Renneke, L. A. Combs, New J. Chem. 1989, 13, 701.
[95] Review: C. L. Hill, Synlett 1995, 127.
[96] T. Sakakura, T. Sodeyama, M. Tanaka, New. J. Chem. 1989, 13, 737.
[97] J. A. Maguire, W. T. Boese, A. S. Goldman, J. Am. Chem. SOC. 1989, 111, 7088.
[98] W. T. Boese, A. S. Goldman, Organometalllics 1991, 10, 782.
[99] W. D. Jones, R. P. Duttweiler Jr., F. J. Feher, E. T. Hessell, New. J. Chem. 1989,
13, 725.
[loo] F. Minisci, F. Fontana, T. Caronna, L. Zhao, Tetrahedron Lett. 1992, 33, 3201.
[ l o l l For a recent example cf. T. Osa, Y. Kashiwagi, Y. Yanagisawa, J. M. Bobbitt, J. Chem.
SOC., Chem. Cornmun. 1994, 2535.
[lo21 T. Hamada, H. Ishida, S. Usui, Y. Watanabe, K. Tsumura, K. Ohkubo, J. Chem. SOC.,
Chem. Cornrnun. 1993, 909.
1078 3.2 Special Catalysts and Processes

[lo31 R. H. Crabtree, S. H. Brown, C. A. Muedas, C. Boojamra, R. R. Ferguson, Chemtech

1991, 21, 634.
[lo41 S. H. Brown, R. H. Crabtree, J. Am. Chem. Soc. 1989, I l l , 2935.
[lo51 S . H. Brown, R. H. Crabtree, J. Am. Chem. Soc. 1989, 111, 2946.
[I061 C. G. Boojamra, R. H. Crabtree, R. R. Ferguson, C. A. Muedas, Tetrahedron Lett. 1989,
30, 5583.
[lo71 J. C. Lee Jr., C. G. Boojamra, R. H. Crabtree, J. Org. Chem. 1993, 58, 3895.
[I081 C. Bartocci, A. Maldotti, G. Varani, V. Carassiti, P. Battioni, D. Mansuy, J. Chem. Soc.,
Chem. Commun. 1989, 964.
[lo91 M. Onishi, M. Matsuda, I. Takaki, K. Hiraki, S. Oishi, Bull. Chem. Soc. Jpn. 1989,
62, 2963.
[110] T. Sakakura, F. Abe, M. Tanaka, Chem. Lett. 1990, 583.
[111] J.-M. Lehn, R. Ziessel, J. Organomet. Chem. 1990, 382, 157.
[112] S. Kuwabata, H. Uchida, A. Ogawa, S. Hirao, H. Yoneyama, J. Chem. Soc., Chem.
Commun. 1995, 829.
[113] I. Willner, D. Mandler, J. Am. Chem. SOC.1989, 111, 1330.
[114] S. A. Jackson, P. M. Hodges, M. Poliakoff, J. J. Turner, E-W. Grevels, J. Am. Chem.
SOC.1990, 112, 1221.
[115] P. M. Hodges, S. A. Jackson, J. Jacke, M. Poliakoff, J. J. Turner, E-W. Grevels, J. Am.
Chem. SOC. 1990, 112, 1234.
[116] D. Chmielewski, F.-W. Grevels, J. Jacke, K. Schaffner, Angew. Chem., Znt. Ed. Engl.
1991, 30, 1343.
[117] Y. Ito, K. Kunimoto, S. Miyachi, T. Kako, Tetrahedron Lett. 1991, 32, 4007.
[118] Y. Ito, J. Chem. Soc., Chem. Commun. 1991, 622.
[119] S. Igueld, M. Baboulkne, A. Dicko, M. Montury, Synthesis 1989, 200.
[ 1201 N. Iranpoor, E. Mottaghinejad, J. Organomet. Chem. 1992, 423, 399.
[I211 K. Meier, Coord. Chem. Rev. 1991, 111, 97.
[122] B. Gita, G. Sundarajan, Tetrahedron Lett. 1993, 34, 6123.
[123] M. W. George, M. T. Haward, P. A. Hamley, C. Hughes, F. P. A. Johnson, V. K. Popov,
M. Poliakoff, J. Am. Chem. SOC. 1993, 115, 2286.

3.2.10 Olefins from Aldehydes

Wolfgang A. Herrmann

3.2.10.1 Introduction
It was the pioneering work of Georg Wittig [ l ] that yielded an industrially appli-
cable olefin synthesis by C-C coupling [Z]: phosphorus ylides affect a nucleophi-
lic attack at aldehydes and certain other organic keto compounds, resulting in a
methylene (alkylidene) group transfer with concomitant formation of the desired
olefin and a phosphine oxide. The latter type of compounds represents the thermo-
dynamic driving force of this reaction. It is evident from eq. (1) that the Wittig
olefination is a stoichiometric process. The phosphine oxide can be recycled by
means of reducing silanes, e. g., chlorodimethylsilane or hexachlorodisilane,
although the procedures are cumbersome and the yields often low. A recent alter-
 Applied Homogeneous Catalysis with Organometallic Compounds
Edited by B. Cornils and W. A. Herrmann
Copyright 0 Wiley-VCH Verlag GmbH, D-69469 Weinheim, 2002

1078 3.2 Special Catalysts and Processes

[lo31 R. H. Crabtree, S. H. Brown, C. A. Muedas, C. Boojamra, R. R. Ferguson, Chemtech

1991, 21, 634.
[lo41 S. H. Brown, R. H. Crabtree, J. Am. Chem. Soc. 1989, I l l , 2935.
[lo51 S . H. Brown, R. H. Crabtree, J. Am. Chem. Soc. 1989, 111, 2946.
[I061 C. G. Boojamra, R. H. Crabtree, R. R. Ferguson, C. A. Muedas, Tetrahedron Lett. 1989,
30, 5583.
[lo71 J. C. Lee Jr., C. G. Boojamra, R. H. Crabtree, J. Org. Chem. 1993, 58, 3895.
[I081 C. Bartocci, A. Maldotti, G. Varani, V. Carassiti, P. Battioni, D. Mansuy, J. Chem. Soc.,
Chem. Commun. 1989, 964.
[lo91 M. Onishi, M. Matsuda, I. Takaki, K. Hiraki, S. Oishi, Bull. Chem. Soc. Jpn. 1989,
62, 2963.
[110] T. Sakakura, F. Abe, M. Tanaka, Chem. Lett. 1990, 583.
[111] J.-M. Lehn, R. Ziessel, J. Organomet. Chem. 1990, 382, 157.
[112] S. Kuwabata, H. Uchida, A. Ogawa, S. Hirao, H. Yoneyama, J. Chem. Soc., Chem.
Commun. 1995, 829.
[113] I. Willner, D. Mandler, J. Am. Chem. SOC.1989, 111, 1330.
[114] S. A. Jackson, P. M. Hodges, M. Poliakoff, J. J. Turner, E-W. Grevels, J. Am. Chem.
SOC.1990, 112, 1221.
[115] P. M. Hodges, S. A. Jackson, J. Jacke, M. Poliakoff, J. J. Turner, E-W. Grevels, J. Am.
Chem. SOC. 1990, 112, 1234.
[116] D. Chmielewski, F.-W. Grevels, J. Jacke, K. Schaffner, Angew. Chem., Znt. Ed. Engl.
1991, 30, 1343.
[117] Y. Ito, K. Kunimoto, S. Miyachi, T. Kako, Tetrahedron Lett. 1991, 32, 4007.
[118] Y. Ito, J. Chem. Soc., Chem. Commun. 1991, 622.
[119] S. Igueld, M. Baboulkne, A. Dicko, M. Montury, Synthesis 1989, 200.
[ 1201 N. Iranpoor, E. Mottaghinejad, J. Organomet. Chem. 1992, 423, 399.
[I211 K. Meier, Coord. Chem. Rev. 1991, 111, 97.
[122] B. Gita, G. Sundarajan, Tetrahedron Lett. 1993, 34, 6123.
[123] M. W. George, M. T. Haward, P. A. Hamley, C. Hughes, F. P. A. Johnson, V. K. Popov,
M. Poliakoff, J. Am. Chem. SOC. 1993, 115, 2286.

3.2.10 Olefins from Aldehydes

Wolfgang A. Herrmann

3.2.10.1 Introduction
It was the pioneering work of Georg Wittig [ l ] that yielded an industrially appli-
cable olefin synthesis by C-C coupling [Z]: phosphorus ylides affect a nucleophi-
lic attack at aldehydes and certain other organic keto compounds, resulting in a
methylene (alkylidene) group transfer with concomitant formation of the desired
olefin and a phosphine oxide. The latter type of compounds represents the thermo-
dynamic driving force of this reaction. It is evident from eq. (1) that the Wittig
olefination is a stoichiometric process. The phosphine oxide can be recycled by
means of reducing silanes, e. g., chlorodimethylsilane or hexachlorodisilane,
although the procedures are cumbersome and the yields often low. A recent alter-
 3.2.10.2 The Catalytic Approach 1079

native comprises transformation of the phosphine oxide into the dichloride

(= P=O -+ = PC12),followed by reductive dechlorination with the help of alumi-
nium granulate [3].

Numerous monographs [4] and reviews [ S ] on the famous Wittig reaction have
been written since its discovery in 1953. The BASF vitamin-A synthesis depends
in the final step on a Wittig coupling between vinyl-p-ionol (C,,) and y-formyl-
crotyl acetate (C,). This application was developed by Pommer et al. [6] of
BASF in the 1960s.
Again noncatalytic, the organotitanium-mediated olefination of aldehydes,
ketones, and carboxylic esters has been developed by Grubbs et al. [7]. They
used the (commercial) “Tebbe reagent” (Structure 1) as a source of methylene
(CH,) groups to be transferred to the keto component (eq. (2a)). A second
route with the same overall result implies previous transformation of 1 into a
titanacyclobutane 2 which again acts as a methylene transfer reagent. In spite of
significant advantages over the Wittig reaction (high selectivities and yields,
mild conditions, broad spectrum of keto precursors, e. g., carboxylic esters and
cyclic lactones), there remain several drawbacks of this type of olefination: (1)
constitutional restriction to titanium-methylene reagents (no higher titanium-
alkylidene homologs are available); (2) no perspective of a catalytic performance.
The latter problem is due to the considerable strength of the titanium-oxo bond.
As a matter of fact, the analogy between the P=O and Ti=O products is obvious
when considering the formation of the (trimeric) organometallic oxide (Structure 3).

R\
H/c=o

+ ’I3

R\
H/c=o 3

3.2.10.2 The Catalytic Approach

An approach to the problem is summarized in eq. (3). Aldehydes are subject to
catalytic olefination when certain aliphatic diazoalkanes are used as alkylidene
group transfer reagents; phosphines are necessary to carry off the 0x0 group,
1080 3.2 Special Catalysts and Processes

once again reminiscent of the above Wittig reaction. However, the olefination of
eq. (3) is catalytic in terms of the olefination components and the deoxygenation
reagent [8-1 01.

3.2.10.3 Catalysts
It is obvious from the overall equation that a catalyst must generate an intermedi-
ate susceptible to C-C coupling, e. g., a metal-carbene species. Three catalytic
systems based on coordination compounds have been described: the molybdeno-
cyl (Mo"') dithiocarbamate 4 [8], the organorhenium (Re"") oxide 5 [9-111, and
the phosphane-rhenium (Re") chloride 6 [ 111, all representing high oxidation-
state metal-oxo complexes (all three compounds are commercially available,
e.g., from Aldrich and Fluka). Methyltrioxorhenium (MTO) 5 is easily synthe-
sized by methylation of dirhenium heptoxide (Re,O,) or its carboxylic esters
03ReOC(=O)R (e.g., R = CF3) with Sn(CH& [12, 131. Binary rhenium oxides
(Re02, Re03, Re207)and perrhenates are totally inactive, neither is there a reac-
tion in the presence of rhenium<arbonyl complexes [ 101. CH3Re03( 5 ) has also
been applied in the presence of polymer-bound triphenylphosphine [9-111. A high-
yield synthesis of this catalyst is described in Ref. [13].

0 p(c6H5 3
(3-43
S,, l I I CI, I ,CI
Et2N---C'( 'Mo ) C-NEt2 R
, e.
'0 \\-
s' II s'
0 0
P(C6H5)3
4 5 6

The catalysts &6 are employed at concentrations of 10 mol % (Mo) and 1-10
mol % (Re), with respect to the aldehyde. Too low a rhenium concentration favors
the formation of ketazines. The reactions are normally conducted at room
temperature (see below).
Methyltrioxorhenium(VI1) 5 is active even at temperatures as low as -35 "C but
is usually administered at 25 "C. The molybdenum(V1) catalyst requires tempera-
tures of 80 "C (boiling benzene) to convert benzaldehyde and ethyl diazoacetate
into the corresponding cinnamic ester [8]. Turnovers are not yet sufficient for
technical applications but the yields range between 75 and 98 % for the Re-
catalyzed process [9-1 I].
 3.2.10.4 Scope of Reaction, Reagents, and Side Reactions 1081

3.2.10.4 Scope of Reaction, Reagents, and Side Reactions

3.2.10.4.1 Diazoalkanes
It is clear from the known diazoalkane reactivity pattern [ 141 that only derivatives
R2R3C=N2 can be employed that do not react with phosphines (cf. Section
3.2.10.5). Transformations can be observed for the easy-to-handle diazoacetates
and diazomalonates as well as for a number of other compounds, e. g., trimethyl-
silyl diazomethane. Aryldiazoalkanes, however, form phosphazenes that do not re-
lease the alkylidene group. Another problem can arise from the (catalytic) forma-
tion of ketazines - again, unreactive byproducts.

3.2.10.4.2 Keto Compounds

So far, arylaldehydes have been the preferred substrates. Normal ketones are of
little or no reactivity while strained cycloketones, particularly cyclobutanone,
undergo olefination (eq. (4)). Within the series of benzaldehydes, electron-
withdrawing substituents (e. g., p-N02) favour the C-C coupling.
H
I
cat. CH3Re03

H0+ H
N*=C: C02Et
+ P(CsH5)3
- O=P(CsH&
- N2
(4)

3.2.10.4.3 Phosphines
No serious restrictions with regard to the oxygen-accepting organophosphanes
PR43seem to apply. While triphenylphosphine is the only well-studied substrate,
trialkylphosphines and the water-soluble TPPTS also work (TPPTS = tris(sodium-
rn-sulfonatopheny1)phosphine;cf. Section 3.1.1.1). Other deoxygenation reagents
have not yet been employed (e. g., silyl and thio compounds).

3.2.10.4.4 Conditions
Depending somewhat on the reactivity of the diazo component, the catalytic C-C
coupling of eq. (3) is normally conducted at room temperature. To avoid early N2
elimination and unwanted side products, the reaction should be finished within
several hours.
1082 3.2 Special Catalysts and Processes

3.2.10.5 Mechanism
Up to now, there is only slight knowledge of mechanistic details, and no kinetic
data are yet available. Both catalytic systems depend on high oxidation-state metal
centers, indicating that (reversible) redox steps MoV’ MotVand Rev” Re”,
respectively, are in operation to move the 0x0 ligand(s) of the catalyst in and
out. The following proposal for the mechanism related to methyltrioxorhenium
(VII) 5 may apply in principle for the molybdenyl catalyst 4, too.

3.2.10.5.1 Catalyst Activation

It is often observed that metal 0x0 complexes undergo reduction by organopho-
sphines. With methyltrioxorhenium(VII), a stoichiometric 1 : 1 reaction occurs to
yield the phosphine oxide complex 7a of Scheme 1, probably via a primary adduct
of type CH3Re03. P(C6H.J3. Careful workup also yielded crystalline 7b, the struc-
ture of which species is composed of CH,Re03 (Lewis acid, ReV”) and CH3Re-
[P(C6H&I2O2(Lewis base via oxygen, ReV). Irrespectiveof the exact nature of
the intermediates, one out of three 0x0 ligands of catalyst 5 is selectively
labilized by the phosphine, as is evident from the facile formation of derivatives
CH3Re02L upon addition of n-Ligands L. A prominent example is acetylene
(Scheme 1) [15,16], which forms the stable complex CH3Re02(HC=CH) 8 in
high yields, while CH3Re03 ( 5 ) does not react with alkynes in the absence of
the “labilizing” (= deoxygenating) phosphine.

5 7a

(73 u
CH3

“ C I
+ 8 H
0

Scheme 1. Deoxygenation of methyltrioxorhenium(VI1) by triphenylphosphine.

 3.2.10.5 Mechanism I083

3.2.10.5.2 Diazoalkane Activation

It is known from previous work that diazoalkanes can form carbene(alky1idene)-
metal complexes [17, 181, cf. eq. (5). It is thus reasonable to assume that a metal-
carbene 9 is formed from the (phosphine oxide-stabilized) species ( CH3ReV02}
(eq. (5)). High oxidation-state metal carbene complexes have ample precedent,
especially through the work of Schrock et al. [19]. Isolation of type-8 species
may be facilitated by sterically more-demanding auxiliary groups (e. g., CsH5 in
place of CH3) or, by using heterocyclic carbenes of pronounced Lewis basicity
(e. g., 1.3-imidazolin-2-ylidene[20]).

3.2.10.5.3 Aldehyde Activation

Since the keto component reacts neither with the catalyst 5 (with or without phos-
phine) nor with the diazoalkane (exceptions below), it is likely to enter the cata-
lytic cycle at the metal-carbene stage 8. If this proposal withstands future mecha-
nistic studies, then the regioselectivity - oxygen to the oxophilic rhenium center -
is reasonable by considering a metallacyclic intermediate 10 (eq. (6)). This
hypothetical “rhena-oxetane” is assumed to eliminate the olefin. As a matter of
fact, catalyst 5 has been detected from such precursors (e. g., 7a, b + diazoalkane
+ aldehyde) by gas chromatography [9, 101.

c 10 J 5

3.2.10.5.4 The Catalytic Cycle

The mechanistic proposal can be summarized in the catalytic cycle of Scheme
2. The catalyst 5 performs so well because it undergoes reactivation by the
phosphine. This is not the case with the organotitanium(1V) oxide 3 (eqs.
(2a), (2b)), thus explaining the noncatalytic reactivity of the Tebbe and Grubbs
reagents.
1084 3.2 Special Catalysts and Processes

R’\
,c=o

Scheme 2. Proposed mechanism of the oxorhenium-catalyzed olefination of aldehydes.

3.2.10.5.5 Catalyst Assessment

The olefination of aldehydes by diazoalkanes depends on catalysts that accept the
keto oxygen from the substrate S. and transfer it to an auxiliary reagent R.. A
redox process M”-* G M“=O is necessarily included in such a sequence (Scheme
3 ) . The reduced step O=Mo’”(S2C-NEt,), has in fact been isolated from the phos-
phine reduction of catalyst 4, and a carbene complex of structure 11 according to
eq. (7) was suggested [8].

NEt2’ a ‘NEtP
C02Et
4
11

From this assessment two requirements concerning the catalyst can be postu-
lated: (1) the oxophilicity has to be high enough to react with the aldehyde in
the catalyst’s reduced state; (2) the reductive potential has to bei high enough
to release the 0x0 ligand in the catalyst’s oxidized state. In addition, the catalyst
must have a configuration that allows the C-C coupling of the alkylidene-group
 References 1085

carriers (aldehyde, diazoalkane). Low-coordinated species such as CH3Re03seem

specifically to meet these requirements.
Cyclopropanation of the olefinic product does not occur; the catalytic metal-
carbene intermediate obviously cannot transfer its CR2R3 unit to the olefinic
double bond (see, however, metal-catalyzed cyclopropanation, Section 3. I .7).

3.2.10.6 Perspectives
At first sight, the olefination reaction of eq. (3) looks rather special with regard to
the diazoalkane substrates and the phosphine which is required to bind the oxy-
gen. However, the most successful diazoalkanes are either commercially available
(e. g., ethyl diazoacetate, trimethyl silyldiazomethane) or can easily be prepared
(e. g., diazomalonates). Furthermore, phosphines may in the future be replaced
by other oxophilic co-reactants, possibly by silyl compounds. Finally, this type
of C-C coupling is catalytic, an uncommon feature in olefination chemistry.
For these reasons and because of the as yet unexplored potential of stereoselectiv-
ity should the little recognized reaction become the subject of intense research.
For example, the immobilization of CH3Re03 and related compounds on oxidic
supports could yield heterogeneous catalysts if the specific balance of oxygen
elimination and addition can be maintained (Scheme 3).

catalyst deactivation

R, :
,c+o
/' \ f-L
M"-* M"=O
R.

R=O
H :
S. u
catalyst activation

Scheme 3. Schematic mechanism of 0x0 transfer at high oxidation-state metal complexes

(R.= reducing agent, e. g. phosphine; S. = substrate = oxygen-donating reagent).

References
[ l ] The German chemist Georg Wittig (1897-1987) was a professor of chemistry at the
Technische Hochschule Braunschweig (Germany) and at the universities of Freiburg,
Tiibingen, and Heidelberg. He received the Nobel Prize for chemistry in 1979, jointly
with Herbert C. Brown; cf. W. Tochtermann, Top. Curr: Chem. 1988, 144 (preface).
[2] (a) G. Wittig, G. Geissler, Liehigs Ann. Chem. 1953, 580, 44; (b) G. Wittig, Angew.
Chem. 1956, 68, 505.
[3] H. G. Hauthal, Nachr: Chem. Tech. h b . (WeinheidGermany)1993, 41, 1015.
[4] M. Schlosser, Top. Stereochem. 1972, 5, 1.
[5] Rompp, Chemie-Lexikon, Vol. 6, 9th ed., Thieme, Stuttgart, 1992, p. 5056.
[6] Reviews: (a) H. Pommer, Angew Chem. 1960, 72, 811; (b) H. Pommer, Angew. Chem.
1977, 89, 437; Angew. Chem., Int. Ed. Engl. 1977, 16, 423; (c) H.-J. Bestman, 0. Vos-
1086 3.2 Special Catalysts and Processes

trowsky, Top. Curc Chem. 1983, 109, 8 5 ; (d) H.-J. Bestmann, R. Zimmermann in:
Houben-Weyl, Methoden der Organischen Chemie, Vol. E l , 4th ed., Thieme, Stuttgart,
1982, p. 616.
[7] (a) Review: R. H. Grubbs, Pure Appl. Chem. 1983, 55, 1733; (b) R. H. Grubbs, L. R.
Gillom, J. Am. Chem. Soc. 1986, 108, 733; (c) H.-U. Reissig, Nuchc Chem. Tech.
Lab. (WeinheidGermany) 1986, 34, 562.
[8] X. Lu, H. Fang, Z. Ni, J. Organomet. Chem. 1989, 373, 77.
[9] (a) Hoechst AG (W. A. Herrmann), DE 4.101.737 (1991) and DE 4.002.505 (1990);
(b) W. A. Herrmann, Mei Wang, Angew. Chem. 1991, 103, 1709; Angew. Chem., Int.
Ed. Engl. 1991, 30, 1641.
[lo] W. A. Herrmann, P. W. Roesky, Mei Wang, W. Scherer, Orgunometullics 1994, 13,4531.
[ l l ] P. W. Roesky, Ph. D. Thesis, Technische Universitat Miinchen, Germany 1994.
[12] W. A. Herrmann, W. R. Thiel, F. E. Kiihn, R. W. Fischer, M. Kleine, E. Herdtweck,
W. Scherer, J. Mink, Inorg. Chem. 1993, 32, 5188.
[I31 (a) W. A. Herrmann, R. W. Fischer, M. Rauch, W. Scherer, J. Mol. Catul. 1994, 86,
243; (b) W. A. Herrmann (Ed.), Synthetic Methods in Inorganic and organometallic
Chemistry, Vol. I , Thieme, Stuttgart, 1996.
[ 141 Monograph: M. Regitz, Diazoalkane: Eigenschaften und Synthesen, Thieme Verlag,
Stuttgart, 1977.
[I51 J. K. Felixberger, J. G. Kuchler, E. Herdtweck, R. A. Paciello, W. A. Herrmann, Angew.
Chem. 1988, 100, 975; Angew. Chem., Int. Ed. Engl. 1988, 27, 946.
[16] W. A. Herrmann, J . K. Felixberger, J. G. Kuchler, E. Herdtweck, Z. Naturforsch. Teil B
1990, 45, 876.
[I71 Review: W. A. Herrmann, Angew. Chem. 1978, 90, 855; Angew. Chem., Int. Ed. Engl.
1978, 17, 800.
[18] Review: W. A. Herrmann, Adv. Organomet. Chem. 1982, 20, 160.
[19] (a) R. R. Schrock, J. Organomet. Chem. 1986, 300, 249; (b) R. R. Schrock in Carbyne
Complexes (Eds: H. Fischer, P. Hofmann, F. R. Kreissl, R. R. Schrock, U. Schubert,
K. Weiss), Verlag Chemie, Weinheim, 1988, pp. 147-204.
[20] W. A. Herrmann, M. Elison, J. Fischer, C. Kocher, G. R. J. Artus,Angew. Chern. 1995,107,
2602; Angew. Chem., Int. Ed. Engl. 1995, 34, 237 1, and references cited therein.

3.2.11 Water-Gas Shift Reaction

WolfgangA. Herrmann, Michael Muehlhofer

3.2.11.1 Introduction
Many catalytic reactions described in this book depend on carbon monoxide and
hydrogen as feedstock chemicals. Hydroformylation (CO + H2) and simple hydro-
genation (H2) are typical examples. In many cases carbon monoxide undergoes
side reactions, among which the “water-gas shift reaction” is well studied in
terms of the mechanism. This explains why carbon monoxide in the presence
of water (e. g., aqueous media) can be used to hydrogenate substrates such as ole-
fins, nitroaromatics, and other unsaturated organic compounds. In a number of
industrial processes (e. g., the hydrocarboxylation of ethylene), however, this is
an unwanted side reaction.
 Applied Homogeneous Catalysis with Organometallic Compounds
Edited by B. Cornils and W. A. Herrmann
Copyright 0 Wiley-VCH Verlag GmbH, D-69469 Weinheim, 2002

1086 3.2 Special Catalysts and Processes

trowsky, Top. Curc Chem. 1983, 109, 8 5 ; (d) H.-J. Bestmann, R. Zimmermann in:
Houben-Weyl, Methoden der Organischen Chemie, Vol. E l , 4th ed., Thieme, Stuttgart,
1982, p. 616.
[7] (a) Review: R. H. Grubbs, Pure Appl. Chem. 1983, 55, 1733; (b) R. H. Grubbs, L. R.
Gillom, J. Am. Chem. Soc. 1986, 108, 733; (c) H.-U. Reissig, Nuchc Chem. Tech.
Lab. (WeinheidGermany) 1986, 34, 562.
[8] X. Lu, H. Fang, Z. Ni, J. Organomet. Chem. 1989, 373, 77.
[9] (a) Hoechst AG (W. A. Herrmann), DE 4.101.737 (1991) and DE 4.002.505 (1990);
(b) W. A. Herrmann, Mei Wang, Angew. Chem. 1991, 103, 1709; Angew. Chem., Int.
Ed. Engl. 1991, 30, 1641.
[lo] W. A. Herrmann, P. W. Roesky, Mei Wang, W. Scherer, Orgunometullics 1994, 13,4531.
[ l l ] P. W. Roesky, Ph. D. Thesis, Technische Universitat Miinchen, Germany 1994.
[12] W. A. Herrmann, W. R. Thiel, F. E. Kiihn, R. W. Fischer, M. Kleine, E. Herdtweck,
W. Scherer, J. Mink, Inorg. Chem. 1993, 32, 5188.
[I31 (a) W. A. Herrmann, R. W. Fischer, M. Rauch, W. Scherer, J. Mol. Catul. 1994, 86,
243; (b) W. A. Herrmann (Ed.), Synthetic Methods in Inorganic and organometallic
Chemistry, Vol. I , Thieme, Stuttgart, 1996.
[ 141 Monograph: M. Regitz, Diazoalkane: Eigenschaften und Synthesen, Thieme Verlag,
Stuttgart, 1977.
[I51 J. K. Felixberger, J. G. Kuchler, E. Herdtweck, R. A. Paciello, W. A. Herrmann, Angew.
Chem. 1988, 100, 975; Angew. Chem., Int. Ed. Engl. 1988, 27, 946.
[16] W. A. Herrmann, J . K. Felixberger, J. G. Kuchler, E. Herdtweck, Z. Naturforsch. Teil B
1990, 45, 876.
[I71 Review: W. A. Herrmann, Angew. Chem. 1978, 90, 855; Angew. Chem., Int. Ed. Engl.
1978, 17, 800.
[18] Review: W. A. Herrmann, Adv. Organomet. Chem. 1982, 20, 160.
[19] (a) R. R. Schrock, J. Organomet. Chem. 1986, 300, 249; (b) R. R. Schrock in Carbyne
Complexes (Eds: H. Fischer, P. Hofmann, F. R. Kreissl, R. R. Schrock, U. Schubert,
K. Weiss), Verlag Chemie, Weinheim, 1988, pp. 147-204.
[20] W. A. Herrmann, M. Elison, J. Fischer, C. Kocher, G. R. J. Artus,Angew. Chern. 1995,107,
2602; Angew. Chem., Int. Ed. Engl. 1995, 34, 237 1, and references cited therein.

3.2.11 Water-Gas Shift Reaction

WolfgangA. Herrmann, Michael Muehlhofer

3.2.11.1 Introduction
Many catalytic reactions described in this book depend on carbon monoxide and
hydrogen as feedstock chemicals. Hydroformylation (CO + H2) and simple hydro-
genation (H2) are typical examples. In many cases carbon monoxide undergoes
side reactions, among which the “water-gas shift reaction” is well studied in
terms of the mechanism. This explains why carbon monoxide in the presence
of water (e. g., aqueous media) can be used to hydrogenate substrates such as ole-
fins, nitroaromatics, and other unsaturated organic compounds. In a number of
industrial processes (e. g., the hydrocarboxylation of ethylene), however, this is
an unwanted side reaction.
 3.2.11.3 Mechanism 1087

3.2.11.2 Definition
Steam reforming [l] following eq. (1) is the technology commonly used to pro-
duce carbon monoxide and hydrogen in an endothermic reaction (130 kJ/mol).

The product is called “water-gas’’ (German “Wussergus”). To optimize the yield

of hydrogen, the equilibrium to eq. (2) is employed. This particular process is
known as the “water-gas shift reaction”, albeit Konvertierungsgleichgewicht
(as the German terminus technicus) seems more appropriate.

The hydrogen required for the production of ammonia is generated thus. The
industrially most important equilibrium (2) is slightly exothermic (42 kJ/ mol)
and is catalyzed by a large number of soluble transition metal complexes, but
the commercial plants work with heterogeneous catalysts. In the typical two-
stage process, chromium(II1) oxides (at 350450 “C) and copper/zinc oxides
(at 200-300 “C) are employed as catalysts [l]. Soluble catalysts are complexes
such as Fe(CO)S and its hydrido derivative [HFe(CO)J, Ru~(CO),~,
[Rh(CO),IJ, and Pt[P(Pr‘)3]3 [2]. The rhodium complex [Rh(CO),IJ - the
key catalytic feature in the Monsanto acetic acid process (Section 2.1.2.1) - is
particularly efficient: in a solution of acetic acid, CO is converted at 80-90 “C
and 0.5 atm into an equimolar amount of C 0 2 and an equivalent volume of H2
[2b]. Although the catalytic turnover is low (five to nine cycles per diem), the
catalytically active species is quite robust.

3.2.11.3 Mechanism
The water-gas shift mechanism was explored mainly by P. C. Ford et al. in the
1970s [2-4], showing that a number of consecutive organometallic reactions are
involved (Scheme 1). All of them have stoichiometric precedents.
The first step is likely to be a so-called “Hieber base reaction” (@in Scheme l),
describing a nucleophilic attack at metal-coordinated carbon monoxide by hydro-
xide. While eq. (3) is the prototypical example as first reported by Walter Hieber
in 1932 [ 5 ] ,several other variants have since become known. For example, azides
and alkyVaryl anions attack metal carbonyls according to eqs. (4) and (3,yielding
metal isocyanates (via a Curtius-type azide degradation step) and metal carbenes,
respectively [6, 71.
1088 3.2 Special Catalysts and Processes

H2
M-CEO
metal carbonyl

co
1

metal dihydride metal carboxylic acid

k I

Scheme 1. Mechanistic proposal for the metal-catalyzed water-gas shift reaction; equilibria
disregarded. M: metal complex, e. g., Fe(C0)4 (see text).

A synthetically useful technique for substituting (C-electrophilic) carbon mon-

oxide ligands from metal carbonyls is a base reaction with the sufficiently nucleo-
philic trimethylamine oxide [8]. As represented by eq. (6), the same mechanistic
scheme applies, with the zwitterionic intermediate breaking down into the (vola-
tile, weakly coordinating) fragments C 0 2 and N(CH,),; at the same time, a reac-
tive fragment (e. g., the 16e-system “Fe(CO),”) is being formed.

This “base reaction” does not depend on hydroxide and proceeds under mild
conditions, thus replacing the often less-clean photoelimination of carbon monox-
ide. Certain cationic metal carbonyls are attacked even by water, a reaction that
 3.2.11.4 Applications 1089

Scheme 2. Tautomerization of a rheniumcarboxylic acid as an example of the synthesis of

oxygen-labeled metal carbonyls.

can be utilized to from oxygen-labeled derivatives (I7O, I8O) from normal CO

complexes through a tautomerization step [9] ; the cationic complex [Re(C0)6]’
is the prototypical example (Scheme 2).
Transition metal carboxylic acids resulting from the above base reaction are
normally unstable with respect to decarboxylation, thus undergoing degradation
to hydrides (reaction @ in Scheme 1) [lo]. Only a few cases of barely stable
derivatives are known, such as ($-CSHs)Fe(C0)2C02H [ 111. As seen in the
historical reaction of eq. (3), the carboxylate system undergoes fast elimination
of CO,. (Oxidation of the resulting anionic hydrido complex [HFe(CO)J by
Mn02 is the standard procedure for synthesis of Fe,(CO),,.)
The anionic metal hydride takes up a proton from the aqueous medium to yield
a dihydride (step 0); a known example is H2Fe(CO), [5 a, 121. In the final step
@, hydrogen elimination through replacement by CO closes the catalytic cycle,
thus furnishing the water-gas shift reaction of eq. (2).

3.2.11.4 Applications
The catalytic formation of hydrogen has been exploited as a means to reduce sub-
strates by carbon monoxide/water. For example, selenium is converted into sele-
nium hydride, SeH,, in the sequence of eqs. (7a-d) under high-pressure autoclave
conditions [ 131.

Se + CO - Se=C=O
OH
Se=C=O + H20 G== H-Se-CL
0
OH
H- Se - C i - SeH2 + C02
A

SeH2 -- Se + H2
A
(74
CO + H20 -
- C02 + H2 (7)
1090 3.2 Special Catalysts and Processes

Once again, a “carbonyl complex” (SeCO) is initially formed, with the latter
forming a carboxylic acid which then decarboxylates to SeH2. Catalytic amounts
of selenium suffice to effect reduction of nitroaromatics according to eq. (8). The
reduction equivalent (H2) originates from the water-gas shift reaction, although
SeH2 also acts as a (strong) reductant! The optimum solvent was found to be
N-methylpyrrolidone. This sequence shows that not only transition metals are
capable of catalyzing the reaction of water with carbon monoxide.

0 N 0 2 + 3CO + H20 -
cat’Se G N H 2 + 3C02

A base reaction is also made responsible for the palladium(I1)-catalyzed reduc-

tive carbonylation of nitroaromatics to isocyanates. Carbon monoxide affects the re-
duction step Pd2+-+ Pdo in protic media [ 141 according to eq. (9). The consecutive
sequence -NOz +-NO --+-N --+ -N=C=O including the two oxygen ab-
straction steps are possible with the Pdo thus generated (cf. Section 3.3.5) [15].

Another interesting application is the selective reduction of aldehyde functions

under water-gas shift reaction conditions [21]. Starting from Rh6(CO)16in the
presence of an amine in aqueous media, the anionic cluster anion [Rh6(C0)1sH]-
forms via nucleophilic attack of hydroxide, followed by elimination of carbon
dioxide. The anionic hydride cluster is thought to be the active species in the
reduction of a number of aldehydes according to eq. (1 0).

10-15 atm, 80°C, amine

+ CO + H20 (10)
Rhs(C0)16 benzene R~
Ri

The reduction proved to be chemoselective for aldehyde functions even in the

presence of keto groups. The yield in homogeneous reactions varies between
9 % and 30%. When aminated polystyrene is used as the basic component,
the active anionic species [Rh6(CO),sH]- is immobilized via interaction with
the supported ammonium cations and leads to an increase in the yields up to
91-99% [22, 231, while the catalyst can be recovered by simple filtration
from the product.

3.2.11.5 The Arc0 Ethylurethane Process

The selenium-catalyzed reduction of nitrobenzene via the water-gas shift reaction
(see eqs. (7a-d)) was exploited by Arc0 Chemicals to make the ethylurethane 1
according to eq. (11). Here, ethanol is being used in place of water [16].
 3.2.11.6 Catalytic Implications and Perspectives 1091

6 + 3CO + C2H5OH -8
cat. Se
(base)
> 200 "C
\N /C02C2H5

1
+ 2 0 2 (11)

The primary product is aniline (eq. (S)), which then undergoes addition of
carbonyl selenide, Se=C=O, in the presence of a strong base [17]. The resulting
urethane can further be converted into the methylene diurethane, which is then
cracked to the diisocyanate MDI 2, a key industrial intermediate for the produc-
tion of polyurethane foams and elastomers (cf. Section 3.3.5). It was probably for
toxicity reasons that completion of a technical plant at one of the Arc0 sites [ 181
was hampered.
/C02C2H5

2H& 1
- + H&=O

- H20
AT *
- 2 C2HsOH (y%J/ 2
/
N, c,o (12)

ethylurethane MDI
("methylenediisocyanate")

The ideal method of reductive carbonylation of nitroaromatics would employ

synthesis gas according to eq. (13): CO as a carbonylation reagent is cheaper
in the form of syngas than pure CO, but it is more expensive as a reducing
agent (eq. (8)) than hydrogen. Unfortunately, there is as yet no catalyst for
the overall conversion of eq. (13); only the stepwise reduction works cata-
lytically.
0

c
NO2

0 I

+ 2H2 + C O -
N

+ 2H20

3.2.11.6 Catalytic Implications and Perspectives

The water-gas shift reaction is normally an unwanted side reaction of homoge-
neous catalysis when carbon monoxide is engaged as a substrate and if water is
present as the medium or as a product. Both a pH-basic medium (formation of
the nucleophilic [OH]-) and metals or metal complexes that deprotonate the
water favor the shift reaction. For example, in the hydrocarboxylation process
to make propionic acid directly from C2H4,CO, and H 2 0 (eq. (14)), the formation
of hydrogen via the water-gas shift reaction leads to (minor) hydrogenation and
hydroformylation products (cf. Section 2.1.2.2).
1092 3.2 Special Catalysts and Processes

C H ~ = C H+~ co + H~O - 0
CH~CH~C’
‘OH
(14)

As a matter of fact, olefin-consuming reactions (by H2) may be a serious

problem in some technical reactions. Palladium complexes and C O ~ ( C O(com-)~
mercial products) are typical catalysts. Problems may also arise in the Fischer-
Tropsch reaction [ 19, 201 where iron oxides of a certain basicity (alkaline-metal
doping) are being used to catalyze the formation of hydrocarbons according to
(the simplified) eq. (15). More details are provided in Section 3.1.8. Since water
is inevitably formed, carbon dioxide can also occur. On the other hand, it is
doubtful whether the CO/H20 system will be used for directed reductions of
organic compounds, since hydrogen is an extremely abundant industrial chemi-
cal. The water-gas shift reaction is thus to be avoided in the vast majority of
cases.
CO + 2H2 - ‘In--(CH2f, + H20 (15)

References
[ 11 (a) Mechanism: K. Tamaru in Catalysis - Science and Technology (Eds.: J. R. Anderson,
M. Boudart), Springer, Berlin, 1991, Vol. 9 pp. 93-94; (b) J. R. Rostrup- Nielsen, ibid.
1984, Vol. 5, pp. 57-58; (c) M. A. Vannice, ibid. 1982, Vol. 3, pp. 190-193.
(a) R. M. Laine, R. G. Rinker, P. C. Ford, J. Am. Chem. Soc. 1977, 99, 252; (b) C. H.
Cheng, D. E. Hendrikson, R. Eisenberg, ibid. 1977, 99, 2791; (c) R. B. King, C. C. Fra-
zier, R. M. Hanes, A. D. King, ibid. 1978, 100, 2925; (d) T. Yoshida, T. Okano, Y. Ueda,
S. Otsuka, ibid. 1981, 103, 341 1; (e) T. Yoshida, Y. Ueda, S. Otsuka, ibid. 1978, 100,
3941.
Reviews: (a) P. C. Ford, Acc. Chem. Res. 1981, 14, 31; (b) P. C. Ford, A. Rokocki, Adv.
Organomet. Chem. 1988, 28, 139.
[4] R. M. Laine, R. B. Wilson, “Recent developments in the homogeneous catalysis of the
water-gas shift reaction”, in Aspects of Homogeneous Catalysis (Ed.: R. Ugo), Vol. 5,
Reidel (Kluwer), Dordrecht 1984.
[5] W. A. Herrmann, J. Organomet. Chem. 1990, 382, 21; (b) Historical review: B. Cornils,
W. A. Herrmann, M. Rasch, Angew. Chem. 1994, 106, 2219; Angew. Chem., lnt. Ed.
Engl. 1994, 33, 2144, and references cited therein; (c) Comprehensive text: W. Hieber,
Adv. Organomet. Chem. 1970, 8, 1; (d) M. Catellani, J. Halpern, Inorg. Chem. 1980,
19, 566.
[6] W. Beck, J. Organomet. Chem. 1990, 383, 143.
[7] (a) E. 0. Fischer, Adv. Organomet. Chem. 1976, 14, 1; (b) K. H. Dotz, H. Fischer,
P. Hoffmann, F. R. Kreissl, U. Schubert, K. Weiss, Transition Metal Carbene Complexes,
Verlag Chemie, Weinheim, 1983.
[S] Review: M. J. Albers, N. J. Coville, Coord. Chem. Rev. 1984, 53, 227.
[9] Other examples: R. H. Crabtree, The Organometallic Chemistry of the Transition
Metals, Wiley Interscience, New York, 1988.
[lo] N. Grice, S. C. Kao, R. Pettit, J. Am. Chem. SOC.1979, 101, 1697.
[ l l ] J. R. Sweet, W. A. G. Graham, Organornetallics 1982, 1, 982.
[I21 (a) W. Hieber, F. Leutert, 2. Anorg. Allgem. Chem. 1932, 204, 145; (b) W. Hieber,
H. Vetter, ibid. 1933, 212, 145.
 3.2.12.1 Introduction 1093

[13] T. Miyata, K. Kondo, S. Murai, T. Hirashama, N. Sonoda, Angew. Chem. 1980, 92, 1040;
Angew. Chem., Int. Ed. Engl. 1980, 19, 1008.
[14] V. A. Golodov, Yu. L. Sheludyakov, R. I. Di, V. K. Kokanov, Kinet. Katal. 1977, 18, 234.
[ 151 (a) A. L. Balch, D. Petrides, Znorg. Chem. 1969, 8, 2245; (b) R. G. Little, R. J. Doedens,
ibid. 1973, 12, 536; (c) S . Otsuka, Y. Aotani, Y. Tatsuno, T. Yoshida, ibid. 1976, 15, 656.
[16] ARC0 Chemicals (J. G. Zajacek, J. J. McCoy, K. E. Fuger), US 3.919.279 (1975) and
3.956.360 (1976).
[I71 Mitsui Toatsu (H. Seiji, H. Yutaka, M. Katsuhara), US 4.170.708 (1979).
[18] (a) Anon., Chem. Eng. News, Oct. 10, 1977, p. 12; (b) Anon., Chem. Week, July 26,
1978, p. 28.
[19] Reviews: (a) W. A. Herrmann, Angew. Chem. 1982, 94, 118; Angew. Chem., Int. Ed.
Engl. 1982, 21, 117; (b) C. K. Rofer-DePoorter, Chem. Rev. 1981, 81, 447.
[20] Monograph: H. H. Storch, N. Golumbic, R. B. Anderson, The Fischer-Tropsch and
Related Syntheses, Wiley, New York, 1951.
[21] K. Kaneda, M. Hiraki, T. Imanaka, S. Teranishi, . IMol. Cutul. 1980, 9, 227; K. Kaneda,
.
Y. Yasumura, T. Imanaka, S. Teranishi, Chem. Commun. 1982, 93.
[22] K. Kaneda, T. Mizugaki, K. Ebitani, Tetrahedron Lett. 1997, 38, 3005.
[23] J.M. Basset, P. Dufour, L. Huang, A. Choplin, S.G. Sanchez-Delgado, A. Tholier,
J. Orgnomet. Chem. 1988, 354, 354; B.T. Heaton, L. Strona, S. Martinengo, D. Stru-
molo, R. J. Goodfellow, I. H. Sadler, .I. Chem. SOC.,Dalton Trans. 1982, 1499.

3.2.12 Catalytic McMurry Coupling:

Olefins from Keto Compounds
Wolfgang A. Herrmann, Horst Schneider

3.2.12.1 Introduction
In 1973 Mukaiyama, Tyrlik, and McMurry discovered a remarkably simple reac-
tion that couples aldehydes or keto compounds reductively to olefins [ 1, 21. This
methodology following eq. (1) differs from that of Section 3.2.10 in that no extra
methylene or alkylidene transfer reagent is required. The stereochemistry of the
product depends on the nature of the substituents R and whether an open-chain
or a cyclic olefin results.

R\
H
,C=O + O=C(
H

R
+ "Ti" - R\
H
,C=C,
,R
H
+ "Ti02" (1)

The driving force of the reaction is the formation of the strong titanium-
oxygen bonds. Low-valent titanium is oxophilic enough to extrude all the oxygen
from the substrate. This C-C coupling process, albeit stoichiometric with regard
to the (inorganic) coupling reagent(s), has become extraordinarily useful in the
synthesis of olefinic compounds, be it either intru- or intermolecularly. The
reaction is compatible with quite a large number of functional groups, e.g.,
hydroxyl, amide, sulfide, ether, and C-C double bonds. Even phenanthrenes
 Applied Homogeneous Catalysis with Organometallic Compounds
Edited by B. Cornils and W. A. Herrmann
Copyright 0 Wiley-VCH Verlag GmbH, D-69469 Weinheim, 2002

3.2.12.1 Introduction 1093

[13] T. Miyata, K. Kondo, S. Murai, T. Hirashama, N. Sonoda, Angew. Chem. 1980, 92, 1040;
Angew. Chem., Int. Ed. Engl. 1980, 19, 1008.
[14] V. A. Golodov, Yu. L. Sheludyakov, R. I. Di, V. K. Kokanov, Kinet. Katal. 1977, 18, 234.
[ 151 (a) A. L. Balch, D. Petrides, Znorg. Chem. 1969, 8, 2245; (b) R. G. Little, R. J. Doedens,
ibid. 1973, 12, 536; (c) S . Otsuka, Y. Aotani, Y. Tatsuno, T. Yoshida, ibid. 1976, 15, 656.
[16] ARC0 Chemicals (J. G. Zajacek, J. J. McCoy, K. E. Fuger), US 3.919.279 (1975) and
3.956.360 (1976).
[I71 Mitsui Toatsu (H. Seiji, H. Yutaka, M. Katsuhara), US 4.170.708 (1979).
[18] (a) Anon., Chem. Eng. News, Oct. 10, 1977, p. 12; (b) Anon., Chem. Week, July 26,
1978, p. 28.
[19] Reviews: (a) W. A. Herrmann, Angew. Chem. 1982, 94, 118; Angew. Chem., Int. Ed.
Engl. 1982, 21, 117; (b) C. K. Rofer-DePoorter, Chem. Rev. 1981, 81, 447.
[20] Monograph: H. H. Storch, N. Golumbic, R. B. Anderson, The Fischer-Tropsch and
Related Syntheses, Wiley, New York, 1951.
[21] K. Kaneda, M. Hiraki, T. Imanaka, S. Teranishi, . IMol. Cutul. 1980, 9, 227; K. Kaneda,
.
Y. Yasumura, T. Imanaka, S. Teranishi, Chem. Commun. 1982, 93.
[22] K. Kaneda, T. Mizugaki, K. Ebitani, Tetrahedron Lett. 1997, 38, 3005.
[23] J.M. Basset, P. Dufour, L. Huang, A. Choplin, S.G. Sanchez-Delgado, A. Tholier,
J. Orgnomet. Chem. 1988, 354, 354; B.T. Heaton, L. Strona, S. Martinengo, D. Stru-
molo, R. J. Goodfellow, I. H. Sadler, .I. Chem. SOC.,Dalton Trans. 1982, 1499.

3.2.12 Catalytic McMurry Coupling:

Olefins from Keto Compounds
Wolfgang A. Herrmann, Horst Schneider

3.2.12.1 Introduction
In 1973 Mukaiyama, Tyrlik, and McMurry discovered a remarkably simple reac-
tion that couples aldehydes or keto compounds reductively to olefins [ 1, 21. This
methodology following eq. (1) differs from that of Section 3.2.10 in that no extra
methylene or alkylidene transfer reagent is required. The stereochemistry of the
product depends on the nature of the substituents R and whether an open-chain
or a cyclic olefin results.

R\
H
,C=O + O=C(
H

R
+ "Ti" - R\
H
,C=C,
,R
H
+ "Ti02" (1)

The driving force of the reaction is the formation of the strong titanium-
oxygen bonds. Low-valent titanium is oxophilic enough to extrude all the oxygen
from the substrate. This C-C coupling process, albeit stoichiometric with regard
to the (inorganic) coupling reagent(s), has become extraordinarily useful in the
synthesis of olefinic compounds, be it either intru- or intermolecularly. The
reaction is compatible with quite a large number of functional groups, e.g.,
hydroxyl, amide, sulfide, ether, and C-C double bonds. Even phenanthrenes
1094 3.2 Special Catalysts and Processes

Thorpe-Ziegler Route

Dieckmann Reaction

Figure 1. Yields from different synthetic routes to C3-CI6carbocycles.

and heterocycles such as arsole, indole, and pyrazole derivatives are thus acces-
sible.
It is specifically noted that this active-metal supported coupling makes cyclic
olefins of otherwise unfavorable ring sizes (n = 8-12) available without problems
(cf. Figure 1). Reactions following eq. (1) thus belong to the modern synthetic
methodology. From a mechanistic point of view, electron transfer (metal to
substrate) is of key importance (e. g., pinacolate-titanium intermediates).

3.2.12.2 Stoichiometric Titanium Compounds,

Other Reagents, and Mechanistic Aspects
A fair number of coupling reagents has been reported for the McMurry reaction.
They mostly contain titanium in an oxidation state smaller than 4. For example,
TiC13 . CH30CH2CH20CH3[ 3 ] , and a system described as “TiC13-LiA1H4-
THF,” known as the “McMurry reagent”. Improvements of the coupling reagent
were reported by Bogdanovic‘ and co-workers, who described a hydridic Ti”
species resulting from treatment of TiCI3 with activated MgH2 [4] according
to eq. (2).

TiCI3*(THF)3 + MgH2 - (TW

- 80 + 25 “C
HTiCI(THF)-o.5 + MgC12
1
+ ’12 H2 (2)

The same active species (1, eq. (2)) could be found in the “McMurry reagent”
system where TiC13becomes reduced by 0.5 equivalent of LiA1H4in THF [2fl. Ti’
 3.2.12.2 Stoichiometric Titanium Compounds 1095

R,’ ,R’
I~~I--O*O-F~I
A R2 R 2

/
2 [Ti]
\
- 2 [Ti]=O

R’ R’ R’
2 p
R

- 2 ri]=O

2 [Ti]

Scheme 1

could be excluded as active species according to EXAFS measurements [5,6], and

more generally, Tio is not presupposed for the McMuny reaction [7]. The mecha-
nism of McMuny type reactions has a dual nature [7, 81, as shown in Scheme 1
11 a, bl.
Dependent of the carbonyl substrate, the Ti compound, the reducing reagents,
and other available compounds, the dual nature of the mechanism can be ob-
served. Less hindered ketones follow pathway (A) with pinacolate intermediates.
Heavily hindered ketones would follow the carbenoid route (B) [2 f, 7, 81.
Other efficient reagents include TiC14/Zn [ 1 a], TiC13/Mg [ 1 b], TiC13/Zn-Cu
[ I el, and TiC13 . (DME)I.,/Zn-Cu [ l d] (DME = 1.2-dimethoxyethane), with
the latter resulting as blue crystals from boiling TiC13 in DME, and M’Cl,/
M2(Hg) (MI = U, Ti, M2 = alkali metal) [8, 91. However, the McMuny reaction
is stoichiometric, since the titanium-oxo bonds (e. g., Ti02) resist (catalytic) re-
activation. Although McMuny coupling reactions play a key role in the synthesis
of numerous natural products (e. g., crassin [lo], taxol [l l ], cembren C [12], and
mevinolen [ 13]), textbooks on catalysis hardly mention this otherwise interesting
(from a mechanistic point of view) and useful synthetic procedure [14] for the
reason mentioned above, and because of problems of reproducibility due to the
manifold combination possibilities of the reagents [7]. Iodine also can activate
low-valent Ti reagents [15], and external ligands, e. g., t-BuOH [16] or pyridine
[17], have been used to direct the reaction.
Other aldehyde-to-olefin coupling reagents of low-valent metals have also been
described ; however, they suffer from being less efficient. The tungsten(II1) alkox-
1096 3.2 Special Catalysts and Processes

CI

H
3 4

ide W2(OCH2B~t)6 . 2py, for example, gives yields up to 66 % [I 81, while tita-
nium-mediated couplings are often beyond 90 % yield.
A variety of low-valent species effects the deoxygenation of eq. (1). The exact
nature of Ti,O, formed during a McMurry coupling (simplified in eq. (1) as Ti02)
now becomes better understood. The nature of the active species is often specu-
lative, although firm evidence for structures 2-4 resulting from a-TiC13/MgH2,
TiCI4/MgH2,or TiC13/LiA1H4/THFhas been presented [2 f, 41.

3.2.12.3 Catalytic Deoxygenation

Furstner et al. discovered [19] that the combination of TiC13/Zn dust and
(CH&SiCI works catalytically with regard to the titanium in reductive aldehyde
coupling. The so-called "instant method" works also in non-etherlike solvents
(e.g., acetonitrile, DMF), and a couple of functional groups are tolerated [2 fl.
Equation (3) can be written for the overall reaction, showing that the chlorosilane
reagent is necessary in a twofold stoichiometric amount based on the aldehyde
(ketone) to be coupled. Acetonitrile or DME are the preferred (coordinating) sol-
vents. While (CH&SiCl as the cheapest of all chlorosilanes requires 5-10 mol %
Tic&, the bis(chlorosi1ane) C1(CH3)2Si-CH2CH2-Si(CH3)2C1 works better
(2 mol % TiC13).A number of heterocycles, e. g., substituted indoles, is thus avail-
able.

2
R\
H
/C=O + 4 (CH3)3SiCI -
cat. Ti R\
H
1
R
/C=C, + 2 (CH3)3Si-O-Si(CH3)3
H
(3)
 3.2.12.4 Perspectives 1097

Chlorosilanes are also capable of activating commercial titanium powder (e. g.,
(CH&SiCl in boiling DME [20]), which then couples oxoamides such as 5 in
isolated yields of > 92 % to the indoles, e. g., 6, according to eq. (4) [21].

& - d5
/
C6H5

NH
I
"active Ti"

/ N
H
C6H5
(4)

Above-stoichiometric amounts of chlorosilanes are necessary for high yields.

The reagent exhibits a strong template effect for intramolecular coupling
processes. Even 36-membered carbocycles and numerous unsaturated crown-
ether derivatives can be made in good yields. Beyond that, multiply C-C-unsatu-
rated compounds such as retinal 7 undergo reductive coupling: in case of eq. ( 5 )
p-carotin 8 is formed in good yields.

" \ \ \ \

p-carotin 8 (85 % yield)

2

The proposal of Scheme 2 appears to be a reasonable approach to the problem.

The chlorosilane obviously does not only destroy the oxidic layer of titanium
powder (activation effect) but also seems to facilitate the electron transfer from
the metal to the substrate [21].

3.2.12.4 Perspectives
The catalytic system of Furstner et al. is to be considered as a breakthrough in
reductive deoxygenating C-C coupling with highly oxophilic low-valent titanium
[22], albeit not too much has been published since the time of this discovery [ 191.
The auxiliary oxygen traps (chlorosilanes) are cheap, easy to handle and to
remove (e. g., they have low boiling points), and relatively unreactive toward
the substrates to be coupled. Beyond that, the catalytic "titanium instant" is an
insoluble and thus easy-to-remove reagent. Considering the vast number of bio-
logically relevant C-C-unsaturated carbo- and heterocycles, the catalytic route
is expected to become a major synthetic approach. It is well known that inter-
1098 3.2 Special Catalysts and Processes

\
5 R3SiCl
6 R3

Scheme 2. Catalytic McMurry coupling of oxoamides to indoles according to Fiirstner [21].

Preferred substituents: R’ = C6Hs, R2 = CF3, CO,Et, R3 = H. The [TiCI] species is
structurally undefined and differs in nature depending upon the conditions of
generation.

mediate-size cyclic compounds (e. g., carbocycles of ring size 8-12; cf. Fig. 1) are
only accessible in reasonable yields by the McMuny coupling [2]. The catalytic
efficiency of titanium (or another cheap metals?) is certainly subject to further
improvement. Suffice it to say that an electrochemical reactivation of the metal
oxide would be the most elegant solution to the intrinsic problem of the McMuny
coupling.

References
[ l ] (a) T. Mukaiyama, T. Sato, J. Hanna, Chem. Lett. 1973, 1041; (b) S. Tyrlik, 1. Wolocho-
wicz, Bull. Soc. Chim. FK 1973, 2147; (c) J.E. McMuny, M. P. Fleming, J. Am. Chem.
Soc. 1974, 96, 4708; (d) J.E. McMurry, J. Org. Chem. 1978, 43, 3255.
[2] Reviews: (a) J.E. McMurry, Arc. Chem. Res. 1983, 16, 405; (b) B.E. Kahn, R.T.
Riecke, Chem. Rev. 1988, 88, 733; J.E. McMuny, Chem. Rev. 1989, 89, 1514; (d)
C. Betschart, D. Seebach, Chimia 1989, 43, 39; (e) D. Lenoir, Synthesis 1989, 8830;
(f) A. Fiirstner, B. Bogdanovic, Angew. Chem. 1996, 108, 2582; Angew. Chem. Int.
Ed. Engl. 1996, 35, 2442.
[3] J. E. McMurry, T. Lectka, J. G. Rico, J. Org. Chem. 1989, 54, 3748.
[4] (a) L. E. Aleandri, B. Bogdanovic, A. Gaidies, D. J. Jones, S. Liao, A. Michalowicz,
J. Rozikre, A. Schott, J. Organomet. Chem. 1993,459, 87; (b) L. E. Aleandri, S. Becker,
B. Bogdanovic, D. J. Jones, J. Rozikre, J. Organomet. Chem. 1994, 472, 97.
[5] H. Bertagnolli, T. S. Ertel, Angew. Chem. 1994, 106, 15; Angew. Chem. Int. Ed. Engl.
1994, 33, 45.
[6] (a) R. Dams, M. Malinowski, I. Westdorp, H. J. Geise, J. Org. Chem. 1982, 47, 248;
(b) R. Dams, M. Malinowski, H. J. Geise, Trunsition Met. Chem. (London), 1982, 7,
37; (c) Bull. Soc. Chim. Belg. 1981, 90, 1141.
[7] M. Ephritikhine, Chem. Commun. 1998, 2549.
 3.2.13.1 Introduction 1099

[XI C. Villiers, M. Ephritikhine, Angew. Chem. 1997, 109, 2477; Angew. Chem. Int. Ed.
Engl. 1997, 36, 2380.
[9] (a) D. Maury, C. Villiers, M. Ephritikhine, New J. Chem. 1997, 21, 137; (b) Angew.
Chem. 1996, 108, 1215; Angew. Chem. Int. Ed. Engl. 1996, 35, 1129; (c) C. Villiers,
R. Adam, M. Lance, M. Nierlich, J. Vigner, M. Ephritikhine, J. Chem. Soc., Chem.
Commun. 1991, 1144.
[ 101 (a) W. G. Dauben, T. Z. Wang, R. W. Stephens, Tetrahedron Lett. 1990, 2393; (b) J. E.
McMurry, R.G. Dushin, J. Am. Chem. Soc. 1990, 112, 6942.
[I I] (a) K. C. Nicolaou, J. J. Liu, Z. Yang, H. Ueno, E. J. Sorensen, C. F. Claibome, R. K. Guy,
C. K. Hwang, M. Nakada, P. G. Nantermet, J. Am. Chem. Soc. 1995, 117, 634; (b) K. C.
Nicolaou, Z. Yang, J. J. Liu, P. G. Nantermet, C.F. Claibome, J. Renaud, R. K. Guy,
K. Shibayama, J. Am. Chem. Soc. 1995, 117, 645.
[I21 Y. Li, W. Li, Y. Li, Synth. Commun. 1994, 24, 721.
[ 131 D. L. J. Clive, K. S. K. Murthy, A. G. H. Wee, J. S. Prasad, G. V. J. da Silva, M. Majewski,
P. C. Anderson, C. F. Evans, R. D. Haugen, L. D. Heerze, J. R. Barrie, J. Am. Chem. Soc.
1990, 112, 3018.
[ 141 Textbook and review on organic synthesis: (a) K. P. C. Vollhardt, Organic Chemistry,
Structure and Function, W.H. Freeman, New York, 1999; (b) D. Seebach, Angew.
Chem. 1990, 102, 1363;Angew. Chem. Int. Ed. Engl. 1990, 29, 1320.
[I51 S. Talukdar, S. K. Nayak, A. Banerji, J. Org. Chem. 1998, 63, 4925.
[16] T. A. Lipski, M. A. Hilfiker, S. G. Nelson, J. Org. Chem. 1997, 62, 4566.
[17] N. Balu, S. K. Nayak, A. Banerji, J. Am. Chem. Soc. 1996, 118, 5932.
[18] M.H. Chisholm, J. A. Klang, J. Am. Chem. SOC.1989, 111, 2324.
[19] A. Furstner, A. Hupperts, A. Ptock, E. Janssen, J. Org. Chem. 1994, 59, 5215.
[20] A. Furstner, B. Tesche, Chem. Muter: 1998, 10, 1968.
[21] A. Furstner, A. Hupperts, J. Am. Chem. SOC. 1995, 117, 4468.
[22] Review on “active titanium”: A. Fiirstner, Angew. Chem. 1993, 105, 171; Angew. Chem.
Int. Ed. Engl. 1993, 32, 164.

3.2.13 Catalytic Hydrogenation of Heterocyclic Sulfur

and Nitrogen Compounds in Raw Oils
Claudio Bianchini, Andrea Meli, Francesco Vizza

3.2.13.1 Introduction
The use of single-site transition metal catalysts to effect the hydrogenation of hete-
roaromatic sulfur and nitrogen compounds finds its primary impetus in the need
for improved understanding of the mechanisms of the hydrodesulfurization
(HDS, eq. (1)) and hydrodenitrogenation (HDN, eq. (2)) processes [ 11. Indeed,
with stringent environmental regulations concerning the amount of sulfur and ni-
trogen permitted in gasoline and city diesel, the development of new HDS and
HDN catalysts is a priority in the petrochemical industry.
Hydrodesulfurization CaHbS+ c H2 - H2S + CaHd (1)
Hydrodenitrogenation CaHbN + c H2 - NH3 + CaHd (2)
 Applied Homogeneous Catalysis with Organometallic Compounds
Edited by B. Cornils and W. A. Herrmann
Copyright 0 Wiley-VCH Verlag GmbH, D-69469 Weinheim, 2002

3.2.13.1 Introduction 1099

[XI C. Villiers, M. Ephritikhine, Angew. Chem. 1997, 109, 2477; Angew. Chem. Int. Ed.
Engl. 1997, 36, 2380.
[9] (a) D. Maury, C. Villiers, M. Ephritikhine, New J. Chem. 1997, 21, 137; (b) Angew.
Chem. 1996, 108, 1215; Angew. Chem. Int. Ed. Engl. 1996, 35, 1129; (c) C. Villiers,
R. Adam, M. Lance, M. Nierlich, J. Vigner, M. Ephritikhine, J. Chem. Soc., Chem.
Commun. 1991, 1144.
[ 101 (a) W. G. Dauben, T. Z. Wang, R. W. Stephens, Tetrahedron Lett. 1990, 2393; (b) J. E.
McMurry, R.G. Dushin, J. Am. Chem. Soc. 1990, 112, 6942.
[I I] (a) K. C. Nicolaou, J. J. Liu, Z. Yang, H. Ueno, E. J. Sorensen, C. F. Claibome, R. K. Guy,
C. K. Hwang, M. Nakada, P. G. Nantermet, J. Am. Chem. Soc. 1995, 117, 634; (b) K. C.
Nicolaou, Z. Yang, J. J. Liu, P. G. Nantermet, C.F. Claibome, J. Renaud, R. K. Guy,
K. Shibayama, J. Am. Chem. Soc. 1995, 117, 645.
[I21 Y. Li, W. Li, Y. Li, Synth. Commun. 1994, 24, 721.
[ 131 D. L. J. Clive, K. S. K. Murthy, A. G. H. Wee, J. S. Prasad, G. V. J. da Silva, M. Majewski,
P. C. Anderson, C. F. Evans, R. D. Haugen, L. D. Heerze, J. R. Barrie, J. Am. Chem. Soc.
1990, 112, 3018.
[ 141 Textbook and review on organic synthesis: (a) K. P. C. Vollhardt, Organic Chemistry,
Structure and Function, W.H. Freeman, New York, 1999; (b) D. Seebach, Angew.
Chem. 1990, 102, 1363;Angew. Chem. Int. Ed. Engl. 1990, 29, 1320.
[I51 S. Talukdar, S. K. Nayak, A. Banerji, J. Org. Chem. 1998, 63, 4925.
[16] T. A. Lipski, M. A. Hilfiker, S. G. Nelson, J. Org. Chem. 1997, 62, 4566.
[17] N. Balu, S. K. Nayak, A. Banerji, J. Am. Chem. Soc. 1996, 118, 5932.
[18] M.H. Chisholm, J. A. Klang, J. Am. Chem. SOC.1989, 111, 2324.
[19] A. Furstner, A. Hupperts, A. Ptock, E. Janssen, J. Org. Chem. 1994, 59, 5215.
[20] A. Furstner, B. Tesche, Chem. Muter: 1998, 10, 1968.
[21] A. Furstner, A. Hupperts, J. Am. Chem. SOC. 1995, 117, 4468.
[22] Review on “active titanium”: A. Fiirstner, Angew. Chem. 1993, 105, 171; Angew. Chem.
Int. Ed. Engl. 1993, 32, 164.

3.2.13 Catalytic Hydrogenation of Heterocyclic Sulfur

and Nitrogen Compounds in Raw Oils
Claudio Bianchini, Andrea Meli, Francesco Vizza

3.2.13.1 Introduction
The use of single-site transition metal catalysts to effect the hydrogenation of hete-
roaromatic sulfur and nitrogen compounds finds its primary impetus in the need
for improved understanding of the mechanisms of the hydrodesulfurization
(HDS, eq. (1)) and hydrodenitrogenation (HDN, eq. (2)) processes [ 11. Indeed,
with stringent environmental regulations concerning the amount of sulfur and ni-
trogen permitted in gasoline and city diesel, the development of new HDS and
HDN catalysts is a priority in the petrochemical industry.
Hydrodesulfurization CaHbS+ c H2 - H2S + CaHd (1)
Hydrodenitrogenation CaHbN + c H2 - NH3 + CaHd (2)
1100 3.2 Special Catalysts and Processes

It is difficult to know whether, and if so which, HDS and HDN modeling

studies have led to the development of new catalysts with improved per-
formance under actual refinery conditions. There is little doubt, however, that
the homogeneous studies have contributed greatly to the elucidation of the bind-
ing of the S- and N-heterocycles to metal centers as well as to the mechanisms
of fundamental steps such as the hydrogen transfer from metal to coordinated
substrate and the C-S or C-N bond scissions [2]. Reference to this important
work is provided in this Section, which, however, is almost exclusively con-
cerned with catalytic hydrogenation reactions of sulfur and nitrogen hetero-
aromatics. Recently, some homogeneous and heterogeneous single-site metal
catalysts have been found to assist effectively the hydrogenation and/or hydro-
genolysis of N- and S-heteroaromatics, and even the desulfurization of thio-
phenic substrates. These reactions, especially those that have provided data on
product distribution, kinetics, and selectivity, are the subject of this Section.
For the sake of completeness, it is worth mentioning that both the hydrogenation
of S- and N-heterocycles and their reductive opening by transition metal com-
plexes are also efficient synthetic routes to a variety of fine chemicals and
materials containing sulfur or nitrogen [3].
Compounds mentioned in this chapter are: pyrrole (abbreviated PYR), indole
(IN), carbazole, pyridine (Py), quinoline (Q), isoquinoline (IQ), acridine (AC),
5,6- and 7,8-benzoquinoline (5,6-BQ; 7,8-BQ), thiophene (T), benzo[b]thiophene
(BT), dibenzo[b,d]thiophene (DBT), etc.

3.2.13.2 Hydrogenation of Sulfur Heterocycles

The principal mechanisms proposed for the heterogeneous HDS of a prototypical
S-heterocycle, namely benzo[b]thiophene (BT), are illustrated in Scheme 1. The
plain hydrogenation of C-C double bonds occurs in step a, involving the regiose-
lective reduction of BT to dihydrobenzo[b]thiophene (DHBT), as well as in step e,
where styrene is reduced to ethylbenzene.

DHBT

( - y L Q y L Q --
J / /

/ SH S S
BT
If lb
@+/ S (ads) d,,
Scheme 1
 3.2.13.2 Hydrogenation of Sulfur Heterocycles 1101

3.2.13.2.1 Homogeneous Systems

In fluid-solution systems, the plain hydrogenation of thiophenes to thioether prod-
ucts has been found to be catalyzed by various transition metal complexes; sur-
prisingly, none of these catalysts contains either molybdenum or tungsten, which
are essential components of heterogeneous HDS catalysts [ 1 b]. Unpromoted
MoS2, on the other hand, is quite active for the HDS of thioethers with no
need of assistance by a late transition metal promoter [I b].
The pseudo-olefinic character of the C2-C3 bond makes BT the easiest
thiophene to hydrogenate to the corresponding thioether. Indeed, no example
of homogeneous hydrogenation of dibenzo[b,d]thiophene (DBT) is known,
whereas a case of catalytic reduction of thiophene (T) to tetrahydrothiophene
(THT) in 1,2-dichloroethane has been reported to occur with the catalyst precur-
sor [IrH2(r'-S-T)2(PPh2)2]PF6 [ 5 ] . BT is actually a better ligand than T or DBT
and can form both r2-C,C and rl-S complexes as single species or in equi-
librium with each other [6].
As a general trend, the homogeneous hydrogenation of thiophenes to thioethers
is catalyzed by complexes that are not sterically demanding with relatively elec-
trophilic metal centers (e. g., d6 metal ions such as Rh"', I?", Ru", or 0s"). This is
because moderate electron density and low steric hindrance at the metal favor the
r2-C,C coordination mode of the thiophene (precursor to hydride migration) over
r'-S binding (precursor to C-S bond cleavage) [7-lo].
In the known hydrogenation catalysts, the metals are stabilized by either cyclo-
pentadienyl or phosphine ligands [2 b, 7-10]. Solvents with good ligating proper-
ties generally slow down the hydrogenation rate as they may compete with the
substrates for coordination. Relatively drastic reaction conditions are generally
employed (20-1 10 bar; 40-170 "C), but there are hydrogenation reactions that
take place even at ambient temperature and pressure with fairly good rates [2 b,
7-10]. In terms of catalytic efficiency, Ru" forms the most active systems with
TOFs as high as 500 [9 a].
Commonly accepted hydrogenation mechanisms of BT catalyzed by metal
precursors devoid of hydride ligands comprise the usual steps of H2 oxidative
addition, r2-C,C coordination of the substrate, hydride transfer to form dihydro-
benzothienyl, and elimination of DHBT by hydride/dihydrobenzothienyl reduc-
tive coupling (Scheme 2). A similar sequence of steps is proposed for catalysts
bearing a hydride ligand (Scheme 3). In this case, the reaction with H2 follows
the addition of the substrate and the hydride migration step. Irrespective of the
structure of the catalyst, the regioselectivity of the first hydride migration step is
still unknown as no hydride (dihydrobenzothienyl) intermediate has ever been
intercepted.
The mechanism of hydrogenation of T to THT does not differ significantly
from that reported above for the hydrogenation of BT. The only peculiar feature
concerns the first hydride migration step (endo migration), which generally
occurs with regio- and stereospecificity to give a thioallyl intermediate. This
is converted to a 2,3-dihydrothiophene ligand, which is hydrogenated like any
other alkene.
1102 3.2 Special Catalysts and Processes

Scheme 2

Kinetic studies of the regioselective hydrogenation of BT to DHBT have been

reported for various catalysts. Using the precursors [Rh(PPh3),(COD)]PF6 (COD
= cycloocta-1,5-diene) [8 b] and [Ir(PPh,),(COD)]PF, [5, 8 a] in THF or 1,2-di-
chloroethane, first-order dependence on both catalyst and H2 concentrations and
zero-order dependence on BT concentration have been observed, while the hy-
dride migration yielding the dihydrobenzothienyl intermediate has been proposed
to be the rate-determining step (rds) (Scheme 2). In contrast, a first-order depen-
dence on catalyst, H2, and substrate concentrations and an rds involving the rever-
sible dissociation of the thioether product from the metal have been reported for

[MI = [Ru(TRIPHOS)$

Scheme 3
 3.2.13.2 Hydrogenation of Sulfur Heterocycles 1103

the hydrogenation of BT promoted by [Ru(MeCN),(TRIPHOS)]BPh, in THF

[TRIPHOS = MeC(CH,PPh,),] [9 a] (Scheme 3).
Valuable information on the mechanism of the regioselective BT hydrogenation
by soluble metal complexes has been obtained by substituting deuterium for
hydrogen gas in the reduction reactions catalyzed by the precursors
[Rh(MeCN),(Cp*)](BF,), [7 a] and [Ru(MeCN),(TRIPHOS)]BPh, [7 a, 9 a].
In situ high-pressure 31P{'H}and 'H NMR experiments have shown that
the hydrogenation of BT with the catalyst precursor [Ru(MeCN),(TRI-
PHOS)](BPh,), in THF involves the preliminary conversion of MeCN to various
nitrogen bases: NH,Et, NHEt,, NEt,, and NH3 [9 a]. The effective catalyst for
the hydrogenation of the thiophene was suggested to be the 14e- fragment
[RuH(TRIPHOS)]+, formed via base-assisted heterolytic splitting of H2. At the
beginning of the catalytic reaction, the Ru" fragment [RuH(TRIPHOS)]+ was
intercepted primarily as the bisacetonitrile complex [RuH(MeCN>,(TRIPHOS)]+,
while, at the end of the catalysis, three monohydride complexes stabilized by
NH3 or NHEt, ligands were observed. The formation of Ru-NH3 bonds that
are stronger than those with BT or DHBT is in line with the hypothesis accord-
ing to which the deactivation of the Ru-based HDS catalysts by nitrogen bases
is due to the formation of very strong (Ru),-N or (Ru),,NH, bonds derived
from the degradation of the ammonia produced in the concomitant HDN process
[I, 91.
Rh and Ir generally go through the hydrogenation catalysis with the I11 --+
I -+ I11 reductiodoxidation cycle, provided the activation of H2 occurs via
oxidative addition. In turn, Ru and 0 s follow the IV + I1 --+ IV reduc-
tiodoxidation cycle. A constant oxidation state along the whole catalysis
cycle should feature the metal center if the activation of dihydrogen occurs
via the y2-H2 pathway and the catalyst contains a hydride ligand [Ill. Indeed,
the possibility of intermediates containing intact H2 ligands cannot be disre-
garded in hydrogenation reactions catalyzed by d6 metal ions. The ability
of the y2-H2 complex [RuH,(H,),(PCy,),] to reduce various S- and N-hetero-
cycles to the corresponding cyclic thioethers and amines has been reported, in
fact [12].
An y2-H2complex has also been detected along the pathway of hydrogenation
of C-S-inserted BT to ethylthiophenol with the [Ir(TRIPHOS)] fragment [ 13 c].
On the other hand, DFT calculations have suggested that the hydrogenation of
thiophenic substrates over Ni,S, clusters (x = 3, 4) may involve adsorbed mole-
cular hydrogen that' subsequently undergoes heterolytic activation to give both
Ni-SH and Ni-H species [13, 141.

3.2.13.2.2 Aqueous-Biphasic Systems

Although still confined to laboratory scale, aqueous-biphase catalysis (cf. Section
3.1.1.1) and related variations such as supported liquid-phase catalysis (cf. Section
3.1.1.3.5) are emerging as viable techniques for the deep HDS of refined fuels
1151.
1104 3.2 Special Catalysts and Processes

The selective hydrogenation of S- and N-heterocycles has been achieved by re-

searchers at PDVSA-INTEVEP with the use of water-soluble Ru" catalysts stabi-
lized by either triphenylphosphine trisulfonate (TPPTS) or triphenylphosphine
monosulfonate (TPPMS) ligands [ 161. The biphasic reactions were performed
under relatively harsh experimental conditions (130-170 "C, 70-1 10 bar H2)
and gave the selective reduction of the heterocyclic ring irrespective of the hetero-
cycle. It was generally observed that nitrogen compounds did not inhibit the
hydrogenation of either T or BT. In some cases, indeed, a promoting effect was
observed. For example, the rate of hydrogenation of BT to DHBT catalyzed by
various Ru" complexes with either TPPMS or TPPTS in water/decalin quadrupled
when quinoline or aniline was used as co-catalyst.
Selective Ru and Rh catalysts for the aqueous-biphasic hydrogenation of BT to
DHBT have been obtained using the polydentate phosphines NaO,S(C,H,)-
CH2)2C(CH2PPh2)2 (Na2DPPPDS) [17] and Na03S(C6H4)CH2C(CH2PPh2)3
(NaSULPHOS) [18] (1, 2).

Na03S S03Na Na03S

PhzP PPh2
PPh2
Na2DPPPDS NaSULPHOS
1 2

In general, Ru-based catalysts are more efficient than Rh-based catalysts for the
selective hydrogenation of BT to DHBT in waterhydrocarbon mixtures [ 191.
Rhodium forms much better catalysts for the hydrogenolysis of thiophenes to
thiols (vide infru).
The binuclear complex Na[ { Ru(SULPHOS)},@-Cl),] [20] and the monomeric
derivative [Ru(MeCN),(SULPHOS)](SO,CF,) [9 a] have been employed as
precatalysts for the hydrogenation of BT to DHBT in wateddecalin or waterln-
heptane showing a very similar rate (TOF 30) in comparable experimental condi-
tions (100-1 40 "C, 3 MPa H2) [ 191. It was therefore suggested that the disruption of
the dimeric structure of the p-Cl, complex may occur under catalytic conditions.
In aqueous biphasic conditions, the zwitterionic Rh' complex Rh(COD)(SUL-
PHOS) has been shown to be a modest catalyst for the hydrogenation of BT to
DHBT (TOF 5) [ 10 a].

3.2.13.2.3 Heterogenized Single-Site Systems

The increased selectivity and much milder experimental conditions required for high
conversions make molecular catalysts compete with heterogeneous ones in many
chemical processes. The application of traditional molecular catalysis in large-
scale reactions such as HDS and HDN, however, is not possible. In order to over-
come this drawback, many research efforts are being directed toward the heteroge-
nization of molecular catalysts [211. Successful applications of heterogenized mole-
cular catalysts in several large-volume reactions have already been obtained [211.
 3.2.13.2 Hydrogenation of Sulfur Heterocycles 1105

The first attempt to hydrogenate sulfur heterocycles with a supported metal

catalyst was reported by Fish in 1985; cf. Structure 3 [22]. Interestingly, the
initial hydrogenation rate of BT was three times faster for the single-site hetero-
geneous catalyst than for the homogeneous derivative Rh(PPh&Cl. This rate
enhancement was also observed for N-heterocycles and was attributed to steric
requirements for the surroundings of the active metal center in the tethered com-
plex, which would favor the coordination of the heterocycles by disfavoring that
of PPh3 [22].

F
F\/ F
C'

SIOz SiOz

3
The use of polymer-supported metal catalysts for the hydrogenation of thiophe-
nic substrates has recently been extended to Ru and Rh complexes anchored to
silica via hydrogen bonding [23, 241.
Inspired by previous work from Angelici and co-workers [25], Bianchini,
Psaro, and co-workers have recently anchored the complex Rh(COD)(SULPHOS)
via hydrogen bonding to silica-containing Pd nanoparticles (4). A sample of
Rh(COD)(SULPHOS)/Pd/SiO, containing 0.5 wt. % Rh' and 10 wt. % Pd' was
employed to hydrogenate BT in n-octane (3 MPa H2, 100 "C). A 12-fold increase
in the hydrogenation rate with no loss of selectivity was observed for the mixed
molecular-metal particle catalyst as compared to Rh(COD)(SULPHOS)/SiO,,
while the catalyst containing exclusively Pd was inactive. The factors which are
responsible for this remarkable synergic effect are not yet understood completely.
1106 3.2 Special Catalysts and Processes

3.2.13.3 Hydrogenolysis of Sulfur Heterocycles

The reaction which transforms a thiophenic substrate into the corresponding
unsaturated thiol is referred to as hydrogenolysis (eq. (3)). Because of the facile
hydrogenation of the unsaturated thiols derived from T or BT, the actual hydro-
genolysis products obtained with molecular catalysts are generally the saturated
thiols.

The hydrogenolysis of thiophenes to thiols is a reaction that only a few metal

complexes catalyze efficiently. Indeed, whereas the metal complexes which are
capable of cleaving and then hydrogenating C-S bonds in thiophenes are rela-
tively numerous [2 b], those which do this in catalytic fashion are very few and
all are characterized by a well-defined molecular architecture as well as remark-
able thermal and chemical stability. C-S bond scission is best accomplished, in
fact, by electron-rich, coordinatively unsaturated systems, commonly 16e- tetra-
or tricoordinate species, with ligand sets that do not generally allow the fragment
to attain the too stable square-planar geometry, e. g., [MH(TRIPHOS)] (M = Rh,
Ir) [3, 10, 131, [Ir€p*] [26], or [Rh(PMe3)Cp*] [27]. Highly energetic metal frag-
ments with filled orbitals of appropriate symmetry are necessary to lower the bar-
rier to C-S insertion which occurs via &(metal) + n*(C-S) transfer [27]. More-
over, the steric crowding at the metal center must be great enough to disfavor the
r2-C,Cbonding mode of the substrate, but not so great to impede the coordination
of the substrate via the sulfur atom [27]. In actuality, the insertion of metal frag-
ments into C-S bonds in T, BT, and DBT is a relatively high-energy process, only
slightly disfavored over C(sp2)-H insertion [28], but much easier than C-N inser-
tion [ l , 21.

3.2.13.3.1 Homogeneous Systems

Tailoring the electronic and steric characteristics of a metal complex is not suffi-
cient per se to form a catalyst for the hydrogenolysis of thiophenes as this reaction
generally requires high temperature and H2 pressure to take even in homogeneous
phase. So far, only the highly chelating tripodal triphosphine TRIPHOS in com-
bination with Ru", Rh' and Ir' has been found capable of forming catalysts that
tolerate the thermal and chemical stress of the hydrogenolysis reactions of thio-
phenes (3 MPa H2, 1O0-16O0C, presence of a strong base).
Irrespective of the metal catalyst, the hydrogenolysis rate of any thiophenic
substrate is significantly accelerated when a strong BrGnsted base, generally
KOBu' in THF, is added to the catalytic mixture in the same concentration as
the substrate [9, 101. The main role of the base is that of speeding up the removal
of the thiol product from M(H)(SR) intermediates, which constitutes the rds of
all hydrogenolysis reactions reported so far. In some cases, strong bases have
 3.2.13.3 Hydrogenolysis of Sulfur Heterocycles 1107

been used as co-catalysts to generate M-H bonds by heterolytic splitting of H2

[9, 101.
The catalytically active species for the homogeneous hydrogenolysis of T (Rh
[ l o b]), BT (Rh [lo], Ru [9 b]), DBT (Ir [29]) and dinaphtho[2,1-b:1’,2’-d]thio-
phene (DNT) (Rh [30], Ir [30]) have the general formula [MH(TRIPHOS)]”
(M = Rh, Ir, n = 0; M = Ru, n = -1). In comparable experimental conditions
using the catalyst [RhH(TRIPHOS)], the hydrogenolysis rate was found to
decrease in the order
BT > T > fused-ring thiophenes higher than DBT > DBT
which reflects the propensity to undergo C-S insertion [I b, 9, 10, 131.
The proposed mechanisms for the base-assisted hydrogenolysis of prototypical
thiophenes to the corresponding thiols catalyzed by [MH(TRIPHOS)]” catalysts
(M = Ru, n = -1 ; Rh, Ir, n = 0) are illustrated in Scheme 4.

S-

Scheme 4

The mechanisms for the model substrates BT (a) and DBT (b) involve the steps
of C-S insertion, hydrogenation of the C-S inserted thiophene to the correspond-
ing thiolate, base-assisted reductive elimination of the thiol (rds) to complete the
cycle (in the catalytic reactions carried out in the absence of base, the displace-
ment of the thiol by the substrate occurs thermally [ l o b, c]). The addition of a
strong base to the catalytic mixtures results in a remarkable rate enhancement;
for example, the TOF relative to the hydrogenolysis of BT to 2-ethylthiophenol
catalyzed by [RhH(TRIPHOS)] increases from 12 to 40 by simply adding an ex-
cess of KOBu‘ to the catalytic mixture [lo b, c].
The importance of the metal oxidation state in controlling the chemoselectivity
of hydrogenation of thiophenes is highlighted by the Ru-TRIPHOS case
(cf. [9 a, b]).
1108 3.2 Special Catalysts and Processes

3.2.13.3.2 Aqueous-Biphasic Systems

The aqueous-biphasic hydrogenolysis of BT has been accomplished in either
water n-decalin or water naphtha mixtures by simply substituting NaSULPHOS
for TRIPHOS in the preparation of the rhodium precursor [Rh(COD)(SUL-
PHOS)]. Rather harsh reaction conditions (160°C, 30 bar H2) and an equivalent
amount of NaOH were required for high conversions of the BT to 2-ethylthiophe-
nolate (TOF 16). In these conditions, the thiolate product was totally recovered in
the aqueous phase, leaving the hydrocarbon phase formally “desulfurized” [ 10 a].
It is generally agreed that the mechanisms of the biphasic reactions are quite
similar to those proposed in single-phase systems (Scheme 4). Experimental
evidence supporting mechanistic analogies in single-phase and biphasic systems
has been provided for the hydrogenolysis of BT to 2-ethylthiophenol catalyzed
by the 16e- fragments [RhH(TRIPHOS)] and [RhH(SULPHOS)]- in THF or
H,O-MeOHln-heptane, respectively [ 101. For Ru catalysts cf. [19].

3.2.13.3.3 Heterogeneous Single-Site Systems

A modified version of TRIPHOS has recently been anchored to a crosslinked
styrene/divinylbenzene polymer yielding a polymeric material, named POLYTRI-
PHOS, containing pendant tripodal triphosphine moieties -C(CH2PPh2)3 [3 1 a].
The simple reaction of POLYTRIPHOS with a CH2C12solution of [RhCl(COD)],
in the presence of AgPF6 gives the polystyrene-supported complex [Rh(COD)-
(POLYTRIPHOS)]PF, (Rh 0.94 wt. %) (eq. (4) and Structure 5).

+H2 -01
’ @+
Cat
KOBU‘/H+
SH + H2S (4)

w 5

The supported Rh complex has been shown to be a powerful catalyst for

the hydrogenolysis of BT to 2-ethylthiophenol (TOF 48) and ethylbenzene
(TOF 2); this represents the first evidence of a successful single-site catalyst in
the heterogeneous HDS of a thiophenic substrate.
 3.2.13.5 Hydrogenation of Nitrogen Heterocycles 1109

3.2.13.4 Hydrodesulfurization in Different Phase

Variation Systems
While metal complexes capable of desulfurizing or hydrodesulfurizing thiophenes
are relatively numerous, homogeneous catalysts are very rare, being limited to
rhodium and iridium TRIPHOS precursors that are unique in tolerating the
harsh experimental conditions required for the second C-S bond cleavage of thio-
phenes [2 b].
The first example of HDS of DBT was obtained using the C-S insertion product
[IrH($-C,S-DBT)(TRIPHOS)] in THF under 30 bar of H2 at 160 "C 1291. 2-Phe-
nylthiophenol, biphenyl, and H2S were produced in excess of the stoichiometric
amounts. Under similar reaction conditions, catalytic production of butane, bu-
tenes, 1- butanethiol, and H2S was observed upon hydrogenation of T in the pre-
sence of the [RhH(TRIPHOS)] catalyst and of a strong BrGnsted base [lo b]. Both
the Ir and Rh systems exhibited very low desulfurization activity, the hydrogeno-
lysis to thiols being the predominant pathway. In the case of the iridium complex,
the elimination of H2S was suggested to proceed via an M(H),(SH) intermediate
which was not detected during the catalysis. However, the complex [Ir(H),(SH)-
(TRIPHOS)] was prepared independently and its reaction with H2 under catalytic
conditions gave H2S [29].
The most efficient single-site HDS catalyst remains the polystyrene-supported
complex [Rh(COD)(POLYTRIPHOS)]PF,(S),which has been shown to catalyze
the HDS of BT yielding ethylbenzene with a TOF of 2 [31 a].
In conclusion, unlike heterogeneous processes with commercial HDS catalysts,
single-site catalysts have been found to desulfurize thiophenes (T, BT, DBT)
exclusively after these have been converted to saturated thiols or thiolates. No
example of catalytic desulfurization of THT or DHBT by a single-site catalyst
has ever been reported, although stoichiometric reactions assisted by both mono-
nuclear and polynuclear complexes are known for THT and other cyclic thioethers
[2 b, 321.
As previously mentioned, the stoichiometric desulfurization of thiophenes has
been achieved with a relatively large number and variety of metal complexes. In
general, polynuclear complexes containing both component (Mo or W) and pro-
moter (Ni, Co, Ir, Ru) metals turn out to be more active than mononuclear com-
plexes containing promoter metals [ l , 21. A paradigmatic case has been reported
in which the hydrogenolysis of BT to either 2-vinylthiophenol or 2-ethylthiophe-
no1 is a facile process for the promoter (Rh), but the desulfurization step to ethyl-
benzene requires the compulsory assistance of a component metal (W) to take
place [33].

3.2.13.5 Hydrogenation of Nitrogen Heterocycles

The principal reaction pathways proposed for the heterogeneous HDN of the
prototypical substrate quinoline (Q) are shown in Scheme 5. Unlike HDS, the
hydrogenation of both the heterocycle and the carbocycle are preliminary to
1110 3.2 Special Catalysts and Processes

I l
+ NH3

Scheme 5

C-N bond scission. Understanding the hydrogenation mechanism is thus of

utmost importance for designing improved HDN catalysts.
On the basis of homogeneous modeling studies, it is now agreed that the 1 1 ’ 4
and r2-N,C coordination modes of the N-heterocycle are crucial for its hydrogena-
tion and hydrogenolysis, respectively [ 1, 2 a]. In particular, the regioselective
hydrogenation of the heteroaromatic rings is best accomplished by late transition
metals in their high oxidation states, preferentially in the presence of protic acids.
The C-N insertion is a much more difficult task that proceeds in hydrolytic fash-
ion and apparently requires action on an r2-N,C-heterocycle by an early transition
metal in relatively low oxidation state [ 1, 2 a].

3.2.13.5.1 Homogeneous Systems

The selective hydrogenation of pyridine (Py) to piperidine was first accomplished
in dimethylformamide at ambient pressure with the catalyst system Rh(Py),C13/
NaBH,, which proved to be active also for the reduction of Q to 1,2,3,4-tetrahy-
droquinoline (THQ) [34]. Later, various metal carbonyls, Rh6(C0)16,Fe(CO)S,
Mn2(C0)8(PBu3)2,and C O ~ ( C O ) ~ ( P Bwere
U ~ ) ~employed
, to reduce Q selectively
as well as several polyaromatic heterocycles (5,6-benzoquinoline (5,6-BQ), 7,8-
benzoquinoline (7,8-BQ), acridine (AC) and isoquinoline (IQ)), applying either
water-gas-shift (WGS) or synthesis-gas (SG) conditions [35]. In all cases, high
temperatures (180-200 “ C )were required even to give very low TOFs. A remark-
able rate enhancement effect was observed by adding a base and a phase-transfer
agent along with the catalyst Fe(CO), [35 b]. Under WGS conditions, RuC1,-
(C0)2(PPh3)2and Ru4H4(CO)12 were inactive, however, due to competitive co-
ordination of CO. With these precursors, the hydrogenation of the substrates
was achieved using only H2 gas [35 c]. The selective hydrogenation of Q has
also been achieved with the 0 s clusters H20~3(CO)I0 and O S ~ ( C O ) ,which
~,
gave a deuteration pattern of THQ with more deuterium in the 4-position and
less in the 2-position, suggesting the occurrence of oxidative addition of the 0 s
cluster to C-H bonds in Q and 1,4-hydrogenation as well [36].
 3.2.13.5 Hydrogenation of Nitrogen Heterocycles 1111

The first kinetic and mechanistic studies were reported by Fish and co-workers
for the hydrogenation of 2-methylpyridine (2-MePy) to 2-methylpiperidine and of
Q to THQ in the presence of the Rh"' precursor [Rh(MeCN)3Cp*]2+[7 a, 371.
Deuterium gas experiments and in situ high-pressure NMR reactions allowed
Fish to propose his own mechanism for the hydrogenation of Q to THQ (40"C,
500 psi HZ,CH,CI,) [7 a, 371.
The catalyst precursor [Rh(MeCN)3Cp*]2'was successfully employed to cata-
lyze the selective reduction of various N-heterocycles with rates that were
found to decrease in the order
AC > Q > 5,6-BQ > 2-MeQ > 2-MePy
In particular, it was reported that the rate decreases with increasing basicity and
steric hindrance at the nitrogen atom. An exception to this rule was 7,8-BQ, which
showed the highest relative rate and, in competitive reactions, was found to en-
hance the rate of hydrogenation of Q and other substrates as well. It was proposed
that the rate enhancement effect is occasioned by a concomitant hydrogen transfer
mechanism [7 a].
The Fish mechanism was demonstrated to be substantially valid also for the
hydrogenation of polyaromatic substrates catalyzed by the Rh' and Ru" complexes
RhCl(PPh& [7 c] and RuHCl(PPh& (85 "C, ca. 2 MPa, benzene) [7 b]. For the
hydrogenation of Q, it was proposed that the activation of the Cx-H bond in the
carbocyclic ring occurs via cyclometallation, while the relative hydrogenation
rates decreased in the order
phenanthridine (PHT) > AC > Q > 5,6-BQ > 7,8-BQ
which again reflects the influence of both steric and electronic effects. All sub-
strates were regioselectively hydrogenated at the heteroaromatic ring; only AC
was converted to a mixture of 9,lO-dihydroacridine and 1,2,3,4-tetrahydroacrii-
dine. The hydrogenation of Q was inhibited by the presence of pyridines and of
THQ in the reaction mixture, due to competing coordination to the metal center,
while all the other substrates had no appreciable effect on the rate of Q hydro-
genation. In the case of the Rh catalyst, a promoting effect on Q reduction was
observed in the presence of IN (indole), PYR (pyrrole), carbazole and even of
sulfur heterocycles such as BT, BT, and DBT [7 c].
The selective hydrogenation of Q to THQ in relatively harsh experimental con-
ditions (150 "C, 30 bar H2, toluene) has been investigated by Sinchez-Delgado and
Gonzales with the use of various Ru, Rh, Os, and Ir metal catalysts [38]. The Rh
complex was found to be the most active (initial rate ca. 200 mol Q (mol cat)-' h-I),
while the 0 s complex was the least efficient (initial rate ca. 5 mol Q (mol cat)-' h-I).
Coordinating solvents such as MeCN or MeOH or added ligands such as CO
quenched the catalysis with (PPh3)3RuHC1(CO).The addition of Brgnsted acids
or bases gave adverse effects, the base acting as an inhibitor, while water did
not apparently affect the catalytic rate. Similar observations were made by
L6pez-Linares and co-workers using Rh, Ir, and Ru catalysts containing Tp or
Tp* ligands (Tp = tris[pyrazolyl]borate; Tp* = tris[3,5-dimethylpyrazolyl]borate)
[40]. Rhodium formed the most active catalysts, while the presence of ligands
1112 3.2 Special Catalysts and Processes

capable of competing with Q for coordination, e. g., COE (cyclooctene) and

ethylene, decreased the hydrogenation rate due to competitive metal insertion
into sp2 C-H bonds.
The mechanism of Q hydrogenation assisted by [Rh(DOD)(PPh,),]PFG has
been studied by Shnchez-Delgado with gas-absorption techniques [40]. They
reported an experimental rate law of the type = kat[Rh][H,]', the isolation
of [Rh(Q),(COD)]PF, at the end of the catalysis (370 K, I0.1 MPa H2, toluene),
and the observation that the rate of hydrogenation of the partially reduced
substrate dihydroquinoline (DHQ) was comparable with that of Q.
Kinetic studies of Q reduction to THQ have been reported also by Rosales and
co-workers for the ruthenium complex [RuH(CO)(MeCN)(PPh,),IBF, [41]. At
low hydrogen pressure, the experimental rate law ri = k,,, [RuO][H2l2is quite
similar to that found by Shnchez-Delgado. In contrast, at high H2 pressure, a
first-order dependence of the reaction rate with respect to the hydrogen concentra-
tion was observed. The proposed mechanism involves a rapid and reversible
partial hydrogenation of bonded Q, followed by a rate-determining second hydro-
genation of DHQ. The catalyst precursor [RuH(CO)(M~CN),(PP~,)~]BF, was
also employed to catalyze the hydrogenation of various polyaromatic N-hetero-
cycles under relatively mild conditions (125 OC, 4 bar H2, xylene or toluene)
[41]. The reactivity order
AC > Q >> 5,6-BQ > 7,8-BQ > IN > IQ
was in line with previous trends and reflects steric and electronic effects. A kinetic
study was carried out of the reduction of AC to 9,lO-dihydroacridine. Unlike Q,
the experimental rate law was r = k,,, [Ru][H2] and the postulated mechanism
involves as rds the hydrogenation of coordinated AC in [RuH(CO)(v'(N)-AC)-
(MeCN)(PPh,)']+ to yield 9,lO-dihydroacridine and the coordinatively unsatu-
rated complex [RuH(CO)(MeCN)(PPh,),1'.
A much more complex kinetic law has been proposed by Macchi, Bianchini,
and co-workers for the reaction catalyzed by the complex [Rh(DMAD)(TRI-
PHOS)]PFG (DMAD = dimethyl acetylenedicarboxylate) [42]. At 60 "C in the
H2 pressure range from 0.4 to 3 MPa and in the range of catalyst concentration
from 36 to 110 mM, the rate showed a first-order dependence on both [H2]
and [Rh], while the hydrogenation rate was found to be inversely dependent
on [Q]. An empiric rate law of the type r = k"[Rh][H,][Q]', where k" = k
(a + b [Q] + c [Q] 2)-' was proposed to account for the inhibiting effect of
high Q concentration and the experimental observation that the rate tends to
be second order for very low Q concentrations and zero order for very high
Q concentrations. Incorporation of kinetic, deuterium labeling, and high-pressure
NMR experiments, and the identification of catalytically relevant intermediates
led to a mechanism which differs essentially from that reported by Shnchez-Del-
gado for the rate-limiting step, i.e. the reversible reduction of the C=N bond
instead of that of the C3=C4 bond (irreversible) (Scheme 6). The overall hydro-
genation of the C=N bond, which actually disrupts the aromaticity of Q, was
proposed as rds also in the light of the independent reduction of isolated 2,3-
dihydroquinoline, which, under comparable experimental conditions, was reduced
 3.2.13.5 Hydrogenation of Nitrogen Heterocycles 11 13

Scheme 6

faster than Q. Moreover, the lack of deuterium incorporation into the carbocyclic
ring of both THQ and Q ruled out the intermediacy of $-Q or $-THQ com-
plexes.
A remarkable rate enhancement was observed by addition of an excess of
CF3S03H to the catalytic mixtures (at 40°C and 3 MPa H2, the TOF was in-
creased from 40 to 95 by addition of a 20-fold excess of acid). The role of triflic
acid was that of aiding the conversion of inactive Rh' (formed in the basic en-
vironment of the reaction) to active Rh"'. The addition of strong protic acids was
found to be of mandatory importance for generating a catalytically active system
from [Ru (MeCN),(TRIPHOS)](O,SCF&, which, under neutral conditions, is al-
most inactive for Q reduction. Treatment of the Ru compound with H2 produces
ammonia, in fact, which prevails over Q for coordination to the metal center;
moreover, in the basic environment of the reaction, traces of water were found
to transform catalytically active [RuH(TRIPHOS)]+ into inactive binuclear
[RU,@-OH>,(TRIPHOS)~]+ [9 a, b]. In this case, the protic acid inhibits the for-
mation of both NH3 adducts and the @-OH), binuclear complex, thus allowing
the hydrogenation of Q to THQ to proceed smoothly with a TOF of 65 [9 a, b].
In homogeneous phase, IN is much more difficult to reduce than Q, as shown
by the limited number of known catalysts (e.g. RuHCl(PPh& [7b] and [RuH-
(CO)(MeCN)(PPh,),]BF4 [43]), which, by the way, are scarcely efficient. The
inertness to hydrogenation exhibited by IN has been attributed to its incapability
of using the nitrogen atom for coordination, In fact, IN binds metal via the $-nC
coordination which does not activate the C=N bond and also occupies too many
coordination sites, disfavoring the oxidative addition of H2 to the metal center. To
11 14 3.2 Special Catalysts and Processes

our knowledge, the only catalyst that is able to hydrogenate IN regioselectively to

indoline with an acceptable TOF is [Rh(DMAD)(TRIPHOS)]PF, in the presence
of a protic acid [42]. By using equivalent IN and triflic acid concentrations, TOFs
as high as 100 were obtained at only 60°C and 3 MPa H2. It was shown experi-
mentally that indoline was formed by reduction of the 3H-indolium cation, which
possesses a localized C=N bond [42 a].

3.2.13.5.2 Aqueous-Biphasic Systems

The catalysts that effect the hydrogenation of thiophenes in aqueous-biphase
systems (see Section 3.2.13.3.2) are also active for the selective reduction of
aromatic heterocycles to cyclic amines using aqueous-biphase catalysts (Struc-
tures 6-10).

P" = TPPMS
8

9 10

The heterocyclic ring in Q, AC, and IQ has been selectively hydrogenated in

water/decalin with Ru" catalysts prepared in situ from RuCI3.3H20 and excess
TPPMS or TPPTS in the same experimental conditions as thiophenes (see Sec-
tion 3.2.13.2.2) [44, 451. The major Ru product isolated from the aqueous phase
after hydrogenation of Q in wateddecalin was RuHCI(TPPMS),(THQ), (Struc-
ture 6). The same termination product was also isolated after hydrogenation
of a Q/BT mixture, which is consistent with the greater binding affinity of
amines to Ru" in comparison with thioethers. The regioselective reduction of
Q to THQ in waterhydrocarbon mixtures has been achieved with catalyst
systems comprising either Na2DPPPDS or NaSULPHOS in combination with
Rh or Ru [17, 18, 461.
 3.2.13.5 Hydrogenation of Nitrogen Heterocycles 1115

The Rh' complex [Rh(H2O>,(DPPPDS)]Na was isolated and employed in

waterln-octane to hydrogenate 1:l mixtures of Q and BT at 160°C yielding
almost exclusively THQ with a TOF of 50, BT hydrogenation to DHBT
being only marginal (TOF 2). A similar selectivity was shown also by the
catalytic system RuCI3 . H20/2Na2DPPPDS prepared in situ. In contrast, the
binuclear complex Na[ { Ru(SULPH0S) } 2(L1-C1)3]was found to hydrogenate Q
and BT at comparable rates (TOF = 30 at 140°C, 3 MPa, waterln-heptane).
The mononuclear complex [Ru(MeCN),(SULPHOS)]' has been found to
catalyze the hydrogenation of Q to THQ in watedn-heptane or waterlmethanoY
n-heptane at fairly fast initial rates, that, however, decreased remarkably with
time due to the formation of the catalytically inactive binuclear p-hydroxy species
[Ru&- OH),(SULPHOS),]- [46]. As in homogeneous phase with the precursor
[Ru (MeCN),(TRIPHOS)](O,SCF,), (see Section 3.2.13.5. l), the addition of a
strong protic acid in excess enhanced hydrogenation TOF from 7 in the absence
of added acid to 37 with 20 equivalents of triflic acid (MeOHlwaterln-heptane,
lOO"C, 3 MPa H2) [46]. Although not essential for good conversions, the use
of an acid co-reagent also improves the catalytic performance of the zwitterionic
Rh' complex Rh(COD)(SULPHOS) in the aqueous-biphasic hydrogenation of
both Q and IN [46].

3.2.13.5.3 Heterogeneous Single-Site Systems

Various N-heteroaromatics have been successfully hydrogenated in the presence
of the single-site catalyst @Rh(PPh2)2C1 obtained by tethering the soluble pre-
cursor Rh(PPh,),Cl to 2 % crosslinked phosphinated polystyrene-divinylbenzene
(benzene, 85 "C, ca. 2.1 MPa H2 [22]). The order of activity was identical to
that in homogeneous phase [7 c], AC > Q > 5,6-BQ > 7,8-BQ, but the initial
rates of the heterogeneous hydrogenations were from 10 to 20 times faster due
to the increased steric hindrance at the tethered Ru (see Section 3.2.13.2.3).
The regioselectivity of hydrogenation was even higher than that in homogeneous
phase as no formation of 1,2,3,4-tetrahydroacridinewas observed. The hetero-
genized Ru catalyst was also employed to hydrogenate N-heterocycles in model
coal liquid containing pyrene, tetralin, p-cresol, 2-methylpyridine, and methyl-
naphthalene. A rate enhancement effect was observed which was attributed to
the ability of some constituents, especially of p-cresol, to stabilize unsaturated
Rh species formed in the course of the catalysis.
It has been discovered recently that a single metal site belonging to the HDSl
HDN promoter class can hydrogenate both the heterocyclic and carbocyclic rings
of Q, although at different rates [3 1 b]. Under relatively mild experimental condi-
tions (80 "C, 3 MPa H2), the polystyrene-supported complex [Rh(COD)(POLY-
DIPHOS)]PF6 has been found to hydrogenate Q in n-octane yielding THQ
(TOF 63) as well as 5,6,7,8-tetrahydroquinoline('THQ) (TOF 13) and decahydro-
quinoline (DeHQ) (TOF 8) (POLYDIPHOS = crosslinked styreneldivinylbenzene
~~s~~-(C~H~)CH~OCH~C(CH~)C(CH,PP~,)~) (eq. (5)).Independent reactions with
isolated samples of THQ and 'THQ showed that both compounds are further
1116 3.2 Special Catalysts and Processes

reduced to DeHQ. Most importantly, no metal leaching was observed and the
catalyst was recycled several times with no loss of catalytic activity and selec-
tivity.
The heterogeneous hydrogenation of Q to THQ has also been achieved with the
silica-supported hydrogen-bonded rhodium catalysts Rh(COD>(SULPHOS)/SiO,
and [Ru(MeCN),(SULPHOS)](S03CF3)/Si02 shown in Structure 3. In the same
experimental conditions employed to hydrogenate BT (n-octane, 100 "C, 3 MPa
H2) (see Section 3.2.13.2.3), THQ was selectively produced with relatively low
TOFS (20-30) [46].

3.2.13.6 Hydrogenolysis of Nitrogen Heterocycles

While the catalytic hydrogenation of the heterocyclic ring in N-heterocycles is re-
latively facile by molecular catalysis in either homogeneous or heterogenous fash-
ion, the hydrogenolysis of the C-N bonds is considerably more difficult to
achieve. Even stoichiometric C-N scissions are very rare [ l , 21, which is not
surprising as C-N bonds exhibit a higher bond energy than C-S bonds
(by 3-9 kcal mol-I). For this reason, the catalysts are less efficient for HDN
than for HDS under comparable experimental conditions [ l , 21.
To our knowledge, the only example of catalytic hydrogenolysis of a nitrogen
heterocycle is the conversion of Py to a mixture of piperidine and various bis-
(piperidiny1)alkanes catalyzed by Rh,(CO) 1 6 under water-gas shift conditions
(150"C, 800 psi CO) [35 d].

3.2.13.7 Perspectives
Over the last 15 years, the homogeneous studies of HDS and HDN processes
have been extremely useful to understand many mechanistic details regarding
the coordination of sulfur and nitrogen heterocycles to metal centers, hydrogen
transfer from metal to coordinated heterocycle, metal insertion into C-S and
C-N bonds, and the desulfurization/denitrogenation paths. Recently, however,
there has been a qualitative leap in molecular catalysis so that crossing the border-
 References 1 117

line between traditional heterogeneous catalysis and molecular catalysis in HDS

and HDN is no longer considered a utopia by the experts in the field. Like sup-
ported metallocenes in olefin polymerization [47] or phosphine-modified Rh
complexes in aqueous hydroformylation of olefins [48], supported metal cata-
lysts, alone or in combination with metal particles or metal sulfides, might indeed
be the key to the development of more efficient catalysts for the deep HDS and
HDN of fossil fuels.

References
[ 11 (a) T. Kabe, A. Ishihara, W. Qian, Hydrodesuljiurization and Hydrodenitrogenation,
Wiley-VCH, Tokyo, 1999; (b) H. TopsGe, B. S. Clausen, F. E. Massoth, Hydrotreating
Catalysis, Springer-Verlag, Berlin, 1996.
[2] (a) C. Bianchini, A. Meli, F. Vizza, Eur: J. Inorg. Chem. 2000, 43; (b) C. Bianchini,
A. Meli, Acc. Chem. Res. 1998, 31, 109.
[3] C. Bianchini, A. Meli, Synlett 1997, 643; (b) C. Bianchini, A. Meli, W. Pohl, F. Vizza,
G. Barbarella, Organornetallics 1997, 16, 15 17.
[4] C. Bianchini, P. Barbaro, G. Scapacci, E. Farnetti, M. Graziani, Organometullics 1998,
17, 3308.
(51 C. Bianchini, A. Meli, M. Peruzzini, F. Vizza, V. Herrera, R. A. Sanchez-Delgado, Orgu-
nometallics 1994, 13, 72 1.
[6] (a) M. J. Robertson, C. L. Day, R. A. Jacobson, R. J. Angelici, Organometallics 1994, 13,
179; (b) M.-G. Choi, R. J. Angelici, Organometallics 1992, 11, 3328.
[7] (a) E. Baralt, S. J. Smith, I. Hurwitz, I.T. Horvith, R. H. Fish, J. Am. Chem. SOC.1992,
114, 5 187; (b) R. H. Fish, J. L. Tan, A. D. Thormodsen, Organometallics 1985, 4 , 1743;
(c) R.H. Fish, J.L. Tan, A.D. Thormodsen, J . Org. Chern. 1984, 49, 4500.
[8] (a) V. Herrera, A. Fuentes, M. Rosales, R. A. Sanchez-Delgado, C. Bianchini, A. Meli,
F. Vizza, Organometallics 1997, 16, 2465; (b) R. A. Sanchez-Delgado, V. Herrera,
L. R i n c h , A. Andriollo, G. Martin, Organometallics 1994, 13, 553; (c) R. A. Sinchez-
Delgado, E. Gonzjlez, Polyhedron 1989, 8, 1431.
[9] (a) C. Bianchini, A. Meli, S. Moneti, W. Oberhauser, F. Vizza, V. Herrera, A. Fuentes,
R.A. Sinchez-Delgado, J. Am. Chem. SOC. 1999, 121, 7071; (b) C. Bianchini,
A. Meli, S. Moneti, F. Vizza, , Organometallics 1998, 17, 2636; (c) C. Bianchini,
D. Masi, A. Meli, M. Peruzzini, F. Vizza, F. Zanobini, Organometallics 1998, 17,
2495.
[lo] (a) C. Bianchini, A. Meli, V. Patinec, V. Sernau, F. Vizza, J. Am. Chem. Soc. 1997, 119,
4945; (b) C. Bianchini, J. Casares, A. Meli, V. Semau, F. Vizza, R. A. SBnchez-Delgado,
Polyhedron 1997, 16, 3099; (c) C . Bianchini, V. Herrera, M. V. JimCnez, A. Meli, R. A.
Sinchez-Delgado, F. Vizza, J. Am. Chem. SOC.1995, 11 7, 8567.
[l I ] (a) D. M. Heinekey, W. J. J. Oldham, Chem. Rev. 1993, 93, 913; (b) P. G. Jessop, R. H.
Morris, Coord. Chem. Rev. 1992, 121, 155.
1121 A. F. Borowski, S. Sabo-Etienne, B. Chaudret, Abstracts ISHC 12, August 27Beptember
1, 2000.
[13] (a) C. Bianchini, P. Frediani, V. Herrera, M. V. JimCnez, A. Meli, L. R i n c h , R. A.
Sinchez-Delgado, F. Vizza, J. Am. Chem. Soc. 1995, 117, 4333; (b) C. Bianchini,
M.V. JimCnez, A. Meli, F. Vizza, Organometallics 1995, 14, 3196; (c) C. Bianchini,
A. Meli, M. Peruzzini, F. Vizza, S. Moneti, V. Herrera, R. A. Sanchez-Delgado,
J. Am. Chem. SOC.1994, 116, 4370; (d) C . Bianchini, A. Meli, M. Peruzzini,
1118 3.2 Special Catalysts and Processes

F. Vizza, P. Frediani, V. Herrera, R.A. Sinchez-Delgado, J. Am. Chem. Soc. 1993,

11.5, 2731.
[14] M. Neurock, R. A. van Santen, J. Am. Chem. SOC. 1994, 116, 4427.
[ 151 C. Bianchini, A. Meli, in Aqueous-Phase Organometallic Catalysis - Concepts and
Applications (Eds.: B. Cornils, W. A. Henmann), VCH, Weinheim, 1998, p. 477.
[16] (a) INTEVEP S.A. (D.E. Piez, A. Andriollo, R. A Sinchez-Delgado, N. Valencia,
F. L6pez-Linares, R. Galiasso), US 08/657.960 (1996); (b) INTEVEP S. A. (D. E.
Paez, A. Andriollo, R. A Sinchez-Delgado, N. Valencia, F. L6pez-Linares, R. Galiasso),
Sol. Patente Venezolana 96-1630 (1996).
[I71 (a) CNR (C. Bianchini, A. Meli, F. Vizza), (1999), PCT/EP97/06493; (b) CNR (C. Bian-
chini, A. Meli, F. Vizza), IT FI96A000272 (1996).
[I81 C. Bianchini, P. Frediani, V. Semau, Organometullics 1995, 14, 5458.
[19] C. Bianchini, A. Meli, S. Moneti F. Vizza, unpublished results.
[20] I. Rojas, F. Lopez Linares, N. Valencia, C. Bianchini, J. Mol. Catul. A: Chemical 1999,
144, 1 .
[21] (a) B. Cornils, W. A. Hermann, in Applied Homogeneous Catalysis with Organometal-
lic Compounds (Eds.: B. Comils, W.A. Henmann), VCH, New York, 1996, Vol. 2,
p. 575; (b) P. Panster, S. Wieland, in Applied Homogeneous Catalysis with Organo-
metallic Compounds (Eds.: B. Cornils, W.A. Henmann), VCH, New York, 1996,
Vol. 2, p. 605.
[22] R. H. Fish, A. D. Thormondsen, H. Heinemann, J. Mol. Catal. 1985, 31, 19 1 .
[23] (a) C. Bianchini, V. Dal Santo, A. Meli, W. Oberhauser, R. Psaro, F. Vizza, Organometallics
2000, 19, 2433; (b) C. Bianchini, D. G. Bumaby, J. Evans, P. Frediani, A. Meli,
W. Oberhauser, R. Psaro, L. Sordelli, F. Vizza, J. Am. Chem. Soc. 1999, 121, 5961.
[24] C. Bianchini, A. Meli, W. Oberhauser, F. Vizza, unpublished results.
[25] H. Gao, R. J. Angelici, Organometallics 1999, 18, 989 and references therein.
[26] J. Chen, L.M. Daniels, R. J. Angelici, J. Am. Chem. Soc. 1990, 112, 199.
[27] (a) A. W. Myers, W. D. Jones, Organometallics 1996, 15, 2905; (b) A. W. Myers,
W.D. Jones, S.M. McClements, J. Am. Chem. Soc. 1995, 117, 11704; (c) L. Dong,
S. B. Duckett, K. F. Ohman, W. D. Jones, J. Am. Chem. Soc. 1992, 114, 151 ; (d) W. D.
Jones, L. Dong, J. Am. Chem. Soc. 1991, 113, 559.
[28] (a) C. Bianchini, J. A. Casares, D. Masi, A. Meli, W. Pohl, F. Vizza, J. Organornet.
Chem. 1997, 5’41, 143; (b) C. Bianchini, M.V. JimCnez, A. Meli, S. Moneti, F. Vizza,
J. Organomet. Chem. 1995, 5’04, 27.
[29] (a) C. Bianchini, M. V. JimCnez, A. Meli, S. Moneti, F. Vizza, V. Herrera, R. A. Sanchez-
Delgado, Organometallics 1995, 14, 2342.
[30] C. Bianchini, D. Fabbri, S. Gladiali, A. Meli, W. Pohl, F. Vizza, Organometallics 1996,
154,4604.
[31] (a) C. Bianchini, M. Frediani, F. Vizza, Chem. Comrnun. 2001, 479; (b) C. Bianchini,
M. Frediani, G. Manlorani, F. Vizza, Organometallics 2001, 20, 2660.
[32] C. Bianchini, A. Meli, W. Oberhauser, F. Vizza, Chem. Commun. 1999, 671.
[33] C. Bianchini, A. Meli, S. Moneti, F. Vizza, Organometallics 1997, 16, 5696.
[34] I. Jardine, F. J. McQuillin, J. Chem. Soc. D 1970, 626.
[35] (a) S. I. Murahashi, Y. Imada, H. Hirai, Tetrahedron Lett. 1987, 28, 77; (b) T. J. Lynch,
M. Banah, H.D. Kaesz, C.D. Porter, J. Org. Chem. 1984, 49, 1266; (c) R.H. Fish,
A. Thormodsen, G.A.D. Cremer, J. Am. Chem. Soc. 1982, 104, 5234; (d) R.M.
Laine, D. W. Thomas, L. W. Cary, J. Org. Chem. 1979, 44, 4964.
[36] (a) R. M. Laine, New J. Chem. 1987, 11, 543; (b) Eisenstadt, C. M. Giandomenico, M. F.
Frederick, R. M. Laine, Organometallics 1985, 4, 2033.
[37] (a) R.H. Fish, H-S. Kim, R.H. Fong, Organometallics 1991, 10, 770; (b) R. H.
Fish, R.H. Fong, A. Than, E. Baralt, Organometallics 1991, 10, 1209; (c) R.H. Fish,
 3.2.14. I Introduction 1119

E. Baralt, H-S. Kim, Organometallics 1991, 10, 1965-1971; (d) R.H. Fish, H-S. Kim,
R. H. Fong, Organometallics 1989, 8, 1375-1377; (e) R. H. Fish, H-S. Kim, J. E. Babin,
R. D. Adams, Organometallics 1988, 7, 2250.
[38] R. A. Sinchez-Delgado, E. Gonzalez, Polyhedron 1989, 8 1431.
[39] Y. Alvarado, M. Busolo, F. Lbpez-Linares, J . Mol. Catal. A: Chemical 1999, 142,
163.
[40] R.A. Sanchez-Delgado, D. Rondbn, A. Andriollo, V. Herrera, G. Martin, B Chaudret,
Organometallics 1993, 12, 4291.
[41] M. Rosales, Y. Alvarado, M. Boves, R. Rubio, H. Soscun, R. Sanchez-Delgado, Trans.
Met. Chem. 1995,20,246.
[42] (a) M. Macchi, Ph. D. Dissertation, Universita di Trieste (Italy), 1999; (b) C. Bianchini,
P. Barbaro, M. Macchi, A. Meli, F. Vizza, Helv. Chim. Acta 2001, 84, 2895.
[43] M. Rosales, J. Navarro, L. Sanchez, A. Gonzales, Y. Alvarado, R. Rubio, C. De la Cruz,
T. Rajmankina, Trans. Met. Chem. 1996, 21, 11.
[44] D. E. PBez, A. Andriollo, F. Lbpez-Linares, R. E. Galiasso, J. A. Revete, R. A. Sanchez-
Delgado, A. Fuentes, Am. Chem. Soc. Div. Fuel Chem. Symp. Prepr. 1998, 43, 563.
1451 (a) INTEVEP S. A. (D. E. Paez, A. Andriollo, R. A. Sanchez-Delgado, N. Valencia, R. E.
Galiasso, F. Lbpez- Linares), US 5.958.223 (1999); (b) INTEVEP S. A. (D. E. PBez,
A. Andriollo, R. A. Sanchez-Delgado, N. Valencia, F. Lbpez-Linares, R. E. Galiasso),
US 5.753.584 (1998).
[46] C. Bianchini, M. Macchi, A. Meli, W. Oberhauser, F. Vizza, manuscript in preparation.
[47] E. Carnahan, G. Jacobsen, CATTECH 2000, 7, 74.
1481 Aqueous-Phase Organometallic Catalysis - Concepts and Applications (Eds.: B. Cor-
nils, W.A. Herrmann), VCH, Weinheim, 1998, pp. 271-340.

3.2.14 Double-Bond Isomerization of Olefins

Wolfgang A. Herrmann, Martina P r i m

3.2.14.1 Introduction
Olefins display an abundant and versatile coordination chemistry with transition
metals. In fact, homogeneous catalysis owes its success mainly to the interactions
between olefins and metals: examples include hydroformylation ( 1 938), poly-
merization (1953), metathesis (1955), and Wacker-Hoechst oxidation (1958).
While all these and numerous other reactions involve structural and chemical
changes of the olefin, there is yet another, sometimes undesirable, metal-induced
phenomenon, olefin isomerization. The C=C double bond may be shifted along
the backbone of the olefin to give a mixture of terminal and cisltrans internal ole-
fins. This chapter details such double-bond isomerization, without considering
skeletal isomerization. Only homogeneously catalysed isomerizations will be
outlined [l, 21, although it should be noted that homogeneous and heterogeneous
catalysis obey the same mechanistic principles in the isomerization of olefins.
Such olefin isomerization is a key step in many industrial processes, among
them the Shell higher olefins process (SHOP) (see Section 2.3.1.3 and [l]),
 Applied Homogeneous Catalysis with Organometallic Compounds
Edited by B. Cornils and W. A. Herrmann
Copyright 0 Wiley-VCH Verlag GmbH, D-69469 Weinheim, 2002

3.2.14. I Introduction 1119

E. Baralt, H-S. Kim, Organometallics 1991, 10, 1965-1971; (d) R.H. Fish, H-S. Kim,
R. H. Fong, Organometallics 1989, 8, 1375-1377; (e) R. H. Fish, H-S. Kim, J. E. Babin,
R. D. Adams, Organometallics 1988, 7, 2250.
[38] R. A. Sinchez-Delgado, E. Gonzalez, Polyhedron 1989, 8 1431.
[39] Y. Alvarado, M. Busolo, F. Lbpez-Linares, J . Mol. Catal. A: Chemical 1999, 142,
163.
[40] R.A. Sanchez-Delgado, D. Rondbn, A. Andriollo, V. Herrera, G. Martin, B Chaudret,
Organometallics 1993, 12, 4291.
[41] M. Rosales, Y. Alvarado, M. Boves, R. Rubio, H. Soscun, R. Sanchez-Delgado, Trans.
Met. Chem. 1995,20,246.
[42] (a) M. Macchi, Ph. D. Dissertation, Universita di Trieste (Italy), 1999; (b) C. Bianchini,
P. Barbaro, M. Macchi, A. Meli, F. Vizza, Helv. Chim. Acta 2001, 84, 2895.
[43] M. Rosales, J. Navarro, L. Sanchez, A. Gonzales, Y. Alvarado, R. Rubio, C. De la Cruz,
T. Rajmankina, Trans. Met. Chem. 1996, 21, 11.
[44] D. E. PBez, A. Andriollo, F. Lbpez-Linares, R. E. Galiasso, J. A. Revete, R. A. Sanchez-
Delgado, A. Fuentes, Am. Chem. Soc. Div. Fuel Chem. Symp. Prepr. 1998, 43, 563.
1451 (a) INTEVEP S. A. (D. E. Paez, A. Andriollo, R. A. Sanchez-Delgado, N. Valencia, R. E.
Galiasso, F. Lbpez- Linares), US 5.958.223 (1999); (b) INTEVEP S. A. (D. E. PBez,
A. Andriollo, R. A. Sanchez-Delgado, N. Valencia, F. Lbpez-Linares, R. E. Galiasso),
US 5.753.584 (1998).
[46] C. Bianchini, M. Macchi, A. Meli, W. Oberhauser, F. Vizza, manuscript in preparation.
[47] E. Carnahan, G. Jacobsen, CATTECH 2000, 7, 74.
1481 Aqueous-Phase Organometallic Catalysis - Concepts and Applications (Eds.: B. Cor-
nils, W.A. Herrmann), VCH, Weinheim, 1998, pp. 271-340.

3.2.14 Double-Bond Isomerization of Olefins

Wolfgang A. Herrmann, Martina P r i m

3.2.14.1 Introduction
Olefins display an abundant and versatile coordination chemistry with transition
metals. In fact, homogeneous catalysis owes its success mainly to the interactions
between olefins and metals: examples include hydroformylation ( 1 938), poly-
merization (1953), metathesis (1955), and Wacker-Hoechst oxidation (1958).
While all these and numerous other reactions involve structural and chemical
changes of the olefin, there is yet another, sometimes undesirable, metal-induced
phenomenon, olefin isomerization. The C=C double bond may be shifted along
the backbone of the olefin to give a mixture of terminal and cisltrans internal ole-
fins. This chapter details such double-bond isomerization, without considering
skeletal isomerization. Only homogeneously catalysed isomerizations will be
outlined [l, 21, although it should be noted that homogeneous and heterogeneous
catalysis obey the same mechanistic principles in the isomerization of olefins.
Such olefin isomerization is a key step in many industrial processes, among
them the Shell higher olefins process (SHOP) (see Section 2.3.1.3 and [l]),
1120 3.2 Special Catalysts and Processes

DuPont’s butadiene-to-adiponitrile synthesis (see Section 2.5.5.1 and [ 11) and

the Takasago synthesis of (-)-menthol from a-pinene (see Sections 2.9, 3.2.14.5,
and 3.3.1).

3.2.14.2 Catalysts, Scope, and Definition

Olefin isomerization is common in petrochemical refining processes (hetero-
geneous catalysis) and, of course, follows the thermodynamic driving forces:
trans-olefins are more stable than their cis isomers, and internal olefins more
stable than terminal olefins (eq. (1)).

R-CH&H=CH2 f- R-CHzCH-CH3
1-olefin 2-olefin

A typical example is the near-equilibrium isomerization of 1-octene to a

mixture of 2 % 1-octene, 36 % 2-octene, 36 % 3-octene, and 26 % 4-octene (cis/
truns mixtures) [3]. If 1-butene is allowed to isomerize until it reaches the ther-
modynamic equilibrium, a mixture of 69 % truns-2-butene, 25 % cis-2-butene,
and 6 % 1-butene is found [4]. Note that the isomerization of olefins is a kinetic
phenomenon. In the isomerization of a-olefins, it is the cis isomer of the resulting
b-olefins that is often formed in kinetic preference and thus these isomers may be
isolated as the major product in the early stages of many reactions. The preference
for cis isomers can be determined by the catalyst used or the presence of certain
functional groups in the olefin, e. g., in 1,2-dichloroethylene, 1-chloropropene,
and 2-butenecarboxylic nitrile. The /?,y-double bond position dominates in the
isomerizations containing carboxylic acids, esters, and nitriles if the b-C atom car-
ries two alkyl groups, e. g., in eq. (2). Furthermore the formation of conjugated di-
and oligoolefins is normally favored over isolated double bonds (eq. (3)). This
type of isomerization finds application in the synthesis of stereoids, an example
of which is illustrated in eq. (4), Here the strong preference of the 14-electron
fragment Fe(C0)3 to bind 1,3-dienes is exploited. The Fe(C0)3 group can be
oxidatively removed from the isomerized diolefin by means of FeC13, and in
some cases by Cr03 [ 5 ] .

CH3\ CH3.
C=CH-CH1X CH -CH =CH -X
CH3’ CH3‘

X=COOH 94% 6 Yo
X=CN 79% 21 Yo

1,4-diolefin 2,4-diolefin
(nonconjugated) (conjugated)
 3.2.14.3 Mechanistic Considerations 112 1

R /’ (4)
Fe(C013
free diene
30-70 Yo 60-90 Yo

In contrast, metals like Pd and Rh prefer the 1:2,5:6-r4-bonding mode (1,5-

dienes) of cycloolefinic structures. They rearrange 1,3-dienes in an apparently
“contrathermodynamic” way to their 1,5-isomers. The products can be cleaved
from the metals by cyanide ions (eq. (5)). Numerous examples are known [6-141.

In the case of substituted olefins, the isomers exhibiting the highest degree of
branching are thermodynamically favored.

3.2.14.3 Mechanistic Considerations

Depending on the specific nature of the olefin and the metal (complex) in ques-
tion, two major mechanisms dominate the scene. The coordination chemistry of
the metal specifies in many cases the path of olefin isomerization [15].

3.2.14.3.1 The n-Ally1 Mechanism (1,3-Hydrogen Shift)

The principle of the n-ally1 mechanism is illustrated in Scheme 1. The catalytic
process is initiated by coordination of the terminal olefin to the metal followed
by activation of the aliphatic C,H-bond, affording the three-carbon arrangement
in n-bonding to the metal. The metal-attached hydride has thus two positions to
which it may be transferred (a and y ) , the a-position being nonproductive and
the y-position leading to the internal olefin. It follows from Scheme 1 that the
,8-C-H entity is not affected.
Proof for this mechanism is found from the high cisltruns ratios of the isomer-
ized olefin formed at an early stage in the reaction [ 161, and little or no deuterium
substitution in the 2-positionu) when deuterated olefins are being used; an exam-
ple is shown in eq. (6).
1122 3.2 Special Cutalysts and Processes

LnM-H
Scheme 1 metal a-ally1

The catalysts Fe3(CO),,, Pd(N=CR),CI,, Pd(N=CR)3, and C1Rh[P(C6HS),I3

(R = alkyl, aryl) are found to follow this mechanism in the olefin isomenzation.
Also, the isomerization of unconjugated to conjugated double bonds using
Fe(CO)s mentioned previously (see Section 3.2.14.2) follows this mechanism.
Note that the ,D migration in the isomerization of 1,4-cyclohexadiene occurs
alongside the metal complexation (FeD intermediates; cf. eq. (7)) [ 171.

A nice model for the n-ally1 mechanism has been reported by Bonnemann [ I S ]
for the pair of nickel complexes 1 and 2 forming a temperature-dependent equili-
brium (eq. (8)).

CHz =CH-CH3 db\

-
H

HzC n C H p
I I
Ni -< -40"C- I
I
I > -40"C
,Ni.
PF3 H PF3
1 2
 3.2.14.3 Mechanistic Considerations 1123

3.2.14.3.2 The Alkyl Mechanism (1,2-Hydrogen Shift)

The “alkyl mechanism” is the preferred pathway of isomerization, if the catalytic
species contains a metal-bonded hydride as illustrated in Scheme 2. It is reminis-
cent of the hydroformylation mechanism (see Section 2.1.1).

I L,M-H I
metal hydride RCHpCH=CHp

I Y P \ a
RCH =CH-CH3 RCHpCH T C H z
I I
L,M - H L,M - H

Scheme 2

Depending on the metal and the specific nature of the ligand sphere (especially
its steric bulk), the hydride migration (“insertion”, step A) in the product-deter-
mining step can follow either the anti-Markovnikov or the Markovnikov path
(Scheme 2). Only in the latter case and if subsequent y-H “elimination” takes
place (step B), does an isomerized olefin result.
Typical catalysts that employ this mechanism are nickel hydrides and Ru hy-
drides such as HRhCl[P(C,H,),], (which is also a classic olefin hydrogenation
catalyst) and [HNi(P(C6Hs)3}3]+,which is present in the system Ni[P(C6Hs)3]4/
CF,COOH according to eq. (9) [19, 201.

r.d.
NiL4 + H+ === [HNiL4]+
-L
[HNiL3]+ (9)

L = P(C~HB)B
r.d. = rate-deterrnining step

The distinction between the 1,2- and the 1,3-shift processes is readily demon-
strated using D-labeled olefins. In the isomerization of 3 (eqs. (1Oa) and (lob)) the
two pathways are discerned by NMR spectroscopy.
1124 3.2 Special Catalysts and Processes

1,3-shift CH3CHZ \
P C=CH-CHpD (lea)
(ally1 mechanism) CH3CH2/

3.2.14.4 Applications
As mentioned previously, large-scale olefin isomerization has found application in
the SHOP technology (see Section 2.3.1.3 and [l]).
In the BASF synthesis of vitamin A (see Chapter 1) the intermediate b-olefin 5
of eq. (11) is obtained from the isomerization of 6-methyl-6-hepten-2-one 4, with
the latter resulting from condensation of acetone, isobutene, and formaldehyde
[211.
No U 0
//
p)CH2)3-C\ CH3 (CH2)2 -C,
CH2 =C CH3 \p- / CH3 (1 1)
\ ,c-c\
CH3 CH3 H
4 5

A comonomer for the synthesis of ethylene/propene elastomers - 2-ethylidene-

norbornene (7)- is synthesised via a Diels-Alder cycloaddition of cyclopenta-
diene and butadiene followed by an isomerization with titanium-based catalysts
of the intermediate 2-vinyl derivative 6 in excellent yield (98 %) (eq. (12)) [22].

The isomerization of functionalized olefins frequently involves a migration pro-

cess of substituents other than hydrogen.
In the DuPont butadiene-to-adiponitrile synthesis (see Section 2.5.5.1 and [ l]),
two olefin isomerization steps are employed: rearrangement of 8 via C-C clea-
vage to the linear isomer 9 (a) is followed by a double-bond shift yielding the
terminal olefin 10 (b). The latter is thermodynamically more stable because of
the cyano functionality (cf. eq. (13) and Section 2.5).
 3.2.14.5 Asymmetric Isomerization 1125

Another example is the vapor-phase chlorination of butadiene, which gives a

mixture of dichlorobutenes of which 3,4-dichloro- 1-butene (12)is the only desired
isomer for the chloroprene synthesis [23, 241 (cf. eq. (14)). It is easily boiled off
from the cisltruns 1,4-dichloro-2-butenes (123 vs. 155 "C). The migratory isomer-
ization of residual 1,4-isomers 11 is effected by Cu' complexes and seems to
operate through n-olefinln-ally1 intermediates. The chloride probably migrates
via the copper center, but no mechanistic details are available.

CICH2CH=CHCH2CI
11
- cat.
f ClCH2 -CH-CH=CH2
12 CI
I
(14)

Yet an important application is the analogous isomerization of 1,4-diacetoxy-2-

butene (13) to the 1,3-isomer 14 (cisltruns mixture) with a Pt'"C14 catalyst - a key
step of the BASF vitamin A synthesis (eq. (15)). The lower-boiling product is en-
riched to a yield of 95 % and is further hydroformylated to form the vitamin A side
chain [25] (see Chapter 1).

AcOCH2CH=CHCH20Ac
13
* AcOCH2 -CH-CH=CHz
14
I
OAC
(15)

3.2.14.5 Asymmetric Isomerization

Of particular interest is the asymmetric isomerization with chiral catalysts (e. g.,
eq. (16)), converting allylic alcohols and ethers as well as allylamines into useful
synthetic building blocks [26-291.

R1 R3 R1 R3
\ / \* /
,c =c CH-C
\ - / \\
R2 CH2X R2 CHX

X = OH, OR; NH2, NR2

The world's biggest application of asymmetric catalysis is Takasago

Perfumery's synthesis of (-)-menthol from myrcene (see Sections 2.9 and
3.3.1) with about 1500 t/a (menthol and other chiral terpenic substances). The
key step is the isomerization of geranyldiethylamine with an Rh'-S-BINAP cata-
lyst to citronella1 (a-enamine (eqs. (1 7)) (BINAP = 2,2'-bis(dipheny1phosphine)-
1,1'-binaphthyl).The geometry of the double bond is 100 % E.
1126 3.2 Special Catalysts and Processes

Scat. = [Rh{(S)-BINAP}(cod)]+
R-cat. = [Rh((R)-BINAP)(cod)]+

The catalytic process is initiated by coordination of the amino nitrogen atom to

the Rh followed by a stereospecific p-hydrogen elimination resulting in an 1,3-hy-
drogen shift with a suprafacial stereochemistry as determined from D-labeling
experiments (eqs. (1 7)). n-Ally1 intermediates account for these unusually clean
stereochemical results. The methyl group at the olefinic bond determines the
configuration of the transition state. Outstanding enantioselectivity (298 %)
and high catalyst efficiency (substratekatalyst ratio -8000: 1) are the remarkable
features of this reaction [30-331.

3.2.14.6 Recent Developments

Double-bond isomerization has been exploited as a desired reaction in organic
synthesis; examples include the synthesis of steroids. It is also an undesired
side reaction of industrially relevant reactions such as hydroformylation (cf. Sec-
tion 2.1. l), hydrogenation (cf. Section 2.2), and hydrosilyation (cf. Section 2.6), it
is a subject of current interest [34-361. Two promising developments are worth
mentioning here because they yielded highly selective catalysts which are, at
the same time, easy to handle.

3.2.14.6.1 Organotitanium Catalysts

Special organotitanium cataysts effect regio- and stereoselective isomerizations
L37-431. Titanocene dichloride with various activating reagents (e. g., Grignard
compounds, lithium organyls, LiA1H4) has been employed to convert a-olefins
into p-olefins with preferred trans geometry according to eq. (18) using the
immobilized catalyst system 15 in the presence of t-butylmagnesium bromide
~401.

trans cis
R = CHz 72 % 28 o/o
.
R = C2H5 85 % 15 %
 3.2.14.6 Recent Developments 1127

15

Vinylcyclohexane and vinylcyclooctane isomerize quantitatively at 180 "C in

the presence of (v5-C5Hs)2TiC12/LiA1H4according to eq. ( 1 9) [37].

/-7 /-7
(CH2) CH-CH=CH2 5 (CH2) C=CH-CHs (19)
0 180 "C
CJ
Nakamura and co-workers discovered outstanding activities and selectivities
for the permethylated titanocene (v5-CSMe5)2TiC12 (Me = CH3) in the presence
of the reducing agent sodium naphthalide. The olefin isomerization proceeds at
ambient temperature, and the preference for the trans products seems to depend
on the steric bulk of the catalyst [36]. Diolefins yield the conjugated isomers. Ex-
amples are given in Table 1. From a mechanistic point of view, Ti" intermediates
of type (R,Ti} (R = C5Hs, C,Me,) must be invoked, suggesting a n-ally1 me-
chanism. No detailed information is yet available, however, with regard to this
question.

Table 1. Isomerization of olefins catalyzed by (qS-CSMe5)2TiC12/Nanaphthalide at 20 "C in

60-120 min (olefinkatalyst ratio 1OO:l): data from [25].
Starting olefin Product Yield [%I trans isomer [%I
~~

1-Butene 2-Butene > 99 99

3-Phenyl- 1-propene 1-Phenyl-1-propene > 99 99
4-Methyl- 1-pentene 4-Methyl-2-pentene 25 99
1,4-Pentadiene 1,3-Pentadiene 99 > 99

An asymmetric variant of double-bond isomerization could be achieved with

the chiral ansa-bis(indeny1)titanium complex [43]. After activation with LiA1H4
it isomerizes meso,trans-4-tert-butyl-l-vinyl-cyclohexaneto the S-alkene with
remarkable enantioselectivity (80 % ee).
I I28 3.2 Special Catalysts and Processes

3.2.14.6.2 Rhodium Complexes with N-Heterocyclic

Carbene Ligands
The ligand sphere of an organometallic homogeneous catalyst has in principle two
functions: stabilization of the low-valent metal and activation of the metal center
by offering vacant coordination sites. Phosphine ligands fulfill these criteria and
therefore have played a key role in homogeneous catalysis. As two-electron do-
nors N-heterocyclic carbenes resemble phosphines and form remarkably strong
metal-carbon bonds with metals from all over the periodic table (see Section
3.1.10 and [44]). In 1994 this ligand class experienced a renaissance with the dis-
covery of the remarkable activity of palladium-N-heterocyclic carbene complexes
in Heck reactions [45]. The fact that N-heterocyclic carbenes are similar to alkyl-
ated phosphines resulted in the development of new generations of ruthenium N -
heterocyclic carbene complexes which are extraordinarily active in ring-opening
metathesis reactions (see Section 2.3.3 and [46]).
Rhodium complexes such as 16 with N-heterocyclic carbenes can be prepared
in one step proceeding from commercially available precursors (e. g. [(v4-1,5-
COD)RhC1I2 (eq. (20)) or Wilkinson’s complex [RhCl(PPh,),] and the free car-
bene, which is generated from the storable imidazolium salt by deprotonation
[47-49]. For more details, see Section 3.1.10.

CH, r
16 HX’
. .=-

3.2.14.7 Perspectives
Double-bond isomerization is one of the major industrial processes in the context
of petrochemical oil-refining steps. Selective olefin isomerization under mild con-
ditions is therefore an important goal. New catalysts need to favor a certain isomer
kinetically, which means that the speed of rearrangement must be high. As always
in homogeneous catalysis, the active species has to maintain its structure for a
long time to give reproducible results. The N-heterocyclic carbene complexes
mentioned above should be borne in mind when further attempts are made at
improvement. Of especial charm is stereoselective double-bond isomerization
1511, for which new, efficient chiral ligands are warranted.
 References 1129

References
[ l ] (a) W. A. Herrmann, Kontakte (Darmstadt), 1991, No. 1 ; (b) W. A. Herrmann, Kontakte
(Darmstadt), 1991, No. 3.
[2] R. A. van Santen, P. W. N. M. van Leeuwen, J. A. Moulijn, B. A. Averill, Catalysis: an
Integrated Approach, 2nd ed., Elsevier Science, Amsterdam, 1999, pp. 209-288.
[3] P.A. Verbrugge, G.J. Heisewolf, GB 1.416.317 (1975).
[4] (a) C. A. Tolman, J. Am. Chem. Soc. 1992, 94,2999; (b) C. A. Tolman, R. J. McKinney,
W. C. Seidel, J. D. Druliner, W. R. Stevens, Adv. Catal. 1985, 33, 1 .
[5] H. Alper, J. T. Edward, J. Organornet. Chem. 1968, 14, 41 1.
[6] (a) MT Orchin, Adv. Catal. 1966, 16, 1; (b) N. R. Davies, Rev. Pure Appl. Chem. 1967,
17, 83.
[71 C. W. Bird, Transition Metal Intermediates in Organic Synthesis, Logos PressElek
Books, London, 1967, pp. 69-87.
181 G.M. Kramer, G.B. McVicker, Acc. Chem. Res. 1986, 19, 78.
191 P. N. Rylander, Organic Synthesis with Noble Metal Catalysts, Academic Press, New
York, 1973, pp. 145-174.
1101 M. M. T. Khan, A. E. Martell, Homogeneous Catalysis, Academic Press, New York,
1974, pp. 9-37.
[ 111 G. W. Parshall, S. D. Ittel, Homogeneous Catalysis, 2nd ed., John Wiley, New York,
1992, pp. 9-24.
[ 121 C. Masters, Homogeneous Transition Metal Catalysis, Chapman and Hall, London,
1981, pp. 70-89.
[ 131 S. G. Davies, Organotransitioii Metal Chemistry: Applications to Organic Synthesis,
Pergamon, Oxford, 1982, pp. 266-303.
[ 141 H. M. Colquhoun, J. Holton, D. J. Thompson, M. V. Twigg, New Pathwaysfor Organic
Synthesis, Plenum, New York, 1984, pp. 173-193.
[ 1.51 J. D. Atwood, Mechanisms of Inorganic and Organometallic Reactions, Brooksicole,
California, 1985.
[16] M. Turner, J. V. Jouanne, H.-D. Brauer, H. Kelm, J. Mol. Catal. 1979, 5, 425, 433, 447.
[17] H. Alper, P. C. LePort, J. Am. Chem. Soc. 1969, 91, 75.53.
[18] H. Bonnemann, Angew. Chem. 1973, 85, 1024; Angew. Chem., Int. Ed. Engl. 1973,
12, 964.
[19] D. Evans, J. Osborn, G. Wilkinson, J. Chem. Soc. (London) A 1968, 3133.
[20] C.P. Casey, C.R. Cyr, J. Am. Chem. Soc. 1973, 95, 2248.
[21] H. Pommer, A. Nurrenbach, Pure Appl. Chem. 1975, 43, 527.
[22] G. Ver Strate, Encycl. Polym. Sci. 1986, 6, 522.
[23] F. J. Bellringer, C.E. Hollis, Hydrocarbon Process, 1968, 4 7 ( l l ) , 127.
[24] G. W. Parshall, S. D. Ittel, Homogeneous Catalysis, 2nd ed., John Wiley, New York,
1992, pp. 300-302.
[25] BASF AG (J. Hartig, H.-M. Weitz, R. Schnabel), DE 2.747.634 (1979).
[26] M. Beller, C. Bolm, Transition Metals for Organic Synthesis, Wiley-VCH, Weinheim,
1998, p. 147.
[27] L. J. Gazzard, W. B. Motherwell, D. A. Sandham, J. Chem. Soc., Perkin Trans. 1999,
I, 979.
[28] S. Fuss, J. Harder, FEMS Microbiol. Lett. 1997, 149, 71.
[29] D. Baudry, M. Ephritikhine, H. Felkin, J. Chem. Soc., Chem. Commun. 1978, 694.
[30] K. Tani, T. Yamagata, S. Otsuka, S. Akutagawa, H. Kumobayashi, T. Taketomi, H.
Takaya, A. Miayshita, R. Noyori, J. Chem. Soc., Chem. Commun. 1982, 600.
[31] K. Tani, T. Yamagata, S. Akutagawa, H. Kumobayashi, T. Taketomi, H. Takaya,
A. Miayshita, R. Noyori, S. Otsuke, J. Am. Chem. Soc. 1984, 106, 5208.
1130 3.2 Special Catalysts and Processes

[32] K. Tani, T. Yamagata, Y. Tasuno, Y. Yamagata, T. Tomita, S. Akutaga, H. Kumobayashi,

S. Otsuka, Angew. Chem. 1985, 97, 232; Angew. Chem., Int. Ed. Engl. 1985, 24, 217.
[33] T. Faitig, J. Soulie, J. Y. Collemand, Tetrahedron 2000, 56, 101.
[34] A. Haynes, J. McNish, J. M. Pearson, J. Organomet. Chem. 1998, 551, 339.
[35] F. M. Moghaddan, R. Emanj, Synth. Cornmun. 1997, 27, 4073.
[36] N. S. Sampson, I. J. Kass, J. Am. Chem. Soc. 1997, 119, 855.
[37] M. Akita, H. Yasuda, K. Nagasuna, A. Nakamura, Bull. Chem. Soc. Jpn. 1983, 56, 554.
[38] R. H. Grubbs, C. Gibbons, L. C. Kroll, W. D. Bonds, Jr., C. H. Brubaker Jr., J. Am. Chem.
Soc. 1973, 95, 2373.
[39] W. D. Bonds, Jr., C. H. Brubaker, Jr., E. S. Chandrasekaran, C. Gibbons, R.H. Grubbs,
L.C. Kroll, J. Am. Chem. Soc. 1975, 97, 2128.
[40] D. E. Bergbreiter, G. L. Parson, .I.Organomet. Chem. 1981, 208, 47.
[41] C.-P. Lau, B.-H. Chang, R.H. Grubbs, C. H. Brubaker, Jr., J. Organomet. Chem. 1981,
214, 325.
[42] K. Mach, F. Turecek, H. Antropiusova, L. Petrusova, V. Hams, Synthesis 1982, 53.
[43] Z. Chen, R. Halterman, J. Am. Chem. Soc. 1992, 114, 2276.
[44] (a) Hoechst AG (W.A. Herrmann, M. Elison, J. Fischer, Ch. Kocher), DE 4.447.066
(1994). Reviews: (b) W. A. Herrmann, C. Kocher, Angew. Chem. 1997, 109, 2256;
Angew. Chem., Int. Ed. Engl. 1997,36, 2162; (c) D. Bourissou, 0. Guerret, F. P. Gabbai',
G. Bertrand, Chem. Rev. 2000, 100, 39; (d) T. Weskamp, V.P.W. Bohm, W.A. Herr-
mann, J. Organomet. Chem. 2000, 600, 12.
[45] (a) W.A. Henmann, M. Elison, J. Fischer, Ch. Kocher, G. R. J. Artus, Angew. Chem.
1995, 107, 2602; Angew. Chem., Int. Ed. Engl. 1995, 34, 2371; (b) J. Fischer, Ph. D.
Thesis, Technische Universitat Miinchen, 1996; (c) W. A. Henmann, Angew. Chem.,
Int. Ed. Engl. 2002, in press (review article on N-heterocyclic carbenes in catalysis).
[46] (a) T. Weskamp, W.C. Schattenmann, M. Spiegler, W.A. Herrmann, Angew. Chem.
1998, 110, 2631; Angew. Chem. Int. Ed. 1998, 37, 2490; (b) T. Weskamp, F. J. Kohl,
W. Hieringer, D. Gleich, W.A. Henmann, Angew. Chem. 1999, 38, 2416; Angew.
Chem., Int. Ed. 1999, 38, 2416.
[47] W. A. Herrmann, M. Elison, J. Fischer, C. Kocher, Chem. Eur: J. 1996, 2, 772.
[48] M. Prinz, Diplomarheit, Technische Universitat Miinchen, 1997.
[49] A. C. Chen, L. Ren, A. Decken, C. M. Crudden, Organometullics, 2000, 19, 3459.
[SO] W. A. Herrmann, J. Unruh, Ch. Kocher, J. Fischer, unpublished results, 19996.
[Sl] (a) R.E. Menill, CHEMTECH 1981, 11, 118; (b) S. Otsuka, K. Tani, in Asymmetric
Synthesis, Vol. 5 (Ed.: J.D. Momson), Academic Press, New York, 1985, Chapter 6,
p. 171.
 Applied Homogeneous Catalysis with Organometallic Compounds
Edited by B. Cornils and W. A. Herrmann
Copyright 0 Wiley-VCH Verlag GmbH, D-69469 Weinheim, 2002

3.3.1.I Introduction and Background I 131

3.3 Special Products

3.3.1 Enantioselective Synthesis

Hans-Ulrich Blase< Benoit Pugin, Felix Spindler

3.3.1.1 Introduction and Background

For many applications of chiral compounds, the racemic form will no longer be
accepted [ I , 21. As a consequence, the importance of enantioselective synthesis
in general and of enantioselective catalysis in particular will undoubtedly increase.
There are various methods available to prepare only one enantiomer of a chiral
product [3]. The resolution of racemates is probably still used most often despite
the fact that the yield of the desired enantiomer is at best 50 % [4 a]. If the unde-
sired enantiomer cannot be isomerized and recycled, it must be disposed of. Simi-
lar problems occur when applying stoichiometric chiral reagents or chiral auxi-
liaries. This question does not arise if a starting material from the chiral pool (iso-
lated from natural products or produced by fermentation) can be used, since nature
has already produced the desired absolute stereochemistry. However, for larger-
scale applications it is not always possible to find the suitable starting material.
Therefore, enantioselective catalysis with either biocatalysts or chiral chemical
catalysts will be applied more frequently in the future because the chiral auxiliary
is required only in substoichiometric quantities. However, it must be stressed that
every method mentioned above can be the most suitable one for solving a parti-
cular problem. There are many factors that influence economical and ecological
aspects and no single approach is able to meet all the requirements of an industrial
process.
Most of the useful enantioselective homogeneous catalysts consist of a central
metal atom and a chiral ligand. Somewhat simplified, the activation of a substrate oc-
curs by binding to the metal center whereas the stereocontrol of the transformation is
exerted by the chiral ligand, resulting in the preferential formation of one enantiomer.
While most applications are in the field of asymmetric synthesis starting from a pro-
chiral substrate, kinetic resolution, i. e., the preferential transformation of one enantio-
mer of a racemic substrate, is of growing technical importance [5]. Up to now, rela-
tively few homogeneous enantioselective catalysts have been used on an industrial
scale 161. One reason is that enantioselective homogeneous catalysis is a relatively
recent discipline, but there are many others and these will be discussed below.
In this overview, the opportunities and problems associated with the industrial
application of chiral metal complexes will be analyzed in detail. In Section
3.3.1.2, the critical factors are discussed which affect the feasibility of an enantio-
selective catalyst. In the following Sections, important families of chiral ligands
are listed and finally about 40 types of catalytic transformations are described
and characterized regarding enantioselectivity, catalyst activity, and productivity,
and their potential for technical applications is assessed.
1132 3.3 Special Products

3.3.1.2 Critical Factors for the Technical Application

of Homogeneous Enantioselective Catalysts
The application of homogeneous enantioselective catalysts on a technical scale
presents some very special challenges and problems [3, 4, 6, 71. Some of these
problems are due to the special manufacturing situation of the products involved,
others to the nature of the enantioselective catalytic processes.

3.3.1.2.1 Characteristics of the Manufacture

of Enantiomerically Pure Products
Optically pure compounds will be used above all as pharmaceuticals and vitamins
[I], as agrochemicals [2], and as flavors and fragrances [8]. Other potential but at
present less important applications are as chiral polymers, as materials with
nonlinear optical properties, or for ferroelectnc liquid crystals [4 b, 91. The manu-
facture of pharmaceuticals and agrochemicals can be characterized as follows
(typical numbers are given in parentheses):

(1) Multifunctional molecules produced via multistep syntheses (five to ten steps
or more for pharmaceuticals, and three to seven for agrochemicals) with short
product lives (often less than 20 years).
(2) Relatively small-scale products (1-1000 t/a for pharmaceuticals, 500-10 000
t/a for agrochemicals), usually produced in multipurpose batch equipment.
( 3 ) High purity requirements (usually > 99 % and < 10 ppm metal residue in
pharmaceuticals).
(4) High added values and therefore tolerant to higher process costs (especially for
very effective, small-scale products).
( 5 ) Short development time for the production process (less than a few months to
1-2 years) since time to market affects the profitability of the product.
(6) Synthetic route often designed around the enantioselective catalysis as key
step.

3.3.1.2.2 Characteristics of Enantioselective

Catalytic Processes
Homogeneous enantioselective catalysis is a relatively young but rapidly expand-
ing field. Up to 1985, only few catalysts affording enantioselectivities up to 95 %
were known [ 101. This situation has changed dramatically in recent years and there
are now a large number of chiral catalysts known that catalyze a variety of trans-
formation with enantiomeric excesses (ee) > 98 % [ 1I , 121. What still remains a
major challenge is the fact that it is difficult to transfer the results obtained for a
particular substrate to even a close analog due to the high substrate specificity
(low tolerance for structure variation even within a class of substrates). Technical
applications of enantioselective catalysts are also hampered because there is little
 3.3.1.2 Critical Factors for the Technical Application 1133

information on catalyst activity or other aspects available (in the literature enan-
tioselectivity is the dominant criterion) and because few applications with “real”
substrates exist (usually simple model reactions are studied). Finally, chiral ligands
and many metal precursors are expensive and/or not easily available.

3.3.1.2.3 Critical Factors for the Application

of Enantioselective Catalysts
In the final analysis, the choice of a specific catalytic step is usually determined by
the answer to two questions:

(1) Can the costs for the overall manufacturing process compete with alternative
routes?
(2) Can the catalytic step be developed in the given time frame?

As a consequence of the peculiarities of enantioselective catalysis described

above, the following critical factors often determine the viability of an enantio-
selective process:

( I ) Enantioselectivity, expressed as enantiomeric excess (% ee), i. e., % desired

- % undesired enantiomer. The ee of a catalyst should be > 99 % for pharma-
ceuticals if no purification is possible (via recrystallization or at a later stage
via separation of diastereomeric intermediates). This case is quite rare and ee
values of > 90 % are often acceptable; for agrochemicals ee values of > 80 %
can be sufficient.
(2) Chemoselectivity (or functional group tolerance) will be very important when
multifunctional substrates are involved.
(3) Catalyst productivity, given as substrate/catalyst ratio (SIC)or turnover number
(TON), determines catalyst costs. These s/c ratios ought to be > 1000 for
small-scale, high-value products and > 50 000 for large-scale or less-expen-
sive products (catalyst re-use increases the productivity).
(4) Catalyst activity, given as turnover frequency for > 95 % conversion (TOF,,,
h-I), determines the production capacity. TOF,, ought to be > 500 h-’ for
small-scale and > 10000 h-’ for large-scale products.
( 5 ) Availability and cost of ligands. In the majority of cases the ligands of the
organometallic catalysts are chiral diphosphines which need special synthetic
know-how and can be rather expensive. Typical prices are US$ 100-500/g for
laboratory quantities and US$ 5000 to > US$ 20 OOO/kg on a larger scale.
Chiral ligands used for early transition metals are usually cheaper.
(6)Availability and cost of starting materials. Starting materials are often expen-
sive and difficult to manufacture on a large scale with the required quality.
(7) Development time. This can be crucial if an optimal ligand has to be developed
for a particular substrate (substrate specificity) and when not much is known
on the catalytic process (technological maturity).
1134 3.3 Special Products

For most other aspects such as catalyst stability and sensitivity, handling pro-
blems, catalyst separation, space-time yield, poisoning, chemoselectivity, process
sensitivity, toxicity, safety, special equipment, etc., enantioselective catalysts have
similar problems and requirements compared to nonchiral homogeneous catalysts.
Which of these criteria will be critical for the development of a specific process
will depend on the particular catalyst and transformation. The following factors
have to be considered: the field of application and the price of the active com-
pound (added value of the catalytic step), the scale of the process, the technical
experience and the production facilities of a company, the maturity of the catalytic
process, and last but not least, the chemist who plans the synthesis must be aware
of the catalytic route!

3.3.1.3 State-of-the-Art and Evaluation

of Catalytic Transformations

3.3.1.3.1 General Comments

In the last few years, information on industrial applications has increased both in
quantity and in quality because smaller technology-based companies especially
are prepared to publish relevant results (cf. Table 1) [6]. From the values in this

Table 1. Statistics for the industrial application of enantioselective catalytic reactions.

Transformation Production"' Pilot") Bench-
scale"
> 5 t/a < 5 t/a > 5 0 k g <50 kg
Hydrogenation of enamides 1 1 2 6 4
Hydrogenation of C=C-COOR and 1 0 3 4 6
C=C-CH-OH
Hydrogenation of other C=C 1 0 1 2 2
Hydrogenation of a- and b-functionalized 2 2 3 6 4
c=o
Hydrogenation/reduction of other C=O 0 0 0 1 4
Hydrogenation of C=N 1 0 1 0 0
Dihydroxylation of C=C 0 1 0 0 4
Epoxidation of C=C, oxidation of sulfide 2 1 2 0 2
Isomerization, epoxide opening, addition 2 0 3 0 1
Total 10 5 15 19 27
a) Production processes are operated on a regular basis. b, Pilot processes are technically on
a similar level but are not (yet) applied on a regular basis. ') Bench-scale processes have an
optimized catalyst system and have been carried out on a kilogram scale.
 3.3.1.3 State-ofthe-Art and Evaluation of Catalytic Transformations 1135

table, it is evident that hydrogenation (enantioselective h.; cf. Section 2.2) is the
transformation with the highest industrial impact, followed by epoxidation and
dihydroxylation reactions. The success with epoxidation and dihydroxylation
reactions can be attributed essentially to the efforts of Sharpless, Katsuki, and
Jacobsen (cf., e. g., Section 3.3.2). Nevertheless, as will be shown in the following
sections, other catalytic transformations have the potential for industrial use too.
In the next sections, synthetically useful enantioselective reactions and the cor-
responding catalysts are reviewed. Critical issues will be discussed and an overall
assessment of the technical maturity will be given.

3.3.1.3.2 Chiral Ligands

Chiral ligands are obviously at the heart of every enantioselective organometallic
catalyst. Over the years a number of ligand types and families have achieved what
Jacobsen once called a “privileged” status. This means that certain ligand types
have a very broad scope, in many cases because they can easily be tailored for
a specific substrate, often have a modular character, and are available in larger
quantities, e. g., 1-16. Many of these catalysts tolerate a wide range of functional
groups and are also chemoselective.

BlAR
biaryl and
heterobiaryl
diphosphines $2; \

1 BlNAP 2 BIPHEP 3 TMBTP

BINO, PAMID
binol-based
ligands

4 BlNOL 5 BlNOP 6 PAMID

p i n e function

FERRO
ferrocenyl-
based ligands

7 JOSIPHOS 8 BPPFA 9 TRAP

1136 3.3 Special Products

R 11
PCYCL DuPHOS ROPHOS
ligands with

OXAZ, PAOXAZ
oxazoline-derivated (-N
ligands 8- N

12 13

NOP
backbone derived 15 16
from amino acids PNNP OXABOR

In order to give an impression of the structural variety of chiral ligands, repre-

sentative examples of the preferred ligand types (and abbreviations) mentioned in
the following tables are given with these structures. Generally, the abbreviation
XAYis used for bidentate ligands with a chiral backbone and X and Y as coordi-
nating atoms. TART and CINCH are tartaric acid and cinchona derivatives, respec-
tively. All other abbreviations have the meanings used in [ 111.

3.3.1.3.3 Addition to C=C Groups

Hydrogenation of Olefins

The enantioselective hydrogenation of olefins is the best-studied reaction with the

most industrial applications [6, 11 a, 12al. Over the most recent decades, a few
privileged substitution patterns have evolved that almost guarantee high ee values
(olefins 17, 18) and the state-of-the-art is summarized in Table 2. With few excep-
tions, Rh and Ru complexes of a limited number of chiral diphosphine families are
the preferred catalysts but, in any case, the optimal complex (metal, ligand, anion,
etc.) has to be determined for each substrate.
 3.3.1.3 State-of-the-Art and Evaluation of Catalytic Transformations 1137

Table 2. State-of-the-art for the hydrogenation of olefins (cf. structures 17-39).

Substrate ee [%I"' TON"' TOF [h-'1") Preferred catalyst typesb'
Type 17 (enamides, enol 90-98 1000-20 000 200-5000 RhPCYCL, RNFERRO,
acetates, itaconates) RuBIAR, RhPPM
Type 18 (C=C-C-OH) 80-95 10 000-50000 1000-5000 RuBIAR
Type 18 (C=C-COOH) 85-95 2000-10 000 500-3000 Ru/BIAR, (RhPCYCL)
tetrasubstituted C=C 85-95 500-2000 200-500 RUIBIAR, RuPCYCL,
Rh/FERRO
C=C without 80-95 20-100 2-5 RuBIAR, Ir/PAOXAZ,
privileged function Rh/PCYCL
"'Typical range for suitable substrate and optimized catalyst. For structures see 1-16.

X=CH,, NR, 0 'HR' X=COOH(R), CR,-OH

R3 x
17 18

Hydrogenation of enamides 17 (X = NR, Y = C, W = R), especially with

R, = COOR, is not only the best-known test reaction but also has a very high
potential for the production of pesticides or pharmaceuticals. The original motiva-
tion for developing this reaction type was the manufacture of a-amino acids but
except for small-scale applications such as L-dopa, the preparation of the enamide
substrates was too expensive and most amino acids are now produced via bioca-
talytic methods [13]. Many different substrates of type 17 can be hydrogenated
with ee values between 95 and 99% [lla, 12a] but much less is reported on
catalyst activity and productivity. In general, more and larger substituents lead
to a decrease in catalyst activity either when directly attached to C=C or when
bound to X or W.
The selected examples (19-27) of applications with type 17 substrates show
what level of catalyst performance can be achieved by process development
(the development status and the relevant company are also shown). In addition,
the selection demonstrates the variety of structural motifs found in biologically ac-
tive compounds and the need for tolerance of functional groups such as pyridyl,
cyano, thienyl groups or other C=C or C=O functions. Preferred catalysts and
ranges for ee values, TONS and TOFs are listed in Table 2. Other type 17 sub-
strates with a similar industrial potential are itaconic and phosphonic acid deriva-
tives.
The hydrogenation of allylic alcohols and a$-unsaturated acids (type 18) is
another class of transformations with a high industrial success rate. Again, some
illustrative examples are Structures 28-33; preferred catalysts are Ru/BINAP
11 38 3.3 Special Products

Me0

19 20 21
Rh/DIPAMP; ee 95 % Rh/DuPHOS; ee 98 % Rh/DuPHOS; ee 96 %
TON 20000; TOF 1000 TON 20000; TOF n.a. TON 50 000; TOF 5200
smal-scale production pilot process, > 200 kg pilot process, kg scale
Monsanto [14] ChiroTech [15] Ciba-Geigy/Solvias [16]

&
0

OOH
NHtBu
22 23 24
Rh/JOSIPHOS; ee 97 % Ru/BIPHEP; ee > 99 % Rh/PBM; ee 99 %
TON 1000; TOF 450 TON 20 000; TOF 830 TON 1600; TOF 1600
pilot process, >200 kg pilot process, > 10 kg bench-scale process
Lonza [17] Roche [12 b, 18 a] HoechstMarionRoussel
[18b, 19a]

qOYO
0
-
&ON
E/Z mixture

a COOMe

OMe
25 26 27
Ru/BIPHEP; ee 98 % Rh/DuPHOS; ee 98 % Rh/DuPHOS; ee 97 %
TON 20 000; TOF 6600 TON 20 000; TOF 5000 TON 1000; TOF n.a.
bench scale process pilot process, multi kg pilot process, > kg scale
Roche [12 b, 18 a] Roche [ l 8 a] ChiroTech [20]

and Ru/BIPHEP but other complexes are also useful. Very high TONS and TOFs
have been achieved for simple allylic alcohols, but more complex substrates and
especially a$-unsaturated acids are reduced with lower efficiency.
Homogeneous hydrogenations of tetrasubstituted olefins are still rare, even
though high ee values and reasonable activities can now be achieved. Three
commercial examples are Structures 34-36; preferred catalysts for this reaction
are Rh and Ru/JOSIPHOS and RuDuPHOS complexes, RuBIPHEP and
Rh/TRAP catalysts are also effective [ 11 a].
The hydrogenation of alkenes without “privileged” functional groups has not
been investigated systematically, probably because much more effort is required
to achieve good enantioselectivity. Successful examples are Structures 37-39.
Of special interest are the Ir phosphine dihydrooxazole (P”0XAZ) catalysts
[27], even though their functional group tolerance is relatively low.
 3.3.1.3 State-ofthe-Art and Evaluation of Catalytic Transformations 1139

28 29 30
RuIBINAP; ee 97 % Ru/BIPHEP; ee > 98 % Ru/BIPHEP; ee 98 %
TON 50 000; TOF 500 TON 100 000; TOF 10 000 TON 5000; TOF 200
production process, 300 t/y pilot process, kg scale bench scale
Takasakago [21] Roche [12 b] Roche I221

Me0&COO"
/

31
/

Ru/BINAP; ee 97 %
32
COOEt

Ru/BIPHEP; ee > 88 %
F3k33
RuAMBTP; ee 92 %
OOH

TON 3000; TOF 300 TON 1000; TOF 40 TON 20 000; TOF 6600
bench scale bench scale pilot process, > 100 kg
Takasago [21] Roche [23] Cherni [24a]

34 35 36
Rh/JOSIPHOS; ee 99 % Ru/JOSIPHOS or DuPHOS; ee >90 % Ru/BIPHEP; ee 94 %
TON 2000; TOF n.a. TON 2000; TOF 200 TON 1000; TOF ca. 400
mediurn-scale production rnediurn-scale production pilot process, > 10 kg
Lonza [25] Firmenich [26] Roche 112 b]

37 38 39
Ru/DuPHOS; ee 93 % Ru/BIPHEP; ee 94 % Ir/PAOXAZ; ee up to 98 %
TON 1000; TOF n.a. TON 1000; TOF 45 TON 200-1 000; TOF 100-500
small-scale production bench scale laboratory procedure
ChiroTech [15] Roche [12 b] Pfaltz [27]

For the enantioselective reduction of olefins, there are few alternatives to homo-
geneous hydrogenation because neither transfer hydrogenations with hydrogen
donors such as HCOOWNEt, [28] nor chiral heterogeneous catalysts [ 12 c] are
ready for larger-scale applications.
1140 3.3 Special Products

Oxidation of Olefins

Enantioselective oxidation of olefins is a very elegant way of introducing oxygen

and in some cases also nitrogen functions into molecules. The catalytic methods
with the highest industrial potential are epoxidation and dihydroxylation, and the
kinetic resolution of racemic terminal epoxides (Table 3).

Table 3. State-of-the-art for the oxidation of olefins (see structures 40-45).

Reaction ee [%I"' TON"' TOF [h-'1"' Preferred catalyst typesb'
Epoxidation of allylic alcohols 85-95 10-40 up to 20 TiRART
Epoxidation of C=C 80-95 50-2000 50-200 MdSALEN
Dihydroxylation of C=C 85-95 100-500 50-100 Os/CINCH
Kinetic resolution of epoxides 98-99 500-1000 2040 Co,Cr/SALEN
a) Typical range for suitable substrate and optimized catalyst. h' Structures 1-16.

The epoxidation of allylic alcohols (Structures 40-42) using Ti/diisopropyl tar-

trate (TiDIPT) or Tgdiethyl tartrate (TiDET) catalysts has been applied in numer-
ous multistep syntheses of bioactive compounds [ l l b, 12dl. In presence of
molecular sieves, the catalyst is effective for a variety of substituents at the
C=C bond and tolerates most functional groups with good to high ee values
but rather low activity. However, application on a larger scale is still restricted,
selected examples of which are given with Structures 40-42 (for details see
[6]). The most important is the manufacture of glycidol developed by Arc0 and
now in operation at PPG-Sipsy [4 c]. The reaction has been carefully optimized
and is run with cumyl hydroperoxide as oxidant. An interesting new development
is a Ta/DIPT attached to silica (ee values up to 97 %, TON up to 25 and TOF < 1)
[30] but its synthetic potential has not yet been explored.

40 41 42
Ti/DIPT; ee 88-90 % TVDET; ee > 98 % TVDIPT ee 96 %
TON>40;TOF<l h TON 8; TOF n.a. TON 20; TOF ca. 1
medium-scale production pilot process, > 10 kg bench scale
Arco/PPG-Sipsy [4 c] Upjohn [29] HoechstMarionRoussel [I9 a]

In the last few years, the epoxidation of unfunctionalized olefins using cheap
NaOCl as oxidizing agent has been developed industrially by Rhodia ChiRex
in collaboration with Jacobsen [31] and an example is given with Structure 43.
Mn/SALEN-type catalysts give good results for terminal and cis-substituted
olefins with ee values up to >97% with moderate to good catalytic activity
[11 c, 12el. New developments are the discovery of the beneficial effect of
pyridine N-oxides [32a] and of new types of SALEN ligands by Katsukj with
 3.3.1.3 State-of-the-Art and Evaluation of Catalytic Transformations 1 141

TONS up to 9000 [I1 c]. Of potential interest is the use of ionic liquids which
allow recycling of the catalyst (cf. Section 3.1.1.2.2) [33]. SALEN complexes
are also eminently suitable for the kinetic resolution of epoxides [12 u]; especially
promising for commercial applications is hydrolytic ring-opening using Co/
SALEN complexes [34] (42-45). @-Unsaturated ketones can be epoxidized
with hydrogen peroxide in presence of a polypeptide catalyst with ee values up
to > 98 % [35].

CI
43 44 45
epoxidation dihydroxylation hydrolytic kinetic resolution
MnISALEN; ee 88 % Os/(DHQD)2PHAL; ee 95 % Co/SALEN; k(rel) ca. 400, ee 98 + 99 %
TON > 250; TOF ca. 250 TON ca. 500; TOF 50-1 00 TON (recycl) > 1500; TOF ca. 40
small-scale process pilot process, 1 1 0 kg medium-scale process
Rhodia ChiRex [31] Rhodia ChlRex [I9 b] Rhodia ChiRex [34]

The asymmetric dihydroxylation (AD) of olefins leads to cis-diols with high to

very high ee values using Os/CINCH complexes [ 11 d, e, 12 fJ). This reaction has
also been developed by Rhodia ChiRex and is carried out on commercial scale on
request [3 11. K3Fe(CN)6-K2C03, the oxidant used in the commercially available
AD mixes is problematic on a larger scale. Recently, it has been shown that oxy-
gen can be used instead, which is more promising for industrial applications [36].
Allylic oxidation [ 12 g], aminohydroxylation [ 11 el, and aziridination [ 12 h] are
not yet mature for technical use, even though in specific cases very high ee values
have been achieved.

Miscellaneous Addition Reactions to C=C Groups

Addition reactions to olefins can be used both for the construction and for
the functionalization of molecules. Accordingly, chiral catalysts have been devel-
oped for many different types of reactions, often with very high enantioselectiv-
ity. Unfortunately, most either have a narrow synthetic scope or are not yet
developed for immediate industrial application due to insufficient activities and/
or productivities. These reactions include hydrocarbonylation [ 1 1 fl, hydrosilyla-
tion [12 i], hydroboration 112j], hydrocyanation [12 k], Michael addition 111 g,
12 1, 12 m], Diels-Alder reaction [ 11 h, 12 n] and the insertion of carbenes in
C-H bonds [ 11 i, 12 p, 12 q, 381. Cyclopropanation [ 11 i, 12 p, 12 q] and the iso-
merization of allylamines [ 12 s] are already used commercially for the manufac-
ture of Cilastatin (one of the first industrial processes) [12r], and citronellol
and menthol (presently the second largest enantioselective process) [ 12t] respec-
tively.
1142 3.3 Special Products

3.3.1.3.4 Addition to C=O Groups

Reduction of Ketones

The hydrogenation of ketones using Rh and Ru diphosphine catalysts is the most

versatile and efficient method for the synthesis of a large variety of chiral alcohols
(see Structures 46-54 [ 11 a, 12 v]). While Rh diphosphine catalysts are often sub-
strate-specific, several RuBIAR-type catalysts have a fairly broad scope. These
catalysts are effective for the hydrogenation of functionalized ketones such as
p-keto esters and 2-amino and 2-hydroxy ketones with high ee values and often
reasonable TONS and TOFs. Due to the low activity of homogeneous catalysts,
a-keto esters are still preferentially hydrogenated with heterogeneous cinchona-
modified Pt catalysts [ 12 c]. New Ru/BINAP/chiral diamine catalysts have been
developed which effectively hydrogenate aryl ketones (TON up to 2 400 000)
and are also suitable for aJ-unsaturated ketones [ 11 a]. Unfunctionalized alkyl
ketones are still a problem: ee values > 9 0 % have been reported for only a
few rare cases [ 11 a]. Structures 46-54 are a selection of ketones for which indus-
trial processes have been developed. Also here, tolerance for functional groups
such as pyridines and C-Cl and C=C bonds is important.
Other reducing agents are of interest, especially for small-scale reductions and/
or when no hydrogenation facilities are available. The reduction with BH3 adducts
in presence of catalytic amounts of amino alcohols [ 12 zc] has already found some
industrial applications, especially by PPG-Sipsy and Rhodia ChiRex (see Struc-
tures 55-57). Transfer hydrogenation [ 11 a] using isopropanol as reducing agent
shows some promise for the reduction of aryl ketones because very efficient Rh
and Ru transfer hydrogenation catalysts with new bidentate NAN, NAO and PAN
ligands have been developed in the last few years. Hydrosilylation [ 11 q] is of less

Table 4. State-of-the-art for the reduction of functionalized ketones (see Structures 4657).
~~~ ~ ~

Substartel ee [%In)TON"' TOF [h-'1"' Preferred catalyst types"

Reducing agent
RCOCHRCOX 90-95 5000-50 000 2000-1 0 000 R W I A R
(X = OH, OR, R)/H2
RCOCOOWH2 90-95 1000-SO00 10-500 RNNOP, RuBIAR,
various
RCOCHRW2 90-95 1000-5000 100-500 RuBIAR, RhRERRO,
X = NHR, OH RNNOP, Rh/DIOP
ArCOR/H* 90-95 5000-20 000 500-10 000 RuBIAR-diamine
ArCOR/R,CHOH 85-95 1000-5000 loo-soo OAN, NAN, PAN
KetoneBH, 85-95 20-50 5-1 0 OXABOR
a) Typical range for suitable substrate and optimized catalyst. Structures 1-16.
 3.3.1.3 State-ofthe-Art and Evaluation of Catalytic Transformations 1143

&COOEt +coo"
/

46 47 48
Pt-AI2O3/HCd; ee 82-94 % Ru/BIPHEP; ee 93 % Ru/BIPHEP; ee 87 %
TON 4000; TOF 1000 TON 2000; TOF 100 TON 2000; TOF 90
small-scale production bench scale bench scale
Ciba-Geigy/Solvias [38] Roche [23] Roche [23]

CI&OOEt JY COOMe
NHCOPh

49 50 51
Rh/PPM; ee 91 % RuTTMBTP; ee 97 % Ru/BINAP; ee 97 %, de > 94 %
TON 200 000; TOF 15 000 TON 20 000; TOF 15 000 TON 1000; TOF 200
pilot process, > 100 kg pilot process, > 100 kg large-scale production
Roche [12 b] Chemi [24a] Takasago [21]

CF3
52 53 54
Ru/BINAP; ee 94 % Rh/BPPFOH; ee 97 % Ru/BIPHEP; ee 92 %
TON 2000; TOF 300 TON 2000; TOF 125 TON 6400; TOF 320
medium-scale production pilot process, > 10 kg bench scale
Takasago [21] Ciba-Geigy/Solvias [32 b] Roche [23]

BnO dc..NO2 R
0

X = CI, Br

55 56 57
OXABOR/BH3 . Me2S OXABOR/BH3 . Me2S OXABOR/BH, . Me,S
ee 9 4 % ee 99 % ee 92 %
TON 17; TOF n.a. TON 20-30; TOF ma. TON 20; TOF ca. 5
pilot process, multi kg small-scale production pilot process, 50 kg
Sepracor (391 PPG-Sipsy [40] Lonza [41]

interest since silanes are very expensive. Activities and productivities for some of
these methods are often low and for large-scale processes the disposal of wastes
from the stoichiometric reducing agent could be problematic.
1144 3.3 Special Products

Miscellaneous Addition Reactions to C=O Groups

Addition reactions to carbonyl groups are very important in synthetic metho-

dology. Even though a wealth of catalysts with high enantioselectivity have been
developed in recent years (Table 5), there are only a few commercial applications.
Most have low to medium catalytic activity and productivity. The aldol reaction
[ l l k, 11 1, 12 w], ene reaction [11 m, 12 x] and hetero Diels-Alder reaction
[ l l h, 1201 are catalyzed by early transition metal and lanthanide complexes.
The addition reaction of ZnR2 and similar reagents to aldehydes [ 12 y] in presence
of catalytic amounts of amino alcohols or early transition metal complexes has
few synthetic applications. Industrial syntheses have been reported for the gold-
aldol reaction [11 k, 421 as an interesting approach to b-hydroxy amino acids and
for the nitro-aldol reaction [ 12 z, 431 (eqs. (1) and (2)).

RCHO
+--+ RHcooEt
GN-CH,COOEt O+N
+ cis isomer
gold-aldol; Au/BPPFA
ee 85-90 %, translcis 20;
TON 100; TOF 5
bench scale, kg scale
Ciba-Geigy [42]

MeNO, matched case

nitro-aldol; LaLi/BINOL complex
ee 96 %, de 98 %; TON 30; TOF < 1
small scale process
Kaneka [43]

Table 5. State-of-the-art for addition reactions to C=O (see eqs. (1) and ( 2 ) ) .
Reaction ee [%I"' TON' TOF [h-'I"' Preferred catalyst typesb'
Aldol reaction 90-95 5-20 1-10 LnBINOL, AgBIAR,
Cu/OXAZ
Ene reaction 90-95 5-20 1-10 TiBINOL
Addition of MR to RCHO 90-95 5-100 1-20 N"O,O"O, NAN
Hetero Diels-Alder 85.95 10-50 2-10 Cu/OXAZ, NAO,OAO,NAN
a' Typical range for suitable substrate and optimized catalyst. b, Structures 1-16.
 3.3.1.3 State-ofthe-Art and Evaluation of Catalytic Transformations 1145

3.3.1.3.5 Reduction of and Addition to C=N Groups

Although chiral amines are important intermediates for biologically active com-
pounds, the asymmetric hydrogenation of C=N has been investigated less system-
atically than that of C=C and C=O groups [ 11 a, 12 za]. In recent years various
Rh and Ir diphosphine complexes were developed with reasonable enantioselec-
tivities. Unfortunately, Rh complexes often have relatively low catalyst activities
and productivities and Ir complexes tend to deactivate. The hydrogenation of acyl
hydrazones with Rh/DUPHOS with ee values up to 95 % and a Ti/EBTHI catalyst
for cyclic imines (ee > 98 %) have some synthetic potential, but the Ti catalysts
unfortunately have a low functional group tolerance and very poor catalytic activ-
ity. Good to high enantioselectivities can be achieved with transfer hydrogenation
and BH3 reduction with medium to very low catalyst activities. With the exception
of Structures 58-60, the metolachlor process carried out by Ciba-GeigyByngenta
(with a volume of > 10 000 t/y the largest known production process) [44], and a
pilot process developed by Lonza [25], no industrial applications are known.
Recently, the first example of a reductive alkylation reaction with high TON
and TOF values has been described, an interesting variant from an industrial
point of view [45].

cH30A WN. H3P0,

(MeO),PHO
+

R, R = Me, Et, (CH,),

58
hydrogenation
WJOSIPHOS; ee 80 %
TON 2 000 000; TOF 400 000
very large-scale production
Ciba-Geigy/Syngenta/Solvias [44]
59 60
hydrogenation hydrophosphonylation
Ir/JOSIPHOS; ee 90 % YbK/BINOL; ee 92-96 %
TON 1500; TOF ma. TON 20; TOF < 1
pilot process, > 100 kg small-scale production
Lonza (Solvias) [25] Hokko Chemical Co. [46]

Several addition reactions to C=N groups have been developed in recent years
with a high synthetic potential but with no commercial use so far [12zb]. The
addition reaction of (Me0)2PH0 to cyclic imines (58-60), an interesting method
for the preparation of a-amino phosphonic acids, seems to be an exception [46].
While ee values of the heterobimetallic catalyst (cf. Section 3.1.5) are very high,
TON and TOF values are relatively low.

3.3.1.3.6 Miscellaneous Transformations

Even though most of the reactions in Table 6 form new C-C bonds asymmetri-
cally, none has been developed to really technical maturity, major problems
being (as usual) catalyst activities and productivities, and possibly also the syn-
thetic scope. The NiPN-catalyzed cross-coupling reactions [ 11 r] tolerate only
1146 3.3 Special Products

Table 6. State-of-the-art for miscellaneous transformations (see Structures 61 and 62).

Reaction ee [%I"' TON") TOF [h-'Ia) Preferred catalyst types"
Cross-coupling 80-90 500-200 2-20 NiPN
Allylic substitution 85-95 50-1000 20-100 PdPNNP, P d P O X A Z ,
PdOXAZOL, various
Heck 80-95 10-100 1-10 PdBIAR, P d P O X A Z
Sulfide oxidation 80-95 2-20 1-5 TiiTART
a) Typical range for suitable substrate and optimized catalyst. b, Structures 1-16.

a few functional groups. Nucleophilic allylic substitution reactions [ 11 n] with

C- and N-nucleophiles catalyzed by Pd/PAP, Pd/PAN, and Pd/NAN complexes
have recently been applied not just in model studies but also in synthetic applica-
tions. The asymmetric Heck reaction is still in an exploratory phase even though
some syntheses of natural products have been reported [ 11 01. The oxidation of
aromatic sulfides [ 11 p] using Ti/TART catalysts exhibits good enantioselectivities
but usually very low catalytic activities; nevertheless two industrial applications
are on record (Structures 61 and 62). One of them is being used to make the chiral
switch for one of the best selling antiulcer drugs [24 b, 471.

61 62
TIITART; ee 92-93 % TIITART; ee 98 %
TON 3-4; TOF 3-4 TON n.a.; TOF ma.
medium-scale production pilot process, < 100 kg
AstraZeneca [24 b, 471 Lonza [I 71

3.3.1.4 Conclusions and Prospects

Since the publication of the first edition of this book in 1996, the industrial appli-
cation of enantioselective homogeneous catalysts has made significant progress.
The list of processes suitable for the manufacture of enantiomerically enriched
compounds is compiled in [6]. Few have actually been implemented as production
processes and run on a regular basis but there is every reason to assume that this
technology is here to stay. The number of commercial applications will increase in
the near future because development chemists who realize technical processes will
be more aware of the potential of enantioselective catalysis. More and more spe-
cialized technology companies such as Solvias, ChiRex, or ChiroTech are devel-
 References 1147

oping the know-how and experience to use enantioselective catalytic processes

and to produce technical quantities of the chiral ligands. Jacobsen [ 12 zd]
predicted the following trends for the next few years: design of new ligands
(e. g., Section 3. I. lo), catalysts, and transformations with good synthetic poten-
tial, in many instances by applying combinatorial approaches (cf. Section
3.1.3); the development of more practical catalyst systems, i. e., with higher activ-
ity, productivity, and robustness in part via high-troughput experimentation; and,
finally, a deeper understanding of the underlying mechanisms that will help to
make catalyst design more rational (cf. Sections 3.1.3 and 3.1.4).

References
[ 1] For periodic updates on chiral pharmaceuticals, see: S. T. Stinson, Chem. Eng. News
1998, September 21, 83; S. T. Stinson, Chem. Eng. News 1999, November 22, S. T. Stin-
son, Chem. Eng. News 2001, May 14, 45.
[2] G. M. Ramos Tombo, H. U. Blaser, in Pesticide Chemistry and Bioscience (Eds.: G. T.
Brooks, T. R. Roberts), Royal Society of Chemistry, Cambridge, 1999, p. 33 and refer-
ences cited therein.
[3] J. Crosby, in Chirality in Industry I (Eds.: A. N. Collins, G. N. Sheldrake, J. Crosby),
John Wiley, Chichester, 1992, p. 1 .
[4] Chirality in Industry II (Eds.: A.N. Collins, G.N. Sheldrake, J. Crosby), John Wiley,
Chichester, 1997: (a) for an overview, see A. Bruggink, p. 81; (b) D. Pauluth, A.E.F.
Wachter, p. 263; (c) W. P. Shum, M. J. Cannarsa, p. 363; (d) B. A. Astleford, L. 0.
Weigel, p. 99; (e) J. C. Caille, M . Bulliard, B. Laboue, p. 391.
[5] J. M. Keith, J. F. Larrow, E. N. Jacobsen, Adv. Synth. Catal. 2001, 343, 5.
[6] For a recent compilation of known industrial processes see: H.U. Blaser, F. Spindler,
M. Studer, Appl. Catal. A: General 2001, 221, 119.
[7] R. A. Sheldon, Chirotechnology, Marcel Decker, New York, 1993.
[8] R. Noyori, Chemtech 1992, 22, 366.
[9] E. Polastro, in Chiral Reaction in Heterogeneous Catalysis (Eds.: G. Jannes, V. Dubois),
Plenum Press , New York, 1995, p. 5.
[lo] Asymmetric Synthesis Vol. 5 (Ed.: J. D. Morrison), Academic Press, New York, 1985.
[ l I] Catalytic Asymmetric Synthesis (Ed.: I. Ojima), Wiley-VCH, Weinheim, 2000: (a) T. Oh-
kuma, M. Kitamura, R. Noyori, p. 1; (b) R. A. Johnson, K. B. Sharpless, p. 231; (c) T.
Katsuki, p. 287; (d) R. A. Johnson, K. B. Sharpless, p. 357; (e) C. Bolm, J. P. Hildebrand,
K. Muniz, p. 399; (f) K. Nozaki, I. Ojima, p. 429; (g) M. Kanai, M. Shibasaki, p. 569; (h)
K. Maruoka, p. 467; (i) M.P. Doyle, p. 191; (k) M. Sawamura, Y. Ito, p. 493; (1) E.M.
Carreira, p. 513; (m) M. Ogasawara, T. Hayashi, p. 651; (n) B.M. Trost, C. Lee, p. 593;
(0) Y. Donde, L. E. Overmann, p. 675; (p) H. B. Kagan, p. 327; (9) K. Mikami, T. Nakai,
p. 543; (r) H. Nishiyama, K. Itoh, p. 111; and references cited in these reviews.
1121 Comprehensive Asymmetric Catalysis (Eds.: E. N. Jacobsen, H. Yamamoto, A. Pfaltz),
Springer, Berlin, 1999: (a) J.M. Brown, p. 121; (b) R. Schmid, M. Scalone, p. 1439;
(c) H.U. Blaser, M. Studer, p. 1353; (d) T. Katsuki, p. 621; (e) E.N. Jacobsen, M.H.
Wu, p. 649; (0I. E. Marko, J. S. Svendsen, p. 713; (g) T. Katsuki, p. 791; (h) E.N. Ja-
cobsen, p. 607; (i) T. Hayashi, p. 319; (j)T. Hayashi, p. 351; (k) T. V. RajanBabu, A. L.
Casalnuovo, p. 367; (1) K. Tomioka, Y. Nagaoka, p. 1105; (m) M. Yamaguchi, p. 1121;
(n) D. A. Evans, J. S. Johnson, p. 1177; (0) T.Ooi, K. Maruoka, p. 1237; (p) A. Pfaltz,
1148 3.3 Special Products

p. 513; (9) K. M. Lydon, M. A. McKervey, p. 539; (r) T. Aratani, p. 1451; (s) S. Akuta-
gawa, p. 813; (t) S. Akutagawa, p. 1461; (u) E. Jacobsen, M. H. Wu, p. 1309; (v) T. Oh-
kuma, R. Noyori, p. 199; w); E. M. Carreira, p. 997; (x) K. Mikami, M. Terada, p. 1143;
(y) K. Soai, T. Shibata, p. 911; (z) M. Shibasaki, H. Groger, p. 1075; (za) H. U. Blaser, F.
Spindler, p. 247; (zb) S. E. Denmark, 0.J.-C. Nicaise, p. 923; (zc) S. Itsuno, p. 289; (zd)
E. N. Jacobsen, p. 1473; and references cited in these reviews.
[13] A. S. Bommarius, M. Schwarm, K. Drauz, Chimia 2001, 55, 50.
[14] W.S. Knowles, Chem. Ind. (Dekker) 1996, 68, 141; W.S. Knowles, Acc. Chem. Res.
1983, 16, 106 and J. Chem. Ed. 1986, 63, 222.
[ 151 M. J. Burk (ChiroTech), personal communication.
[ 161 H. U. Blaser, F. Spindler, Topics Catal. 1997, 4, 275.
[I71 W. Brieden, Proc. ChiraSource ‘99 Symposium 1999, The Catalyst Group, Spring
House, USA, 1999; W. Brieden (Lonza AG), personal communication.
[18] Proc. ChiraTech ‘97 Symposium 1997, The Catalyst Group, Spring House, USA, 1997:
(a) M. Scalone, R. Schmid, E.A. Broger, W. Burkart, M. Cereghetti, Y. Crameri,
J. Foricher, M. Henning, F. Kienzle, F. Montavon, G. Schoettel, D. Tesauro, S. Wang,
R. Zell, U. Zutter; (b) H. Jendralla.
[ 191 Proc. ChiraTech ‘96 Symposium 1996, The Catalyst Group, Spring House, USA, 1996:
(a) G. Beck; (b) A. A. Smith.
[20] M. J. Burk, F. Bienewald, M. Harris, A. Zanotti-Gerosa, Angew. Chem. Int. Ed. 1998,
37, 1931.
1211 S. Akutagawa, Appl. Catal. 1995, 128, 171; H. Kumobayashi, Recl. Trav. Chim. Pays-
Bas 1996, 115, 201.
[22] E.A. Broger (Roche), Book of Abstracts of EuropaCat I 1993, and personal com-
munication.
[23] R. Schmid, E. A. Broger, Proc. Chiral Europe ‘94 Symposium, Spring Innovations,
Stockport, UK, 1994, p. 79.
[24] Proc. ChiraSource 2000 Symposium, 2000, The Catalyst Group, Spring House, USA,
2000: (a) T. Benincori, S. Rizzo, F. Sannicolo, 0. Piccolo; (b) H. J. Federsel.
[25] R. Imwinkelried, Chimia 1997, 51, 300.
[261 V. Rautenstrauch Proc. Int. Symposium on Chirality, 1999, Spring Innovations, Stock-
port, UK, 1999, p. 204.
[27] A. Lightfoot, P. Schnider, A. Pfaltz, Angew. Chem., Int. Ed. 1998, 37, 2897.
[28] W. Leitner, J.M. Brown, H. Brunner, J. Am. Chem. Soc. 1993, 115, 152; M. Saburi,
M. Ogasawara, T. Takahashi,Y. Uchida, Tetrahedron Lett. 1992, 33, 5783; and references
therein.
[29] B. K. Sharpless, Janssen Chem. Acta 1988, 6 , 3.
[30] D. Meunier, A. Piechaczyk, A. de Mallmann, J.-M. Basset, Angew. Chem. 1999, 111,
3738.
[311 See information given in www.chirex.com (technology).
[32] Process Chemistry in the Pharmaceutical Industry (Ed.: K. G. Gadamasetti), Marcel
Dekker, New York, 1999: (a) C. H. Senanayake, E. N. Jacobsen, p. 347; (b) H. U. Blaser,
R. Gamboni, G. Rihs, G. Sedelmeier, E. Schaub, E. Schmidt, B. Schmitz, F. Spindler,
Hj. Wetter, p. 189.
[33] C.E. Song, E.J. Roh, Chem. Commun. 2000, 837.
[34] J.M. Keith, J. F. Larrow, E.N. Jacobsen, Adv. Synth. Catal. 2001, I , 5.
[35] M. Porter, J. Skidmore, Chem. Commun. 2000, 1215 and references cited therein.
[36] C. Dobler, G. M. Mehltretter, U. Sundermeier, M. Beller, J. Am. Chem. SOC.2000, 122,
10289.
[37] M. P. Doyle, M. N. Protopopova, Proc. Chiral USA ‘97 Symposium, Spring Innovations,
Stockport, UK, 1997, p. 11.
 3.3.2.1 Introduction 1149

1381 H. U. Blaser, M. Studer, Chirality 1999, 11, 459.

[39] R. Hett, Q. K. Fang, Y. Gao, S. A. Wald, C. H. Senanayake, Org. Proc. Res. Dev.1998,
2, 96; A. K. Ghosh, S. Fidanze, C. H. Senanayake, Synthesis 1998, 937.
[40] J. C. Caille (PPG-Sipsy), personal communication.
[41] W. Brieden, WO 9616971 (1994) (assigned to Lonza AG) and W. Brieden (Lonza),
personal communication.
[42] A. Togni, S. D. Pastor, G. Rihs, Helv. Chim. Actu 1989, 72, 1471.
[43] H. Sasai, W.-S. Kim, T. Suzuki, M. Shibasaki, Tetrahedron Lett. 1994, 35, 6123;
M. Shibasaki (University of Tokyo), personal communication.
[44] H. U. Blaser, H. P. Buser, K. Coers, R. Hanreich, H. P. Jalett, E. Jelsch, B. Pugin, H. D.
Schneider, F. Spindler, A. Wegmann, Chimiu 1999, 53, 275.
[45] H.U Blaser, H. P. Buser, H. P. Jalett, B. Pugin, F. Spindler, Synlett 1999, 867.
[46] H. Groger, Y. Saida, H. Sasai, K. Yamaguchi, J. Martens, M. Shibasaki, J. Am.
Chem. Soc. 1998, 120, 3089; M. Shibasaki (University of Tokyo), personal communi-
cation.
[47] H. Cotton, T. Elebring, M. Larsson, L. Li, H. Sorensen, S. von Unge, Tetru-
hedron: Asymmetry 2000, 11, 8319; H. J. Federsel (AstraZeneca), personal communi-
cation.

3.3.2 Diols via Catalytic Dihydroxylation

Matthias Bellel; K. Barry Sharpless

3.3.2.1 Introduction
The oxidative functionalization of olefins is of major importance for both organic
synthesis and the industrial production of bulk and fine chemicals. Among the dif-
ferent oxidation products of olefins, 1,2-diols are used in a wide variety of appli-
cations. Ethylene glycol and propylene glycol are produced on a multi-million ton
scale per annum, due to their importance as polyester monomers and anti-freeze
agents [ 11. A number of 1,2-diols such as 2,3-dimethyl-2,3-butanediol, 1,2-octa-
nediol, 1,2-hexanediol, 1,2-pentanediol, and 1,2- and 2,3-butanediol are of inter-
est for the fine chemicals industry. In addition, chiral 1,2-diols are employed as
intermediates for pharmaceuticals and agrochemicals. At present 1,2-diols, e. g.,
2,3-dimethyl-2,3-butanediol, 1,2-pentanediol and higher nonfunctionalized gly-
cols obtained thanks to the availability of cheap terminal olefins (SHOP process;
cf. Section 2.3.1.3), have so far been manufactured industrially by the reaction of
alkenes with organic peracids via the corresponding epoxides [ 11. Usually perfor-
mic acid or peracetic acid produced in situ by mixing hydrogen peroxide with the
carboxylic acid have been employed as oxidants.
Besides stoichiometric epoxidation and subsequent hydrolysis to diols, metal-
catalyzed methods for converting olefins to glycols are also known in the litera-
ture. The classical method utilizes hydrogen peroxide in the presence of catalytic
amounts of acidic metal oxides (Milas reagents) [2]. Typically, strong oxidants
such as osmium [3] and ruthenium tetroxides [4], permanganate [ 5 ] , and chro-
 Applied Homogeneous Catalysis with Organometallic Compounds
Edited by B. Cornils and W. A. Herrmann
Copyright 0 Wiley-VCH Verlag GmbH, D-69469 Weinheim, 2002

3.3.2.1 Introduction 1149

1381 H. U. Blaser, M. Studer, Chirality 1999, 11, 459.

[39] R. Hett, Q. K. Fang, Y. Gao, S. A. Wald, C. H. Senanayake, Org. Proc. Res. Dev.1998,
2, 96; A. K. Ghosh, S. Fidanze, C. H. Senanayake, Synthesis 1998, 937.
[40] J. C. Caille (PPG-Sipsy), personal communication.
[41] W. Brieden, WO 9616971 (1994) (assigned to Lonza AG) and W. Brieden (Lonza),
personal communication.
[42] A. Togni, S. D. Pastor, G. Rihs, Helv. Chim. Actu 1989, 72, 1471.
[43] H. Sasai, W.-S. Kim, T. Suzuki, M. Shibasaki, Tetrahedron Lett. 1994, 35, 6123;
M. Shibasaki (University of Tokyo), personal communication.
[44] H. U. Blaser, H. P. Buser, K. Coers, R. Hanreich, H. P. Jalett, E. Jelsch, B. Pugin, H. D.
Schneider, F. Spindler, A. Wegmann, Chimiu 1999, 53, 275.
[45] H.U Blaser, H. P. Buser, H. P. Jalett, B. Pugin, F. Spindler, Synlett 1999, 867.
[46] H. Groger, Y. Saida, H. Sasai, K. Yamaguchi, J. Martens, M. Shibasaki, J. Am.
Chem. Soc. 1998, 120, 3089; M. Shibasaki (University of Tokyo), personal communi-
cation.
[47] H. Cotton, T. Elebring, M. Larsson, L. Li, H. Sorensen, S. von Unge, Tetru-
hedron: Asymmetry 2000, 11, 8319; H. J. Federsel (AstraZeneca), personal communi-
cation.

3.3.2 Diols via Catalytic Dihydroxylation

Matthias Bellel; K. Barry Sharpless

3.3.2.1 Introduction
The oxidative functionalization of olefins is of major importance for both organic
synthesis and the industrial production of bulk and fine chemicals. Among the dif-
ferent oxidation products of olefins, 1,2-diols are used in a wide variety of appli-
cations. Ethylene glycol and propylene glycol are produced on a multi-million ton
scale per annum, due to their importance as polyester monomers and anti-freeze
agents [ 11. A number of 1,2-diols such as 2,3-dimethyl-2,3-butanediol, 1,2-octa-
nediol, 1,2-hexanediol, 1,2-pentanediol, and 1,2- and 2,3-butanediol are of inter-
est for the fine chemicals industry. In addition, chiral 1,2-diols are employed as
intermediates for pharmaceuticals and agrochemicals. At present 1,2-diols, e. g.,
2,3-dimethyl-2,3-butanediol, 1,2-pentanediol and higher nonfunctionalized gly-
cols obtained thanks to the availability of cheap terminal olefins (SHOP process;
cf. Section 2.3.1.3), have so far been manufactured industrially by the reaction of
alkenes with organic peracids via the corresponding epoxides [ 11. Usually perfor-
mic acid or peracetic acid produced in situ by mixing hydrogen peroxide with the
carboxylic acid have been employed as oxidants.
Besides stoichiometric epoxidation and subsequent hydrolysis to diols, metal-
catalyzed methods for converting olefins to glycols are also known in the litera-
ture. The classical method utilizes hydrogen peroxide in the presence of catalytic
amounts of acidic metal oxides (Milas reagents) [2]. Typically, strong oxidants
such as osmium [3] and ruthenium tetroxides [4], permanganate [ 5 ] , and chro-
1150 3.3 Special Products

- Hxq
H20 + 0
’ ‘OH

X = 0 , NR; M = Os, Ru, Mn

Scheme 1. General representation of dihydroxylation and related reactions.

mium(V1) are used as oxometals. The first three reagents are considered to effect
directly the addition of two hydroxy groups to double bonds. The intermediate
cyclic esters could be either hydrolyzed to glycols or undergo C-C bond cleavage
to carbonyl compounds. A simplified representation of dihydroxylation and
related oxyamination reactions is shown in Scheme 1.
As an oxometal component, osmium tetroxide is the most reliable reagent on
the laboratory scale to produce cis-diols. Ruthenium tetroxide in the presence
of NaI04 effects oxidative cleavage of olefins [4], but has been successfully
employed for so-called lightning dihydroxylation reactions using a two-phase
medium [6].
Because most olefins are prochiral starting materials, the dihydroxylation reac-
tion creates one or two new stereogenic centers in the products. Since the discov-
ery of the first stoichiometric asymmetric dihydroxylations [7], catalytic versions
with considerable improvements in both scope and enantioselectivity have been
developed [8]. From the standpoint of general applicability, scope, and limitations,
the osmium-catalyzed asymmetric dihydroxylation (AD) of alkenes has reached a
level of effectiveness which is unique among asymmetric catalytic methods. As
there are recent reviews in this field [9], this section is primarily oriented toward
a summary of aspects of fundamental understanding and interesting practical
application of catalytic dihydroxylations.

3.3.2.2 History and General Features of

Osmium Catalyzed Dihydroxylation Reactions
The dihydroxylation of olefins with osmium compounds has been known since
the first work of Philipps in 1894 [lo] and was also pioneered by Criegee in
the 1930s using OsO, stoichiometrically [Ill. The chief drawback of using stoi-
chiometric amounts of expensive Os04 has been overcome by inclusion of a co-
oxidant in the reaction which reoxidizes the osmium(V1) species to the osmium
tetroxide oxidation level. This allows for the use of the metal in catalytic amounts.
Historically, chlorates [ 121 and hydrogen peroxide in t-butanol [ 131 were first ap-
plied as co-oxidants. With hydrogen peroxide the reaction is reported to proceed
via formation of peroxoosmic acid, H,OsO,, which causes cleavage of inter-
mediate diols to carbonyl compounds. However, Backvall and co-workers were
 3.3.2.2 History and General Features 1 151

recently able to improve the H202 reoxidation process significantly by using

N-methylmorpholine together with flavin as co-catalysts in the presence of
hydrogen peroxide [58].
Other reoxidants which minimize overoxidation are t-butyl hydroperoxide in
the presence of Et4NOH [4], tertiary amine oxides, and most importantly N-
methylmorpholine N-oxide (NMO) (Upjohn process) [ 141, although for tri- and
particularly tetrasubstituted alkenes as substrates, trimethylaminoxide is superior
to NMO [ 14 c]. The introduction of potassium hexacyanoferrate(II1) in the pre-
sence of potassium carbonate [ 151 substantially improved the selectivities in chiral
dihydroxylations [ 161, although it was first reported as a co-oxidant in 1975 [ 171.
Industrial efforts led to an electrochemical oxidation of potassium ferrocyanide to
ferricyanide in order to use electricity as the actual co-oxidant [18].
Oxygen is the most economical as well as the most environmentally friendly
oxidation reagent known. However until very recently only a few investigations
using O2 in dihydroxylation reactions had been carried out. Initially it was demon-
strated by several groups that in the presence of Os04 and oxygen mainly non-
selective oxidation reactions take place [19]. Krief et al. successfully designed a
reaction system consisting of oxygen with catalytic amounts of Os04 and of
selenides for the dihydroxylation of a-methylstyrene under irradiation with visible
light [20]. More recently Beller and co-workers reported that the 0s-catalyzed
dihydroxylation of aliphatic and aromatic olefins proceeds efficiently in the pre-
sence of dioxygen at ambient conditions [59]. The new dihydroxylation procedure
constitutes a significant advance compared with other reoxidation procedures. The
yield of the diol remains good to very good (87-96 %), independently of the oxi-
dant used. The dihydroxylation process with oxygen is clearly the most ecologi-
cally favorable procedure, when the production of waste from a stoichiometric
reoxidant is considered. In the presence of K3[Fe(CN),J approximately 8.1 kg
of iron salts per kg of product are formed. However, in the case of the Krief or
Backvall procedure significant amounts of by-products also arise due to the
large amounts of co-catalysts and co-oxidants used. It should be noted that only
salts and by-products formed from the oxidant have been included in the calcula-
tion. Other waste products have not been considered.
With regard to the price and safety issues it is important to note that it is also
possible to use air rather than pure oxygen gas as stoichiometric oxidant [60].
Considering the chemoselectivity of the process and that olefins are the starting
materials, no other known organic reaction combines such enormous scope with
such high selectivity. Although some electron-deficient olefins have long been
described as “bad” substrates, Henmann et al. demonstrated that even perfluori-
nated olefins could be efficiently dihydroxylated [2 11.
In general, dihydroxylations are carried out in mixtures of aqueous and organic
solvents, although catalytic osmylations have been performed under virtually an-
hydrous conditions in toluene [21] or dichloromethane [22]. In combination with
water, organic solvents such as acetone, t-butanol, methyl t-butyl ether, and others
are employed.
It had already been recognized by Criegee that addition of certain ligands, e. g.,
amines, greatly accelerates the rate of formation of osmium(V1) ester complexes
1152 3.3 Special Products

[23]. This, together with the finding of Hentges and Sharpless [7] that stoichio-
metric amounts of chiral ligands derived from cinchona alkaloids can transfer
chirality from the catalyst to olefins, has opened the door for the development
of catalytic asymmetric methods. An important advance regarding the reuse of
the expensive osmium catalyst has been reported by Jacobs et al. [61]. They
immobilized Os04 elegantly to a tetrasubstituted olefin which is covalently linked
to a silica support. The Osv' monoglycolate complex is then oxidized to a Osv"'
glycolate complex which is able to react with additional olefins. Due to the
much slower hydrolysis of the tetrasubstituted glycolate, the catalyst can be
recycled.
An interesting offshoot of the work on osmium-catalyzed dihydroxylations is
vicinal hydroxyamination [24]. Here, imido analogs of Os04 react with olefins
to produce P-aminoalcohols by a cis-addition process. The oxyamination reaction
can be made catalytic in Os04 by employing chloramine salts of arylsulfonamides
(ArS02NC1Na) or carbamates.

3.3.2.3 Mechanism of Osmium-Catalyzed Dihydroxylations

In the last decade the mechanism of the osmium-catalyzed dihydroxylation was
discussed extensively. Originally, Boseken [2S] suggested that the reaction
proceeds by a thermally allowed concerted [3 + 21 cycloaddition leading directly
to the monoglycolate ester, while Sharpless et al. [26] proposed an alternative
reversible [2 + 21 cycloaddition leading to a metallaoxetane intermediate which
undergoes irreversible reductive insertionof the 0s-C bond into an Os=O bond
leading to the monoglycolate ester (Scheme 2).

I roi

second cycle first cycle

Scheme 2. General mechanism of osmium-catalyzed dihydroxylation.

 3.3.2.4 Scope and Limitation of Asymmetric Dihydroxylation 1153

Recent theoretical investigations clearly favor the [3 + 21 mechanism [27, 621.

The calculation of the respective transition states using DFT methods show signif-
icantly lower activation barriers for the [3 + 21 addition compared with the [2 + 21
reaction path. Subsequently, these results were also supported by the theoretical and
experimental determination of the kinetic isotope effect of the AD reaction [28].
Depending on the reaction media and the substrates, the rate-determining step
in catalytic dihydroxylations can be either the attack of the Os04 on the olefin
[28], or oxidation of the Osv' glycolate complex to the 0s""' complex [29], or
in cases of bulky olefins the hydrolysis of the osmium glycolate complexes.
The problem of hydrolysis could be overcome by the addition of methyl sulfona-
mide [9 b, 301 or sometimes tetraethylammonium acetate. In the presence of one
equivalent of CH3S02NH2dihydroxylations could be as much as 50 times faster.
Alternatively, the hydrolysis of sterically hindered osmium glycolates can be
performed more efficiently under controlled pH conditions. By using buffered
solutions (pH 11-13) or by applying an autotitrator the dihydroxylation can be
significantly speeded up [63].
Under homogeneous conditions with the co-oxidant in the same phase as the
intermediate osmium(V1) glycolate, two competitive catalytic cycles can operate,
involving either direct hydrolysis of the reoxidized osmate(VII1)-glycolate com-
plex or its reaction with a second olefin to give an osmium(V1) bisglycolate
("second cycle") [313. For enantioselective dihydroxylations the low selectivity-
generating second cycle could be completely suppressed by the use of
K,Fe(CN)6 in the presence of K2C03 [ 161.
Of particular mechanistic interest in AD is the question of how chirality is
transmitted from the chiral alkaloid ligand to the Osvl glycolate complex [33].

3.3.2.4 Scope and Limitation of Asymmetric

Dihydroxy lation
The enormous synthetic utility of AD depends on the one hand on the broad
applicability of the osmium-catalyzed dihydroxylation for nearly every class of
olefins, and on the other hand on the high selectivities which can be reached
with optimized catalyst-ligand systems.
In the past it has been shown that AD is responsive to substantial enantioselec-
tivity improvement through ligand variation. Chiral auxiliaries used for effecting
asymmetric dihydroxylation are mainly cinchona alkaloid derivatives [8], some
monodentate amine ligands [34], and a variety of bidentate chiral diamines [35]
(Structures 1-10). Complexes derived from osmium tetroxide with diamines
do not undergo catalytic turnover because diamines form very stable chelate
complexes with the Osvl glycolate products, whereas dihydroquinidine and dihy-
droquinine derivatives induce very effective catalysis. The Sharpless group has
undertaken a systematic ligand optimization study in recent years [8, 9b]. It
soon became clear that the binding constant of the ligand to Os04 is important
to deliver selectivity. Consequently, quinuclidine derivatives which show much
 1154 3.3 Special Products

higher affinity to Os04 (e. g., compared with pyridine) were used. Interestingly,
nature provides quinine and quinidine, “pseudoenantiomeric” cinchona alkaloids,
as starting materials for ligand variation. So far more than 500 cinchona alkaloid
derivatives have been tested. Other groups described minor modifications of the
ligands originally discovered, but the corresponding catalyst systems showed no
real methodological improvements [36].

Meo*

1 2 3
Dihydroquinidine (DHQD) Dihydroquinine (DHQ) Diamines [30]

Sharpless et al. [9] Snyder, Ito, Corey, Fuji,

Tomioka, Hanessian,
Hirama et al.

X-ray analysis of osmium tetroxide-cinchona alkaloid complexes [37] demon-

strated that the chiral center in the alkaloid ligand is quite remote from the 0x0
ligand. Therefore it is unlikely that the complex itself is responsible for the

The ethyl group has a small effect on the

reaction rates: however it increases binding

R has a very large effect on

the rates, but only a small
influence on the binding to 0 s .

An oxygen atom at C9 is essential

to allow binding; even a methylene
group is too bulky.

Only erythro configuration allows

high rates and binding to the metal.
MeO-increases binding
as well as rates.

/
The flat, aromatic ring system increases binding and rates;
the nitrogen atom has no influence.

Figure 1. Influence of structural features of the cinchona ligands on binding and

reaction rates.
 3.3.2.4 Scope and Limitation of Asymmetric Dihydroxylation 1155

high enantioselectivities observed in the addition to alkenes. Nevertheless, the

alkaloid core is ideally set up to ensure high rates, binding, and solubility. It
soon became evident that the rates and enantioselectivity are influenced consider-
ably by the nature of the 0-9 substituent, while binding to Os04 is almost inde-
pendent of that substituent. Variations in the alkaloid backbone have only rela-
tively minor effects. The relationship between ligand structure, binding, and reac-
tion rate is generalized in Figure 1.
Careful ligand screening has led to three different ligand classes based on
cinchona alkaloids, which taken together are very effective catalysts for nearly
every olefin (vide infra) with the six possible substitution patterns. This grouping
is shown in Figure 2.
The phthalazine (PHAL) (4) [38] and diphenylpyrimidine (PYR) ( 5 ) [39]
ligands contain two independent alkaloid units, attached to a heterocyclic spacer,
while the indolinyl carbamyl (IND) (6) [40] ligand is attached to only one
alkaloid. PHAL ligands are recommended for 1,l- and 1,2-truns disubstituted

Olefin
class

Ligands PYR, PHAL, PHAL, DPP, IND, PYR, PHAL. DPP, PHAL, DPP. PHAL, PYR
DPP, AQN PYR, AQN DPP, AQN AQN AQN

ee range 30-97% 70-97% 20-80% 90-99% 90-99% 20-97%

PHAL PY R IND
4 5 6

N- N

x x
Ph
w Ph

X=N: DPP AQN

X = CH: DP-PHAL

7 8

Figure 2. Ligand types (Structures 4-6) for the different olefin classes.
 3.3.2.4 Scope and Limitation of Asymmetric Dihydroxylation 1157

Table 1. AD of nonfunctionalized olefins: selectivities [%I a)

Ligand
PHAL (DHQD) PYR (DHQD) IND (DHQD)
Olefin 11/41 ~ 5 1 [I161

"0 /

"0 I

r" Ph 7 2 (1R,2S)

56 (1R,2S)

a) For original references see [9 b].

ucts with reasonable to very high selectivities. For illustration, Table 1 shows
selected examples from the large numbers of simple olefins which have been
used so far [9 b].
Moreover, and more importantly for practical purposes, functionalized olefins
with nearly all kinds of substituents attached to the olefin can be dihydroxylated.
Thus, acrylic acid esters, unsaturated amides and ketones, dienes, enynes, vinyl
silanes, acrolein acetals, and allylic halides, as well as allylic ethers and sulfur-
1158 3.3 Special Products

Table 2. AD of functionalized olefins: selectivities [%I a)

Ligand
PHAL (DHQD) PYR (DHQD) IND (DHQD)
Olefin 11/41 ~ 5 1 W61

Ph &CO*Et 97 (2S,3R)

P h y P h
OMe

OMe
I

c C 0 2 E t
78 (2R,3R)
Ph
a) For original references see [9 b].

containing olefins [9], have been successfully dihydroxylated. In Table 2 an

attempt is made to summarize representative examples in this area. Due to the
fact that OsO, reacts as an electrophilic reagent, osmylation of unsaturated carbo-
nyl compounds can be a very slow process. This problem has been solved by
increasing the amount of catalyst to 1 mol % and adding one equivalent of methyl
sulfonamide [29]. A special case is the asymmetric dihydroxylation of enol ethers
and ketone acetals leading directly in a one-pot process to hydroxycarbonyl
compounds [9].
It is clear that there is an exception to every rule: even in AD there are a few
cases known where other ligands gave improved stereoselectivities compared with
PHAL, PYR, or IND. Thus, allylic phosphine oxides undergo AD to yield diols
which could be used for the synthesis of optically active allylic alcohols [43].
 3.3.2.5 Selected Applications of Osmium-Catalyzed Dihydroxylations 1159

Warren and co-workers reported best enantiomeric excesses with the original
p-chlorobenzoate or phenanthryl ether ligands that contain only one quinuclidine
unit 1441. A similar trend in enantioselectivity has been reported for the asym-
metric dihydroxylation of allylic trimethylsilanes [45].
To explore the possibility of recycling alkaloid-0s0, complexes, several
polymer-bound alkaloid derivatives have been used for heterogeneous catalytic
asymmetric dihydroxylations. As chiral ligands, polymerized cinchona alkaloids
or copolymers of quinine derivatives with acrylonitrile or styrene were studied
[46]. In general, lower selectivities and decreased rates were observed.
Sharpless and co-workers reported the first catalytic asymmetric hydro-
xyamidation method [47]. Enantioselectivities between 33-8 1 % could be ob-
tained with disubstituted cis- or trans-olefins in the presence of K20s02(OH),,
TsNClNa . 3H20 and (DHQD),PHAL or (DHQ),PHAL as ligands. This methodi-
cal improvement is another breakthrough in asymmetric catalysis because it offers
easy access to chiral b-aminoalcohols which are widely used as pharmaceuticals
from cheap olefins. Despite the sometimes moderate enantioselectivities the
method is already useful for practical purposes because selectivities could be
improved by simple crystallization.

3.3.2.5 Selected Applications of Osmium-Catalyzed

Dihy droxylations
From an industrial point of view, olefins are in principle a ubiquitious feedstock
for the synthesis of diols. From the standpoint of economically interesting targets,
three areas have to be distinguished. In the area of commodity products, ethylene
glycol and propylene glycol are valuable targets for osmium-catalyzed air oxida-
tion [59, 601. Catalyst lifetime and activity in the presence of air as oxidant still
have to be improved. The same is true for bulk intermediates and fine chemicals
like 1,2-pentanediol, pinacol, and others. On the other hand, chiral diols - as
intermediates mainly for pharmaceuticals but also for fungicides, insecticides,
and pesticides - will tolerate production costs with terminal oxidants other than
air. In this respect the electrocatalytic AD and the new Backvall variant especially
offer advantages. The use of optically pure diols as valuable materials is promis-
ing because there exists a wealth of chemical knowledge for the differentiation
and manipulation of the hydroxyl groups of diols, which has recently been re-
viewed [9b]. In order to enable further refinement, activation of diols has been
pursued by selective arenesulfonylation; reactions to cyclic sulfates, halohydrin
esters and epoxides; and formation of cyclic carbamates and lactones.
Synthetic applications of AD which have already appeared and which are of
potential industrial interest include the synthesis of propranolol (9)[48], diltiazem
(10) [49], carnitine, and 4-amino-3-hydroxybutyric acid (11) [50], azole anti-
fungals (12) [5 11, chloramphenicol (13) [52], reticuline intermediates (14)[53],
camptothecin analogs (15) [54], khellactone (16)derivatives [55], taxol C-13
side chain (17)[56], halosarin [64], dehydro-em-brevicomin 1651, and antimalar-
ial active cyclopenteno-l,2,4-trioxanes[57], as summarized in Figure 4.
1160 3.3 Special Products

a;$oAc
Structures

OH

0
&O NHPr' Fi
Propranolol [47] Diltiazem [48]
9 10

OH
H2N &C02H OH
OH
GABOB [49] Azole antifungals [50]
11 12
OR

Chloramphenicol [51] OR

13 Reticuline intermediate [52]

14

x i OH
Et" o
X = C , N; R = H, OMe
Camptothecin intermediate [53]
Po OR
OR

Khellactone [54]
C /
H C
NHBz

0 2 H

C13 Taxol [55]

side chain
15 16 17

(-)-Halosarin [64] Dehydro-exo-brevicomin [65]

Figure 4. Selected examples of chiral diols of potential industrial interest made by AD.
 References 1161

Besides the synthesis of intermediates for pharmacologically active com-

pounds, asymmetric dihydroxylations have been successfully applied to other
fields: synthesis of natural products, as well as of a number of chiral auxiliaries
for other asymmetric transformations. More detailed information is available in
[9b]. In conclusion, the possible synthetic transformations of chiral diols to inter-
esting building blocks and the technically useful characteristics of the osmium-
catalyzed process make it very likely that future industrial realizations of this
methodology will be seen in the area of “finest chemical synthesis”.

References
[ I ] J. Schlossig, F. Merger, J. Paetsch, H. Grafje, W. Reiss, F. Heinrich, N. Wilke, P. T. von
Bramer, G. B. Bowen, G. Pohl, H. Gaube, P. Werle, L. Scott in Ullmann’s Encycl. Ind.
Chem. 5th ed., 1985, Vol. A l , p. 305.
[2] (a) N. A. Milas, S. Sussman, J. Am. Chem. Soc. 1936, 58, 1302; (b) N. A. Milas, J. Am.
Chem. Soc. 1937, 59, 2342.
[3] (a) M. Schroder, Chem. Rev. 1980, 80, 187; (b) J. L. Courtney in Organic Syntheses by
Oxidation with Metal Compounds (Eds.: W. J. Mijs, C. R. H. I. de Jonge), Plenum, New
York, 1986, p. 449.
[4] (a) K. B. Sharpless, K. Akashi, J. Am. Chem. Soc. 1976, 98, 1986; (b) P. H. J. Carlsen,
T. Katsuki, V. S. Martin, K. B. Sharpless, J. Org. Chem. 1981, 46, 3936; (c) F. X. Web-
ster, J. Rivas-Entemos, R. M. Silverstein, J. Org. Chem. 1987,52, 689; (d) V. s. Martin,
M. T. Nunez, C. E. Tonn, Tetrahedron Lett. 1988, 29, 2701; (e) M. Caron, P. R. Carlier,
K. B. Sharpless, J. Org. Chem. 1988, 53, 5185.
[ S ] (a) A. J. Fatiadi, Synthesis 1987, 85; (b) D. G. Lee, T. Chen, J. Am. Chem. Soc. 1989,
111, 7534; (c) T. Ogino, N. Kikuiri, J. Am. Chem. Soc. 1989, 111, 6175.
[6] T. K. M. Shing, V. W.-F. Tai, E. K. W. Tam, Angew. Chem. 1994, 106, 2408; Angew.
Chem., Int. Ed. Engl. 1994, 33, 2312.
[7] S. G. Hentges, K. B. Sharpless, J. Am. Chem. SOC.1980, 102, 4263.
[8] Selected examples: (a) E. N. Jacobsen, I. Marko, W. S. Mungall, G. Schroder, K. B.
Sharpless, J. Am. Chem. Soc. 1988, 110, 1968; (b) E. N. Jacobsen, I. Marko, M. B.
France, J. S. Svendsen, K. B. Sharpless, J. Am. Chem. Soc. 1989, 111, 737; (c) K. B.
Sharpless, W. Amberg, M. Beller, H. Chen, J. Hartung, Y. Kawanami, D. Liibben,
E. Manoury, Y. Ogino, T. Shibata, T. Ukita, J. Org. Chem. 1990, 56, 4585; (d) K. B.
Sharpless, W. Amberg, Y. L. Bennani, G. A. Crispino, J. Hartung, K.-S. Jeong, H. L.
Kwong, K. Morikawa, Z.-M. Wang, D. Xu, X.-L. Zhang, J. Org. Chem. 1992, 57,
2768; (e) G. A. Crispino, P. T. Ho, K. B. Sharpless, Science 1993,259, 64; (f) G. A. Cris-
pino, K.-Y. Jeoung, H.C. Kolb, Z.-M. Wang, D. Xu, K.B. Sharpless, J. Org. Chem.
1993, 58, 3785; (g) H. Becker, S.B. King, M. Taniguchi, K.P.M. Vanhessche, K.B.
Sharpless, J. Org. Chem. 1995, 60, 3940; (h) H. Becker, K.B. Sharpless, Angew.
Chem. 1996, 108, 447; Angew. Chem. Int. Ed. 1996, 35, 448; (i) L. Wang, K.B. Sharp-
less, J. Am. Chem. Soc. 1992, 114, 7568.
[9] Reviews: (a) R. A. Johnson, K. B. Sharpless in Catalytic Asymmetric Synthesis (Ed.:
I. Ojima), VCH, Weinheim, 1993, p. 227; (b) H. C. Kolb, M. S. Van Nieuwenhze,
K. B. Sharpless, Chem. Rev. 1994, 94, 2483; (c) H. Waldmann, Nuchr: Chem. Tech.
Lab. 1992, 40, 702; (d) B. B. Lohray, Tetrahedron Asymm. 1992, 3, 1317; (e) H.C.
Kolb, K. B. Sharpless, in Transition Metals for Organic Synthesis, Vol. 2 (Eds.: M. Bel-
ler, C. Bolm), VCH, Weinheim, 1998, p. 219; (f) I. E. Mark6, J. S. Svendsen, in Compre-
1162 3.3 Special Products

hensive Asymmetric Catalysis I1 (Eds.: E. N. Jacobsen, A. Pfaltz, H. Yamamoto),

Springer, Berlin, 1999, p. 713.
[lo] F. C. Philipps, Z. Anorg. Allg. Chem. 1894, 6 , 229.
[ l l ] (a) R. Criegee, Liebigs Ann. Chem. 1936, 522, 75; (b) R. Criegee, Angew. Chem. 1937,
50, 153.
[12] K. A. Hofmann, Chem. Ber: 1912, 45, 3329.
[I31 N. A. Milas, J.-H. Trepagnier, J. T. Nolan, M. I. Iliopulos, J. Am. Chem. Soc. 1959,
81, 4730.
[I41 (a) Upjohn (W. P. Schneider, A. V. McIntosh), US 2.769.824 (1956); (b) V. Van Rheenen,
R. C. Kelly, D. Y. Cha, Tetrahedron Lett 1976, 17, 1973; (c) R. Ray, D. S. Matteson,
Tetrahedron Lett. 1980, 21, 449.
[15] M. Minato, K. Yamamoto, J. Tsuji, J. Org. Chem. 1990, 55, 766.
[16] Y. Ogino, H. Chen, H.-L. Kwong, K. B. Sharpless, Tetrahedron Lett. 1991, 32, 3965.
[ 171 M. P. Singh, H. S. Singh, B. S. Arya, A. K. Singh, A. K. Sisodia, IndianJ. Chem. 1975,13,112
[18] (a) Sepracor Inc. (Y. Gao, C. M. Zepp), PCT Int. Appl. WO 9.317.150 (1994); (b) Anon.,
Chem. Eng. News. 1994, 72(24), 41.
[19] (a) J. F. Cairns, H. L. Roberts, J. Chem. Soc. C 1968, 640; (b) Exxon Corp. (R. C.
Michaelson, R. G. Austin), EP 0.077.201 (1982); Chem. Abstr: 1983, 99, 7 0 1 9 8 ~ ;
(c) Exxon Corp. (R. S. Myers, R. C. Michaelson, R. G. Austin), US 4.496.779 (1984);
Chem. Abstr: 1985, 102, 148721f; (d) Exxon Corp. (R.C. Michaelson, R.G. Austin),
US 4.533.772 (1985); Chem. Abstl: 1986, 104, 8 9 1 8 3 ~(e) ; R. G. Austin, R. C. Michael-
son, R.S. Myers, in Catalysis of Organic Reactions, Dekker, New York, 1985, 269;
(f) Celanese Corp., GB 1.028.940 (1966); Chem. Abstl: 1966, 65, 3064f.
[20] (a) A. Krief, C. Colaux-Castillo, Tetrahedron Lett. 1999, 40, 4189; (b) A. Krief,
C. Delmotte, C. Colaux-Castillo, Pure Appl. Chem. 2000, 72, 1709.
[21] W. A. Herrmann, S. J. Eder, W. Scherer, Angew. Chem. 1992,104, 1371; Angew. Chem.,
Int. Ed. Engl. 1992, 31, 1345.
[22] G. Poli, Tetrahedron Lett. 1989, 29, 7385.
[23] R. Criegee, B. Marchand, H. Wannowius, Liebigs Ann. Chem. 1942, 550, 99.
[24] (a) K. B. Sharpless, D. W. Pattrick, L. K. Truesdale, S. A. Biller, J. Am. Chem. Soc. 1975,
97,2305; (b) D. W. Pattrick, L. K. Truesdale, S. A. Biller, K. B. Sharpless, J. Org. Chem.
1978, 43, 2628; (c) E. Herranz, K. B. Sharpless, J. Org. Chem. 1978, 43, 2544;
(d) E. Herranz, S. A. Biller, K. B. Sharpless, J. Am. Chem. Soc. 1978, 100, 3596.
[25] J. Boseken, Recl. Trav. Chim. 1922, 41, 199.
[26] K. B. Sharpless, A. Y. Teranishi, J.-E. Backvall, J. Am. Chem. SOC.1977, 99, 3120.
[27] (a) S. Dapprich, G. Ujaque, F. Maseras, A. Lledbs, D. G. Musaev, K. Morokuma, J. Am.
Chem. Soc. 1996, 118, 11660; (b) U. Pidun, C. Boehme, G. Frenking, Angew. Chem.
1996, 108, 3008; Angew. Chem., Int. Ed. Engl. 1996, 35, 2817; (c) M. Torrent,
L. Deng, M. Sola, T. Ziegler, Organometallics 1997, 16, 13.
[28] E. N. Jacobsen, I. Marko, M. B. France, J. S. Svendsen, K. B. Sharpless, J. Am. Chem.
SOC.1989, 111, 737.
[29] E. Erdik, D. S. Matteson, J. Org. Chem. 1989, 54, 2472.
[30] Y. L. Benanni, K. B. Sharpless, Tetrahedron Lett. 1993, 34, 2079.
[31] (a) J. P. S. Wai, I. Marko, J. S. Svendsen, M. G. Finn, E. N. Jacobsen, K. B. Sharpless,
J. Am. Chem. Soc. 1989, I l l , 1123; (b) E. N. Jacobsen, I. Marko, W. S. Mungall,
G. Schroder, K. B. Sharpless, J. Am. Chem. SOC.1988, 110, 1968.
[32] R. L. Haltermann, M. A. McEvoy, J. Am. Chem. Soc. 1992, 114, 980.
[33] T. Gobel, K. B. Sharpless, Angew. Chem. 1993,105, 1417; Angew. Chem., Int. Ed. Engl.
1993, 32, 1329.
[34] (a) T. Oishi, M. Hirama, Tetrahedron Lett. 1992, 33, 639; (b) Y. Imada, T. Saito,
T. Kawakami, S.-I. Murahashi, Tetrahedron Lett. 1992, 33, 5081.
 References 1163

[35] (a) T. Yamada, K. Narasaka, Chem. Lett. 1986, 131; (b) M. Tokles, J. K. Snyder, Tetru-
hedron Lett. 1986,27, 3951; (c) K. Tomioka, M. Nakajima, K. Koga, J. Am. Chem. Soc.
1987, 109, 6213; (d) E. J. Corey, P. D. Jardin, S. Virgil, P.-W. Yuen, R. D. Connel, J. Am.
Chem. SOC. 1989, 111, 9243; (e) M. Nakajima, K. Tomioka, Y. Itaka, K. Koga, Tetra-
hedron 1993, 49, 10793.
[36] (a) G. A. Crispino, A. Makita, Z.-M. Wang, K. B. Sharpless, Tetrahedron Lett. 1994, 35,
543; (b) E. J. Corey, M. C. Noe, M. J. Grogan, Tetrahedron Lett. 1994,35,6427;(c) E. J.
Corey, M. C. Noe, J. Am. Chem. Soc. 1993, 115, 12579; (d) E. J. Corey, M. C. Noe,
S. Sarshar, J. Am. Chem. Soc. 1993, 115, 3828; (e) B. B. Lohray, V. Bushan, Tetrahedron
Lett. 1992, 33, 5113.
[37] (a) J. S. Svendsen, I. Marko, E. N. Jacobsen, C. P. Rao, S. Bott, K. B. Sharpless, J. Org.
Chem. 1989,54,2263; (b) R. M. Pearlstein, B. K. Blackburn, W. M. Davis, K. B. Sharp-
less, Angew. Chem. 1990, 102, 710; Angew. Chem., fnt. Ed. Engl. 1990, 29, 639.
[38] K. B. Sharpless, W. Amberg, Y. L. Bennani, G. A. Crispino, J. Hartung, K.-S. Jeong,
H.-L. Kwong, K. Morikawa, Z.-M. Wang, D. Xu, X.-L. Zhang, J. Org. Chem. 1992,
57, 2768.
[39] G. A. Crispino, K.-S. Jeong, H. C. Kolb, Z.-M. Wang, D. Xu, K. B. Sharpless, J. Org.
Chem. 1993, 58, 3785.
[40] (a) L. Wang, K. B. Sharpless, J. Am. Chem. Soc. 1992, 114, 7568; (b) Z.-M. Wang,
K. Kakiuchi, K. B. Sharpless, J. Org. Chem. 1994, 59, 6895.
[41] D. J. Berrisford, C. Bolm, K. B. Sharpless, Angew. Chem. 1995, 107, 1159; Angew.
Chem., Int. Ed. Engl. 1995, 34, 1059.
[42] H. C . Kolb, P. G. Anderson, K. B. Sharpless, J. Am. Chem. Soc. 1994, 116, 1278.
[43] N. J. S. Harmat, S. Warren, Tetrahedron Lett. 1990, 31, 2473.
[44] A. Nelson, P. O’Brien, S. Warren, Tetrahedron Lett. 1995, 36, 2685.
[45] S. Okamato, K. Tani, F. Sato, K. B. Sharpless, Tetrahedron Lett. 1993, 34, 2509.
[46] (a) B. H. Kim, K. B. Sharpless, Tetrahedron Lett. 1990, 31, 3003; (b) D. Pini, A. Petri,
A. Nardi, C. Rosini, P. Salvadori, Tetrahedron Lett. 1991, 32, 5175; (c) B. B. Lohray,
A. Thomas, P. Chittari, J. R. Ahuja, P. K. Dhal, Tetrahedron Lett. 1992, 33, 5453.
[47] G. Li, H.-T. Chang, K. B. Sharpless, Angew. Chem. 1996,35,451; Angew. Chem. 1996,
108, 449.
[48] Z.-M. Whang, X.-L. Zhang, K. B. Sharpless, Tetrahedron Lett. 1993, 34, 2267.
[49] (a) ICI Australia Operations (M. Gredley) PCT Int. Appl. WO 8.902.428 (1989);
(b) K. G. Watson, Y. M. Fung, M. Gredley, G. J. Bird, W. R. Jackson, H. Gountzos,
B. R. Matthews, J. Chem. Soc., Chem. Commun. 1990, 1018.
[50] H. C. Kolb, Y. L. Bennani, K. B. Sharpless, Tetrahedron Asymm. 1993, 4, 133.
[51] P. Blundell, A. K. Ganguly, V. M. Girijavallabhan, Synlett 1994, 263.
[52] A. V. R. Rao, S. P. Rao, M. N. Bhanu, J. Chem. Soc., Chem. Commun. 1992, 859.
[53] R. Hirsenkom, Tetrahedron Lett. 1990, 7591.
[54] (a) D. P. Curran, S.-B. KO, J. Org. Chem. 1994, 59, 6139; (b) F. G. Fang, S. Xie, M. W.
Lowery, J. Org. Chem. 1994,59, 6142; (c) S.-S. Jew, K.-D. Ok, H.-J. Kim, M. G. Kim,
J. M. Kim, J. M. Hah, Y.-S. Cho, Tetrahedron Asymm. 1995, 6 , 1245.
[55] L. Xie, M. T. Crimmins, K.-H. Lee, Tetrahedron Lett. 1995, 36, 4529.
[56] Z.-M. Wang, H. C. Kolb, K. B. Sharpless, J. Org. Chem. 1994, 59, 5104.
[57] C. W. Jefford, D. Misra, A. P. Dishington, G. Timari, J.-C. Rossier, G. Bernardinelli,
Tetrahedron Lett. 1994, 35, 6275.
[58] (a) K. Bergstad, S.Y. Jonsson, J.-E. Backvall, J. Am. Chem. Soc. 1999, 121, 10424;
(b) S. Y. Jonsson, K. Famegirdh, J.-E. Backvall, J. Am. Chem. Soc. 2001, 123, 1365.
[59] (a) C. Dobler, G. Mehltretter, M. Beller, Angew. Chem. fnt. Ed. 1999, 38, 3026;
(b) C. Dobler, G. Mehltretter, U. Sundermeier, M. Beller, J. Am. Chem. Soc. 2000,
122, 10289.
1164 3.3 Special Products

[60] C. Dobler, G. Mehltretter, U. Sundermeier, M. Beller, J. Organomet. Chem. 2001,621,70.

[61] A. Severeyns, D. E. de Vos, L. Fiermans, F. Verpoort, P. J. Grobet, P. A. Jacobs, Angew.
Chem. 2001, 113, 606.
[62] A. J. DelMonte, J. Haller, K. N. Houk, K. B. Sharpless, D. A. Singleton, T. Strassner,
A. A. Thomas, J. Am. Chem. Sac. 1997, 119, 9907.
[63] G. Mehltretter, C. Dobler, U. Sundermeier, M. Beller, Tetrahedron Lett. 2000, 41, 8083.
[64] H. Takahata, M. Kobuta, T. Momose, Tetrahedron Lett. 1997, 38, 345 1 .
[65] T. Tashiro, K. Mori, Eul: J. Org. Chem. 1999, 2167.

3.3.3 Hydrovinylation
Peter W Jolly, Giinther Wilke

3.3.3.1 Introduction
The hydrovinylation reaction has its origin in the observations made in 1963 that
propene dimerizes at a quite remarkable rate in the presence of certain organo-
nickel catalysts and that the product distribution can be influenced by introducing
auxiliary P-donor ligands [l]. In 1967 it was discovered that in the presence of the
chiral ligand P(truns-myrtanyl)3, 2-butene can be co-dimerized with propene to
give 4-methyl-2-hexene in an enantioselective manner and the extension of this
co-dimerization reaction to ethylene has become known as hydrovinylation.
H
RC’H R,I CH=CH2
*C’
(1 + CH2=CH2 -+ I (1)
H R4-H
H

Hydrovinylation is thus the addition of the elements of ethylene (H/CH=CH2)

to the neighboring C-atoms of a second alkene molecule (eq. (1)). The term
has been coined in analogy to hydroformylation (the addition of H/CHO) and
although it does have its merits, it is rather general and in its widest sense
would include the whole range of ethylene oligomerization reactions from
dimerization to polymerization as well as the co-oligomerization of ethylene
with substituted alkenes. For the purpose of this review, we have therefore
restricted ourselves to reactions in which ethylene is codimerized with activated
alkenes or with cyclic 1,3-dienes; particular attention is given to those reactions
in which a new chiral center is generated (eq. (1)). Related reactions involving
noncyclic 1,3-dienes have not been included since this topic, and in particular
the hydrovinylation of buta- 1,3-diene to hexa- 1,4-diene, has been adequately
reviewed [2].
The historical development of the field and the results obtained by the principal
authors have been presented in a series of review articles [3-71 and doctoral theses
[8 a-i] .
 Applied Homogeneous Catalysis with Organometallic Compounds
Edited by B. Cornils and W. A. Herrmann
Copyright 0 Wiley-VCH Verlag GmbH, D-69469 Weinheim, 2002

1164 3.3 Special Products

[60] C. Dobler, G. Mehltretter, U. Sundermeier, M. Beller, J. Organomet. Chem. 2001,621,70.

[61] A. Severeyns, D. E. de Vos, L. Fiermans, F. Verpoort, P. J. Grobet, P. A. Jacobs, Angew.
Chem. 2001, 113, 606.
[62] A. J. DelMonte, J. Haller, K. N. Houk, K. B. Sharpless, D. A. Singleton, T. Strassner,
A. A. Thomas, J. Am. Chem. Sac. 1997, 119, 9907.
[63] G. Mehltretter, C. Dobler, U. Sundermeier, M. Beller, Tetrahedron Lett. 2000, 41, 8083.
[64] H. Takahata, M. Kobuta, T. Momose, Tetrahedron Lett. 1997, 38, 345 1 .
[65] T. Tashiro, K. Mori, Eul: J. Org. Chem. 1999, 2167.

3.3.3 Hydrovinylation
Peter W Jolly, Giinther Wilke

3.3.3.1 Introduction
The hydrovinylation reaction has its origin in the observations made in 1963 that
propene dimerizes at a quite remarkable rate in the presence of certain organo-
nickel catalysts and that the product distribution can be influenced by introducing
auxiliary P-donor ligands [l]. In 1967 it was discovered that in the presence of the
chiral ligand P(truns-myrtanyl)3, 2-butene can be co-dimerized with propene to
give 4-methyl-2-hexene in an enantioselective manner and the extension of this
co-dimerization reaction to ethylene has become known as hydrovinylation.
H
RC’H R,I CH=CH2
*C’
(1 + CH2=CH2 -+ I (1)
H R4-H
H

Hydrovinylation is thus the addition of the elements of ethylene (H/CH=CH2)

to the neighboring C-atoms of a second alkene molecule (eq. (1)). The term
has been coined in analogy to hydroformylation (the addition of H/CHO) and
although it does have its merits, it is rather general and in its widest sense
would include the whole range of ethylene oligomerization reactions from
dimerization to polymerization as well as the co-oligomerization of ethylene
with substituted alkenes. For the purpose of this review, we have therefore
restricted ourselves to reactions in which ethylene is codimerized with activated
alkenes or with cyclic 1,3-dienes; particular attention is given to those reactions
in which a new chiral center is generated (eq. (1)). Related reactions involving
noncyclic 1,3-dienes have not been included since this topic, and in particular
the hydrovinylation of buta- 1,3-diene to hexa- 1,4-diene, has been adequately
reviewed [2].
The historical development of the field and the results obtained by the principal
authors have been presented in a series of review articles [3-71 and doctoral theses
[8 a-i] .
 3.3.3.2 The Catalyst 1165

3.3.3.2 The Catalyst

The most active hydrovinylation catalysts contain nickel or palladium. Reactions
have been reported which involve ruthenium [9], rhodium [9-111 or cobalt [12]
but in these cases the reaction is invariably accompanied by considerable isomer-
ization of the primary product. Isomerization is also the main reaction observed
using ligand-free palladium catalysts, such as PdCI2 or [(PhCH:CH2)PdCl2I2
[13-151, but this can be suppressed by adding suitable P-donor ligands and active
catalysts have been derived from palladium salts, e. g., Pd(PhCN)2C12-AgBF4-
PBu3 [16], aryl-Pd compounds, e. g., PhPd(PPh3)2Br-BF3 . OEt,-H20 [17],
alkene-Pd compounds, e. g., [(PhCH:CH2)2PdC12]2-BF3. OEt,-PPh3 [ 181, or
7'-allyl-Pd compounds, e. g., [(v3-C3HS)Pd(Ph2PC2H4C02R)]+ SbF6- [ 18-20].
The main interest has, however, concentrated on nickel-containing catalysts and
although investigations have been reported involving a nickel salt, e. g., Ni-
(a~ac)~-Et~AlBr/Et~Al-PBu~ [ l l , 12, 21-27], aryl-Ni compounds, e. g., mesityl-
Ni(PPh3)2Br-BF3 . OEt, [28-321, and alkene-Ni compounds, e. g.,
Ni-Et2A1C1-Ph2PN(Me)R [25, 27, 33-36], most attention has been given to cala-
tysts prepared by treating [(73-C3HS)NiC1]2with a Lewis acid and a P-donor
ligand [3-8, 37-39].
The most active nickel and palladium catalysts are either ionic or contain a
Lewis acid as a co-catalyst. In the case of palladium, activation has been reported
in the presence of BF3 . OEt, [ 17, 181 while ionic species have been prepared by
reacting [(~3-2-MeC3H,)Pd(cod)]+BF4-with a donor ligand [20] or by treating the
appropriate halide with a silver salt (e.g., eq. (2)) [16, 19, 201.

\ ', U

OEt

The active nickel catalysts have been prepared similarly but here the most fre-
quently used Lewis acid is Et3A12C13or a related organoaluminum species, while
individual examples have been reported which involve BF3 . OEt, or BBr3 [2 1, 23,
29-32] or methyl aluminoxane (MAO) [8h-i, 371. One active ionic species,
namely [~~s~~~~N~(P(CH,P~)~),(M~CN)]+BF,- [28], has been reported while
others have been prepared in situ by reacting [(r3-C3H5)NiC1l2with a silver salt
in the presence of a donor ligand [4, 6, 7, 881.
Bearing in mind that in many cases the active species is believed either to be
ionic or to contain a strongly polarized metal-halide bond (through interaction
with the Lewis acid), it is not surprising that the preferred solvent for the hydro-
vinylation reaction is CH2C12or C6HsCI. However, examples have been reported
where the reaction proceeds satisfactorily in acetone [16], THF [28], dioxane [28],
toluene [31, 32, 351 or p-xylene [25]. In two cases, the effect of varying the
solvent has been studied [21, 271.
1166 3.3 Special Products

A P-donor ligand is generally an essential component of the hydrovinylation

catalyst. In a few cases it has been demonstrated that the catalyst is inactive
in the absence of a suitable ligand (e. g., the hydrovinylation of cyclopentadiene
[8 g]). Enantioselective control is invariably associated with the presence of a
chiral ligand and particular attention has been given to systems containing Homer
phosphines in which the ligand has chiral centers at phosphorus and/or at a
P-bonded organic group, e. g., PBu'(Ph)Me, P(menthyl)(Bu')Et. The effect of
the donor ligand upon the reaction is discussed in detail in Section 3.3.3.3;
here we confine ourselves to a short discussion of the effect upon the
activity of the catalyst. Generalizations are, however, not possible since the
effects are metal- and alkene-specific and each class of reaction will be treated
separately. The structures of the 1-azaphospholene and related ligands are
shown in Figure 1.

Me

El

Me Ph
Me

Me 2, R ' = Ph Me
3, R ' = H
Me 4, R ' = Me Me
1 5

Me
Me
8 'Me
Me
Me
Me 8, R'= Me, menthyl
7
Me

Figure 1. Structures of the I-azaphospholene and related ligands; the convention adopted in
the text refers to the configuration of the starting material used in their preparation,
e. g., (R,R)-1 is prepared from (-)-(R)-myrtenal and (+)-(R)-1-phenylethylamine.
 3.3.3.2 The Catalyst 1167

3.3.3.2.1 The Hydrovinylation of Styrene

The activity of the [($-2-MeC,H4)Pd(cod)]+BF4--2PR, catalysts (based upon
styrene conversion) is found to increase in the order [20]:

PPr; < P(O-menthyl)2Ph < PPh,(O-menthyl)

< P(O-menth~1)~< PPh3 < P(OPh),
Since the active species is believed to contain only one ligand molecule, it is
not surprising that in the presence of bidentate ligands, the conversion is either
very low (e.g., diop or Ph2PC2H4NMe2)or that no reaction occurs (e.g.,
Ph,PC(Me)HC(Me)HPPh,). In contrast, complexes containing a hemilabile
ligand such as Ph2P(CH2),C02R ( n = 1-3, R = Me, Et, menthyl) show a higher
activity than systems containing monodentate ligands and this is attributed to
the facile displacement of the 0-donor atom from the metal by the reacting alkene
119, 201.
Nickel catalysts have been reported which are modified by a range of tertiary
phosphines and phosphites, e. g., P(CH,Ph), [28], P(menthyl),Me [4, 161,
PPh, [29, 301 and P(OPh), [21-241 as well as 1-substituted azaphospholenes
[5, 8 h-i, 371. There is some evidence that the activity increases with the steric
requirements of the ligand. For example, the [mesitylNi(PR,),(MeCN)]'BF,- cat-
alyst containing P(CH2Ph), is eight times more active than the analogous PBu',-
modified system [28], while an active catalyst is formed in the presence of 2 (R' =
Ph) or (R,R)-1whereas no activity is observed in the presence of 3 or 4 (R' = H,
Me) [8 i, 371. Initial results also suggest that catalysts containing the bidentate
ligands 9 [8 i] and (PhCH2)2PCH2P(CH2Ph)2[28] are inactive.

3.3.3.2.2 The Hydrovinylation of Bicycloheptene

The only catalysts which have been investigated are nickel-containing systems of
the type [($-C3HS)NiCl],-Et3Al2Cl3-Lig. It has been shown that the activity of
the catalyst modified by P(menthyl)*Pr' is independent of the ligand concentration
within the range Ni:P = 1: 1 to 1:3 [3, 8 c]. The activity of the catalyst modified by
the 1-substituted azaphospholene ligands is very sensitive to changes in the geo-
metry of the ligand: the species having Et substituents at phosphorus ( 5 ) or an iso-
propyl group at nitrogen (6) as well as the P-Me-substituted dimer 1 having an
1168 3.3 Special Products

(R,S)-configuration (see caption to Figure 1) show similar poor to moderate activ-

ity, but the (R,R)-isomer of 1 (or the related (S,S)-isomer) is remarkably active
(TON 20000 cycles/Ni-atom h at -65 “C). In contrast, the catalyst involving
the monomeric azaphospholene 3 (R’ = H) shows very low activity, as do catalysts
modified by the phospholene and phospholane derivatives 7 and 8 (R’ = Me,
menthyl). The phosphaimidazoline derivative 10 (R’ = menthyl) is reported to
show some activity whereas the analogous species where R’ is Me or Ph are
inactive, as are the related systems R’P(N(Me)CH(Ph)Me), [5, 8 e, 401.

Me YPh

Me*Ph
10

3.3.3.2.3 The Hydrovinylation of Cyclic 1,3-Dienes

The reaction has only been reported using nickel catalysts in the presence
of tertiary phosphines (e. g., PBu3, P(m~rtany1)~ [3, 25, 27]), aminophosphines
(e.g., 11 and 12 [27, 34]), aminophosphine phosphinites (e.g., 13 [33]) and
1-substituted azaphospholenes (e. g., (R,R)-1 [6, 7, 8 g]). In addition, a catalyst
has been prepared by grafting an aminophosphine onto a styrene/2 % divinyl-
benzene copolymer and reacting the product (14) with (cod),Ni-Et,AlCl [35].
In contrast to 12 and 13, bidentate ligands such as Ph2PC2H4PPh2and
dipyridyl are reported to deactivate the catalyst [25], as do Ph,PCl, P(SR)3,
R3As, Ph3Sb and NEt, [25, 271.
Me
Me
Me
\ H
\
L,H
I HN’
CH-CH2
Me, ,C< ‘OPPhp
N
,, /H ‘NH N CH2
Ph2P
Ph’‘\Me
I
PhpP I I I
PPhp Ph2P OPPhp

11 12 13

@--@H2-O~N~ph2 Me

14

15
 3.3.3.3 The Product 1169

The effect of varying the P-donor ligand upon the activity of the catalyst has
been studied in detail for the hydrovinylation of cyclopentadiene [8 g]: whereas
catalysts involving PPr;, PCy,, PPriBu' and PMe3 are inactive, that involving
PPh, is of comparable activity to the chiral ligands which are shown below in
the order of decreasing activity:

PBuk(menthy1) > (R,R)-1> PPh,(menthyl) > P(menthyl)(Bu)Me

The optimal Ni:ligand ratio appears to be ligand- and substrate-dependent. In

the case of the hydrovinylation of cyclohexa-1,3-diene in the presence of 11,
changing the ratio from 1:1 to 1:lO has little effect upon the activity [34],
while for PBu3 it is claimed that 1:2 is optimal [25], whereas with PPh, the
best results are obtained with a 1: 1 ratio. In this last example, a 1:5 ratio leads
to catalyst deactivation [27]. For many of the reactions involving chiral ligands
a ratio of 1 : 1.2 has been chosen, but in the case of the hydrovinylation of cy-
cloocta-l,3-diene in the presence of P(menthy1hPr' the catalyst is still quite active
at a 1:3.8 ratio [3, 391.

3.3.3.3 The Product

The reactions which have been reported are listed in Table 1 along with repre-
sentative catalysts. In the presence of the appropriate ligand and under suitable
conditions, many of the reactions proceed with a surprising chemoselectivity,
regioselectivity, and enantioselectivity. The main side reactions are the isomeriza-
tion of the primary hydrovinylation product or its further reaction with a second
molecule of ethylene and the oligomerization or polymerization of the individual
alkenes. These side reactions frequently become of significance only after the
consumption of one of the reacting alkenes or at elevated temperatures. The
hydrovinylation products are presented briefly below and this is followed by a
more detailed discussion of the enantioselective control.
Styrene is converted into 3-phenyl- 1-butene with remarkably high selectivity in
the presence of nickel and palladium catalysts modified by P-donor ligands. After
consumption of the styrene, the same catalysts isomerize the primary product
mainly to 2-phenyl-2-butene. In contrast, the product of the reaction catalyzed
by ligand-free palladium catalysts, e. g., [(PhCH:CH2)PdC1J2at elevated tempera-
tures is mainly 1 -phenyl-1-butene [9, 13-15, 181. Alkene-substituted styrene de-
rivatives, e. g., stilbene, are much less reactive but ring-substituted derivatives can
be readily hydrovinylated: the yield varies considerably with the position of the
substituent. Divinylbenzene reacts with almost exclusive dihydrovinylation and,
for example, p-divinylbenzene is converted into 15. Recent interest has centered
on the hydrovinylation of p-isobutylstyrene and p-chlorostyrene since the prod-
ucts are potential precursors to the a-arylpropanoic acid derivatives ibuprofen
and suprofen, while the ready conversion of 2-vinylnaphthalene to 3-naphthyl-
1-butene suggests that naproxen should also be accessible [6, 7, 8 h, 381. These
and related compounds are important nonsteroidal antiflammatory agents [42].
Table 1. The hydrovinylation of activated alkenes and cyclic 1,3-dienes. e
e
4
Alkene Primary product Typical catalyst precursor a) Ref. 0

Fe
?3.
E

RhC13 ' 3 H 2 0
Ni(PBut3),C1-Et2A1CI

RhC13 3HzO
Ni(S:C(NEt2)C(NEt2):S)2-Et,AICI-P(OPh),
Ni(acac),-Et3AVBF3 . OEt2-P(OPh)3
ArNi(PR3)2Br-BF3 . OEt,
[ArNi(PRJ2(MeCN)]+BF4-
(v3-C3H5)Ni(PR3)O2CCF3-BF3. OEt2
[(~3-C3Hs)NiCI]2-Et3A12C13-PR3
(C~~)~N~-E~~A~~CI~-PR,
Pd(PhCN)2CI2-PBu,-AgBF,
PhPd(PPh3)2X-H20
[(v3-C3H5)PdClI2-BF3-PPh3
[($-C3Hs)Pd(Ph2PC2H4C02Et)]+SbF6-
[(v3-2-MeC3H,)Pd(cod)]+BF4--PPh20-menthyl
Table 1. (Continued)
Alkene Primary product Typical catalyst precursor a) Ref.
NiX2-A1Et3/BF3 . OEt,-P(OPh),
R - p p R- d ArNi(PPh3),Br-BF3 . OEt,
R = 2-Me, 3-Me, 4-Me, [ArNi(PR,),(MeCN)]'BF,-
3-Et, 4-Et, 2-C1, 3-C1, [(q3-C3Hs)NiCI]2-Et2AIC1-PR3
4-C1, 4-OMe, 4-CH2CHMe,

[ArNi(PR3),( MeCN)I+BFc
R - p p

R = 2-CH:CH2, R = CH,:CHC(Me)H
3-CHlCH2, 4-CH:CHz

Me0 Me0

Ni(acac),-AIEt,/BF, . OEt,-P(OPh), [21, 23, 241

d. ArNi(PPh&Br-BF, . OEt, 1291

1172 3.3 Special Products

W F

5 c

0
ci

c a
cg, 0

s
I
N
h

2
2
v

u3:3:
u
z
'ei
E

h 8 8 8
Table 1. (Continued)
Alkene Primary product Typical catalyst precursor a) Ref.
Ni(a~ac)~-Et,AlBr/AlEt~-PR~
Ni(PR3),Cl2-Et2AlC1
(cod),Ni-Et2A1C1-PR3
(cod),Ni-Et2A1Br/A1Et3-PR,

Nixat. (not specified)

Q Me Me (Mer)

[25-271

0 [25-27, 411
[3, 8a, 8b, 391
“i
a) acac = acetylacetonate; cod = cycloocta-l,5-diene. “i
“i
bJ
1174 3.3 Special Products

The nickel-catalyzed hydrovinylation of bicycloheptene has been used as a

standard reaction to test the efficacy of a new ligand. The reaction occurs with
complete diastereoselectivity to give em-2-vinylbicycloheptane (16) and none
of the endo-isomer is formed. The same species, however, catalyze the iso-
merization of the primary product to cis- and trans-2-ethylidenebicycloheptane
(17) and the codimerization with further ethylene to the butenyl derivatives
18 and 19. The product distribution is dependent upon the nature of the ligand
[3, 8 c, 401.

H
16 17 18 19

The reaction has been extended to bicycloheptadiene and to bornene. In the for-
mer case, monohydrovinylation is the main reaction and is accompanied by iso-
merization and the formation of CI1-codimers whereas in the latter case only
the isomerization product, 3-ethylidenebornane, could be isolated. Of interest in
this reaction is the observation of an enantioselective hydrovinylation: the (+)-en-
antiomer of bornene in the racemic starting material reacts preferentially and the
unreacted substrate becomes enriched in the (-)-enantiomer [3, 8 c].
The nickel-catalyzed hydrovinylations of cyclo-1,3-pentadiene, -hexadiene,
-heptadiene and -0ctadiene have been reported. Cyclopentadiene has only been
successfully reacted using [(1;13-C3HS)NiC1]2-Et3A12C13-PR3 or related catalysts
[6, 7, 8 g, 381 and ligand-free systems [8 g] or the combination N ~ ( P B U ~ ) ~ -
Cl2-Et2A1Br/A1Et, [25,411 are inactive. The product of the reaction, 3-vinylcyclo-
pent-1-ene, is readily converted into chaulmoogric acid 20 (eq. (3)),which is of
interest as a bacteriostatic drug [43].

20
The rate of reaction of the other three dienes studied decreases with increasing
ring size [27] ; in the case of cycloocta- 1,3-diene, hydrovinylation is accompanied
by isomerization or reaction with a second ethylene molecule, and the yield of
3-vinyl-cyclooct-1-ene never exceeds 50 %.

3.3.3.3.1 Enantioselective Control

The main interest in the hydrovinylation reaction lies in the generation of a new
asymmetric center (eq. (1)) and considerable effort has been invested in obtaining
high enantioselectivity by modifying the metal atom with optically active ligands.
Selected results have been brought together in Table 2, in which only those
 3.3.3.3 The Product 1175

Table 2. Selected enantioselective hydrovinylation reactions.

Product ee(%) T("C) Ligand Catalyst )' Ref.
95.2 -70 (R,R)-1 A
-70 (S,S)-1 A
6 -70 (RS1-1 A
60 -60 (R)-2 B
22 -60 P(menthyl),Pr ' A
58 rt b, PPh20-menthyl C
32 rt PPh20C(Me)HC02Et2 D

80-95 -50 to -70 (R,R)-1 A

(R, see Table 1)

53 -65 (R,R)-1 A [38, 401

40 -65 (R,0 1 A [38, 401
3 -70 ( 0 3 A 1401
65 -70 P(menthyl),Pr ' A [8c, 8e]"

Qy' 77.5 -65 P(menthyl),Pr ' A 13, 8cl

93
90

0" 93
85
47d'

cp 53 -75

A, [(r3-C3HS)NiCl2-Et3Al2Cl3-ligand;
P(menthy]),Me A [3, 8 a , 391

B, [(~3-C3Hs)NiCI]2-MAO-ligand;
C, [(r'-2-MeC3H4)Pd(cod)]+BF4--ligand;
D, [($-2-MeC3H4)Pd(PPh20C(Me)HCOzEt)]+SbF,-;
E, (cod),Ni-Et2A1C1-ligand.
b, rt, room temperature.
') See [gel, p. 8.
dl The original value of 73.5 % [34] has been revised [33].
1176 3.3 Special Products

reactions having high chemoselectivity have been included since isomerization of

the primary product to achiral compounds can falsify the results due to a kinetic
racemate separation associated with the difference in the rate of isomerization of
the enantiomers. A particularly convincing example of this effect has been
observed during the isomerization of 3-phenyl- 1-butene by an [(r3-2-MeC3H4)-
Pd(cod)]' BF4--P(O-menthyl)3 catalyst: a 3: 1 mixture of 3-phenyl- 1-butene
(ee 20%) and 2-phenyl-2-butene is converted in 72 h to a 1:2 mixture having
an ee of 38% [20].
The hydrovinylation of cyclopentadiene in the presence of an [(q3-C3H5)-
NiClIz-Lewis acid-PR3 catalyst shows complete chemo- and regioselectivity
and, with a suitable choice of catalyst components, an optical yield of 94% can
be obtained. The effect of varying the ligand upon the optical yield shows no ob-
vious correlation between structure and optical yield [3, 6-8 a, g, 391. Particularly
surprising is the relative ineffectiveness of the Horner-type phosphines having
both a chiral P-atom and a chiral substituent, e.g. P(menthyl)(Bu')Et, but it is
conceivable that the influences of the two centers of induction (chiral P-atom/
menthyl group) are opposed to each other. However, very low optical induction
has also been observed during hydrovinylation of cycloocta- 1,3-diene in the
presence of "true" Homer phosphines, such as PBu'(Ph)Me [39].
Acceptable optical yields are obtained in the presence of the I-substituted
azaphospholene (R,R)-1. The effect of varying the complex anion in the presence
of this particular ligand upon the enantioselectivity has been studied by reacting
[(q3-C3HS)NiC1l2with either a silver salt (AgX; X = BF,, S03CF3, C104, PF6,
SbF6) or Et,A1C13-, and Et3A12C13in CH,Clz at -70 "C. The results have been
compared with the molar conductivity of the catalyst solution in CH2C12 at
-40 "C and are shown in Figure 2. The enantioselectivity is high for those systems
in which the complex anion can be expected to interact with the metal atom and
low for those systems in which it is likely that the ions are separated. These results
suggest that effective enantiomeric control is associated with the occupation of
a coordination site at the nickel atom by the complex anion. The mechanistic
implications are discussed in the following section.
These results, however, should be contrasted with those observed earlier for the
hydrovinylation of styrene using a similar catalyst activated by P(menthyl),Pr' [4] :
the optical yield was found to decrease in the order

SbF6-(ee 37 %) > PF6- - Et3A12C13- BF4- > CF3S03- - C104- (ee 12 %)

Moreover, the absolute configuration of the product in the presence of chlorate
is opposite to that observed in the other cases. However, this could be the result of
an enantioselective isomerization of the primary product to achiral 2-phenyl-2-
butene under the reaction conditions (-10 "C).
The high activity of the nickel catalysts frequently enables the hydrovinylation
reaction to be carried out at low temperatures, thereby allowing full implementa-
tion of the small differences in the free activation enthalpy for the formation of the
diastereomeric intermediates. The increase in the diastereomeric excess with
decreasing reaction temperature for the hydrovinylation of p-divinylbenzene to
 3.3.3.3 The Product 1177

90-

80-

70 -

60-

50 -

40-

30-

20-

10-

0 -
I I I I
1 2 3 4
A eq [S em2mor1](40°C)

Figure 2. The enantioselectivity of the hydrovinylation of cyclopentadiene to

(-)-(R)-3-vinyl cyclopent-1 -ene as a function of the molar conductivity of
[(~'-C,H,)NiCl],-(R,R)-l-AgX or Et,,AlCl,-, in CH2C12 [6, 7, 8 g].

1,4-bisbutenylbenzene in the presence of (R,R)-1 reaches a maximum of 80 % at

ca. -50 "C [8 h]. A similar effect is observed during the hydrovinylation of bicy-
cloheptene in the presence of (R,R)-l [40] and of cyclohexa-1,3-diene in the pre-
sence of Ph,PN(Me)CH(Me)Ph [34]. In other cases, e. g., the hydrovinylation of
cyclopentadiene [8 g] or of styrene [40] in the presence of (R,R)-l,or of cyclo-
hexa-1,3-diene in the presence of 13 (threophos) [33], the optical yield at 0 "C
is so high that cooling the reaction has no significant effect, while the results
for reactions involving bicycloheptadiene [8 c] or cycloocta-1,3-diene [8 a, b, 391
in the presence of P(menthyl)*R are unreliable due to significant isomerization
of the primary product and the formation of codimers at all temperatures. The
1178 3.3 Special Products

high enantioselectivity obtained at very low temperatures in these last cases may
result in part from a restriction of rotation of the donor ligand about the P-Ni bond
which has been demonstrated by variable-temperature NMR spectroscopy and
which causes the ligand to adopt a conformer in which the isopropyl group asso-
ciated with the menthyl substituent takes up a position above the coordination
plane (see Section 3.3.3.4) [48, 491.

3.3.3.4 The Mechanism

It is frequently assumed that the mechanism of the hydrovinylation reaction is
identical for catalysts containing the same metal, irrespective of the nature of
the metal precursor. However, it is questionable whether this assumption can be
extended to different metals and it should not, for example, be assumed that the
nickel-catalyzed reactions have mechanisms identical to those of the palladium-
catalyzed reactions.
Although important details remain unclear, it is generally accepted that the key
intermediate in the nickel-catalyzed linear oligomerization of alkenes in general,
and of hydrovinylation in particular, is a nickel hydride species which is bonded
to a donor ligand, an electronegative group X (generally a halide), and alkene mo-
lecules. The Lewis acid promoter is assumed to interact with the halide atom and
the observation that these reactions in general proceed satisfactorily in polar sol-
vents (CH2C12,PhC1) suggests that polar species are involved. It has still to be
decided whether interaction with the Lewis acid results in polarization of the
Ni-X bond or whether complete electron transfer occurs to give a close ion
pair. Although the formation of an ionic species would create an additional coor-
dination site, there is in the case of nickel no supporting evidence whereas it has
been shown by X-ray crystallography that the product (21) of the reaction between
(v3-C3H5)Ni(PCy3)Cl(Cy = cyclohexyl) and MeA1C12 contains a chlorine atom
which bridges the two metal atoms [3]. Furthermore, as mentioned in the previous
section, the optical induction in the hydrovinylation of cyclopentadiene in the
presence of the ionic species generated from ($-C3Hs)Ni[(R,R)-1]C1-AgPF6 is
much lower than that obtained in the presence of (q3-C3H5)Ni[(R,R)-l]-
Cl-Et,AlCl, suggesting not only that the complex anion remain attached to the
nickel atom, but that it also plays an important role in determining the geometry
of the intermediates generated during the catalysis.

\ Cl-AIMeC12
21

The hydrovinylation reaction is suggested to proceed by an extension of the

conventional Cossee-type mechanism: addition of a Ni-H species to the alkene,
insertion of a second alkene molecule into the resulting Ni-alkyl bond followed
by p-H transfer with elimination of the product and regeneration of the hydride.
 3.3.3.4 The Mechanism 1179

YNi: L

T
Figure 3. A schematic representation of the mechanism of the nickel-catalyzed
hydrovinylation of styrene [8 h].

This is shown schematically in Figure 3 for the hydrovinylation of styrene;

the individual steps will be discussed further for the reaction catalyzed by
[(q3-C3Hs)NiC1]2-(R,R)-1-EtA1C12.
A detailed mechanism must account for the high stereoselectivity (>90 % ee)
combined with high regioselectivity and high chemoselectivity (>90 % 3-phenyl-
1-butene). The formation of 3-phenyl- 1-butene in the catalytic reaction indicates
that initially a styrene molecule, and not the sterically less demanding ethylene
molecule, complexes to the metal. This presumably has an electronic origin and
has been confirmed at least for zerovalent nickel complexes of the type (a1kene)-
Ni[P(OC6H4Me-2)3]2using equilibrium constant data [44, 451. The arrangement
of the styrene molecule in the intermediate dictates the stereochemistry of the
hydrovinylation product and insight has been obtained by using structural in-
formation to construct model compounds. The crystal structure of (R,R)-1 (and
of (R,S)-l)has been determined by X-ray diffraction and has been used to con-
struct the model of the HNi[(R,R)-11C1-A1EtC12 species shown in Figure 4.
The arrangement of the groups around the central metal atom is governed by the
size of the complex anion (X) and the relatively rigid geometry of the bulky 1-sub-
stituted azaphospholene molecule, which limits rotation of the N-bonded
1180 3.3 Special Products

Figure 4. A model of the HNi[(R,R)-1]X species (X = EtAIC1,) [ 5 ] (reproduced by permission

from G. Wilke, Angew. Chem. 1988, 100, 189-21 1).

CH(Ph)Me group about the N-C axis to ca. 40°, hence forcing this group to
occupy a position above the Ni atom. Rotation of the two halves of the aza-
phospholene ligand about C1-C1' is also constrained (to ca. 50") and as a result
the methylene groups at C5 and C8 intrude into the coordination sphere of the Ni
atom, forcing the complex anion (X) to occupy an opposing site. The styrene
molecule can be expected to approach the Ni atom by a pathway which will mini-
mize the interaction between the phenyl substituent and both the complex anion
(X) and the N-bonded substituents of the ligand. A possible square-planar arrange-
ment is shown below (22) but a trigonal-pyramidal geometry cannot be excluded.

Ni ,'
,/ \,'
H.--...-.-.---.-CH
2
Ph H C
''
H' ) i H
Ph Me
22 23 24
The regiochemistry of the hydrovinylation product (3-phenyl- 1-butene)
requires the exclusive addition of the Ni atom to the phenyl-substituted olefinic
C atom (Ni+C2) and of the hydrogen atom to the terminal C atom. The pathway
for this addition, which is presumably accompanied by an anticlockwise rotation
of the styrene molecule about the Ni-alkene axis in 22, is not clear but has pre-
cedence in the preferred Ni+C2 addition which is observed in the initial step
 3.3.3.4 The Mechanism 1181

of the dimerization of propene using related catalysts [46]. That the further reac-
tion involves an ethylene molecule and not a second styrene molecule will cer-
tainly be the result of the further steric restriction placed upon the system with
the formation of the Ni-CH(Ph)Me fragment (23). Elimination of the 3-phenyl-
1-butene molecule presumably proceeds by /3-H transfer and it is conceivable
that the suppression of the insertion of further ethylene molecules is either the re-
sult of an immediate /3-H transfer with elimination of the product, or of the stabi-
lization of the Ni-CH,CH,CH(Ph)Me fragment by the formation of a relatively
strong agostic /3-H interaction with the metal atom (24) which prevents the com-
plexation of a further ethylene molecule. It should be mentioned in this context
that a density functional calculation for a hypothetical EtNi(acac) species suggests
that here a /3-agostic bond has a strength of 10 kcal mol-' [47].
The difference in enantioselectivity and catalytic activity for the hydrovinyl-
ation of styrene in the presence of (R,R)-1 (ee 95 % at -70 "C, TON 1800
cycles/Ni atom h) or of (R,S)-1 (ee 8 %, TON 50 cyclesmi atom h) [S,401 will
be associated with differences in the spatial environment around the Ni atom in
the active species. This is shown in Figure 5.
Whereas with (R,R)-1 (Figure 5 a) the N-bonded substitutents and the CMe2
bridge of the pinene fragment lie on opposite sides of the PNC3 ring, with
(R,S)-1 (Figure 5 b) they lie on the same side. As a result, one would expect
that in the presence of (R,S)-l not only will the approach of the styrene molecule
to the metal atom be energetically more difficult than in the presence of (R,R)-1
but that also the steric differentiation of the two sides of the Ni plane will be
less pronounced and hence enantioselectivity will be lost.
The crucial role of the bulky substituent at C1 in (R,R)-1 in maintaining the
rigidity of the intermediate species is supported by a molecular modeling investi-
gation and it has also been shown experimentally that whereas the introduction
of a phenyl group at C 1 is sufficient to produce a highly enantioselective catalyst,
the introduction of an H atom or a Me group results in deactivation of the catalyst
[8 i, 371.

Figure 5. A comparison of the spatial environment of the Ni atom upon complexation

to (R,R)-1 (a) and (R,S)-1 (b). The global minimum obtained from molecular
modeling is shown in each case. The second half of the azaphospholene molecule
is designated as R': the chirality at the P atom is ( R )in (a) and (S) in (b) [S].
(Adapted from K. Angermund, A. Eckerle, F. Lutz, Z. Naturforsch. Teil B 1988,
50, 488-502).
1182 3.3 Special Products

Arguments similar to those presented above for the hydrovinylation of styrene

will dictate the stereochemical course of the reactions involving the other alkenes
investigated. Thus, interference of the methylene bridge of a complexed bicyclo-
heptene molecule (25) with the substituents on the donor atom and with the com-
plex anion will direct the course of the hydrovinylation reaction to the em-isomer
of (+)-(lS,2S,4R)-2-~inylbicycloheptane (eq. (4)) [3], while the arrangement of
the five-membered ring with respect to the coordination plane will result in the
conversion of cyclopentadiene into (-)-(R)-3- vinylcyclopentane.

25

The blocking of a coordination position at the Ni atom by a substituent attached

to the donor ligand, which probably plays a decisive role in inducing enantioselec-
tivity in the hydrovinylation reactions involving the azaphospholene 1, may well
be a general phenomenon and has also been observed in complexes containing
menthyl-substituted phosphine ligands: a crystal structure determination of (r3-
C,H,>Ni[P(menthyl)(Me)Bu']Cl (26), shows that the isopropyl group occupies a
position below the coordination plane and that the unique H atom lies between
the secondary C atom and the metal atom [48].Furthermore, variable-temperature
NMR spectroscopic studies have shown that rotation about the Ni-P bond in 26 is
restricted [48]. Similar steric effects have been observed for ( ~ ~,3-Me2C3H3)-
- 1
Ni[P(menthyl)*Me]Me [49]and a number of related rhodium, nickel, and palla-
dium complexes [50-521.

26

It is generally accepted that the nickel-catalyzed hydrovinylation of cyclic 1,3-

dienes proceeds in an analogous manner to that discussed for styrene with an
initial 1,2-addition of the Ni-H species. However, it should be stressed that an
initial 1,4-addition has not been excluded. The observation of two isomeric prod-
ucts from the reaction involving hexadeuterocyclopentadiene suggests that the
 3.3.3.4 The Mechanism 1183

intermediate cycloalkenyl-Ni system rearranges through an (y3-cyclopenteny1)Ni

species [8 g]. The involvement of y3-allyl species has also been discussed for the
reactions involving the other cyclic dienes [8 a, b, 25, 271 and it is even concei-
vable that the initial intermediate formed in the hydrovinylation of styrene (23)
stabilizes itself as an ($- 1-MeCHC,H,)Ni species. A similar mechanism has
been discussed in detail for the codimerization of ethylene with buta-l,3-diene
to give hexa-1,4-diene which is catalyzed by a variety of transition metals [2],
and for the Pd-catalyzed hydrovinylation of styrene [20].
The origin of the initial Ni-H species in the catalysis is a source of speculation.
It has been suggested that the (y3-allyl)Ni precursors react with insertion of an
ethylene molecule followed by p-H transfer (e.g., eq. (5)), while in the case of
the zerovalent nickel species the ethylaluminum component could react directly
either with alkyl transfer or with an intermediate Ni(CH,Cl)Cl species formed
by the oxidative addition of dichloromethane, e.g., eq. (6) [3, 5, 61. Related
organopalladium compounds, e. g. C1CH2Pd(Cy2PC2H4PCy2)C1,have been
characterized by X-ray diffraction [54-561.

(cod),Ni + CH,CI, -
2 PPh,
-2 cod
[CICH,Ni(PPh,),CI] -
- ICHZI
Ni(PPh,),CI,
(6)
Et,AICI
(X = EtAICI,)
- EtNi(PPh,),X -
-C,H,
HNi(PPh,),X

Although a number of stable nickel hydride compounds have been isolated,

e.g., HNi(PCyJ2C1 [8 g, 57, 581, only two examples are known which react
further with an alkene and neither of these is catalytically active [5, 8 f, 591.
It is significant, however, that in eq. (7) the expected N A C 2 addition is ob-
served.
r 1
H
I
1184 3.3 Special Products

An example of the further reaction of a Ni-alkyl species with an alkene is

shown in eq. (8) [60].

In the case of palladium, a number of neutral and ionic hydrido complexes,

e. g., HPd(PCy,),Cl and [HPd(PBu',),(MeCN)]+BPh; [6 1,621, have been isolated
and the latter have been shown to react with cyclic 1,3-dienes to give ionic
(y3-ally1)Pd compounds [63].
It has been suggested that (y3-1-MeCHC6H,)metal species play a role in the
hydrovinylation of styrene [20, 21, 24, 281. Although both yl- and y3-benzyl
complexes of nickel have been isolated, e. g., PhCH2Ni(PMe3)2C1,(y3-PhCH2)-
Ni(PMe3)C1, and [(y3-PhCH2)Ni(PPh3)JPF< [64, 651, the only derivative pre-
pared from styrene has not been fully characterized [66, 671. In contrast, palla-
dium- and platinum-containing compounds have been prepared by the protonation
of complexed styrene (eq. (9)) and the crystal structure, with an anti configuration
of the Me group, has been confirmed by X-ray diffraction for the platinum
compound derived from p-bromostyrene [68, 691.

7,5 -M\
P

R2
+ HBF4 - Q
M
: '7
P

R2
+[sF4]- (9)

M = Pd, Pt

The relevance of these observations to catalysis is, however, questionable since

NMR spectroscopic studies indicate that in particular the (y3-benzyl)Ni complexes
undergo a facile suprafacial exchange which, if projected to the catalytic reaction,
would result in the loss of enantioselectivity.

3.3.3.5 Outlook
Progress in the enantioselective hydrovinylation of alkenes has been slow:
although the reaction has been investigated for over 25 years, it is still confined
to a handful of alkenes and, whereas spectacular selectivity has been obtained
in some cases, the optimization of each new system has been largely empirical
and dependent upon the synthesis of new ligand types. However, it can be antici-
pated that, with the aid of molecular modeling, it will be possible to predict the
space-filling requirements of a ligand for the hydrovinylation of a particular
alkene. This will necessitate a more detailed understanding of the mechanism
 3.3.3.6 Postscript 1185

and here the help of both theoreticians and experimental organometallic chemists
will be needed - the former to define more precisely the course of the reaction and
the latter to design stoichiometric reactions which model the individual steps in
the mechanism (it is, for example, surprising how little is known about the effect
of chiral ligands upon the chemistry of nickel-alkyl species), and to develop
rational syntheses of suitable ligands.
The high activity of some of the nickel catalysts, which allows the reactions to
be carried out at low temperature, will presumably preclude their use on a techni-
cal scale and these systems will have to be modified to give acceptable results at
higher temperatures. In this respect, it should be noted that the cationic systems
[ArNi(PR,),(MeCN)]+ [28] and [(q'-allyl)Pd(PR3)2]+[ 191 give satisfactory results
at ambient temperatures, whereby only the latter has as yet been modified for
enantioselective synthesis.

3.3.3.6 Postscript
Significant progress has been made in the last few years in optimizing the Ni- and
Pd-catalysts and this has been reviewed in part [70-741. Most attention has been
given to the systems [(q3-C3H5)NiBr],-Ligand-AgX or NaBAr4 [75-791 and
[(q'-allyl)Pd(Ligand)]+ BF4- [SO-851 and less attention to catalysts derived from
[Ni(MeCN),][BF,], [86, 871 and [me~itylNi(PR,)~(NCMe)]+ BF4- [88]. The use
of P~(OAC)~-CF,SO,H-BU~PC~H~PBU~ has been patented [89]. A heterogenized
version of a Pd catalyst has been prepared by reaction of [(q3-2-MeC3H4)
Pd(cod)]+ BF,- with a phosphine-substituted carbosilane dendrimer and used to
catalyze the hydrovinylation of styrene whereby isomerization of the product
can be minimized by carrying out the reaction in a membrane reactor [81].
Attempts continue to optimize the optical yield of the product of the hydrovi-
nylation of styrene [75-77, 80, 82, 83, 85, 881 and vinylnaphthalene [75, 76, 821
and their derivatives. In the case of the Ni catalysts the best results (ee 80-90 %)
are obtained with the system [($-C3H5)NiBr]2-Ligand-NaB(C6H3(CF3-3,5)2)4 in
the presence of the azaphospholene 1 [77] or the hemilabile ligand 27 [75, 761.
There is an indication that the disadvantage of carrying the reaction out at low
temperatures can be avoided by using liquid or supercritical CO, as the reaction
medium [77] (cf. Section 3.1.13). Similar enantioselectivities under mild condi-
tions have been obtained using the [(q3-allyl)Pd(Ligand)]+X- system in the pre-
sence of P-chiral ligands, e. g., 28 [80, 82,8.51 or the Cr-complex 29 [83], whereby
isomerization of the product can be suppressed by terminating the reaction before
completion.

27 28 29
1186 3.3 Special Products

Interestingly, the monodentate phosphine-modified Ni and Pd catalysts respond

differently to variation of the counterion: the best results for the Ni catalysts are
obtained in the presence of weakly coordinating counterions such as OTf-
whereas the analogous Pd catalysts require the presence of a noncoordinating
counterion such as BAr, or SbF6-. The latter are also the preferred anions for
Ni-catalysts modified by 1 or the hemilabile ligand 27 [75-77, 801.
The title reaction has been extended to the codimerization of propene and
vinylarene derivatives using a Ni-catalyst [78]. The same catalyst, as well as
the analogous Pd-system, is also active for the intramolecular hydrovinylation
of a,w-diolefins to give cyclic products (eq. (10)) [79].

[Nil I [Pd]

It has also been reported that a classical metathesis catalyst, RCH=Ru(PCy,),

(CO)Cl, catalyzes the reaction between ethylene and alkynes to give mainly
hydrovinylation products [90].

References
[ l ] Studiengesellschaft Kohle mbH, NL Appl. 6.409.179 (1965); DE Appl. Aug. 10, 1963;
Chem. Abstr: 1965, 63, 5770h.
[2] A. C. L. Su, Adv. Organomet. Chem. 1979, 17, 269.
[3] B. Bogdanovid, Angew. Chem. 1973, 85, 1013.
[4] B. Bogdanovid, Adv. Organomet. Chern. 1979, 17, 105.
[5] G. Wilke, Angew. Chem. 1988, 100, 189.
[6] G. Wilke in Organometallics in Organic Synthesis 2 (Eds.: H. Werner, G. Erker),
Springer, Berlin, 1989, pp. 1-20.
[7] G. Wilke, K. Angermund, G. Fink, C. Kriiger, T. Leven, A. Mollbach, J. Monkiewicz,
S. Rink, H. Schwager, K. H. Walter, in New Aspects of Organic Chemistry 11, Kon-
dansha, Tokyo, 1992, pp. 1-18.
[8] Ph. D. Theses, Ruhr-Universitat Bochum: (a) B. Meister, 1971; (b) B. Henc, 1971;
(c) A. Losler, 1973; (d) H. Brandes, 1979; (e) H. Kuhn, 1983; (0T. Leven, 1988;
(g) S. Rink, 1989; (h) P. Eckerle, 1992; (i) A. Eckerle, 1994.
[9] H. Umezaki, Y. Fujiwara, K. Sawara, S. Teranishi, Bull. Chem. Soc. Jpn. 1973,46, 2230.
[lo] T. Alderson, E. L. Jenner, R. V. Lindsey, J. Am. Chem. Soc. 1965, 87, 5638.
[ 111 U. M. Dzhemilev, L. Y. Gubaidullin, G. A. Tolstikov, Bull. Acad. Sci. USSR 1976, 2009.
[12] S. M. Pillai, G. L. Tembe, M. Ravindranathan, J. Mol. Catal. 1993, 84, 77.
[13] K. Kawamoto, A. Tatani, T. Imanaka, S. Teranishi, Bull. Chem. Soc. Jpn. 1971,44, 1239.
[14] K. Kawamoto, T. Imanaka, S. Teranishi, Bull. Chem. Soc. Jpn. 1970, 43, 2512.
[15] M. G. Barlow, M. J. Bryant, R. N. Haszeldine, A. G. Mackie, J. Organomet. Chem.
1970, 21, 215.
[ 161 Mitsubishi Chem. Ind. (S. Hattori, K. Tatsuoka, T. Shimizu), JP 72 25.133 (1972); Chem.
Abstr: 1973, 78, 3922.
[I71 H. Nozima, N. Kawata, Y, Nakamura, K. Maruya, T. Mizoroki, A. Ozaki, Chem. Lett.
1973, 1163.
 References 1187

[IS] T. Ito, K. Takahashi, Y. Takami, Nippon Kagaku Kaishi 1974, 1097; Chern. Abstr: 1974,
81, 77567.
[I91 G. J. P. Britovsek, W. Keim, S. Mecking, D. Sainz, T. Wagner, J. Chem. Soc., Chem.
Commun. 1993, 1632.
[20] G. J. P. Britovsek, Dissertation, Techn. Hochschule Aachen, 1993.
1211 G. A. Mamedaliev, A. G. Azizov, Polym. J. (Tokyo)1985, 17, 1075.
[22] A. G. Azizov, D. B. Akhmedov, S. M. Aliyev, Nefekhimiya 1984,24,3.53;Chem. Abstr:
1984, 101, 110309.
1231 A. G. Azizov, G. A. Mamedaliev, S. M. Aliev, V. S. Aliev, Azerb. Khim. Zh. 1978, 3-8;
Chem. Abstr: 1979, 90, 6002.
[24] A. G. Azizov, G. A. Mamedaliev, S. M. Aliev, V. S. Aliev, Azerb. Khim. Zh. 1979,
3; Chem. Abstr: 1980, 93, 203573.
12.51 B. Adler, J. Beger, C. Duschek, C. Gericke, W. Pritzkow, H. Schmidt, J. Prakt. Chem.
1974, 316, 449.
[26] J. Beger, C. Duschek, C. Gericke, J. Prukt. Chem. 1974, 316, 9.52.
[27] G. Peiffer, X. Cochet, F. Petit, Bull. Soc. Chim. FK ZZ, 1979, 41.5.
1281 R. Ceder, G. Muller, J. I. Ordinas, J. Mol. Cutul. 1994, 92, 127.
[29] N. Kawata, K. Maruya, T. Mizoroki, A. Ozaki, Bull. Chem. Soc. Jpn. 1974, 47, 413.
[30] N. Kawata, K, Mamya, T. Mizoroki, A. Ozaki, Bull. Chem. Soc. Jpn. 1971, 44, 3217.
1311 Mitsubishi Yuka Fine Chem. Co. (S. Kitatsume, S. Otaba), JP 8691.138 (1986); Chem.
Abstr: 1986, 105, 227505.
[32] Tokyo Inst. Technol. (A. Ozaki, T. Mizoroki), DE-OS 2.211.745 (1973); Chern. Abstr:
1973, 78, 110835.
[33] G. Buono, C. Siv, G. Peiffer, C. Triantaphylides, P. Denis, A. Mortreux, F. Petit, J. Org.
Chem. 1985, 50, 1781.
[34] G. Buono, G. Peiffer, A. Mortreux, F. Petit, J. Chem. Soc., Chem. Commun. 1980, 937.
[3.5] X. Cochet, A. Mortreux, F. Petit, C. R. Hebd. Seances Acad. Sci., Ser: C 1978,288, 105.
[36] Soc. Chim. Charbonnages (M. Petit, A. Mortreux, F. Petit, G. Buono, G. Peiffer), FR
2.550.201 (1985); Chem. Abstr: 1986, 104, 149172.
1371 K. Angermund, A. Eckerle, F. Lutz, Z. Naturjiorsch. Teil B 1995, 50, 488.
[38] Studiengesellschaft Kohle mbH (G. Wilke, J. Monkiewicz, H. Kuhn), DE-OS 3.618.169
(1987); Chem. Abstr: 1988, 109, 673.5.
1391 B. Bogdanovic’, B. Henc, B. Meister, H. Pauling, G. Wilke, Angew. Chem. 1972, 84,
1070. Angew. Chem., Int. Ed. Engl. 1972, 11, 1023.
1401 J. Monkiewicz, G. Wilke, unpublished results, 1987.
1411 R. G. Miller, T. J. Kealy, A. L. Barney, J. Am. Chem. Soc. 1967, 89, 3756.
[42] H. R. Sonawane, N. S. Bellur, J. R. Ahuja, D. G. Kulkami, Tetrahedron: Asymmetry
1992, 3, 163.
[43] M. Hooper, Chem. Soc. Rev. 1987, 16, 437.
[44] C . A. Tolman, W. C. Seidel, J. Am. Chem. Soc. 1974, 96, 2774.
[45] C. A. Tolman, J. Am. Chem. Soc. 1974, 96, 2780.
[46] See, for example, P. W. Jolly in Comprehensive Organornetallic Chemistry (Eds.:
G. Wilkinson), F. G. A. Stone, E. W. Abel), Pergamon Press, Oxford, 1982, Vol. 8,
pp. 618-623.
1471 L. Fan, A. Krzywicki, A. Somogyvari, T. Ziegler, Znorg. Chem. 1994, 33, 5287.
[48] H. Brandes, R. Goddard, P. W. Jolly, C. Kriiger, R. Mynott, G. Wilke, Z. Naturjiorsch.
Teil B 1984, 39, 1139.
[49] B. L. Barnett, C. Kriiger, J. Organomet. Chem. 1974, 77, 407.
[SO] D. Valentine, J. F. Blount, K. Toth, J. Org. Chern. 1980, 45, 3691.
[SI] K. Kan, Y. Kai, N. Yasuoka, N. Kasai, Bull. Chem. Soc. Jpn. 1977, 50, 1051.
1521 K. Kan, K. Miki, Y. Kai, N. Yasuoka, N. Kasai, Bull. Chem. Soc. Jpn. 1978, 51, 733.
1188 3.3 Special Products

[53] M. Barkowsky, Ph. D. Thesis, Ruhr-Universitat Bochum, 1991.

[54] A. Dohring, R. Goddard, G. Hopp, P. W. Jolly, N. Kokel, C. Kriiger, Inorg. Chim. Acta
1994, 222, 179.
1551 G. Ferguson, B. L. Ruhl, Acta CrystallogK, Sect. C 1984, 40, 2020.
1.561 W. A. Herrmann, W. R. Thiel, C. BroBmer, K. Ofele, T. Priermeier, W. Scherer, J. Orga-
nomet. Chem. 1993, 461, 51.
[57] M. L. H. Green, T. Saito, P. J. Tanfield, J. Chem. Soc. A 1971, 152.
1581 K. Jonas, G. Wilke, Angew. Chem. 1969, 81, 534.
1591 U. Muller, W. Keim, C. KrLiger, P. Betz, Angew. Chem. 1989, 101, 1066; W. Keim,
Angew. Chem. 1990, 102, 251.
[60] G. T. Crisp, S. Holle, P. W. Jolly, Z. Naturforsch. Teil B 1982, 37, 1667.
[61] P. M. Maitlis, P. Espinet, M. J. H. Russell, in Comprehensive Organometallic Chemistry
(Eds.: G. Wilkinson, F. G. A. Stone, E. W. Abel), Pergamon Press, Oxford, 1982, Vol. 6,
pp. 340-342.
1621 M. Sommovigo, M. Pasquali, P. Leoni, P. Sabatino, D. Braga, J. Organomet. Chem.
1991, 418, 119.
[63] D. J. Mabott, P. M. Maitlis, J. Chem. Soc., Dalton. Trans. 1976, 2156.
[64] E. Carmona, J. M. Marin, M. Paneque, M. L. Poveda, Organometallics 1987, 6, 1757.
[65] E. Carmona, M. Paneque, M. L. Poveda, Polyhedron 1989, 8, 285.
[66] J. R. Ascenso, M. A. A. F. deC. T. Carrondo, A. R. Dias, P. T. Gomes, M. F. M. Piedade,
C. C. Romao, A. Revillon, I. Tkatchenko, Polyhedron 1989, 8, 2449.
[67] J. R. Ascenso, A. R. Dias, P. T. Gomes, C. C. Romao, Q. T. Pham, D. Neibecker,
I. Tkatchenko, Macromolecules 1989, 22, 998.
1681 L. E. Crascall, S. A. Litster, A. D. Redhouse, J. L. Spencer, J. Organornet. Chem. 1990,
394, c35.
[69] L. E. Crascall, J. L. Spencer, J. Chem. Soc., Dalton Trans. 1992, 3445.
1701 S. Hashiguchi, R. Noyori, Kagaku, Zokan (Kyoto)1995, 124, 203.
[71] F. Kakiuchi, Kagaku (Kyoto)1998, 53, 71.
[72] N. Nomura, J. Jin, H. Park, T. V. RajanBabu, M. Valluri, M. A. Avery, Chemtracts 1999,
12, 52.
1731 T. V. Rajanbabu, in Comprehensive Asymnzetric Catalysis (Eds.: E. N. Jacobsen,
A. Pfaltz, H. Yamamoto), Springer, Berlin, 1999, pp. 417-427.
1741 T. V. RajanBabu, N. Nomura, J. Jin, B. Radetich, H. Park, M. Nandi, Chem. Eur: J. 1999,
5, 1963.
17.51 N. Nomura, J. Jin, H. Park, T.V. RajanBabu, J. Am. Chem. Soc. 1998, 120, 459.
[76] M. Nandi, J. Jin, T. V. RajanBabu, J. Am. Chem. Soc. 1999, 121, 9899.
[77] A. Wegner, W. Leitner, J . Chem. Soc., Chem. Commun. 1999, 1583.
1781 J. Jin, T. V. RajanBabu, Tetrahedron 2000, 56, 2145.
[79] B. Radetich, T.V. RajanBabu, J. Am. Chern. Soc. 1998, 120, 8007.
1801 R. Bayersdorfer, B. Ganter, U. Englert, W. Keim, D. Vogt, J. Organomet. Chem. 1998,
552, 187.
1811 N. J. Hovestad, E. B. Eggeling, H. J. Heidbuchel, J. T. B. H. Jastrzebski, U. Kragl,
W. Keim, D. Vogt, G. van Koten, Angew. Chem.1999, 111, 1763; Angew. Chem., Int.
Ed. 1999, 38, 1655.
[82] J. Albert, J. M. Cadena, J. Granell, G. Muller, J. I. Ordinas, D. Panyella, C. Puerta,
C. Sanudo, P. Valerga, Organometallics 1999, 18, 3511.
1831 U. Englert, R. Haerter, D. Vasen, A. Salzer, E.B. Eggeling, D. Vogt, Organometallics
1999, 18, 4390.
[84] G. J. P. Britovsek, K. J. Cavell, W. Keim, J. Mol. Catal. A: 1996, 110, 77.
[85] Hoechst A.-G. (W. Keim, D. Vogt, R. Bayersdorfer), DE 19.512.881 (1996); Chem.
Abstr. 1996, 125, 248773.
 3.3.4.1 Introduction 1189

1861 A. L. Monteiro, M. Seferin, J. Dupont, R. F. de Souza, Tetrahedron Lett. 1996,37, 1157.

1871 V. Fassina, C. Ramminger, M. Seferin, A. L Monteiro, Tetrahedron 2000, 56, 7403.
[881 G. Muller, J. 1. Ordinas, J. Mol. Cutal. A: 1997, 125, 97.
[89] Shell Oil Co. (E. Drent), US 5.227.561 (1993); Chem. Abstr. 1994, 120, 31520.
[90] C. S. Yi, D. W. Lee, Y. Chen, Organometullics 1999, 18, 2043.

3.3.4 Carbon Dioxide as a C1 Building Block

Eckhard Dinjus, Roland Fornika, Stephan Pittel;
Thomas Zevaco

3.3.4.1 Introduction
The use of carbon dioxide (CO,) as a raw material in chemical syntheses is a
research area of extraordinary scientific, economic, and ecological interest [ 1-31.
The removal of CO, from emissions of industrial processes in order to reduce
the generally and controversially discussed greenhouse effect encourages chemists
to initiate research in this field [2]. The possibility of recycling large amounts of
C 0 2 would be rather more attractive than storage if economical and ecologically
beneficial processes are developed for the conversion of C 0 2 into useful products.
For synthetic chemists two different approaches are possible to achieve this goal:
firstly, the conversion of carbon dioxide into bulk chemicals, allowing the fixation
of large amounts of CO,; secondly, the synthesis of fine chemicals from COz and
other readily available substrates. Carbon monoxide (CO) and phosgene (COC1,)
are currently used as C,-building block in many industrial processes, but for rea-
sons of working safety and ecological doubt COz is an ideal raw material in many
respects: it is nontoxic, easy to store, to transport, and to handle, and - another
important aspect - cheap!
The most important chemical process running on Earth is the fixation of carbon
dioxide by green plants using solar energy. Photosynthesis and other enzymic ex-
amples of carboxylation with essential metals represent the natural carbon dioxide
activation processes which have been optimized over all the years of development
[ 1 a, f, g]. In photosynthesis, carbon dioxide is reduced by water into carbohy-
drates using sunlight as energy source. C 0 2 can also be reduced to carbon mon-
oxide or hydrogenated to methanol or methane with heterogeneous or enzymic
and thus homogeneous catalysts. In spite of the large amount of C 0 2 available,
only a few processes using carbon dioxide as a C,-building block have been de-
veloped in the synthetic chemical industry up to now. The most important pro-
cesses are the synthesis of urea by reaction with ammonia, the synthesis of sali-
cylic acid (Kobe-Schmidt reaction) as a process for forming a new C-C bond
and as an example of the use of the whole or intact carbon dioxide molecule
for synthesis (cf. Figure 1). For oxidative coupling reactions many stoichiometric
processes are known and detachment of the reaction components from the metal
 Applied Homogeneous Catalysis with Organometallic Compounds
Edited by B. Cornils and W. A. Herrmann
Copyright 0 Wiley-VCH Verlag GmbH, D-69469 Weinheim, 2002

3.3.4.1 Introduction 1189

1861 A. L. Monteiro, M. Seferin, J. Dupont, R. F. de Souza, Tetrahedron Lett. 1996,37, 1157.

1871 V. Fassina, C. Ramminger, M. Seferin, A. L Monteiro, Tetrahedron 2000, 56, 7403.
[881 G. Muller, J. 1. Ordinas, J. Mol. Cutal. A: 1997, 125, 97.
[89] Shell Oil Co. (E. Drent), US 5.227.561 (1993); Chem. Abstr. 1994, 120, 31520.
[90] C. S. Yi, D. W. Lee, Y. Chen, Organometullics 1999, 18, 2043.

3.3.4 Carbon Dioxide as a C1 Building Block

Eckhard Dinjus, Roland Fornika, Stephan Pittel;
Thomas Zevaco

3.3.4.1 Introduction
The use of carbon dioxide (CO,) as a raw material in chemical syntheses is a
research area of extraordinary scientific, economic, and ecological interest [ 1-31.
The removal of CO, from emissions of industrial processes in order to reduce
the generally and controversially discussed greenhouse effect encourages chemists
to initiate research in this field [2]. The possibility of recycling large amounts of
C 0 2 would be rather more attractive than storage if economical and ecologically
beneficial processes are developed for the conversion of C 0 2 into useful products.
For synthetic chemists two different approaches are possible to achieve this goal:
firstly, the conversion of carbon dioxide into bulk chemicals, allowing the fixation
of large amounts of CO,; secondly, the synthesis of fine chemicals from COz and
other readily available substrates. Carbon monoxide (CO) and phosgene (COC1,)
are currently used as C,-building block in many industrial processes, but for rea-
sons of working safety and ecological doubt COz is an ideal raw material in many
respects: it is nontoxic, easy to store, to transport, and to handle, and - another
important aspect - cheap!
The most important chemical process running on Earth is the fixation of carbon
dioxide by green plants using solar energy. Photosynthesis and other enzymic ex-
amples of carboxylation with essential metals represent the natural carbon dioxide
activation processes which have been optimized over all the years of development
[ 1 a, f, g]. In photosynthesis, carbon dioxide is reduced by water into carbohy-
drates using sunlight as energy source. C 0 2 can also be reduced to carbon mon-
oxide or hydrogenated to methanol or methane with heterogeneous or enzymic
and thus homogeneous catalysts. In spite of the large amount of C 0 2 available,
only a few processes using carbon dioxide as a C,-building block have been de-
veloped in the synthetic chemical industry up to now. The most important pro-
cesses are the synthesis of urea by reaction with ammonia, the synthesis of sali-
cylic acid (Kobe-Schmidt reaction) as a process for forming a new C-C bond
and as an example of the use of the whole or intact carbon dioxide molecule
for synthesis (cf. Figure 1). For oxidative coupling reactions many stoichiometric
processes are known and detachment of the reaction components from the metal
1190 3.3 Special Products

unsaturated
hvdrocarbons I H2
I

hydrogenation

acids esters lactones pyrones

\
-C -COOH
/
I Kolbe-Schmidt

+
reaction
1
u
1
CH4 CHBOH CO
1
hetero- heterogeneous
geneous or
enzymatic
catalysis
1
HCOOH

homogeneous
catalysis

catalysis
4-COOH
I

Figure 1. Examples of industrially useful reactions of carbon dioxide with energy-rich

co-substrates (without additional use of other energy sources).

center leads to products of great interest. Further work is necessary in this research
area to transfer these reactions into a catalytic cycle.
The binding of carbon dioxide to a transition metal center, which can be
brought about in various ways, generally involves activation of the molecule
and several spectroscopic methods are suitable allowing the characterization of
COz complexes [30]. In order to obtain a better understanding of carbon dioxide
activation several C 0 2 complexes have been investigated and described but the
formation of a transition metal-C02 complex is not a necessary prerequisite for
catalytic processes converting CO, into usable chemical products [ 1 b].
Owing to the generally high activation barriers for reactions involving the
highly oxidized and thermodynamically stable C 0 2 molecule, catalysts are
required in most of these reactions. Apart from hydrogenation of C02, C-C
coupling reactions are hitherto the domain of homogeneous catalytic reactions,
e. g., catalyst development for synthesis of lactones and pyrones. Examples of
both above-mentioned approaches to C 0 2 activation will be given in this section.
Homogeneous organometallic catalysts possess an adjustable molecular struc-
ture and offer high selectivity for the formation of a wide range of small to
large products. Industrial applications of catalytic processes so far have used
heterogeneous catalysts by reason of getting higher reaction rates and quite
easy separation from the reaction product. The creation of a highly effective
homogeneous catalytic system therefore requires increased reactivity, elimination
of slow mass transfer and diffusion, reactants in high concentrations, and a weak
solvatation sphere around the catalyst.
 3.3.4.2 Catalytic C-C Bond-Forming Reactions 1191

The catalytic efficiency is also often determined by the nature of the coordinat-
ing ligands. The electronic and steric nature of the ligand has a remarkable influ-
ence on the activity of the catalytic systems and many attempts have been made to
obtain a comprehensive system of ligand classification that allows correlation of
catalytic activity and ligand structure. In this section it will be shown how homo-
geneous catalysts for C 0 2 transforming reactions can be developed and optimized
on the basis of these concepts by combination of experimental and theoretical
work.

3.3.4.2 Catalytic C-C Bond-Forming Reactions

3.3.4.2.1 Palladium-Catalyzed Synthesis

from 1,3-Dienes and C 02
There is an ongoing interest in catalytic C-C bond-forming reactions of C 0 2 [ 3 ]
and much work has been invested in palladium-catalyzed synthesis of S-lactone 2
from butadiene 1 and C 0 2 [3 e, 3 f, 41. Table 1 presents the catalyst development
for this catalytic coupling reaction, and the optimum conditions as known up to
now are summarized in eq. (1).

1 2
up to 45 %

After the pioneering work of Inoue et al. [7] and Musco [ 5 ] ,the most detailed
study of the cyclotrimerization of butadiene and C 0 2 has been carried out by Behr
using catalysts formed in situ from Pd(acac)2 (acac = acetylacetonate) and three
equivalents of a suitable phosphine ligand [4].
These studies also revealed the formation of several other coupling products
from which isomeric C!, y-lactones and isomeric octadienyl esters of nonatriene-
carbonic acid have been isolated. A number of more and less effective variations
of phosphine-palladium-based catalysts were reported [ 3 e, f, 4, 81. Efforts to
establish an enantioselective catalytic synthesis of the S-lactone by use of chiral
coligands, remained unsuccessful however [8 e, fl.
Basic trialkyl phosphines are best suited as ligands for the palladium-catalyzed
cyclotrimerization of 1 and C02, and a strong influence of the ligand structure on
the performance of the catalyst is observed. As noted earlier [4 c], the Tolman con-
cept [ 10 a] of electronic (Z;)and steric (@)parameters is obviously not sufficient
to explain the observed ligand effects. The steric parameter ER,recently developed
for phosphine ligands on the basis of molecular mechanics [ I l l , also failed to
show any correlation with the experimental results. The understanding of these
1192 3.3 Special Products

Table 1. Selected catalytic systems for butadiene-C07 reactions.

Catalyst Adducts Solvent Temp. Yield [%] (based on butadiene)
[Oc1 Lactones Esters Buta- Ref.
(time [h])
diene
dimers
Ni(cod)2 P(i-Pr)3 CH3CN 90(15) 1.5 0.1 14 cl
Pd(acac), P(i-Pr)3 CH3CN 90 (15) 40.3 1.3 [4 bl
Pd(acac), P(n-Buh CH,CN 90 (15) 3.1 14.5 14 bl
Pd(acac), P(i-Pr)3 + CH,CN 90 (15) 58.8 2.8 14 C I

[Pd(PPh,),@-
ph3pD0H
0
NEt,, H20 CH3CN 60 (18) 62.3 0.9 22 [6]
benzoquinone)]
[Pd(PPh,),@- PPh3, N- CHiCN 60 (3) 51 1.7 2.8 [6]
benzoquinone)] ethylpiperidine,
hydroquinone,
p-benzoquinone
[Pd(PPh,)Z(p- PPh?, N- CH3CN 60(18) 81 3.5 2.6 [6]
benzoquinone)] ethylpiperidine,
hydroquinone,
p-benzoquinone
[(q3-2-Me-C3H,) P(i-Pr)3 C6Hh 70 (20) 27 19 25 [5b]
Pd(OAc)]

effects is, however, a necessary prerequisite for the development of new and more
effective catalysts. Recent results from an investigation that combines classical
ligand concepts and a simple molecular modeling approach show a strong depen-
dence between solid-state structure parameters of transition metal-phosphine
complexes and their catalytic activity [9].
The accepted mechanistic suggestion [ 3 a] as shown in Scheme 1 is related to
butadiene oligomerization and telomerization (with nucleophiles): analogously,
two molecules of butadiene undergo a C-C coupling at a low-valent palladium
complex (Structure 3) with formation of a bis(ally1)palladium intermediate ( 5 ) .
The necessary coordination site is made available by dissociation of one ligand
(e. g., a phosphine ligand). The following steps are C 0 2 insertion resulting inter-
mediate 6 in and reductive elimination of the product molecule with simultaneous
isomerization (6 is also reported to be the intermediate for coupling products other
than 2 [3fl). The effects of the various additives (see Table 1) on the catalytic
cycle have not yet been understood in full detail.
 3.3.4.2 Catalytic C-C Bond-Forming Reactions 1193

insertion
2
1. reductive
elimination

2. isomerization
6

Scheme 1. Key steps of the catalytic cycle for the formation of 2.

The observation that nitrile solvents are mostly necessary to achieve a high
catalytic efficiency ([4c]; see also Table 1) led to the development of palladium
catalysts with hemilabile ligands of the general formula R2P(CH2),CN [ 13 a].
Pitter et al. showed that these P,N ligands enable a conversion in a number
of alternative solvents such as tetrahydrofurane (THF) or benzene [13 b]. The
nitrile group of the hemilabile ligand obviously compensates the polar function
of the usually applied solvent, acetonitrile. Also, in the absence of any solvents
(homogeneous catalysis in liquid butadiene/C02) a butadiene conversion of
up to 95% is achieved; this is advantageous for future process development,
since no supplementary solvent is needed and the separation of the solvent
from the product is unnecessary. Reasonable yields of 2 are only obtained with
a spacer length of more than five CH2 units, in accordance with the hemilabile
character of the P,N ligand including a chelating coordination mode at the
palladium atom.
Progress in process development for the synthesis of 2 recently was made
by Behr and co-workers. Extraction of a palladium-phosphine catalyst by use
of 1,2,4-butanetriol as extractant offers an effective separation from 2 and
also an easy catalyst recycling [14]. Pitter et al. have shown that immobilization
of homogeneous palladium catalysts on a polystyrene support is an alternative
to the homogeneously catalyzed synthesis which enables easy catalyst recovery
~51.
1194 3.3 Special Products

A bis(dicyclohexy1phosphino)butane (DCPB)-based palladium catalyst was

found to catalyze the analogous reaction between isoprene and COz [Ill. A mix-
ture of lactones 7 and 8 is obtained but the yield of co-oligomerization products is
significantly lower (8 %) than for the reaction of 1,3-butadiene.

7 a

3.3.4.2.2 Nickel Catalyzed Cotrimerization of Alkynes

and C02 to 2-Pyrones
Investigations in Homogeneous Solution Under Classical Conditions

The formation of 2-pyrones (9) from C 0 2 and alkynes was first described by
Inoue and co-workers using Ni(cod), and chelating phosphines as catalysts
[16]. Yields were very low, however, even under drastic reaction conditions. It
was shown that the catalytic system Ni(cod),/PR, in acetonitrile/THF gave higher
turnover numbers and a very high selectivity under mild conditions (cf. eq. (2))
[17]. The catalytic conversion of alkynes with C 0 2 represents the sole example
until now of a homogeneous catalytic reaction which yields C-C bond formation
with C 0 2 and selective formation of cyclooligomers using a cheap 3d-metal com-
plex catalyst. The variation of alkyne substituents allows the synthesis of a wide
range of 2-pyrones (mono- and disubstituted alkynes and alkynes with functional
groups such as -OR and -0OR [ 181).
R
I
Ni(cod)*, PR3
COz + 2 R e
CHSCNTTHF,C02,60 "C (2)
10 bar
9

By systematic variation of the phosphine ligands it was found that the most
efficient catalyst systems are formed from basic phosphines with small cone
angles. The optimum ligand-to-metal ratio ranges between one and two. A phos-
phine excess decreases the catalytic activity, probably due to the formation of
inactive coordinatively saturated nickel complexes. The reaction is inhibited at
CO, pressures above 30 bar in conventional solvents. The decrease in catalytic
activity may be caused by the formation of inactive Ni(C03) and Ni(C0)4 at
high CO, pressure. Analogously, Tsuda and co-workers synthesized novel poly-
 3.3.4.2 Catalytic C-C Bond-Forming Reactions 1195

meric materials (eq. (3)) by reaction of long-chain n,w-dialkynes also by nickel

catalysis [ 18 el.

CH3CN, 90 "C. 10 bar

Ni(cod)2/ dppb
Et

and regio isomers

Principle mechanisms of pyrone formation are summarized in Scheme 2. The

probable pathway via Structures 10-11-12 is based on related stoichiometric reac-
tions with model complexes [ 191 and X-ray structural investigations on precata-
lysts, and is consistent with the experimental details. In 11, the sp2 center next
to nickel is suitable for the insertion of further alkynes, yielding the intermediate
12. Reductive elimination of the product 9 and addition of a further alkyne mole-
cule closes the cycle. Analogous complexes to the intermediate 11 were shown to
be versatile stoichiometric reagents for transformations to unsaturated acids and
esters, by the groups of Hoberg, Dinjus, and Walther [20].
Dunach and co-workers synthesized unsaturated carboxylates instead of
pyrones, using electrochemically generated Nio centers from alkynes and C02,
and they proposed the same initial coupling product, 11. The formation of unsat-

CH3CN '
I

Et

CH3CN '
R 3 p \ N i 3 E Et
t Et

it
12 O

Scheme 2. Postulated mechanism for catalytic 2-pyrone formation.

1196 3.3 Special Products

urated acids is a catalytic process relating to Ni" but the necessary presence of
Mg2+ions is realized by use of a sacrificial Mg anode [21].
In 1993 Reetz et al. [22a] and later Dinjus [22b] reported on a nickel-cata-
lyzed 2-pyrone synthesis in supercritical (sc) C 0 2 by means of ([Ni(cod)J/
Ph2P(CH2)4PPh2=dppb)as catalyst (see also [ 14, 221). The utilization of supercri-
tical fluids, in particular COz, recently thoroughly reviewed in [23], shows - apart
from the well-known technologies - many advantages in chemical reactions with
respect to its special properties such as variable density, high fluidity, and mis-
cibility with other gases. The use of (2 PMe,/Ni(cod),) as catalyst enables faster
2-pyrone formation in sc C 0 2 than with dppb [24].

3.3.4.3 Transition Metal Catalyzed Formation

of Formic Acid and its Derivatives from
C 0 2 and H2
Transition metal catalyzed C-C bond-forming reactions involving CO, as a
C l-building block offer an interesting approach to highly functionalized organic
molecules. The catalytic addition of hydrogen to COz also provides an important
starting point for the utilization of CO,, as several technically important basic
chemicals can be produced in this way (Scheme 3). Equivalents necessary for
the reduction of C 0 2 are also available from direct electron transfer processes.
Both cases yield formic acid as product with the oxidation number +2.

HCHO CH30H

- H20 3 T Z 0

co *
H2
- H20 @ * CnH2n+2
Fischer-Tropsch

4 t H 2 0

HCOOH CH4

Scheme 3. Theoretical possibilities for the reduction of COz.

 3.3.4.3 Transition Metal Catalyzed Formation of Formic Acid 1197

3.3.4.3.1 Direct Synthesis of Formic Acid and Formates

Thermodynamic Situation in the Hydrogenation of C 0 2

The formation of formic acid from carbon dioxide and hydrogen is an exothermic
but strongly endergonic process under standard conditions. The equilibrium in eq.
(4) lies therefore far to the left (AHe = -31.6 kJ mol-’; dGe = +32.9 kJ mol-’).

- cataIy st L
HCOOH (I) (4)
This unfavorable situation is ruled by the large difference in entropy between
the two gaseous reactants and a liquid product that forms very strong intermole-
cular hydrogen bonds. A suitable set of reaction conditions for the formation of
formic acid from CO, and H2 has to decrease this entropic gap.High pressure
and relatively low temperatures will obviously help to shift the equilibrium to
the right. Even more important is the choice of the right solvent, as solvation
will not only lower the entropy of the reactants by enclosing them in a solvent
cage, but may also break up the strong hydrogen bonds between HC0,H mole-
cules. The small negative value of the Gibbs free energy in aqueous solutions
strongly supports these considerations. Base addition will work in the same direc-
tion, especially if amines are used, as they are known to form stable adducts with
carbon dioxide. Another possibility of shifting the equilibrium (cf. eq. (4)) to the
right is by trapping formic acid in the form of derivatives such as esters or N,N-
dimethylformamide (DMF). The first report on the direct formation of formic acid
from carbon dioxide and hydrogen was published as early as 1970 by Haynes
et al. [25]. Wilkinson’s catalyst (Ph3P)3RhCland other Group 9 and 10 transition
metal complexes were used as catalysts [25 b-d]. A positive effect of small
amounts of water was also described. Industrial research groups became interested
in this reaction [26a-el.

Investigations Under Classical Conditions

The first homogenously catalyzed example was demonstrated by Inoue et al. in

1976 [26 fl. They used rhodium(1) phosphine complexes, including Wilkinson’s
catalyst for the catalytic hydrogenation of CO, in benzene solution in the presence
of tertiary amines. Inoue’s catalyst showed a better performance when small
amounts of water were added but the TON did not reach more than 150, even
under drastic reaction conditions. Other investigations showed the possibility of
obtaining higher yields when an isopropanoVamine mixture containing up to
20 % water was used [26 d]. Aqueous solutions often have higher rates and yields
than the systems in organic solvents. The accelerating effect of small amounts of
water in organic solvents allows several mechanistic explanations [26, 271. It is
possible that a donating interaction between water and the CO, carbon atom
increases the nucleophilicity of the CO, oxygen atoms and that the capacity of
the CO, to bind to a metal center is intensified in this way. Calculations by ab
1198 3.3 Special Products

initio SCF methods confirm that a C02-water interaction, as described, is more

stable than either of the two species [25]. Carbon monoxide is shown not to act
as an intermediate in C 0 2 hydrogenation. The addition of CO as reactor co-gas
using RuCl,/PPh,/NEt, as the catalytic active system shows a drastic decrease
in activity forming a catalytically inactive R u ( C O ) , ( P P ~ ~
species
)~ [28 d].
Rhodium formate complexes 14 have been inferred as possible key intermedi-
ates during the catalytic cycle of CO, hydrogenation in DMSO/NEt, mixtures
[29 a, b]. Therefore, the complexes [ { R2P-(X)-PR,}Rh(hfacac)] (Structure 13)
have been introduced as stable model compounds for 14 [30].

(y$ o+ 13
\ 0- - '

CF3
/ \o*
14
Different complexes of Structure 13 were synthesized in order to further
improve the catalytic activity by variation of the ligand structure.
Very fast formation of HC02H is observed when a solution of
[{Ph2P(CH2)4PPh2}Rh(hfacac)](2.5 X mol dm-3) in DMSO/NEt, (5: 1) is
stirred under H2/C02(1: 1, 4 MPa) in a stainless steel autoclave at 25 "C [31].
Complexes 13 are ideally suited for a systematic study of structural changes in
rhodium-phosphine chelates upon small changes in the ligand structure, as there
is no steric interaction between the phosphine ligand and the hfacac moiety
[30-321.
The influence of the ligand on the coordination sphere of rhodium complexes
13 in the solid state is prevalent in solution also, as seen from the linear correlation
between the P-Rh-P angles and the Io3Rhchemical shifts [31, 321. The chemical
shift of the lo3Rh nucleus has been determined from 2D-(3'P,'03Rh)-( 'H) -NMR
experiments. For the series of ligands R2P(CH2),PR2 of complexes 13 a linear
increase of the relative catalytic activity in C 0 2 hydrogenation with increasing
&values is observed. The fact that larger ligands coordinated to the rhodium cen-
ter accelerate the catalytic activity is reflected by the results of CAMD calcula-
tions. The elimination of the product (formic acid) seems to be the rate-determin-
ing step. Up to 2200 mol of HC02H per mol of rhodium with turnover frequencies
as high as 374 h-' can be achieved with the in situ catalyst [Rh(cod)H],/dppb
[29 b].
The accessible molecular surface (AMS) model is introduced as a unique
approach for the description of steric ligand effects in homogeneous rhodium-
catalyzed hydrogenation of CO, to formic acid [33].

Hydrogenation of COz in Aqueous Solution

As C 0 2 removal from process waste gases is predominantly carried out in water,

the hydrogenation of C 0 2 in aqueous solution is a very attractive starting point for
 3.3.4.3 Transition Metal Catalyzed Formation of Formic Acid 1199

the utilization of the raw material C02. Only a few attempts have been made in
recent decades to carry out catalytic hydrogenation of C 0 2 in water as solvent
[35-371. Transition metal complexes incorporating phosphine ligands which
have been proved as catalysts in organic solvents are not suitable for use in aque-
ous solution for reasons of nonsolubility under these conditions. Only when com-
plexes of rhodium, containing the water-soluble phosphine P(C6H4-m-S03Na),
(TPPTS, cf. Section 3.1.1.1) [38] were used homogeneous catalytic systems
could be obtained, which show higher activities and better yields as catalysts in
organic solvents [39]. For the hydrogenation of C 0 2 in aqueous solution, catalysts
formed in situ from suitable precursors and TPPTS are used, but the most effective
system until now is found with the water-soluble analog of Wilkinson's catalyst
[ClRh(TPPTS),]. Equation (5) presents the reaction conditions leading to a
TON of 3440 and a TOF of 1365 h-' [39]. It is noteworthy that the amine concen-
tration is never exeeded by formic acid concentration in aqueous systems, and for-
mic acid formation is absolutely suppressed without addition of any amine [39 a].
[CIRh(TPPTS)3]
H2 HCOOH
+
40bar. 12h, r . t . * (5)
H20, Me2NH
TON = 3440

Homogeneous catalytic hydrogenation of HC03- to HC02- in aqueous solution

has been reported for the first time [36 a, b].

Mechanistic Investigations of the Hydrogenation of C 0 2

The key step in the catalytic formation of formic acid from carbon dioxide and
dihydrogen is the formation of a new formate C-H bond. The formate unit on
the metal center could be theoretically realized firstly by insertion of CO, into
a metal-hydride bond and secondly by hydride transfer to coordinated CO,. In
all cases where the catalytically active intermediates in the hydrogenation of
C 0 2 to formic acid has been proved by spectroscopic methods, the formation
of a formate complex was found. Many stoichiometric reactions give hints to
the generally accepted mechanism of CO, insertion based on experimental and
theoretical work [40-43]. Extensive mechanistic studies on the formation of for-
mic acid have been carried out with the rhodium complex [Rh(Me2PPh),-
(nbd)]BF4 (15) in THF under increased pressure in absence of amines, using IR
and NMR spectroscopical methods, [27]. These investigations proved the forma-
tion of a cationic dihydro complex (16) leading to compounds 17 and 18 with a
r'- and r2-bound formate ligand by insertion of C 0 2 into the Rh-H bond (cf.
Scheme 4). This mechanism is not transferable to the considerably more effective
rhodium catalyzed hydrogenation of C 0 2 to formic acid in DMSONEt, mixtures.
For the most active catalytic systems containing a Rh/P2 ratio of 1: 1 (P2 = chelat-
ing bisphosphane), the mechanism presented in Scheme 5 has been postulated.
The catalytic cycle starts with an electronically unsaturated 14-electron species,
the neutral hydrido complex of Structure 20, which has been already described
in the literature [45, 461.
1200 3.3 Special Products

r l+

16
Y +
P P
P,.. I ..H P,,, I .,H
Rh, Rh,
S‘I 0 S‘I 0
O<
H ‘0 H

i 17 18
HCOOH

Scheme 4. Catalytic cycle for the hydrogenation of COz with catalyst [(nbd)Rh(Me,PPh),]
[BF,] in THF according to [27]. S = solvent.

HCOOH
C:;
--,( ‘02

H ““>>H
HI.. dh c>Rh:oFH

L:2’o+ H2 21

Scheme 5. Postulated mechanism for the hydrogenation of C 0 2 to formic acid with the most
active catalytic system dppb/Rh with a ligand/metal ratio of 1 :1. P = PPh2.
 3.3.4.3 Transition Metal Catalyzed Formation of Formic Acid 1201

These mechanistic investigations are supported by theoretical studies on the

model compound [(PH,),RhH] and they confirm the formation of a formate
unit coordinating in a Vl-binding mode in the presence of three phosphine ligands
[47]. Recent ab initio calculations pointed out that the y2-formate unit is the most
stable coordination mode in complexes, but the species incorporating the
$-bonded formate seems to be the more reactive intermediate [48].
In spite of the elimination of formic acid in a couple of steps changing the
oxidation number of the rhodium metal center from +1 to +3 and vice versa,
the reaction could take place by an alternative mechanistic pathway via a-meta-
thesis between the coordinated formate unit and the nonclassical bound hydrogen
molecule [48,49]. Initial rate measurements of a complex of the type 13 show that
kinetic data are consistent with a mechanism involving a rate-limiting product
formation by liberation of formic acid from an intermediate that is formed via
two reversible reactions of the actual catalytically active species, first with CO,
and then with HZ. The calculations provide a theoretical analysis of the full cata-
lytic cycle of C 0 2 hydrogenation. From these results s-bond metathesis seems to
be an alternative low-energy pathway to a classical oxidative additiodreductive
elimination sequence for the reaction of the formate intermediate with dihydrogen
[48 a].

Hydrogenation of C 0 2 Under Supercritical Conditions

Carbon dioxide in its supercritical state is a reaction medium of great interest.

Noyori and co-workers [50] recently discovered that ruthenium(I1)-phosphine
complexes of structure [(X),Ru(PMe,),] (23 (X = H) and 24 (X = Cl)) can act
as highly active catalysts for an effective transition metal catalyzed hydrogenation
of CO, to formic acid in a supercritical mixture of CO,, H2, and NEt, without use
of any further solvent. According to eq. (4) a TON of 7200 per mol Ru in scC02/
Et,N at 50 “C is reached. In the supercritical state the reaction rate is about
18 times higher than under comparable conditions in THE This observation is
explained by particular properties of the supercritical phase relating to miscibility
and mass transport of the reactants. The catalysts were also selected because of
their good solubility, which is similar to that in hexane. In order to guarantee a
homogeneous supercritical phase during the reaction process, the reaction condi-
tions (pressure and temperature) have to be more drastic than those described up
to now. It is noteworthy that traces of water are indicated as necessary for reaching
a high reaction rate, too [51].
PMe3

PMe3 CI

23 24
1202 3.3 Special Products

After reaching the equilibrium concentration, the HC02H/NEt3 ratio is about

1.6: 1. The formic acid reacts with dimethylamine, if present in the reaction mix-
ture, to give DMF; without addition of any amine, no formation of formic acid
takes place. The high performance of the formic acid production in the case of
ruthenium complex catalysis is bound to the supercritical C 0 2 phase. If the reac-
tion is carried out in liquid COz with comparable C 0 2 concentrations, but at 15 "C
instead of 50 "C under otherwise identical reaction conditions, the TON decreases
from 7200 to 20 and the TOF from 1400 to 1.3 h-'. This means that the remark-
able catalytic activity and efficiency are based on the characteristic properties of
scCOz, such as the extremely high miscibility with hydrogen [ S 1-53] and a good
mass-transfer capability.
Under these conditions, scC02 becomes an excellent medium for its own
hydrogenation [7 a, 27, 29 c, 3 1, 39 a, 50 b]. If it is possible to develop a continu-
ous-flow system to solve the problems of extracting and recycling amine and cat-
alyst after the release of formic acid, the industrial realization of this high-pressure
process can be expected.

3.3.4.3.2 Synthesis of Formic Acid Derivatives

Under suitable conditions the hydrogenation of C 0 2 can lead to amides or esters
in the presence of amines or alcohols, with formation of free formic acid in
between. These derivatives of formic acid are stable under standard conditions
in the presence of the catalyst.

Synthesis of Alkyl Formates

In 1970 the transition metal catalyzed formation of alkyl formates from COz, H2,
and alcohols was first described. Phosphine complexes of Group 8 to Group 10
transition metals and carbonyl metallates of Groups 6 and 8 show catalytic activity
(TON 6-60) and in most cases a positive effect by addition of amines or other
basic additives [26a, 54-58]. A more effective catalytic system has been found
when carrying out the reaction in the supercritical phase (TON 3500) [S4a].
Similarly to the synthesis of formic acid, the synthesis of methyl formate in
scC02 is successful in the presence of methanol and ruthenium(I1) catalyst sys-
tems [54b].
The reaction mixture forms a single supercritical phase. The time dependence
of the product formation shows that formic acid is formed first with a subsequent
esterification which must take place thermally. Amine is an inhibitor of esterifi-
cation but its presence is required for reasonable yields in the hydrogenation step.
The use of supercritical conditions for the homogeneous hydrogenation of COz
with following thermal esterification leads to high yields of methyl formate under
mild conditions. Therefore, it might be possible to develop an industrial procedure
for the synthesis of methyl formate with C 0 2 as C,-building block when catalysts
and reaction conditions are optimized.
 3.3.4.3 Transition Metal Catalyzed Formation of Formic Acid 1203

Catalytic Production of Dimethylformamide (DMF) from scC0,

DMF as a useful polar solvent is produced industrially on a large technical scale

(250 000 tondyear) by carbonylation of dimethylamine in the presence of metha-
nol [59]. Using Raney nickel as catalyst, the synthesis of DMF from dimethyl-
amine, C02, and hydrogen was first discovered by Farlow and Adkins [60].
The formation of DMF from dimethylamine, H,, and CO, is thermodynamically
favorable under standard conditions; thermodynamic data are given for aqueous
reactants and liquid products in eq. (6) [61]. The enthalpy of DMF production
(A@ = -56.5 kJ mol-I, dG" = -0.75 kJ mol-l, AS" = -119 kJ mol-'K-') is more
favorable than that for methyl formate (AHo = -15.3 kJ mol-I).

H 0

C02 +
I

H3C"\CH3 + H2 - H
I
+ H20 (6)

Homogeneous catalysis of this reaction was first reported by Haynes et al.

in 1970 [62]; with palladium catalyst in benzene as a solvent and at 5.6 MPa
(H2/C02) and 100 "C they could realize a TON of 1200 within 17 h. More
efficient was a ruthenium complex with dppe as a chelating phosphine ligand
described by Kiso and Saeki [63] with a TON of 3400 in hexane and similar
conditions. Jessop et al. [64] found that, in the presence of a catalytic amount
of RuC1,- [P(CH,),] as a catalyst precursor, scC0, reacts with H2 and dimethyl-
amine to give DMF with a TON up to 370000 within 37 h. As a source of
dimethylamine they used liquid dimethylammonium dimethylcarbonate, but
dimethylamine gave identical results. The conversion of dimethylamine reached
94 %, and the selectivity for DMF was 99 %. The TON of 370 000 is superior to
the largest TON of 3400 for DMF formation from CO, in a conventional liquid
solvent. The authors discuss the production of DMF from scC0, proceeding in
two steps on the basis of the composition of the product as a function of reac-
tion time.
Complexes prepared from RuC13 and bidentate phosphine ligands (dppm, dppe,
dppp, dmpe) have been shown to be the most active catalyst precursors in DMF
synthesis from CO, in the presence of dihydrogen and dimethylamine known up
to now. The highest TOF of 360000 h-' can be reached with RuCl,(dppp), as
precursor. To avoid difficulties in separating the homogeneous catalysts from
the products a solvent-free reaction design is extended to this hydrogenation reac-
tion. The advantages of both homogeneous and heterogeneous catalysts were
combined by anchoring catalytically active metal complexes via organic groups
within an oxide network. For this, silyl ether complex analogs of group VIII
metal complexes have been incorporated into a silica matrix by the sol-gel
method, resulting in stable hybrid-gel catalysts, which can be easily separated
from the reaction mixture by filtration (TOF up to 1860 h-') [54 b].
The fast Ru-catalyzed hydrogenation of CO, to formic acid is followed by the
slower thermal condensation of formic acid and dimethy lamine. Dimethylamine
1204 3.3 Special Products

acts as a base to stabilize the formic acid in the first step and serves as a reactant in
the second step.
The driving force for this process is probably the existence of a two-phase
system with a supercritical phase and a liquid phase. The overall combination
of the steps in a one-pot procedure is also responsible for the high rate of DMF
production (cf. eqs. (7) and (8)). With this improved catalytic efficiency and the
lower toxicity of CO, compared with CO, the reaction of C 0 2 with hydrogen
and dimethylamine could become competitive with the carbonylation of dimethyl-
amine as an industrial method for DMF production.

Ru catalyst
CO2 + H2
base
+ HCOOH (7)

Catalytic Syntheses of Formoxysilanes from C 0 2

Independently, in 1981 two groups reported the hydrosilylation of carbon dioxide

into formoxysilanes of the type R,R'SiOCHO (R,R' = alkyl) catalyzed by transi-
tion metal complexes, preferably based on ruthenium (eq. (9)) [65].

Ligand-modified Ir, Ru, or Pd catalysts achieve TONS up to 465 and TOFs up

to 232, and yields up to 90 % [65 a, b, 66 a, 67, 691.
Jessop reported on the utilisation of sc C 0 2 as substrate and solvent for the
hydrosilylation reaction, but conversion and selectivity are comparatively low
[68]. Most recently, Pitter and co-workers reported the use of trans-[Ru"CI-
(MeCN),] [Ru"'C~~(M~CN)~] derived from partial reduction of Ru"' in acetonitrile
solution as a highly efficient catalyst for the synthesis of several formoxysilane
derivatives under moderate conditions [69]. Analogously, Et2SiH2, Ph2SiH2,
and p-C6H4(Me2SiH)2yield Et,Si(OOCH),, Ph2Si(OOCH)2,and p-C6H,(Me,Si-
OOCH),, respectively. Such multifunctional fonnoxysilanes are discussed as
potential cross-linking agents in RTV silicones. Interestingly, the catalysts have
been found to be almost completely recyclable, thus giving rise to much higher
TONS [69].
 3.3.4.4 Catalyzed Formation of Organic Carbonates 1205

3.3.4.4 Catalyzed Formation of Organic Carbonates

Organic carbonates can be roughly classified into three groups (Structures 25-27).

R1-0’ cI I \ 0 - R z
0

25
RI
?
9
26
R2
Lo,!\ 1. 0-PI

27
Linear Carbonates Cyclic Carbonates Polycarbonates

Linear dialkyl carbonates and in particular dimethyl carbonate (DMC) are used
in many industrial applications in the industry [70, 711. The usual way of syn-
thesizing carbonates involves reactive c, agents such as phosgene or CO [72].
Although these methods are from an economical viewpoint more than profitable,
the development of an environmentally friendly industrial process involving C 0 2
as a C,-building block attracts an ever-increasing interest.
Besides a heterogeneous catalytic system [73] involving hydroxo tin(1V) com-
pounds, a homogeneous system for the synthesis of DMC from C 0 2 was recently
reported by Sakakura et al. [74]. This synthesis is also based on the use of a
dehydrating agent (an orthoester [74 a] or, less expensively, an acetal [74 c])
and methanol as substrates. A dibutyltin(1V) alkoxide, Bu2Sn(OMe)*,acts as cata-
lyst and tetrabutylphosphonium iodide as a co-catalyst. The authors proposed the
formation of an active tin-methylcarbonato species, Bu2Sn(OMe)(C03Me), as the
key intermediate of the reaction [74 b]. It should be mentioned that the formation
of DMC from methanol and COz in the presence of tin derivatives had already
been reported in earlier work by Kitzlink [75]. Dibutyltin dialkoxides have been
known for a long time to react with CO,, hence forming tin-carbonato derivatives
[76, 74b, 771. In comparison, tin aryloxides display no noticeable reactivity
toward COZ.
The second main class of organic carbonates, the cyclic carbonates, also known
as dioxolanones, have found many applications as versatile intermediates in or-
ganic synthesis [70]. They also represent promising building blocks for the pro-
duction of polyurethane- and polycarbonate-based polymers. The catalytic syn-
thesis of cyclic carbonates is the topic of a regularly increasing number of publi-
cations [78] and has led to some noteworthy industrial applications [70]. A gen-
eral mechanism is summarized in Scheme 6. The catalyst possessing both basic
and acidic sites favours the approach of the reactants, epoxide and carbon dioxide,
to result in an intermediate (Structure 28). Some remarkable epoxide-Lewis acid
adducts recently were characterized structurally by Darensbourg et al. in the case
of cadmium(I1) pyrazolylcarboxylato derivatives [78 fl. The coordinated epoxide
would then undergo a nucleophilic attack of the “activated” CO, molecule. The
desired cyclic carbonate is formed via an “intramolecular” ring closure from the
alkoxo-alkylcarbonato compound 29, the active metal center being available after-
wards to perform the next cycle.
1206 3.3 Special Products

J
29

Scheme 6. Key steps of the catalytic synthesis of cyclic carbonates involving COz.

The last class of organic carbonates, the polycarbonates, finds ever-increasing

use in our modern consumer society [80]. The usual industrial method of
synthesizing polycarbonates involves phosgene and bisphenol A derivatives.
Two principal classes of catalysts involving CO, as a C,-building block have
been reported in the literature. One comprises zinc(I1) carboxylates which are
obtained from dicarboxylic acids of the type H02C(CH2),C02H, with IZ varying
from 1 to 10 [79, 811; their common synthesis is based on the reaction of zinc
oxide with dicarboxylic acids in aprotic media. The structure of most of these
dicarboxylates is still under debate and, despite comprehensive studies on the
reactivity of the Zn(II)/C02/epoxide system, the overall mechanism remains a
subject of discussion. First attempts to use scC0, as reagent and solvent have
been newly reported by Beckmann's group [82]; the use of a fluorinated half-
ester from maleic acid and tridecafluorooctanol as ligand allows a better solu-
bility of the catalyst in the scC02 and results in a higher TON and a far better
selectivity. Other developments for soluble zinc dicarboxylates with carboxylates
bearing unsaturated spacers like ferrocenes or constrained alkenes have been
reported [83].
The second class of catalysts are zinc(I1) mono- or dialkoxides obtained from
polyhydric phenols and dialkylzinc with partly polymeric structures. This system,
extensively studied by Kuran [84], is an optimization of the wateddiethylzinc and
polyphenol/diethylzinc systems developed by Inoue [85]. The use of soluble zinc
phenoxides and their analogous cadmium complexes as catalyst for the copoly-
merization of C 0 2 and epoxide was studied extensively by the Darensbourg
group [86]. This work focused on the use of mononuclear phenoxide derivatives
with bulky substituents, e. g., phenyl- and tert-butyl groups, on the aromatic
ring to a homogeneous catalytic system and thus enhance the activity of the
Zn" phenoxides. The catalysts developed are stabilized through ancillary neutral
 3.3.4.4 Catalyzed Formation of Organic Carbonates 1207

ligands and include, to give an example, (2,6-(C6H5)2C6H30)Zn(THF)2, (2,4,6-

(C4H9)3C6H20)Zn(THF)2.
The high reactivity of these two classes of catalysts, carboxylate and alkoxide
derivatives, has been confirmed by recent work of Coates and co-workers [87].
They reported the synthesis of two new types of Zn” diimido complexes (30
and 31) as shown in Scheme 7 and successfully utilized both types of complexes
in the copolymerization of C 0 2 with epoxides. Their high activities and selectivies
in regard to the carbon dioxide insertion (up to 96% carbonate linkages) are
unprecedented.
Both catalytic systems, alkoxides and carboxylates, are often described as
“efficient” catalysts for the copolymerization of C 0 2 and epoxides but some draw-
backs which hamper a widespread industrial utilization need to be pointed out.
The phenoxides, though displaying good selectivities, have up to now only
been tested with model substrates, e. g., propylene- and cyclohexene oxides,
and the carboxylates, though active, present low-to-fair selectivities. Cyclization

solid state structure

Scheme 7. New high-active copolymerization catalysts displaying a$-diimine backbone.

1208 3.3 Special Products

is an important side-reaction due to the thermodynamic stability of the five-mem-

bered dioxolan-2-one; this phenomenon is more likely to occur at higher tempera-
tures. Their presence in the reaction mixture, although they are attractive building
blocks for other organic syntheses, complicates the separation and purification
procedure of the desired polycarbonates.

3.3.4.5 Summary and Outlook

Recent research has shown that COz can be utilized as a C,-building block for the
synthesis of both bulk and fine chemicals. There are quite a few examples of very
efficient processes using homogeneous catalysts and some of their mechanisms
are fairly well understood. Mostly the catalysts consist of transition metal-
phosphine complexes and in some special cases it was shown that classical ligand
concepts, together with the use of modern computing methods, may lead to a
better understanding of ligand effects and finally to the development of more ac-
tive catalysts. Compared with conventional processes utilizing other C sources, it
has to be pointed out that alternative routes with C 0 2 require a marketable basis,
as for example in the production of polycarbonates.
The use of ecologically harmless scC0, as solvent and substrate in chemical
reactions is a particularly intriguing prospect. Increased governmental and envir-
onmental restrictions on solvent emission make this supercritical fluid more and
more attractive as a reaction medium because it can be easily separated from
the product and recycled more efficiently than conventional liquid solvents. The
special properties (miscibility, transport properties, etc.) of sc C 0 2 require a devel-
opment of suitably adjusted catalysts. A simple transformation of catalyst proper-
ties from conventional solvents to scC02 will mostly fail, and will not lead to
higher catalytic efficiency. Supported catalysts could perhaps play a particular
role in this field as the possibility of product extraction by depressurization of
the supercritical phase and subsequent compression of the CO, (solventhubstrate)
should permit the development of a profitable continuous process.
The optimization of existing processes, the investigation of current reaction
pathways, and the search for novel catalytic reactions involving CO, as a chemical
feedstock still remain an important and motivating research area.

References
[l] (a) Organic and Bio-Organic Chemistry of Carbon Dioxide (Eds.: S . Inoue, N. Yama-
zaki), John Wiley, New York, 1982; (b) A. Behr, Carbon Dioxide Activation by Metal
Complexes, VCH, Weinheim, 1988; (c) Catalytic Activation of Carbon Dioxide (Ed.:
W. M. Ayers), ASC Symposium Series 363, American Chemical Society, Washington
DC, 1988; (d) Enzymatic and Model Carboxylation and Reduction Reactions f o r Car-
bon Dioxide Utilization (Eds.: M. Aresta, J. V. Schloss), NATO AS1 Series C, 3 14,
Kluwer Academic Press, Dordrecht, 1990; (e) Electrochemical and Electrocatalytic Re-
actions of Carbon Dioxide (Eds.: B. P. Sullivan, K. Krist, H. E. Guard), Elsevier, Amster-
 References 1209

dam, 1993; (f) M. M. Halmann, Chemical Fixation of Carbon Dioxide, CRC Press, Boca
Raton, 1993; (8) Carbon Dioxide Chemistry: Environmental Issues (Eds.: J. Paul,
C.-M. Pradier), Royal Society of Chemistry, London, 1994; (h) W. Leitner, E. Dinjus,
F. GaBner, C 0 2 Chemistry, in Aqueous Phase Organometallic Cutalysis - Concepts
and Applications (Eds.: B. Cornils, W. A. Herrmann), WileyNCH, Weinheim, 1998,
Chapter 6.15, p. 486.
[2] (a) Greenhouse Gas Emissions from Power Stations, IEA Greenhouse Gas R&D Pro-
gramme, Cheltenham, 1993; (b) C.-D. Schonwiese, B. Diekmann, Der Treibhauseffekt.
Der Mensch verandert das Klima, Rowohlt, 1990; (c) W. Seifritz, Der Treibhauseffekt,
Carl Hanser Verlag, Munich, 1991; (d) The Handbook of Environmental Chemistry,
Vol. I , Part A (Ed.: 0. Hurtzinger), Springer Verlag, Berlin, 1980; (e) R. Kummel,
S. Papp, Umweltchemie, VEB Deutscher Verlag fur Grundstoffindustrie, Leipzig,
1990; (f) E.T. Sundquist, Science 1993, 259, 934; (8) P.S. Zurer, Chem. Eng. News
1991, 69(13),7; (h) J. J. Sarmiento, Chem. Eng. News 1993, 71(22),30.
131 (a) A. Behr, Angew. Chem. 1988, 100, 681; Angew Chem. Int. Ed. Engl. 1988,27, 661;
(b) I.S. Kolomnikov, T.V. Lysak, Russ. Chem. Rev. (Engl. Transl.) 1990, 59, 344;
(c) D. Walther, Nachc Chem. Tech. Lab. 1992, 40, 1214; (d) M. Aresta, E. Quaranta,
I. Tommasi, New J. Chem. 1994, 18, 133; (e) A. Behr, Asp. Hom. Catal. 1988, 6 , 59;
(f) P. Braunstein, D. Matt, D. Nobel, Chem. Rev. 1988,88,747; (8) P. G. Jessop, T. Ikaria,
R. Noyori, Chem. Rev. 1995, 95, 259; (h) W. Leitner, Coord. Chem. Rev., 1996;
(i) D. Walther, E. Dinjus, J. Sieler, Z. Chem. 1983, 23, 237; (k) D. J. Darensbourg,
R.A. Kudaroski, Adv. Organomet. Chem. 1983, 22, 129; (1) D. Walther, Coord.
Chem. Rev. 1987, 79, 135; (m) P. G. Jessop, T. Ikaria, R. Noyori, Chem. Rev. 1995,
95, 259; (n) W. Leitner, Angew. Chem. 1995, 107, 2391; (0) W. Leitner, Coord.
Chem. Rev. 1996, 153, 257; (p) V. Haack, E. Dinjus, S. Pitter, Angew. Makromol.
Chem. 1998, 257, 19.
[4] (a) A. Behr, K.-D- Juszak, W. Keim, Synthesis 1983, 574; (b) A. Behr, K.-D. Juszak,
J. Organomet. Chem. 1983, 255, 263; (c) A. Behr, R. He, K.-D. Juszak, C. Kriiger,
Y.-H. Tsay, Chem. Ber: 1986, 119, 991.
[5] (a) A. Musco, C. Prego, V. Tartiari, Znorg. Chim. Acta 1978, 28, L147; (b) A. Musco,
J. Chem. Soc., Perkin Trans. I 1980, 693.
[6] I. C. I. (J. A. Daniels), EP 0.050.445 (1982); Chem. Abstr: 1982, 97, 1 2 7 5 0 0 ~ .
[7] (a)Y. Sasaki, Y. Inoue, H. Hashimoto, 1. Chem. Soc., Chem. Commun. 1976, 605;
(b) Y. Inoue, Y. Itoh, H. Kazama, H. Hashimoto, Bull. Chem. Soc. Jpn. 1980, 53, 3329.
181 (a) P. Braunstein, D. Matt, D. Nobel, J . Am. Chem. Soc. 1988, 110, 3207; (b) Universite
de Strasbourg Louis Pasteur (P. Braunstein, D. Matt, D. Nobel), FR 2.617.163 (1988); (c)
Shell (E. Drent) EP 0.234.668 (1987); (d) Montedison S. p. A. (A. Musco, R. Santi, G. P.
Chiusoli), DE 2.838.610 (1979); (e) A.R. Elsagir, PhD Thesis, University of Jena
(1997); (f) M. Nauck, PhD Thesis, University of Heidelberg (1998).
191 Huls AG (W. Keim, A. Behr, B. Hegenrath, K.-D- Juszak), DE 3.317.013 (1984); Chem.
Abstr: 1985, 102, 787238.
[lo] C. A. Tolman, Chem. Rev. 1977, 77, 313.
[ I l l T. L. Brown, Inorg. Chem. 1992, 31, 1286.
[ 121 E. Dinjus, W. Leitner, Appl. Organomet. Chem. 1995, 9, 43.
[13] (a) E. Dinjus, S. Pitter, H. Gorls, B. Jung, 2. Naturforsch. Teil B 1996, 51, 934;
(b) E. Dinjus, S. Pitter, J. Mol. Cat. 1997, 125, 39.
[14] A. Behr, M. Heite, Chem. f n g . Tech. 2000, 72, 58.
[I51 (a) N. Holzhey, S. Pitter, E. Dinjus, J. Organomet. Chem. 1997, 541, 243; (b) For-
schungszentrum Karlsruhe (S. Pitter, N. Holzhey, E. Dinjus), DE 197.25.735 (1998);
(c) S. Pitter, N. Holzhey, J. Mol. Cat. 1999, 146, 25.
[I61 Y. Inoue, Y. Itoh, H. Hashimoto, Chem. Lett. 1977, 855.
1210 3.3 Special Products

[ 171 D. Walther, E. Dinjus, H. Schonberg, J. Sieler, J. Organomet. Chem. 1987, 334, 377.
[I81 (a) T. Tsuda, S. Morikawa, R. Sumiya, T. Saegusa, J. Org. Chem. 1988, 55, 3140;
(b) T. Tsuda, S. Morikawa, T. Saegusa, J. Chem. Soc., Chem. Commun. 1989, 9 ;
(c) T. Tsuda, S. Morikawa, K. Kunisada, N. Nagahama, Synth. Commun. 1989, 19,
1575; (d) T. Tsuda, S. Morikawa, N. Haseguwa, J. Org. Chem. 1990, 55, 2978;
(e) T. Tsuda, Polym. Matel: Sci. Eng. 1999, 80, 449.
[19] (a) G. Burkhart, H. Hoberg, Angew. Chem. 1982, 92, 75; Angew. Chem. Int. Ed. Engl.
1982, 21, 76; (b) H. Hoberg, A. Schafer, G. Burkhart, C. Kriiger, M.-J. Ramso, J. Orga-
nomet. Chem. 1984 , 266, 203; (c) D. Walther, G. Braunlich, R. Kaupe, J. Sieler,
J. Organomet. Chem. 1992,436, 109.
[20] (a) D. Walther, E. Dinjus, H. Schonberg, J. Sieler, J. Organomet. Chem. 1987, 334, 377;
(b) 0. Lindqvist, L. Anderson, Z. Anorg. Chem. 1988, 560, 119; (c) E. Dinjus, J. Kaiser,
J. Sieler, D. Walther, Z. Anorg. Allg. Chem. 1981, 483, 63; (d) J. Kaiser, J. Sieler,
U. Braun, L. Golic, E. Dinjus, D. Walther, J. Organomet. Chem. 1982, 224, 81;
(e) D. Walther, E. Dinjus, V. Herzog, Z. Chem. 1982, 22, 303; (f) D. Walther, E. Dinjus,
J. Sieler, J. Kaiser, 0. Lundquist, L. Andersen, J. Organomet. Chem. 1982, 240, 289;
(8) D. Walther, E. Dinjus, V. Herzog, Z. Chem. 1983,23, 188; (h) D. Walther, E. Dinjus,
V. Herzog, Z. Chem. 1984, 24, 260; (i) D. Walther, E. Dinjus, Z. Chem. 1984, 24, 296;
(k) D. Walther, E. Dinjus, Z. Chem. 1982, 22, 228; (I) E. Dinjus, D. Walther, H. Schutz,
W. Schade, Z. Chem. 1983, 23, 303; (m) D. Walther, E. Dinjus, J. Sieler, N.N. Thanh,
W. Schade, I. Leban, Z. Natu$orsch. Teil B 1983, 38, 835; (n) D. Walther, E. Dinjus,
Z. Chem. 1984, 24, 63; ( 0 ) D. Walther, E. Dinjus, H. Gorls, J. Sieler, 0. Lindquist,
L. Andersen, J. Organomet. Chem. 1985, 286, 103; (p) D. Walther, E. Dinjus, J. Sieler,
L. Andersen, 0. Lindquist, J. Organomet. Chem. 1984, 276, 99; (9) E. Dinjus,
D. Walther, H. Schutz, Z. Chem. 1983, 23, 408; (r) H. Hoberg, D. Schaefer, J. Organo-
met. Chem. 1982,236, C28; (s) H. Hoberg, Y. Peres, A. Milchereit, J. Organomet. Chem.
1986, 307, C38; (t) H. Hoberg, Y. Peres, A. Milchereit, J. Organomet. Chem. 1986, 307,
C41; (u) H. Hoberg, D. Schaefer, J. Organomet. Chem. 1983,238, 383; (v) G. Burkhart,
H. Hoberg, Angew. Chem. 1982, 94, 75; (w) H. Hoberg, D. Schaefer, G. Burkhart,
J. Organomet. Chem. 1982, 228, C21; (x) H. Hoberg, D. Schaefer, G. Burkhart,
C. Kriiger, M.J. Ramao, J. Organomet. Chem. 1984, 266, 203; (y) H. Hoberg,
D. Schaefer, J. Organomet. Chem. 1983, 251, C51.
[21] S. Derieu, J.-C. Clinet, E. Dunach, E., J. Perichon, J. Org. Chem. 1992, 58, 2578 and
references cited therein.
[22] (a) M.T. Reetz, W. Konen, T. Strack, Chimia 1993, 97, 493; (b) E. Dinjus, Reactions
under Extreme and Nonclassical Conditions, COST, Lahnstein, March 1995;
(c) E. Dinjus, R. Fornika, M. Scholz in Chemistry under Extreme or Non-classical
Conditions (Eds.: R. v. Eldik, C. D. Hubbard), Spektmm Akademischer Verlag, Heidel-
berg, 1997.
[23] Chemical Syntheses Using Supercritical Fluids (Eds.: P. G. Jessop, W. Leitner), Wiley-
VCH, Weinheim, 1999.
[24] E. Dinjus, C. Geyer, F. Plenz, unpublished results.
[25] (a) P. Haynes, L.H. Slaugh, J.F. Kohnle, Tetrahedron Lett. 1970, 365; (b) K. Kudo,
H. Phala, N. Sugita, Y. Takezaki, Chem. Lett. 1977, 1495; (c) S. Schreiner, J. Y. Yu,
L. Vaska, J. Chem. Soc., Chem. Commun. 1988, 602.
[26] (a) Mitsubishi Co. (Y. Hashimoto, Y. Inoue), JP 138.614 (1976); Chem. Abstr: 1977, 87,
; Tjin Ltd. (T. Yamaji), JP 166.146 (1981); Chem. Abstr: 1982, 96, 122211~;
6 7 8 5 3 ~ (b)
(c) Tjin Ltd. (T. Yamaji), JP 140.948 (1981); Chem. Abstr: 1982, 96, 68352d; (d) BP Ltd.
(D. J. Drury, J. E. Hamlin), EP 95.321 (1983); Chem. Abstl: 1984, 100, 174262k; (e) BP
Ltd. (A.G. Kent), EP 151.510 (1985); Chem. Abstr: 1986, 104, 109029h; (f) Y. Inoue,
 References 1211

H. Izumida, Y. Sasaki, H. Hashimoto, Chem. Lett. 1976, 863; (8) C. P. Lau, Y. Z. Chen,
J. Mol. Catal. 1995, 101, 33.
[27] J.-C. Tsai, K. M. Nicholas, J. Am. Chem. Soc. 1992, 114, 5117.
[28] M.T. Ngyen, T.-K. Ha, J. Am. Chem. Soc. 1984, 106, 599.
[29] (a) T. Burgemeister, F. Kastner, W. Leitner, Angew. Chem. 1993, 105, 781; Angew. Chem.
Int. Ed. Engl. 1993, 32, 739; (b) W. Leitner, E. Dinjus, F. GaBner, J. Organomet. Chem.
1994, 475, 257; (c) E. Graf, W. Leitner, J. Chem. Soc., Chem. Commun. 1992, 623.
[30] (a) P. J. Fennis, P. H. M. Budzelaar, J. H. G. Frijns, A. G. Orpen, J. Organomet. Chem.
1990, 393, 287; (b) W. Leitner, E. Dinjus, R. Fornika, H. Gorls, J. Organomet. Chem.
1996, 511, 145; (c) R. Fornika, PhD Thesis, Universitat Jena (1994).
[31] R. Fornika, H. Gorls, R. Seemann, W. Leitner, J. Chem. Soc., Chem. Commun. 1995,
1479.
[32] (a) R. Benn, H. Brenneke, R.-D. Reinhardt, Z. Nuturforsch. Teil B 1985, 40, 1763;
(b) R. Benn, H. Brenneke, A. Rufinska, J. 0rganomet.Chem. 1987, 320, 115.
[33] (a) K. Angemund, W. Baumann, E. Dinjus, R. Fornika, H. Gorls, M. Kessler, C. Kriiger,
W. Leitner, M. Lutz, Chem. Eur: J. 1997, 3, 755; (b) W. Leitner, M. Buehl, R. Fornika,
Ch. Six, W. Baumann, E. Dinjus, M. Kessler, C. Krueger, A. Rufinska, Organometallics
1999, 18(7), 1196.
[34] W. Leitner, E. Dinjus, F. GaBner, J. Organomet. Chem. 1994, 475, 257.
[35] K. Kudo, N. Sugita, Y. Takeszaki, Nippon Kagaku Kaishi 1977, 302.
[36] C. J. Stadler, S. Chao, D. P. Summers, M. S. Wrighton, J. Am. Chem. Soc. 1983, 105,
6318.
[37] (a) M. M. Taqui Khan, S. B. Halligudi, S. Shukla, J. Mol. Catal. 1989,53,305; (b) M. M.
Taqui Khan, S. B. Halligudi, S. Shukla, J. Mol. Catal. 1989, 57, 47.
1381 (a) Ruhrchemie AG (R. Gartner, B. Cornils, H. Springer, P. Lappe), DE 3.235.030
(1982); Chem. Abstl: 1984, 101, 55331t; (b) Ruhrchemie AG (L. Bexten, B. Comils,
D. Kupies), DE 3.431.643 (1984); Chem. Abstr: 1986, 105, 11700911; (c) W. A. Herr-
mann, C.W. Kohlpaintner, Angew. Chem. 1993, 105, 1588; Angew. Chem. Int. Ed.
Engl. 1993, 32, 1524.
[39] (a) F. GaRner, W. Leitner, J. Chem. Soc., Chem. Commun. 1993, 1465; (b) F. GaBner,
PhD Thesis, Universitat Jena ( 1 994).
[40] (a) J.R. Pugh, M.R. Bruce, B.P. Sullivan, T. J. Mayer, Inorg. Chem. 1991, 30, 86;
(b) K.K. Pandey, K.H. Garg, S.K. Tiwari, Polyhedron 1992, 947; (c) J.C. Berthet,
M. Ephritikhine, New J. Chem. 1992, 16, 767; (d) D. Nietlispach, H. W. Bosch,
H. Berke, Chem. Bel: 1994, 127, 2403.
[41] (a) B. P. Sullivan, T. J. Meyer, Organometallics 1986, 5, 1500; (b) D. J. Darensbourg,
M. J. Darensbourg, L.Y. Groh, P. Wiegreffe, J. Am. Chem. Soc. 1987, 109, 7539; (c)
D. J. Darensbourg, H. P. Wiegreffe, P. W. Wiegreffe, J. Am. Chem. Soc. 1990, 112, 9252.
[42] (a) A. Dedieu, C. Bo, F. Ingold, in Ref. [3a], p. 22; (b) N. Koga, K. Morokuma, Chem.
Rev. 1991, 91, 283.
[43] (a) S. Sakaki, K. Ohkubo, Inorg. Chem. 1988, 27, 2020; (b) C. Bo, A. Dedieu, Inorg.
Chem. 1989, 28, 304.
[44] (a) S. Sakaki, K. Ohkubo, Organometallics 1989, 8, 2973; (b) S. Sakaki, K. Ohkubo,
Inorg. Chem. 1989, 28, 2583.
[45] (a) V. W. Day, M. F. Fredrich, G. S. Reddy, A. J. Sivak, W. R. Pretzer, E. L. Muetterties,
J. Am. Chem. Soc. 1977, 99, 8091; (b) A. J. Sivak, E. L. Muetterties, J. Am. Chem. Soc.
1979, 101, 4878.
[46] (a) M. D. Fryzuk, Can. J. Chem. 1983, 61, 1347; (b) M. D. Fryzuk, T. Jones, F. W. B.
Einstein, Orgunometullics 1984, 3, 185; (c) M.D. Fryzuk, W.E. Piers, S. J. Rettig,
F. W.B. Einstein, T. Jones, T. A. Albright, J. Am. Chem. Soc. 1989, 111, 5709; (d)
1212 3.3 Special Products

M. D. Fryzuk, W. E. Piers, Organometallics 1990, 9, 986; (e) M. D. Fryzuk, W. E. Piers,

F. W. B. Einstein, T. Jones, Can. J. Chem. 1989, 67, 883.
[47] S. Sakaki, Y. Musahi, J. Chem. Soc., Dalton Trans. 1994, 3047.
[48] F. Hutschka, A. Dedieu, W. Leitner, Angew. Chem. 1995, 107, 1905; Angew. Chem. Int.
Ed. Engl. 1995, 34, 1742.
[49] P.G. Jessop, R. H. Morris, Coord. Chem. Rev. 1992, 121, 155.
[SO] (a) P.G. Jessop, Y. Hisao, T. Ikariya, R. Noyori, J. Am. Chem. SOC.1996, 118, 344; (b)
P. G. Jessop, T. Ikariya, R. Noyori, Science 1995, 269, 1065; (c) P. G. Jessop, T. Ikariya,
R. Noyori, Nature (London) 1994, 368, 231; (d) T. Ikariya, P.G. Jessop, R. Noyori,
JPAppl. 274.721 (1993).
[Sl] C. Y. Tsang, N.B. Streett, Chem. Eng. Sci. 1989, 36, 993.
[52] S. M. Howdle, M. Poliakoff, J. Chem. SOC., Chem. Commun. 1989, 1099.
[53] S. M. Howdle, M.A. Healy, M. Poliakoff, J. Am. Chem. SOC. 1990, 112, 4804.
[54] (a) P.G. Jessop, Y. Hsiao, T. Ikariya, R. Noyori, J. Chem. Soc., Chem. Commun. 1995,
707; (b) 0. Krocher, R.A. Koppel, A. Baiker, Chimia 1997, 48.
1551 (a) I. S. Kolomnikov, T. S. Lobeeva, M. E. Vol’pin, Izv. Akad. Nauk. Ser: Khim. 1970,
2650; (b) T. S. Lobeeva, M. E. Vol’pin, Izv. Akad. Nauk. Ser: Khim. 1972, 2329.
[56] Y. Inoue, Y. Sasaki, H. Hashimoto, J. Chem. Soc., Chem. Commun. 1975, 718.
[57] (a) D. Darensbourg, C. Ovalles, M. Pala, J. Am. Chem. Soc. 1983, 105, 5937; (b) D. Dar-
ensbourg, C. Ovalles, J. Am. Chem. Soc. 1984, 106, 3750; (c) D. Darensbourg,
C. Ovalles, J. Am. Chem. Soc. 1987, 109, 330.
[58] G. 0. Evans, C. J. Newell, Inorg. Chim. Acta 1978, 31, L387.
[59] H. Bipp, U. K. Kicezka, Ullmann’s Encycl. Ind. Chem. 5th ed., 1989, Vol. A12, pp. 1-12.
[60] M. W. Farlow, H. Adkins, J. Am. Chem. Soc. 1935, 57, 2272.
[61] S . Schreiner, J. Y. Yu, L. Vaska, J. Chem. SOC.,Chem. Commun. 1988, 602.
[62] P. Haynes, H. Slaugh, J. F. Kohnle, Tetrahedron Lett. 1970, 365.
[63] Y. Kiso, K. Saeki, Kokai TokkyoKoho, JP 36.617 (1977).
[64] P. G. Jessop, Y. Hsiao, T. Ikariya, R. Noyori, J. Am. Chem. Soc. 1994, 116, 8851.
[65] (a) H. Koinuma, F. Kawakami, H. Kato, H. Hirai, J. Chem. Soc., Chem. Comm. 1981,
213; (b) G. Suss-Fink, J. Reiner, J. Organomet. Chem. 1981, 221, C36.
[66] (a) A. Jansen, H. Gorls, S. Pitter, Organometallics 2000, 19, 135; (b) Forschungszentrum
Karlsruhe (S. Pitter, A. Jansen, E. Dinjus), DE 199.11.616 (2000).
[67] T. C. Eisenschmid, R. Eisenberg, Organometallics 1989, 8, 1822.
[68] P.G. Jessop, Top. Catal. 1998, 3, 9.5.
[69] S. Pitter, A. Jansen, unpublished results.
[70] A.-A.G. Shaikh, S. Sivaram, Chem. Rev. 1996, 96, 681.
[71] M.A. Pacheco, C. L. Marshall, Energy & Fuels 1997, 11, 2.
[72] (a) G. Illuminati, U. Romano, R. Tesei, DE 2.528.412 (1979); (b) F. Merger, F. Towee,
L. Schroff, EP 0.000.162 (1979); (c) A. Bomben, M. Selva, P. Tundo, Recl. Trav. Chim.
Pays-Bas 1996, 115, 256.
[73] A. Wagner, W. Loffler, B. Haas, WO 94/22805, 1994.
[74] (a) T. Sakakura, Y. Saito, M. Okano, J.-C. Choi, T. Sako, J. Org. Chem. 1998, 63, 7095;
(b) T. Sakakura, Y. Saito, M. Okano, J.-C. Choi, T. Sako, J. Am. Chem. Soc. 1999, 121,
3793; (c) T. Sakakura, Y. Saito, M. Okano, J.-C. Choi, T. Sako, J. Org. Chem. 1999, 64,
4506.
[75] J. Kizling, Collect. Czech. Chem. Comm. 1993, 58, 1399; (b) J. Kizling, I. Pastucha,
Collect. Czech. Chem. Commun. 1994, 59, 2116; ( c ) J. Kizling, I. Pastucha, Collect.
Czech. Chem. Commun. 1995, 60, 687.
[76] (a) In A. G. Davies, Organotin Chemistry, Weinheim, VCH, 1997; (b) A. J. Bloodworth,
A. G. Davies, S. C. Vasishtha, J. Chem. Soc. (C) 1967, 1309; (c) A. G. Davies, P. G.
 References 1213

Harrison, J. Chem. Soc. (C) 1967, 1313; (d) A. G. Davies, D. C. Kleinschmidt, P. R.

Palan, S. C. Vasishtha, J. Chem. Soc. (C) 1971, 3972.
[77]J. Kummerlen, A. Sebald, H. Reuter, J. Organomet. Chem. 1992, 427, 309.
[78]For some recent examples of C 0 2 insertion into epoxides, see: (a) K. Kasuga, N. Kabata,
Znorg. Chim. Acta 1997, 257, 277; (b) T. Yano, H. Matsui, T. Koike, H. Ihiguro,
H. Fujihara, M. Yoshihara, T. Maeshima, J. Chem. Soc., Chem. Commun. 1997, 1129;
(c) K. Yamaguchi, K. Ebitani, T. Yoshida, H. Yoshida, K. Kaneda, J. Am. Chern. SOC.
1999, 121, 4526; (d) K. Kasuga, S. Nagao, T. Fukumoto, M. Handa, Polyhedron
1996, 15, 69;(e) W. J. Kruper, D. V. Dellar, J. Org. Chem. 1995, 60, 725;(f) D.Darens-
bourg, M. W. Holtcamp, B. Khandelwal, K. K. Klausmeyer, J. H. Reibenspies, J. Am.
Chem. SOC.1995, 117, 538.
[79](a) S.A. Motika, T. L. Pickering, A. Rokicki, B. K. Stein, US 5.026.676(1991);(b) H.-N.
Sun, US 4.783.445(1988);(c) H.-N. Sun, US 4.789.727(1988);(d) A. Rokicki, US
4.943.677(1990);(e) W. E. Carroll, S. A. Motika, US 4.960.862(1990);(0H. Kawachi,
S. Minami, J. N. Armor, A. Rokicki, B. K. Stein, US 4.981.948(1991);(g) S. Inoue,
M. Kanbe, T. Takada, N. Miyazaki, M. Yokokawa, US 3.953.383.
[80] (a) H. Schnell, Chemistry and Physics of Polycarbonates, in Encyclopedia of Polymer
Science and Technology, Vol. 10, John Wiley, New York, 1964; (b) H. Schnell,
Angew. Chern. 1966, 73, 629; (c) W. Kuran, in Polymeric Material Encyclopedia,
Vol. 9, CRC Press, Boca Raton, 1996.
[81] (a) S. Inoue, Makromol. Chem., Rapid Commun. 1980, 1, 775;(b) K. Soga, K. Uenishi,
S. Ikeda, J. Polym. Sci.: Polym. Chem. Ed. 1979, 17, 415.
[82](a) E. J. Beckmann, T. Hoefling, D. Stofesky, M. Reid, R. Enick, J. Supercrit. Fluids
1992, 5, 237; (b) M. Super, E. Berluche, C. Costello, E. J. Beckman, Macromolecules
1997, 30, 368.
[83] (a) T.A. Zevaco, H. Gorls, E. Dinjus, Polyhedron 1998, 17, 613; (b) T.A. Zevaco,
H. Gorls, E. Dinjus, Znorg. Chem. Commun. 1998, 1, 170; (c) T. A. Zevaco, H. Gorls,
E. Dinjus, Polyhedron 1998, 17, 2199.
[841 (a) W. Kuran, S. Psynkiewicz, Makromol. Chem. 1979, 180, 1253;(b) W. Kuran, A. Ro-
kicki, D. Romanowska, J. Polym. Sci., Polym. Chem. Ed. 1979, 17, 2003;(c) w . Kuran,
T. Listos, Macromol. Chem. Phys. 1994, 195, 1011;(d) P. Gorecki, W. Kuran, J. Polym.
Chem.: Polyrn. Lett Ed. 1985, 23, 299.
[85] (a) S. Inoue, H. Koinuma, T. Tsuruta, Makromol. Chem. 1969, 130, 210; (b) S. Inoue,
H. Koinuma, T. Tsuruta, Makromol. Chern. 1971, 143, 97.
[86]J. Darensbourg, M. W. Holtcamp, Coord. Chern. Rev. 1996, 153, 155; (b) D. J. Darens-
bourg, N. W. Stafford, T. Katsuaro, J. Mol. Catal. A 1995, 104, L1-L4.
[87](a) M. Cheng, E.B. Lobkovsky, G.W. Coates, J. Am. Chem. Soc. 1998, 120, 11018;
(b) M. Cheng, N.A. Darling, E.B. Lobkovsky, G.W. Coates, J. Chem. Soc., Chem.
Commun. 2000,2007.
[88] (a) T.Aida , S. Inoue, Acc. Chem. Res. 1996,29, 39;(b) S.Hiroshi, K. Chikara, T. Aida,
S. Inoue, Macromolecules 1994,27,2013; (c) Y. Watanabe, T. Yasuda, T. Aida, S. Inoue,
Macromolecules 1992, 25, 1396;(d) T.Aida , S. Inoue, J. Am. Chem. Soc. 1983, 105,
1304.
 Applied Homogeneous Catalysis with Organometallic Compounds
Edited by B. Cornils and W. A. Herrmann
Copyright 0 Wiley-VCH Verlag GmbH, D-69469 Weinheim, 2002

1214 3.3 Special Products

3.3.5 Reductive Carbonylation of Nitro Compounds

Markus Dugal, Daniel Koch, Guido Naber$eld, Christian Six

3.3.5.1 Introductory Remarks

Reductive carbonylation of nitro compounds, especially nitroaromatic compounds
according to eq. (I), has been the subject of thorough industrial research starting
in 1962 and continuing until the beginning of the 1990s due to the demand for a
new, phosgene-free method for the production of isocyanates [I] and the discus-
sions on the chlorine cycle in industry.

Ar-N02 + 3 CO -Ar-NCO + 2C01 (1)

The “dream reaction” leading to industrially relevant isocyanates would be a

low-cost one-step synthesis starting from the corresponding nitro precursors
[2, 31. Arising problems favored an alternative two-step reaction via urethanes,
which seemed to represent a feasible technical method to reduce the costs of iso-
cyanate production by about 25-30 % [4]. All the announcements referring thereto
have been shown to be invalid, simply because the abundant observations claimed
in numerous patents and other publications led to an inadequate and optimistic
evaluation, although the chemistry was very poorly understood at that time.
After 1969 research on homogeneous reductive carbonylation of nitro compounds
using compounds of ruthenium, rhodium, and palladium as catalysts increased in
academic laboratories. The most recent period is characterized by in-depth studies
in academia on the one hand on the mechanism of activation and catalysis and the
nature of the catalytic species, and a declining interest in industry on the other
hand, at least when speaking of the manufacture of large-scale diisocyanates
which typically find use in the polyurethane industry.
The purpose of this section is to summarize the results of this continuous devel-
opment, focusing on the most interesting compounds: isocyanates and urethanes.
Analogous reactions of this type leading to different products will just be men-
tioned in passing [ 1, 5-71.

3.3.5.2 Synthesis of Isocyanates

3.3.5.2.1 Manufacture with Phosgene

At least 90 % of the worldwide production of isocyanates is accounted for by two
aromatic isocyanates, toluene diisocyanate (TDI), a distilled compound, and poly-
methylene polyphenylene polyisocyanate (PMDI), an undistilled isocyanate mix-
ture with a low vapor pressure (Structures 1-3). Together these two products cur-
 3.3.5.2 Synthesis of Isocyanates 1215

rently amount to a total annual world production of 3.3 Mt. They are mainly used
for the production of a broad spectrum of polyurethanes, e. g., foams, elastomers,
and coatings [8, 91.

Nco

1 2
2,4 - TDI 2,6 TDI
*

3
PMDl

Aromatic isocyanates are produced commercially by phosgenation of the corre-

sponding amine base [lo]. Phosgene excess, HC1, and solvent are recycled. Phos-
gene, which is produced catalytically on charcoal from carbon monoxide and
chlorine, is a highly active, poisonous, and corrosive gas. Therefore, numerous
attempts have been made to develop phosgene-free processes, i. e., methods for
the production of isocyanates without handling chlorine, one of them being the
homogeneous catalytic carbonylation of nitroaromatic compounds.

3.3.5.2.2 Attempts with Carbon Monoxide

Numerous patents [3, 11-13] and other publications [3, 14-16] describe the direct
carbonylation of nitroaromatic compounds to isocyanates or alternatively a modi-
fied carbonylation to urethanes in the presence of alcohol, followed by a thermal
transformation to isocyanates [4, 17-19] (eq. (2)).
- Ar-NHCOOR

1
ROH
cat. AT, - ROH
Ar-N02 + 3CO ___
- 2 c02

- Ar-NCO

Ar = aromatic group
ROH = aliphatic alcohol
1216 3.3 Special Products

Direct Carbonylation to Isocyanates

In the first reported direct N-carbonylation of nitroaromatics to isocyanates,

simple Pd- or Rh-based systems were used to catalyze the reaction of aromatic
mononitro compounds with carbon monoxide [ l l , 121. Later, it became possible
to work without the drastic reaction conditions that had been required initially, by
using Lewis acid co-catalysts [ 131. Various catalysts and catalyst mixtures,
normally based on Ru, Rh, or Pd complexes with co-catalysts, were described
in numerous patents and publications [ l , 3, 14-16]. The careful choice of the com-
position of the triad consisting of metal salt, co-catalysts and ligand (preferably
aromatic amines) led to efficient catalyst systems [ 14 a-el for the direct reductive
carbonylation process. A quite active Pd-phenanthroline-H' system with non-
coordinating carboxylic acids such as 2,4,6-trimethlybenzoic acid as proton
source is worth mentioning [ 14 d].
However, although promising results have been achieved with mononitro
compounds, dinitro compounds can be converted only with low selectivities
and using high catalyst concentrations. Furthermore, in spite of extensive inves-
tigations of the reaction mechanism (see Section 3.3.5.3. l), questions that still
remain unanswered are, whether the active catalytic species is a heterogeneous
one or a soluble species generated in situ, and what the function of the co-
catalyst is.
The difficulties of utilizing the direct reductive carbonylation of nitroaromatic
compounds for the production of industrially relevant isocyanates are docu-
mented by three publications discussing different palladium-based catalysts. A
metallacyclic complex from the reaction of nitrobenzene with carbon monoxide
in the presence of Pd-o-phenanthroline decomposes to phenyl isocyanate
only in moderate yield, which may be an indication of an intrinsic limitation
related to the mechanistic pathway of the catalytic reaction [20]. Heteropoly-
compounds with high redox potentials effectively modify the thoroughly
investigated catalyst PdC12, resulting in good selectivities but poor conversion
of nitrobenzene to phenyl isocyanate [14e]. Another study has focused on the
reductive carbonylation of 2,4-dinitrotoluene to 2,4-TDI [ 14 b]. Although the
conversions and selectivities reported are prohibitive for commercial use, for
the first time a deeper understanding of parts of the reaction pathways has
been obtained.
Summarizing, from the investigations in this field it can be concluded that from
an industrial viewpoint the direct carbonylation of nitroaromatics to isocyanates
represents no economically feasible alternative, for the conventional phosgenation
process, for the following reasons:

(1) High catalyst concentrations are necessary due to generally low turnover num-
bers, while insufficent stability and unsolved problems in catalyst recycling,
especially in continuous processes, remain.
(2) Despite promising results for the model reaction of mononitroaromatic com-
pounds to monoisocyanates, the selectivities for the industrially important
reaction of dinitrotoluene to TDI are unacceptable (for PMDI see [21]).
 3.3.5.2 Synthesis of Isocyanates 1217

Reductive Carbonylation to Urethanes

Simultaneously with the disclosure of the direct carbonylation to isocyanates, in

1962 ICI patents claimed the formation of urethanes from nitroarenes by reductive
carbonylation in the presence of alcohols. This approach can be pictured as a
direct carbonylation step followed by a trapping reaction of the isocyanate pro-
duced with an alcohol with the formation of urethanes. Subsequent work used
complexes of ruthenium [22], rhodium [23] and palladium [24], which also
showed good selectivity and high yield for dinitroaromatic substrates in some
cases [25]. Despite the fact that these interesting reactions were discovered
more than 40 years ago a clear picture of the mechanisms with group VIII cata-
lysts is still not in sight. It turns out that the nature of the catalyst and the alcohol
itself seems to have a strong impact on the elementary steps of this interesting
transformation. For instance, it was discovered that the presence of alcohol
often had a strong influence on the activity of a system. Further, it was found
that temperature effects in the presence or absence of alcohol was often not com-
patible with the hypothesis of a common carbonylation mechanism. All these
results suggested that the alcohol interacts with the catalyst and does not simply
trap the isocyanate, which implies that the catalytic cycle is different from the
catalytic cycle of the direct carbonylation [28-301. Obviously, more work is
needed to rationalize the current data.
Taken altogether, the two-stage process based on the reductive carbonylation to
urethanes operates under milder conditions, with lower catalyst concentrations and
a good selectivity to the intermediate urethane, but causes a new problem that for
a long time was underestimated, i.e., the thermal cracking to isocyanates [26],
especially to TDI. Although it was apparently practicable as an industrial process,
the carbonylation reaction conditions and the high temperatures required for split-
ting the urethane obviously limited its applicability as a general synthetic method.
Therefore, the announcement of the construction of a pilot plant for TDI [4] turned
out to be falsely optimistic.
More recently a new approach employing BC13 as reactant (Scheme 1) has been
proposed as a substitute for the industrial thermal cracking process [27]. In most
cases, quantitative conversion to the product isocyanates was achieved under mild
conditions but with the disadvantage of a high BC13 consumption.

X*B,
A r
J
H
N
0
y0\
l
3 -Ar/Nyo,R
- TX2
Ar-NCO + BX,(OR)

CI 0 X=CIorOR

Scheme 1
1218 3.3 Special Products

3.3.5.3 Thermodynamics, Kinetics, and Mechanism

3.3.5.3.1 Direct Carbonylation of Nitroaromatics

In this section, available kinetic and mechanistic data for the reaction of nitro-
aromatic compounds with carbon monoxide are summarized. This reaction is ther-
modynamically favorable, being characterized by high equilibrium constants [32]
and negative reaction enthalpies (eqs. (3) and (4)) [ l , 14bl. Without catalysis high
activation barriers (high temperatures, high pressure) have to be overcome, leading
to azo derivatives [33]. Due to the high exothermicity of the reaction an optimized
catalyst system and optimized reaction conditions are required to ensure selective
isocyanate formation.

+ 3co -Q NCO
+ 2c02 (3)

AH = -1 29 kcal/rnol

kNo2+
NO2
6CO -@Nco+

NCO
4co2 (4)

AH = -228 kcal/mol

For the direct carbonylation with group VIII transition metal catalysts two main
types of mechanisms have been proposed so far, involving the formation of a
metal-imido (e. g., Structure 4) or a metallacyclic intermediate (e. g., Structure 5 )
[31.
0

co

co \ .p' 1 CO

Scheme 2. Mechanism for the direct carbonylation involving a metal-imido intermediate [3].
 3.3.5.3 Thermodynamics, Kinetics, and Mechanism 1219

\
J co
-Ar

Structure 5

Scheme 3. Mechanism for the direct carbonylation involving a metallacyclic intermediate [3].

The Metal-Imido Mechanisms

In an early publication [16] the carbonylation of nitroaromatics was described as a

stepwise deoxygenation of the nitro group, generating an excited singlet nitrene
(probably stabilized by coordination on a metal center). Based on this description,
the formation of a metal-imido intermediate was usually assumed in most of the
proposed mechanisms until the mid-1980s [5, 34-38].
The intermediacy of an imido species does in fact rationalize the formation of
most of the minor typical by-products isolated after carbonylation reactions : after
the deoxygenation of the nitro group the resulting excited singlet nitrene is spon-
taneously intercepted by carbon monoxide to form an isocyanate. In the case of
lack of carbon monoxide, intersystem crossing to the ground-state triplet nitrene
occurs, which is responsible for unwanted side reactions. Therefore, optimized re-
action conditions (high carbon monoxide pressure and temperature) are obligatory
to ensure reasonable selectivity.

The Metallacyclic Mechanism

Despite several experimental facts [3] rendering a transient metal-imido species a

likely source for many products of the carbonylation reaction, its role as an actual
intermediate in the catalytic transformation of simple nitroaromatic substrates has
never been proven. Accordingly, a type-5 mechanism (Scheme 3, involving no
such intermediate) could also be operative for the formation of isocyanate. In
this case, an imido complex could also be generated by a parallel minor pathway
1220 3.3 Special Products

[ Pd] precursor PhNO,

in situ / co 0
\\
initiating species
PhNHC0,Et hl

(N-N)Pd,\
,o
(N-N)Pd
N,Ph

ico
I I
Structure 6

or

Scheme 4. Reaction cycle to the metallacyclic complex and products [20].

and account for the by-products isolated. Such a mechanism, although proposed
very early [39, 401, has gained more consideration just recently from investiga-
tions conducted on the ([Pd]/phen/H’) system [20, 411. A surprisingly stable
1: 1 intermediate metallacyclic complex (Structure 6, N-N = o-phenanthroline)
could be isolated from the reaction of nitrobenzene, carbon monoxide, and
Pd-o-phenanthroline and structurally characterized [42, 431.
General evidence for that kind of mechanism comes from ab initio theoretical
calculations performed on a related platinum complex [3, 441 and from the reac-
tivity of four- and five-membered heterometallacyles [45] structurally close to
some of the intermediates in postulated mechanisms (e.g., Scheme 3). Moreover,
related metallacycles have often been isolated from the reaction medium after
nitroaromatic carbonylation, indicating that such species can easily be generated
under typical carbonylation conditions [46, 471.

3.3.5.3.2 Indirect Carbonylation of Nitroaromatics

Conceptually, the indirect carbonylation of nitroaromatics can be pictured as a
direct carbonylation reaction, followed by a scavenger reaction of the highly re-
active intermediate isocyanate by the alcohol in a subsequent step before by-prod-
uct formation comes into play. The latter is known to occur spontaneously at am-
bient temperature [48,49] and is catalyzed efficiently by many compounds having
 3.3.5.3 Thermodynamics, Kinetics, and Mechanism 1221

either Lewis acidity or basicity [50-531. Since this follow-up reaction is very
much favored on thermodynamic grounds, the complete indirect carbonylation
process is even more exothermic than the direct one [3].
For a long time, the indirect carbonylation reaction was believed to proceed via
that modified direct carbonylation mechanism. In the early 1970s, such a belief
was also supported by the demonstration that the described scavenger reaction,
known to be feasible with free isocyanates, could be applied as well to isocyanates
complexed on various metal centers [54, 551
Around the mid- 1980s, however, more and more experimental facts accumu-
lated that indicated distinct mechanistic differences between the direct and indirect
carbonylation reactions. For instance, it was discovered that the presence of alco-
hol often had a strong influence on the activity of a given system when compared
with the corresponding direct process [56-581. Moreover, the reported influence
of temperature using the same catalysts, whether in the presence of alcohol or
not, was often not likely to be compatible with the hypothesis of a common car-
bonylation mechanism for both processes [59]. Finally, it was reported in many
instances that the nature of the alcohol itself was decisive regarding the yield in
carbamate [56]. In some cases, depending on the catalyst used, alcohols having
active hydrogen acted as a molecular hydrogen source in the medium and led
to a noticeable increase in the formation of aniline or other hydrogenated products
compared with alcohols commonly used in these processes [60, 611. All of these
facts indicate that the alcohol interacts with the catalyst during the carbonylation
process and does not simply trap the intermediate isocyanate. Therefore mecha-
nisms in which the alcohol took part in the formation of the actual active species
were considered.
In Scheme 5 (a) and (b) for instance, the alcohol intervenes very early in the
catalytic cycle and it is essential for the efficient carbonylatiorddeoxygenation
of the substrate [56, 62-64]. Among the mechanisms proposed, only Scheme
5 (c) [3] remains somewhat related to the simple scheme mentioned earlier invok-
ing isocyanate as the primary reaction product, subsequently trapped by alcohol.
In the mechanisms according to Scheme 5(a)-(c) the initial steps (nitro acti-
vation and first deoxygenation) are believed to be similar to those delineated
for direct carbonylation (cf. Schemes 2 and 3). None of these, however, includes
a step where a metal-imido intermediate is generated and subsequently carbon-
ylated to give the isocyanate. Since the early studies on imido complexes, the car-
bonylation of such an intermediate in relation to competitive protonation to give
an amido species was thought questionable when a proton donor like alcohol was
present [65-681. In this respect, the mechanism (Scheme 5 (a)) initially advanced
for Ru3(C0)12/TBAC1[3, 56, 691 and other cluster-based systems was the first
serious proposal for indirect carbonylation, despite presenting very little experi-
mental support. Now, Scheme 5 (b) is clearly established for [(dppe)R~(CO)~]
[3, 31, 70-721 and appears to be the mechanism operative with R U ~ ( C O )in ~*
the presence of dppe [3], and possibly also with other cluster-based systems for
which Scheme 5 (a) had formerly been proposed. This mechanism finds indubita-
bly the strongest experimental support among the proposed mechanisms.
Remarkably, Scheme 5 (c), which has been discussed for the ([Pd]/phen/H+) [3]
1222 3.3 Special Products

(4 ArNO,

ArNHC0,R

Y
0
[MI” =kAr
>R ROH
O u
co
ArNHC0,R
ArNO,

ArNHC(0)NHAr

ArNO,
ArNHC0,R

[ml

Ar

Scheme 5. Mechanisms for the indirect carbonylation involving an interaction of the alcohol
with the catalyst (a and b) or an isocyanate intermediate (c) [ 3 ] .
 References 1223

system, is the only mechanism that allows a catalyst to retain its activity for iso-
cyanate production without the presence of alcohol. Indeed, no free isocyanate
can possibly be generated by mechanism 5 (a) or (b) under direct conditions. A
Brmsted acid promoter was present in most catalytic systems for which mecha-
nism 5(c) has been put forward. In that respect, the absence of carbamoyl or
alkoxycarbonyl intermediates in Scheme 5 (c) is consistent with the presence of
protons, which are known to disfavor the formation of such complexes [73-761.
Now, if one wants to tie together all the mechanistic data available for indirect
carbonylation reactions on group VIII catalysts, no unifying picture currently
emerges and, depending on the nature of the catalytic system used, the mechanism
according to either Scheme 5 (b) or (c) appears very likely to be operative.

3.3.5.4 Outlook
Although in principle it is a practicable industrial process, catalytic reductive car-
bonylation of nitroaromatic compounds has not become a general synthetic
method on a technical scale so far: this type of reaction remains a laboratory
tool for special products, although excellent selectivities are already observed.
The situation will change, if the comprehensive studies of the catalytic cycle,
especially from a kinetic and mechanistic viewpoint, should lead to the design
of a continuous catalytic process with significant improvement in catalyst load,
lifetime, and turnover frequency in combination with a practice-oriented concept
in catalyst recovery or regeneration. Results of relevant investigations are sum-
marized here, focusing on industrially relevant aspects. Summing up, a “Golden
Age” cannot be predicted yet for a large-scale industrial application of homoge-
neous catalytic carbonylation with noble metallacyclic complexes of nitroaromatic
compounds to the corresponding isocyanates. The classic phosgenation route
remains the only economically attractive route for industrial production of com-
modity isocyanates.

References
[ l ] S. Cenini, M. Pizzotti, C. Crotti, Corrado, Aspects Homogen. Catal. 1988, 6, 97, and
references cited therein.
[2] Plastics Handbook - Polyurethanes, Vol. 7, 3rd ed. (Eds.: G. Oertel, L. Abele), Carl
Hanser, Munich, 1993.
[3] For a comprehensive review see: F. Paul, Coord. Chem. Rev. 2000, 203, 269.
[4] Anon., Chemical Week 1997, March 9, 43.
[5] A.F.M. Iqbal, Chem. Technol. 1974, 4(9), 566.
[6] H. M. Colquhoun, D. J. Thompson, M. V. Twigg (Eds.), Carbonylation - Direct Syn-
thesis of Carbonyl Compounds, Plenum, New York, 1991, p. 164.
[7] H. Ulrich, Chemistry and Technology of Zsocyanates, Wiley, Chichester, 1996,
pp. 333-334, 375-379.
[8] J. K. Backus et al., Encycl. Polym. Sci. Eng., 1988, 13, 243.
1224 3.3 Special Products

[9] H. Ulrich, Isocyanates, Organic, in Ullmann’s Encycl. Ind. Chem., 6th ed., Wiley-VCH,
Weinheim, 2001 (electronic version).
[lo] H. J. Twichett, Chem. SOC. Rev. 1974, 3(2), 209.
[ l l ] American Cyanamid (W. B. Hardy, R. P. Bennet), DE 1.237.103 (1963).
[I21 American Cyanamid (W.B. Hardy, R.P. Bennet), US 3.461.149 (1965).
[I31 Olin Mathieson Corp. (G. F. Ottmann, E. H. Kober, D. F. Gavin), US 3.523.962; (E. H.
Kober, W.J. Schnabel, T.C. Kraus, G.F. Ottmann), US 3.523.965; (W.J. Schnabel,
E.H. Kober, T.C. Kraus), US 3.714.216 (1967), (E. H. Kober, W. J. Schnabel), DE
2.018.299 (1970); (G. F. Ottmann, W. J. Schnabel, E. Smith), 3.728.370 (1970); (P. D.
Hammond, J. A. Scott), US 3.812.169; (P. D. Hammond, W. C. Clarke, W. I. Denton),
US 3.832.372 (1972).
[ 141 (a) V. I. Manov-Yuvenskii, B. A. Redoshkin, B. K. Nefedov, G. P. Beyaeva, Bull. Acad.
Sci. USSR Div. Chem. Sci. 1980, 29, 117; (b) R. Ugo, R. Psaro, M. Pizotti, P. Nardi,
C. Dossi, A. Andretta, G. Caparella, J. Organomet. Chem. 1991, 417, 211;
(c) Y. Izumi; Y. Satoh, K. Urabe, Chem. Lett. 1990, 795; (d) S. Cenini, F. Ragaini,
M. Pizotti, F. Porta, G. Mestroni, E. Alessio, J. Mol. Catal. 1991, 64, 179; (e) Y. Izumi,
Y. Satoh, H. Kondoh, K. Urabe, J. Mol. Catal. 1992, 72, 37.
[15] W.B. Hardy, R.P. Bennett, Tetrahedron Lett. 1967, 961.
[16] F.J. Weigert, J. Org. Chem. 1973, 38, 1316.
[I71 ICI (B.A. Mountfield), GB 993.704 (1962); (A. Ibbotson), GB 1.080.094; (G. A.
Gamlen, A. Ibbotson), GB 1.092.157 (1965).
[18] Mitsui Toatsu (F. Zunistein sen. et al.), DE 2.555.557 (1974).
[19] Shell (E. Drent, P. W. van Leeuwen), EP 0.086.281 (1981).
[20] P. Leconte, F. Metz, A. Mortreux, J. A. Osbom, F. Paul, F. Petit, A. Pillot, J. Chem. Soc.,
Chem. Commun. 1990, 1616.
[21] The only economic process for PMDI is the reaction via aniline-formaldehyde and sub-
sequent phosgenation.
[22] S. Cenini, C. Crotti, M. Pizzotti, F. Porta, J. Org. Chem. 1988, 53, 1243.
[23] C. V. Rode, S. P. Gupta, R. V. Chaudhari, C. Pirozhkov, A. L. Lapidus, J. Mol. Catal.
1994, 91 195.
[24] A. Bontempi, E. Alessio, G. Chanos, G. Mestroni, J. Mol. Catal. 1987, 42, 67.
[25] Montedison (E. Alessio, G. Mestroni), EP 0.169.650 (1985).
[26] M.Z.A. Badr, M.M. Aly, S.A. Mahgoub, A.A. Attallah, Rev. Roum. Chim. 1992,
37, 489.
[27] D.C. D. Butler, H. Alper, Chem. Commun. 1998, 2575.
[28] S. Bhaduri, H. Khwaja, N. Sapre, K. Sharma, A. Basu, P. G. Jones, G. Carpenter, J. Chem.
Soc., Dalton Trans. 1990, 1313.
[29] S. Bhaduri, H. Khwaja, K. Sharma, P.G. Jones,J. Chem. Soc., Chem. Commun. 1989,515.
[30] G. Mestroni, G. Zassinovich, E. Alessio, M. Tomatore, J. Mol. Catal. 1989, 49, 175.
[31] J. D. Gargulak, W. L. Gladfelter, 1. Am. Chem. SOC.1994, 116, 3792; J. D. Gargulak,
A. J. Berry, M. D. Noirot, W. L. Gladfelter, J. Am. Chem. Soc. 1992, 114, 8933.
[32] K. Schwetlick, K. Unverferth, H. Tietz, SYSpur Rep. 1981, 3.
[33] G. D. Buckley, N. H. Ray, J. Chem. Soc. 1949, 1154; E. Glaser, R. van Beneden, G e m . -
1ng.-Tech. 1957, 29, 512.
[34] T. Kajimoto, J. Tsuji, Bull. Chem. SOC.Jpn. 1969, 42, 827.
[35] B. K. Nefedov, V. I. Manov-Yuvenskii, S. S. Novikov, Doklady Chem. (Proc. Acad. Sci.
USSR) 1977, 234, 347.
[36] L. V. Gorbunova, I. L. Knyazeva, E.A. Davydova, G.A. Abakumov, Bull. Acad. Sci.
USSR Div. Chem. Sci. 1980, 29, 761.
[37] F. Lefebvre, P. Gelin, B. Elleuch, C. Naccache, Y. Ben Taarit, Bull. Chim. SOC.Fr: 1984,
361.
 References 1225

[38] V. I. Manov-Yuvenskii, K. B. Petrovskii, A. L. Lapidus, Bull. Acad. Sci. USSR Div.

Chem. Sci. 1986, 34, 1561.
[39] K. Unferverth, K. Schwetlick, React. Kinet. Catal. Lett. 1977, 6, 231; K. Unferverth,
R. Hiintsch, K. Schwetlick, J. Prakt. Chem. 1979, 321, 928.
[40] K. Unferverth, R. Hontsch, K. Schwetlick, J. Prakt. Chem. 1979, 321, 86.
[41] F. Paul, J. Fischer, P. Ochsenbein, J. A. Osbom, Organometallics 1998, 11, 2199.
[42] A.S. 0 Santi, B. Milani, G. Mestroni, L. Randaccio, J. Organomet. Chem. 1997,
545-546, 89.
[43] N. Masciocchi, F. Ragaini, S. Cenini, A. Sironi, Organometallics 1998, 17, 1052.
[44] P. Fantucci, M. Pizzotti, F. Porta, Inorg. Chem. 1991, 30, 2277.
[45] F. Paul, J. Fischer, P. Ochsenbein, J. A. Osborn, Angew. Chem., lnt. Ed. Engl. 1993,
32, 1638.
[46] F. Ragaini, S. Cenini, Organometallics 1994, 13, 1178; F. Ragaini, S. Cenini, F. Demar-
tin, J. Chem. SOC.,Chem. Commun. 1992, 1467.
[47] L. Dahlenburg, C. Prengel, Inorg. Chim. Acta 1986, 122, 55.
[48] 0. Agherghinei, C. Prisacariu, A.A. Caraculacu, Rev. Roum. Chim. 1991, 36, 9.
[49] A. A. Caraculacu, I. Agerghinei, M. Gaspar, C. Prisacariu, J. Chem. Soc., Perkin Trans.
1990, 1343.
[50] D. P. N. Satchell, R. S. Satchell, Chem. Soc. Rev. 1975, 4, 231.
[51] G. Hazzard, S. A. Lammiman, N. L. Poon, D. P. N. Satchell, R. S. Satchell, J. Chem. SOC.,
Perkin Trans. II 1985, 1029.
[52] J. J. Tondeur, G. Vandendunghen, M. Watelet, Chim. Nouv. 1992, 10, 1148.
[53] K. Schwetlick, R. Noak, F. Stebner, J. Chem. Soc., Perkin Trans. II 1994, 599.
[54] K. von Werner, W. Beck, Chem. Ber: 1971, 104, 2907.
[55] K. von Werner, W. Beck, Chem. Ber: 1972, 105, 3947.
[56] S. Cenini, C. Crotti, M. Pizzotti, F. Porta, J. Org. Chem. 1988, 53, 1243.
[57] S. Bhaduri, H. Khwaja, K. Sharma, P.G. Jones, J. Chem. Soc., Chem. Commun. 1989,
515.
[58] H.A. Alper, K.E. Hashem, J. Am. Chem. Soc. 1981, 103, 6514.
[59] S. Bhaduri, H. Khwaja, N. Sapre, K. Sharma, A. Basu, P.G. Jones, G. Carpenter, J. Chem.
SOC.,Dalton Trans. 1990, 1313.
[60] C.-H. Liu, C.-H. Cheng, J. Organomet. Chem. 1991, 420, 119.
[61] G. Mestroni, G. Zassinovich, E. Alessio, M. Tornatore, J. Mol. Catal. 1989, 49, 175.
[62] A. Bassoli, B. Rindone, S. Cenini, J. Mol. Catal. 1991, 66, 163.
[63] A. Bassoli, B. Rindone, S. Tollari, S. Cenini, C. Crotti, J. Mol. Catal. 1990, 60, 155.
[64] E. Bolzacchini, R. Lucini, S. Meinardi, M. Orlandi, B. Rindone, J. Mol. Catal. A Chem.
1996, 110, 227.
[65] S. Cenini, M. Pizzotti, F. Porta, G. La Monica, J. Organomet. Chem. 1975, 88, 237.
[66] W. Beck, M. Bauder, G. La Monica, S. Cenini, R. Ugo, J. Chem. SOC.,PartA 1971, 113.
[67] D. E. Wigley, Prog. Inorg. Chem. 1994, 42, 239.
[68] A. L. Lapidus, S. D. Pirozhkov, A. R. Tumanova, A. V. Dolidze, A.M. Yukhimenko, Bull.
Acad. Sci. USSR Div. Chem. Sci. 1992, 41, 1672.
[69] S. Cenini, M. Pizzotti, C. Crotti, F. Porta, G. La Monica, J. Chern. SOC.,Chem. Commun.
1984, 1286.
[70] A. J. Kunin, M.D. Noirot, W. L. Gladfelter, J. Am. Chem. SOC.1989, I l l , 2739.
[71] S.J. Skoog, W.L. Gladfelter, J. Am. Chem. Soc. 1997, 119, 11049.
[72] J.D. Gargulak, W.L. Gladfelter, J. Am. Chem. SOC.1994, 116, 3792.
[73] G. Cavinato, L. Toniolo, J. Organomet. Chem. 1993, 444, C65.
[74] J.E. Byrd, J. Halpem, J. Am. Chem. Soc. 1971, 93, 1634.
[75] R. J. Angelici, Ace. Chem. Res. 1972, 5, 335.
[76] C. R. Green, R. J. Angelici, Inorg. Chem. 1972, 11, 2095.
 Applied Homogeneous Catalysis with Organometallic Compounds
Edited by B. Cornils and W. A. Herrmann
Copyright 0 Wiley-VCH Verlag GmbH, D-69469 Weinheim, 2002

1226 3.3 Special Products

3.3.6 New Approaches in C-H Activation of Alkanes

Ayusrnan Sen

3.3.6.1 Introduction
Alkanes are by far the most abundant but the least reactive members of the hydro-
carbon family; the known reserves of methane alone approach those of petroleum
[l]. Unfortunately, a significant portion of the methane produced is not utilized
because of the difficulty associated with the transportation of a flammable, low-
boiling gas. Its possible use as an automobile fuel is also limited by the intrinsic
disadvantages of gaseous fuels, i.e., low energy content per unit volume and the
hazards associated with handling and distribution. Consequently, the selective cat-
alytic activation and functionalization of C-H bonds of methane in particular, and
alkanes in general, to form useful organics constitute a “Holy Grail” in chemistry.
In this context, Table 1 presents thermodynamic data indicating which alkane
functionalizations are feasible and, therefore, worth pursuing.
The lack of reactivity of alkanes stems from their unusually high bond energies
(C-H bond energy of methane: 104 kcal/mol) and most reactions involving the
homolysis of a C-H bond occur at fairly high temperatures or under photolytic
conditions. Moreover, the selectivity in these reactions is usually low because
of the subsequent reactions of the intermediate products, which tend to be more
reactive than the alkane itself. Using methane as an example, its homolytic
C-H bond energy is 10 kcal/mol higher than that in methanol. Therefore, unless
methanol can be removed as soon as it is formed, any oxidation procedure that
involves hydrogen-atom abstraction from the substrate C-H bond would normally
cause rapid over-oxidation of methanol. For example, the radical-initiated chlori-
nation of methane invariably leads to multiple chlorinations [2] (chlorination,
however, is more specific in the presence of superacids [3]). In order to achieve

Table 1. Ace at 298 K for selected alkane functionalizations.

Reaction Ace [kcal/mol] a)

+ 16.4
-40.3
+ 24.1
- 32.6
+ 14.3
+ 13.2
- 27.6
-48.3
’) 1 kcaVmol = 4.184 kJ/mol.
 3.3.6.2 Radical Pathways 1227

the selective functionalization of alkanes, it is therefore necessary in most in-

stances to promote a pathway that does not involve C-H bond homolysis as
one of the steps. The problem is compounded by the fact that practically econom-
ical processes usually require the direct use of dioxygen as the oxidant. Because of
its triplet electronic configuration, reactions between dioxygen and alkanes most
often involve unselective radical pathways (cf. Section 2.8.1) [4].
Apart from the selectivity with respect to the degree of oxidation, a second
selectivity issue arises for C3 and higher alkanes: the selectivity with respect
to the particular C-H bond that is functionalized. Again, since the homolytic
bond energies decrease in the order: primary C-H > secondary C-H > tertiary
C-H bonds, radical pathways involving C-H bond homolysis almost al-
ways show a marked preference for the functionalization of tertiary C-H bonds.
This is in contrast to many commodity chemicals that are terminally functiona-
lized 1.51.
In principle, the above selectivity problems can be avoided in suitably designed
homogeneous metal-ion-catalyzed oxidation procedures. Transition metals,
particularly those whose most stable oxidation states differ by 2e-, often promote
nonradical pathways even in the presence of dioxygen [6]. Moreover, since metal-
carbon bond strengths parallel those of C-H bonds and because of steric factors,
the preferential functionalization of primary C-H bonds becomes possible [7].
As a bonus, metal-ion catalyzed reactions usually operate at low temperatures
(-100 "C or below) [8].
Below, we describe homogeneous catalytic systems for the catalytic activation
and functionalization of C-H bonds of alkanes. The account only highlights some
of the recent advances in the area, focusing especially on oxidative functionali-
zations involving dioxygen as the oxidant: these are of particular importance
since the vast majority of commercially important organic chemicals (alcohols,
aldehydes, ketones, acids) are derived from alkanes through one or more oxidative
functionalization steps [5]. Some reviews have appeared 191. For convenience the
reactions are classified into three pathways: radical, oxidative addition, and
electrophilic, although the mechanism is not known in every case and several
pathways may be operating simultaneously.

3.3.6.2 Radical Pathways

This involves the metal as a le- oxidant, as shown in eqs. (1) and (2). From a ther-
modynamic standpoint, the le- oxidation of alkanes is generally less favorable
than the corresponding 2e- oxidation [lo] and, therefore, requires the use of either
very strong oxidants or relatively high temperatures. Sometimes, as shown in eq.
(2), an auxiliary ligand on the metal may participate in the C-H bond-breaking
step. Equation (2) appears to represent nature's preferred route to alkane C-H
activation. For example, it is generally accepted that in the enzyme cytochrome
P-450, the species responsible for alkane C-H cleavage is a porphyrinato-Fev=O
complex [ 111. The C-H activating species in methane monooxygenase has been
less well characterized but a high-valent Fe=O species similar to that in cyto-
1228 3.3 Special Products

chrome P-450 has been postulated [ 111. The high specificity observed in enzymic
systems is presumably a result of steric restraints. More commonly, however, the
organic free radicals generated will participate in a multitude of reaction pathways
leading to a large number of products [4]. Thus, most commercial metal-catalyzed
processes belonging to this group, such as the Co"'-catalyzed oxidation of cyclo-
hexane, are generally carried out at fairly low conversion levels (< 10 %) to
enhance selectivity [4 a].
MN+ + R-H M(N-')+ + R' + H+ (1)
MN+=o + R-H G= M(N-~)+-oH + R' (2)
In an effort to mimic the chemistry of cytochrome P-450, a large amount
of work has been performed on alkane oxidations mediated by transition metal-
porphyrin complexes [ 121. Particularly noteworthy are the shape-selective
oxidations of terminal methyl groups using bulky porphyrin ligands [13]. Addi-
tionally, Hill and others have published work on the polyoxometallate-catalyzed
alkane functionalizations [ 141. Here again, a high-valent metal-oxo species is
thought to be responsible for the C-H activation step. Unfortunately, with some
exceptions, dioxygen cannot be used as the oxidant; instead, hydrogen peroxide
and related organic and inorganic peroxo species are usually used. This further
underscores the problem of simultaneous activation of the alkane C-H bond
and dioxygen in a practically useful catalytic system. One notable exception is
a system described by Lyons and Ellis which directly utilizes dioxygen to oxidize
isobutane and propane [ 151. Polyhalogenated metalloporphyrin complexes are
used as catalysts and only the weak tertiary and secondary C-H bonds are
attacked. Although a high-valent metal-oxo species was initially proposed as
the C-H activating agent, recent work tends to support a radical pathway initiated
by metal-catalyzed decomposition of alkyl hydroperoxides [ 161.
Several interesting variations on the above radical chemistry have been
described recently. One such system is copper salt catalyzed alkane oxidation
by dioxygen in the presence of an aldehyde [17]. The proposed mechanism
involves the initial autoxidation of the aldehyde to the corresponding peracid,
which is the real oxidant for the Cu"-mediated oxidation of the alkane (eqs.
(3)-(5)). The ratio of alkane oxidized to aldehyde converted is relatively low be-
cause much of the peracid formed reacts with the aldehyde to form two molecules
of carboxylic acid.
R'CH0+02 - R'COBH (3)
CU" + R'COsH - CU"'-O. + R'COPH (4)
CU"'-O* + R-H - CU" + R-OH (5)

Related to the above is the "Gif' system discovered by Barton [18]. In essence,
it involves Fe" + O2 + reducing agent or Fe"' + H202.The mechanism is unsettled
although a high-valent Fe=O species has been implicated in the C-H cleavage
step. The reactivity profile appears to be inconsistent with the generation of
 3.3.6.3 Oxidative Addition Pathways 1229

free radicals, e.g., secondary C-H bonds are attacked in preference to tertiary
C-H bonds. Instead, Barton has postulated the [2 + 21 addition of a C-H bond
across the Fe=O bond as the key step in this system. If so, this may be regarded
as an example of ligand-assisted electrophilic C-H activation (cf. eq. (13 b), see
below). A (perhaps) related system involving high-valent Ru=O species has
been reported by Drago [19]. This system converts methane to methanol and
formaldehyde using H 2 0 2 as the oxidant.
The sulfoxidation of alkanes to alkane sulfonic acids using a combination of
sulfur dioxide and dioxygen and catalyzed by vanadium compounds has been
reported [20]. The mechanism involves intermediacy of alkyl radicals which
are trapped by sulfur dioxide and then further oxidized to the product.
The final variation on metal-mediated radical chemistry of alkanes involves
mercury-sensitized photochemical dimerization of alkanes [2 11. The high selec-
tivity in the reaction arises from the fact that the sequence of steps (eqs.
(6)-(9)) occurs in the gas phase and the dimerization product is invariably less vo-
latile than the starting alkane. Using this procedure, Crabtree has even achieved
the cross-dimerization of alkanes with functional organics.

Hg + hv - Hg* (6)
Hg* + R-H - R' + H' + Hg (7)
H' + R-H - R' + H2 (8)
2R' + R-R (9)

3.3.6.3 Oxidative Addition Pathways

The second C-H cleavage pathway involves the oxidative addition of the C-H
bond to a low-valent metal center (eq. (lo)), and was initially reported by Berg-
man, Graham, and Jones [22]. Unlike the systems described in the previous
section, there is a strong preference for attack at the primary C-H bond.
,R
MN+ + R-H & MW+~)+ (10)
'H
A two-center version of the oxidative addition reaction described above has
also been observed by Wayland with porphyrinato Rh-Rh-bonded dimers [23].
By using a sterically encumbered ligand, such as tetramesitylporphyrin (TMP),
the Rh-Rh bond energy is considerably reduced, permitting the formation of a
(TMP)Rh-R and a (TMP)Rh-H species (Scheme 1).

Scheme 1
(por)Rh"-Rh"(por)
[(por)Rh-R-H-Rh(por)] -
e 2 (por)Rh"'
(por)Rh"'-R + (por)Rh"'-H
1230 3.3 Special Products

The presence of reactive low-valent metal species prevents the simultaneous

presence of most oxidizing agents that are capable of functionalizing the bound
hydrocarbyl group in the oxidative addition product. Thus, it is difficult to con-
struct a “one-pot’’ catalytic oxidation procedure, although nonoxidative catalytic
functionalizations based on eq. (10) have been demonstrated. For example, first
Crabtree and then Tanaka and Goldman have reported the efficient transfer
dehydrogenation of alkanes to olefins under photochemical, as well as thermal,
conditions (eq. (11)) [24]. Typically, a second olefin, such as f-butylethylene or
norbornene, was the hydrogen acceptor. A particularly notable recent achievement
has been the selective dehydrogenation of long-chain alkanes to a-olefins [24 a].
The related photochemical carbonylation of alkanes to aldehydes and the anal-
ogous isocyanide insertions have also been reported [24 c, d, 251. Photons are
required since the carbonylation of alkanes to aldehydes is thermodynamically
disfavored (see Table 1).

cat. = [Ir(PR3)2(solv)2H2]+or Rh(PR3)&I

Another reaction of some synthetic utility is the insertion of olefins into

aromatic C-H bonds [9d]. This reaction is catalyzed by ruthenium compounds
and requires a coordinating group (typically, ketone) on the aromatic ring. The
group binds to the metal and the orfho C-H bonds are activated due to the result-
ing chelate effect.
Although oxidizing agents are not tolerated by most systems that activate C-H
bonds through an oxidative addition pathway, they are compatible with boranes.
In a series of elegant papers, Hartwig has demonstrated the selective formation of

A/V\ABl0>
\

Scheme 2 0 5
 3.3.6.4 Electrophilic Pathways 1231

terminal alkyl boranes starting with an alkane, a diboron compound, and a catalyst
(Scheme 2) [26]. The mechanism is believed to involve the oxidative addition of
a B-B (or a B-H) bond, as well as a terminal C-H bond of the alkane, and is
followed by the reductive elimination of alkyl borane.

3.3.6.4 Electrophilic Pathways

The activation of C-H bonds by an electrophilic pathway is shown schematically
in eq. (12) and has been observed with a number of late transition metal ions [9].
A driving force for the reaction shown in eq. (12) is the stabilization of the leaving
group, H+, by solvation in polar solvents. The related four-center electrophilic
activation by transition, lanthanide, and actinide metal centers has also been
reported, (eqs. (13a) and (13b)) [9b,c,g, 271. In these instances, a ligand on
the metal assists the reaction by acting as the base.
MN+ + R-H T== MN+-R + H+ (12)

The most significant advantage of the C-H activation pathway shown in

eq. ( I 2) is that the late transition metal electrophiles are compatible with oxidants,
including dioxygen. Therefore, in principle, it should be possible to design a cata-
lytic oxidation procedure that is based on an initial electrophilic C-H cleavage
step, as shown in Scheme 3 and first demonstrated by Shilov and his colleagues
using the Pt” ion as the C-H activating species (see below) [28].

R-H H+

MN+ MN+-R-

[Ox]”
, .
?.
I
I .
.

.*-.
M(N-Z)+ 4t R-NU
Nu-

Scheme 3. Initial electrophilic C-H cleavage step. Ox = 2e- oxidant; Nu- = nucleophile.
1232 3.3 Special Products

For two reasons much of the work in this area has been carried out in strong
acids. First, the conjugate bases of strong acids are poorly coordinating, thereby
enhancing the electrophilicity of the metal ion. Second, the esterification of the
alcohol, the primary product of alkane oxidation, protects it from overoxidation.
One impressive achievement in this area is the Hg"-catalyzed oxidation of
methane to methyl sulfate in pure sulfuric acid, described by Catalytica, Inc.,
workers [29]. Both high selectivity and high conversion have been achieved.
The sulfuric acid serves both as the solvent and the reoxidant for the metal.
Although an electrophilic mechanism similar to Scheme 3 has been claimed,
further studies indicate that a radical pathway, occumng at least in parallel, cannot
be ruled out [30]. More recently, a 2,2'-bipyrimidyl complex of Pt" has been em-
ployed for the same reaction [31]. Again, an electrophilic mechanism has been
suggested for this reaction. Theoretical examination of this and related C-H
activation chemistry by Pt" suggests that the mechanism of C-H activation is
either u-bond metathesis (cf. eq. (7a)) or oxidative addition, depending on the
anionic ligand present [32]. Overall, as reported, the system does not appear to
be commercially viable since dioxygen cannot be directly employed as the
oxidant. Moreover, for ethane and higher alkanes, significant amounts of decom-
position products are formed through the sulfuric acid-induced dehydrations
[30a]. Other noteworthy results in the area of electrophilic C-H activation in
strong acids are the Pd" and Pt" catalyzed insertion of acetylenes into aromatic
C-H bonds [33], and the Pd"/Cu" catalyzed carbonylation of alkanes, including
methane, in trifluoroacetic acid [34]. In this case, the oxidant was the peroxydisul-
fate ion. These and related reactions [35] build upon an earlier report of electro-
philic activation and functionalization of alkanes by the Pd" ion in trifluoroacetic
acid [36].
Electrophilic C-H activations can also be effected in water. At first glance,
water would appear to be particularly unpromising as a solvent for such reactions.
Because of their extremely poor coordinating ability alkanes should not be able to
compete with water for coordination sites. Moreover, the intermediate metal-alkyl
species would be prone to hydrolytic decomposition. In one respect, however,
water is an almost ideal medium for C-H functionalization: the O-H bond energy
exceeds the corresponding C-H bond energy of even methane. Indeed, the selec-
tive oxidation of methane to methanol is carried out by methane monooxygenase
in aqueous medium.
Shilov and his co-workers were the first to demonstrate metal-mediated alkane
functionalization in water [28]. They showed that simple Pt" complexes, such as
PtC12-, will activate and oxidize the C-H bonds of alkanes in the presence of an
oxidizing agent, most notably Pt'" salts. Although Shilov suggested a Pt"" cycle
in accordance with Scheme 3, subsequent work with model systems suggest that a
ptlI/lV
cycle is more likely (Scheme 4) [9 b]. Additionally, the exact nature of the
C-H activation step remains uncertain [32]. Sen [30a, 371, and also Bercaw and
Labinger [38], have followed up on aspects of this work and have shown that a
wide variety of substrates including methane can be functionalized with unusual
selectivity. Thus, although the homolytic C-H bond energy of methane is 10 kcall
mol higher than that in methanol, a C-H bond of methanol would not be expected
 3.3.6.4 Electrophilic Pathways 1233

to be significantly more susceptible to electrophilic cleavage than that of methane.

Indeed, Sen has observed that in water at 100 "C, the rate constant for the oxida-
tion of methane to methanol by the PtC1,2-/PtC1,2p combination (the Pt'" species
acts merely as a reoxidant for the Pto + Pt" step; see Scheme 4) is only one-
seventh of that for methanol oxidation by the same system [30a]. The observed
similarity in rates is even more striking, given the much higher binding ability
of methanol to the Pt" center. Moving to substrates with C-H bonds somewhat
weaker than those in methane results in actual reversal of commonly observed
selectivity. Thus, the relative rate of C-H bond activation by the Pt" ion
decreases in the order H-CH2CH3>H-CH2CH20H >H-CH(OH)CH,, i. e.,
an order that is exactly the opposite of that expected on the basis of homolytic
C-H bond energies [30a]. On a practical level, this shows that the direct con-
version of ethane to 1,2-ethanediol (ethylene glycol) is possible.

Pp-R Pt"-R

Scheme 4

The preferential oxidation of the methyl group of ethanol by the PtC12-/ PtC12-
combination in water at 90 "C was first reported by Bercaw and Labinger [38 a]
and subsequently confirmed by Sen [30 a], who observed the exclusive oxidation
of the methyl group in ethanol resulting in the formation of 1,2-ethanediol as the
sole product. A chelate effect which results in a less strained transition state for the
oxidation of the methyl group of ethanol may be responsible for the observed
selectivity (Scheme 5 ) [37]. Indeed, for n-propanol, the methyl group is the
preferred site of attack and 1,3-propanediol is formed. Thus, the remote oxidation
of highly flexible linear and branched alkyl chains with unprecedented regioselec-
tivity becomes possible. The order of reactivity is a-C-H<B-C-H<y-C-H<
6-C-H for alcohols and a-C-H4B-C-H<y-C-H?&C-H for the acids [37].
These reactions are also very specific with respect to the degree of oxidation:
only hydroxylation is observed, and further oxidation to the corresponding alde-
hyde or carboxylic acid functionality does not occur. This is a result of the strained
transition state that is involved in the activation of a C-H bond a to the hydroxyl
group (see Scheme 5).
1234 3.3 Special Products

X
Pt+\ I & (H)X-CH(OH)CH2CH2-
CHCH2CH2-

(H)X ’x\
pi‘ ,CH~ (H)X-CH2CH(OH)CH2-
\
Pt2+ CHCH2-

Scheme 5. Transition state during the activation of a C-H bond (X = ligating atom; note that
in acids there is an extra atom between X and the C-H bond being attacked).

The activation and functionalization of C-H bonds by the Pt” ion is particularly
attractive because of the unusual regioselectivity, high oxidation level specificity,
and mildness of reaction conditions. Moreover, Sen has recently reported that, in
the presence of copper chloride at 12O-16O0C, Shilov chemistry can be made
catalytic with dioxygen as the ultimate oxidant [39]. A number of aliphatic
acids were tested, and turnover numbers of up to 15hour with respect to platinum
were observed. H/D exchange studies also confirm the marked preference for
the activation of primary C-H bonds in the presence of weaker secondary C-H
bonds. This study constituted the first example of the direct use of dioxygen in
the catalytic oxidation of unactivated primary C-H bonds under mild conditions
that does not involve the use of a co-reductant (e.g., sacrificial metals, 2H’
+ 2e-, dihydrogen, or carbon monoxide; see below).
Recently, Sen has reported two catalytic systems, one heterogeneous and the
other homogeneous, which simultaneously activate dioxygen and alkane C-H
bonds, resulting in direct oxidations of alkanes. In the first system, metallic pal-
ladium was found to catalyze the oxidation of methane and ethane by dioxygen
in aqueous medium at 70-110 “C in the presence of carbon monoxide [40]. In
aqueous medium, formic acid was the observed oxidation product from methane
while acetic acid, together with some formic acid, was formed from ethane [40 a].
No alkane oxidation was observed in the absence of added carbon monoxide. The
essential role of carbon monoxide in achieving “difficult” alkane oxidation was
shown by a competition experiment between ethane and ethanol, both in the pre-
sence and absence of carbon monoxide. In the absence of added carbon monoxide,
only ethanol was oxidized. When carbon monoxide was added, almost half of the
products were derived from ethane. Thus, the more inert ethane was oxidized only
in the presence of added carbon monoxide.
Studies indicate that the overall transformation encompasses three catalytic
steps in tandem (Scheme 6) [9a, 401. The first is the water-gas shift reaction
involving the oxidation of carbon monoxide to carbon dioxide with the simulta-
neous formation of dihydrogen. It is possible to by-pass this step by replacing
 3.3.6.4 Electrophilic Pathways 1235

carbon monoxide with dihydrogen. The second catalytic step involves the combi-
nation of dihydrogen with dioxygen to yield hydrogen peroxide (or its equivalent).
The final step involves the metal-catalyzed oxidation of the substrate by hydrogen
peroxide (or its equivalent).
Whereas acetic acid was formed in good yield from ethane, the analogous for-
mation of formic acid from methane proceeded only in low yield because of the
general instability of the latter acid under the reaction conditions. Since formic
acid is a much less desirable product from methane than is methanol, the possi-
bility of halting the oxidation of methane at the methanol stage was examined.
Simply changing the solvent in the Pd-based catalytic system from water to a
mixture of water and a perfluorocarboxylic acid (some water is necessary for the
reaction; see Scheme 6) had no significant effect on product composition: formic
acid was still the principal product from methane. However, the addition of Cu’ or
Cu” chloride to the reaction mixture had a dramatic effect. Methanol and its ester
now became the preferred products, with virtually no acetic and little formic acid
being formed [40 b]. The activation parameters for the overall reaction determined
under the condition when the rate was first order in both methane and carbon
monoxide were: A = 2 X lo4 s&; E, = 15.3 kcal mol-I. Since methyl trifluoro-
acetate is both volatile and easily hydrolyzed back to the acid and methanol, it
should be possible to design a system where the acid is recycled and methanol
is the end product. Lee and co-workers have recently reported on the further
characterization of the catalyst in this bimetallic Pd/Cu system [41].
Free alkyl radicals appear not to be intermediates. Thus, primary C-H bonds
are at least as reactive (usually much more) than secondary, tertiary, or benzylic
C-H bonds, or C-H bonds a to an alcohol functionality. For example, alkane oxi-
dation proceeds much faster than the oxidation of the corresponding alcohol. Even
the relatively unselective HO. radical shows a significantly higher preference for
attack on secondary than on primary C-H bonds.
The reactivity pattern suggests the presence of a strongly electrophilic oxidant.
This is supported by the following observations [43]. For a series of para-substi-
tuted phenols, the rate of reaction decreased with increasing electronegativity of
the para substituent, with an approximately linear correlation between the electron
affinity of the substituent and the ratio of the log of the rate of oxidation of sub-

t I

Scheme 6. Catalytic steps in tandem.

1236 3.3 Special Products

LxRh-R -r" kC0

R-NU
LxRh-COR & RCO-NU

Scheme 7 (NU = OH,C3F7CO2)

stituted phenol to the parent phenol. This is consistent with an initial electrophilic
attack at the ring. Additionally, the ease of oxidation decreased in the order
(CH3)*S > (CH3)*S0 > (CH3)*S02,which further supports the conclusion that
the system acts as an electrophilic oxidant.
In the metallic Pd-based system, the role of the metal is two-fold. First, it gen-
erates hydrogen peroxide (or its equivalent) in accordance with Scheme 6 [9 a, 40,
42, 431. Second, it causes nonspecific over-oxidation of the organic substrate
using the hydrogen peroxide thus generated. This latter reaction is suppressed
when CuC12 is added. In the bimetallic Pd/CuCI*-based system, experiments
suggest that the principal role of metallic palladium is to generate hydrogen
peroxide in situ and the species responsible for the remote hydroxylation of the
substrate by hydrogen peroxide is Cu chloride [42].
In the second (slower) system, RhC13, in the presence of several equivalents of
C1- and 1- ions, was found to catalyze the direct functionalization of methane in
the presence of carbon monoxide and dioxygen at 80-85°C [44]. The reaction
proceeded in water to give acetic acid as the principal product [44a]. However,
a much higher rate was observed in a 6: 1 (v/v) mixture of perfluorobutyric acid
and water, the products being methanol and acetic acid [44 b]. It is possible to
form either methanol or acetic acid selectively by a simple change in the solvent
system. The ratio of alcohol derivative to the corresponding higher acid may be
assumed to be a function of the relative rates of nucleophilic attack versus carbon
monoxide insertion into a common Rh-alkyl bond (i. e., kNu/kco;see Scheme 7).
While, to a first-order approximation, kco is likely to be independent of the sol-
vent, kNu would depend on the nature of the nucleophile derived from the solvent.
Presumably, the perfluorobutyrate ion is a better nucleophile than water since
more of the alcohol derivative was formed in perfluorobutyric acid-water mixture
than in pure water. This also explains why acetic acid was once again the major
product when the perfluorobutyrate ion was tied up as the ester. Consistent with
the mechanistic scenario shown in Scheme 7 was also the observation that the
ratio of acetic acid to methanol derivative formed from methane increased with
increasing pressure of CO although the overall reaction was sharply inhibited at
high CO pressures.
In addition to Sen's work on the Rh-catalyzed oxidative carbonylation of
methane, Grigoryan has also reported a similar reaction in acetic acid [45]. Predic-
tably, the reaction rate is between that observed in pure water and in the perfluoro-
 3.3.6.4 Electrophilic Pathways 1237

carboxylic acid-water mixture. Finally, Otsuka has reported the oxidative carbon-
ylation of methane to acetic acid by rhodium-doped iron phosphate [46]. The Pd/
Cu and the Rh-based systems show similar selectivity patterns that are, for the
most part, without precedent. For example, in both cases, methane is significantly
more reactive (at least five times) than methanol [9a, 40, 441. For the Rh-based
system, even methyl iodide was found to be less reactive than methane [44 b]!
A more interesting reactivity pattern exhibited by these two systems is their pre-
ference for C-C cleavage over C-H cleavage for higher alkanes [40b, 44bl.
Indeed, we are unaware of any other catalytic system that effects the oxidative
cleavage of alkane C-C bonds under such mild conditions. For example, the
Rh-based system converts ethane to a mixture of methanol, ethanol, and acetic
acid, with a ratio of products formed through C-H relative to C-C cleavage of
approx. 0.6 on a per-bond basis [44 b]. As with methanol, control experiments
indicated ethane is more reactive than ethanol. Additionally, neither ethanol nor
acetic acid is the precursor to methanol. Finally, part of the acetic acid is even
formed by initial C-C cleavage of ethane followed by carbonylation of the re-
sultant C1 fragment. For C4 and higher alkanes, C-C cleavage products were vir-
tually all that were observed; especially noteworthy was the formation of ethanol
from n-butane, which indicates that vicinal diols are not the precursors to the C-C
cleavage products. The above reactivity profile exhibited by the two systems,
together with other observations, appears to be inconsistent with the intermediacy
of free alkyl radicals in the oxidation process.
A curious aspect of the Pd- and Rh-based systems is that, apart from their abil-
ity to activate both dioxygen and the alkane, both require a co-reductant (carbon
monoxide) [40, 441. Thus, there is a striking resemblance to monooxygenases
[ 1I]. In nature, while the dioxygenases utilize the dioxygen molecule more effi-
ciently, it is the monooxygenases that carry out “difficult” oxidations, such as
alkane oxidations. In the latter, one of the two oxygen atoms of dioxygen is
reduced to water in a highly thermodynamically favorable reaction and the free
energy gained thereby is employed to generate a high-energy oxygen species,
such as a metal-oxo complex, from the second oxygen atom (eq. (14)). The
“Gif’ system of Barton [I81 is also designed on this premise. In at least the
Pd-based Sen system [40], the co-reductant, carbon monoxide, is employed to
generate dihydrogen (eq. (15)), the latter being formally equivalent to 2H’ + 2e-
that is employed in the biological systems (cf. eqs. (14) and (16)).
O2 + 2H+ + 2e- - H20 + [O] (14)
CO + H20 - COz + H2 (15)
0 2 + H2 - H20 + [O] (16)
How general is this requirement for a co-reductant (e. g., CO or H2) in achiev-
ing “difficult” catalytic hydrocarbon oxidations by dioxygen? Sen’s work has
provided two examples of catalytic systems that operate in this manner (i.e., as
monoxygenase analogs) [40, 441. There have been other recent publications on
catalytic systems for the oxidation of hydrocarbons, including olefins and aro-
1238 3.3 Special Products

matics, that also call for either CO or H2 as the coreductant [48]. While, from a
practical standpoint, it is more desirable for both oxygen atoms of O2 to be
used for substrate oxidation, with the exception of the Shilov system, there
appears to be no currently known catalytic system that operates as an artificial
“dioxygenase” under mild conditions toward “difficult” substrates, such as
those possessing unactivated primary C-H bonds.

3.3.6.5 Conclusions
While few of the catalytic systems discussed above meet the criteria for successful
commercial processes, it is clear that impressive progress has been made in recent
years in the field of alkane activation and functionalization. Who, for example,
would have believed that it is possible to functionalize methane in water at or
below 100 “C with reasonable turnover rates [40, 44]! A rich new area of organo-
metallic chemistry and catalysis that is both fundamentally interesting and useful
beckons. Future progress will depend on a better understanding of the organo-
metallic chemistry of metal complexes with nontraditional, “hard”, ligands (as
opposed to soft, easily oxidizable, ligands that are traditionally used for metal
complexes that catalyze “reductive” chemistry, such as hydrogenation and car-
bonylation [S]). Radically different reactivity patterns may be anticipated. For
example, Pt’” complexes of the type, PtCl,R2-, which are the proposed intermedi-
ates in alkane hydroxylation by the PtC12-PtCl;- combination, react with water
to form alcohols [37 a, 38 a, 491. The formation of an alcohol by hydrolysis implies
a Pt-C bond polarity that is the opposite of that normally observed for metal-
alkyls (metal-alkyls generally yield alkane and metal hydroxide upon hydrolysis).

References
[l] (a) M. G. Axelrod, A. M. Gaffney, R. Pitchai, J. A. Sofranko, in Natural Gas Conversion
11 (Eds.: H. E. Curry-Hyde, R. F. Howe), Elsevier, Amsterdam, 1994, p. 93; (b) C. D.
Masters, D. H. Root, E.D. Attanasi, Science 1991, 253, 146; (c) C. Starr, M.F. Searl,
S. Alpert, Science 1992, 256, 981.
[2] (a) J. March, Advanced Organic Chemistry, Wiley, New York, 1985, p. 620 and refer-
ences therein; (b) M.L. Poutsma, in Free Radicals (Ed.: J. K. Kochi), Wiley, New
York, 1973, Vol. 11, p. 159.
[3] G. Olah, Acc. Chem. Res. 1987, 20, 422.
[4] Reviews: (a) G. W. Parshall, S. D. Ittel, Homogeneous Catalysis, Wiley, New York, 1992,
p. 237; (b) J. A. Howard, in ref. [2 b], p. 3.
[5] D. E. Collins, F. A. Richey, in Riegel’s Handbook of Industrial Chemistry (Ed.: J. A.
Kent), Van Nostrand Reinhold, New York, 1992, p. 800.
[6] Reviews: (a) R. S. Drago, Coord. Chem. Rev. 1992, 117, 185; (b) L. I. SimBndi, Catalytic
Activation of Dioxygen by Metal Complexes, Kluwer Academic, Dordrecht, 1992, p. 74.
[7] (a) H. E. Bryndza, L. K. Fong, R. A. Paciello, W. Tam, J. E. Bercaw, J. Am. Chem. Soc.
1987, 109, 1444; (b) R.G. Bergman, Science 1984, 223, 902.
[8] Review: G. W. Parshall, S. D. Ittel, Homogeneous Catalysis, Wiley, New York, 1992.
 References 1239

[9] General reviews on the problem of C-H activation and functionalization in solution: (a)
A. Sen, Acc. Chem. Res. 1998, 31, 550; (b) S.S. Stahl, J.A. Labinger, J.E. Bercaw,
Angew. Chem. Int. Ed. 1998, 37, 2181; (c) W.D. Jones, Top. Organomet. Chem.
1999, 3, 9 ; (d) F. Kakiuchi, S. Murai, Top. Organomet. Chem. 1999, 3, 47; (e) A. Sen,
Top. Organomet. Chem. 1999, 3, 81; (f) R. H. Crabtree, Chem. Rev. 1995, 95, 987;
(g) B. A. Amdtsen, R. G. Bergman, T.A. Mobley, T. H. Peterson, Acc. Chem. Res.
1995, 28, 154; (h) J. A. Labinger, Fuel Process. Technol. 1995,42, 325; (i) Selective Hy-
drocarbon Oxidation and Functionalization (Eds.: J. A. Davies, P. L. Watson, A. Green-
berg, J.F. Liebman), VCH, New York, 1990; (i) Activation and Functionalization of
Alkanes (Ed.: C.L. Hill), Wiley, New York, 1989; (k) A.E. Shilov, Activation of
Saturated Hydrocarbons by Transition Metal Complexes, D. Reidel, Dordrecht, 1984.
[lo] See ref. [9k], p. 125.
I l l ] Reviews: (a) S.E. Groh, M.J. Nelson, in ref. [9i], p. 305; (b) Oxygenuses and Model
Systems (Ed.: T. Funabiki), Kluwer, Dordrecht, 1997, Ch. 5-8; (c) J. S. Valentine, in Bio-
inorganic Chemistry (Eds.: I. Bertini, H. B. Gray, S. J. Lippard, J. S. Valentine), Univer-
sity Science Books, Mill Valley, CA, 1994, p. 253; (d) D. Mansuy, P. Battioni, in Bio-
inorganic Catalysis (Ed.: J. Reedijk), Marcel Dekker, New York, 1993, p. 395;
(e) L. Que, in Bioinorganic Catalysis (Ed.: J. Reedijk), Marcel Dekker, New York,
1993, p. 347; (f) Cytochrome P-450 (Eds.: T. Omura, Y. Ishimura, Y. Fujii-Kuriyama),
VCH, New York, 1993, p. 17; (g) K.E. Liu, S.J. Lippard, Adv. Inorg. Chem. 1995,
42, 263; (b) A.L. Feig, S. J. Lippard, Chem. Rev. 1994, 94, 759.
[ 121 Reviews: (a) Metalloporphyrins in Catalytic Oxidutions (Ed.: R. A. Sheldon), Marcel
Dekker, New York, 1994; (b) Metalloporphyrins Catalyzed Oxidations (Eds.: F. Monta-
nari, L. Casella), Kluwer, Dordrecht, 1994; (c) B. Meunier, in Catalytic Oxidations with
Hydrogen Peroxide as Oxidant (Ed.: G. Strukul), Kluwer, Dordrecht, 1992, p. 153.
[13] K. S. Suslick, in ref. [Sj], p. 219.
[I41 Reviews: (a) G. Strukul, in ref. [12c], p. 177; (b) C.L. Hill, in ref. [12c], p. 253;
(c) C.L. Hill, A.M. Khenkin, M.S. Weeks, Y. Hou, ACS Symp. Ser: 1993, 523, 67;
(d) R. A. Sheldon, Topics Cum Chem. 1993, 164, 21. Also see: (e) D. Mansuy, J.-F.
Bartoli, P. Battioni, D.K. Lyon, R.G. Finke, J. Am. Chem. Soc. 1991, 113, 7222;
(d) R. Neumann, M. Dahan, Nature 1997, 388, 353.
[I51 J. E. Lyons, P. E. Ellis, in ref. [12a], p. 297.
[16] M. W. Grinstaff, M. G. Hill, J. A. Labinger, H. B. Gray, Science 1994, 264, 1311.
[I71 N. Komiya, T. Naota, Y. Oda, S.-I. Murahashi, J. Mol. Catal. A: Chem. 1997, 117, 21.
1181 D. H. R. Barton, D. Doller, Acc. Chem. Res. 1992, 25, 504.
[ 191 A. S. Goldstein, R. S. Drago, J. Chem. Soc., Chem. Conzmun. 1991, 21.
[20] Y. Ishii, K. Matsunaka, S. Sakaguchi, J. Am. Chem. Soc. 2000, 122, 7390.
[21] R. H. Crabtree, S.H. Brown, C.A. Muedas, P. Krajnik, R.R. Ferguson, Adv. Chem. Ser:
1992, 230, 197.
[22] (a) Refs. [9c,g]; (b) W. D. Jones, F. J. Feher, Acc. Chem. Res. 1989, 22, 91.
[23] (a) X.-X. Zhang, B.B. Wayland, J. Am. Chem. Soc. 1994, 116, 7897; (b) B. B. Wayland,
S. Ba, A.E. Sherry, J. Am. Chem. Soc. 1991, 113, 5305.
[24] (a) F. Liu, E. B. Pak, B. Singh, C.M. Jensen, A. S. Goldman, J. Am. Chem. Soc. 1999,
121, 4086; (b) J.A. Maguire, A. Petrillo, A. S. Goldman, J. Am. Chem. Soc. 1992,
114, 9492; (c) J. A. Maguire, W.T. Boese, M. E. Goldman, A. S. Goldman, Coord.
Chem. Rev. 1990, 97, 179; (d) M. Tanaka, T. Sakakura, Adv. Chem. Sex 1992, 230,
181; (e) M. J. Burk, R. H. Crabtree, J. Am. Chem. Soc. 1987, 109, 8025.
[25] (a) A. J. Kunin, R. Eisenberg, Organometallics 1988, 7, 2124; (b) W. D. Jones, in ref.
[9i], p. 113.
[26] (a) H. Chen, S. Schlecht, T. C. Semple, J. F. Hartwig, Science 2000,287, 1995; (b) K. M.
Waltz, J. F. Hartwig, J. Am. Chem. Soc. 2000, 122, 11358.
1240 3.3 Special Products

[27] Reviews: (a) I. P. Rothwell, in ref. [9 i], p. 43; (b) P. L. Watson, in ref. [9 i], p. 79; (c) R. F.
Jordan, Adv. Organomet. Chem. 1991, 32, 325; (c) L.M. Slaughter, P.T. Wolczanski,
T.R. Klinckman, T.R. Cundari, J. Am. Chem. Soc. 2000, 122, 7953.
[28] Ref. [9 k], p. 142.
[29] R. A. Periana, D. J. Taube, E. R. Evitt, D. G. Loffler, P. R. Wentrcek, G. Voss, T. Masuda,
Science 1993, 259, 340.
[30] (a) A. Sen, M.A. Benvenuto, M. Lin, A.C. Hutson, N. Basickes, J. Am. Chem. Soc.
1994, 116, 998. Also see: (b) I. P. Stolarov, M. N. Vargaftik, D. I. Shishkin, I. I. Moiseev,
J. Chem. Soc., Chem. Cornmun. 1991, 938.
[31] R. A. Periana, D. J. Taube, S. Gamble, H. Taube, T. Satoh, H. Fujii, Science 1998,280,560.
[32] (a) T.M. Gilbert, I. Hristov, T. Ziegler, Organometallics 2001, 20, 1183; (b) H. Heiberg,
L. Johansson, 0. Gropen, 0.B. Ryan, 0. Swang, M. Tilset, J. Am. Chem. Soc. 2000,122,
10831; (c) P.E.M. Siegbahn, R. H. Crabtree, J. Am. Chem. Soc. 1996, 118, 4442.
[33] C. Jia, D. Piao, J. Oyamada, W. Lu, T. Kitamura, Y. Fujiwara, Science 2000, 287, 1992.
[34] (a) Y. Fujiwara, K. Takaki, Y. Taniguchi, Synlett 1996, 591; (b) K. Nakata, Y. Yamaoka,
T. Miyata, Y. Taniguchi, K. Takaki, Y. Fujiwara, J. Organomet. Chem. 1994, 473, 329;
(c) K. Nakata, T. Miyata, T. Jintoku, A. Kitani, Y. Taniguchi, K. Takaki, Y. Fujiwara,
Bull. Chem. Soc. Jpn. 1993, 66, 3755.
[35] (a) K. Nomura, S. Uemura, J. Chem. Soc., Chem. Cornmun. 1994, 129; (b) M.N.
Vargaftik, I. P. Stolarov, I. I. Moiseev, J. Chem. Soc., Chem. Cornmun. 1990, 1049.
[36] Review: A. Sen, Platinum Metals Rev. 1991, 35, 126.
[37] (a) A. C. Hutson, M. Lin, N. Basickes, A. Sen, J. Organornet. Chem. 1995, 504, 69;
(b) N. Basickes, A. Sen, Polyhedron 1995, 14, 197; (c) L.-C. Kao, A. Sen, J. Chem.
Soc., Chem. Commun. 1991, 1242; (d) A. Sen, M. Lin, L.-C. Kao, A.C. Hutson,
J. Am. Chem. Soc. 1992, 114, 6385.
[38 (a) G. A. Luinstra, L. Wang, S. S. Stahl, J. A. Labinger, J.E. Bercaw, J. Organomet.
Chem. 1995, 504, 75; (b) G.A. Luinstra, L. Wang, S. S. Stahl, J. A. Labinger, J.E. Ber-
caw, Organometallics 1994, 13, 755; (c) J. A. Labinger, A.M. Herring, D. K. Lyon, G. A.
Luinstra, J. E. Bercaw, I. T. Horvath, K. Eller, Organometallics 1993, 12, 895; (d) G. A.
Luinstra, J. A. Labinger, J. E. Bercaw, J. Am. Chem. Soc. 1993, 115, 3004.
[39 M. Lin, C. Shen, E. A. Garcia-Zayas, A. Sen, J. Am. Chem. SOC.2001, 123, 1000.
[40] (a) M. Lin, A. Sen, J. Am. Chem. Soc. 1992, 114, 7307; (b) M. Lin, T. E. Hogan, A. Sen,
J. Am. Chem. Soc. 1997, 119, 6048.
[41] E.D. Park, S . H . Choi, J.S. Lee, J. Catal. 2000, 194, 33.
[42] C. Shen, E. A. Garcia-Zayas, A. Sen, J. Am. Chem. SOC.2000, 122, 4029.
[43] A. Pifer, T. Hogan, B. Snedeker, R. Simpson, M. Lin, C. Shen, A. Sen, J. Am. Chem.
Soc. 1999, 121, 7485.
[44] (a) M. Lin, A. Sen, Nature 1994, 368, 613; (b) M. Lin, T.E. Hogan, A. Sen, J. Am.
Chem. Soc. 1996, 118, 4574.
[45] (a) E. G. Chepaikin, G. N. Boyko, A. P. Bezruchenko, A. A. Leshcheva, E. H. Grigoryan,
J. Mol. Cat. A: Chem. 1998, 129, 15; (b) E.G. Chepaikin, A.P. Bezruchenko, A.A.
Leshcheva, G.N. Boiko, I.V. Kuzmenkov, E.H. Grigoryan, A.E. Shilov, J. Mol. Cat.
A: Chem. 2001, 169, 89.
[46] Y. Wang, M. Katagiri, K. Otsuka, J. Chem. Soc., Chem. Commun. 1997, 1187.
[47] I. Yamanaka, M. Soma, K. Otsuka, Chemistry Lett. 1996, 565.
[48] Representative examples: (a) I. Tabushi, Coord. Chem. Rev. 1988, 86, 1 ; (b) M. Otake,
Chemtech 1995, 36; (c) T. Miyake, M. Hamada, Y. Sasaki, M. Oguri, Appl. Catal. A:
General 1995, 131, 33; (d) T. Teranishi, N. Toshima, J. Chem. Soc., Dalton Trans.
1995, 979; (e) Y. Wang, K. Otsuka, J. Catal. 1995, 155, 256.
[49] L. A. Kusch, V.V. Lavrushko, Yu. S. Misharin, A.P. Moravsky, A.E. Shilov, Nouv. J.
Chim. 1983, 7, 729.
 Applied Homogeneous Catalysis with Organometallic Compounds
Edited by B. Cornils and W. A. Herrmann
Copyright 0 Wiley-VCH Verlag GmbH, D-69469 Weinheim, 2002

3.3.7. I Introduction 1241

3.3.7 Pauson-Khand Reaction

Wolfgang A. Herrmann

3.3.7.1 Introduction
When P. L. Pauson et al. reported in 1971 the surprising formation of cyclopent-2-
en- 1-ones from precursor compounds as simple as carbon monoxide, olefins, and
alkynes [l], there was hardly any hope of catalytic procedures to come. Rather, an
almost stoichiometric amount of octacarbonyldicobalt CO*(CO)~ was necessary
to achieve this obviously metal-mediated C-C coupling reaction. Three car-
bon-carbon bonds form during this remarkable process (eq. (1)). Typical reaction
conditions were heating in suitable solvents such as isooctane or toluene. In most
cases, the easily available alkyne complexes 1 were reacted at 60-120 OC, usually
in an atmosphere of carbon monoxide, with the corresponding alkene (eq. (2)). So
far, dicobaltoctacarbonyl has been the mediator reagent of choice. However, good
results were also reported with other organometallic compounds. For example,
yields up to 80 % resulted from the first intramolecular Pauson-Khand reactions
(PKRs) that were mediated by R u ~ ( C O )[34].
,~

RZ

I
R'
1

The PKR represented by eq. (1) and - in more general terms - eq. ( 3 )
has a number of advantages for the synthetic organic chemist. There are many
natural products that contain cyclopentenone units. Three C-C-bonds are
sequentially formed around one (or several?) cobalt centers. There is a high
degree of regioselectivity (vide infru). Particularly, the larger of the two alkyne
substituents (RL) prefers the a-position of the carbonyl group. Beyond that,
asymmetric varieties in inter- and intramolecular PKRs are possible. In the
meantime, catalytic versions with decent activities but excellent selectivities are
available [2-4].
1242 3.3 Special Products

RS
R’ R3
RS r R L + )=( + C O -
RL
(3)
R2 R4
f
0
R3

S = small
substituent
L = large

The key disadvantage of the PKRs is the multiplicity of reactions that carbonyl-
cobalt complexes can undergo with olefins and alkynes. The majority of thermal
degradation products, e. g. cluster compounds, are not or only slightly reactive in
the desired C-C coupling reactions. Therefore, the yields of many PKRs were
disappointingly low. An improvement was the use of amine N-oxides R,N+O
that effect easy CO elimination to form vacant coordination sites at cobalt [5].
This is a version of the so-called Hieber base reaction. A significant acceleration
of the PKR was thus achieved (in hours instead of days). Note that the CO elim-
ination from CO*(CO)~ is thought to be the rate-determining step of the PKR se-
quence. Presumably the best protocol for the stoichiometric PKR was recently
presented by Sugihara et al. [6], who added organic amines to the reaction mix-
tures. After several minutes, excellent yields were obtained in PKRs following
eqs. (4) and (5).

Bu
10-15 min

92-94%

-
I
c0Z(c0)6 Ph
P
-/h

20-30 rnin

89-90%

Phosphine sulfides R,P=O also accelerate PKRs in the presence of Co,(CO), ;

only atmospheric pressure of carbon monoxide is necessary in this case [35].

3.3.7.2 The Catalytic Option

Only catalytic versions fulfill the economic demands of industry. The handling of
huge amounts of cobalt carbonyls in the stoichiometric versions is cumbersome,
expensive, and environmentally unpleasant. A first breakthrough was made by
Rautenstrauch at Firmenich S. A., Geneva [7, 81. He showed that the dihydrojas-
 3.3.7.2 The Cutulytic Option 1243

+ H2C=CH2 + CO

heptyne( 1) + ethylene + carbon monoxide

I 14 MPa (4 MPa H2C=CH2,

10 MPa CO)
150°C/ 16h
0.22 Mol-% CO,(CO)~

98-99 % regioselectivity
299 % conversion
Scheme 1 48 % isolated yield

monate precursor was formed under quasi-catalytic conditions in acceptable yields

when pressure conditions (carbon monoxide, ethylene) were applied (Scheme 1)
[4d, 7, 81.
Subsequent work of the Korean group of Jeong and Chung [9] led to further
improvements via catalyst modification - e. g. addition of phosphites - or the ap-
plication of supercritical (sc) media [ 101. Supercritical carbon dioxide at 20 MPa
and 90 "C at a CO partial pressure of 3 MPa gave an 82 % product yield after 24
hours according to eq. (6) (cf. Section 3.1.13).

sc co2 E
Et02C t o \ 2 c (6)
~ ~

Good yields also resulted from the photoactivation of C O ~ ( C Oat) ~only low
CO pressure [ll]. However, from experience with the photochemistry of this
particular class of metal carbonyl compounds there is not the slightest chance
of an upscaled application of this procedure.

E$\'' -
-
+
co
(1 bar)
- h'v
1244 3.3 Special Products

Two Japanese research groups reported also on an efficient Ru-based catalytic

PKR: 2 mol% of the commercial Ru3(CO),, effected intramolecular PKRs in good
yields at 140-160 “C under a CO pressure of 1-1.5 MPa 112, 131.

3.3.7.3 Related Reactions

Metallacyclopentenes typically undergo CO insertion to form the corresponding
cyclopentenones. This principle was exploited by Negishi et al. [14] to generate
zirconocene-type intermediates 2 from enynes and convert them into the PK prod-
ucts 3 (Scheme 2).
Iminoclopentenones 4 result from enynes and isocyanides upon treatment with
stoichiometric amounts of [Ni(cod),] in the presence of tris(n-buty1)phosphane
[l5]. On this basis, Buchwald et al. developed a route that first traps the titana-
cyclopentenes with the isocyanide, followed by hydrolysis; cf. Scheme 2 1161.
The sequence became catalytic when (C,H,),Ti[P(CH,),], was used as a catalyst,
with trialkylsilyl cyanides acting as sources for the isocyanides [ 171.
A major step was made when titanocenes were employed for the cyclization: a
number of functional groups are tolerated, the C-C coupling works even with dis-
ubstituted olefins, only low CO pressure is necessary, and the yields are beyond
85 %. Stereoselectivity is induced by ansa-titanocenes such as [(S,S)-(ebthi)-
Ti(CO),] as chiral catalyst. Ees of up to 96 % are thus achieved (see eq. (8)). How-
ever, the “catalyst” is still required in amounts of 5-20 mol% [18].

_.

/ -
X R + co * x&o
L toluene
12-16 h, 90°C
H (8)
85-94 % yield
74-96 % ee

Methylene cyclopentenones can be made with allenes - instead of alkenes - as

precursor compounds. Thus, iron-, molybdenum-, cobalt- and titanium-mediated
PK-type C-C coupling reactions lead preferentially to the b-methylene cyclopen-
tenones [25, 261. A side reaction is the polymerization of allenes in the presence of
CO,(CO)~if the allenes are not at least disubstituted. An example using CO,(CO)~/
N-methylmorpholine N-oxide (6 equiv.) in THF/CH2C12at -80/+20 “C is shown
in eq. (9) (cf. [25]).
 3.3.7.4 Stereoselective PKRs and Hetero-Reactions 1245

X /J
b

M = Zr. Ti

Scheme 2 4

3.3.7.4 Stereoselective PKRs and Hetero-Reactions

Enantioselectivities up to 44 % were reached in intermolecular PKRs when chiral
aminoxides R*,N+O were used [19]. Although the mechanism is not known, it
seems likely that the chiral N-oxide discriminates between the prochiral carbonyl
cobalt units, either oxidizing one carbon monoxide selectively to produce a vacant
site for the alkene insertion, or stabilizing a vacant site on one of the cobalts
preferentially. This approach was modified by application of chiral precursor
substrates [20]. Albeit the synthesis of the latter is cumbersome, the concept
was successfully applied in several total syntheses, for example of hirsutene
[21], brefeldine A [22], P-cuparenone [23], and (+)-15-norpentalenene [24]
(eq. (10)). Stoichiometric amounts of the mediator compound C O ~ ( C Oare ) ~ still
necessary in this useful version of the Pauson-Khand reaction.

d.s. a w l I
yield 63%

y-Butyrolactones are formed upon cyclization of enones with carbon monoxide

mediated by a titanocene species (eq. (11)) [27]. The yield is nearly quantitative
when toluene is employed at 105°C for 15-18 hours under a slight pressure
(1.2 bar) of carbon monoxide. Formally, this PKR-type coupling process is a
[2+2+1] addition reaction.
1246 3.3 Special Products

*) Mediator reagent: (C5H5)2Ti[P(CH,),]2

3.3.7.5 Degenerate (Intermittent) and Domino PK Reactions

According to observations made by Krafft et al. [28], monocyclic products are
formed in the presence of air-oxygen; C O ~ ( C Omediates
)~ the cyclization process,
which is stopped oxidatively at the alkyne during the first C-C bond formation.
Equation (12) gives a typical example of this “degenerate” PKRs (sometimes
called “intermittent”). Several consecutive PKR can be used to synthesize compli-
cated hydrocarbons elegantly that are otherwise not available or only with diffi-
culty. In such cases, it is not of primary interest how much of the mediator,
e. g. C O ~ ( C O )is~necessary.
, An excellent example is the construction of the fer-
restrane framework according to Scheme 3, as reported by Thommen and Keese
in 1997 [29].

dR* x
0 2

C O ~ ( C O toluene,
)~,
90°C, 1h

52-80% yield

iR

minor by-product (PK-product)

 3.3.7.6 Substitution Effects, Selectivity, and Mechanism 1247

3.3.7.6 Substitution Effects, Selectivity, and Mechanism

Best efficiencies under the standard “quasi-catalytic’’ PK conditions are gained
with electron-poor alkynes, strained olefins (e. g., norbomene), and open-chain
olefins with low substitution (e.g., ethylene). Ethylene has the advantage that it
can be applied in large excess by pressurizing the reaction system. Equations
(13) and (1 4) are standard examples.

78%

*) N-methyl-morpholine-N-oxide (NMO)
CH2CIzI 0-25°C I CO~(CO),

-Co(CO),
60”C, 4h (14)

v 55-70%
from Co2(CO), and
MeCECMe

Steric effects play a major role in the selectivity of the PK cyclization, too. This
can be seen especially with highly unsymmetrically substituted alkynes : the large
substituent L preferentially shows up adjacent to the carbonyl functionality
(Figure 1).
There is a plausible mechanistic proposal for the standard PKR on the basis of
C O ~ ( C Oas
) ~mediator and/or catalyst. Clearly the well-known p-alkyne dicobalt

0
Figure 1. Effect of ligand structure.
1248 3.3 Special Products

l-heptyne

(CO)&o- Co(C0)d

R - b o

co 4
Scheme 4
h
co &
LR
cyc013
- Co(CO),

complexes (R-C =C-R)CO~(CO)~ are initially formed via CO dissociation. This is

thought to be the rate-determining step. An alkene addition with subsequent C-C
coupling (alkyne/alkene coupling) then follows. The first C-C coupling step takes
place between the less bulky end of the alkyne (S) and the alkene, and it is this
step that explains the regioselectivity with respect to the alkyne. The carbonyla-
tion step comes prior to the n-decomplexation of the cyclopentenone, which
final step regenerates the carbonylcobalt species. Scheme 4 summarizes the gen-
erally accepted textbook mechanism [ 2 4 , 301.
The main side reactions are cyclotrimerization (of the alkyne), co-cyclotrimer-
ization (alkyne/alkyne/alkene), and formation of cyclopentadienones 5 and 6. In
addition, spirofuranones such as 7 and 8 can form, with the latter being the
Diels-Alder product of 7 with ethylene. It is generally observed that high ethylene
and CO pressures disfavor the formation of side products. Further details on the
side-product formation were given in [4 d].
 3.3.7.7 Commercial Perspectives 1249

dR
R QR II

5
R

6
F
R d. 7
R
8

It is noteworthy that the cobalt cluster C O ~ ( C O )-, for

~ many years thought to
be inactive in PKRs - does also work in more or less stoichiometric versions
under modest conditions, e. g., 70 "C, 0.1 MPa CO [31]. However, the reported
turnovers (TON) are below 15. Additives such as cyclohexylamine seem to
facilitate disproportionation of the zerovalent cobalt. It is thus doubtful whether
Coo is retained throughout the catalytic cycle, albeit this still is the textbook
opinion on the mechanism.

3.3.7.7 Commercial Perspectives

Cyclopentenones are building blocks of fragrances. For this reason, intensive
research has been performed at Firmenich S.A., Geneva. Thus, the methyl-
dihydrojasmonates - the so-called hediones' - are important perfumery chemicals
[32]. Their production is well above 1500 tons per year. The conventional
synthesis is based on an aldol reaction between cyclopentanone and n-valeralde-
hyde. The resulting aldol is then converted into 2-pentylcyclopent-2-en- 1-one 10
(R = n-pentyl). Michael addition of dimethyl malonate and saponification/
decarboxylation gives the hediones' in an approx. 95:5 truns/cis mixture. The
PK approach under the best conditions gave 48% 10 (toluene, 0.22 mol%
Co,(CO), based on 1-heptyne). The overall turnover number (TON) was ca.
220, the overall turnover frequency (TOF) ca. 150h. The regioselectivity was
excellent, ranging as high as 98-99 % [4 d, 7, 81. The Pauson-Khand approach
has not yet led to an industrial synthesis of methyldihydrojasmonate. An en-
antioselective ruthenium-catalyzed hydrogenation of the vinylog P-oxoester was
recently reported by Rautenstrauch anc co-workers [33].

0 0

9 10
1250 3.3 Special Products

3.3.7.8 Outlook
Compared with the status reported in ref. [4 d], significant progress has been made
in the quasi-catalytic PK approach, particularly in the synthesis of natural prod-
ucts. In addition, the regio- and stereoselectivity has been improved by various
additives such as specific solvents, drop-in ligands (e. g., chiral amine oxides),
and combinations of cobalt salts with reducing agents (e. g., Co(acac),/Na[BH,]
or CoBrJZn) (cf. [34, 351). The greatest challenge, however, remains a truly
catalytic version of this unique triple C-C coupling process. It is clear that the
chemistry occurring around the mediator metal, so far most efficiently cobalt,
must become more favorable. In particular, the degradation of the active carbonyl-
cobalt species with its detrimental effect upon the catalytic performance must be
avoided. Much scientific imagination should be applied to the design of a (binuc-
lear) cobalt complex exhibiting an anchoring ligand to stabilize the system toward
the formation of clusters and the bulk metal. Bimetallic catalysts taking care of the
different types of C-C coupling chemistry combined in PKRs are another pos-
sibility for a solution for the as-yet poor catalytic performance. Supercritical
reaction conditions [36] should be given further attention, too.

References
[I] (a) I. U. Khand, G. R. Knox, P. L. Pauson, W. E. Watts, J. Chem. Soc., Chem. Commun.
1971, 36; (b) I. U. Khand, G. R. Knox, P. L. Pauson, W.E. Watts, J. Chem. Soc., Perkin I
1973, 975; (c) I . U . Khand, G.R. Knox, P.L. Pauson, W.E. Watts, M.I. Foreman,
J. Chem. Soc., Perkin I 1973, 977; (d) P. L. Pauson, I. U. Khand, Ann. NY Acad. Sci.
1977, 295, 2.
[2] (a) N. E. Schore, Chem. Rev. 1988, 88 1081; (b) N. E. Schore, in Comprehensive Organic
Synthesis (Eds.: B. M. Trost, I. Fleming, L. A. Paquette), Vol. 5, Pergamon, Oxford, 1991:
(c) N. E. Schore, Org. React. 1991, 40, 1.
131 (a) L. S. Hegedus, Organische Synthese mit Ubergangsrnetallen, VCH, Weinheim, 1995;
(b) R. Noyori, Asymmetric Catalysis in Organic Synthesis, Wiley, New York, 1994;
(c) P.L. Pauson, Tetrahedron 1985, 41, 5855; (d) P.L. Pauson, in Organometullics in
Organic Synthesis (Eds.: A. de Meijere, H. tom Dieck), Springer, Berlin, 1987, p. 233:
(e) N. E. Schore, Org. React. 1991, 40, 1.
[4] Recent review articles: (a) A. J. Fletches, S. D. R. Chustie, J. Chem. Soc., Perkin Trans.
I , 2000,1657; (b) 0. Geis, H . G . Schmalz, Angew. Chem. 1998,/10,955; Angew. Chem.
Int. Ed. 1998, 37, 911; (c) K.M. Brummond, J.L. Kent, Tetrahedron 2000 56, 3263;
(d) V. Rautenstrauch, in: Applied Homogeneous Catal~ysiswith Orgunometullic Com-
pounds (Eds.: B. Cornils, W. A. Herrmann), I st ed., Wiley-VCH, Weinheim, 1996.
1.51 (a) S. Shambayati, W.E. Crowe, S.L. Schreiber, Tetrahedron Lett. 1990, 31, 5289;
(b) N. Jeong, Y. K. Chung, B. Y. Lee, S. H. Lee, S.-E. Yoo, Synlett 1991, 204; (c) A. R.
Gordon, C. Johnstone, W. J. Kerr, Synlett 1996, 1083.
[6] (a) T. Sugihara, M. Yamada, H. Ban, M. Yamaguchi, C. Kaneko, Angew. Chem. 1997,
109, 2884; Angew. Chem. Int. Ed. Engl. 1997, 36, 2801; (b) T. Rajesh, M. Periasamy,
Tetrahedron Lett. 1998, 39, 117.
[7] V. Rautenstrauch, P. MCgard, J. Conesa, W. Kiister, Angew. Chem. 1990, 102, 1441;
Angew. Chern. Int. Ed. Engl. 1990, 29, 1413.
 References 125 1

181 Firmenich S.A. (V. Rautenstrauch, W. Keim), CH 68 1.224 (1990).

[9] (a) N. Jeong, S. H. Hwang, Y. Lee, Y. K. Chung, J. Am. Chem. Soc. 1994, 116, 3159; (b)
B. Y. Lee, Y. K. Chung, N. Jeong, Y. Lee, S. H. Hwang, J. Am. Chem. Soc. 1994, 116,
8793; (c) N.Y. Lee, Y. K. Chung, Tet.rahedron Lett. 1996, 37, 3145; (d) N. Jeong,
S.H. Hwang, Y.W. Lee, Y.S. Lim, J. Am. Chem. Soc. 1997, 119, 10549.
[lo] N. Jeong, S. H. Hwang, Angew. Chem. 2000, 112, 650; Angew. Chem. Int. Ed. 2000,
39, 636.
[ 11 1 B. L. Pagenkopf, T. Livinghouse, J. Am. Chem. Soc. 1996, 118, 2285.
[I21 T. Kondo, N. Suzuki, T. Okada, T.-A. Rflitsudo, J. Am. Chem. Soc. 1997, 119, 6187.
1131 T. Morimoto, N. Chatani, Y. Fukumoto, S. Murai, J. Org. Chem. 1997, 62, 3762.
1141 (a) E.-I. Negishi, S. J. Holmes, J. M. Tour, J. A. Miller, J. Am. Chem. Soc. 1985, 107,
2568; (b) E.-I. Negishi, F. E. Cederbaum, T. Takahashi, Tetrahedron Lett. 1986, 27,
2829; (c) E.-I. Negishi, S. J. Holmes, J . M. Tour, J. A. Miller, F. E. Cederbaum, D. R.
Swanson, T. Takahashi, J. Am. Chem. Soc. 1989, 111, 3336.
[IS] (a) K. Tamao, K. Kobayashi, Y. [to, J. Am. Chem. SOC. 1988, 110, 1286; (b) K. Tamao,
K. Kobayashi, Y. Ito, Synlett 1992, 539
[I61 R. B. Grossmann, S. L. Buchwald, J. Org. Chem. 1992, 57, 5803.
[I71 (a) S. C. Berk, R. B. Grossmann, S. L. Buchwald, J. Am. Chem. Soc. 1993, 115, 4912;
(b) S. C. Berk, R. B. Grossmann, S.L. Buchwald, J. Am. Chem. Soc. 1994, 116, 8593;
( c ) F. A. Hicks, S. C. Berk, S. L. Buchwald, J . Org. Chem. 1996, 61, 2713.
[18] F.A. Hicks, S.L. Buchwald, J. Am. Chem. Soc. 1996, 118, 11688.
[I91 W. J. Kerr, G. G. Kirk, D. Middlemiss, Synlett 1995, 1085.
[20] (a) J. Castro, A. Moyano, M. A. Pericis, A. Riera, A. E. Greene, Tetrahedron: Asymme-
try 1994,5, 307; (b) V. Bernardes, X. Verdaguer, N. Kardos, A. Riera, A. Moyano, M. A.
Pericas, A.E. Greene, Tetrahedron Lett. 1994, 35, 575; (c) X. Verdaguer, A. Moyano,
M. A. Pencis, A. Riera, V. Bernardes, A. E. Greene, A. Alvarez-Larcna, J. F. Piniella,
J. Am. Chem. Soc. 1994, 116, 2153; (d) S. Fonquerna, A. Moyano, M . A . Pericas,
A. Riera, Tetrahedron 1995, 51, 4239; (e) S. Fonquerna, A. Moyano, M. A. Periciis,
A. Riera, J. Am. Chem. Soc. 1997, 119, 10225; (f)E. Montenegro, M. Poch, A. Moyano,
M. A. Pencis, A. Riera, Tetrahedron Lett. 1998, 39, 335.
[21] J. Castro, H. Sorensen, A. Riera, C. Morin, A. Moyano, M. A. Pencis, A. E. Greene,
J. Am. Chem. Soc. 1990, 112, 9388.
[22] V. Bernardes, N. Kann, A. Riera, A. Moyano, M. A. Pencis, A. E. Greene, J. Org. Chem.
1995, 60, 6670.
[23] J. Castro, A. Moyano, M. A. Pericas, A,. Riera, A. E. Greene, A. Alvarez-Larena, J. F.
Piniella, J. Org. Chem. 1996, 61, 9016.
1241 J. Tormo, A. Moyano, M. A. PericBs, A Riera, J. Org. Chem. 1997, 62, 485 1.
[25] (a) M. Ahmar, F. Antras, B. Cazes, Tetrahedron Lett. 1995, 36, 4417; (b) M. Ahmar,
0. Chabanis, J. Gauthier, B. Cazes, Tetrahedron Lett. 1997, 38, 5277; ( c ) M. Ahmar,
C. Locatelli, D. Colombier, B. Cazes, T~trahedronLett. 1997, 38, 5281.
[26] (a) R. Aumann, H.-J. Weidenhaupt, Chcpm. Ber. 1987, 120, 23; (b) J.L. Kent, H. Wan,
K. M. Brummond, Tetrahedron Lett. 19!)5, 36, 2407.
[27] (a) N. M. Kablaoui, F.A. Hicks, S.L. Buchwald, J. Am. Chem. Soc. 1996, 118,
5818; (b) N.M. Kablaoui, F. A. Hicks, S.L. Buchwald, J. Am. Chem. Soc. 1997, 119,
4424.
[28] M. E. Krafft, A.M. Wilson, 0. A. Dasse, B. Shao, Y. Y. Chung, Z. Fu, L. V. R. Bongaga,
M.K. Mollmann, J. Am. Chem. Soc. 1996, 118, 6080.
[29] M. Thommen, R. Keese, Synlett 1997, 2!31.
[30] I. L Scott, J. Org. Chem. 1992, 20, 5277.
[31] M.E. Krafft, L. V. R. Boiiaga, Angew. C'hem. 2000, 112, 3822; Aizgew. Chem. Int. Ed.
2000, 39, 3676.
1252 3.3 Special Products

[32] Reviews: (a) E.P. Demole, in Fragrance Chemistry: The Science of the Sense of
Smell (Ed.: E.T. Theimer), Academic Press, New York, 1982, p. 374; (b) G. Ohloff,
Riechstoffe und Geruchssinn: Die molekulare Welt der Dufte, Springer, Berlin, 1990,
pp. 149-152.
[33] D. A. Dobbs, K. P. M. Vanhessche, E. Brazi, V. Rautenstrauch, J.-Y. Lenoir, J.-P.
Gentt, S.H. Bergens, Angew. Chem. 2000, 112, 2080; Angew. Chem. Int. Ed. 2000,
39, 1992.
[34] T. Kondo, N. Suzuki, T. Okada, T. Mitsudo, J . Am. Chem. Soc. 1997, 119, 6187.
[35] M. Hayashi, Y. Hashimoto, Y. Yamamoto, I. Usuki, K. Saigo, Angew. Chem. 2000, 112,
645; Angew. Chem. Int. Ed. 2000, 39, 631;
[36] Review: P.G. Jessop, T. Ikariya, R. Noyori, Chem. Rev. 1999, 99, 475.

3.3.8 Cyclooligomerization of Alkynes

Helmut Bonnemann, Werner Brijoux

3.3.8.1 Introduction
The transition metal-catalyzed cyclotrimerization of acetylene (eq. (1)) was
discovered by Berthelot [ 11 back in the mid-19th century using heterogeneous
systems.

3 HC-CH -0
cat'

The merits of homogeneous catalysts in this field were demonstrated most con-
vincingly by Reppe [2]. In 1973, Yamazaki and Wakatsuki [3] first reported the
homogeneous catalytic cycloaddition of alkynes and nitriles. Since then Vollhardt
[4] has developed a number of elegant synthetic organic applications. Bonnemann
and co-workers [5] focused their work on the development of highly reactive
organocobalt catalyst for the homogeneous synthesis of a-substituted pyridines
according to eq. (2).

In 1988 Schore [6] published a comprehensive review of cycloaddition reac-

tions of alkynes mediated by transition metal complexes and their application
in organic synthesis.
This section focuses on the transition metal-catalyzed formation of ring systems
using alkynes in the homogeneous phase. Because of the great number of possible
products, this survey is restricted to five- and six-membered heterocycles, and six-
and eight-membered carbocycles.
 Applied Homogeneous Catalysis with Organometallic Compounds
Edited by B. Cornils and W. A. Herrmann
Copyright 0 Wiley-VCH Verlag GmbH, D-69469 Weinheim, 2002

1252 3.3 Special Products

[32] Reviews: (a) E.P. Demole, in Fragrance Chemistry: The Science of the Sense of
Smell (Ed.: E.T. Theimer), Academic Press, New York, 1982, p. 374; (b) G. Ohloff,
Riechstoffe und Geruchssinn: Die molekulare Welt der Dufte, Springer, Berlin, 1990,
pp. 149-152.
[33] D. A. Dobbs, K. P. M. Vanhessche, E. Brazi, V. Rautenstrauch, J.-Y. Lenoir, J.-P.
Gentt, S.H. Bergens, Angew. Chem. 2000, 112, 2080; Angew. Chem. Int. Ed. 2000,
39, 1992.
[34] T. Kondo, N. Suzuki, T. Okada, T. Mitsudo, J . Am. Chem. Soc. 1997, 119, 6187.
[35] M. Hayashi, Y. Hashimoto, Y. Yamamoto, I. Usuki, K. Saigo, Angew. Chem. 2000, 112,
645; Angew. Chem. Int. Ed. 2000, 39, 631;
[36] Review: P.G. Jessop, T. Ikariya, R. Noyori, Chem. Rev. 1999, 99, 475.

3.3.8 Cyclooligomerization of Alkynes

Helmut Bonnemann, Werner Brijoux

3.3.8.1 Introduction
The transition metal-catalyzed cyclotrimerization of acetylene (eq. (1)) was
discovered by Berthelot [ 11 back in the mid-19th century using heterogeneous
systems.

3 HC-CH -0
cat'

The merits of homogeneous catalysts in this field were demonstrated most con-
vincingly by Reppe [2]. In 1973, Yamazaki and Wakatsuki [3] first reported the
homogeneous catalytic cycloaddition of alkynes and nitriles. Since then Vollhardt
[4] has developed a number of elegant synthetic organic applications. Bonnemann
and co-workers [5] focused their work on the development of highly reactive
organocobalt catalyst for the homogeneous synthesis of a-substituted pyridines
according to eq. (2).

In 1988 Schore [6] published a comprehensive review of cycloaddition reac-

tions of alkynes mediated by transition metal complexes and their application
in organic synthesis.
This section focuses on the transition metal-catalyzed formation of ring systems
using alkynes in the homogeneous phase. Because of the great number of possible
products, this survey is restricted to five- and six-membered heterocycles, and six-
and eight-membered carbocycles.
 3.3.8.2 Survey of the Catalysts 1253

3.3.8.2 Survey of the Catalysts

Alkyne cyclotrimerization occurs at various homogeneous and heterogeneous
transition metal and Ziegler-type catabysts [7]. Substituted benzenes have been
prepared in the presence of iron, cobalt, and nickel carbonyls [8] as well as
trialkyl- and triarylchromium compounds [9]. Bis(acrylonitri1e)nickel [lo] and
bis(benzonitri1e)palladium chloride [ 111 catalyze the cyclotrimerization of tolane
to hexaphenylbenzene. NiC12 reduced by NaBH, has been utilized for the trimer-
ization of 3-hexyne to hexaethylbenzerie [ 121. Ta,Cl,(tetrahydr~thiophene)~and
Nb,Cl,(tetrahydr~thiophene)~as well as $-Cp-, T5-Ind-, and T5-Flu-rhodium
complexes (Cp = cyclopentadienyl; Incl = indenyl; Flu = fluorenyl) were found
to cyclotrimerize terminal alkynes [ 131. Hexaisopropyl- and hexa-t-butylbenzene
can only be synthesized in the presence of highly active cobalt catalysts [14].
Appropriate catalysts for alkyne cyclotrimerizations were surveyed by Jhingan
and Maier in 1987 [15].
In contrast to carbocyclic alkyne c yclotrimerizations, the catalytic pyridine
synthesis from alkynes and nitriles relies exclusively on cobalt catalysts with a
few exceptions where rhodium [16] and iron complexes [17] could be applied.
The cobalt-catalyzed pyridine synthesis can even be carried out in a one-potreac-
tion generating the catalyst from CoClz . 6 H20/NaBH4 + nitrilehlkyne in situ

This system may be recommended for the quick exploration of new synthetic
applications in research laboratories which do not specialize in organometallic
techniques because the cobalt salts can be used in the hydrated form under air,
and no sophisticated ligands are necessary. Cobalt(1) halide complexes of the
type [XCoL3] having a moderate activity in the synthesis of 2-alkylpyridines
are also easily accessible (eq. (3)) [19].

Two types of pre-prepared organocobalt complexes proved to be most effective

catalysts for the co-cyclization of alkynes and nitriles: the allylcobalt type, where
the organic group is $-bonded to the mletal (Structure l), and also the $-Cp- and
$-Ind-cobalt half-sandwich compounds; (2, 3). During the catalytic cycle in the
case of the $-allylcobalt catalyst a 12-electron system is regenerated, whereas
in the case of the $-Cp- and y'-Ind-cobalt complexes the catalytic reaction in-
volves a 14-electron moiety. In fact, the cobalt-catalyzed pyridine synthesis was
one of the first examples where 7'-Cp groups were used as controlling ligands
in homogeneous catalysis [5 f, g]. The modification of the basic r'-Cp ligand sys-
tems by additional substituents, R, transferring electron-donating or -withdrawing
effects to the $-Cp group, results in strong changes in catalyst activity and selec-
tivity. In addition, $-borininato liganda, may be used as 6n-electron ligands for
cobalt (4).
1254 3.3 Special Products

bR
’T’
co
T co R

1 2

=B-R R
R I
co co 5

3 4

Yamazaki’s complex (Structure 5 ) contains two alkyne molecules linked

together to form a five-membered metallacycle. Arene-solvated cobalt atoms,
obtained by reacting cobalt vapor and arenes, have been used by Italian workers
to promote the conversion of a,w-dialkynes and nitriles giving alkynyl-substituted
pyridines [20]. $-Tolueneiron(O) complexes have also been utilized for the
co-cyclotrimerization of acetylene and alkyl cyanides or benzonitrile giving
a-substituted pyridine derivatives. However, the catalytic transformation to the
industrially important 2-vinylpyridine fails in this case: acrylonitrile cannot be
co-cyclotrimerized with acetylene at the iron catalyst [ 171.
In 1989 Oehme et al. reported a photoassisted synthesis of a-substituted pyri-
dines under mild conditions using $-Cp-cobalt complexes as the catalyst [2 11.
Bonnemann and co-workers [22] and others [23] have tried acetylacetonato-
and $-Cp-rhodium as well as resin-attached $-Cp-rhodium complexes as cata-
lysts in the pyridine synthesis [23]. However, rhodium catalysts are generally
less effective than the analogous cobalt systems.

3.3.8.3 Five- and Six-Membered Heterocycles

The classic pyridine syntheses have been extensively reviewed by Abramovitch
[24]. Many of them rely on the condensation of aldehydes or ketones with ammo-
nia in the vapor phase. However, these processes suffer from unsatisfactory selec-
tivity. Soluble organocobalt catalysts allow a selective one-step access to pyridine
and a wide range of a-substituted derivatives from acetylene and the correspond-
ing cyano compounds (eq. (2)).
The homogeneous catalytic [2+2+2]-cycloaddition of alkynes and nitriles was
first discovered by Yamazaki and Wakatsuki [3] using the phosphine-stabilized
cobalt(II1) complex (Structure 5 ) . At the same time, Bonnemann and co-workers
[5] observed the co-cyclization (eq. (2)) at cobalt catalysts prepared in situ, as well
as using phosphine-free organocobalt(1) diolefin complexes.
The substituent on the alkyne and the cyano group can be widely varied. The
basic catalytic reaction (eq. (2)) was developed into a general synthetic method for
the selective preparation of pyridines. Only small amounts of benzene derivatives
are formed as the by-product.
 3.3.8.3 .Five- and Six-Membered Heterocycles 1255

3.3.8.3.1 Pyridine
The parent compound has been prepared under mild conditions using the homo-
geneous $-1-phenylborininatocobalt cod ( 1,5-~yclooctadiene)catalyst (eq. (2),
R = H) [26]. However, the turnover number was very limited (about 100). The
strong incentive for further developments lies in the fact that both HCN and
acetylene are cheap bulk chemicals in industry. The introduction of boron into
the carbocyclic ligand attached to the cobalt enhances the catalytic activity consid-
erably, probably via the suppression of the protolytic 1,4-addition of HCN to the
olefinic cobaltacycle; the resulting cyamo-substituted 1,3- dienes cannot be dis-
placed from the cobalt center by ace1.ylene and the catalytic cycle is stopped
(eq. (4)).
CN
I

3.3.8.3.2 Alkyl-, Alkenyl-, and Arylpyridines

A two-step process for the production (of a-picoline has been commercialized by
DSM in the Netherlands. Acrylonitrile is first reacted with a large excess of ace-
tone [27] (eq. ( 5 ) ) .In the liquid phase a monocyanoethylation product is formed
initially, catalyzed by a primary amine and a weak acid. The ring closure in the
vapor phase giving a-picoline is catalyzed by a palladium contact.

Nippon Steel has developed an interesting liquid-phase process for a-picoline

from ethylene and ammonia [28]. The catalyst is reminiscent of the well-
known Wacker process, viz. the Pd2+/Cu2+redox system (eq. (6)).

4 H2C-CH2 + 4 [Pd(hlH&]2'
rn
The preferred catalysts for the one-step co-cyclization of acetylene and
acetonitrile (or alkyl cyanides in general) to give a-picoline (or 2-alkylpyridines)
are $-Cp-cobalt cod or ~5-trimethylsilyl-Cp-cobaltcod (eq. (2)). The a-picoline
synthesis is best performed in pure nitrile without any additional solvent [5 d].
1256 3.3 Special Products

A significant outlet for a-picoline is the production of 2-chloro-6-(trichloro-

methyl)pyridine, which is used as a nitrification inhibitor in agricultural chemistry
and in the manufacture of the defoliant 4-amino-2,5,6-trichloropicolinic acid.
However, the major commercial outlet for a-picoline is still its use as a starting
material for the two-step production of 2-vinylpyridine. The total yield of 2-vinyl-
pyridine formed via eq. (7) can be as high as 90%.

+ HCHO - Q/ (7)

2-Vinylpyridine may also be obtained in almost quantitative yields from

2-alkylaminopyridine derivatives (directly available through cobalt catalysis)
using a supported (e. g., A1203) alkali metal hydroxide [29].
a-Ethylpyridine, a-undecylpyridine, and other a-alkylpyridines can be prepared
in an analogous way from acetylene and the alkyl cyanides. The preferred catalyst
is the ~5-trimethylsilyl-Cp-cobaltsystem. 2-Undecylpyridine is formed similarly
(94% yield) and can be easily separated from the reaction mixture [30]. The
hydrochlorides and methiodides of a number of 2-alkylpyridines have an effect
on the aqueous surface tension and show antibacterial properties. The salts of
2-pentadecylpyridine show the best results [3 11.
Starting from optically active nitriles, Botteghi and co-workers [32] have applied
the cobalt-catalyzed reaction for the prepartion of optically active 2-substituted
pyridines (eq. (8)). The chiral center is maintained during the alkyne-nitrile co-
cyclization reaction. This reaction has recently been extended to the synthesis
of bipyridyl compounds having optically active substituents [33] and provides
an access to chiral ligands of potential interest in transition metal-catalyzed
asymmetric synthesis.

R3
Ri = H, alkyl, aryl, COOMe, etc., R’ # R2 # R3

The reaction of monosubstituted alkynes with nitriles (see eq. (9)) gives a mix-
ture of isomeric trialkylpyridines (collidines). Collidines have been prepared using
$-Cp-cobalt cod at 130 “C with high turnover numbers [5 d, h].

R‘, R2 = H, alkyl, aryl, COOMe, etc.

 3.3.8.3 Five- and Six-Membered Heterocycles 1257

The catalytic reaction may also be carried out using two different alkynes. For
example, the co-cyclization of acetylene and propyne with acetonitrile yields a
mixture of dimethylpyridines (lutidines) in addition to a-picoline and the isomeric
collidines. The co-cyclization, however, turned out to be nonselective. For experi-
mental details see [5 g]. The cobalt-calalyzed co-cyclization of benzonitrile and
acetylene at $-Cp-cobalt cod gives 2-phenylpyridine in high yield.
The most interesting application from an industrial point of view is the cobalt-
catalyzed one-step synthesis of 2-vinylpyridine from acetylene and acrylonitrile
(eq. (10)). In this way the fine chemical can be manufactured using equal amounts
by weight of the comparatively inexpensive components, acetylene and acryloni-
trile. The 2-vinylpyridine synthesis must be carried out in pure acrylonitrile below
130-1 40 OC, otherwise acrylonitrile and the product 2-vinylpyridine undergo
thermal polymerization [34]. Therefore only very active catalysts can be applied
in the reaction of eq. (10). The best results were obtained using y6-l-phenyl-
borininatocobalt cod as the catalyst (productivity: 2.78 kg 2-vinylpyridine per g
cobalt [5 el.

The outlet for 2-vinylpyridine is the manufacture of copolymers for the use in
tire cord binders [35]. 2-Vinylpyridine is also an additive in dyeing processes for
acrylic fibers: 1-5 9% of copolymerized 2-vinylpyridine provides the reactive sites
for the dye.

3.3.8.3.3 2-Amino- and 2-Alk.ylthiopyridines

A wide variety of substituents at the cyano group is tolerated by the cobalt cata-
lyst. For example, monomeric cyanamide reacts with acetylene in the presence of
y6-borininato cobalt half-sandwich complexes ([Co-B]) to give 2-aminopyridine
I5 el (eq. (1 1)).

2-Aminopyridine is prepared conventionally by the substitution of the pyridine

ring via the so-called Chichibabin reaction using sodium amide in dimethylaniline
[36]. 2-Aminopyridine is used in the manufacture of several chemotherapeutics
and of dyes for acrylic fibers, and as an additive for lubricants [37]. Alkyl
thiocyanates react [38] to give 2-alkylthiopyridines (eq. (12)) which are otherwise
accessible only by multistep synthetic pathways [39]. The catalytic reaction
(eq. (12)) seems to offer on easy entry into the pyrithione systems.

2HCECH + NCS-CH3 O S , C H 3
1258 3.3 Special Products

In classical access, 2-chloropyridine-N-oxide reacts with sodium hydrogensul-

fide to give pyrithione which, in the form of its zinc salt, is added to hair cosmetics
as a general antifungal agent [40].

3.3.8.3.4 Bipyridines
The industrial route for 2,2’-bipyridyl consists in the dehydrodimerization of
pyridine on Raney nickel using a process developed by Imperial Chemical Indus-
tries [41]. 2,2’-Bipyridyl reacts with ethylene bromide to give 1,l ’-ethylene-2,2’-
bipyridylium dibromide (diquat, which is widely used as a herbicide).
The cobalt-catalyzed synthesis enables 2,2’-bipyridyl to be prepared directly
from 2-cyanopyridine and acetylene in a 72 % yield with a 2-cyanopyridine con-
version of 21 % (eq. (13)) [5d].

+ SHCZCH

Starting from readily available cyanopyridines, reaction with alkynes leads to

substituted bipyridyls. Polynuclear pyridine derivatives can also be synthesized
[42]. Substituted alkynes give two positional isomers.

3.3.8.3.5 Miscellaneous
An interesting variation is the reaction of a,w-diynes on $-Cp-cobalt diene com-
plexes. 1,7-Octadiyne initially undergoes an intramolecular process to give, in the
presence of an excess of nitrile, derivatives of tetrahydroisoquinoline (eq. ( 14)).

R = alkyl, alkenyl, aryl, etc.

The annelated pyridine is also obtained with $-Cp-cobalt dicarbonyl as catalyst

[43]. Using this variant of the cobalt-catalyzed cycloaddition, Schleich and co-
workers [44] opened up a new route to pyridoxine (vitamin B6) as its hydrochlo-
ride (eq. (15)).

Me3Si-C-C
To\C-C--SiMe3 + H3C-CN -
[Col ‘$xl--
Me3Si N
H o f i H

N+
I
H CI-

(15)
 3.3.8.3 Five- and Six-Membered Heterocycles 1259

Applying the versatility of the cobalt-catalyzed pyridine formation (eq. (2)),

Vollhardt [45] has varied the basic reaction extensively. Using rather sophisticated
alkyne and nitrile precursors with $-Cp-cobalt dicarbonyl as the catalyst, the pre-
paration of a number of polyheterocyclic systems having physiological interest
was brought about. Using eq. (14) a synthetic route to the isoquino[2,1-b]
[2,6]naphthyridine nucleus (eq. (16)) was developed [46].

6-Heptyne nitrile was incorporated into the indole system giving a pyridine
derivative related to the ergot alkaloids [47].

3.3.8.3.6 Dihydroindoles
The cobalt-catalyzed co-cyclization of alkynes with heterofunctional substrates is
not limited to nitriles. $-Cp-cobalt l-ialf-sandwich complexes are capable of
co-oligomerizing alkynes with a number of C=C, C=N, C=O, or C=S bonds in
a Diels-Alder-type reaction. Chen has observed that these cycloadditions are
best performed in the presence of a Ismall amount of ketones or esters [48].
This modified cycloaddition may be used for the formation of dihydroindole
systems at the y'-Cp-cobalt catalyst (eql. (17)).
R

R = COOMe I
R
Similar cycloaddition reactions of C=C bonds have been described starting
from substituted pyrrole and imidazole derivatives (eq. (1 8)) [49].
R'

\ I n

R', R2 = SiMe3, CH2CH3, COOMe, OMe; X = 0, Ha; n = 2 , 3

1260 3.3 Special Products

The resulting heterocycles in the complex may be further reduced or desilylated

(either in the complex or after demetallation). Further synthetic potential exists in
the use of the primary products, obtained by cobalt-mediated cycloadditions,
as synthons in organic chemistry. For example, indole derivatives have been
co-cyclized at the v5-Cp-cobalt catalyst to give 4a,9a-dihydro-9H-carbazoles or,
after oxidation, precursors for strychnine [50].Remarkably, the cycloaddition of
acrolein in the presence of a small amount of methyl acetate occurs at the carbo-
nyl, rather than at the C=C double bond, to give vinylpyran selectively (eq. (19))
~481.
Ph

Ph

3.3.8.3.7 Related Reactions

Yamazaki [5 13 has reviewed a number of stoichiometric cycloaddition reactions
at the cobaltacyclopentadiene ring system that lead to a plethora of heterocycles.
For example, five- and six-membered heterocycles containing nitrogen, sulfur,
selenium, and phosphorus have been made accessible by this route (eq. (20))
[52]. The co-cyclization of substituted alkynes and isocyanates in the presence
of a rhodium metallocycle gives 2-pyridones (eq. (21)) [53].

Ph

Ph&; * ~

Ph
I
R
R = alkyl, aryl; X = 0,s, Se
 3.3.8.4 S x - and Eight-Membered Carbocycles 1261

2 R1- COOMe + R2-NCO -LRh] Meoo; &,OOMe

(+ arene) (21)
R', R2 = alkyl, aryl, etc. I
R2

R R

R = H, alkyl, aryl, COOMe, etc.

The stability of the us-Cp-cobalt ccore even allows elemental sulfur to be

incorporated in the alkyne co-cyclization. In the presence of excess alkynes the
q'-Cp-cobalt half-sandwich complexes catalyze the formation of thiophenes
(eq. (22)) [54]. Kajitani [55] has expan'ded this work to rhodium complexes and
included selenium as an additional heteroatom.

3.3.8.4 Six- and Eight-Membered Carbocycles

The cyclotrimerization of acetylene to benzene (eq. (1)) is highly exothermic.
The free energy of this process was estimated to be 595 kJ per mol of product
[56]. Monosubstituted acetylenes give 1,2,4- or 1,3,5-trisubstituted benzene
derivatives (eq. (23)). The regioselectivity of the cyclization may be controlled
by the electronic properties and the steric demand of the catalyst, as well as by
the reaction conditions. Because of the inherent sensitivity of organometallic
catalysts to heteroatoms, this reaction is mainly limited to alkyl-, alkenyl- or
aryl-substituted acetylenes. Educts containing polar heteroatoms are only
processed by very few homogeneous ciitalysts such as the organocobalt systems
discussed above.
R

k R
R = alkyl, aryl, COOMe, etc.

3.3.8.4.1 Substituted Benzenes and Cyclohexadienes

In practice the alkyne cyclotrimerization to benzene and its derivatives may be
performed using both homogeneous anld heterogeneous catalysts. Most catalysts
reported in the survey of the catalysts (cf. Section 3.3.8.2) may be applied, giving
good yields, to the cyclotrimerization of unsymmetrically substituted terminal
and also internal alkynes. As mentioned above, in the case of terminal alkynes
1262 3.3 Special Products

1,2,4- and 1,3,5-trisubstituted benzenes are formed (eq. (23)). For example, a
chromium(V1) catalyst trimerizes propyne to give pseudocumene and mesitylene
in a 4: 1 ratio [57]. The cyclotrimerization of 1-hexyne, 1-octyne, methyl propio-
late, and phenylacetylene at organorhodium half-sandwich complexes was inves-
tigated by Ingrosso and co-workers [ 13 b]. In the case of the alkyl-substituted ace-
tylenes the regioselectivity of the trimerization was found to be independent of the
rhodium catalyst applied. The cyclization of methyl propiolate at the y5-Flu-rho-
dium catalyst gave a higher proportion of the symmetrically substituted benzene
derivatives than were found at the y5-Ind-rhodium complex. The $-Ind-rhodium-
bis(ethy1ene) complex was found to be unusually selective in the cyclotrimeri-
zation of 3,3-dimethyl-l-butyne, giving a 76 % yield of 1,2,4-tri-t-butylbenzene
[58]. The 1,3,5-isomer is available from 3,3-dimethyl-l-butyne in the presence
of PdC12 [59]. This type of catalytic alkyne reaction has been reviewed by Maitlis
[60]. The mechanism for the trimerization of disubstituted alkynes at Mo or W
vinyl complexes was studied by Davidson et al. [61]. They found two different
reaction pathways which were dependent on the substituents at the vinyl groups
and the acetylene.
The regiochemical product distribution of the co-cyclization of two or three
different alkynes occurs statistically. In some cases carefully controlled reaction
conditions allow isolation of a main product from mixed cyclotrimerizations.
For example, 1,2,3,4-tetraphenyl-5,6-diethylbenzene can be obtained from
cobalt-catalyzed reaction of tolane and 3-hexyne in good yield [62]. The first
example of an intermolecular, regiospecific cross-benzannulation reaction cata-
lyzed by Pd(PPh& was reported by Yamamoto [63]. The reaction of 2-alkyl-
but-1-ene-3-yne with disubstituted diynes leads exclusively in high yields to
1,4-diaIkyl-2-ethynylbenzene.No other isomers are formed. The selective syn-
thesis of radiolabeled toluene and p-xylene via co-cyclotrimerization was obtained
using a heterogeneous chromium catalyst described in [57, 641.
Instead of a second or third alkyne, an alkene C=C double bond may be in-
corporated into the cyclotrimerization reaction. Iron [65], rhodium [66], nickel
[67], palladium [68], or cobalt [69] catalysts have been used to form cyclohexa-
dienes. However, the preparative use of this catalytic co-cyclization is disturbed
by consecutive side reactions of the resulting dienes such as cycloaddition or
dehydrogenation. Itoh, Ibers and co-workers [70] have reported the straight
palladium-catalyzed co-cyclization reaction of C2(C02Me)2 and norbornene
(eq. (24)).

R = COOMe d 'R

Jonas and Tadic [7 11 have investigated the homogeneous cobalt-catalyzed

co-cyclotrimerization of acetylene and olefins. The reaction with $-Ind-cobalt
bis(ethy1ene) as the catalyst was carried out with ethylene, a-olefins and 2-butene
as well as cyclohexene and cyclooctene (eq. (25)).
 3.3.8.4 Six- and Eight-Membered Curbocycles 1263

(25)

The reaction according to eq. (25) leads exclusively to cis-hexahydronaph-

thalene (cis-hexaline), a product which is otherwise accessible only by multistep
synthetic pathways 1721. Macomber [73] reported the [2+2+2] cycloaddition
reaction of diphenylacetylene or C2(C:02Me)2 and endo-dicyclopentadiene or
norbornylene, respectively, in the presence of $-Cp-cobalt dicarbonyl or
$-methyl-Cp-cobalt dicarbonyl in refluxing toluene.

-
Intramolecular cyclohexadiene syntheses have been developed by Vollhardt
[74]. Enediynes with a terminal double bond react in isooctane at 100 "C in the
presence of $-Cp-cobalt dicarbonyl giving a three-ring system [75] according
to eq. (26).

-SiMe3

SiMe3

Malacria and co-workers reported an improved diastereoselectivity of the Co-

catalyzed cycloaddition of substituted linear enediynes by introducing substituents
such as esters, sulfoxide, or phosphine oxide at the terminal position of either the
double or the triple bond [76].
With an appropriate precursor C-ring,, dienyl steroids have been made acces-
sible in a remarkably highly stereoselective process [77]. Intramolecular cyclo-
addition reactions of enediynes containing a terminal alkyne group have also
been observed by Vollhardt [78] (eq. (27)).

Supercritical water exhibits better solvent properties for apolar organic com-
pounds than water itself and was applied by Jerome and Parsons [79] as well
as Dinjus and co-workers [80] as the solvent for the Co-mediated cyclotrimeriza-
tion of monosubstituted acetylenes to benzene derivatives. Eaton et al. published
the cyclotrimerization of acetylenes bearing functional groups in a watedmethanol
(80:20) mixture using an R-Cp cobalt cod complex as the catalyst. The water
solubility of the Co complex was achieved by the special substituent
R=CO(CH2)2CH20H on the Cp ligand [81].
1264 3.3 Special Products

3.3.8.4.2 Phenylenes
o-Diethynylbenzene, available from o-diiodobenzene, can easily co-cyclize with
internal alkynes to 2,3-disubstituted diphenylenes [82] with y5-Cp-cobalt dicar-
bony1 as the catalyst (eq. (28)).

R’, R2 = H, alkyl, aryl, COOMe, SiMes

In the case of R’ = R2 = SiMe, the successive synthesis of polyphenylenes has

been reported. Subsequent iodination of the trimethylsilyl group generates a new
o-diiodoarene as the educt for the subsequent o-diethynylarene, which can react
with further bis(trimethylsily1)acetylene forming terphenylene, and so on. Multi-
phenylenes synthesized in this way have been claimed to represent a new type
of organic semiconductor [83].

3.3.8.4.3 Cyclooctatetraenes
As early as 1948, Reppe et al. reported the discovery of the “cyclic polymerization
of acetylene” to cyclooctatetraene (eq. (29)) using nickel catalysts [84]. This dis-
covery represented a true landmark in transition metal catalysis.

Recently, researchers of this reaction propose a bis(cyc1ooctatetraene) dinickel

complex as the active catalyst for the cyclotetramerization of acetylene [85].
Monosubstituted alkynes may be included in this cyclization giving 1,2,4,7-,
1,2,4,6-, and 1,3,5,7-tetrasubstitutedcyclooctatetraene derivatives [86]. A special
case is the cyclotetramerization of 1 -phenylpropyne giving the octasubstituted Cx
product besides the hexasubstituted benzene derivative [87] (eq. (30)).
 References 1265

References
[ I ] M. Berthelot, Liebigs Ann. Chem. 1866, 141, 173.
[2] (a) W. Reppe, Chemie und Technik der Acetylen-Druck-Reaktionen, 2nd ed., VCH,
Weinheim, 1952; (b) J. W. Copenhaver, IM.H. Bigelow, Acetylene and Carbon Monox-
ide Chemistry, Reinhold, New York, 19419; (c) C. W. Bird, Transition Metal Intermedi-
Utes in Organic Synthesis, Academic Press, New York, 1967.
[3] (a) H. Yamazaki, Y. Wakatsuki, Tetruhea'ron Lett. 1973, 3383; (b) H. Yamazaki, Y. Wa-
katsuki, f . Organomet. Chem. 1977, 139, 157; (c) Y. Wakatsuki, H. Yamazaki, f . Orga-
nomet. Chem. 1977, 139, 169; (d) Y. Wakatsuki, H. Yamazaki, J. Chem. Soc., Dalton
Trans. 1978, 1278.
[4] (a) K. P. C. Vollhardt, Ace. Chem. Res. 11977, 10, 1; (b) A. Naiman, K. P. C. Vollhardt,
Angew. Chem. 1977, 89, 758; Angew. Chem., Int. Ed. Engl. 1977, 16, 708; (c) J. R.
Fritch, K. P. C. Vollhardt, Angew. Chem. 1980, 92, 570; Angew. Chem., Int. Ed. Engl.
1980, 19, 559; (d) G. Ville, K. P. C. Vollhardt, M. J. Winter, J. Am. Chem. Soc. 1981,
103, 5267; (e) J. P. Tane, K. P. C. Vollhardt, Angew. Chem. 1982, 94, 642; Angew.
Chern. Int. Ed. Engl. 1982, 21, 617; ( f ) J . R. Fritch, K. P. C. Vollhardt, Orgunometallics
1982, I , 590; (g) J. S. Drage, K. P. C. Vollhardt, Orgunometallics 1982, I , 1545; (h) D. J.
Brien, A. Naiman, K. P. C. Vollhardt, J. Am. Chem. Soc. 1982, 104, 133.
[5] (a) H. Bonnemann, R. Brinkmann, H. Schenkluhn, Synthesis 1974, 575; (b) Studien-
gesellschaft Kohle mbH (H. Bonnema.nn, H. Schenkluhn), US 4.006.149 (1975);
(c) H. Bonnemann, Angew. Chem. 1978. 90, 517; Angew. Chem., Int. Ed. Engl. 1978,
17, 505; (d) H. Bonnemann, W. Brijoux, Asp. Homogeneous Cutul. 1984, 5, 75;
(e) H. Bonnemann, W. Brijoux, R. Brinkmann, W. Meurers, R. Mynott, W. von Philips-
born, T. Egolf, J. Orgunomet. Chem. 1984,272, 231; (0H. Bonnemann, Angew. Chem.
1985, 97, 264; Angew. Chem., Int. Ed. Engl. 1985, 24, 248; (g) H. Bonnemann,
W. Brijoux, Adv. Heterocycl. Chem. 1990, 48, 177; (h) J. S. Viljoen, J. A. K. du Plessis,
J. Mol. Cutul. 1993, 79, 75; (i) J. A. K. do Plessis, J. S. Viljoen, J. Mol. Cutul. A: Chem.
1995, 99, 7 1.
[6] N. E. Schore, Chem. Rev. 1988, 88, 1081.
[7] (a) F. W. Hoover, 0. W. Webster, C. T. Handy, J. Org. Chem. 1961, 26, 2234;
(b) B. Franzus, P. J. Canterino, R. A. CVickliffe, J. Am. Chem. Soc. 1959, 81, 1514;
(c) Studiengesellschaft Kohle mbH (K. Ziegler), DE 1.233.374 (1967), GB 831.328
(1960); (d) J. J. Eisch, W. C. Kaska, 1. Am. Chem. Soc. 1966, 88, 2213; (e) E. F.
Lutz, J. Am. Chem. Soc. 1961, 83, 2551 ; (f) A. F. Donda, G. Moretti, J. Org. Chem.
1966, 31, 985; (g) T. Masuda, Y.-X. Deng, T. Higashimura, Bull. Chem. Soc. Jpn.
1983,56, 2798; (h) V. A. Sergeev, Y. A. Chernomordik, V. S. Kolesov, V. V. Gavrilenko,
V. V. Korshak, Zh. Org. Khim. 1975, 11, 777; (i) W. Schonfelder, G. Snatzke, Chem.
Ber: 1980, 113, 1855; (j) V. 0. Reichsfel'd, B. I. Lein, K. L. Makovetskii, Dokl.
Akud. Nauk. SSSR 1970, 190, 125; (k) C. J. Baddeley, R. M. Ormerod, A. W. Stephen-
son, R. M. Lambert, J. Phys. Chem. 1995, 99, 5146.
[8] (a) U. KrLierke, W. Hiibel, Chem. Ber: 196,1,94, 2829; (b) H. Hopff, A. Gati, Helv. Chim.
Arta 1965, 48, 509; (c) W. Reppe, H. Vetter, Liebigs Ann. Chem. 1953, 133, 585;
(d) U. Kriierke, C. Hoogzand, W. Hiibel, Chem. Ber: 1961, 94, 2817.
[9] (a) M. Tsutsui, H. Zeiss, J. Am. Chem. Soc:. 1959, 81, 6090; (b) W. Herwig, W. Metlesics,
H. Zeiss, J. Am. Chem. Soc. 1959, 81, 6203; (c) H. Zeiss, M. Tsutsui, J. Am. Chem. Soc.
1959, 81, 6255; (d) H. P. Throndesen, W. Metlesics, H. Zeiss, J. Orgunomet. Chem.
1966, 5, 176.
[lo] G. N. Schrauzer, Chem. Bel: 1961, 94, 1403.
[11] (a) A. T. Blomquist, P. M. Maitlis, J. Am. Chem. Soc. 1962, 84, 2329; (b) P. M. Maitlis,
D. Pollock, M. L. Games, M. J. Pride, Can. J. Chem. 1965, 43, 470.
1266 3.3 Special Products

[12] L. B. Luttinger, J. Org. Chem. 1962, 27, 1591.

[13] (a) F. A. Cotton, W. T. Hall, K. J. Cann, F. J. Karol, Macromolecules 1981, 14, 233;
(b) A. Borrini, P. Diversi, G. Ingrosso, A. Lucherini, G. Serra, J. Mol. Catal. 1985,
30, 181; (c) K. Abdulla, B. L. Booth, C. Stacey, J. Organomet. Chem. 1985, 293, 103.
[14] E. M. Amett, J. M. Bollinger, J. Am. Chem. Soc. 1964, 86, 4729.
[15] A. K. Jhingan, W. F. Maier, J. Org. Chem. 1987, 52, 1161.
[16] P. Cioni, P. Diversi, G. Ingrosso, A. Lucherini, P. Ronca, J. Mol. Cutul. 1987, 40, 337.
[I71 (a) U. Schmidt, U. Zenneck, J. Organomet. Chem. 1992,440, 187; (b) D. Bohm, F. Koch,
S. Kummer, U. Schmidt, U. Zenneck, Angew. Chem. 1995,107,251 ; Angew. Chem., Int.
Ed. Engl. 1995, 34, 198.
[ 181 Studiengesellschaft Kohle mbH (H. Bonnemann, H. Schenkluhn), DE 2.416.295 (1974).
[I91 (a) M. Aresta, M. Rossi, A. Sacco, Inorg. Chim. Acta 1969, 3, 227; (b) P. Diversi,
A. Guisti, G. Ingrosso, A. Lucherini, J. Organomet. Chem. 1981, 20.5, 239.
[20] G. Vitulli, S. Bertozzi, M. Vignali, R. Lazzaroni, P. Salvadori, J. Organomet. Chem.
1987, 326, C33.
[21] W. Schultz, H. Pracejus, G. Oehme, Tetrahedron Lett. 1989, 30, 1229.
[22] (a) D. M. M. Rohe, Ph. D. Thesis, RWTH Aachen, (1979); (b) Studiengesellschaft Kohle
mbH (H. Bonnemann), DE 3.117.363.2 (1981); (c) Studiengesellschaft Kohle mbH
(H. Bonnemann), US 4.588.81 5 (1984).
[23] P. Diversi, L. Ermini, G. Ingrosso, A. Lucherini, J. Organomet. Chem. 1993, 447, 291.
[24] R. A. Abramovitch, Chem. Heterocycl. Compd. 1974, 1975, 14, Suppl. Parts 1-4, Wiley,
New York, 1975.
[25] (a) W. Ramsay, Philos. Mag. [5] 1876, 4, 269; (b) W. Ramsay, Philos. Mag. [ 5 ] 1877, 5,
24; (c) N. Ljubawin, J. Russ. Phys.-Chem. Ges. 1885,250; (d) R. Meyer, A. Tanzen, Ber:
Dtsch. Chem. Ges. 1913, 46, 3 186.
[26] (a) G. Herberich, W. Koch, H. Leuken, J. Organomet. Chem. 1978, 160, 17; (b) Studien-
gesellschaft Kohle mbH (H. Bonnemann, B. Bogdanovic), DE Appl. 310.550.1 (1982);
(c) Studiengesellschaft Kohle mbH (H. Bonnemann, B. Bogdanovic), EP Appl. 83/
101.246.3 (1983).
[27] (a) Stamicarbon N. V. (J. M. Deumens, S. H. Green) GB 1.304.155 (1973); (b) Stamicar-
bon N. V. (J. M. Deumens, S. H. Green) US 3.780.082 (1973); (c) Chem. Mark. Rep.
1977.
[28] (a) Y. Kusunoki, H. Okazeku, Hydrocarbon Process, 1974,53 ( 1 l), 129, 13 1 ; (b) Y. Ku-
sunoki, H. Okazaki, Nippon Kugaku Kaishi 1981, 12, 1969; (c) Y. Kusunoki, H. Oka-
zaki, Nippon Kaguku Kaishi 1981, 12, 1971.
[29] (a) Lonza AG (P. Hardt), CH Appl. 76/14.399 (1976); (b) Lonza AG (P. Hardt) DE
2.75 1.072 (1978).
[30] S. Goldschmidt, M. Minsinger, DE 952.807 (1956); (b) J. P. Wibaut, C. Hoogzand,
Chem. Weekhlad 1956, 52, 357.
[31] M. J. Birchenough, J. Chem. Soc. 1951, 1263.
[32] (a) D. Tatone, Trane Cong Dich, R. Nacco, C. Botteghi, J. Org. Chem. 1975, 40, 2987;
(b) G. Cavinato, L. Toniolo, C. Botteghi, S. Gladiali, J. Organomet. Chem. 1982,229, 93.
[33] C. Botteghi, private communication, 1975.
[34] R. Brinkmann, private communication, 1982.
[35] D. B. Wootton, Dev. Adhes. 1977, I , 181.
[36] Schering AG, DE 663.891 (1936).
[37] P. Arnall, N. R. Clark, Chem. Process. (London) 1971, 17, (lo), 9, 11-13, 15.
[38] H. Bonnemann, G. S. Natarajan, Erdd, Kohle, Erdgas, Petrochem. 1980, 33, 328.
[39] R. A. Abramovitch, Chem. Heterocycl. Compd. 1975,/4, Suppl. Part 4, Chapter 15, 189.
[40] (a) E. Shaw, J. Bemstein, K. Losse, W. A. Lott, J. Am. Chem. Soc. 1950, 72, 4362;
(b) Olin Mathieson Chemical Corp. (S. Semenoff, M. A. Dolliver), US 2.745.826 (1956).
 References 1267

[41] (a) G. M.Badger, W. H. F. Sasse, Adv. Heterocycl. Chem. 1963, 2, 179; (b) M. A. E.
Hodgson, Chem. Ind. (London) 1968. 49; (c) L. A. Summers, The Bipyridiniurn
Herbicides, Academic Press, New York, 1980.
[42] H. Bonnemann, R. Brinkmann, Synthesis 1975, 600.
[43] A. Naiman, K. P. C. Vollhardt, Angew. Chem. 1977, 89, 758; Angew. Chem., Int. Ed.
Engl. 1977, 16, 708.
[44] R. E. Geiger, M. Lalonde, H. Stoller, K. Schleich, Helv. Chim. Acta 1984, 67, 1274.
[45] (a) K. P. C. Vollhardt, J. E. Bercaw, R. Ci. Bergman, J. Am. Chem. Soc. 1974, 96, 4996;
(b) C. A. Pamell, K. P. C. Vollhardt, Tetrahedron 1985, 41, 5791 ; (c) K. P. C. Vollhardt,
Lect. Heterocycl. Chem. 1987, 9, 59.
[46] (a) D. J. Brien, A. Naiman, K. P. C. Vollhardt, Chem. Soc., Chem. Commun. 1982, 133;
(b) K. P. C. Vollhardt, Lect. Heterocycl. Chem. 1987, 9, 60.
[47] K. P. C. Vollhardt, f l t h Int. Congr: Heterocycl. Chem. Heidelberg, 1987.
[48] H. Bonnemann, X. Chen, Proc. Swiss Chern. Soc. Autumn Meet, 1987, Bem, 1987, 39.
[49] (a) G. S. Sheppard, K. P. C. Vollhardt, J. Org. Chem. 1986, 51, 5496; (b) R. Boese, H.-J.
Knolker, K. P. C. Vollhardt, Angew. Chem. 1987, 99, 1067; Angew. Chem., Int. Ed. Engl.
1987, 26, 1035.
[50] (a) R. B. Woodward, M.P. Cava, W. D. Ollis, A. Hunger, H. U. Daeniker, K. Schenker,
Tetrahedron 1963, 19, 247; (b) D. B. Grotjahn, K. P. C. Vollhardt, J. Am. Chem. Soc.
1986, 108, 2091; (c) K. P. C. Vollhardt, Lect. Heterocycl. Chem. 1987, 9, 61.
[SI] (a) H. Yamazaki, Y. Wakatsuki, Kagaku Sosetsu 1981,32, 161; (b) H. Yamazaki, J. Synth.
Org. Chem. 1987, 45, 244.
[52] (a) R. A. Earl, K. P. C. Vollhardt, J. Am. Chem. Soc. 1983, 105, 6991; (b) P. Diversi,
G. Ingrosso, A. Lucherini, S. Malquori, J. Mol. Catul. 1987, 40, 267.
(531 S . T. Flynn, S. E. Hasso-Henderson, A. W. Parkins, J. Mol. Catal. 1985, 32, 101.
[54] M. Kajitani, T. Suetsugu, A. Igarashi, T. Akiyama, A. Sugimori, H. Bonnemann, 30th
Symp. Organomet. Chem., Kyoto, Japan, 1983, Abstr. A206.
[55] (a) M. Kajitani, T. Suetsugu, A. Igarashi, T. Akiyama, A. Sugimori, J. Organomet.
Cheme. 1985, 293, C15; (b) M.Kajitaini, R. Ochiai, N. Kobayashi, T. Akiyama, A.
Sugimori, Chem. Lett. 1987, 245.
[56] S. W. Benson, Thermochemical Kinetics, Wiley, New York, 1968.
[57] R. A. Femeri, A. P. Wolf, J. Phys. Chem 1984, 88, 2256.
[58] P. Caddy, M. Green, E. O’Brien, L. E. Smart, P. Woodward, J. Chem. Soc., Dalton Trans.
1980, 962.
[59] (a) P. M. Maitlis, Acc. Chem. Res. 1976, 9, 93; (b) P. M. Maitlis, E. A. Kelly, J. Chem.
Soc., Dalton Trans. 1979, 167; (c) F. Canziani, C. Allevi, L. Garlaschelli, M. C. Mala-
testa, A. Albinati, F. Ganazzoli, J. Chem. Soc., Dalton Trans. 1984, 2637.
[60] P. M.Maitlis, J. Organomet. Chem. 19810, 200, 161.
[61] N. M.Agh-Atabay, L. Carlton, J.L. Davidson, G. Douglas, K. W. Muir, J. Chem. Soc.,
Dalton Trans. 1996, 999.
[62] (a) W. Hiibel, C. Hoogsand, Chem. Ber: 1960, 93, 103; (b) 0. S. Mills, G. Robinson,
Proc. Chem. Soc. 1964, 187.
[63] V. Gevorgyan, A. Takeda, Y. Yamamoto, J. Am. Chem. Soc. 1997, 119, 11.313.
1641 M.Speranza, R. A. Femeri, A. P. Wolf, F. Cacace, J. Labeled Compd. Radiopharm.
1982, 19, 61.
[65] A. Carbonaro, A. Greco, G. Dall’Asta, 7etrahedron Lett. 1968, 5129.
[66] D. M. Singleton, Tetrahedron Lett. 1973., 1245.
1671 A. Chalk, J. Am. Chem. Soc. 1972, 94, 5928.
[68] L. D. Brown, K. Itoh, H. Suzuki, K. Hirai, J. A. Ibers, J. Am. Chem. Soc. 1978 100, 8232.
[69] E. Dunach, R. L. Halterman, K. P. C. Vollhardt, J. Am. Chem. Soc. 1985, 107, 1664.
[70] H. Suzuki, K. Itoh, Y. Ishii, K. Simon, J. A. Ibers, .I. Am. Chem. Sue. 1976, 98, 8494.
1268 3.3 Special Products

[71] M. G. J. Tadic, Ph. D. Thesis, Ruhr-Universitat Bochum, 1990.

[72] (a) W. G. Dauben, M. S. Kellog, J. Am. Chem. Soc. 1980, 102,4456; (b) W. G. Dauben,
E. G. Olson, J. Org. Chem. 1980, 45, 3377.
[73] D. W. Macomber, A. G. Verma, Orgunometallics 1988, 7, 1241.
[74] K. P. C. Vollhardt, Pure Appl. Chem. 1985, 57, 1819.
[75] (a) W. D. Sternberg, K. P. C. Vollhardt, J. Am. Chem. Soc. 1980, 102, 4841; (b) E. D.
Sternberg, K. P. C. Vollhardt, J, Org. Chem. 1984, 49, 1564.
[76] F. Slowinski, C. Aubert, M. Malacria, Tetrahedron Lett. 1999, 40, 707.
[77] (a) E. D. Sternberg, K. P. C. Vollhardt, J. Org. Chem. 1984,49, 1574; (b) H. Butenschon,
M. Winkler, K. P. C. Vollhardt, J. Chem. Soc., Chem. Commun. 1986, 388.
[78] T. R. Gadek, K. P. C. Vollhardt, Angew. Chem., Jnt. Ed. Engl. 1981, 20, 802.
[79] K. S. Jerome, E. J. Parsons, Organometallics 1993, 12, 2991.
[SO] H. Borwieck, 0. Walter, E. Dinjus, J. Rebizant, J. of Organomet. Chem. 1998, 570, 121.
[81] B. R. Eaton, M. S. Sigmund, A. W. Fatland, J. Am. Chem. Soc. 1998, 120, 5 130.
[82] B. C. Berris, Y.-H. Lai, K. P. C. Vollhardt, J. Chem. Soc., Chem. Commun. 1982, 953.
[83] K. P. C. Vollhardt,Angew. Chem. 1984,96,525;Angew.Chem., Jnt. Ed. Engl. 1984,23,539.
[84] W. Reppe, 0. Schlichting, K. Klager, T. Toepel, Liebigs Ann. Chem. 1948, 560, 1.
[85] G. Wilke, Angew. Chem. 1988, 100, 189; Angew. Chem., Jnt. Ed. Engl. 1988, 27, 185.
[86] (a) P. Cini, N. Palladino, A. Santambrogio, J. Chem. Soc. C 1967, 835; (b) J. R. Leto,
M. F. Leto, J. Am. Chem. Soc. 1961, 83, 2944.
1871 L. H. Simons, J. J. Lagowski, Fund. Res. Homogeneous Cutul. 1978, 2, 73.

3.3.9 Chemicals from Renewable Resources

Jochen l? Zoller

3.3.9.1 Introduction and General Developments

Sustainable development, responsible care, and process-integrated protection of
the environment are the guidelines of chemistry and the chemical industry in
the new millennium. A high percentage of industrial processes are based on the
catalytic transformation of substrates. The main focus of industrial research is
the further development of transformation processes toward sustainability, and
the use of renewable resources as substrates.
The use of renewable resources as substrates in chemical processes has recently
been reviewed [I]. There are two major topics of current research: (1) oleochem-
ical reactions, and (2) chemical transformation of carbohydrates. Nevertheless, the
chemical possibilities of renewable resources as substrates - using homogeneous
catalysis - are still very far from being fully exploited.

3.3.9.2 “Oleo Chemistry”

Natural oils and fats comprise the greatest proportion of renewable resources as
substrates, since they are produced easily from vegetables and animals. The
range of possibilities was summarized in 1988 [2].
 Applied Homogeneous Catalysis with Organometallic Compounds
Edited by B. Cornils and W. A. Herrmann
Copyright 0 Wiley-VCH Verlag GmbH, D-69469 Weinheim, 2002

1268 3.3 Special Products

[71] M. G. J. Tadic, Ph. D. Thesis, Ruhr-Universitat Bochum, 1990.

[72] (a) W. G. Dauben, M. S. Kellog, J. Am. Chem. Soc. 1980, 102,4456; (b) W. G. Dauben,
E. G. Olson, J. Org. Chem. 1980, 45, 3377.
[73] D. W. Macomber, A. G. Verma, Orgunometallics 1988, 7, 1241.
[74] K. P. C. Vollhardt, Pure Appl. Chem. 1985, 57, 1819.
[75] (a) W. D. Sternberg, K. P. C. Vollhardt, J. Am. Chem. Soc. 1980, 102, 4841; (b) E. D.
Sternberg, K. P. C. Vollhardt, J, Org. Chem. 1984, 49, 1564.
[76] F. Slowinski, C. Aubert, M. Malacria, Tetrahedron Lett. 1999, 40, 707.
[77] (a) E. D. Sternberg, K. P. C. Vollhardt, J. Org. Chem. 1984,49, 1574; (b) H. Butenschon,
M. Winkler, K. P. C. Vollhardt, J. Chem. Soc., Chem. Commun. 1986, 388.
[78] T. R. Gadek, K. P. C. Vollhardt, Angew. Chem., Jnt. Ed. Engl. 1981, 20, 802.
[79] K. S. Jerome, E. J. Parsons, Organometallics 1993, 12, 2991.
[SO] H. Borwieck, 0. Walter, E. Dinjus, J. Rebizant, J. of Organomet. Chem. 1998, 570, 121.
[81] B. R. Eaton, M. S. Sigmund, A. W. Fatland, J. Am. Chem. Soc. 1998, 120, 5 130.
[82] B. C. Berris, Y.-H. Lai, K. P. C. Vollhardt, J. Chem. Soc., Chem. Commun. 1982, 953.
[83] K. P. C. Vollhardt,Angew. Chem. 1984,96,525;Angew.Chem., Jnt. Ed. Engl. 1984,23,539.
[84] W. Reppe, 0. Schlichting, K. Klager, T. Toepel, Liebigs Ann. Chem. 1948, 560, 1.
[85] G. Wilke, Angew. Chem. 1988, 100, 189; Angew. Chem., Jnt. Ed. Engl. 1988, 27, 185.
[86] (a) P. Cini, N. Palladino, A. Santambrogio, J. Chem. Soc. C 1967, 835; (b) J. R. Leto,
M. F. Leto, J. Am. Chem. Soc. 1961, 83, 2944.
1871 L. H. Simons, J. J. Lagowski, Fund. Res. Homogeneous Cutul. 1978, 2, 73.

3.3.9 Chemicals from Renewable Resources

Jochen l? Zoller

3.3.9.1 Introduction and General Developments

Sustainable development, responsible care, and process-integrated protection of
the environment are the guidelines of chemistry and the chemical industry in
the new millennium. A high percentage of industrial processes are based on the
catalytic transformation of substrates. The main focus of industrial research is
the further development of transformation processes toward sustainability, and
the use of renewable resources as substrates.
The use of renewable resources as substrates in chemical processes has recently
been reviewed [I]. There are two major topics of current research: (1) oleochem-
ical reactions, and (2) chemical transformation of carbohydrates. Nevertheless, the
chemical possibilities of renewable resources as substrates - using homogeneous
catalysis - are still very far from being fully exploited.

3.3.9.2 “Oleo Chemistry”

Natural oils and fats comprise the greatest proportion of renewable resources as
substrates, since they are produced easily from vegetables and animals. The
range of possibilities was summarized in 1988 [2].
 3.3.9.2 “Oleo Chemistry” 1269

The main applications of chemical processes in the field of oleo chemistry in-
volve oxidation and metathesis. Neither is yet involved in industrial processes, but
their application moves realistically nearer as the interest in this topic increases.

3.3.9.2.1 The Oxidation of Oils and Fats

As mentioned above, fatty materials as educts for chemical processes are available
from vegetables and animals in such purity that they can be used for further
chemical conversion.
Unsaturated fatty compounds are the preferred educts in industrial epoxidation.
Numerous methods are available to transform then to the corresponding epoxides.
Epoxidation with molecular oxygen [3], dioxiranes [4], hydrogen peroxide with
methyltrioxorhenium as catalyst [5, 61, the Halcon process [7], or enzymatic reac-
tions [8] are the most important industrial processes (cf. Section 2.4.3).
Due to the excellent stability and activity of oxidized “vegetable oils”, these are
used as stabilizers in polymerization chemistry. Epoxidation of vegetable oils by

&-
the enzyme Novozym 435 [8] (eq. (1)) is an example.

5 ma1H202
35%
“ovozym4351RT acid
free fany 16h

_ _ _
(1)

Furthermore, oxidation of fatty acids to vicinal diols, as well as their oxidative

cleavage, are important industrial applications. Vicinal diols of unsaturated fatty
compounds can be prepared by nucleophilic ring opening of the epoxides after
epoxidation, but difficult technical conditions are necessary to achieve this ring
opening [9]. The use of Re- [ 101, W- [ 1I], or Mo [ I]-based catalysts with hydro-
gen peroxide can give a syn-diol via the epoxide as intermediate (eq. (2)).

-COOCH, - + A C O O C H ,
OH
(2)
The cleavage of oleic acid to azelaic acid and pelargonic acid with ozone as
oxidant is one of the important industrial applications of ozonolysis [2]. However,
finding a catalytic alternative to this unsuitable and hard-to-handle oxidant is in
the interests of research groups all over the world. The cleavage of internal
C=C double bonds by use of a Re, Mo, or W catalyst with H202as oxidant, or
a Ru catalyst with peracetic acid [ 121, is known.
Oxidative cleavage with hydrogen peroxide as oxidant is more important in
oxidation processes of natural products. The use of a three-fold excess of hydro-
gen peroxide without further additives, except for the catalyst methyltrioxorhe-
nium (MTO), enables the oxidation of certain natural products drawn from styrene
1270 3.3 Special Products

OH OH OH OH

R: -CH3 = lsoeugenol
-COOH = trans-ferulic acid

Scheme 1

and its derivatives (cf. Section 3.3.13). Thus, a new method for the synthesis
of vanillin out of renewable resources such as isoeugenol and trans-femlic
acid should be mentioned. Both are derived from renewable resources by the
extraction of sawdust (isoeugenol) or agricultural waste (trans-femlic acid)
(Scheme 1) [13].

3.3.9.2.2 The Metathesis of Oils and Fats

Metathesis of olefins, through the use of transition metal catalysis, is an important
application in the petrochemical as well as in the polymer chemical industry for
the production of special olefins and polymers (cf. Section 2.3.3). This chemistry
is also applicable to unsaturated fatty acid esters, such as acetic acid methyl ester.
However, the high price and unsustainability of the catalysts, compared with the
fatty acids as substrates, have made commercial utilization not yet possible; never-
theless they are of great interest for researchers in this field.
Starting from the anchored heterogeneous catalysts such as Re207. B203/A1203
. Si02, activated by SnR4, or CH3Re03 + B203 . A1203 . SiO, [14], the use of
homogeneous catalysts then gained importance. Here, the “Grubbs catalyst” is
under investigation [ 151. Methyltrioxorhenium is also suitable for the metathesis
of unsaturated fatty compounds [ 161.
From the industrial point of view the co-metathesis of unsaturated fatty com-
pounds, especially methyl oleate, with ethylene to form methyl 9-decenoate and
1-decene is becoming more important (eq. (3)).

-
-
\COOCH3 H,C=CH(CH,),CH,
1-decene
+ catalyst
+
RT, 20h
25-50bar
H,C=CH(CH2),COOCH3
H,C=CH,
methyl 9-decenoate

catalyst: CH3Re03+ B203 . AIzO3 . SiOz

or Rez07.B203I Al2O3 SiOp + SnR4
 3.3.9.4 The Chemistry of Starch 1271

As generation of oils and fats from of natural products is inexpensive, the

investigation of these oils as educts in chemical processes is the focus of current
research.

3.3.9.3 The Chemistry of Carbohydrates

Today, metal-catalyzed oxidation with oxygen, being simple, is the most impor-
tant technology for the conversion of hydrocarbons to bulk industrial chemicals.
Such processes involve the use of heterogeneous catalysts. In the manufacture of
fine chemicals, the replacement of stoichiometric inorganic oxidants is still the
focus of investigations. These catalytic processes employ cheap and environmen-
tally friendly oxidants. Within the same environmental context, carbohydrates are
of interest as renewable raw materials in the manufacture of fine chemicals. Oxi-
dation is an obvious method for upgrading carbohydrates, since a mass increase
takes place and the character of the carbohydrate compound changes tremen-
dously. Several reviews are available in the field of carbohydrate oxidation [17].
Recently, the oxidative formation of the c6 group in carbohydrates has became
a strong focus of investigation, since when it is applied to the starch molecule,
superabsorbing material based on renewable resources can be produced. There-
fore, the development of new catalytic methods for the selective oxidation of
terminal alcohols c6 by applying simple and cheap oxidants such as hydrogen
peroxide still remains challenging.

3.3.9.4 The Chemistry of Starch

Strong oxidizing agents (KMn04, Mn02, Se02, etc.) in stoichiometric amounts
are necessary to perform the oxidation of alcohols [18]. The selective oxidation
of primary alcohols, in the presence of secondary ones, is preferred when the
stable organic nitroxyl radical 2,2,6,6-tetramethyl-l-piperidinyloxy(TEMPO;
Structure 1) is used as a mediator [19-211. The nitrosonium ion (2) is the inter-
mediate oxidizing species; it becomes reduced to the hydroxylamine 3 during
the oxidation process, then it regenerates to 1 during further reaction.

1 2 3

The c6 primary alcohol group in carbohydrates can be oxidized selectively by

the in situ generation of the nitrosonium ion 2 using hypochlorite as oxidant and
the bromidehypobromide co-catalyst in water [21, 221. An analogous system was
applied to monosaccharide [22]. Recently it has been reported that MTO also
1272 3.3 Special Products

catalyzes the conversion of alcohols to aldehydes in the presence of hydrogen

peroxide [23].
From an industrial point of view, the complete oxidation of the C6-hydroxy-
methyl group of potato starch yielding the corresponding carboxylic acid would
be preferred since such biopolymers can be used in a variety of applications,
e. g., as superabsorbing agents. To generate carboxylated starch exclusively by
extensive oxidation of the hydroxymethyl groups of the starch molecules to
carboxylic acid units, the application of a three-component system (H202/MTO/
NaBr) without TEMPO is useful; further oxidation of the intermediate aldehyde
is expected to occur [23]. The main advantage of this method is the use of aqueous
reaction media and the substitution of bleach as an oxidant.
The water-soluble starch used contains 27 % amylose and 73 % amylopectin,
and the oxidized starch can be isolated as a gel. The characteristic signal for
the carboxylic C6 group was monitored at 6 = 176.5. Signals due to the cor-
responding aldehyde groups were not seen (Structure 4).

6- 176s pprn
b o & o & f
oHO j 61.9 pprn

-0 OH HO
HO
n
4

The mechanistic proposals for the oxidation of alcohols with MTO/H202

and NaBr as a co-catalyst are demonstrated in Scheme 2. Further formation of
hypobromite in the presence of excess hydrogen peroxide takes place during
r: 1

Scheme 2
 References 1273

the oxidation process. This is a reasonable explanation for the observation that no
aldehyde is formed, but only the preferred carboxylic acid.
The. use of bifunctional cross-linking reagents, such as divinylsulfone, leads to
the additional covalent bonding of oxidized starch molecules. This allows a
further increase in the water-absorbing properties. Thus, ecologically problematic
oxidants such as bleach or NO, are becoming obsolete [24].

References
[I] J. 0. Metzger et al., Angew. Chem. Int. Ed. 2000, 39, 2206.
[2] H. Baumann, M. Buhler, H. Fochem, F. Hiersinger, H. Zoebelein, J. Falbe, Angew.
Chem., Int. Ed. Engl. 1988, 27, 41.
[3] M.C. Kuo, C. T. Chou, Int. Eng. Chem. Res. 1987, 26, 277.
[4] W. Adam, J. Bialas, L. Hadjiarapoglou, Chem. Ber. 1991, 124, 2377.
[5] W. A. Henmann, R. W. Fischer, M. U. Rauch, W. Scherer, J. Mol. Catal. A: Chem. 1994,
86, 245.
[6] W.A. Herrmann, R. W. Fischer, D. W. Marz, Angew. Chem., Int. Ed. Engl. 1991,
30, 1638.
[7] R. Landau, G. A. Sullivan, D. Brown, CHEMTECH 1979, 602.
[8] M. Riisch gen. Klass, S. Warwel, Ind. Crops Prod. 1999, 9, 125.
[9] B. Dahlke, S. Hellbarbt, M. Paetow, W. H. Zech, J. Am. Oil Chem. Soc. 1995, 72, 349.
[ 101 W. A. Herrmann, D. W. Marz, J. G. Kuchler, G. Weichselbaumer, R. W. Fischer, DE
3.902.357 A l ; Chem. Abstr. 1991. 114, 143714.
[ I l l T. M. Luong, H. Schriftmann, D. Swem, J. Am. Oil Chem. Soc. 1967,44, 316.
[12] S. Wanvel, M. Riisch gen. Klaas, US 5.321.158 (1994); Chem. Abstr: 1996, 125, 136578.
(131 W. A. Herrmann, T. Westkamp, J. P. Zoller, R. W. Fischer, J. Mol. Catal. A: Chem. 2000,
153, 49.
[I41 S. Warwel, P. Bavay, M. Riisch gen. Klaas, B. Wolff, Perspectiven nachwachsender
Rohstoffe in der Chemie, VCH, Weinheim, 1996, p. 119.
[I51 T. Weskamp, F. J. Kohl, W. Hieringer, D. Gleich, W. A. Herrmann, Angew. Chem. 1999,
I l l . 2573.
[I61 W. A. Herrmann, W. Wagner, U. N. Flessner, U. Volkhardt, H. Komber, Angew. Chem.,
Int. Ed. Engl. 1991, 30 ,1636.
1171 A. J. H. F. Arts, E. J. M. Mombarg, H. van Bekkum, R. A. Sheldon, Synthesis, 1997, 597.
[ 181 J. March, Advanced Organic Chemistry: Reaction, Mechanisms and Structure, 4th ed.,
John Wiley, New York, 1992.
[19] M.F. Semmelhack, C. S. Chou, D. A. CortCs, J. Am. Chem. Soc. 1983, 105, 4492.
[20] H. van Bekkum, A. C. Besemer, Carbohydrates in Europe, Carbohydrate Research
Foundation, 1995, p. 16.
[21] H. van Bekkum, A. E. J. de Nooy, A. C. Besemer, Synthesis 1996, 1153.
[22] S.L. Flitsch, N. J. Davis, Tetrahedron Lett. 1993, 34, 1181.
[23] W.A. Henmann, J. P. Zoller, R. W. Fischer, J. Organomet. Chem. 1999, 579, 404.
[24] A. Fischbach, Diplomarbeit, Technische Universitat Miinchen 2001, unpublished results.
 Applied Homogeneous Catalysis with Organometallic Compounds
Edited by B. Cornils and W. A. Herrmann
Copyright 0 Wiley-VCH Verlag GmbH, D-69469 Weinheim, 2002

1274 3.3 Special Product,$

3.3.10 Special Reactions in Homogeneous Aqueous Systems

3.3.10.1 Synthesis of Polymers

Bruce M. Novak

3.3.10.1.1 Introduction
Although the synthesis of polymers relies on the same fundamental bond-forming
reactions that are commonly used in small molecule synthesis, polymerizations
are often complicated by their own distinct issues of high viscosities, low solubi-
lities, and slow molecular diffusion (cf. Sections 2.3.1.1 and 2.3.1.2). Problems
emanating from these issues are often amplified, and additional problems intro-
duced, when polymerizations are adapted to aqueous conditions. In spite of
these added complications, the use of aqueous media in polymer synthesis is
highly desirable. In addition to the more obvious environmental factors, there
are a number of kinetic advantages that can be derived by running organic poly-
merizations under aqueous emulsion conditions.
Aqueous polymerizations can be run homogeneously, heterogeneously, or
under emulsion conditions [ 11. The standard aqueous-emulsion polymerization
system is composed of a water-insoluble (or partially soluble) monomer, an emul-
sifier, and a water-soluble initiator. One example of a commercial emulsion sys-
tem is the formation of a styrene-butadiene latex rubber, using sodium dodecyl-
sulfate as a surfactant for the two monomers, with a hydroperoxide-ferrous ion
redox system as the initiator [2]. The advantages associated with aqueous-emul-
sion polymerizations are many and include ease of processing, improved heat
transfer [3], reduced viscosities [4], and kinetic advantages that allow for the for-
mation of high-molecular-weight polymer at high polymerization rates [ 5 ] . In a
standard radical polymerization there is an inverse relationship between the poly-
merization rate and the polymer’s molecular weight (eq. (1)) [6]:

In this equation, Y is the kinetic chain length and R, is the rate of polymerization
(RP= k, [M](fk,[I]/k,)”*; [MI = monomer concentration; k, = propagation rate
constant;f= frequency factor; kd = initiator composition constant; k, = termination
rate constant; [I] = initiator concentration). From a practical viewpoint, this in-
verse relationship makes it difficult to effect large changes in the molecular weight
of the polymer. In particular, the difficulty arises in trying to form high-molecular-
weight polymer at rapid rates because the high concentration of radicals necessary
for fast rates also favors bimolecular termination processes (low-molecular-weight
polymer can always be made by the incorporation of chain-transfer agents). The
compartmentalization of the reaction within micelles acts to nullify the bimolecu-
lar termination by allowing only one propagating chain per micelle.
 3.3.10.I Synthesis of Polymers 1275

For obvious reasons, cationic and anionic polymerizations, as well as any other
technique that propagates through water-sensitive intermediates, are not applicable
to emulsion conditions. Currently, only radical emulsion processes are used com-
mercially.

3.3.10.1.2 Step-Growth Polymerizations

Polymerizations in which chain growth occurs in a stepwise manner are called
step-growth polymerizations, or condensation polymerizations [ 11. The “step” ter-
minology is used because it accurately reflects the kinetics of the process wherein
high-molecular-weight polymers are assembled in a stepwise fashion as mono-
mers react to form dimers. In turn, dimers form tetramers, tetramers become
octomers, and so on. This orderly growth scheme is naturally complicated by frag-
ments of any and all sizes reacting with one another (monomer with tetramer, for
example). Step-polymers are formed by allowing difunctional monomers with
complementary functional groups to react with one another. There are two com-
mon types of step-growth processes, involving either the reaction between
A-A- and B-B-type monomers or the self-condensation of A-B monomers. In
both cases, the A functional groups react exclusively with B groups and B groups
exclusively with A groups.
This stepwise method of construction of polymer chains has important conse-
quences for both the molecular weights and the molecular weight distributions of
the polymers produced. Probability dictates that the most abundant species tend to
co-condense; thus, at the reaction’s inception, small chains most likely react with
other small chains. This tendency persists to very high conversion, and conse-
quently, high-molecular-weight polymers are not produced until very late in the
reaction (i.e., past 99 % conversion) when there is finally a greater probability
of larger chains reacting with one another. This statistically determined molecular
weight profile means that only very high- yielding reactions can be used to form
step-growth polymers. This restriction points to an important distinction between
small-molecule organic reactions and step-growth polymerizations. Although
a reaction that typically yields 85 % of the desired product is considered “good”
in organic synthesis, the same reaction is essentially useless for step-growth poly-
merizations because high-molecular-weight polymers will never be formed at such
low conversions. The successful preparation of high-molecular-weight polymer
using step-growth polymerizations is dependent on both the extent of reaction
and the stoichiometric match of complementary reacting groups. These relation-
ships can be seen from the Carothers equation (eq. (2)) [7]:

where X , = the degree of polymerization, r = ratio of reacting functional groups

NJN,, and p = fraction of the reactive groups converted. It is clear that incidents
that alter the stoichiometric ratio of reactive groups or in any way limit the con-
version will drastically reduce the resulting molecular weights.
1276 3.3 Special Products

A long-standing goal in polymer synthesis has been the preparation of soluble

poly@-phenylene) derivatives. Of the various approaches attempted, transition
metal-mediated coupling reactions have proved to be the most promising. Un-
fortunately, most of these coupling approaches are incompatible with aqueous
conditions [8]. One method, however, the Suzuki coupling of aryl halides and
aryl boronic acids, is carried out in aqueous emulsions using a Pdo catalyst
(eq. (3)) (cf. Section 2.11) [9].

z 98 Yo

This reaction is significant in that it is one of the few examples of a metal-

mediated, carbon-carbon bond-forming reaction that proceeds in the presence
of water. This coupling method has been used in the synthesis of a variety of sub-
stituted poly@-phenylenes) which are soluble in organic solvents by virtue of
long-chain alkyl substituents [ 101. Wallow and Novak [ 1I] showed that this
Pdo-catalyzed cross-coupling can be carried out homogeneously in water [ 121
by making use of water-soluble phosphine ligands [ 131. Specifically, a water-
soluble poly@-phenylene) derivative (Structure 1) was synthesized by an aqueous
adaptation of the Suzuki cross-coupling reaction (eq. (4)).

COOH

HOOC HOOC
1
L z TPPMS (cf. Section 3.1.1.1) (4)

Although side reactions associated with the supporting phospine ligands do not
greatly affect small molecule couplings, they can affect polymerizations dramati-
cally. The effect of one of these side reactions will be discussed. A general cata-
lytic cycle for the Suzuki coupling process is shown in Scheme 1 .
The coupling pathway in this scheme is complicated by a facile exchange of the
aryl groups between the Pd center of Structure 3 and a bound triphenylphosphine
ligand [ 141. In small-molecule chemistry, this exchange process yields small
amounts of unsubstituted biphenyl, but in polymer synthesis, exchange introduces
the possibility of incorporating flexible phosphines within the polymer backbone.
Specifically, repeated exchanges on the same phosphine result in the formation of
new trifunctional monomers that can act as either branch or crosslinking points
(Scheme 2) [15].
In the case of bifunctional haloaromatics, this exchange process introduces
reactive functionality onto the phosphine ligands. As these catalytic systems
have been fine-tuned to insure complete conversion of these functional groups,
the probability of incorporating an exchanged phosphine into the polymer struc-
ture becomes high. Incorporating the functionalized phosphine after a single
 3.3.10.1 Synthesis o j Polymers 1277

PdLj

desired product exchange product

(from 4a) (from 4b)

6-
O-
7Ar2
q d - B r
PAr3
y PAr3
3b
4a

rB(OW3Brl-
Scheme 1

Br

t t

linear chains
flexible link

phosphine end cap

branch points/
Scheme 2 crosslinks
1278 3.3 Special Products

exchange leads to endcapped chains. Incorporation after a double exchange intro-

duces a flexible link into the polymer chain, and incorporation after a triple ex-
change leads to branches and/or crosslinks. Hence, polymers synthesized under
conditions in which aryl exchange is facile would be expected to be branched,
random-coil polymers rather than rigid rods. Phenomenologically, this is observed
when comparing the properties of polymers synthesized in the presence or
absence (vide infru) of phosphine ligands. The sodium and cesium salts of car-
boxylated poly(pheny1enes) synthesized in the presence of phosphines are highly
soluble, have very high molecular weights and shape factors consistent with coils
rather than rods, and show no evidence of anisotropic behavior in solution. In
contrast, sodium salts of carboxylated poly(pheny1enes) synthesized in the ab-
sence of phosphines are completely insoluble and precipitate during polymeriza-
tion. The Cs' salts of the phosphine-free polymers are sparingly soluble only after
prolonged heating. This difference indicates that these materials must be structu-
rally very distinct, although the insolubility is currently acting as an impediment to
the full characterization of the polymers from the ligandless systems. Direct evi-
dence for the incorporation of phosphorus into these poly(pheny1ene) backbones
comes from 31P-NMR.
In order to avoid these side reactions, the most obvious modification would be
to remove the phosphine ligands altogether [16]. This can be accomplished,
although not without penalty, because the reduced palladium centers tend to
form colloidal particles that eventually show attenuated activity. The details of
this phosphine-free approach have been reported [ 171. Convenient sources of
Pdo include CpPd($-C,H,) and Pd2(dba), . ChHS (where dba = dibenzylidene
acetone). Some of these reactions can be exceedingly fast (99% yield with
0.02 % Pd2(db& . C,H, in 45 min).

3.3.10.1.3 Chain-Growth Polymerizations

Chain-growth polymerizations involve sequential addition reactions, either to un-
saturated monomers or to monomers possessing other reactive functional groups.
Both conceptually and phenomenologically, this approach differs greatly from
step-growth processes. As a consequence, chain-growth polymerizations are cap-
able of producing high-molecular-weight polymers relatively early in the reaction,
long before all of the monomer is consumed.
The reactive intermediates used in chain-growth polymerizations include
radicals, carbanions, carbocations, and organometallic complexes. Of the three
common metal catalyzed polymerizations - coordination-insertion, ring-opening
metathesis and diene polymerization - the last appears to possess the greatest tol-
erance toward protic solvents. The polymerization of butadiene in polar solvents
was first reported in 1961 using Rh3+salts [18]. It was discovered that these poly-
merizations could be performed in aqueous solution with an added emulsifier
(sodium dodecyl sulfate, for example).
This Rh-catalyzed reaction is selective for the formation of highly crystalline
truns- 1,4-polybutadiene. The activity of the catalyst shows a marked dependence
 3.3.10.1 Synthesis of Polymers 1279

on the nature of the counterions present. Using RhCl, in 95 % ethanol, no polymer

was obtained after 6 h at 80 "C, whereas the nitrate salt displays a polymerization
rate of 7 g polymer/g Rh under the same conditions (cf. Section 2.3.2.2).
The following year, the emulsion polymerization of butadiene was reported
using a number of transition metal catalysts (Rh3+, Rh', Pd2+, I?', Ru3+, and
Co') in polar solvents [19]. It was found that the microstructure could be varied
from all truns-1,4 (>99.5 %), to high cis-1,4 (88 %), to high 1,2-insertion
(>98 %), depending on the metal catalyst employed. Molecular weights
varied greatly with choice of catalyst. For example, the Pd2+-catalyzedreactions
produce low-molecular-weight oligomers ( M , = 1000-1 SOO), while the Co+
catalyst produces molecular weights of approximately 300 000 (cf. Section
2.3.2.2).
It was discovered that the addition of 1,3-~yclohexadieneto the Rh3'-catalyzed
reactions increased the rate of butadiene polymerization by a factor of over 20
[20]. Considering the reducing properties of 1,3-~yclohexadiene, this effect
could be due to the reduction of Rh3+to Rh+ and stabilization of this low oxidation
state by the diene ligands. With neat 1,3-cyclohexadiene, Rh3+ is reduced to the
metallic state. These emulsion polymerizations are sensitive to the presence of
Lewis basic functional groups. A stoichiometric amount of amine (based on
Rh) is sufficient to inhibit polymerization completely. It was also discovered
that styrene could be polymerized using the Rh" catalyst. However, the atactic
nature of the polymer, along with the kinetic behavior of the reaction, indicated
that a free-radical process, rather than a coordination-insertion mechanism, was
operative.
There have been suggestions in the literature that the mechanisms of these
metal-catalyzed reactions are, in fact, either cationic [21] or free-radical in nature
[20]. This assessment, however, is inconsistent with all of the facts. Cationic poly-
merizations do have a tendency to produce high trans-] ,4 polymer. For example,
using a TiCl,/H,O catalyst, polymer containing approximately 7.5 % trans- 1,4
units is obtained. However, typical cationic polymerizations are generally carried
out at low temperature (-78 "C is common), to reduce the amount of insoluble,
crosslinked polymer obtained. In contrast, the Rh"+ systems are run between
+SO and +SO "C, without appreciable crosslinking occurring. In some polymeriza-
tions there does seem to be a competitive free-radical process [22]. This, however,
was determined to be due to radical impurities in the surfactants used, and not to a
Rh-catalyzed reaction. In fact, Rh3+was found to act as a free-radical inhibitor for
these reactions. Because of this, the free-radical mechanism was determined to be
unimportant at high Rh3+ concentrations [23]. In addition, common free-radical
inhibitors do not quench the Rh3+polymerizations [19]. All of these facts point
strongly to a polymerization mechanism that is substantially different from a
classical free-radical or cationic mechanism.
The ring-opening metathesis polymerization (ROMP, cf. Section 2.3.3) of
strained-ring cyclic alkenes has attracted considerable attention in recent years
due to the discovery that well-characterized metallacyclobutane [24] and metal
alkylidene [25] complexes catalyze the living polymerization of monomers such as
norbornene. Unfortunately, these catalysts often suffer deactivating side reactions
1280 3.3 Special Products

when used with monomers possessing polar functional groups [26]. Significantly
greater tolerance to functional groups is observed using catalysts based on later
transition metals. For example, 7-oxanorbornene (Structure 5 ) derivatives can
be polymerized using Group VIII complexes (eq. ( 5 ) ) [27] that were first reported
as ROMP catalysts in the early 1980s 1281.

&zy RuCI3 / 24 hrs.

tP3
~

CBHSCI/ EtOH

5 Me0 (5)
70 - 80 %

The observation that these polymerizations proceeded in alcoholic solution led

to the discovery that selected Ru3+ and Ru2+complexes catalyze the ROMP of
these 7-oxanorbornene derivatives in water alone to provide quantitative yields
of the desired ring-opened polymer (eq. (6)) [29].

RuC13 / 35 min.
H2O

Water appears to co-catalyze this reaction, as evidenced by a decrease in the

induction time for the reaction from nearly 24 h in dry organic solvents to
10-15 min in pure water. In addition, conducting the polymerization in protic
solution increases the molecular weight by a factor of over 4 ( M , increases
from 3.38 X lo5 to 1.34 X lo6), and decreases the polydispersity from 1.98 to
1.23. The fact that very high-molecular-weight materials form under these aque-
ous conditions indicates that, if chain-termination or chain-transfer reactions
involving the hydrolysis of the carbon-metal bonds are occurring in either the
metallacycle or metal alkylidene intermediates, they proceed at a much slower
rate (by several orders of magnitude) than the rate of propagation of the polymer.
From the average corrected degree of polymerization of the poly-1 obtained from
these aqueous reactions, it can be estimated that approximately 2500-2700 turn-
overs occur before each termination step.
It was also found that the recycled aqueous catalyst solutions were actually
more active than the original solutions. This increase in activity was attributed
to the in situ formation of ruthenium(I1) olefin complexes that were shown,
after isolation, to be highly active ROMP catalysts. The mechanism involved in
converting these olefin complexes to either metallacyclobutane or metal carbene
species remains unknown.
Later, Grubbs and co-workers showed that water-stable ruthenium(I1) carbenes
can be synthesized by allowing 3,3-diphenylcyclopropene to react with
R U C ~ ~ ( P(eq.P ~ (7))
~ ) ~~301.
 3.3.10.1 Synthesis of Polymers 128 1

It was found that 6 (a variant of the latter Grubbs catalyst [34]) would catalyze
the living polymerization of norbornene in organic solvents. Although not soluble
in water, complex 6 will initiate aqueous emulsion polymerizations. To date, all
attempts to solubilize 6 in aqueous solution by the incorporation of sulfonated
phosphine ligands have failed to yield active catalysts.
PI.
Ph Ph

PPh3 PPh3

As was shown earlier with the Suzuki coupling reactions, organopalladium

intermediates can show good stability to water and other protic sources. This
stability has been exploited in the synthesis of polyacetylene under air- and mois-
ture-stable conditions. It was found that simple palladium(I1) salts (PdCl,,
Pd(CH3C02)2,etc.) can be used to initiate the 1,2-insertion polymerization of
strained cyclic alkenes in water (eq. (8)) [31]. Once formed, poly-8 can be con-
verted to polyacetylene through a retro-Diels-Alder reaction.

ROOC' COOR

Using a related reaction, Sen showed that the palladium-catalyzed alternating

copolymerization of CO and olefins could be carried out under aqueous conditions
by using either the sulfonated chelating phosphine ligand, 1,3-bis(diphenyl-
phosphino)propane (dppp), or a sulfonated phenanthroline ligand, Phen-S03Na
(eq. (9)) ~321.

[Pd(Phen-S03Na)(MeCN)2](BF4)2
A + co
H20

Na03S (9)

phen-SOsNa
1282 3.3 Special Products

Finally, there has been at least one report of coordination polymerization of

ethylene occurring in aqueous solution. Using CnRh(CH,),(OTf)-, (where Cn
= 1,4,7-trimethyl-1,4,7-triazacyclononane,OTf = triflate or trifluoromethanesulfo-
nate, and n = 1,2), Flood and co-workers reported the very slow oligomerization
of ethylene in aqueous solution (90 days, at 24 "C, M , = 5100) [ 3 3 ] .Although not
practical at the present time, this example does help to illustrate the remarkable
stability of some of the Group VIII alkyls toward protic solvents.
The stability to water and polar functional groups that characterizes many of the
later transition metal organometallics makes this a rich area for new catalyst de-
velopment. This tolerance extends to a wide range of intermediates and includes
metal alkyls, acyls, aryls, and allyls. Coupled with the number of metals that are
currently represented, these examples have the potential of acting as the founda-
tion for versatile polymerization catalysts of the future.

References
[ l ] G. Odian, Principles of Polymerization, 2nd ed., Wiley, New York, 1981.
[2] D. C. Blackley, Emulsion Polymerization, Applied Science, London, 1975.
[3] I. Piirma, J. L. Gardon (Eds.), Emulsion Polymerizations. ACS Symp. Series No. 24,
American Chemical Society, Washington, DC, 1976.
[4] D. R. Basset, A. E. Hamielec (Eds.), Emulsion Polymers and Emulsion Polymerizations.
ACS Symp. Series No. 165, American Chemical Society, Washington, DC, 1981.
[ S ] J. L. Gardon, in Polymerization Processes (Ed.: C. E. Schildknecht), Wiley-lnterscience,
New York, 1977.
[6] Ref. [1] p. 319.
(71 R. B. Seymour, C. E. Carraher, Polymer Chemistry: An Introduction, 3rd ed., Marcel
Dekker, New York. 1992, p. 215.
[8] (a) J. K. Stille, Angew. Chem., fnt. Ed. Engl. 1986, 25, 508; (b) I. Colon, D. R. Kelsey,
J. Org. Chem. 1986, 51, 2627.
[9] For a review: A. Suzuki, Acc. Chem. Res. 1982, 15, 178.
[lo] (a) M. Rehahn, A.-D. Schluter, G. Wegner, W. J. Feast, Polymer 1989, 30, 1061;
(b) M. Rehahn, A.-D. Schluter, G. Wegner, Makromol. Chem. 1990, 191, 1991;
(c) A.-D. Schluter, G. Wegner, Actu Polymer 1993, 44, 59.
1111 T. I. Wallow, B. M. Novak, J. Am. Chem. Soc. 1991, 113, 7411.
[12] A. L. Casalnuovo, J. C. Calabrese, J. Am. Chem. Soc. 1990, 112, 4324.
1131 S. Ahrland, J. Chatt, N. R. Davies, A. A. Williams, J. Am. Chem. Soc. 1958, 90, 276.
1141 K.-C. Kong, C.-H. Cheng, J. Am. Chem. Soc. 1991, 113, 6313.
[IS] (a) T. I. Wallow, T. A. P. Seery, F. E. Goodson, B. M. Novak, ACS Polymer Prepr: 1994,
35, 710; (b) T. A. P. Seery, T. I. Wallow, B. M. Novak, ACS Polymer Prepr: 1993,
34, 727.
[ 161 I. P. Beletskaya, J. Organomet. Chem. 1983, 250, 55 1.
[17] T. I. Wallow, B. M. Novak, J. Org. Chem. 1994, 59, 5034.
[18] R. E. Rinehart, H. P. Smith, H. S. Witt, H. Romeyn, J. Am. Chem. Soc. 1961, 83, 4864.
[ 191 A. J. Canale, W. A. Hewett, T. M. Shryne, E. A. Yongman, Chem. fnd. (London)1962,1054.
1201 Ph. Teyssie, R. Dauby, J. Polym. Sci., Polym. Lett. 1964, 2 , 413.
1211 D. P. Tate, T. W. Bethea, in The Encyclopedia of Polymer Science and Technology, 2nd
ed., Wiley-Interscience, New York, 1985, Vol. 2.
1221 R. E. Rinehart, H. P. Smith, H. S. Witt, H. Romeyn, J. Am. Chem. Soc. 1962, 84,4145.
 3.3.10.2 Homogeneous Catalysis in Living Cells 1283

[23] R. Dauby, F. Dawans, Ph. Teyssie, J. Polyn. Sci. Part C, 1967, 16, 1989.
[24] (a) L. R. Gilliom, R. H. Grubbs, .I. Am. Chem. Soc. 1986, 108, 733; (b) K. C. Wallace,
R. R. Schrock, Macromolecules 1987, 20, 450; (c) K. C. Wallace, A. H. Liu, J. C.
Dewan, R. R. Schrock, J. Am. Chem. Soc. 1988, 110, 4964; (d) L. F. Cannizzo, R. H.
Grubbs, Macromolecules 1987, 20, 1488; (e) L. F. Cannizzo, R. H. Grubbs, Macromo-
lecules 1988, 21, 1961; (f) W. Risse, R. H. Grubbs, Macromolecules 1989, 22, 1558.
(a) R. R. Schrock, J. Feldman, L. F. Cannizzo, R. H. Grubbs, Macromolecules 1987,
20, 1169; (b) R. R. Schrock, R. T. DePue, J. Feldman, C. J. Schaverien, J. C. Dewan,
A. H. Liu, J. Am. Chem. Soc. 1988,110, 1423; (c) K. Knoll, S. A. Krouse, R. R. Schrock,
J. Am. Chem. Soc. 1988, 110, 4424; (d) R. R. Schrock, Acc. Chem. Res. 1990, 23, 158.
For references on the metathesis of polar substrates (both cyclic and acyclic) see:
(a) J. S. Murdzek, R. R. Schrock, Macromolecules 1987, 20, 2640; (b) P. D. van
Dam, M. C. Mittelmijer, C. Boelhouwer, J. Chem. Soc., Chem. Commun. 1972, 1221;
(c) J. C. Mol, J. Mol. Catul. 1982, 15, 35; (d) S. Matsumoto, K. Komatsu, K. Igarashi,
ACS Polym. P r e p 1977, 18, 110. (e) S. Matsumoto, K. Komatsu, K. Igarashi, ACS
Polyrn. P r e p 1977, 18, 110.
[27] (a) B. M. Novak, R. H. Grubbs, Proc. Am. Chem. Soc. Div. PMSE 1987, 57, 651;
(b) B. M. Novak, R. H. Grubbs, J. Am. Chem. Soc. 1988, 110, 960.
I281 The list of active Group VIII complexes include a number of Ir3+, I f , Os3+,Ru3+, and
Ru2+compounds. See: (a) F. W. Michelotti, W. P. Keaveney, ACS Polym. P r e p 1963,
4, 293; (b) F. W. Michelotti, W. P. Keaveney, J. Polym. Sci. 1965, A-3, 895; (c) F. W.
Michelotti, J. H. Carter, ACS Polym. Prepr: 1965, 6 , 224; (d) H. T. Ho, K. J. Ivin,
J. J. Rooney, J. Mol. Catal. 1982, 15, 245; (e) L. Porri, P. Diversi, A. Lucherini,
R. Rossi, Makromol. Chem. 1975, 176, 3131; (f) L. Porri, R. Rossi, P. Diversi,
A. Lucherini, Markomol. Chem. 1974, 175, 3097.
[29] B. M. Novak, R. H. Grubbs, J. Am. Chem. Soc. 1988, 110, 7542.
1301 S. T. Nguyen, L. K. Johnson, R. H. Grubbs, J. Am. Chem. Soc. 1992, 114, 3974.
[31] A. L. Safir, B. M. Novak, Macromolecules 1993, 26, 4072.
[32] Z. Jiang, A. Sen, Macromolecules 1994, 27, 7215.
[33] L. Wang, R. S. Lu, R. Bau, T. C. Flood, J. Am. Chem. Soc. 1993, 115, 6999.
[34] B. Comils, W.A. Herrmann, R. Schlogl, C.-H. Wong, Catalysis from A to Z, Wiley-
VCH, Weinheim, 2002.

3.3.10.2 Homogeneous Catalysis in Living Cells

La’szlo Vigh, Ferenc Job

3.3.10.2.1 Fundamentals
At present, the sole purposeful modification in living cells known to be catalyzed
by organometallic complexes is the homogeneous hydrogenation of the polar lipid
constituents of cell membranes [l]. The aim of such a modification is the con-
trolled change (modulation) of membrane fluidity which, in turn, is reflected in
the functioning of membrane-bound proteins. The latter comprise a wide range
of proteins such as - among others - various enzymes, constituents of the
light-harvesting complexes in algae and plants, receptors of very highly diverse
 Applied Homogeneous Catalysis with Organometallic Compounds
Edited by B. Cornils and W. A. Herrmann
Copyright 0 Wiley-VCH Verlag GmbH, D-69469 Weinheim, 2002

3.3.10.2 Homogeneous Catalysis in Living Cells 1283

[23] R. Dauby, F. Dawans, Ph. Teyssie, J. Polyn. Sci. Part C, 1967, 16, 1989.
[24] (a) L. R. Gilliom, R. H. Grubbs, .I. Am. Chem. Soc. 1986, 108, 733; (b) K. C. Wallace,
R. R. Schrock, Macromolecules 1987, 20, 450; (c) K. C. Wallace, A. H. Liu, J. C.
Dewan, R. R. Schrock, J. Am. Chem. Soc. 1988, 110, 4964; (d) L. F. Cannizzo, R. H.
Grubbs, Macromolecules 1987, 20, 1488; (e) L. F. Cannizzo, R. H. Grubbs, Macromo-
lecules 1988, 21, 1961; (f) W. Risse, R. H. Grubbs, Macromolecules 1989, 22, 1558.
(a) R. R. Schrock, J. Feldman, L. F. Cannizzo, R. H. Grubbs, Macromolecules 1987,
20, 1169; (b) R. R. Schrock, R. T. DePue, J. Feldman, C. J. Schaverien, J. C. Dewan,
A. H. Liu, J. Am. Chem. Soc. 1988,110, 1423; (c) K. Knoll, S. A. Krouse, R. R. Schrock,
J. Am. Chem. Soc. 1988, 110, 4424; (d) R. R. Schrock, Acc. Chem. Res. 1990, 23, 158.
For references on the metathesis of polar substrates (both cyclic and acyclic) see:
(a) J. S. Murdzek, R. R. Schrock, Macromolecules 1987, 20, 2640; (b) P. D. van
Dam, M. C. Mittelmijer, C. Boelhouwer, J. Chem. Soc., Chem. Commun. 1972, 1221;
(c) J. C. Mol, J. Mol. Catul. 1982, 15, 35; (d) S. Matsumoto, K. Komatsu, K. Igarashi,
ACS Polym. P r e p 1977, 18, 110. (e) S. Matsumoto, K. Komatsu, K. Igarashi, ACS
Polyrn. P r e p 1977, 18, 110.
[27] (a) B. M. Novak, R. H. Grubbs, Proc. Am. Chem. Soc. Div. PMSE 1987, 57, 651;
(b) B. M. Novak, R. H. Grubbs, J. Am. Chem. Soc. 1988, 110, 960.
I281 The list of active Group VIII complexes include a number of Ir3+, I f , Os3+,Ru3+, and
Ru2+compounds. See: (a) F. W. Michelotti, W. P. Keaveney, ACS Polym. P r e p 1963,
4, 293; (b) F. W. Michelotti, W. P. Keaveney, J. Polym. Sci. 1965, A-3, 895; (c) F. W.
Michelotti, J. H. Carter, ACS Polym. Prepr: 1965, 6 , 224; (d) H. T. Ho, K. J. Ivin,
J. J. Rooney, J. Mol. Catal. 1982, 15, 245; (e) L. Porri, P. Diversi, A. Lucherini,
R. Rossi, Makromol. Chem. 1975, 176, 3131; (f) L. Porri, R. Rossi, P. Diversi,
A. Lucherini, Markomol. Chem. 1974, 175, 3097.
[29] B. M. Novak, R. H. Grubbs, J. Am. Chem. Soc. 1988, 110, 7542.
1301 S. T. Nguyen, L. K. Johnson, R. H. Grubbs, J. Am. Chem. Soc. 1992, 114, 3974.
[31] A. L. Safir, B. M. Novak, Macromolecules 1993, 26, 4072.
[32] Z. Jiang, A. Sen, Macromolecules 1994, 27, 7215.
[33] L. Wang, R. S. Lu, R. Bau, T. C. Flood, J. Am. Chem. Soc. 1993, 115, 6999.
[34] B. Comils, W.A. Herrmann, R. Schlogl, C.-H. Wong, Catalysis from A to Z, Wiley-
VCH, Weinheim, 2002.

3.3.10.2 Homogeneous Catalysis in Living Cells

La’szlo Vigh, Ferenc Job

3.3.10.2.1 Fundamentals
At present, the sole purposeful modification in living cells known to be catalyzed
by organometallic complexes is the homogeneous hydrogenation of the polar lipid
constituents of cell membranes [l]. The aim of such a modification is the con-
trolled change (modulation) of membrane fluidity which, in turn, is reflected in
the functioning of membrane-bound proteins. The latter comprise a wide range
of proteins such as - among others - various enzymes, constituents of the
light-harvesting complexes in algae and plants, receptors of very highly diverse
1284 3.3 Special Products

agents, transport proteins, etc. In such a way, modulation of membrane fluidity

triggers a whole array of response reactions in a living cell. Selective homo-
geneous (or heterogeneous) hydrogenation of the unsaturated fatty acyl moieties
esterified in polar lipids of the various cell membranes provides a way of confin-
ing such modifications to selected regions of the cell (e. g., the plasma membrane)
or into selected group of constituents (e. g., a given group of lipid classes). Con-
sequently, the concomitant changes in cell metabolism or in other characteristics
(e. g., stress tolerance, viability, etc.) can be directly related to the primary effect of
hydrogenation on the fatty acid composition of the membranes.
When discussing synthetic manipulations of living cells it should be always
borne in mind that such living creatures always strive to maintain whatever
chemical composition or physical state is sensed as “optimal” for the cells
under the given physiological conditions (temperature, pH, osmotic pressure,
etc.). Therefore, the consequences of catalytic hydrogenation should be examined
immediately after the cell modification; even then some compensatory changes
might have already occurred.
Although the first attempts at biomembrane hydrogenations [2] involved the
use of water-insoluble catalysts, such as RhCl(PPh&, modification of living
cells was made possible only by the introduction of water-soluble hydrogenation
catalysts [3, 41. Complexes of monosulfonated triphenylphosphine (TPPMS, cf.
Section 3 . I . 1. l), such as RhCl(TPPMS)3 and RuC12(TPPMS)2,gained limited
use [5] and by far the most widely used catalyst is the Pd” complex of alizarin
red, Pd(QS), (see Structure 1, [6]). The mechanism of hydrogenations with this
catalyst is complex and far from being fully understood. Most probably it involves
a heterolytic activation of H2 (extensive deuteration of substrates occurs in D 2 0
solutions under H2 [7]) and participation of the anthraquinone- type ligand in elec-
tron transfer to the substrate through formation of semiquinones (as suggested by
characteristic ESR spectra of the intermediates [6]).

&
J,d
p\ : - ‘o \ / ’ \o
Na03S OH / \
-
1

The fatty acid composition of lipids is usually analyzed by gas chromatography

following transesterification into methyl esters. Unmodified lipids can be analyzed
by HPLC or by soft chemical ionization mass spectrometry. In the course of sam-
ple preparation it is often necessary to separate the various membrane fractions
(plasma membrane, thylakoid, microsomal, mitochondrial, etc.) by sophisticated
gradient centrifugations, as well as the individual lipid classes within a membrane
fraction, usually by thin-layer chromatography (TLC).
 3.3.10.2 Homogeneous Catalysis in Living Cells 1285

gel phase phase separation fluid phase

normal temperature
low temperature

Figure 1. Phase behavior and molecular geometry of membrane phospholipids at

normal (physiological) or low temperature.

Membrane fluidity is determined by following anisotropic rotation of fluores-

cent or spin probes. Liquid-crystalline (or fluid) to gel thermotropic phase transi-
tion of lipids (Figure 1) (cf. Section 3.1.11)in liposomes or intact biomembranes
can be followed by Fourier transform infrared (FTIR) spectroscopy or differential
scanning calorimetry (DSC).
Cells do survive limited hydrogenation [8] and their viability is checked in each
and every case when whole-cell characteristics are investigated. The effects of
hydrogenation on the physiology or molecular biology of the cells is characterized
by the most diverse techniques available, ranging from the very simple (determi-
nation of photosynthetic activity by measuring O2 production with a Clark-type
oxygen electrode) to the rather sophisticated (Northern blot hybridization analysis
of gene expression).
Fatty acids are usually designated by giving their carbon number:number of
usaturated bonds, e. g., 16:O is palmitic acid, 18: 1 oleic acid, etc.

3.3.10.2.2 Compensatory Response of Cells

Protoplasts prepared from tobacco (Nicotiana plumbaginifolia) leaf were hydro-
as) ~catalyst [9]. Surprisingly, in the first 30 min
genated using R u C ~ ~ ( T P P M S
of the rather slow reaction the general unsaturation of lipids increased (Table 1)
and this was reflected in fluidization of the membranes as shown by ESR mea-
surements. By pulse labeling the protoplasts with [1-14C] oleate, precursor of de
now fatty acid synthesis, it could be unambiguously demonstrated that hydroge-
nation of the original unsaturated lipid pool of the protoplast membranes triggered
an immediate and fast synthesis of fatty acids replacing the hydrogenated ones on
the glycerin backbone. Radioactivity was highest in the 18:3 (linolenate) content
of phosphatidylcholine, showing that de n o w fatty acid synthesis was accompa-
nied by vigorous desaturase action. Limited resources of the cells (lack of the O2
required by desaturase enzymes) resulted in gradual loss of unsaturated acids upon
prolonged hydrogenation (Table 1, data for 60 min).
1286 3.3 Special Products

Table 1. Changes in the fatty acid composition of living protoplasts from N . plumhaginifoh
during hydrogenation with RuCI~(TPPMS)~ (adapted from [9])."'
Fatty acid composition [wt. %Ib)
Fatty acid 0 min 30 min 60 min
C C H C H
16:O 15.6 15.8 16.0 16.1 20.5
16:l 0.7 0.7 tr 0.5 tr
18:O 3.2 3.1 3.4 3.2 12.2
18: 1 13.0 13.1 10.1 13.5 21.5
18:2 11.9 11.7 6.8 12.8 15.0
18:3 55.6 55.3 63.8 53.9 30.8
a) Conditions: 2 X lo5 protoplasts/mL, 0.5 mg/mL catalyst, 0.7 MPa HZ,30 "C,
in 20 mL of W-6 medium.
') C = control; H = hydrogenated; tr = trace.

This example strikingly demonstrates the activity of living systems and their
ability to maintain the optimal state of their membranes, and is a clear example
of so-called homeoviscous adaptation. A definite advantage of homogeneous
hydrogenation as compared with other methods is that isothermal conditions
could be used.

3.3.10.2.3 Temperature Perception and Cold Acclimatization

of Plants and Algae
Frost resistance or sensitivity of culture plants is a problem of highest economic
importance. Furthermore, low (or high) temperature is only one of the several
types of environmental shock (draught, high or low salt concentration, etc.) and
there are indications that plants use a fairly common strategy to cope with the
different kinds of such stress. It has long been debated whether temperature accli-
matization is achieved through the intrinsic temperature dependence of the activity
of certain enzymes or through specific modification of the lipid composition of the
membranes, and consequently their physical state, which in turn leads to altered
genetic and enzymic activity. This complex question could be addressed by selec-
tive hydrogenation of blue-green algae, well characterized photosynthetic organ-
isms which are often regarded as simple models of higher plants.
Anacystis nidulans has a rather simple membrane structure (mainly plasma
membrane and thylakoid); furthermore, these membranes have fairly simple
lipid compositions. The latter changes distinctly with the growth temperature,
the lipids being more unsaturated (more fluid) when the algae are grown at
lower temperatures (Table 2, columns 1 and 3). By careful hydrogenation of
 3.3.10.2 Homogeneous Catalysis in Living Cells 1287

Table 2. Fatty acid composition of total lipids of A. nidulans grown at 28 "C (l), grown and
hydrogenated at 28 "C (2) and grown at 38 "C (3) (adapted from [lo])."
Fatty acid Fatty acid composition [mol %]
I 2 3
14:O 2.1 3.7 1 .5
14: 1 4.3 2.5 1.1
16:O 44.9 50.5 48.5
16:l 43.5 38.2 37.8
18:O 1.8 2.2 4.8
18:l 3.4 2.5 6.3
a) Conditions of hydrogenation: 0.1 mM catalyst, 0.7 MPa H2, 28 "C, in 20 mL Kratz and
Myers medium C, cell density 10 mg chlorophyllL.

the cells acclimatized at low temperature (28 "C) [lo], their lipids could be
saturated to the point when the overall composition resembled very closely that
of the membranes of cells grown at 38 "C (Table 2, column 2).
When such algae cells are gradually cooled down from their growth temperature,
the fluidity of their membranes decreases and - depending on the lipid composition
- finally a gel-like state is reached. In parallel with these phase transitions, the

photosynthetic oxygen evolution activity drops considerably, the greatest change

being observed around a well-defined transition temperature (Figure 2).
It is seen from Figure 2 that, independently of their actual growth temperature,
the cells with similar lipid composition behaved very similarly, the transition tem-
peratures being 15 "C and 12 "C, as opposed to 4 "C in case of nonhydrogenated

100
-
c
Y

c
.-
c
0
-
3
0
>
50
0"
+-
0

0
10 20
Chilling temperature (T)
Figure 2. Temperature dependence of the photosynthetic O2 evolution in Anacystis
nidulans cells grown at 28 "C (0),grown and hydrogenated [Pd(QS), catalyst]
at 28 "C ( 0 )and grown at 38 "C (n).(Adapted from [l]).
1288 3.3 Special Products

algae adapted at 28 "C. In further studies [ 111 it could also be demonstrated that
selective hydrogenation of plasma membrane in A. nidulans resulted in the same
changes of photosynthetic activity despite the fact that the photosynthetic appara-
tus is located exclusively in the thylakoid (inner) membrane, which remained
untouched during short-term hydrogenations. In a broader context it can be
concluded that changes in the plasma membrane fluidity are the primary signals
of temperature (stress) for the cells.
The latter point was unambiguously proven with an other species of blue-green
algae, Synechocystis PCC6803. It was observed [ 121 that lowering the tempera-
ture resulted in increased production of mRNA on the desA desaturase gene
(Figure 3 A). Mild isothermal hydrogenation [13] of permeaplasts of Synecho-
cystis PCC6803 at the growth temperature of the algae led to the same level of

0 30 60 90 120
Incubation time (min)

0 30 60 90 12
Incubation time (min)

Figure 3. Changes in the desA transcript level in Synechocystis permeaplasts upon a

shift of temperature from 36 "C to 22 "C (A) and upon 4 min hydrogenation
at 36 "C followed by incubation at 36 "C (B). In both cases the transcript
level is expressed in units relative to the level determined at 60 min incubation
time. (Adapted from [12] and [13]).
 References 1289

gene transcript (Figure 3 B). All this evidence allows the conclusion that the
primary signal for biological perception of temperature in algae and plants is
the change of fluidity of cell plasma membranes [14].

3.3.10.2.4 Other Uses of Organometallic Catalysis

in Living Cells
The usefulness of hydrogenating living cells has been demonstrated here by
describing rather simple examples. However, the scope of such catalytic mani-
pulations is much wider, including investigations on surface expression of anti-
gens (receptors) in tumor cells [15, 161. Other, related reactions are also practiced
(deuteration [ 171 and isomerization [ 181 of lipid fatty acids) or considered (selec-
tive catalytic oxidation). Heterogeneous hydrogenation catalysts find their use in
this field, too [ 19, 201.

References
[ l ] P. J. Quinn, F. Jo6, L. Vigh, Prog. Biophys. Molec. Bid. 1989, 53, 71.
[2] D. Chapman, P. J. Quinn, Chem. Phys. Lipids 1976, 17, 363.
[3] P. A. Chaloner, M. A. Esteruelas, F. Job, L. A. Oro, Homogeneous Hydrogenation
(Catalysis by Metal Complexes), Kluwer, Dordrecht, 1994, pp. 183-233.
[4] W. A. Henmann, C. W. Kohlpaintner, Angew. Chem. 1993, 105, 1588; Angew. Chem.,
Int. Ed. Engl. 1993, 32, 1524.
[5] L. Vigh, F. Job, P. R. van Hasselt, P. J. C. Kuiper, J. Mol. Catal. 1983, 22, 15.
[6] F. Job, N. Balogh, L. I. Horvith, G. Filep, I. Horvith, L. Vigh, Anal. Biochem. 1991,
194, 34.
[7] F. Job, L. Vigh, in Handbook of Nonmedical Applications of Liposomes, Vol. 111, (Eds.:
Y. Barenholz, D. Lasic), CRC Press, Orlando, FL, USA, 1995, pp. 257-271.
[8] L. Vigh, I. Horvith, G. A. Thompson, Jr., Biochim. Biophys. Acta 1988, 937, 42.
[9] L. Vigh, F. Job, A. CsCpl6, Eul: J. Biochem. 1985, 146, 241.
[ 101 L. Vigh, F. Job, FEBS Lett. 1983, 162, 423.
[ I l l L. Vigh, Z. Combos, F. Job, FEBS Lett. 1985, 191, 200.
[12] D. Los, I. Horvith, L. Vigh, N. Murata, FEBS Lett. 1993, 318, 57.
[13] L. Vigh, D. A. Los, I. Horvith, N. Murata, Proc. Nutl. Acad. Sci. USA 1993, 90, 9090.
[14] B. Maresca, A. R. Cossins, Nature (London) 1993, 36.5, 606.
[15] S . Benko, H. Hilkmann, L. Vigh, W. J. van Blitterswijk, Biochim. Biophys. Acta 1987,
896, 129.
[16] E. Duda, S. Benko, I. Horvath, E. Caliba, T. Pali, F. Job, L. Vigh, in Advances in
Psychoneuroimmunology (Eds.: I. Berczi, J. SzClenyi), Plenum Press, New York,
1994, pp. 181-190.
[I71 Z. Torok, B. Szalontai, F. Jo6, C. Wistrom, L. Vigh, Biochem. Biophys. Res. Commun.
1993, 192, 518.
[18] Y. Pak, F. Job, L. Vigh, A. Kath6, G. A. Thompson, Jr., Biochim. Biophys. Acta 1990,
1023, 230.
[19] F. Job, S. Benko, I. Horvath, Z. Torok, L. Nidaski, L. Vigh, React. Kinet. Catal. Lett.
1992, 48, 619.
[20] F. Jo6, F. Chevy, 0. Colard, C. Wolf, Biochim. Biophys. Acta 1993, 1149, 231.
 Applied Homogeneous Catalysis with Organometallic Compounds
Edited by B. Cornils and W. A. Herrmann
Copyright 0 Wiley-VCH Verlag GmbH, D-69469 Weinheim, 2002

1290 3.3 Special Products

3.3.11 Cyclic Hydrocarbons from Diazoalkanes

Wolfgang A. Herrmann, Horst Schneider

3.3.11.1 Introduction
Diazoalkanes 1 form a versatile class of functionalized organic compounds [I].
Their undisputed significance in organic synthesis is manifested in a number of
organometallic and other metal-induced reactions [2], some of which have entered
catalytic applications. Cyclopropanation is one of them (cf. Section 3.1.7) but
intramolecular carbon-hydrogen insertion appears of much potential in syn-
thesis, too. This type of reaction relates to the easily available, normally nonex-
plosive a-diazocarbonyl compounds (a-diazoketones, Structure 2).

1 2

3.3.11.2 Scope and Definition

The remote functionalization of carbon-hydrogen bonds by a-diazoketones
according to the general eq. (1) is efficiently catalyzed by rhodium(I1) complexes
and yields cyclopentanones, lactams, and lactones, depending on the substituent
Y [3, 41. Typical reaction conditions are boiling methylene chloride or boiling
benzene.
0
II

Rhodium(I1) acetate (Structure 3), a dinuclear molecule of D4 symmetry and

vacant coordination sites (+) at each metal atom, is the most commonly em-
ployed catalyst for this reaction. Copper catalysts are no longer used because
they are inferior in terms of both activity and selectivity. The diazoalkane consti-
tution in eq. ( I ) includes compounds with

Y = H, COCH?, COOR
 3.3.11.3 Mechanistic Considerations 1291

In addition, an amide group can be attached to the carbonyl function. A pos-

sible side reaction is carbene dimerization [I], which can be suppressed by slowly
adding the diazoalkane to the catalyst at a temperature appropriate for smooth N2
elimination. The precise conditions depend on the nature of the a-diazoketone and
vary broadly in terms of stability and reactivity [ l , 21.
CH3
I

3.3.11.3 Mechanistic Considerations

It is commonly accepted that rhodium-carbene intermediates are the active spe-
cies preceding the c-C bond-forming insertion step (cf. Scheme 1 with M = Rh).
The in situ generation of carbenes is in line with the characteristics of diazoalkane
reactivity [ l , 21. However, neither has the “carbenoid” primary adduct B been
observed nor is there any spectroscopic evidence of the metal-carbene species
C. It is likely that the electrophilic addition of the “active catalyst” A (e. g., sol-

y*
N2=c R2
/
N2+- c \ Rz

-+”
R1

R1
ML,*solv. -
- SOIV.

+ MLn
sob.
L,M=C
/
\
R2
C

Scheme 1 Z H Z-H
1292 3.3 Special Products

vent-free rhodium(I1) acetate, 3) is the rate-determining step; N2 elimination takes

place around -20 "C in case of ethyl diazoacetate.
It remains unclear whether the catalyst retains the quadruply bridged structure
throughout the catalytic cycle. If this is the case, the insertion step of the carbene
CR2 into the Z-H hydrocarbon would proceed in a sterically rather congested
environment (basically a square-planar Rho, unit!). Since C-H insertion is an elec-
trophilic process, the metal seems to stabilize the carbene in the carbocation form.

3.3.11.4 Catalytic Cyclization

The literature on catalytic cyclization of a-diazoketones has a rather recent history,
with the majority of papers originating from the 1980s. The copper catalysts
originally used (e.g., CuS04) suffer from an unspecific product spectrum [ 5 ]
and have largely been replaced by rhodium catalysts, mainly through the work
of Doyle and colleagues [ 3 ] .

3.3.11.4.1 Cyclopentanones
A broad spectrum of a-diazo-P-ketoesters (e. g., 4), -sulfones, and -phosphonates
(e.g., 6) have been converted in one-step procedures and in decent yields into
cyclopentanones such as 5 and 7, respectively (eqs. (2) and (3)).

COlCH3

- cat.
- N2

6 7

Outstanding regioselectivities have been reported when rhodium(I1) acetate

was employed as a catalyst [6-111. The reactivity of the hydrocarbon component
decreases in the order tertiary > secondary > primary C-H [8]. While the a,d-in-
sertion yields the preferred cyclopentanones, the a,y-mode has occasionally been
observed, too: both the four-membered spirocycle (Structure 10) and the bicyclic
 3.3.11.4 Catalytic Cyclization 1293

(five-membered) product 9 result in a 2:3 ratio from the a-diazoketone 8 at 83 %

conversion (eq. (4)) [ 121.

a 9
y: fert.CH
6: sec. CH
(4)
+ &:0*c2"5 10

There is supporting evidence from numerous other examples that the

regioselectivity is not simply explainable from electronic factors; the (unknown)
geometries and energies of the transition states seem to govern the final result in a
particularly subtle way [ 11.

3.3.11.4.2 Lactams
a-Diazoacetamides undergo cyclization to /?-lactams Rhodium(I1) acetate is once
again much more efficient than copper catalysts. For example, the /?-lactam 12 is
obtained in 75 % yield (Rh) vs. 25 % yield (Cu) from the a-ketodiazoacetamide 11
according to eq. ( 5 ) 1131.

N2 =to
11
-cat.
- Nz
F
0

12

/?-Lactam formation (eqs. (5)-(7)) can result in either cis or trans configuration;
the stereochemistry is not yet easy to predict but seems to depend on the type
of bridging ligand on the Rh2(02CR)4catalysts. For example, the diazoacetamide
13 gives exclusively the trans isomer 14 in 96 % isolated yield if R = CH3, while
structure 15 gives in 89 % yield the cis isomer 16 if R = CF3(CF&CF2 (cf. eqs. (6)
and (7)) [14]. Recent literature lends support to the generality of this lactam
synthesis [ 151.
1294 3.3 Special Products

N2 t
13 14

-cat.

16

3.3.11.4.3 Lactones
The first case of an intramolecular C-H carbenoid insertion was reported by Cane
and Thomas in 1984 [12], with the special diazoacetate 17 forming the spirocyclic
b-lactone 18 in 45 % yield according to eq. (8). Doyle et al. recognized that this is
a general methodology for the synthesis of y-butyrolactones [16]. The reactivity of
the C-H bond toward carbene insertion is increased in the vicinity of an ether
functionality. Thus, the 3(2H)-furanone 20, as a useful building block in the
total synthesis of (+)-muscarhe, results in 40% yield from the diazo precursor
compound 19 [17].

0 0

19 20
R = isobutyl
 3.3.11.6 Perspectives 1295

3.3.11.5 Enantioselective Cyclization

Chiral catalysts with structures related to rhodium(I1) acetate should principally
afford optically pure enantiomeric y-lactones from diazoacetates of type 21. As
a matter of fact, Doyle et al. have obtained alkoxy-substituted y-lactones 22 in
85-90 % ee (eq. (10)) upon using a Rh,X,-catalyst derived from chiral 2-pyrroli-
dinones [18]. Related results suggest that the catalyst has a rigid stereochemistry
throughout the catalytic cycle [ 191, which conclusion had already been drawn for
enantioselective cyclopropanation [20] (cf. Section 3.1.7).

21 22

Related results suggest that the catalyst has a rigid stereochemistry throughout
the catalytic cycle [19, 201, a conclusion which had already been drawn for
enatioselective cyclopropanation [2 11 (cf. Section 3.1.7). In some cases even
b-lactones could be obtained as major products when using this catalyst [22].
In general, acyclic diazoacetates give higher yields of /3-lactones than cyclic
ones [23].

3.3.11.6 Perspectives
The intramolecular cyclization according to eq. (1) has great potential in the
synthesis of four-, five-, and six-membered carbo- and heterocycles. The mecha-
nistic knowledge of this reaction is still rudimental, however, and for this reason
even crude rules of how to direct regio- and stereoselectivity are lacking. We sug-
gest the catalyst structure to be modified beyond the bridging ligands. The most
significant progress is expected from chiral catalysts; enantioselective formation
of carbo- and heterocyclic compounds should soon enter the methodological
arsenal of natural product synthesis, especially since the required diazo precursor
compounds are normally easy to synthesize by standard techniques [l]. A pre-
requisite of mechanistic knowledge is further establishment of the coordination
chemistry of diazoalkanes, of which only a few general lines are yet visible
12, 241.
1296 3.3 Special Products

References
[I] Monograph: M. Regitz, Diazoalkanes, Thieme, Stuttgart, 1977.
[2] Review: W. A. Henmann, Angew. Chem. 1978, 90, 855; Angew. Chem., Int. Ed. Engl.
1978, 17, 800.
[3] Reviews: (a) M. P. Doyle, Acc. Chem. Res. 1986, 19, 348; (b) M. P. Doyle, Chem. Rev.
1986, 86, 919.
[4] G. Maas, Top. Curr: Chem. 1987, 137, 75.
[5] S. D. Burke, P. A. Grieco, Org. React. 1979, 26, 361.
[6] D. F. Taber, E. H. Petty, J. Org. Chem. 1982, 47, 4808.
[7] D. F. Taber, E. H. Petty, K. J. Raman, J. Am. Chem. Soc. 1985, 107, 196.
[8] D. F. Taber, R. E. Ruckle jr., J. Am. Chem. Soc. 1986, 108, 7686.
[9] H. J. Monteiro, Tetrahedron Lett. 1987, 28, 3459.
[lo] B. Corbel, D. Hernot, J.-P. Haelters, G. Sturtz, Tetrahedron Lett. 1987, 28, 6605.
[ l l ] D. F. Taber, S. A. Salch, R. W. Korsmeyer, J. Org. Chem. 1980, 45, 4699.
[12] D. E. Cane, P. J. Thomas, J. Am. Chem. Soc. 1984, 106, 5295.
[I31 R. J. Ponsford, R. Southgate, J. Chem. Soc., Chem. Commun. 1979, 846.
[I41 M. P. Doyle, J. Taunton, H. Q. Pho, Tetrahedron Lett. 1989, 30, 5397.
[15 (a) M. P. Doyle, M. N. Protopopova, W. R. Winchester, K. L. Daniel, Tetrahedron Lett.
1992, 33, 7819; (b) M. P. Doyle, L. J. Westrum, N. E. W. Wolthuis, M. M. See, W. P.
Boone, V. Bagheri, M. M. Pearson, J. Am. Chem. Soc. 1993, 115, 958.
[16 (a) M. P. Doyle, V. Bagheri, M. M. Pearson, J. D. Edwards, Tetrahedron Lett. 1989, 30,
7001; (b) M. P. Doyle, A. B. Dyatkin, J. Org. Chem. 1995, 60, 3035.
117 J. Adams, M.-A. Poupart, L. Grenier, Tetrahedron Lett. 1989, 80, 1749.
[ 181 M. P. Doyle in Homogeneous Transition Metal Catalyzed Reactions (Eds.: W. R. Moser,
D. W. Slocum), Adv. Chem. Ser., Vol. 230, American Chemical Society, Washington DC,
1992, pp. 443461.
[I91 (a) M. P. Doyle, Q.-L. Zhou, C. E. Raab, G. H. P. Roos, Tetrahedron Lett. 1995, 36,
4745; (b) M. P. Doyle, A. B. Dyatkin, S. Jason, ibid. 1994, 35, 3853; (c) M. P. Doyle,
A. B. Dyatkin, G. H. P. Roos, F. Canas, D. A. Pierson, A. von Basten, P. Mueller,
P. Polleux, J. Am. Chem. Soc. 1994, 116, 4507; (d) N. McCarthy, M. A. McKervey,
T. Ye, M. McCann, E. Murphy, M. P. Doyle, Tetrahedron Lett. 1992, 33, 5983.
[20] (a) M. P. Doyle, D. G. Ene, D. C. Forbes, T. H. Pillow, Chemcomm, 1999, 1691; (b) M. P.
Doyle, J.S. Tedrow, A.B. Dyatkin, C. J. Spaans, D.G. Ene, J. Org. Chem. 1999,
64, 8907.
[21] M. P. Doyle, R. J. Pieters, S. F. Martin, R. E. Austin, C. J. Oalmann, P. Muller, J. Am.
Chem. Soc. 1991, 113, 1423.
[22] M.P. Doyle, A. V. Kalinin, D.G. Ene, J. Am. Chem. Soc. 1996, 118, 8837.
[23] H. W. Yang, D. Romo, Tetrahedron, 1999, 55, 6403.
[24] W. A. Henmann, Adv. Organomet. Chem. 1981, 20, 159.
 Applied Homogeneous Catalysis with Organometallic Compounds
Edited by B. Cornils and W. A. Herrmann
Copyright 0 Wiley-VCH Verlag GmbH, D-69469 Weinheim, 2002

3.3.12.2 Scope and Technological Features 1297

3.3.12 Acrolein and Acrylonitrile from Propene

Wolfgang A. Herrmann

3.3.12.1 Introduction
Propene, as one of the most powerful petrochemical feedstocks, depends to a
large extent upon metal-containing catalysts for its further “refinement” [ 11.
While hydroformy lation (Rh) is the prototype of homogeneous catalysis, and
the Ziegler-type polymerization (Ti, Zr) has at least molecular mechanistic fea-
tures (but is normally microheterogeneous), the oxidation of propene is based
on heterogeneous catalysts [2]. Of key importance in industry is a group of reac-
tions leading to the allylic oxidation products acrolein and acrylonitrile (eqs. (1)
and (2)), commonly referred to as SOH10 (Standard Oil of Ohio) oxidations [ 3 ] .
The major follow-up product is acrylic acid, resulting from acidic hydrolysis
of acrylonitrile (eq. (3)). Alternative routes to acrylic acid, including oxidative
carbonylation of ethylene (homogeneous Pd catalysis; Union Oil process), have
been discussed in Chapter 1.
0
H2CZCH-CH3 + 02 aH2C=CH-C: + H20 + 368 kJlmol (1)
H

The allylic oxidation of propene typifies the so-called “bimetallic hetero-

geneous catalysis” [4], a terminus technicus to emphasize cooperative effects
in catalytic conversions (for multicomponent homogeneous catalysis, see Section
3.1 S ) . Nevertheless, the SOHIO-type oxidation is included in this book because
one can imagine a number of mechanistic implications on a molecular platform,
too. Studies on organometallic model compounds and reactions are available in
ref. [2].

3.3.12.2 Scope and Technological Features

The oxidation of propene to acrolein has been applied in industry since 1958,
when Shell introduced a gas-phase oxidation based on a Cu20/SiC/12catalyst sys-
tem. This process made acrolein a commodity product. A more efficient technol-
ogy, still state-of-the-art, was subsequently developed by Standard Oil of Ohio
(from 1957 onward), using bismuth molybdate and bismuth phosphatecatalysts
1298 3.3 Speciul Products

in a fixed-bed tube reactor to handle the strongly exothermic oxidation process.

Typical side products (from over-oxidation) are acetaldehyde, acrylic acid, and
carbon dioxide.
The SOH10 “ammoxidation” to make acrylonitrile is a modification of the
simple allylic oxidation. It converts an activated methyl group into a carbonitrile
functionality (eq. (2)). Equimolar amounts of propene and ammonia are reacted in
a fluidized-bed reactor at ca. 450 “C/O.O3-0.2 MPa with oxygen from air. After
the product has been washed with water, the acrylonitrile is refined by multistep
distillation to > 99% purity, as is mandatory for the production of fibers. The
product selectivity is L 70 %. The side products are acetonitrile which is normally
burned. Hydrogen cyanide which, at a production of ca. 15 wt. % relative to the
propene conversion, contributes significantly to the capacities of this base chem-
ical. It is interesting to note that the directed synthesis of hydrogen cyanide is also
based on an ammoxidation-type reaction, namely the direct conversion of methane
in the Andrussow process according to eq. (4). However, a Pt/Rh catalyst is used
in this particular case since a n-ally1 intermediate cannot be traversed (see Section
3.3.12.3). An additional technology is applied by Degussa AG in the so-called
“BMA process” (Blausaure-Methan-Ammoniak) (eq. (5)). Heterogeneous Pt,
Ru, or A1 catalysts are being used for this dehydrogenation reaction at 1250°C
with methane conversions of approx. 90% [20]. In contrast to the ammonoxida-
tion, this reaction of hydrocarbons with ammonia is called ammondehydrogena-
tion (ammonolysis + dehydrogenation).

CH4 + 3/202 + NH3 cat._ HC=N + 3 H20 + 480 kJ/rnol (4)

CH4 + NH3 HC=N + 3H2 (5)

Other applications of the ammoxidation include the reactions of isobutene
(-+ a-methacrylonitrile), a-methylstyrene (+ atropanitrile), P-picoline (+ nico-
tine nitrile and nicotinamide), toluene (+ benzonitrile), and xylenes (+ phthalo-
nitrile, terephthalonitrile, and isophthalonitrile on the way to fiber- grade dia-
mines).

3.3.12.3 Catalyst Principles and Mechanism

Most efficient in the ammoxidation of propene are catalysts containing simul-
taneously

(1) multivalent Main-Group elements - preferably bismuth, antimony,

or tellurium,
(2) oxidic molybdenum, and
, or u~+‘~+,
(3) a redox-active component: Fe2+13+,Ce3+14+

in solid-state matrix [ 5 ] . The standard catalyst could in an utterly simplistic way

be formulated as Bi203. nMo03. The first SOH10 patent on this type of catalyst
 3.3.12.3 Catalyst Principles and Mechanism 1299

was filed in 1957. Ammoxidation is a six-electron reaction, indicating that a

number of mechanistic steps must be traversed.
According to common opinion, both the SOH10 oxidation (-+ acrolein) and
the propene ammoxidation (-+ acrylonitrile) receive their unexpected
selectivites (albeit far off 100%) from a specific type of crystal-lattice oxygen
as the actual reagent, quite typically exemplifying the Mars/van Krevelen
mechanism. In support of this view, bismuth molybdate is reduced by propene
and can be reoxidized by air or oxygen yielding the original valence state;
this was shown by I8O2labeling experiments [6]. The catalysts have to fulfill
the following demands:

(1) strong oxidative power with regard to the hydrocarbon to be converted,

(2) susceptibility to regeneration by elemental oxygen,
( 3 ) activation of ammonia (in the case of ammoxidation).

In the presence of ammonia, some oxidic molybdenum sites (Mo=O) are likely
to be replaced by imino (Mo=NH) or diimino functions (Mo(=NH)*) which then
couple with the ally1 group. The final product, acrylonitrile, is obtained after
dehydrogenation and the catalyst is reoxidized with air.

,,reoxidation site<<

I acrolein I
y+
Bi-Mo =NH

rcCaN
Scheme 1
I +
acrylonitrile I H20
1300 3.3 Special Products

At the same time, degradation and side reactions should be suppressed (see
above).
The ammoxidation mechanism was investigated intensively by Grasselli and
his team in the Standard Oil of Ohio laboratories. Despite supporting experimental
evidence, the textbook mechanism remains speculative to a certain extent. It can
be taken for granted, however, that the commonly employed BiMo catalysts ex-
ercise their double-site activation such that the propene undergoes a-H abstraction
at a BiO functionality while the remaining allyl group coordinates to the high-
valent molybdenum (Scheme 1). The bond-making step to follow in case of the
acrolein synthesis is little defined.
The key allyl species in the Grasselli mechanism [5a] remains unspecified:
does it coordinate to the high-valent molybdenum in a c/nfashion, or does it
occur as radicals? What is the role of free allyl radicals? Also, the product-forming
C-0 and C-N connection steps, respectively, leave open questions. For example,
are there intramolecular rearrangements like those shown in Scheme 2 responsible
for the formation of the new bonds? How are the product precursors detached
from the metal(s)?

Scheme 2

3.3.12.4 Organometallic Models

Ally1 coordination to high-valent metal oxides was unknown until very recently
[7, 81. Strinkingly, this ligand coordinates at heptavalent rhenium in a c rather
than in a n mode, and the same is true for the related indenyl derivative (cf.
Structures 1 and 2) although the ligand sphere would not be sterically congested
in the case of n coordination (cf. Structure 3). The a-ally1 complex undergoes a
radical-path decomposition, yielding predominantly 1,5-hexadiene [7 c, 81. The
rhenium-oxygen bond is probably too strong for the formation of oxygenated
hydrocarbons to occur, even if there was a Re -+ 0 rearrangement of the
allyl group. Whether lower metal oxidation states favor n-bonding, as in the tung-
sten(1V) complex 4 [9], is not likely to be so simple a motive in coordination
 3.3.12.5 The “Arnrn(on)dehydrogenation ” 1301

chemistry. The n-donating effects of the 0x0 ligands in 1 and 2 partly explain the
structural details (Structure 3 contains the electron-rich ligand C,Me,).

1 2 3 Me=CH3 4

While an allyl-to-oxo coupling step is not available from any molecular model
system, a rearrangement of allyl groups from one to another 0x0 group has been
detected for the oxomolybdenum(V1) complex 5a G 5b [lo-121. The intramole-
cular isomerization is thought to involve a cationic allylic intermediate via a [3,3]-
sigmatropic shift similar to a Claisen rearrangement [ 111. Further, an oxygen-to-
nitrogen allyl migration is known from the chemistry of allyloxo imido complexes
of tungsten(V1); cf. eq. (7) for Structure 6 [12]. A plethora of 0x0-, imido-, and
nitridomolybdenum complexes is known in the meantime; they offer stoichio-
metric model reactions in the context of the SOH10 oxidation [13, 141.

i i
5a L = CD&N 5b

R‘

3.3.12.5 The “Amm(on)dehydrogenation”

There are recent literature reports according to which alcohols and aldehydes
dehydrogenate in the presence of ammonia to form nitriles. Process are operated
by Rohm & Haas, Ruhrchemie, and Bayer [21-231. Molybdenum nitrides were
found most efficient as heterogeneous catalysts [15]; cf. eqs. (8) and (9) (R =
n-C,H,). They also effect dehydrogenation of amines, as demonstrated for
n-butylamine in eq. (10).
1302 3.3 Special Products

Using supported y-Mo2N as a surface-mediated catalyst, a new proposal for the

manufacture of aromatic nitriles and dinitriles from the relatively cheap aldehydes
was made [16, 171. Thus, isophthalic dinitrile can be produced in a gas-phase
“amm(on)dehydrogenation” (cf. Section 3.3.12.2) at 400 “C according to eq.
(11) with 80 % conversion when a 50-fold excess of ammonia is used [16]. It is
obvious that imine intermediates are formed (from the aldehyde and ammonia)
which then dehydrogenate under the reaction conditions.

H,
c=o C-N

c=o C-N
HI
This type of reaction also works with complex catalysts resulting from the
decomposition of molecular molybdenum nitrides such as 7 [ 14, 171. The thermo-
lysis product (Structure 8) is mostly 6-MoN (eq. (12)), and the incorporated
oxygen is likely to originate from air and moisture. In the absence of ammonia,
a product with lower nitrogen content (Mom = 1:0.68) is obtained [17].
N

+p
111
1 bar, NH3
* ~ ~ ~ o . ~ ~ [ ~ o . ~ E ~ o . ~ ~ (12)
~ o . ~ o ~
AT 8 (+ volatile products)

7
Since little is known about the mechanism other than that ammonia reacts first
to form an imine (-CH=NH, [IS]), studies related to the chemistry of Mo=N
structures (e.g., 15N labeling experiments) seem necessary in order to find out
at which step the surface nitrogen enters the reaction. It would also be interesting
to see which surface sites (N vs. Mo) are taken by the hydrogen resulting from
dehydrogenation of the intermediate imine. Surface grafting of molecular pre-
cursors such as 7 [19] may be a new technique to generate molecularly defined
catalyst species.
 References 1303

3.3.12.6 Perspectives
More than 5 million tons of acrylonitrile are made annually. It is synthesized
industrially by the gas-phase heterogeneous ammoxidation of propene. New
catalysts based on Bi-Mo or V-Sb oxides may lead to manufacture of this impor-
tant compound from propane. Although the new process has a considerably lower
selectivity to acrylonitrile, the lower cost of the alkane makes it economically
interesting (the propane method can cut at least 20% from the production costs
of the propene route). Nevertheless, increases in the selectivity of the catalysts,
especially at higher conversions, will be necessary for this process to compete
with the usual process of acrylonitrile synthesis [24].
Propene oxidation by means of oxidic bimetallic catalysts is a unique example
of selectivity synergism in heterogeneous catalysis. The secret seems to be the
specific reactivity of certain lattice-oxygen atoms (ions?) upon the surface-gener-
ated allyl intermediates. Now that this basic mechanistic feature has strong
support, organometallic molecular chemistry should search deliberately for the
electronic prerequisites of well-defined metal-oxo species to engage in allyl-oxy-
gen coupling reactions. Complexes of type H2C=CH-CH2-MO, may be screened
for their reactivity pattern, e. g., under electrochemical conditions, to learn more
about the circumstances under which an MO, fragment is ready to undergo
0-C coupling (this question, by the way, does not apply only to allyl species).
In this context, a synthetic study related to oxygen-bridged bismuth-molybdenum
model compounds is worth the laborious efforts to be expected on this uncharted
sea: 40 years after the first SOH10 patent on this topic!

References
[ I ] K. Weissermel, H.-J. Arpe, Industrial Organic Chemistry, 3rd ed., VCH Publishers, New
York, 1988.
[2] Summary: W. A. Herrmann, Kontakte (Merck, Darmstadt), No. 3, 1991, pp. 29-52.
[3] (a) P. N. Rylander in Catalysis - Science and TechnoLogy (Eds.: J. R. Anderson, M. Bou-
dart), Springer, New York, 1983, Vol. 4, p. 27; H. Heinemann, in ibid. 1981, Vol. 1, p. 30;
(b) R. K. Grasselli, J. Chem. Educ. 1986,63,216; (c) H. Schaefer, Chem.-Tech. 1978,7,231.
[4] J. H. Sinfelt, Bimetallic Cata1y.st.Y (Exxon Monograph), John Wiley, New York, 1983.
[5] Mechanistic studies: (a) R. K. Grasselli, J. D. Burrington, Adv. Catal. 1981, 30, 133; (b)
G. W. Keulks, L. D. Krenzke, T. M. Notermann, ibid. 1978,27, 183; (c) J. D. Burrington,
C. T. Kartisek, R. K. Grasselli, J. Catal. 1984, 87, 363; (d) R. K. Grasselli, J. D. Burring-
ton, J. F. Brazdil, Faruduy Discuss. Chem. SOC.1982, 72, 203; (e) L. C. Glaeser, J. F.
Brazdil, M. A. Hazle, M. Mehicic, R. K. Grasselli, J. Chem. Soc., Furaday Trans. 1
1985, 81, 2903.
[6] (a) G. W. Keulks, J. Cutul. 1970, 19, 232; (b) C. C. McCain, G. Cough, G. W. Godin,
Nature (London) 1963, 198, 989.
[7] (a) W. A. Herrmann, F. E. Kuhn, C. C. Romao, H. Tran Huy, J. Orgunomet. Chem. 1994,
481, 227; (b) W. A. H e m a n n , F. E. Kuhn, ibid. 1995, 495, 209; (c) F. E. Kuhn, Ph.D.
Thesis, Technische Universitat Munchen, 1994.
[8] Review: W. A. Herrmann, J. Organomet. Chem. 1995, 500, 149.
[9] L. M. Atagi, S. C. Critchlow, J. M. Mayer, J. Am. Chem. SOC. 1992, 144, 1483.
1304 3.3 Special Products

[lo] J. Belgacem, J. Kress, J. A. Osborn, J . Chem. Soc., Chem. Commun. 1993, 1125.
[ l l ] J. Belgacem, J. Kress, J. A. Osborn, J. Am. Chem. Soc. 1992, 114, 1501.
[12] J. Belgacem, J. Kress, J. A. Osborn, J. Mol. Cutal. 1984, 86, 267.
[ 131 W. A. Nugent, J. M. Mayer, Metal-Ligand Multiple Bonds, Wiley-Interscience, New
York, 1988, and references cited therein.
[ 141 W. A. Henmann, S. Bogdanovit, R. Poli, T. Priermeier, J . Am. Chem. Soc. 1994,116,4989.
[15] See, for example: H. Abe, A. T. Bell, I. Cutul. 1993, 142, 430.
[16] SKW Trostberg AG (J. Graefe, K. Wernthaler, H.-G. Erben), DE Patent appl.
P 195.18.398.3 (1995).
[ 171 N. Hansen, Diploma Thesis, Technische Universitat Munchen, 1995.
[18] Ruhrchemie AG (H. Goethel, B. Comils, H. Feichtinger, H. Tummes, J. Falbe), DE
2.048.750 (1970).
[I91 W. A. Herrmann, A. W. Stumpf, Th. Priermeier, J.-M. Basset, Angew. Chem. Int. Ed.
1996, 35, 2803.
[20] F. Endter, Chem. Ing. Tech. 1958, 30, 305; F. Endter, Dechema Monogr. 1959, 33, 28.
[21] Rohm & Haas (L.R.U. Spence, E. Park, D.J. Butterbaugh, F.W. Robinson, US
2.337.421 (1941) and US 2.337.422 (1941).
[22] Ruhrchemie AG (G. Horn, D. Frohlich, H. Liebern), EP 0.038.507 Al (1981).
[23] Bayer AG (F. Hagedom et al.), DE 3.216.382 (1983).
[24] (a) G. Centi, S. Perathoner, Chemtech 1998,28, 13; (b) G. Centi, S. Perathoner, J. Chem.
Soc., Furaduy Trans. 1997, 93; (c) G. Senti, S. Perathoner, C&EN 1997, 75, 15.

3.3.13 Chemistry of Methyltrioxorhenium (MTO)

3.3.13.1 Fine Chemicals via Methyltrioxorhenium

as Catalyst
Fritz E, Kuhn, Michelle Groarke

3.3.13.1.1 Introduction
The title compound has been known for less then 25 years [l]. For a considerable
part of this time, it has been widely regarded as a mere curiosity. This picture
changed dramatically during the last decade. Today, not only is an amazing wealth
of derivatives and reaction products known and easily accessible, several of these
compounds, most notably methyltrioxorhenium(VI1) itself, have found numerous
very interesting applications in both catalysis and material sciences.

3.3.13.1.2 Synthesis of Methyltrioxorhenium

Methyltrioxorhenium(VI1) (l),usually abbreviated to MTO, was first reported in
1979 by Beattie and Jones [2]. Due to the difficult synthesis and the low yields of
1 that could be obtained, the compound was not examined further. The break-
 Applied Homogeneous Catalysis with Organometallic Compounds
Edited by B. Cornils and W. A. Herrmann
Copyright 0 Wiley-VCH Verlag GmbH, D-69469 Weinheim, 2002

1304 3.3 Special Products

[lo] J. Belgacem, J. Kress, J. A. Osborn, J . Chem. Soc., Chem. Commun. 1993, 1125.
[ l l ] J. Belgacem, J. Kress, J. A. Osborn, J. Am. Chem. Soc. 1992, 114, 1501.
[12] J. Belgacem, J. Kress, J. A. Osborn, J. Mol. Cutal. 1984, 86, 267.
[ 131 W. A. Nugent, J. M. Mayer, Metal-Ligand Multiple Bonds, Wiley-Interscience, New
York, 1988, and references cited therein.
[ 141 W. A. Henmann, S. Bogdanovit, R. Poli, T. Priermeier, J . Am. Chem. Soc. 1994,116,4989.
[15] See, for example: H. Abe, A. T. Bell, I. Cutul. 1993, 142, 430.
[16] SKW Trostberg AG (J. Graefe, K. Wernthaler, H.-G. Erben), DE Patent appl.
P 195.18.398.3 (1995).
[ 171 N. Hansen, Diploma Thesis, Technische Universitat Munchen, 1995.
[18] Ruhrchemie AG (H. Goethel, B. Comils, H. Feichtinger, H. Tummes, J. Falbe), DE
2.048.750 (1970).
[I91 W. A. Herrmann, A. W. Stumpf, Th. Priermeier, J.-M. Basset, Angew. Chem. Int. Ed.
1996, 35, 2803.
[20] F. Endter, Chem. Ing. Tech. 1958, 30, 305; F. Endter, Dechema Monogr. 1959, 33, 28.
[21] Rohm & Haas (L.R.U. Spence, E. Park, D.J. Butterbaugh, F.W. Robinson, US
2.337.421 (1941) and US 2.337.422 (1941).
[22] Ruhrchemie AG (G. Horn, D. Frohlich, H. Liebern), EP 0.038.507 Al (1981).
[23] Bayer AG (F. Hagedom et al.), DE 3.216.382 (1983).
[24] (a) G. Centi, S. Perathoner, Chemtech 1998,28, 13; (b) G. Centi, S. Perathoner, J. Chem.
Soc., Furaduy Trans. 1997, 93; (c) G. Senti, S. Perathoner, C&EN 1997, 75, 15.

3.3.13 Chemistry of Methyltrioxorhenium (MTO)

3.3.13.1 Fine Chemicals via Methyltrioxorhenium

as Catalyst
Fritz E, Kuhn, Michelle Groarke

3.3.13.1.1 Introduction
The title compound has been known for less then 25 years [l]. For a considerable
part of this time, it has been widely regarded as a mere curiosity. This picture
changed dramatically during the last decade. Today, not only is an amazing wealth
of derivatives and reaction products known and easily accessible, several of these
compounds, most notably methyltrioxorhenium(VI1) itself, have found numerous
very interesting applications in both catalysis and material sciences.

3.3.13.1.2 Synthesis of Methyltrioxorhenium

Methyltrioxorhenium(VI1) (l),usually abbreviated to MTO, was first reported in
1979 by Beattie and Jones [2]. Due to the difficult synthesis and the low yields of
1 that could be obtained, the compound was not examined further. The break-
 3.3.13.1 Fine Chemicals via Methyltrioxorhenium as Catalyst 1305

through came in 1987, when Herrmann and co-workers presented the first effi-
cient synthetic route, starting from dirhenium heptoxide and tetramethyltin
(eq. (1)) P I .

1 (MTO)

This preparation of 1 has been improved considerably since then [2]. Since
1993, MTO has been commercially available (cf. Section 3.3.13.1.3). In 1997,
the synthetic method starting from trimethylstannyl perrhenate has been extended
to other perrhenates so that the moisture-sensitive Re2O7can be replaced by more
conveniently handled starting materials [2]. Nowadays 1 can be synthesized
directly from rhenium powder in amounts of several kilograms. This synthetic
progress was accompanied by the discovery of a plethora of derivatives and
catalytic applications of organorhenium(VI1) oxides. The use of these complexes
in catalysis, however, is still strongly dominated by 1 itself [2, 31.
At room temperature 1 is a colorless solid, crystallizing in colorless needles. It
is readily sublimed and soluble in all common solvents. MTO decomposes only
above 300°C. Heated in water to ca. 70°C for several hours it forms a golden
polymer of empirical formula { H0.5[(CH3)0.92Re031 ) [41.

3.3.13.1.3 Applications of Methyltrioxorhenium(VI1)

in Catalysis
Oxidation Catalysis

The catalytic activity of 1 and some of its derivatives is known [5]. However, the
breakthrough in the understanding of the role of MTO in oxidation catalysis was
the isolation and characterisation of the reaction product of MTO with excess
H,02; it is a bis(peroxo) complex of stoichiometry (CH3)Re(02)20(2) [6a].
In the solid state, it is isolated as an adduct with a donor ligand L (L = H20, 2a;
L = O=P(N(CH,),), , 2b) [2, 3, 6 a], which is lost in the gas phase. The structures
of 2 (electron diffraction) [3], 2a and 2b (X-ray diffraction) were determined; the
structure of ligand-free complex 2 is known from the gas phase.

2a 2b
1306 3.3 Special Products

I70-NMR experiments showed that 2a, b exchange their ligand L rapidly in

solution, especially in coordinating solvents [2, 3, 6 a]. Only the terminal oxygen
atom is involved in an oxygen exchange with water [6].
Experiments with the isolated bis(peroxo)complex 2a have shown that it is an
active species in oxidation catalysis, e. g., in the oxidation of olefins [6 a]. In situ
experiments show that the reaction of MTO with one equivalent of H202leads to a
monoperoxo complex 3 [2-4]. Complex 3 has never been isolated and exists only
in equilibrium with MTO and 2 [3, 6 b].
The decomposition of 1, 2, and 3 in solution was also examined 13, 71. The full
kinetic pH profile for the base-promoted decomposition of complex 1 to CH4 and
[ReOJ has been examined. In the presence of hydrogen peroxide, complexes
2 and 3 decompose to methanol and perrhenate with a rate that is dependent on
[H2021 and [H@I+ PI.
The activation parameters for the coordination of H202 to MTO indicate a
mechanism involving nucleophilic attack (see also [S]).

Oxidation of Alkenes

One of the most intensively examined catalytic processes using organorhenium

(VII) oxides, in particular MTO, as catalysts is in the epoxidation of alkenes
[2, 3, 9, 101. Usually, less than 85 wt. % of H202 is employed and MTO is
typically used in concentrations of 0.2-1.0 mol %. Turnover numbers of up to
2000 [mol/mol catalyst] and turnover frequencies of ca. 1200 [moVmol catalyst
per hour] can be achieved.
The catalytic MTO/H202 system is already active below room temperature,
e. g., at -30 "C. The reaction between 2 and alkenes are ca. one order of magnitude
faster in semi-aqueous solvents (e. g., 85 % H202)than in methanol. The rate con-
stants for the reaction of 2 with aliphatic alkenes correlate closely with the number
of alkyl groups on the alkene carbons. Theoretical calculations support these
results [ 10 a, b]. The reactions become significantly slower when electron-with-
drawing groups, such as -OH, -CO, -C1, and -CN are present.
Two catalytic pathways for the alkene epoxidation may be described, cor-
responding to the concentration of the hydrogen peroxide used. If 85 % hydrogen
peroxide is used, only 2 appears to be responsible for the epoxidation activity
(Scheme 1, cycle I).
When a solution of 30 wt. % or less of H202is used the monoperoxo complex 3
is also responsible for the epoxidation process and a second catalytic cycle is
involved, as shown in Scheme 1, cycle 11.
For both cycles, a concerted mechanism is suggested in which the electron-rich
double bond of the alkene attacks a peroxidic oxygen of 2. It has been inferred,
from experimental data, that the system may involve a spiro arrangement [3,
5a]. The selectivity toward epoxides can be enhanced by the addition of Lewis
0- or N-bases such as quinuclidine, pyridine, pyrazole or 2,2'-bipyridine to the
system 13, 6d, log-k]. Lewis acids catalyze ring-opening reactions and diol
formation. These reactions are suppressed after the addition of Lewis bases. An
 3.3.13.1 Fine Chemicals via Methyltrioxorheniurn as Catalyst 1307

cycle I

3a
Scheme 1

excess of aromatic N-base ligands, especially under two-phase conditions, leads to

accelerated reactions [3, 10 a, b, g-k]. Functionalized epoxides can be prepared in
high yields by this method [2, 31. The activity of the peroxo complexes in these
cases depends on the Lewis bases, the redox stability of the ligands, and the ex-
cess of the ligands. Nonaromatic nitrogen bases were found to reduce the catalytic
performance. It is known that polar noncoordinating solvents increase the rate of
the epoxidation reaction [2, 31. The epoxidation of alkenes in the presence of
0.1 mol % MTO using H202 (60 %) has also been successfully achieved in tri-
fluoroethanol with only 5 mol % of pyrazole present [lo c].
In comparison with the standard system for epoxidation which uses m-chloro-
peroxybenzoic acid as oxidizing agent, the MTO/H202/aromatic Lewis base sys-
tem displays several advantages: (a) it is safer but equal in price; (b) due to the
suppression of epoxide ring opening, it has a much broader scope; (c) its selectiv-
ity is higher, and (d) it is more reactive, requires less solvent, the product work-up
is easier, and the only by-product formed is water.
Another possibility for enhancing the selectivity toward epoxides is use of the
urea-H202 (UHP) adduct. This enables the oxidation to be carried out in water-
free solutions, thus avoiding formation of any diols and other side reactions. In
the case of the oxidation of chiral allylic alcohols (see below) high diastereo-
selectivities have been achieved [ 3 ] . The ability to transform olefins to epoxides
diastereoselectively seems to indicate that the reaction proceeds through a peracid-
like transition state. However, a drawback of the urea-H202 system is the insolu-
bility of the polymeric complex.
The zeolite NaY acts as an efficient heterogeneous host for MTO-catalyzed
selective epoxidation of alkenes with H202(85 %) [ 10 d]. The supernatant liquid
1308 3.3 Special Products

was found to be catalytically inactive, even in the presence of pyridine. The Re

catalyst is located inside 12 A supercages of the zeolite. This inhibits the Lewis
acid assisted hydrolysis of the epoxide to the diol by steric means. This catalytic
system is comparable with the MTOKJHP and MTO/H202 (30%)/pyridine sys-
tems although conversions may be improved by the addition of catalytic amounts
of pyridine.
By tailoring the reaction conditions, alkenes may be cleaved oxidatively to
yield aldehydes and carboxylic acids [ l O f l . The presence of a Bronsted acid,
e.g., HBF4 or HC104, required to accelerate the oxidation of the olefin with
respect to the deactivation of the catalyst, results in the synthesis of the aldehyde
without overoxidation to the acid. Significant quantities of the diol are also pre-
sent, however. A three-fold excess of H202 is required to oxidize the alkene to
the acid. However, this also results in the simultaneous oxidation of the methyl
tert-butyl ether solvent to the peroxide.

Oxidation of Conjugated Dienes

Conjugated dienes are oxidized to epoxides (or diols, if water is present) with the
MTO/H202system [ 111. Urea/H202avoids the subsequent epoxide ring opening.
Electron-rich and conjugated dienes are more easily oxidized than electron-poor
dienes and dienes with isolated double bonds. According to kinetic measurements
complex 3 plays no important role as catalyst in this case. Compound 2 is an
active species [ 1la].
The biphasic system MTO/H,O,/CH,Cl, oxidizes 1,4-polybutadiene efficient-
ly. The oxidation system is highly efficient and the extension of epoxidation
(10-50 %) can be modulated by the amount of oxidant added, without significant
change in the molecular weight of the polymer [ 1lb] (cf. also Section 3.1.1.1.2).

Epoxidation of Allylic Alcohols and 1,3-Transpositionof Allylic Alcohols

Allylic alcohols are epoxidized to the epoxy alcohols by hydrogen peroxide in the
presence of MTO [3, 121. Provided acid is not added, the product is mostly epox-
ide, accompanied by small amounts of triol that results from acid-catalyzed ring
opening of the epoxide. With added acid, only the triol is obtained. According
to kinetic data only the bisperoxo complex 2 and not the monoperoxo complex
3 acts as a catalyst.
Furthermore, MTO catalyzes the 1,3-transposition of allylic alcohols (eq. (2))
[12c]. This reaction does not require the presence of peroxides or peroxo
complexes. Theoretical investigations on the allylic rearrangement have also
been performed [12d]. Recently it has been reported that allylic alcohols as
well as alkenes can be oxidized in an ambient-temperature ionic liquid using
MTO and the urea hydrogen peroxide [ 12 el.
 3.3.13.1 Fine Chemicals via Methyltrioxorhenium as Cutalyst 1309

Oxidation of Aromatic Compounds

Arenes are oxidized to para-benzoquinones by hydrogen peroxide with MTO as

catalyst [2, 3, 131. The high regioselectivity achieved is noteworthy, particularly in
the industrially interesting synthesis of vitamin K3 (see eq. (3)). Since water is an
inhibitor, concentrated (85 wt. %) H202is preferred. Alternatively, commercially
available 35 % H202in acetic anhydride can be employed; a considerable regio-
selectivity is obtained with this system. The conversion is higher for electron-rich
arenes (nearly 100 %) and selectivities of more than 85 % have been reached
[ 13 a]. Biphenylene can be oxidized with the MTO system in chloroform affording
an o-quinone product (83 % conversion) [ 13 b]. Hydroxy-substituted arenes can
be oxidized by aqueous hydrogen peroxide (85 wt.%) in acetic acid to afford
the corresponding p-quinones in isolated yields of up to 80% [3]. It has been
shown that using a mixture of acetic acid and acetic anhydride further improves
the product yield [ 13 d, el. Instead of acetic acid, HBF, in EtOH may also be
used [2, 31. Anisol was also found to undergo selective oxidation with the
MTO/H2O2 system to yield 0- and p-methoxyphenols. There is no need to use
a solvent in this case. For the mechanism of the arene oxidation see ref. [ 13 el.

mc[MTO]/H202
H 3

- WCH3
CH3COOH / 25 "C \
(3)

Benzaldehydes with hydroxyl or methoxy substituents in ortho or para

positions are oxidized to the corresponding phenols (carboxylic acids are formed
as by-products) in good yields [2, 31. The yield is temperature- and solvent-depen-
dent.

Baeyer-Villiger Oxidation and Dakin Reaction

y-Butyrolactones are obtained in good yields and high regioselectivity from

the corresponding cyclobutanones on oxidation with H202 catalyzed by MTO.
Lactonization was found to be chemoselective in the presence of double bonds,
aromatic rings, and chlorine substitutents [3, 14al. It has been shown that 2
also acts as an active species in the Baeyer-Villiger oxidation of ketones
(eq. (4)) and in the Dakin reaction [14].

It is somewhat surprising that the MTO/H202system presents this activity since

these oxidations involve nucleophilic attack at the carbonyl group which is in con-
trast to all the preceding examples where the substrates attacked the electrophilic
1310 3.3 Speciul Products

Re-peroxo complexes, e. g., in olefin epoxidation. Nevertheless, 2 reacts stoichio-

metrically with cyclobutanone in the absence of H202. This reversed behavior
may be due to substrate binding to rhenium. The unsymmetrical geometry of com-
pound 2a, displaying a polarity within the peroxo ligands, may also be responsible
for the observed behavior.
Using thiantrene-5-oxide as a mechanistic probe for oxygen transfer reactions,
the Baeyer-Villiger reaction was found to be strongly solvent-dependent [ 14 b,
151. Donor solvents such as acetonitrile seem to enhance the nucleophilicity of
the peroxo groups. Low H202concentrations are sufficient and no H202decom-
position is observed at temperatures up to 70 "C. This is an advantage of the cata-
lytic MTO/H,O, system over the known transition-metal Baeyer-Villiger catalysts
containing V, Mo, Mn, or 0 s . However, the nucleophilic character of the peroxidic
atoms in 2 is not as pronounced as in Pt or Ir peroxo complexes that react with
C 0 2 or SO2 to give isolable cycloaddition products [2, 31. In the case of 2
TOFs of 18 000 [mol/mol catalyst per hour] are obtained for cyclobutanone, but
in other cases TONS of up to 100 are usual [3]. Cycloketones can be converted
into lactones even below room temperature (15 "C) by dilute hydrogen peroxide
(1 0 wt. %).

Oxidation of Sulfur Compounds

Organic sulfides can be oxidized to the corresponding sulfoxides by hydrogen

peroxide in the presence of MTO (eq. (5)) [2, 3, 161. Both complexes 2 and 3
appear to be active in this reaction but kinetic results indicate that 3 might be
more active than 2. Using ethanol as solvent, the MTO/H202 system can be
used to oxidize dialkyl, diaryl, and alkyl aryl sulfides to sulfoxides (R2S/H202
= 1:l.l) or sulfones (R2S/H202= 1:2.2) with excellent yields and selectivity
even in the presence of oxidatively sensitive functions on the sulfide side
chain [3, 161. The rate constants for the oxidation of sulfoxides to sulfones are
significantly smaller than for the oxidation of sulfides to sulfoxides and the re-
action rate is negligible without a catalyst. MTO can also be used in the oxidation
of sulfides with the water-free ureahydrogen peroxide system as oxidant in
acetonitrile.
The results of a kinetic study are consistent with a nucleophilic attack of the
sulfur atom on the peroxide oxygen group. While the bisperoxo complex 2 is
an active catalyst, the monoperoxo complex 3 shows no activity [I 6 a].

Sulfoxides are also readily accessible by the oxidation of thioether Fischer

carbenes using 4 % MTO and H202in a methanoUmethylene chloride solvent [3].
Aryl disulfides are oxidized to thiosulfinates using MTO-catalyzed H202.The
use of an excess of H202eventually affords the sulfonic acids through thiosulfi-
 3.3.13.I Fine Chemicals via Methyltrioxorhenium as Catalyst 131 1

nate intermediates [ 16 b]. Disulfides themselves may be oxidized by H202in the

absence of MTO but this requires a large excess of oxidant, and elevated tempera-
tures.
Thioketones are sequentially oxidized through sulfines (thioketone-S-oxide) to
sulfur monoxide and the parent ketone on treatment with the relevant amount of
H202catalyzed by MTO. A 1: 1 ratio of the R2CS/H202generates the sulfine with-
out further oxidation or side product synthesis. A second equivalent of H202 re-
sults in the oxidative cleavage of the sulfine to release SO and the corresponding
ketone [ 16 c, d]. However, this step occurs much more slowly. An application of
this approach is in the synthesis of bridged SO species [16e].

Oxidation of Phosphines, Arsines and Stibines

Tertiary phosphines, triarylarsines, and triarylstibines are converted to their

oxides, R3E0 (E = P, As, Sb) by MTO/H202.Kinetic studies lead to the assump-
tion that 2 and 3 have similar catalytic activities in all cases. The kinetic data sup-
port a mechanism involving nucleophilic attack of the substrate at the rhenium
peroxides.
In the absence of peroxides, MTO also catalyzes the oxidation of tertiary phos-
phines to phosphine oxides [3, 171.

Oxidation of Anilines and Amines

A broad range of aromatic and aliphatic amines are readily oxidized to their cor-
responding N-oxides using the MTO/H202catalytic system. The oxidation of aryl
amines proceeds ca. 50 times faster than without catalyst [3, 181. Nitrosobenzene
is obtained by the oxidation of aniline (eq. (6)) while the oxidation of 4-substi-
tuted N,N-dimethylanilines yields the N-oxide as the only product. It has been
found that electron-withdrawing substituents present on the substrate inhibit the
reaction.

Kinetic results suggest that both compounds 2 and 3 are involved in the oxida-
tion process [2, 31. It is proposed that the rate-determining step is the nucleophilic
attack of the nitrogen lone-pair electrons of the aromatic amines on a peroxidic
oxygen of the catalyst. Electron-donating groups attached to the nitrogen atom
of aniline increase the rate constant. In general, the reactions are facile and
high yielding at or below room temperature [3]. Furthermore, a broad variety of
aromatic and aliphatic secondary amines are oxidized to the corresponding N-oxi-
des [3]. The amines are converted to the corresponding hydroxylamines before
transformation to the nitrones in very good yields. The hydroxylamine formation
is rate-determining [2, 31. Both H202and the urea-hydrogen peroxide complex
1312 3.3 Special Products

can be used together with MTO. Benzylamines are selectively oxidized to oximes.
Primary amines are oxidized to nitro compounds by MTO catalysis (eq. (7)) [ 3 ] .

RNH2 -HZOZ

[MTOI
RNO? (7)

Oxidative Cleavage of N,N-Dimethylhydrazones

N,N-Dimethylhydrazones of aldehydes react with hydrogen peroxide in the

presence of catalytic amounts of MTO to give the corresponding nitriles in
high yield [19]. The reaction commences with the oxidation of the N,N-dimethyl-
hydrazone and presumably proceeds through an intermediate which can undergo a
Cope-type elimination to yield the nitrile (eq. (8)) [3, 19 b].

A more recent development shows that N,N-dimethylhydrazones derived from

ketones may be cleaved oxidatively to revert back to the parent carbonyl com-
pound in excellent yield [19c].

Oxidation of Halide Ions

Another application of the MTO/H202system is the catalytic oxidation of chloride

and bromide ions in acidic aqueous solutions. The chloride oxidation steps are
three to four orders of magnitude slower than the corresponding bromine oxida-
tion steps. Both compounds 2 and 3 have been shown to be active catalysts in
these processes. In both cases the catalyzed reactions were about los times faster
than the uncatalyzed ones under similar conditions. In a first step HOX is formed,
then HOX reacts with X- to form X2. When H202is used in excess the reaction
yields O2 [2, 3, 201.

Oxidation of C-H and Si-H Bonds

MTO/H202also catalyzes the insertion of oxygen into a variety of activated and

nonactivated C-H bonds. Alcohols or ketones are formed as shown in eq. (9). In
the case of tertiary substrates alcohols are obtained as products. Suitable substrates
proved that the reaction is stereospecific with retention of the configuration [2, 31.
The reaction can be accelerated by the addition of pyrazine-2-carboxylic acid,
which also increases the total yield [ 3 ] .
 3..?. 13.I Fine Chemicals via Methyltrioxorhenium as Cutalyst 1313

The catalyst system MTO/H202also catalyzes oxygen atom insertion into Si-H
bonds. Silanols and disiloxanes are formed as products, with the latter being the
major ones [3, 21 a]. When UHP is used as an oxygen source instead of aqueous
H202, 1 catalyzes the oxidation of silanes to silanols in high conversions and
excellent selectivities in favor of the silanol (eq. (10)).

major product
More recently, it has been found that MTO absorbed in NaY zeolite allows the
selective oxidation of silanes to silanols in the presence of H202(85 %) in excel-
lent yield [ 10 el. No oxidation was found in the absence of MTO. In most cases
studied, yields of disiloxanes were low (<6 %).
In the presence of catalytic amounts of 1, methyl trimethylsilyl ketene acetals
are oxidized with urea hydrogen peroxide to afford a-hydroxy and a-siloxy esters
[3, 21 b].

Oxidation of Other Compounds

Internal alkynes yield carboxylic acids and a-diketones when oxidized with the
MTO/H202system [22]. Rearrangement products are observed only for aliphatic
alkynes. Terminal alkynes give carboxylic acids, derivatives thereof and a-keto
acids as the major products. The yields of these products vary with the solvent
used [22].
Primary and secondary alcohols are oxidized using the MTO/H202 catalyst
system to aldehydes and ketones, respectively [23]. The dominant and reactive
form of the catalyst is compound 2 [lo;]. The addition of a catalytic quantity
of bromide ions, such as HBr or NaBr, significantly enhances the reaction rate
[23 b]. The bromide is oxidized to the hypobromide ion, BrO- which combines
with additional bromide to give bromine. Bromine oxidizes the alcohols to alde-
hydes and ketones. The system MTO/H202/HBr/TEMP0 (TEMPO = 2,2,6,6-tet-
ramethyl- 1-piperidinyloxy) catalyzes the selective oxidation of terminal alcohols
to the corresponding aldehydes with excellent selectivities and yields [23 c].
The system allows the oxidation of alcohols either selectively to aldehydes or
to the corresponding acids, depending on the reaction parameters. This technique
is especially applicable to the oxidation of carbohydrates [23 c].
The MTO/hydrogen peroxide system oxidatively cleaves furans in yields usually
> 70 % to enediones. Substituted pyranones are obtained from furans with hydro-
xymethyl groups at the 2-position. The yields in this case are > 75 %. Acetonitrile
as solvent leads to the fastest reactions although the work-up is reported to be easier
in CH2Cl2 [23d]. Silyl enol ethers are oxidized to a-hydroxy ketones by MTOI
H202 with subsequent desilylation with KF (eq. (13)) [23e]. Yields are usually
> 90 %. In the case of conjugated systems, the yields are significantly lower.
1314 3.3 Special Products

The MTO/H202 system furthermore catalyzes the oxidation of cyclic /3-dike-

tones to carboxylic acids (eq. (11)) [15]. Conversions are usually above 85 %;
the product selectivity is nearly quantitative. It has been assumed that enolic
forms which exist in solution are initially epoxidized. After a rearrangement
step the C-C bond is cleaved and an oxygen inserted. Then an a-diketone inter-
mediate forms which is finally oxidized to the carboxylic acid [15].

Oxidation of Metal Carbonyls

MTO catalyzes the oxidation of metal carbonyls to metal oxides with H202
(eq. (12)) [24a-c]. These reactions proceed at room temperature and yields of
up to 90 % are obtained. However, only organometal carbonyls with oxidation-
resistant organic groups can be oxidized, e. g., (pentamethylcyclopentadieny1)tri-
carbonylrhenium(1) [24 a]. In all other cases, the organic ligand is also oxidized,
leading to decomposition of the product complex [24c].
R' R'

3.3.13.1.4 Aldehyde Olefination and Related Reactions

Aldehydes or strained cycloketones, treated with aliphatic diazoalkanes in the pre-
sence of an equimolar amount of a tertiary phosphine and 1 as catalyst, afford an
olefinic coupling product in good yields already at room temperature according to
eq. (13) (cf. also Section 3.2.10) [2, 3, 251.

The trans selectivity is between 60 and 95 %, depending on the substrate, and

the yields are around 85%. The advantage of this method over Tebbe-Grubbs
coupling is that it does not require the use of a stoichiometric amount of an
organometallic coupling reagent [3, 251.
The deoxygenation of epoxides, sulfoxides, N-oxides, and triphenylarsine and
triphenylstibine oxides at room temperature is also catalyzed by MTO with PPh3
as oxygen acceptor [26]. Again, a Re" intermediate, containing the (ligand-stabi-
lized) methyldioxorhenium, seems to be involved. A catalytic amount of MTO
 3.3.13.1 Fine Chenzicals via Methyltrioxorhenium as Catalyst 1315

also allows the stereospecific desulfurization of thiiranes (episulfides) by Ph,P

[25 b]. It is proposed that the Re" again is the active catalyst in this reaction.
When MTO is initially treated with H2S the reaction rate is significantly enhanced.
It is not entirely clear what the active species in the MTO/H2S system is.

3.3.13.1.5 Olefin Metathesis

The system Re207/A1203is an effective heterogeneous catalyst for carrying out
olefin metathesis under mild conditions and its activity can be further increased
by the addition of tetraalkyl tin compounds (cf. Section 2.3.3) [3, 261.
Since tin-containing co-catalysts are essential for the metathesis of functiona-
lized olefins [26], it was soon discovered that l supported on acidic metal oxides
forms metathesis catalysts that are active without additives even for functionalized
olefins [26]. Standard supports are A1203-Si02, or Nb2OSand the activity is re-
lated to the surface acidity [2, 3, 261. A high metathesis activity is observed
when MTO is chemisorbed on the surface. No evidence for a surface carbene
species was obtained, but there appears to be a correlation between the catalytic
activity and the presence of an alkyl fragment on the surface [26a-c].
It was also possible to encapsulate 1 in zeolite, maintaining its metathesis
activity. IR and EXAFS data indicate that the structure of 1 remains unchanged
and that it is anchored by hydrogen bridges to the zeolite oxygens [2, 31. Adsorp-
tion of water causes the de-aggregation of the guest molecules. Thermal treatment
around 120 "C is found to yield methane and water together with the formation of
an intrazeolite cluster species containing Re-Re bonds [2, 31.
The MTO supported on A1203-Si02 catalyzes in particular the self-metathesis
of ally1 aldehydes, ethers, silanes, and unsaturated carboxylates and nitriles, but
also the ethenolysis of olefins with internal double bonds [26]. The catalyst sys-
tem is also suitable for the metathesis of simple open-chain and cyclic olefins.
Otherwise, frequent side reactions such as double-bond isomerization and olefin
dimerization are insignificant. Ring-opening polymerization is catalyzed by the
homogeneous catalyst MTO/R,,A1C13~,(R = CH3, C2Hs; y1 = 1, 2). As in the
case of the heterogeneous olefin metathesis, the reaction can be performed at
room temperature [26a]. Several functionalized diolefins cyclize to hydroazulenes
via olefin metathesis in the presence of 1 [26d].

3.3.13.1.6 Diels-Alder Reaction

MTO enhances the Diels-Alder reactivity of unsaturated C=C compounds, the
standard case of which is given in eq. (14) [2, 3, 271.

endo I ex0
1316 3.3 Special Products

MTO proves to be an efficient and effective catalyst in this reaction when

the dienophile is an a$-unsaturated ketone or aldehyde. It is especially active
in water, usually with isolated yields > 90%. Kinetic studies show that the
reaction rate is proportional to the catalyst concentration. The desirability of
1 as a Diels-Alder catalyst stems from a combination of favorable properties:
the tolerance for many substrates, the inertness to air and oxygen, the use of
aqueous medium, and the absence of product inhibition. The initial step ap-
pears to be the coordination of the carbonyl oxygen to the rhenium center.
Steric crowding around rhenium inhibits reactions of the larger dienophiles
~71.

3.3.13.1.7 Other Reactions

In the presence of 1 the catalytic alkoxylation of cyclohexene oxide with second-
ary and tertiary alcohols can be performed. This catalyst is known to cause dispro-
portionation of epoxides, yielding olefins and diols. FT-IR spectroscopy indicated
the formation of an active intermediate composed of 1 and epoxide. The carboca-
tionic intermediate species is highly reactive with respect to nucleophilic com-
pounds [28].
Ethyl diazoacetate (EDA) decomposes in the presence of 1, thereby allowing
access to a wide range of products. In the absence of other reactants, this decom-
position results in the formation of both fumarate and diethyl maleate with the
azine (EtO,CC=N-N=CCO,Et) also being formed [29 a]. Excellent yields of alk-
oxy and phenoxy esters are achieved from the OH insertion of low molecular
weight primary and phenyl alcohols into EDA in the presence of MTO. SH and
NH insertion reactions are accessible by treatment of EDA with thiols and amines
in the presence of MTO to give excellent yields of thio esters and glycine esters,
respectively [29 a]. The EDA decomposition in the presence of MTO allows the
formal addition of a carbene to unsaturated systems. One such addition is the
formation of epoxides from aldehydes and ketones [50].Carbene addition to aro-
matic imines yields aziridines in excellent yields whereas the addition to alkenes
furnishes cyclopropanes [29 b].
MTO has also been claimed to be the first transition metal complex to cata-
lyze the direct, solvent-independent formation of ethers from alcohols [30].
Aromatic alcohols give better yields than aliphatic ones and reactions between
different alcohols have been used to prepare asymmetric ethers. Also catalyzed
by 1 is the dehydration of alcohols to form olefins at room temperature. When
primary or secondary amines, respectively, are used as the limiting reagents,
direct amination of alcohols gives the expected secondary or tertiary amines
in yields of ca. 95 %. Disproportionation of alcohols to carbonyl compounds
and alkanes is also observed for aromatic alcohols in the presence of MTO as
catalyst.
MTO has found application in the cyclotrimerization of aldehydes to yield
1,3,5-trioxanes in excellent yield [31]; 1 mol% of the catalyst is employed
and water was found to inhibit the reaction. No other products were observed.
 References 1317

However, the introduction of bulky or electron-withdrawing substituents at the

a-position limits the rate of formation of the trioxane.

References
[I] G. Rouschias, Chem. Rev. 1974, 74, 531.
[2] Recent reviews on organorhenium oxides: (a) W. A. Henmann, F. E. Kiihn, Acc. Chem.
Res. 1997, 30, 169; (b) C. C. Romlo, F. E. Kuhn, W. A. Henmann, Chem. Rev. 1997,
97, 3197.
[3] Recent reviews dealing with catalytic applications of methyltrioxorhenium: (a) J. H.
Espenson, M.M. Abu-Omar, ACS Adv. Chem. 1997, 253, 3507; (b) G.S. Owens,
J. Arias, M. M. Abu-Omar, Catal. Today, 2000, 55, 317; (c) W. Adam, C. M. Mitchell,
C. R. Saha-Moller, 0. Weichold, in Structure and Bonding (Ed.: B. Meunier), Springer
Verlag, Berlin, 2000, Vol. 97, p. 237.
[4] (a) W. A. Henmann, W. Scherer, R. W. Fischer, J. Blumel, M. Kleine, W. Mertin,
R. Gruehn, J. Mink, H. Boyson, C. C. Wilson, R. M. Iberson, L. Bachmann, M. R. Matt-
ner, J. Am. Chem. Soc. 1995, 117, 3231.
[5] (a) W.A. Henmann, R.W. Fischer, D. W. Marz, Angew. Chem., Int. Ed. Engl. 1991,
30, 1638.
[6] (a) W.A. Henmann, R. W. Fischer, W. Scherer, M.U. Rauch, Angew. Chem., Int. Ed.
Engl. 1993, 32, 1157; (b) P. Gisdakis, S. Antonczak, S. Kostlmeier, W. A. Herrmann,
N. Rosch, Angew. Chem., Int. Ed. Engl. 1998, 37, 2211.
[7] (a) J. H. Espenson, H. Tan, S. Mollah, R. S. Houk, M.D. Eager, Inorg. Chem. 1998, 37,
462 I ; (b) K. A. Brittingham, J. H. Espenson, Inorg. Chem. 1999, 38, 744.
[8] 0. Pestovsky, R. vanEldik, P. Huston, J.H. Espenson, J . Chem. Soc., Dalton. Truns.
1995, 133.
[9] S. Yamazaki, J. H. Espenson, P. Huston, Inorg. Chem. 1993, 32, 4683.
[lo] (a) F.E. Kiihn, A.M. Santos, P. W. Roesky, E. Herdtweck, W. Scherer, P. Gisdakis, I. B.
Yudanov, C. Divalentin, N. Rosch, Chem. Eur. J . 1999, 5, 3603; (b) M.C. A. VanVliet,
I.W.C.E. Arends, R.A. Sheldon, J . Chem. Soc., Chem. Commun. 1999 821;
(d) W. Adam, C.R. Saha-Moller, 0. Weichold, J. Org. Chem. 2000, 65, 2897;
(e) W. Adam, C. R. Saha-Moller, 0. Weichold, J. Org. Chem. 2000, 65, 5001;
(f) W.A. Herrmann, T. Weskamp, J.P. Zoller, R. W. Fisher, J . Mol. Catal. A, 2000,
153, 49; (8) M. Nakajima, Y. Sasaki, H. Iwamoto, S. Hashimoto, Tetrahedron Lett.
1998, 39, 87; (h) W. A. Henmann, R.M. Kratzer, H. Ding, W. R. Thiel, H. Glas, J. Or-
ganomet. Chem. 1998, 555, 293; (i) H. Rudler, J. R. Gregorio, B. Denise, J. M. Br6-
geault, A. Deloffre, J. Mol. Catal. A 1998, 133, 255; (i) W. D. Wang, J. H. Espenson,
J. Am. Chem. Soc. 1998, 120, 11335; (k) A. L. Villa de P., D. E. DeVos, C. C. deMontes,
P. A. Jacobs, Tetrahedron Lett. 1998, 39, 8521.
[ I I ] (a) H. Tan, J. H. Espenson, Inorg. Chem. 1998, 37,467; (b) J. R. Gregrio, A. E. Gerbase,
M. Martinelli, M. A. M. Jacobi, L. de Luca Freitas, M. L. A. v. Holleben, P. D. Marcico,
Macromol. Rapid Commun. 2000, 21, 401.
[ 121 (a) H. R. Tetzlaff, J. H. Espenson, Inorg. Chem. 1999, 38, 881; (b) W. Adam, C. M.
Mitchell, C. R. Saha-Moller, Eur: J. Org. Chem. 1999, 785; (c) J. Jacob, J. H. Espenson,
J. H. Jensen, M. S. Gordon, Organometallics, 1998, 17, 1835; (d) S. Bellemin-Laponnaz,
J.P. LeNy, A. Dedieu, Chem. Eur: J. 1999, 5, 57; (e) G. S. Owens, M. M Abu-Omar,
J. Chem. Soc., Chem. Commun. 2000, 1165.
[I31 (a) W. Adam, W. A. Henmann, J. Lin, C. R. Saha-Moller, R. W. Fischer, J. D. G. Correia,
Angew. Chem., Int. Ed. Engl. 1994, 33, 2475; (b) W. Adam, M. Balci, H. Kilic, J. Org.
1318 3.3 Special Products

Chem. 1998,63, 8544; (c) F. E. Kiihn, J. J. Haider, E. Herdtweck, W. A. Henmann, A. D.

Lopes, M. Pillinger, C. C. Romiio, Znorg. Chim. Actu 1998,279,44; (d) W. A. Henmann,
J. J. Haider, R. W. Fischer, J. Mol. Catal. A, 1999, 138, 115; (e) J. Jacob, J. H. Espenson,
Inorg. Chim. Actu 1998, 270, 55.
[14] (a) A.M. F. Phillips, C. Romiio, Eur: J. Org. Chem. 1999, 1767; (b) W. A. Henmann,
R. W. Fischer, J.D. J. Correia, J. Mol. Catal. A 1994, 94, 213.
[IS] M. M. Abu-Omar, J. H. Espenson, Organornetullics 1996, 15, 3543.
[ 161 (a) D. W. Lahti, J. H. Espenson, Inorg. Chem. 2000, 39, 2164: (b) Y. Wang, J. H. Espen-
son, J . Org. Chem. 2000,65, 104; (c) R. Huang, J. H. Espenson, J. Org. Chem. 1999,64,
6935; (d) R. Huang, J.H. Espenson, J. Org. Chem. 1999, 64, 6374; (e) R. Huang, I. A.
Guzei, J. H. Espenson, Organometullics 1999, 18, 5420; (f) H. N. Q. Gunaratne, M. A.
McKervey, S. Feutren, J. Finlay, J. Boyd, Tetrahedron Lett. 1998, 39, 5655.
[ 171 M. D. Eager, J. H. Espenson, Inorg. Chem. 1999, 38, 2533.
[18] (a) Z. Zhu, J. H. Espenson, Synthesis 1998, 417.
[I91 (a) H. Rudler, B. Denise, J. Chem. Soc., Chem. Commun. 1998, 2145; (b) S. Stankovic,
J.H. Espenson, J. Chem. Soc., Chem. Commun. 1998, 1579; (c) S. Stankovic, J.H.
Espenson, J. Org. Chem. 2000, 65, 2218.
[20] (a) J.H. Espenson, 0. Pestovsky, P. Huston, S. Staudt, J. Am. Chem. Soc. 1994, 116,
2869; (b) P. J. Hansen, J. H. Espenson, Znorg. Chem. 1995, 34, 5389.
[21] (a) W. Adam, C. M. Mitchell, C. R. Saha-Moller, 0. Weichold, J. Am. Chem. Soc. 1999,
121, 2097; (b) S. Stankovic, J. J. Espenson, J. Org. Chem. 2000, 65, 5528.
(221 Z. Zhu, J.H. Espenson, J. Org. Chem. 1995, 60, 7728.
[23] (a) T.H. Zauche, J.H. Espenson, Znorg. Chem. 1998, 37, 6827; (b) J.H. Espenson,
Z. Zhu, T. H. Zauche, J. Org. Chem. 1999, 64, 1191; (c) W. A. Henmann, J. P. Zoller,
R. W. Fischer, J. Organomet. Chem. 1999, 581, 404; (d) J. Finlay, M. A. McKervey,
H. N. Q. Gunaratne, Tetrahedron Lett. 1998, 5651: (f) S. Stancovic, J. H. Espenson,
J. Org. Chem. 1998, 63, 4129.
[24] (a) W. A. Henmann, J. D. G. Correia, F.E. Kiihn, G. R. J. Artus, C. C. Romiio, Chem.
J. Eur: 1996, 2, 168; (b) W.R. Thiel, R. W. Fischer, W.A. Henmann, J. Organomet.
Chem. 1993, 459, C9; (c) W.A. Herrmann, M.R. Geisberger, F.E. Kuhn, G.R.J.
Artus, E. Herdtweck, Z. Anorg. Allg. Chem. 1997, 623, 1229.
[25] (a) W. A. Herrmann, M. Wang, Angew. Chem., Znt. Ed. Engl. 1991,30, 1641: (b) J. Jacob,
J.H. Espenson, J. Chem. Soc., Chem. Commun. 1999, 1003.
1261 (a) W.A. Henmann, W. Wagner, U.N. Flessner, U. Volkhardt, H. Komber, Angew.
Chem., Znt. Ed. Engl. 1991, 30, 1636; (b) R. Buffon, A. Auroux, F. Lefebvre, et al.,
J. Mol. Catal. A 1992, 76, 287; (c) R. Buffon, A. Choplin, M. Leconte, et al., J. Mol.
Catal. A 1992, 72, L7; (d) T.M. Mathews, J.A.K. duPlessis, J. J. Prinsloo, J. Mol.
Catal. A 1999, 148, 157.
[27] Z. Zhu, J.H. Espenson, J. Am. Chem. Soc. 1997, 119, 3501.
1281 A. B. Kholopov, A. V. Nikitin, V. L. Rubailo, Kinet. Kutal. 1995, 36, 101.
[29] (a) Z. Zhu, J.H. Espenson, J. O r , . Chem. 1995, 60, 7090; (b) Z. Zhu, J.H. Espenson,
J. Org. Chem. 1995, 60, 7728.
1301 Z. Zhu, J.H. Espenson, J. Am. Chem. Soc. 1995, 118, 9901.
[31] Z. Zhu, J. H. Espenson, Synthesis 1998 417.
 Applied Homogeneous Catalysis with Organometallic Compounds
Edited by B. Cornils and W. A. Herrmann
Copyright 0 Wiley-VCH Verlag GmbH, D-69469 Weinheim, 2002

3.3.13.2 Pilot-Plant Synthesis of MTO 1319

3.3.13.2 Pilot-Plant Synthesis of MTO

Wolfgang A. Herrrnann

3.3.13.2.1 Introduction
The simple organorhenium(VI1) compound methyltrioxorhenium (Structure 1 in
Scheme 1) - called MTO - has developed a plethora of applications in catalytic
processes [l]. This rapid development occurred in the decade of 1990-2000.
The epoxidation of olefins (cf. Section 2.4.3) became attractive to industrial
applications. There is sound evidence that MTO represents the most efficient
catalyst for this process, being active even for highly dilute solutions of hydrogen
peroxide. The latter oxidant is not decomposed by MTO, as opposed to many
other metal complexes (cf. Section 3.3.13.1).
Due to the increasing industrial demand, a laboratory pilot-plant synthesis of
the catalyst was developed. In the period of 1993-2000, a total of 189 papers
and patents on MTO applications have appeared, showing the great interest in
both academia and industry.

3.3.13.2.2 Principle of Synthesis

MTO is generated by methylation of oxidic Re"" precursor compounds under
nonreducing conditions. Thus, dimethylzinc and methyl Grignard compounds
are not very well suited for this purpose. The first commonly applied synthesis
started from dirhenium heptoxide using the toxic tetramethyltin as methylating
reagent (eq. (1)). The major drawback in this otherwise excellent approach is
the loss of half of the Re due to formation of the low-reactivity trimethylstannyl
perrhenate [2].

Re207 t Sn(CH3), - CH3Re03 t (CH3)3SnORe03

1
(1)

An improvement was the use of the mixed ester of perrhenic and trifluoroacetic
acid, avoiding the chemical loss of rhenium [3,4]. At the same time, the much less
toxic tris(n-buty1)methyltin was used for the selective methylation in eq. (2). This
route reached the laboratory pilot-plant stage in 1999.

- @a)
-
1/2 Re20, t 1/2 [CF3-C(=O)]20 [CF3-C(=O)O]Re03

[CFrC(=O)O]Re03 t ("Bu),SnCH3 CH3Re03 t ("Bu)~S~-OC(=O)CF~ (2b)

1

A second industrially feasible synthesis has particularly focused on cheap

starting compounds, abandoning both the trifluoric acetic anhydride and the
1320 3.3 Special Products

(hygroscopic) dirhenium heptoxide. Instead, easily available perrhenates

M'[ReOJ are used (M+ = Ag+, [NH,]', Na+, K+). They result from easy H202
oxidation of elemental Re according to eq. (3).

Re - H202
H[Re041 - + MX
- HX
M+[Re04] (3)

According to Scheme 1, the perrhenate is converted into the silylperrhenate,

which undergoes subsequent stepwise transformation to the reactive chlorotrioxo-
rhenium [S-71. Half of the rhenium from the chlorination process of Re20, is
recycled to the trimethyl stannyl perrhenate. The final methylation of C1ReO3 is
achieved by tetramethyltin in near quantitative yields.
,Si(CH3)3
0
I
M+[Re04Y

Scheme 1. Synthesis of MTO 1 from perrhenates.

The net reaction follows eq. (4). The overall yields range between SO and 8.5 %
based on rhenium. This methodology has the advantage that cheap precursor com-
pounds can be used and that a basically unlimited scale-up is possible. Amounts
up to 500 g of pure MTO 1 have thus been made.

M+[ReO4T + 2 (CH3)3SiCI + SII(CH~)~ - (4)

CH3Re03 + [(CH3)$iI20 + (CH3)3SnCI + MCI

The silver perrhenate, especially, forms reproducible, analytically pure, off-

white MTO [8]. Selected catalytic applications of MTO are treated in Section
3.3.13.1.
 3.3.I3.2 Pilot-Plant Synthesis of MTO 1321

3.3.13.2.3 Synthetic Procedures

The Mixed-Anhydride Route

Trifluoroacetic anhydride (105.1 g, 70.7 mL, 0.5 mol) is dissolved in 1500 mL of

anhydrous acetonitrile. Freshly sublimed dirhenium heptoxide (Re2O7) (243.2 g,
0.5 mol) is added with vigorous stirring to avoid aggregation of Re207.After the
Re207has completely dissolved, the solution turns slightly green. Tris(n-buty1)-
methylstannane (305.1 g, 1 mol) is added, whereby the color of the solution
changes to dark brown. The mixture is stirred overnight (ca. 12 h); longer
reaction times have no negative influence on yield and purity. The solvent is
then removed at room temperature in an oil-pump vacuum Tom) until the
residue forms a paste. The product sublimes at 80 "C/lO-* Torr as colorless
needles. If necessary the sublimate is washed with cold n-pentane to remove
the last impurities. The off-white product was then dried in vucuo. Yield:
4 0 0 4 5 0 g (80-90%).

The Perrhenate Route

Method A

Sodium perrhenate [NaReO,] (100 g, 0.366 mol) is suspended in 1.5 L of aceto-

nitrile. After addition of I02 mL (0.8 mol) of trimethylchlorosilane [ClSi(CH,),]
and 56 mL (0.4 mol) of tetramethyltin, the reaction mixture is heated for 10 h
under reflux. At ambient temperature, the yellow-orange mother liquor is sepa-
rated from the insoluble residue by filtration; the solvent is evaporated under re-
duced pressure. After the trimethylchlorotin has been removed as the first fraction
of the sublimation, MTO is separated from the remaining residue by sublimation
at 50 "C and lo-* mbar. The MTO obtained may contain small amounts of tri-
methylchlorotin (detectable by its characteristic smell; caution: trimethylchloro-
tin is highly poisonous!). In this case, either a second careful sublimation (in
several fractions) is recommended, or the MTO is stored on a filter paper in a
flask under a slight vacuum until the undesired, very volatile by-product has
gone. However, care has to be taken not to lose the MTO, too. Yield: 60-70 g
(65-75 %).

Method B

The following reagents and respective amounts are needed: 1.5 L of acetonitrile,
1400 g (39 mol) of silver perrhenate [AgReO,], 1080 mL (85 mol) of trimethyl-
chlorosilane [ClSi(CH,),], 600 mL (4.3 mol) of tetramethyltin.The quick forma-
tion of the reactive intermediate species is indicated by the spontaneous precipita-
tion of silver chloride after the silver perrhenate and the trimethylchlorosilane are
mixed together. Yield: 780-880 g (80-90 %).
1322 3.3 Special Products

The product thus obtained is of higher purity than MTO made in the same way
from sodium perrhenate.
The perrhenates M'[ReOJ (M' = Ag+, K+) are made from rhenium powder
according to [9].

3.3.13.2.4 Properties
Methylrhenium trioxide MTO can be stored at room temperature without decom-
position. The compound forms pale yellow needles, m. p. 112 "C. Direct exposure
to light should be avoided.

IR (KBr): = 1002 (vs), 950 cm-'(vs. br. Re=O).

1H NMR (CDC13, 28 "C): 6 = 2.61 (s, CH3).
13C NMR (CDC13, 28 "C): 6 = 19.03 [d, 'J(C, H) =138 Hz, CHJ.
"0 NMR (CDC13, 28 "C): 6 = 829.
EI-MS: d z = 248/250 (molecular ion peak with correct isotope distribution
's5Re/187Refor CH3Re03, 249.21).

Solubility in water: SO g/L (0.20 mol/L)

pKs(H20, 25 "C): 7.5 (sat. solution, pH = 4)
p = 4.103 g ~ m - p~ = ; 2.6 D (C6H6, 25 "C); magnetic susceptibility x =
-55 . cm-3 mol-I; ionization potential I I = 11.80 eV; dissociation energy
D(CH,-Re) = 319 kJ . mol-' (calc.).

Solid-state crystal structure (X-ray): d(Re-C) = 204(3) pm, d(Re-0) =

168(2) pm.

Small amounts of MTO are also available commercially from (a) Aldrich:
41,291-0 (100 mg, 500 mg) and (b) Fluka: 69489 (SO mg, 250 mg).

References
[I] Reviews: (a) W. A. Herrmann, F. E. Kuhn, Acc. Chem. Res. 1998, 30, 169; (b) C . C .
Romiio, F. E. Kuhn, W. A. Herrmann, Chem. Rev. 1997, 97, 3 197; (c) Aqueous-Phase
Orgunometullic Catalysis-Concepts and Applications (Eds.: B. Cornils, W. A. Herr-
mann), 1998, pp. 529-538; (d) Trunsition Metal Catalyzed Reactions (Eds.: W. A. Hem-
mann, F. E. Kuhn, in: s.I. Murahashi, s. G. Davies), IUPAC Series for the 21st Century
Monographs, Blackwell Science, 1999, pp. 375-390; (e) Structure and Bonding (Eds.:
F. E. Kuhn, W. A. Herrmann, in: B. Meunier), 2000, 97, pp. 21 1-234. Recent applica-
tions: W. A. Herrmann, J. P. Zoller, R. W. Fischer, J. Organomet. Chem. 1999, 579,
404; W. A. Herrmann, T. Weskamp, J. P. Zoller, R. W. Fischer, J. Mol. Catal. A: Chemi-
cal, 2000, 153, 49.
[2] W.A. Henmann, J.G. Kuchler, J. K. Felixberger, E. Herdtweck, W. Wagner, Angew.
Chem. 1988, 100,420; Angew. Chem., Int. Ed. Engl. 1988, 27, 394.
 3.3.14.2 Chemical Background 1323

[3] W.A. Henmann, F.E. Kuhn, R. W. Fischer, W.R. Thiel, C.C. RomBo, Inorg. Chem.
1992, 31, 4431; W. A. Henmann, R. W. Fischer, M. U. Rauch, W. Scherer, J. Mol.
Catal. 1994, 86, 243.
[4] R. W. Fischer, Ph.D. Thesis, Technische Universitat Munchen, 1994.
[ 5 ] W. A. Herrmann, R. M. Kratzer, R. W. Fischer, Angew. Chem. 1997, 109, 2767; Angew.
Chem., bit. Ed. 1997, 36, 2652.
[6] R. Kratzer, Ph.D. Thesis, Technische Universitlt Munchen, 1998.
[7] F. E. Kuhn, R. W. Fischer, W. A. Henmann, Chem. Unserer Zeit, 1999, 33, 192.
[8] Further information on MTO and its uses are available at the author’s homepage under
the following Internet address: http://aci.anorg.chemie.tu-muenchen.de
[9] W. A. Henmann, R. W. Fischer, M. Groarke, F. E. Kuhn, in: Synthetic Methods of Orga-
nometallic and Inorganic Chemistry (Ed.: W. A. Henmann), Vol. 10, Enke Verlag, Stutt-
gart, 2001.

3.3.14 Acetoxylations and Other Palladium-Promoted or

Palladium-Catalyzed Reactions
Reinhard J i m

3.3.14.1 Historical and Economic Background

Acetoxylations (oxyacylations) have to be seen in context with olefin oxidation to
carbonyl compounds (Wacker process, Section 2.4.1). With the lowest olefin,
ethylene, acetaldehyde is formed. In water-free acetic acid no reaction takes
place. Only in the presence of alkali acetates - the acetate ion shows higher nu-
cleophilicity than acetic acid - ethylene reacts with palladium salts (eq. (1)) to
give vinyl acetate, the expected product, as first reported by Moiseev et al. [l].
Stem and Spector [2] independently used [HP04]*- as base in a mixture of iso-
octane and acetic acid. This reaction could be exploited for a commercial process
to produce vinyl acetate and closed the last gap replacing acetylene by the cheaper
ethylene, a petrochemical feed material, for the production of large-tonnage
chemical intermediates.

H2C=CH2 + Pd2+ + CH&OO- - @o k + Pd + H+ (1)

The industrial and scientific success of these two reactions initiated a boom in
palladium chemistry which is still continuing.

3.3.14.2 Chemical Background

Acetoxylation of olefins according to eq. ( 1 ) is an oxidative reaction which can
be widely applied. However, it does not occur in such a distinct manner as olefin
 Applied Homogeneous Catalysis with Organometallic Compounds
Edited by B. Cornils and W. A. Herrmann
Copyright 0 Wiley-VCH Verlag GmbH, D-69469 Weinheim, 2002

3.3.14.2 Chemical Background 1323

[3] W.A. Henmann, F.E. Kuhn, R. W. Fischer, W.R. Thiel, C.C. RomBo, Inorg. Chem.
1992, 31, 4431; W. A. Henmann, R. W. Fischer, M. U. Rauch, W. Scherer, J. Mol.
Catal. 1994, 86, 243.
[4] R. W. Fischer, Ph.D. Thesis, Technische Universitat Munchen, 1994.
[ 5 ] W. A. Herrmann, R. M. Kratzer, R. W. Fischer, Angew. Chem. 1997, 109, 2767; Angew.
Chem., bit. Ed. 1997, 36, 2652.
[6] R. Kratzer, Ph.D. Thesis, Technische Universitlt Munchen, 1998.
[7] F. E. Kuhn, R. W. Fischer, W. A. Henmann, Chem. Unserer Zeit, 1999, 33, 192.
[8] Further information on MTO and its uses are available at the author’s homepage under
the following Internet address: http://aci.anorg.chemie.tu-muenchen.de
[9] W. A. Henmann, R. W. Fischer, M. Groarke, F. E. Kuhn, in: Synthetic Methods of Orga-
nometallic and Inorganic Chemistry (Ed.: W. A. Henmann), Vol. 10, Enke Verlag, Stutt-
gart, 2001.

3.3.14 Acetoxylations and Other Palladium-Promoted or

Palladium-Catalyzed Reactions
Reinhard J i m

3.3.14.1 Historical and Economic Background

Acetoxylations (oxyacylations) have to be seen in context with olefin oxidation to
carbonyl compounds (Wacker process, Section 2.4.1). With the lowest olefin,
ethylene, acetaldehyde is formed. In water-free acetic acid no reaction takes
place. Only in the presence of alkali acetates - the acetate ion shows higher nu-
cleophilicity than acetic acid - ethylene reacts with palladium salts (eq. (1)) to
give vinyl acetate, the expected product, as first reported by Moiseev et al. [l].
Stem and Spector [2] independently used [HP04]*- as base in a mixture of iso-
octane and acetic acid. This reaction could be exploited for a commercial process
to produce vinyl acetate and closed the last gap replacing acetylene by the cheaper
ethylene, a petrochemical feed material, for the production of large-tonnage
chemical intermediates.

H2C=CH2 + Pd2+ + CH&OO- - @o k + Pd + H+ (1)

The industrial and scientific success of these two reactions initiated a boom in
palladium chemistry which is still continuing.

3.3.14.2 Chemical Background

Acetoxylation of olefins according to eq. ( 1 ) is an oxidative reaction which can
be widely applied. However, it does not occur in such a distinct manner as olefin
1324 3.3 Special Products

oxidation in aqueous solution. Depending on reaction conditions, diverse primary

and secondary by-products arise. Thus, a main by-product in vinyl acetate syn-
thesis is ethylidene diacetate; this has been shown to be a primary by-product,
since with CH,COOD as a reactant the product does not contain any deuterium
[3] . This would not be the case if deuterated acetic acid adds to vinyl acetate
in a secondary reaction. Glycol mono- and diacetates are found in the presence
of a large amount of lithium nitrate [4] and nitric acid [5].
With higher olefins the product distribution becomes more variable. Not only
the expected enol acetates but also allylic acetates are formed. Thus, propene
forms isopropenyl acetate along with some n-propenyl acetate and ally1 acetate
[6, 71. Higher and cyclic olefins react to form mainly allylic esters [8-181; more-
over pre-isomerization of the olefins give rise to an even broader spectrum of
products. The results published differ from each other, probably because of differ-
ent reaction conditions and composition of reaction mixtures.
Quite analogously to the olefin oxidation in aqueous medium, acetoxylation
of olefins can also be carried out catalytically by addition of oxidants such as ben-
zoquinone [ 11 , cupric chloride, and cupric acetate (a survey of the patent literature
has been given by Krekeler and Schmitz [19] and Miller [20]) which oxidize the
metallic palladium to the active oxidation state Pd" (eq. (2)). Cuprous chloride
is reoxidized by oxygen (eq. (3)) and the overall reaction according to eq. (4)
becomes catalytic.

Pd + 2CuC12 - PdCl2 + 2CuCl (2)

2CuCl + 2HCI + -
'/202 2CuC12 + H20 ( 31

HpC=CH2 + PdC12 + CH3COOH

H3CCOONa - 6 0k+
0
Pd + 2HCI
(14
0
PdCIp, CuC12, H3CCOONa * +
H2C=CH2 + CH3COOH + '/202 H20

Since water is formed in this reaction, acetaldehyde is also a by-product. It

can arise (1) directly according to olefin oxidaton (Wacker process), (2) through
hydrolysis of vinyl acetate which occurs very easily in the presence of PdC12,
or - rather unlikely - (3) through an interaction of vinyl acetate with acetic
acid in the presence of palladium chloride, a reaction according to eq. ( 5 ) and
published by Clement and Selwitz [21] forming acetaldehyde and acetic an-
hydride.
0
Ao- + CH3COOH - PdCIp
-0 +AoA
0 0
(5)
 3.3.14.3 Kinetics and Mechanism 1325

In vinyl acetate synthesis in the presence of cupric chloride according to

eq. (4), other by-products are mono- and diacetates of glycol and /l-chloroethyl
acetate which under certain conditions become the predominant products
[22]. In order to avoid side reactions, chloride-free catalyst systems such as
Pd11/HgPMo6V6040 have been described [23].
For the commercial production of vinyl acetate, a procedure with a heteroge-
neous fixed-bed catalyst is exclusively applied today. The catalysts usually consist
of palladium salts, mostly the acetate, or palladium metal together with alkali
acetate supported on a carrier such as alumina, silica, or carbon without any addi-
tional oxidant. This process avoids the formation of larger amounts of by-prod-
ucts. Thus, from ethylene vinyl acetate and from propene, ally1 acetate is obtained
exclusively.

3.3.14.3 Kinetics and Mechanism

3.3.14.3.1 Homogeneous Reaction

Kinetic investigations have been carried out in the presence and absence of
chloride. They seem to give a somewhat confusing picture of the mechanistic
features of this reaction. However, some details also show certain similarities
with the kinetics of the Wacker reaction in aqueous medium.
If eq. (6), derived by Ninomiya et al. [24] by studying the reaction of ethylene
with palladium chloride in a mixture of acetic acid and p-xylene, is transformed by
replacing [NaOAc] with l/[H+], it adopts the form of eq. (13) of Section 2.4.1
[25], showing an activating or an inhibiting effect of H’ ions at low or higher
H’ concentrations, respectively. A similar behavior of C1- ions, also shown in
the equation mentioned, was observed by van Helden et al. [26]. Clark et al.
[27] published a rate equation (eq. (7)) quite similar to that of the Wacker reaction
in aqueous system (see eq. (9) in Section 2.4.1).
-d LC2H.d k [PdCI2] [HOAc]’ [NaOAc] [C2H4]
- (6)
dt 1 + K [NaOAcI2

-d [c2H41 k [Pd(ll)] [LiOAc] [CZH~]

- (7)
dt [LiCI]1-2

Other authors found other rate expressions. Thus, Moiseev et al. [28] found
at high sodium acetate concentration a dependence according to eq. (8): while
sodium acetate accelerates the reaction at low concentration (also found by Grover
et al. [29]). They interpreted the activation by sodium acetate in terms of the
formation of a mononuclear Pd complex from polynuclear palladium chloride
according to eqs. (9) and (1 0).
-d [c2H41 k K “a2Pd(OAc)41 [C~HI]
-
dt [NaOAcI2 (8)
1326 3.3 Special Products

Pd,CI2, + n NaOAc === Na2Pd2C14(OA~)2 (9)

AcO,
CI
/ \ ,CI
CI’ Pd\ c I / p d ~ O A ~

1 2-
+ 2 ACO- - 2 [PdC12(0Ac)2I2-

For a possible mechanism most authors assume an acetoxypalladation step after

complexing of the olefin analogous to the reaction in aqueous medium (eq. (1 1)
with X = C1-, OAc-, solvent).

CH2
-[
+PdX3
b H *1 1- + ACO- AcO%PdX3]
2
2- (11)

A trans attack, i.e., an attack of the acetoxy anion from the solution, is as-
sumed [30] but a cis attack, i.e., a ligand insertion, cannot be excluded since
trans attack has been proven with a cyclic olefin consisting of a rigid skeleton;
but this is not typical for linear olefins, and the above interpretation of the ac-
tivation by sodium acetate [27] would make some sense with two coordinated
acetate ligands of which one would be in a cis position relative to a coordinated
olefin.
Vinyl acetate is formed by a j3-elimination of a hydridopalladium moiety (Struc-
ture 3). which was the first step of the hydride shift in the acetaldehyde mechan-
ism (eq. (12)) (Section 2.4.1).
1 -

[ Aco-Pdx3] 2-

2
3

f i +~ ~+
Pd + HX X- ~
Extraction of a hydridopalladium moiety by ,&elimination is a common step in
many palladium-catalyzed sequences of reactions.
Hydride shift, as in olefin oxidation in aqueous medium, forming carbonyl
compounds (see eq. (20) in Section 2.4.1) is completed under conditions in
which, instead of vinyl compounds, ethylidene diacetate or acetals are formed,
since using deuterated acids or alcohols, e. g., AcOD or ROD, the respective prod-
ucts do not contain any deuterium [3] . According to eqs. (13) and (14) with R =
OAc-, 0-alkyl-, the step leading to these products can be interpreted as reductive
elimination.
 3.3.14.3 Kinetics and Mechanism

4
3a

For the formation of glycol derivatives such as glycol mono- and diacetates
and 1-acetoxy-2-chloroethane, the initial acetoxypalladation complex 2 might
be the key intermediate. The diacetate may arise out of this complex through a
@-elimination together with a coordinated acetate. As this reaction preferably
occurs in the presence of nitrates and nitrites, coordinated nitro groups may assist
[ 5 ] . For the monoacetate a less simple route has to be assumed as, surprisingly,
with an 'XO-labelednitrocomplex the "0 appears exclusively in the acetate group
of the monoester [31]. An acetyl group shift via the nitro ligand has been pro-
posed. 1-Acetoxy-2-chloroethaneis formed in the presence of a high excess of
cupric chloride [22]. A bi- or oligonuclear Pd-Cu cluster may be responsible
(see also the formation of 2-chloroethanol in aqueous medium described in Sec-
tion 2.4.1.5.1).

3.3.14.3.2 Heterogeneous Reaction

Commercial production of vinyl acetate is nowadays carried out in the gaseous
phase with a fixed-bed catalyst. A mixture of acetic acid, ethylene and oxygen
is led over a catalyst consisting of palladium acetate or paladium-metal and alkali,
mostly potassium acetate, and occasionally some activating metals such as gold or
others on a carrier such as silica, alumina, or active carbon. The question is
whether the reaction takes place in a pure heterogeneous phase or as a homo-
genous catalysis in a heterogenized liquid phase on the surface or in the pores
of the carrier. Some authors assume the first case and give proof for this assump-
tion [32-341. Thus Davidson et al. [33] reached this conclusion from the fact that
with higher olefins allylic esters are formed exclusively. From an initial-rate
kinetic study [34] a mechanism with hydrogen abstraction from absorbed ethylene
and acetic acid followed by combination of the radicals and of the absorbed
hydrogen with activated oxygen has been proposed. Carbon dioxide, the main
by-product, should be formed mainly by oxidation of acetic acid. At least this
fact contradicts the findings with the commercial process, where a yield of
99% with respect to acetic acid has been obtained while C 0 2 formation is
7-14% with respect to the carbon feed (see Section 3.3.14.4).
Others [35-381 assume a principally liquid-phase reaction on the carrier,
although their kinetic investigations are less helpful to prove this assumption.
1328 3.3 Special Products

Some experimental hints, however, give more information. Thus, finely divided
palladium metal is readily oxidized under the reaction conditions by oxygen in
the presence of acetic acid, even in the absence of any additional oxidant
(eq. (15)) [27, 391.
Pd + 2ACOH + '1202 + Pd(0Ac)p + H20 (15)
Accordingly, whether the original catalyst is metallic or a bivalent salt, it will
adopt the same configuration after some time. The effect of additional activators
such as gold is to prevent agglomeration of the palladium metal, which would
gradually deactivate the catalyst. Even chloro compounds, which to a great extent
inhibit the gaseous-phase reaction completely, activate in trace amounts [40], and
it can be assumed that they facilitate the oxidation of palladium into the bivalent
state. A study on the selectivity of vinyl acetate formation [38] shows that for the
formation of vinyl acetate and carbon dioxide, the main by-product, two different
active centers of the catalyst are responsible. Only a recent investigation on the
role of acetic acid in this reaction [41] showed the likelihood that Pd" is the active
species of the catalyst.
If for this gas-phase reaction the contemporary presence of a palladium"
species, acetic acid, alkali acetate, ethylene, and oxygen is necessary, a classical
heterogeneous catalysis seems to be rather unlikely; preferably a sequence of
single reactions, as in the homogeneous phase, has to be assumed. This could
occur within the acetic acid film adsorbed on the carrier. Thus vinyl acetate
formation in the gas-phase might occur according to eq. (lb) (M = Li, Na, K)
and the overall reaction follows eq. ( I 6).
AcOH, AcOM
HzC=CHz + Pd(OAC)2 * /'oA~ + AcOH + Pd (1b)

H2C=CHp + AcOH + '/202

Pd(OAc)z, AcOH, AcOM
- e O A c + H20

(16) = (Ib) + (15)

3.3.14.3.3 Allylic Oxidation
This reaction describes the entrance of a nucleophile into the allylic position of an
olefin. In aqueous medium this reaction is of minor importance but in nonaqueous
medium, particularly under the conditions of acetoxylation, it attracts broad inter-
est. As already mentioned above and outlined later (see Section 3.3.14.6), higher
and cyclic olefins give exclusively allylic esters. Two mechanisms have been
proposed. One possibility is according to eq. (17) hydride abstraction through
the palladium of an oxypalladation moiety by P-elimination from the adjacent
C-atom which had not been added to the nucleophile [9].

OAc
 3.3.14.4 Commercial Processes 1329

The other route includes a n-allylpalladium intermediate according to

eq. (1 8). n-Ally1 complexes can be obtained from olefins, preferably branched
at the double bond. Their formation is often supported by a base for proton ab-
straction [42-44].
CHR" /cI, CHR"
2 R Y R " + 2 PdC12 -+ R@<(-Pd Pd-)kR' + 2HCI (18)
R' CHR 'CI/ CHR

n-Ally1 complexes are also formed from 1,3-diolefins [45], from allyl halides
[46-48], and from allyl alcohol [44, 491. By the latter reaction Hafner and co-
workers [44] obtained the first n-ally1 complex of palladium and firstly described
the n-allylic bond as a three-hapto, four-electron bond if the palladium is assumed
to be in the oxidation state Pd".
n-Ally1 palladium complexes react with nucleophiles to give allylic com-
pounds, e. g., according to eq. (19):

CHR" /cI,
R'<(-Pd
CHR 'CI/
Pd
CHR"
-))-
CHR
R'

c R

R'
G

+:
R"
R'

This route shows a possible intermediate from which the allylic product is
O

obtained by reductive elimination. Also, for the formation of allyl acetate in the
A

CI

OAc
C + Pd + CI-

(19)

palladium-catalyzed gas-phase oxidation of propene, a n-allylic species on the

catalyst surface has been proposed [35]. n-Ally1 complexes of various metals
have been synthesized in recent years. For many catalytic reactions they are
assumed to be intermediates [50-531.

3.3.14.4 Commercial Processes

3.3.14.4.1 Vinyl Acetate

Vinyl acetate is the basis of a broad spectrum of polymers and copolymers mainly
used as emulsions for adhesives, paints, concrete admixtures, coatings, and bind-
ing agents for paper, textiles, etc.
Thus, immediately after the publication by Moiseev et al. [ 11 (cf. Section 2.4.2),
many industrial laboratories focused their research activities on development of
1330 3.3 Special Products

a commercial vinyl acetate manufacturing process quite analogous to the liquid-

phase Wacker acetaldehyde process. Commercial plants have been operated by
1C1 (UK), Celanese (USA), and Tokuyama Petrochemical (Japan) [54], but they
have been shut down already. Not only the large number of by-products -
acetaldehyde is the main one because of the water formed during the catalytic
reaction according to eq. (4) - but evidently enormous corrosion problems
might have been the reasons for this, since titanium (the construction material
in the Wacker process) is not stable against the corrosive cupric chloride in non-
aqueous media.
More than 80% of the world's capacity of vinyl acetate is now produced by
gas-phase technology. Hoechst/Bayer [55-571 and National Distillers Products
Corporation [58] have developed their respective processes.
Although recent literature gives evidence for a homogeneous reaction on
the catalyst surface (cf. Section 3.3.5.3.2) the commercial processes show typical
features of heterogeneous catalysis and do not comply with the definition of
homogeneous catalysis given in the preface. Therefore a description of the
manufacturing process is not included here but it is dealt with in [59].

3.3.14.4.2 Allyl Acetate

Allyl Acetate can be a starting material for polymers as a comonomer, for glycidyl
acetate as a component of epoxy resins, for glycerol, for allyl alcohol by hydro-
lysis, and for the synthesis of allyl esters of higher acids or other compounds
by transesterification or transallylation. Processes for the commercial production
of allyl acetate have been developed by Bayer and Hoechst [60], and some
Japanese companies. Such processes work in the gas-phase under similar condi-
tions to those used in vinyl acetate manufacture and are currently operated by
Showa Denko and Daicel [61].

3.3.14.4.3 1,4-Diacetoxy-2-Butene
Butene- 1,4-diol is obtained by hydrolysis of 1,4-diacetoxybutene and is an
intermediate for the production of tetrahydrofuran, pharmaceuticals, terpenes,
polyesters, etc. [62, 631. According to eq. (20), 1,4-diacetoxybutene is formed
by acetoxylation of butadiene over a palladium catalyst.

Pd" Pd AcO
+ 2AcOH + 0 2 A
- H20 -0Ac

This reaction has been commercialized by Misubishi Kasei Corporation

[61, 62, 641 using a Pd-on-carbon catalyst activated by tellurium in the liquid
phase.
 3.3.14.5 Transvinylation 1331

3.3.14.5 Transvinylation
Vinyl compounds undergo acetoxylation or generally oxyacylation with replace-
ment of the nucleophile of the vinylic compound by the entering carboxylic
group (eqs. (21) and (22)). Thus, vinyl chloride gives vinyl acetate with acetic
acid in the presence of palladium chloride [65, 661.

If vinyl esters react with carboxylic acids, an equilibrium between the two vinyl
esters is of course obtained [67]:

It has been shown that it is the vinyl group that is transferred in this reaction,
not an alcoholic one as in acid- or alkali-catalyzed transesterification of esters with
saturated alcoholic components. With "0-labeled acetic acid in the transvinyla-
tion of vinyl-propionate, the labeled oxygen remained completely in the acetate
group [68].
This reaction gained technical importance for the synthesis of vinyl esters of
higher carboxylic acids [69-721. Thus, divinyl adipate is now produced by
Wacker-Chemie from adipic acid and vinyl acetate.
Alkyl-substituted vinyl groups such as iso- and n-propenyl groups can be
transferred in the presence of palladium salts [68, 731. The new group enters
exclusively at that carbon atom to which the leaving group is bound.
Transvinylation occurs stereospecifically, but a difference between vinylic
esters and chlorides has been observed. While the transvinylation of n-propenyl
esters is accompanied by an inversion of the geometric configuration (i.e., the
cis starting ester results in a trans product and vice versa [68]), in the case of
the corresponding chlorides the resulting esters retain their configuration
[50, 741. This can be explained in the first case by a cis addition (cis-carboxy-
palladation) and cis elimination or trans addition and trans elimination, and in
the second case by a trans addition and cis elimination or vice versa. It cannot
yet be decided which of the two versions would in fact occur. But if it is assumed
that cis-elimination is the most likely route in both cases the acetoxypalladation
(addition) must be trans (Anti) in vinyl transfer from vinyl chloride and cis
(syn) in that from vinyl esters. syn-acetoxypalladation was also found in addition
to chiral allylic alcohols [75]. These findings prove that in Wacker-type reactions
both cis (syn) and trans (anti) addition reactions are possible, depending on sub-
strates and reaction conditions.
The vinyl group can also be transferred to alcohols to form vinyl ethers
starting from vinyl chloride [66], vinyl esters [76], and vinyl ethers [77].
The transfer to water corresponds to a hydrolysis which readily takes place
with all vinylic compounds in the presence of palladium salts to form acetal-
dehyde [78].
1332 3.3 Special Products

3.3.14.6 Acetoxylation in Organic Synthesis

Acetoxylation is a valuable method for the introduction of an OH group into
organic compounds, which can be used for further syntheses. In Section
3.3.14.2 it has been mentioned that acetoxylation of higher and cyclic olefins
with palladium salts, or catalyzed by palladium salts or metal, mostly leads to
allylic derivatives. This also takes place in the catalytic acetoxylation of terpenic
olefins [79, SO].
In the presence of nitrates [4, 811, palladium nitro complexes [5, 311, and with
different oxidants, glycol derivatives are produced according to eq. (23):

CHz=CHz + oxidant + AcOH % -0Ac (23)

A survey of this reaction is given by Henry [82]. The oxidants include K2Cr207,
NaN02, CuBr,, MnO,, Pb(OAc),, etc. Ferric and molybdic salts and others are
inactive; they are more suitable as oxidants in monoacetoxylation of olefins,
e. g., to form vinyl acetate. Although 1-acetoxybutadiene was found in the reac-
tion of butadiene with PdC12 [2], in the presence of oxidants generally linear
[83-861 and cyclic 1,3-diolefins [87] undergo diacetoxylation to form 1,4-diace-
toxy-2-enes with homogeneous and heterogeneous palladium" and metal
catalysts. This reaction occurs regio- and stereospecifically, as could be proven
with cyclic 1,3-dienes [88].
In the presence of LiC1, palladium acetate catalyzes the regio- and stereospeci-
fic 1,4-acetoxychlorination of linear and cyclic 1,3-dienes. The oxidant is benzo-
quinone (eq. (24)) [89].

w+()-d 0

OAc
0-

(24)

0 0-

Examples of the use of 1,4-addition products in organic synthesis have been

given by Backvall [90, 911.
Acetoxylation of aromatics (eq. (25)) was first carried out by Davidson and
Triggs [92] to produce phenyl acetate, which could give rise to the development
of a new phenol synthesis. The formation of phenyl acetate is accompanied by the
formation of biphenyl (see Section 3.3.14.7.2). In the presence of oxidants such as
Pb(OAc),, NaNO,, NaN03, KMn04, K,CrO, [93] and P-Mo-V heteropolyacids
[94], phenyl acetate is the main product. The favored ring acetoxylation with high-
oxidation-state Pd catalyst over dimerization with low-oxidation-state catalyst has
recently been confirmed [95]. With toluene, probably in an allylic-like oxidation,
benzyl acetate is obtained [92].

8 + Pd(0Ac)P AcoH,AcoNa-

Q+ Pd + AcoH
(25)

OAc
 3.3.14.7 Other Palladium-Promoted or Palladium-Catalyzed Reactions 1333

3.3.14.7 Other Palladium-Promoted or

Palladium-Catalyzed Reactions

3.3.14.7.1 Alkoxylations
Reactions of olefins with alcoholic solutions of palladium salts lead mainly to
acetals or ketals [93] (eq. (26) with R = H, alkyl; R' = alkyl).

PR
+ 2R'OH + PdX2 JoxRR'+ Pd + 2 HX

Corresponding vinyl ethers are formed only to a minor extent. Their formation
can, however, be favored by diluting the reaction mixture with an inert solvent [2].
With glycols, cyclic acetals are obtained, e. g., dioxolanes from I ,2-glycols and
1,3-dioxanes from 1,3-glycols [97]. This reaction has been claimed as an alter-
native to the Wacker route producing acetaldehyde when it is carried out in the
presence of suitable oxidants.
Acetals or ketals respectively are primary products since, quite analogously to
the formation of ethylidene diacetate in the acetoxylation of ethylene with ROD,
only deuterium-free acetals or ketals are obtained [3]. The mechanism ought to be
analogous, too (cf. Section 3.3.14.3).

3.3.14.7.2 Oxidative Coupling

C-C coupling of aromatics is catalyzed by Pd(OAc), in the presence of sodium
acetate (eq. (27)) [98].

Biphenyls are also by-products of acetoxylation of aromatics [92]. Their

formation is favored with a palladium metal catalyst in the absence of oxidants
[93-951. Vinyl acetate undergoes oxidative coupling under similar conditions to
form 1,4-diacetoxy-1,3-butadiene [99], and aromatics and heterocycles can sub-
stitute an olefinic H-atom [IOO] according to eq. (28) (with X = H, CN, AcO,
EtO) [loo-1021.

+ Pd(0Ac)z + 2AcOH + Pd (28)

R R' R R'

(see also Section 3.1.9 and Heck reaction, Section 3.1.6).

Pd(OAc):, also activates aromatic hydrogen atoms for non-oxidative addition to
alkenes and alkynes [103, 1041.
1334 3.3 Special Products

3.3.14.7.3 Catalytic Coupling Using Organometallics

Main-group organometallics such as those of Li, Mg, Sn, Pb, T1, Hg, etc., react
with olefinic compounds and palladium(I1) compounds to give coupling products
according to the general scheme in eq. (29):

The organometallics can be derived from aliphatics and aromatics, even func-
tionalized ones; the olefinics also show a broad spectrum in their applicability.
Heck [105-1071 studied this reaction extensively with M = Hg. With oxidants
like CuC12 the reaction can be carried out catalytically. It is now known as the
“Heck reaction”. Special applications are referenced in [ 108-1 121; see also Sec-
tions 2.1.2 and 3.1.6.

3.3.14.7.4 Oxidative Carbonylation (Carboxylation)

This reaction was first published by Tsuji et al. [113], who reacted ethylene with
carbon monoxide in the presence of palladium chloride (eq. (30)).

CH2=CH2 + CO + PdC12 -
benzene
CI
(30)

In acetic acid as solvent, acrylic acid is produced (eq. (31)), accompanied by

some acetoxypropionic acid [ 1141.
AcOH, H20
CH2=CH2 + CO + PdC12 * &COOH + Pdo + 2 HCI (31)

With alcohols, esters are formed. Oxidants like CuC1, render the reaction
catalytic, too (cf. Section 2.1.2.5).
Similarly, aromatic [ 115-1 171 and even aliphatic [ 1 18, I 191 compounds are
carboxylated catalytically to give aromatic and aliphatic carboxylic acids respec-
tively with carbon monoxide and oxidants such as K2S208,t-BuOOH or O2 in the
presence of palladium acetate, copper acetate and trifluoroacetic acid. Acetic acid
has also been obtained in high yield by carboxylation of methane with CO in the
presence of VO(acety1acetonat0)~[120] and CaC1, . H 2 0 [121] as catalysts, and
oxidants like K2S,0, and trifluoroacetic acid. Excitingly, aromatic 11221 and
aliphatic compounds such as methane [ 1191 react under similar conditions with
carbon dioxide also to give the respective carboxylic acids. These reactions are
evidently promoted by a simultaneous aromatic and aliphatic C-H bond
activation through the transition metal compound.
 3.3.14.7 Other Palladium-Promoted or Palladium-Catalyzed Reactions 1335

3.3.14.7.5 Dimerization
The dimerization of olefins catalyzed by noble metal compounds is a non-oxida-
tive reaction (eq. (32)). It takes place in the absence of any other reactant and often
accompanies other reactions [78].
PdCl
2 C H 4 H 2 ---% (32)

Cramer studied the mechanism using Rh compounds [123, 1241. The linear
dimerization of acrylonitrile in the presence of hydrogen and a ruthenium catalyst
to form 1,4-dicyano-l-butene [ 125-1271 received much interest in industrial
laboratories, mostly in Japan, so a large number of patents have been filed, in
some of which palladium catalysts have also been claimed. The above compound
can be hydrogenated to give the industrially important adipodinitrile and hexa-
methylene diamine.

3.3.14.7.6 Telomerization
Telomerization is the functionalization of olefins simultaneously with oligomeri-
zation, e. g., eq. (33) (cf. Section 2.3.5) [128, 1291.

+ AcOH Pd(OAc)2/PPhs*
- ' OAc' d
OAc

/
(33)
Telomerization with other nucleophiles, such as OH-, or through carbonylation
has also been described.

3.3.14.7.7 Double-Bond Shift (Isomerization)

Non-oxidative isomerizations often occur when olefinic compounds react with
noble metal compounds, e. g., in Wacker oxidation of higher olefins. An example
is found in the oxidation of 1-octene where octane-2-, 3-, and 4-ones are formed,
in this example with an immobilized Pd" catalyst [ 1301. A plausible mechanism
with a hydridorhodium species as catalytically active moiety has been described
by Cramer [131].
In another example substituted ally1 alcohols undergo non-oxidative double-
bond shift if there is no labile coordination site available for the hydride trans-
fer. Isomerization is explained by a reversible hydroxypalladation reaction
[132].
1336 3.3 Special Products

3.3.14.7.8 Skeletal Rearrangement

Skeletal rearrangement takes place, for instance, with vinylcycloalkanes which
react under ring extension taking the vinyl group into the ring to form the respec-
tive enlarged cycloalkenes, e. g., vinylcyclopropane gives cyclopentene [ 1331.
Further examples are listed in [50, pp. 143-146, Table XIII].

3.3.14.7.9 Addition Reactions

Other non-oxidative reactions catalyzed by palladium compounds are addition
reactions e.g., eq. (34). Thus, alcohols easily add to double bonds of olefinic
ketones [ 1341.
0 o 0 ~ 3
R’ bR2
+ ~ 3
PdC12(CH&N)2
0 ~
CH2C12,Ar
(34)

Alcohols and amines add also to acetylenic compounds in the presence of

palladium compounds to form intermediates for syntheses of heterocycles,
e. g., furans and pyrroles [135].

3.3.14.8 Conclusions
This brief listing of reactions, not including oxyacylations, ought to demonstrate
the broad applicability of palladium reagents in synthetic organic chemistry. These
reactions are used in multistep syntheses to produce pharmaceuticals, fragrances,
natural products, etc., and are documented in recent publications. Surveys are
given in many review articles and books [50-53, 136-1481.

References
[l] I. I. Moiseev, M. N. Vargaftik, Y. K. Syrkin, Dokl. Akad. Nauk SSSR 1960, 133, 377.
[2] E. W. Stem, M. L. Spector, Proc. Chem. Soc. (London) 1961, 370.
[3] I. I. Moiseev, M. N. Vargaftik, Izv. Akad. Nauk SSSR, Ser: Khim. 1965, 759.
141 M. Tamura, T. Yasui, Chem. Commun. 1968, 1209.
[5] M. G. Volkhonskii, V. A. Likholobov, Yu. I. Ermakov, Kinet. Katal. 1983, 24, 347, 578;
Kinet. Katal. Engl. Transl. 1983, 24, 289, 488.
161 A. P. Belov, G. Yu. Pek, I. I. Moiseev, lzv. Akad. Nauk SSSR, Ser: Khim. 1965, 2204.
171 I. I. Moiseev, A. P. Belov, Y. K . Syrkin, Izv. Akad. Nauk SSSR, Ser: Khim. 1963, 1527.
[8] A. P. Belov, I. I. Moiseev, Izv. Akad. Nauk SSSR, Ser: Khim. 1966, 139.
[9] W. Kitching, Z . Rappoport, S. Winstein, W. G. Young, J. Am. Chem. Soc. 1966, 88,
2054.
[lo] M. N. Vargaftik, I. I. Moiseev, Y. K. Syrkin, V. V. Yakshin, Izv. Akad. Nauk SSSR, Otd.
Khim. Nauk 1962, 930.
[ l l ] C . B. Anderson, S. Winstein, J. Org. Chern. 1963, 28, 605.
 References 1337

S. Hansson, A. Heumann, T. Rein, B. Akermark, J. Org. Chem. 1990, 55, 975.

St. E. Bystrom, E. M. Larsson, B. Akermark, J. Org. Chem. 1990, 55, 5674.
B. Akermark, S. Hansson, T. Rein, J. Vigberg, A. Heumann, J.-E. Backvall, J. Organo-
met. Chem. 1989,0369,433.
A. Heumann, B. Akermark, S. Hansson, T. Rein, Org. Synth. 1990, 68, 109.
S. Uemura, Sh. Fukuzawa, A. Toshimitsu, M. Okano, Tetrahedron Lett. 1982, 23, 87.
M. Green, R. N. Haszeldine, J. Lindley, J. Organomet. Chem. 1966, 6, 107.
Y. Odaira, T. Yoshida, S. Tsutsumi, Technol. Report, Osaka Univ. 1966, 16, 737; Chem.
Abstr: 1967, 67, 90334.
H. Krekeler, H. Schmitz, Chem.-1ng.-Tech.1968, 40, 785.
S. A. Miller in Ethylene and its Industrial Derivatives (Ed.: S . A. Miller, Ernest Benn),
London, 1969, p. 946.
W. H. Clement, C. M. Selwitz, Tetrahedron Lett. 1962, 1081.
P. M. Henry, J. Org. Chem. 1967, 32, 2575.
I. V. Kozhevnikov, V. E. Taraban’ko, K. I. Matveev, V. D. Vardanyan, React. Kinet.
Catal. Lett. 1977, 7, 297.
R. Ninomiya, M. Sato, T. Shiba, Bull. Jpn. Pet% Inst. 1965, 7, 31.
R. Jira, J. Sedlmeier, J. Smidt, Liebigs Ann. Chem. 1966, 693, 99.
R. van Helden, C. F. Kohll, D. Medema, G. Verberg, T. Jonkhoff, Rec. Trav. Chim. Pays-
Bas 1968, 87, 961.
D. Clark, P. Hayden, R. D. Smith, Disc. Faraday Soc. 1967, 46, 98.
I. I. Moiseev, A. P. Belov, V. A. Igoshchin, Y. K. Syrkin, Dokl. Akad. Nauk SSSR 1967,
173, 863.
G. S. Grover, R. V. Chaudhari, Chem. Eng. J. 1986, 32, 93.
0. S. Andell, J.-E. Backvall, J. Organomet. Chem. 1983, 244, 401.
F. Mares, St. E. Diamond, F. J. Regina, J. P. Solar, J. Am. Chem. Soc. 1985, 107, 3545.
S. Nakamura, T. Yasui, J. Catal. 1971, 23, 315.
J. M. Davidson, P. C. Mitchell, N. S. Raghavan, Front. Chem. React. Eng. 1984, I , 300.
H. Debellefontaine, J. Besombes-VailhC, J. Chim. Phys. Phys.-Chim. Biol. 1978, 75, 801.
T. Kunugi, H. Arai, K. Fujimoto, Bull. Jpn. Pet% Inst. 1970, 12, 97.
S. A. H. Zaidi, Appl. Catal. 1988, 38, 353.
B. Samanos, P. Boutry, R. Montarnal, J. Catal. 1971, 23, 19.
A. Rabl, A. Renken, Chem.-1ng.-Tech.1986, 58, 434.
R. Jira, unpublished results.
Wacker-Chemie GmbH, Hoechst AG (D. Dempf, L. Schmidhammer, G. Dummer,
G. Roscher, K.-H. Schmidt, E. Selbertinger, R. Strasser), EP 48.946 (1982).
St. M. Augustine, J. P. Blitz, J. Catal. 1993, 142, 312.
R. Huttel, H. Christ, Chem. Be%1963, 96, 3101.
R. Huttel, H. Christ, Chem. Be%1964, 97, 1439.
J. Smidt, W. Hafner, Angew. Chem. 1959, 71, 284.
B. L. Shaw, Chem. Ind. (London) 1962, 1190.
R. Huttel, J. Kratzer, Angew. Chem. 1959, 71, 456.
R. Huttel, J. Kratzer, M. Bechter, Chem. Ber: 1961, 94, 766.
R. Jira, J. Sedlmeier, Tetrahedron Lett. 1971, 1227.
W. Hafner, H. Prigge, J. Smidt, Liebigs Ann. Chem. 1966, 693, 109.
R. Jira, W. Freiesleben in Organornetallic Reactions, Vol. 3 (Eds.: E. Becker, M. Tsu-
tsui), John Wiley, New York, 1972.
[51] P. M. Maitlis, The Organic Chemistry of Palladium, Vol. 2, Academic Press, New York,
1971.
1521 P. M. Henry in Palladium Catalyzed Oxidation of Hydrocarbons, D. Reidel, Dordrecht,
1980, pp. 41-223.
1338 3.3 Special Products

[53] J. Tsuji, Organic Synthesis with Palladium Compounds, Springer, Berlin, 1980.
[54] Anon., Eur: Chem. News 1973, 21, 22.
[55] Bayer AG, BE 627.888 (1963).
[56] Knapsack AG, DE 1.244.766 (1965).
[57] Hoechst AG, DE 1.296.138 (1967).
[58] Nat. Distillers, US 3.190. 912 (1962), GB 976.613 (1963).
[59] G. Roscher, E. Hofmann, K. A. Adey, W. Jeblink, H.-J. Klimisch, H. Kieczka, Ullmann ’s
Encycl. Techn. Chem. 4th ed. 1983, Vol. 23, pp. 601-604.
[60] J. Grolig, Ullrnann’s Encycl. Techn. Chern. 5th ed. 1985, Vol. A l , pp. 434436.
[61] I am indebted to Dr. Akio Mitsutani, Nippon, Chemtec Consulting Inc., 665-0022
Takarazuka City, Nogami 3-chome, 11-10, Japan for leaving to me respective chapters
of the evaluation reports of the company.
[62] Mitsubishi Kasei Corp., Chemtech 1988, 759.
[63] H. Pommer, A. Nurrenbach, Pure Appl. Chem. 1975, 43, 527.
[64] Y. Tanabe, Hydrocarbon Proc. 1981, 60, 187.
[65] C. F. Kohll, R. van Helden, Rec. Trav. Chirn. Pays-Bas 1968, 87, 481.
[66] E. W. Stem, J. Catal. 1966, 6 , 152.
[67] J. Smidt, W. Hafner, R. Jira, R. Sieber, J. Sedlmeier, A. Sabel, Angew. Chern. 1962,
74, 93; Angew. Chern. Int. Ed. Engl. 1962, I , 80.
[68] A. Sabel, J. Smidt, R. Jim, H. Prigge, Chem. Ber: 1969, 102, 2939.
[69] Consortium fur Elektrochem. Ind. (J. Smidt, A. Sabel), DE 1.127.888 (1962).
[70] Wacker-Chemie GmbH (K. Blum, R. Strasser), DE-OS 3.047.347 (1982).
[71] A. A. Ketterling, A. S. Lisitsyn, A. V. Nosow, V. A. Likholobov, Appl. Catal. 1990,
66, 123.
[72] F. J. Waller, Chem. Ind. (Dekker) 1994, 53, 397.
[73] Consortium fur Elektrochem. Ind. (J. Smidt, A. Sabel), DE 1.277.246 (1968).
[74] E. W. Stem, Catal. Rev. 1967, I, 73, 125.
[75] 0. Hamed, P.M. Henry, Organornetallies 1997, 16, 4903.
[76] Imperial Chemical Industries (D. Clark, P. Hayden), NL Appl. 6.703.724, DE 1.273.525
(1968).
[77] Imperial Chemical Industries (D. Clark, P. Hayden), DE 1.275.532 (1968).
[78] J. Smidt, W. Hafner, R. Jira, J. Sedlmeier, R. Sieber, R. Ruttinger, H. Kojer, Angew.
Chem. 1959, 71, 176.
[79] L. El Firdoussi, A. Benharref, S. Allaoud, A. Karim, Y. Castanet, A. Mortreux, F. Petit,
J. Mol. Catal. 1992, 72, L1.
[80] L. El Firdoussi, A. Bagga, S. Allaoud, B. Ait Allal, A. Karim, Y. Castanet, A. Mortreux,
J. Mol. Catal. A: 1998, 135, 11.
[81] E. J. Mistrik, A. Mateides, Chern. Technol. 1983, 35, 90.
[82] P. M. Henry, J. Or,. Chem. 1973, 38, 1681.
[83] Kuraray (T. Shimizu, T. Yasui, S. Nakamura), GB 1.368.505 (1974); Chem. Abstr: 1975,
83, 9234a.
[84] Mitsubishi Chem. Ind. (T. Onoda, A. Yamura, J. Toriya, I. Kasahara, M. Sato, N. Ishi-
zaki), JP 74.101.322 (1974); Chem. Abstr: 1975, 82, 8 6 0 8 9 ~ .
[85] Mitsubishi Chemical (T. Onoda, J. Haji), DE-OS 2.217.452 (1972), Chem. Abstr: 1973,
78, 57786a.
[86] BASFAG (H. M. Weitz, J. Hartwig), DE-OS 2.421.408 (1975); Chem. Abstr: 1976, 84,
58665~.
[87] R. G. Brown, J. M. Davidson, J. Chem. Soc. ( A ) 1971, 1321.
[88] J.-E. Backvall, St. E. Bystrom, R. E. Nordberg, J. Org. Chem. 1984, 49, 4619.
[89] J.-E. Backvall, R. E. Nordberg, J.-E. Nystrom, Tetrahedron Lett. 1982, 23, 1617.
[90] J.-E. Backvall, Pure Appl. Chern. 1983, 55, 1669.
 References 1339

[91] J.-E. Backvall, Pure Appl. Chem. 1992, 64, 429.

[92] J. M. Davidson, C. Triggs, J. Chem. Soc. A 1968, 1331.
[93] P. M. Henry, J. Org. Chem. 1971, 36, 1886.
[94] L. Pachkovskaya, K. I. Matveev, G. N. Il’inich, N. K. Eremenko, Kinet. Katal. 1977,
18, 1040; Kinet. Katal. Engl. Transl. 1977, 18, 854.
[95] J. E. Lyons, G. Suld, C. Y. Hsu, Chem. Ind. (Dekker)(Catal. Org. React.) 1988, 33, 1.
[96] I. I. Moiseev, M. N. Vargaftik, Dokl. Akud. Nauk SSSR 1966, 166, 370.
[97] W. G. Lloyd, B. J. Luberoff, J. Org. Chem. 1969, 34, 3949.
[98] R. van Helden, G. Verberg, Rec. Truv. Chim. Pays-Bas 1965, 84, 1263.
[99] C. F. Kohll, R. van Helden, Rec. Trav. Chim. Pays-Bas 1967, 86, 193.
[loo] S. Danno, I. Moritani, Y. Fujiwara, Tetrahedron 1969, 25, 4819.
[loll C. Jia, W. Lu, T. Kitamura, J. Fujiwara, Org. Lett. 1999, 1, 2097.
[lo21 K. Hirota, H. Kuki, Y. Maki, Heterocycles 1994, 37, 563.
[I031 C. Jia, D. Piao, J. Oyamada, W. Lu, T. Kitamura, Y. Fujiwara, Science 2000, 287, 1992.
[lo41 C. Jia, W. Lu, J. Oyamada, T. Kitamura, K. Matsuda, M. Irie, Y. Fujiwara, J. Am. Chem.
Soc. 2000, 122, 7252.
[I051 R. F. Heck, J. Am. Chem. Soc. 1968, 90, 5518.
[I061 R. F. Heck, J. Am. Chem. SOC. 1968, 90, 5535.
[lo71 R. F. Heck, J. Am. Chem. Soc. 1968, 90, 5538.
[ 1081 J. K. Stille, Pure Appl. Chem. 1985, 57, 177 1.
[lo91 R. C. Larock, Pure Appl. Chem. 1990, 62, 653.
[110] S. Cacchi, Pure Appl. Chem. 1990, 62, 713.
[ 1111 E. Negishi, T. Takahashi, K. Akiyoshi, J. Organomet. Chem. 1987, 334, 181 .
[ 1121 A. Suzuki, Pure Appl. Chem. 1985, 57, 1749.
[ 1 1 31 J. Tsuji, M. Morikawa, J. Kiji, Tetrahedron Lett. 1963, 1061.
[I141 D. M. Fenton, K. L. Olivier, Chern. Technol. 1972, 220.
[115] T. Jintoku, Y. Fujiwara, I. Kawata, T. Kawauchi, H. Taniguchi, J. Organornet. Chem.
1990, 385, 297.
[ 1161 Y. Taniguchi, Y. Yamaoka, K. Nakata, K. Takaki, Y. Fujiwara, Chem. Lett. 1995, 345.
[ 1 171 W. Lu, Y. Yamaoka, Y. Taniguchi, T. Kitamura, K. Takaki, Y. Fujiwara, J. Organomet.
Chem. 1999, 580, 290.
[ 11 81 K. Nakata, T. Miyata, T. Jintoku, A. Kitani, Y. Taniguchi, K. Takaki, Y. Fujiwara, Bull.
Chem. Soc. Jpn. 1993, 66, 3755.
[119] M. Kurioka, K. Nakata, T. Jintoku, Y. Taniguchi, K. Takaki, Y. Fujiwara, Chem. Lett.
1995, 244.
11201 Y. Taniguchi, T. Hayashida, H. Shibasaki, D. Piao, T. Kitamura, T. Yamaji, Y. Fujiwara,
Org. Lett. 1994, I , 557.
[121] M. Asadullah, T. Kitamura, Y. Fujiwara, Angew. Chem., Int. Ed. Engl. 2000, 39, 2475.
[ 1221 H. Sugimoto, I. Kawata, H. Taniguchi, Y. Fujiwara, J. Organomet. Chem. 1984,266,C44.
[123] R. Cramer, J. Am. Chem. Soc. 1965, 87, 4717.
[I241 R. Cramer, Acc. Chern. Res. 1968, I , 186.
[I251 A. Misono, Y. Uchida, M. Hidai, H. Kanai, Chem. Commun. 1967, 357.
[126] W. Strohmeier, A. Kaiser, J. Organomet. Chem. 1976, 114, 273.
[127] D. T. Tsou, J. D. Bumngton, E. A. Maher, R. K. Grasselli, J. Mol. Catal. 1985,30, 219.
[I281 J. Tsuji, Acc. Chem. Res. 1973, 6, 8.
[I291 J. Tsuji, Adv. Organomet. Chem. 1979, 17, 141.
11301 H. C. Tang, D. C. Sherrington, J. Mol. Catal. 1994, 94, 7.
[I311 R. Cramer, J. Am. Chem. Soc. 1966, 88, 2272.
[132] J. W. Francis, P.M. Henry, J. Mol. Catal. A: Chem. 1996, 112, 317 and literature cited
therein.
[I331 K. Hiroi, Y. Arinaga, Tetrahedrin Lett. 1994, 35, 153.
1340 3.3 Special Products

11341 T. Hosokawa, T. Shinohara, Y. Ooka, S. Murahashi, Chem. Lett. 1989, 2001.

[I351 K. Utimoto, Pure Appl. Chem. 1983, 55, 1845.
[136] J. Tsuji, Pure Appl. Chem. 1981, 53, 2371.
11371 R. F. Heck, Pure Appl. Chem. 1981, 53, 2323.
11381 R. A. Sheldon, J. A. Kochi, Metal-Catalyzed Oxidations of Organic Compounds,
Academic Press, New York, 1981.
[I391 R. F. Heck, Palladium Reagents in Organic Synthesis, Academic Press, New York,
1985.
[140] R. G. Schultz, D. E. Gross, ACS Adv. Chem. Ser: 1968, 70, 97.
[141] Review on oxidative coupling: E. Negishi, Acc. Chem. Res. 1982, 15, 340.
11421 J. Tsuji, Synthesis 1990, 739.
[143] J. Tsuji, Palladium Reagents, in Znnovation in Organic Synthesis, John Wiley, New
York, 1996.
11441 A. Yamamoto, T. Yamamoto, F. Ozawa, Pure Appl. Chem. 1985, 57, 1799.
11451 M. Catellani, G. P. Chiusoli, M. Costa, Pure Appl. Chem. 1990, 62, 623.
[I461 S. Cacchi, Pure Appl. Chem. 1990, 62, 713.
[147] T. Hayashi, A. Kubo, F. Ozawa, Pure Appl. Chem. 1992, 64, 421.
[ 1481 J. Tsuji, Transition Metal Reagents and Catalists, in: Innovation in Organic Synthesis,
Wiley, New York 2000.
 4
Epilogue
 Applied Homogeneous Catalysis with Organometallic Compounds
Edited by B. Cornils and W. A. Herrmann
Copyright 0 Wiley-VCH Verlag GmbH, D-69469 Weinheim, 2002

4.1 Homogeneous Catalysis - Quo vadis?*

Wolfgang A. Herrmann, Boy Cornils

“The discovery of truly new reactions is likely to be limited

to the realm of transition-metal organic chemistry, which will
almost certainly provide us with additional ‘miracle reagents’
in the years to come.”
D. Seebach
Angew. Chem., Int. Ed. Engl. 1990,29, 1320

The impact of homogeneous catalysis on industrial process technology has grown

since 1960 to the same extent as organometallic chemistry has developed as a
science (cf. Figure 1 in Chapter 1). As a matter of fact, new knowledge regarding
the structure and reactivity of organometallic compounds has, with a certain time
delay, created new catalytic processes in industry or has re-estabilished old cata-
lytic features under improved conditions. Important examples include the replace-
ment of cobalt by rhodium in a number of processes that are otherwise not feasible
industrially (or not as elegantly or economically, e. g., methanol carbonylation and
hydroformylation), which during the 1964-1 976 period caused much scepticism
directed at the recycling of the precious noble metal. Nowadays, ironically, it is
often the price of a more or less sophisticated ligand that dictates the economics
of a new process, while the metals themselves - even rhodium, palladium, or
platinum - are irrelevant in this respect; cf. Table 3 in Chapter 1.
Homogeneous catalysis and organometallic chemistry have stimulated and sup-
ported each other since the early days of hydroformylation (1938), olefin polymer-
ization (1 953), and acetaldehyde synthesis (1 959), to name just the “battleships”
of organometallic catalysis [ 11. While it is certainly true that many epoch-making
discoveries came along by serendipity [2], a typical such case being Karl Ziegler’s
“Metallorganische Mischkutulysatoren” [3], the majority of homogeneous cata-
lytic applications has resulted from continued step-by-step development of indus-
trial laboratory and plant-site research alongside the scientific growth of organo-
metallic chemistry.
This brings to mind the first comprehensive monograph on Die Chemie der
Metullorganischen Verbindungen (The Chemistry of Organometallic Com-
pounds), written by E. Krause and A. von Grosse. It appeared in 1937 [4], shortly
before hydroformylation was discovered. In this 900-page book only a little is
reported on the present-day champions of homogeneous catalysis (e. g., platinum:
three pages and six references), and there is no mention of cobalt, rhodium, and
palladium. What a contrast, when the monumental work entitled Comprehensive

* Homogeneous Catalysis - where now?

1344 4.1 Homogeneous Catalysis - Quo vadis?

Organometallic Chemistry - nine volumes, 8750 printed pages - appeared

45 years later, with the second edition comprising 14 volumes already in print
by 1996 [S]! A total of approx. 30500 organometallic compounds has been
registered by the Chemical Abstracts Service up to the time of writing [6, 71.
The Journal of Organometallic Chemistry was chartered in 1963 and, since
then, has seen over 600 volumes with a total of 25 000 papers on 230 000 journal
pages [8]. Two more key journals - the Journal of Molecular Catalysis and
Organometallics - broadly cover catalytic applications of organometallic com-
pounds [9]. This was why the Preface of this book referred to homogeneous
catalysis as a success story of organometallic chemistry. It is indeed the over-
whelming diversity of structures and reactivities which forms the basis of so
many applications mentioned in this book. Early monographs and reviews have
recognized this interdependence [lo]. No chemistry student leaves university
today without having been introduced to the basic principles of homogeneous cat-
alysis. Nevertheless, heterogeneous catalysis strongly dominates the industrial
scene, where approx. 80 % of all known catalytic processes being heterogeneous
would probably be a good estimate.
Homogeneous catalysis and industry have their own “love affair”: wherever it
appeared economically and technically useful, the advantages of homogeneous
catalysis have been exploited: more than nine million tons each of 0x0 products
[ 1321 and terephthalates, nearly three million tons of acetic acid and anhydride,
and hundreds of thousands of tons of organic feedstocks (acetic aldehyde,
carboxylic acids, w,w ’-dinitfiles, di- and oligoolefins, etc.) are convincing proof
of this. On the way are products of which the potential has been recognized but
markets are still small: they come from partial hydrogenation of unsaturated
aldehydes, amidocarbonylations, copolymerizations of carbon monoxide, hydro-
dimerizations, and the growing number of stereoselective catalytic syntheses.
Of specific potential are several processes which presently experience (or even
surpass) the pilot-plant stage: vinyl acetate from syngas, precursors of polymers
such as polycarbonate and polyurethanes via reductive or oxidative carbonylation,
methyl methacrylates and adipic acid through alternative routes, polypropene and
COCs (cf. Section 4.1.14) by means of metallocenes (cf. Section 2.3.1.5) - new
routes have been opened in all these cases. The last-named example emphasizes
in an almost classical way the principle of tailor-making novel, optimized, homo-
geneous catalysts. Chapter 3 should again be consulted for details.
Numerous scientific and industrial problems of catalysis in general, and
homogeneous catalysis in particular, remain to be solved. Depending on their
viewpoint, objectives, and position, readers will have identified pending problems
- these of a general and those of a specific nature - in every section of this

book. Organometallic catalysis is far from being a mature scientific field. In the
Editors’ opinion (which is shared by a great number of colleagues in industry
and academics), the following key problems of catalysis warrant intensive
research [ 1371.
 4.1.1 Immobilization of Homogeneous catalysts I345

4.1.1 Immobilization of Homogeneous Catalysts

It has been proven in this book over and over again that the strength of organo-
metallic catalysts - activity, chemo-, regio-, and stereoselectivity - result from
this simple concept: specific ligands keep the catalytic metal in a low-nuclearity,
normally mononuclear state of molecularly defined stereochemistry ; at the same
time, these metal complexes participate in dissociation equilibria, thus promoting
the reactivity of the metal center by making appropriate coordination sites avail-
able. While solubility in common organic solvents is an additional advantage in
terms of site availability, it constitutes a severe methodological drawback in
terms of catalyst recycling (cf. the Introduction and Figure 1 in Chapter 1). The
relationships between heterogeneous and homogeneous catalysis are sketched in
Scheme 1, which shows the link between surface organometallic catalysis and
phase transfer catalysis (cf. Sections 3.1.1.1, 3.1.1.4, and 3.2.4).

catalysis organornetallic - heterogeneous

catalysis

catalysis
Scheme 1

The royal road (Kiinigsweg) to overcome the problem is liquid/liquid two-

phase catalysis (cf. Section 3.1.1. I). Here, the catalyst retains its beneficial mole-
cularity, but nevertheless becomes immobilized as such (by forming a second
liquid phase as a “liquid support”). Another approach to facilitating catalystlprod-
uct separation has long been the attachment of the catalyst to a polymeric resin
[ l 11, be it organic (e. g., polystyrene) or inorganic (polysiloxanes). However, no
resin-bound catalyst of industrial - e. g., economic - importance is known: cata-
lyst “leaching” remains the central problem indeed (cf. Section 3.1.1.3). Potent
catalysts such as osmium tetraoxide (for stereoselective cis-hydroxylation of ole-
fins) will not see an industrial plant before a reliable immobilization technique is
available; product contamination, toxicity, and the costs related to insufficient
metal recycling must be mentioned in this context.
The leaching normally results from the dissociation of the metal from one of the
anchored ligands (eq. (1 )), thus liberating the (active) molecular catalyst. Leaching
can also originate from structural changes with concomitant weakening of certain
bonds during the catalytic cycle, where the coordination sphere of a metal under-
goes continuous changes [ 1321.
For this reason, the specific type of bonding between catalyst and support ap-
pears crucial. The disadvantage of leaching has hitherto only been discussed with
regard to the metal centers of catalysts; it is noted, however, that bleeding losses
can also involve expensive ligands, especially those necessary in stereoselective
catalysis. Nevertheless, every possible class of catalysis-supporting ligand should
be considered further for methods of immobilization. N-Heterocyclic carbenes
(eq. (2)) promise a successful approach to the problem: they effect certain catalytic
C-C coupling reactions [12] but, unlike phosphines, they do not engage in disso-
 4.1.2 Colloidal Organornetallic Catalysts 1347

In view of the growing industrial successes, it is suffice to say that two-phase

catalysis (1iquidAiquid) has not yet reached its culmination point [93]. Novel
(water-soluble) ligands pose a challenge to the synthetic chemist. New reaction
media will be required, too, but it seems questionable whether the recently an-
nounced perfluorinated hydrocarbons (cf. Section 3.1.1.2. l), supercritical fluids
(cf. Section 3.1.13), or non-aqueous ionic liquids (cf. Section 3.1.1.2.2) indicate
a true breakthrough in this direction [21]. These studies have shown, however,
that temperature-dependent miscibility of the different reactants and solvents
could be exploited as a simple means of verifying the “single-phase catalysis/
two-phase separation” concept without additional solubilizers. It is to be seen
how the elegant possibility of “re-immobilization’’ (cf. Section 3.1.1.6) can be
exploited for industrial syntheses. There could be a bright future in the combina-
tion of such catalysts with the avantgarde membrane reactors [22].

4.1.2 Colloidal Organometallic Catalysts

Metal colloids - links between homogeneous and heterogeneous catalysts [24, 83,
851 - represent a fairly underestimated group of catalysts, in spite of the fact that
their pre-stage organometallic clusters enjoyed strong scientific interest for some
time (cf. Section 3.1.1.5) [23]. Although oligo- and multinuclear metal aggregates
are subject to degradation (denucleation) under a number of catalytic conditions
(e. g., high-pressure carbonylation) or undergo conglomeration to yield the bulk
metal (e. g., temperature effects, depletion of stabilizing ligands), there is some
evidence that colloidal systems are engaged even in catalysis that is normally
considered “homogeneous” [24, 251. A good example is the long-known hydro-
silylation where low-valent colloidal platinum seems to work best [25 d]. Little
is known as to how conventional ligands and other ingredients stabilize metal
colloids during a given “homogeneous” process. Such knowledge would set the
scene for the directed application of “colloid ligands”. Both the theory of colloids
(formation, structure, stability) and their catalytic performance will clearly form a
center of gravity of future research.
Recent progress has been reported by the groups of Bonnemann, Toshima,
and Schmid [24, 251. Nanometal colloids were generated from metal halides
by reduction with (surfactant) hydridoboranates (e. g., [N(octyl),] [HB(C,H,),]).
Applied on supports, the resulting catalysts are claimed to be of much higher
activity than the currently used (heterogeneous) catalysts. Chiral cinchonidine-
“stabilized” platinum colloids effect the hydrogenation of ketones to alcohols
with conversions of 50-100 % and 69-85 % ee, depending on the particle size
[25e]. Chiral protective shells may induce stereoselective reactions at metal
colloid catalysts and may act, at the same time, as inhibitors of catalyst poisoning.
1348 4.1 Homogeneous Catalysis - Quo vadis.7

4.1.3 Multicomponent and Multifunctional Catalysis

Bimetallic multicomponent and multifunctional catalysis is a common feature in
heterogeneous catalytic processes [26, 271. There is hardly a reaction that just
employs a “pure metal” catalyst. Usually, doping additives exhibit electronic or
steric effects (e. g., Ag-Re/Cs in the Shell oxirane process, a heterogeneous cata-
lysis), and for many conversions intermetallic phases have been developed. It
would once again be attractive to implement this as a concept on the molecular
level into homogeneous catalysis. To become catalytic, numerous reactions
require the activation of at least two substrates by different metals. On the other
hand, a single-site (molecular) catalyst could take advantage of a second metal
nearby (e.g., as an electronic reservoir) to become re-activated. This is not an
easy synthetic problem, since the coordination chemistry of each of the metals
to be coupled for such purposes is normally quite different (e.g., Pd-Cu in the
Wacker-Hoechst oxidation). Beyond that, molecular seats of Lewis and Brgnsted
acidity - like those so crucial for surface-type catalysts (SiOH, A13+)- could be
combined with a catalytic metal site. This topic implies high-risk research from
both the synthetic and the catalytic-mechanistic sides, but is of great methodolog-
ical importance to the future “refinement” of homogeneous catalysts. Literature
does not yet discriminate clearly enough between multicomponent and multifunc-
tional catalyst systems. Multicomponent catalysts contain two or several metals that
enforce the catalytic effect upon a given reaction (e. g., Pt/Sn in hydroformylation).
Multifunctional catalysts effect different reactions (e. g., simultaneous or subse-
quent oligomerization combined with hydroformylation; cf. Section 3.1 S ) .

4.1.4 Stereoselective Catalysis

It is an undisputed fact that the homogeneous catalysis of the future will have its
greatest strength of versatility in stereoselective synthesis. The chiral-drug market
of the world was estimated for 1994 to comprise a sales total amounting to US$
45.2 billion, which corresponds to an increase of 27 % in one single year. An an-
nual growth of ca. 9 % has been predicted for the near future, only including drugs
that have already been approved by drug authorities worldwide [28]. Among these
products, the leading anti-inflammatory drug (S)-(+)-ibuprofen alone is expected
to have a sales potential of US$ 1 billion per year as an over-the-counter drug. It is
remarkable to see that only 11 % of the chiral pharmaceuticals introduced before
1983 were produced in the single stereoisomeric form; this fraction increased to
26 % for synthetic drugs introduced from 1983 to 1987, and there is a conservative
estimate that now 80% of all chiral pharmaceuticals will be produced optically
pure [29, 961.
This implies an enormous challenge to stereoselective synthesis as a major
branch of “applied homogeneous catalysis”. At the same time, the organic
synthesis of tomorrow will be governed by the “chiral selection principle” [30].
Optically stable ligands - in addition to phosphines and others - will continue
to be targets for the synthetic organic and organometallic chemist [31]. Once
 4.1.4 Stereoselective Catalysis 1349

again, immobilized and surface-anchored catalysts are in high demand, not only
for toxicity reasons. Chiral modification of (metal) surfaces seems to bring
about stereoselectivity [32], again an area of hitherto little emphasis. It looks as
if bidentate ligands of axial chirality (atropisomers) will dominate future develop-
ment, at least in the area of the ubiquitous organophosphines. The prototype
BINAP (Structure 1) [33a] is being succeeded by a number of related systems,
of which enantiopure BINAS (2) [33b] and BINAPHOS (3) [33c-g] seem to
solve even the notoriously difficult problem of enantioselective hydroformylation
[95I.
The area of (chiral) NIO-oligodentate ligand synthesis - see, for example, the
known Structures 4-6 - also merits future attention. Smart ideas are required
because these ligands become more and more sophisticated [34]. Logically,
N/O-ligands are more resistant to oxidation than phosphines, one of the reasons

PAr2

S03Na
Ar = C6H4-m-S03Na
(-)-BINAP (-)-BINAS R,S-BINAPHOS
1 2 3

R3

R2= ~ 0 c 8 H " " R3 = -C(CH&OH

But
5 6

n
1350 4.1 Homogeneous Catalysis - Quo vadis?

why tetradentate salicylaldimine derivatives like 7 prove so successful in stereo-

selective epoxidation [35, 361 (cf. Sections 2.4.3and 2.9). High optical inductions
are also seen for Cu"- or Co"-attached semicorrin and Schiff-base ligands in olefin
cyclopropanation reactions with diazoalkanes [37] (cf. Section 3.1.7). This work
has opened new access to insecticides (permethrin) and drugs (Cilastatin@by
Sumitomo). It seems that rigid ligands in an equatorial arrangement around the
metal are particularly efficient in chirality transfer.
Ligands from the "chiral pool" have previously been underrepresented inboth
coordination chemistry and stereoselective catalysis, e. g., sugars, cyclodextrins,
and amino and nucleic acids. Furthermore, almost nothing is known about orga-
nometallic chemistry in biological systems such as cells.
Of particular interest is the phenomenon of so-called chirality amplification,
where a chiral ligand of low optical purity yields products of high enantioselec-
tivity. For example, a 95 % ee alcohol forms from the achiral substrates benzalde-
hyde and diethylzinc when some (-)-DAIB ((-)-3-exo-(dimethylamino)borneol)
as all-organic catalyst of only 15 % optical purity is present (eq. (3)) [37 a, b].

97 % yield
2 95 Yo ee

N7
' O H
I\N (S) -isomer
low enrichment (2 %)
B
N'7
N
O (S) -isomer
H
high enrichment (+ 89 O h )

Y
N H
' B JI
znf( U-LII

N
chiral catalyst B
N+ N

pyrimidine-5-
carboxaldehyde
 4.1.5 Metals from Stoichiometric Reactivity to Catalytic Efliciency 135 1

This is a case where chiral and achiral metal complexes compete with each
other (> 600: 1 by rate). Asymmetric autocatalysis is certainly an attractive, yet
still largely unexplored field. Two-phase processes for stereoselective syntheses
are under investigation [38], and phase transfer catalysis must be mentioned in
this context.
A recent convincing case of chiral amplification opens a wide horizon in
stereoselective catalysis [37 c] : thus, when a 5-pyrimidyl alcohol with a small
(2 %) enantiomeric excess is treated with diisopropylzinc and pyrimidine-5-
carboxaldehyde, it undergoes an autocatalytic reaction to generate more of
the alcohol. The chiral catalyst is formed from the initial alcohol. The ee result
of the (S)-isomer was successively increased in the series 2 % + 10 % + 57 %
+ 81 % + 89 %. Amplification factors of up to ca. 1700 were recorded with
the catalytic system of Scheme 2 [37c]. This is the first case in which the
enantiomeric excess of the product is greater than that of the chiral catalyst
[971.

4.1.5 Metals from Stoichiometric Reactivity

to Catalytic Efficiency
Almost every new synthetic procedure in organic chemistry includes a metal-
mediated step. However, most of these metal-containing reagents suffer from
only working stoichiometrically, so that a “true catalysis chemist” would not
count them in his area of research. One typical example is the cobalt-mediated
Pauson-Khand reaction which makes cyclopentenones as useful synthetic build-
ing blocks available from cheap precursors (Section 3.3.7). Metals that were pre-
viously unheard of in organic synthesis now effect synthetic steps with good
yields and perfect selectivities: niobium(III), for example, N-C-couples aldehydes
with imines or alkynes [39]; samarium(I1) iodide is a selective one-electron
reductant that C-C-couples keto compounds [40, 411. It is a challenge to sur-
round these metals with ligand spheres so as to make their individual reactions
catalytic (i.e., 4 1 mol % of catalyst). The titanium-mediated McMuny reaction
to synthesize olefins from keto compounds needs further improvement in terms
of catalytic applications (Section 3.2.12). Immobilization techniques such as
sol/gel entrapment [16, 171, use of templates [17, 761 and hostlguest relationships
[18, 84, 851, and molecular recognitions [18, 19, 77, 851 promise success in this
area, too.
Great potential is seen in the relatively little-explored organic chemistry of the
rare earth metals (cf. Section 3.2.5), where a tuning of reactivity seems most
feasible because of the gradation of properties within the lanthanoids. Normally,
the “tuning” in organometallic catalysis works through the ligands, while in the
lanthanoid series the metal properties (size, Lewis acidity) come to the fore.
Superacidic soluble and immobilized catalysts may well have their future in the
chemistry of the lanthanoids, including their “smaller brothers” scandium and
yttrium [92].
1352 4.1 Homogeneous Catalysis - Quo vadis?

It is obvious that toxicity/price reasons (cf. Table 3 in Chapter 1) must push all
these marvelous reagents toward their catalytic application and then, just one step
beyond, to their perfect separation from the product(s) [41 1. “Miracle reagents”
(Seebach) must become “miracle catalysts” to enter the industrial scene success-
fully. Thus, for any newly discovered reagent one always should think of a proper
“ligand outfit” to (re-)enter a catalytic cycle. Tremendous efforts in the coordina-
tion and organometallic chemistry of these ligands are to be made, especially with
regard to synthesis and structure.

4.1.6 Mechanistic Knowledge and Theory -

Keys to Catalyst Design
The declared goal of “going catalytic” with metal-containing reagents will depend
on a firm foundation of mechanistic studies, including thermodynamic considera-
tion. This is not a new concept, but should always be kept in mind [lo, 42, 431.
Carefully determined conversion/time diagrams, in situ spectroscopic studies, and,
if possible, kinetic time laws are among the fundamentals of catalysis research.
Such data will pave the way toward a mechanistic understanding. It is frequently
seen here that certain discoveries are not taken up quickly enough in an interdis-
ciplinary effort. The versatile Heck reaction, for example, has long remained an
“organic chemistry domain,” where it has its synthetic benefits. It was only
recently that through an accurate mechanistic study new catalysts - phospha-pal-
ladacycles (8) - were found to be superior to the conventional ones (cf. Section
3.1.6) [44 a]. These new catalysts mediate other C-C and N-C coupling reactions,
too [44 b]. It is certainly not a matter of chance that the latest synthesis of the
famous antitumor reagent taxol (9) depends on an intramolecular palladium
catalyzed Heck coupling [44 c, d].
H
NBZ
CHn

CH3
R = 0-tolyl, mesityl
phospha-palladacycles taxol
a 9

Homogeneous catalysis faces a number of obviously trivial but still unresolved

problems that depend primarily on mechanistic insight. For example, why do
some metal oxides (V20s, Moo3, CH,ReO,) catalyze olefin expoxidation while
others ( 0 ~ 0catalyze
~ ) olefin hydroxylation? What are the stereoelectronic pre-
4.1.7 Catalyst Perj%rmance/New Techniques to Generate und Activate Catalysts 1353

requisites for this fundamentally different reactivity? If these differences become

known, how can a “switchable catalyst” be synthesized?
Unfortunately, only a few reliable thermodynamic data of catalytically relevant
bonding situations are available in the literature, for which reason this area of phy-
sico-organometallic chemistry should receive greater emphasis. In this context,
theoretical approaches should be integrated in mechanistic studies much better
than previously. Quantum chemical calculations, most notably the density func-
tionality theory (DFT) taking care of relativistic effects of the (heavier) metals,
should quickly become established in homogeneous catalysis research [45].
Furthermore, molecular modeling has reached a predictive state, at least when
series of similar catalysts (e.g., the ligand periphery of a given metal) are to be
compared with each other (cf. Section 3.1.2). Spectroscopic techniques are begin-
ning to enter the scene to support theoretical approaches [46]. There are cases in
which older mechanistic schemes or kinetic data are superseded by new and more
detailed proposals due to improved theoretical methodology [47,48]. It remains to
be seen whether this improvement entails a new catalyst and process design or
even new techniques.

4.1.7 Catalyst Performance/New Techniques

to Generate and Activate Catalysts
An ideal situation is reached when the catalytic intermediates and at least the rate-
determining step(s) are established. This body of knowledge normally takes a long
time to attain and will depend strongly on the above-mentioned kinetic studies. In
addition, however, only the overall catalyst performance finally decides the indus-
trial feasibility: what is the stability of the catalyst, under which process condi-
tions, and how can the catalyst lifetime be improved? From experience, continu-
ous micro(1aboratory) plants are of pivotal importance to predict the performance
of a new catalyst. In situ spectroscopy (mainly IR and NMR techniques, e.g.,
parahydrogen labeling) are to be applied here as a means of detecting structural
features of the catalytic species involved. Chemical (model) reactions with the
(pre-)catalyst outside the reactor, and either in the absence of one component or
in the real reaction conditions, will always give only part of the truth with regard
to the catalytic reaction. Mass and energy transport features are worth of consid-
eration at the beginning of a catalytic project.
Catalyst performance has of course been a permanent theme in industry.
For example, the catalytic activity of 0x0 catalysts (in hydroformylation) has
improved in the past 50 years by a factor of 10000: change from diadic and
triadic process technology to continuous plant operation, replacement of cobalt
by rhodium, tailoring of the ligand sphere (phosphines), change of phase appli-
cation (from mono- to two-phase processes). At the same time, an improvement
of selectivity has been achieved, apart from the ease of productkatalyst separa-
tion [132]. A similar development seems to occur in the Monsanto acetic acid
process [49].
1354 4.1 Homogeneous Catalysis - Quo vadis?

Homogeneous catalysts applied in typical captive-use situations normally imply

a high degree of specific in-house expertise, for which reason not many details are
known in the “open” literature. Often generated in situ, these may remain secret
upon licensing, so any independent industrial catalysis research to some extent
risks the duplication of known science.
Increasing desire for easy-to-make, storable, organometallic catalysts is a
common trend. Their stability to air, water, and temperature is decisive in their
success. In many cases, only the precatalysts fully share these requirements.
Therefore, techniques to generate the active catalyst species are desirable. Beyond
chemical in situ techniques, some physical methods have recently come to the
fore. For example, the microwave technique 1991 was used to generate a catalyst
system for allylic alkylations with high regio- and stereoselectivities (cf. eq. (4))
[loo]. The reaction times are remarkably short. Due to the high temperatures
attained by microwave heating (up to 220 “C), the active catalyst species, how-
ever, must be thermally robust.
0 0
0 <MO(C0)6> (*I M e 0=OMe
r O A O M e

D*o^”
‘ 5 min 250 W
microwave,

87 % (98 YOee)
(4)

(*) chiral ligand + B S 4 P(CeH&, ‘CH(C02Me)2

Ultrasound is involved in another technique of catalyst activation. Known from

(stoichiometric) ligand substitution, catalytic applications have now become
available.
A methodological breakthrough in the elucidation of catalytic mechanisms
comes from the ultrafast electron diffraction (UED) technique. Even though only
the most simple models are accessible as yet, it is possible in principle to view
“hot” reaction intermediates on a multi-picosecond (and femtosecond [ 10I]) time-
scale after their formation, as shown for CO elimination from Fe(CO), [ 1011.
The characterization of catalysts has become the object of high-throughput
screening. Experimental arrays employing microsystems techniques are now avail-
able. The area is promising, at least to identify relative data of catalyst activity and
selectivity [ 1021. Combinatorial catalysis, as the field is called, will not replace the
innovative chemical idea, as amply shown in this book (cf. Section 3.1.3).

4.1.8 Organometallic Electrocatalysis

and Biomimetic Catalysis
For a long time, electrocatalysis (cf. Section 3.2.8) has not been considered im-
portant in organometallic chemistry although numerous known processes depend
on redox reactions (e. g., Wacker-type catalysis, oxidative olefin carbonylation,
1356 4.1 Homogeneous Catalysis - Quo vudis?

10 11

/
NADH
'
NAD+
R = alkyl, aryl, halide

4.1.9 New Chemical Feedstocks for Homogeneous

Catalysis and Renewable Resources
Organometallic catalysis has largely been based on feedstock chemicals such as
alkynes, alkenes, dienes, carbon monoxide, and hydrogen. The classical mecha-
nistic principles - dn-complexation, oxidative addition, insertion/migration, re-
ductive elimination - suffice to explain the majority of reactions thus comprising
catalytic cycles. Unfortunately, only reluctant reactivity has been seen for alter-
native, particularly cheap, feedstock chemicals. Methane, ethane, propane, and
carbon dioxide deserve specific mention because of their general and abundant
availability. Saturated C building blocks suffer from the failure that their
metal chemistry is not really catalytic as yet [54-561. Nevertheless, possible
advantages are clear to see:

(1) Methane as an abundant natural resource chemical could partially substitute

for both olefins (refinery ethylene and propene) and carbon monoxide.
 4.1.9 New Chemical Feedstocks for Homogeneous Catalysis 1351

(2) Propane is the most prominent refinery gas (av. 60%), followed by butane
(ca. 30 %), so their functionalization has been a serious topic in heterogeneous
catalysis research for a long time.
(3) Carbon dioxide could at least be engaged in the synthesis of carboxylic
compounds and certain heterocycles, quite apart from the consideration that
it may eventually substitute for the more expensive carbon monoxide in spe-
cific applications. For reductive processes, however, a C02-based feedstock
stituation could prove more expensive since an extra equivalent of a reductant
is required (cf. Sections 3.2.11 and 3.3.4).
The selective and catalytic C-C and C-H bond cleavage of (unreactive, satu-
rated) hydrocarbons, like ethane and methane, is still another “Holy Grail” in
chemistry. It is obvious then, that the catalytic activation of such molecules
under mild (e. g., nonphotolytic) conditions would revolutionize catalysis. This
capability would contrast the classical high-temperature reforming processes of
the petrochemical industry, which constitute the largest-scale industrial catalyses.
No solution to the problem is available as yet. However, a number of recent ap-
proaches regarding C-H, C-C, and C-F bonds appear promising (cf. Sections 2.8,
3.1.6, or 3.3.6).

Carbon-Hydrogen Bonds
Methane is broken up at +10 “C upon treatment with the iridium complex
(y5-C5Me5)IrH(PMe3).CH2Cl2to give the oxidative addition product ($-C5Me5)
Ir(H)2(PMe3)CH3[57a]. This reaction matches with earlier findings according to
which the less dissociation-labile carbonyl complex (y5-C5Hs>Ir(CO),affords
the hydrido-methyl derivative (y5-CSHs)Ir(CO)H(CH,)under photochemical con-
ditions [54 c]. The reader is further reminded of Watson’s elegant work concerning
“CH3 vs. ‘*CH3exchange in the “metal-acidic’’lutetium(II1) complex (y5-C5Me5)2
Lu(CH3) by means of methane [57 b] and to a novel approach of methane activa-
tion by N-heterocyclic carbenes [ 1351.

Carbon-Carbon Bonds
Milstein et al. demonstrated (Scheme 6) that a methyl group is first C-H-activated
before it eliminates as methane via hydrogenolysis from the intermediate 10 [57 c].
The prior C-H bond activation occurs readily, and is expectedly much more rapid
than the subsequent C-C-cleavage reaction. It is certainly true that the formation
of the new rhodium-phenyl bond of 13, in addition to the very special type of
chelating tC,P-coordination, is the driving force here, but nevertheless the cleav-
age of a low-reactivity bond between sp2- and sp3-hybridized carbon atoms has
been achieved. The more difficult problem to cQpe with is the cleavage of purely
aliphatic C-C bonds because their directed sp3-orbitals along the bond axis are
inaccessible to metals and are thus much less reactive.
Transfer of a C-H-activated methyl group after consecutive C-C bond cleavage
as a methylene unit to other substrates is an interesting alternative. Starting from
1358 4.1 Homogeneous Catalysis - Quo vadis?

Scheme 6

CH3

CH3
(Me0)3Si-Si(OMe)3 (Me0)3Si-CH*-Si(OMe)3
14 15

Scheme 7

the strained rhodacycle 14,for example, the insertion reactions of Scheme 7 were
achieved, at least in stoichiometric reactions [57 d, el.
It must be noted that the cleavage of strong C-C bonds by transition metal
insertion under mild conditions depends thermodynamically on an auxiliary
chemical reaction coupled to the cleavage process (e. g., hydrogenation). The
work of Milstein shows that an oxidative addition process according to the sim-
plifying eq. (6) is highly dependent on the electron density of the metal center,
but can be thermodynamically more favorable than the competing C-H activation
process. C-C bond cleavage may start with a sterically less hindered C-H bond
activation.

0 -
M" + C-C

A challenging example of a paraffinic C-C bond metathesis is the recently dis-

covered conversion of ethane into methane and propane under mild conditions
1360 4.1 Homogeneous Catalysis - Quo vadis?

the thermodynamics of which clearly relies on the strength of the silicon-fluorine

bond. The perfluorophenyl-rhodium bond of complex 16 also favors this kind of
C-F bond activation [57 g]. The related rhodium-phosphine complex was found
to allow the catalytic hydrogenolysis of hexafluorobenzene: when this fluorocar-
bon is used as a solvent, it eliminates fluorine upon heating with the catalyst
(PMe&RhH in the presence of a base (e. g., NEt, or NEt3/K2C03)and hydrogen;
the released hydrogen fluoride is captured by the base. The proposed catalytic
cycle for the hydrogenolysis (Scheme 9) involves electron-rich hydridorhodi-
um(1)-phosphine complexes as the species that induce cleavage of C-F bonds.
This implies that other complexes which can serve as a good source of such
species are also likely to be active. The synthetic potential of carbon-fluorine
activation is enormous, provided that efficient catalysts can be found. So far, turn-
over numbers up to only 114 have been recorded [57 h]. Heterogeneously cata-
lyzed hydrogenolysis of carbon-fluorine bonds is known; however, it requires
very high temperatures and is nonselective, once again showing the future poten-
tial of homogeneous organometallic catalysis (cf. also [ 1361).

L3Rh-SiR3 + FV F - L3Rh+$-F + R3Si-F

(9)
L = P(CH3)3 F F F F
R = CsHs
16

IH
L,,, I .,H
Rh',
L' 1 L

L = P(CH3)s
Scheme 9 base = N ( C ~ H ~ ) ~ / K Z C O ~
 4.1.9 New Chemical Feedstocks f o r Homogeneous Catalysis 136 1

In this context, the catalytic degradation of polymers as a possible new basic

feedstock for organic chemicals seems worthy of reinforced efforts [15, 57 i-11.
Catalytic activation of methane and other hydrocarbons remains of central interest
in catalysis research in general [54]. To this end, any stoichiometric chemistry of
this molecule has a significance of its own.
The wealth of present-day chemistry is based on petroleum feedstock and
inorganic minerals, such as rock salt, pyrite, dolomite, and bauxite. As far as
the enormous variety of chemicals and their refined products (e. g., pharmaceuti-
cals) are concerned, it is quite obvious that, in two or three generations from now,
a new feedstock basis is inevitable. Even if large-scale recycling technologies are
available by then (e. g., in the plastics area), there will not be enough easily avail-
able oil to cover the entire demand of the chemical industry and energy genera-
tion. Instead, we shall depend more and more on renewable resources.
However, little attention is as yet given to this chemistry. First of all, new
brands of plant materials are necessary that grow fast enough, especially under
bad climate and soil conditions, and exploit a specific property. Plant genetics
clearly is the way to produce new “industrial” plant species that, for example, con-
tain just the desired chemical and not a mixture of many products (which natural
plants normally do).
Again, chemical catalysis must take on the duty of performing the necessary
transformations. The main problem is normally the complex chemical compo-
sition of natural products, and the presence of numerous functional groups,
e. g., NH2, CH20H, COOH, SH. This requires highly developed catalysts that
are both selective and resistant to functional groups.

R I \ /

I
R

Scheme 10
1362 4.1 Homogeneous Catalysis - Quo vadis?

Slow but significant progress is visible in this area. For example, potato starch
(containing 27 % amylase and 73 % amylopectin) can be oxidized to superabsorb-
ing biopolymers. The three-component system H202/HBr/CH3Re03works in
the formation of carboxylated starch according to the mechanism proposed in
Scheme 10 [104].
Isoeugenol, a product from sawdust, and the agricultural waste product trans-
ferulic acid can be converted into vanillin by consecutive oxidation steps, again
employing CH3Re03as a catalyst and hydrogen peroxide as a “green”, yet still
expensive, oxidant [ 1051. Biological wastes are thus shown to form highly
value-added products by virtue of organometallic catalysis.

4.1.10 Catalysis Under Supercritical Conditions

and Supported by Ionic Liquids
Earlier, no emphasis was given to homogeneous catalysis in supercritical fluids,
albeit the technique per se is now well established in extraction technology
(e. g., for coffee, tea, hops, spices, and natural flavors). Incorporated in homoge-
neous catalyst processes [58-601, supercritical conditions can dramatically change
the solubility profile of solvents and the reactivity of certain chemicals.
A comprehensive review ( 1999) highlighted the enormous opportunities
afforded by supercritical fluids (SCF) in organometallic catalysis (cf. Section
3.1.13) [106].
Of particular interest is carbon dioxide (scC02) because of its relative chemi-
cal inertness and the convenient critical data. In contrast, water (21.8 MPa,
374°C) is a rather bad candidate for both the critical data and the reactivity.
Generally, catalytic reactions in SCFs are limited to narrow temperature ranges.
The T, has to be little below or within the desired range, otherwise too much
pressure is required. It is relevant to the kinetics of the catalytic reactions that
the dielectric constant, viscosity, and other physical data of an SCF medium
stongly depend on the pressure (via the density function). Since many reactions
have polarized reactants, products, or transition states, or exhibit a polar solvent
effect, the pressure dependence can be exploited to optimize a process. There-
fore, mechanistic studies can benefit from polarity effects tunable in supercritical
media. Since supercritical carbon dioxide has a high degree of compressibility,
it provides the opportunity to explore density as an additional reaction para-
meter. The schematic phase diagram of carbon dioxide is seen in Figure 1 of
Section 3.1.13.
With regard to organometallic reactivity, little is known on the various
SCFs. Even carbon dioxide can be reactive if it inserts in M-H, M-R,
M-OR, or M-NR2 bonds. In this case, scC0, can be used simultaneously as C I
building block.
An impressive example of selectivity effects comes from olefin metathesis.
A certain Ru-carbene catalyst strictly yields the ring-closure metathesis product
in supercritical carbon dioxide at densities above 0.65 g mL-’ (eq. (1 0)), while
 4.1.10 Catalysis Under Supercritical Conditions 1363

at lower densities acyclic oligomers are formed [107]. The separation of the
muscarine fragrant exhibiting Structure 17 is so easy that olefin metathesis should
gain a new profile of application with the SCF-OMC technique (cf. [108]).
0

Ru cat (RCM)
+ C2H4
sccop
d > 0,65g mL”
17, RCM product

Ru cat (ADMET)
*
SCCO?
d c 0,65g mL-’

Convincing results also became available for C 0 2 hydrogenation using the

catalyst RuH,[P(CH,),], at 50 “CB.5 MPa H2: while in standard solvents, e. g.,
N(C2HS),, H20, or THF, initial TOFs < 100 h-’ were recorded, activities far
above 4000 h-’ could be achieved in scC02/CH30H and scC02/DMS0 [109].
Furthermore, a strictly alternating polyketone was made in scC0, from C2H4
and CO in the presence of the Ni” catalyst; 11 kg of the polyketone per g of
Ni was obtained, which represents the best data reported as yet [110].
The asymmetric hydrovinylation (cf. Section 3.3.3) of styrene with excellent
chemo-, regio-, and stereoselectivity was achieved in scC0, using the known
Ni” catalyst but - instead of the flammable co-catalyst (C2Hs)3A12C13 - the bo-
ranate (“BARF’). This was possible because all components are soluble in
scC0, [ 1111 (cf. eq. (6) of Section 3.1.13).
Beyond these effects, carbon dioxide is an “environmentally responsible”
solvent and deserves investigation of its technical uses for this reason, too.
Asymmetric hydrogenation combined with catalyst recycling using ionic
liquids and scC0, highlights the potential of supercritical media [ 1121.
Ionic liquids are salts that are liquid at low temperature, at least below 100 “C.
They form biphasic systems with many organic compounds and product mixtures
(cf. Section 3.1.1.2.2).
Within a given class of ionic liquids, the melting ranges and viscosities can
be adjusted greatly by changing the substituents, but the anions also have a strong
influence. The density changes mainly according to the bulkiness of the groups R.
Advantages of ionic liquids in homogeneous catalysis are as follows [113, 1141:

(1 ) They are nonmolecular, ionic solvents.

(2) Product separation is facile, due to negligible vapor pressure.
(3) Ionic liquids have good solubility for organometallic compounds.
(4) Their melting ranges, viscosities, densities, solubility characteristics, acidity,
and coordination ability are easily adjustable.
( 5 ) They are available commercially.
(6) Recovery and clean-up are easy due to biphasic process technology.
1364 4.1 Homogeneous Catalysis - Quo vadis?

Vl
18, ionic liquid

! -HCI I -2HCI
!

t t

L H

I ionic liquid + anionic catalyst I

Scheme 11

A main question - not yet really considered - concerns the inertness of ionic
liquids. Not only are the anions potential ligands, especially for neutral and catio-
nic metal complexes; one has also to take into consideration what is known for
cations like (imid)azolium: formation of carbene complexes via deprotonation
is a rather facile process especially if ligands of sufficient basicity are present,
e. g., -OR, -NR2. Therefore, several of the impressive catalytic results [ 1131
deserve mechanistic investigation to find out whether they are really limited to
the ionic liquid effects. For example, solvent and complexation effects are likely
to enhance one another in the Heck coupling reactions that were run in the
presence of Structure 18, Scheme 11 [115].
Promising results have been reported by various laboratories since 1990 on
catalysis in molten salts, notably for catalytic hydrogenation, hydroformylation,
oxidation, alkoxycarbonylation, hydrodimerization/telomerization, oligomeriza-
tion, and Trost-Tsuji coupling [ 1131. A continuous-flow application to the linear
dimerization of 1-butene on an ionic-liquid nickel catalyst system reached activ-
ities with TON > 18 000 [116].
 4.1.11 New Reactions, Improved catalysts 1365

4.1.11 New Reactions, Improved Catalysts

Oxygen, watel; and ammonia are preeminent when inorganic reagents of applied
homogeneous catalysis are under discussion. As a matter of fact, oxidative pro-
cesses comprise the greatest share among all homogeneous catalytic processes
if metal-mediated gas-phase oxidations (e. g., terephthalic acid; Section 2.8.1.2)
are included [61]. A specific opportunity for homogeneous catalysis can be
seen in the knowledge that oxidation processes are limited in their selectivities
(ca. 85 %) when they operate on the basis of heterogeneous catalysis. Neverthe-
less, selective activation of elemental oxygen is difficult to achieve, and in a num-
ber of cases coupled processes, such as the combination of a secondary alcohol
with oxygen, are required [62]. Ironically, the Wacker-type reactions - prototypes
of organometallic oxidations - exploit the catalyst metal to oxidize the ethylene,
while the oxygen only reactivates the palladium (cf. Section 2.4.1). No other oxy-
gen reaction using organometallics as activators is close to being given any appli-
cation. Here is an ostensibly rich field for high-oxidation state organometallic
chemistry [63].
Hydrogen peroxide is a more reactive but more expensive substitute for oxy-
gen. It has a broad and relatively well-investigated metal coordination chemistry
[62a]. While it normally does not meet the tight economic requirements for the
oxidative production of industrial bulk chemicals, the priority list

oxygen > hydrogen peroxide > t-butyl peroxide > other oxidants
is generally accepted [61 a-c]. It is sure enough that stoichiometric oxidants such
as "chromic acid" will be excluded in future times from technical-scale
applications for environmental reasons, even if higher-price chemicals such as
vitamin K3 and others are concerned [61 d-fl. Catalytic synthesis is often the
only reasonable alternative (cf. Section 3.3.13). It is questionable, even for stereo-
selective oxidations, whether oxidants yielding appreciable amounts of salt (e. g.,
NaOCl bleach) [63] will be able to access large-scale applications. It is thus by
force of demand that the old topic of oxygen activation enters the high-priority
list of future research in both coordination/organometallic chemistry and homoge-
neous catalysis. It has to be noted that the apparently primitive question of oxygen
transfer from peroxometal intermediates to olefins is not undisputed in terms of
the mechanism. While the Os0,-mediated dihydroxylation of olefins with hydro-
gen peroxide has long been known, atmospheric oxygen can now be employed for
the same purpose. It may be of strong industrial relevance that transformations fol-
lowing eq. (1 1) are effected by catalytic amounts (0.5 mol%) of K 2[O~02(0H)4],
with convincing evidence for stereoselective varieties, as tested with 1-octene and
a-methylstyrene [ 1 171. Relatively low pressures (0.3-0.9 MPa) at low catalyst
loadings (cathubstrate 1 :4000) are promising features of this elegant reaction. It
seems that the oxygen regenerates the active 0s""' species from the reduced
form [OSO,(OH),]~~ of hexavalent osmium. This is reminiscent of the Wacker-
type oxidation of ethylene where the oxygen also serves to reoxidize the catalyst
metal (Pd" + Pd") (cf. also Section 2.4.1).
1366 4.1 Hornogerieous Catalysis - Quo vadis?

4- lR
R2
+ 112 02 + H20 - HoxR2 R1 OH

olefin 1,2diol

Water is another ideal, environmentally sound reagent with exciting prospects,

but numerous questions are still open. Could water be added to olefins in the anti-
Markownikov mode? Primary alcohols would thus be cheaply available (eq. (12)).
Similarly, what is the appropriate catalyst to add ammonia across a double bond
(hydroamination, eq. (13), Section 2.7) to yield organic amines as starting materi-
als for a number of fine chemicals?
R-CH=CH2 + H20 R-CH2-CH20H (12)

R-CH=CH2 + NH3 R-CH2-CH2NH2 (13)

n CH2=CH2 + n CO -
(Y:i f CH2-CH2-C
Il
polyketones

On the other hand, several well-established reactions are missing certain

speciality applications. For example, what would be an efficient catalyst for the
hydroformylation of (per)fluoroalkenes, of which the products are of broad use
as pharmaceuticals [64]? How can functionalized olefins enter industrial appli-
cations, based upon a recent development employing special tungsten-carbene
complexes 19 for the metathesis even of C-C-unsaturated thioethers [65]? Is
the directive ethylenekarbon monoxide coupling of Drent et al. according to
eq. (14) (cf. Section 2.3.4) [66 a-c] and the structural principle 20 (intermediate)
of general use (e. g., to obtain functionalized olefins such as fluoroolefins, or to
use isonitriles in place of carbon monoxide)? What are the structural prerequisites
for multiple carbonylation reactions? A highly enantioselective alternating co-
polymerization of propene or styrene and carbon monoxide with a chiral phos-
phine-phosphite (BINAPHOS; 3) palladium catalyst was achieved (eq. (15)).
The optically active polymer had a molecular weight of about lo5 and M,/M,
= 1.6 when the cationic catalyst [CH3Pd(R,S-BINAPHOS)(N=C-CH3)]+ was ap-
plied [66d].

19 Ar= 20 @ = polymer chain

Ph Ph
 4.1.11 New Reactions, Improved Catalysts 1367

A new generation of polymers, e. g., Shell’s Carilon, was developed from the
discovery of the perfect CO/olefin alternating principle within the short time
span of less than ten years. Systematic mechanistic work in this area has yielded
a highly efficient carbonylation of propene (TON = 4 X lo4) in the presence of
palladium(I1) catalysts to methyl methacrylate (cf. Section 2.3.2.3) [66 el.
It is noteworthy that the attractive homologation reaction - a formal methylene
(CH,) insertion (cf. Section 3.2.7) - according to eq. (16) has received little atten-
tion as yet [67]. This synthetic principle looks promising for homologous com-
pounds of which only one certain derivative is easily available.
R-Y + CO + 2 H2 R-CH2-Y + H20

40 (16)
Y=OH, C,
OH

Novel C-C coupling reactions are about to enter the scope of metal complex
catalysis. Examples are asymmetric aldolizations (Mukaiyama [79]), Diels-Alder
reactions [80], and indium- or zinc-mediated alkylations [86].
The topic of molecular recognition should gain increased attention in catalyst
design. For example, specific structural interactions of higher olefins (e. g., l-de-
cene) with chemically modified B-cyclodextrins allow efficient hydrofonnylation
in a two-phase aqueous system even though the olefin is completely insoluble in
water; at the same time, olefin isomerization at the rhodium catalyst is hampered
P11.
Efficient chiral molybdenum catalysts (Structure 21) which are, at the same
time, easy to handle were generated in situ and used without further purification
in asymmetric olefin metathesis. For example, the RCM following eq. (17) yields
> 80 % of the desired product at > 88 % stereoselectivity [118].

21
1368 4.1 Homogeneous Catalysis - Quo vadis?

Significant progress is being made in catalytic N-C bond formation. Thus, the
stereoselective hydroamination of styrene derivatives [ 1191 and norbornene [ 1201
was achieved with BINAP catalysts (Pd and Ir, respectively) (cf. eq. (18)).

[{(S)-BINAP}lrCI] 2 93 % ee

4.1.12 A New Generation of Catalyst Ligands

Since the first edition of this book went into print (1996), many new catalyst
ligands have been discovered. They very closely resemble one another in terms
of their structural features and their coordination behavior. However, there has
also come along a completely new generation of ligands that in part substitutes
and in part supplements the ubiquitous organophosphanes (Structure 22): N-het-
erocyclic carbenes 23 (cf. also Section 3.1.10) [121].
R
I
R-
R -.P I "3
d YR
i 22 i
j.
23

Scheme 12 24 25

Whereas phosphanes have a conical shape, much of which is decisive in

stereoselective catalysis, the N-heterocyclic carbenes (NHCs) exhibit flat core
structures. More importantly, phosphanes dissociate from metal centers in com-
mon catalysts, whereas the C-coordination of the new ligands is much more stable
under catalysis conditions, thus preventing the catalytically active metal from
aggregating and precipitating. Theoretical studies (DFT; cf. Section 3 . I .2) showed
that the phosphanes in the Ru metathesis catalyst 24 dissociate much more easily
(ca. 27 kcal/mol) from the metal than the carbene in 25 (ca. 21 kcallmol); the
 4.1.13 Rare Earth Catalysts 1369

remaining phosphane of the latter is labilized by the trans-carbene (dissociation of

Ru-PMe3: ca. 25 kcallmol). The NHC ligands strengthen the n-olefin bonding to
initiate their metathesis transformations at the catalytic site. This result is in accord
with the experimental results concerning olefin metathesis [ 1221. However, a
strong discrimination in terms of ligand-to-metal bonding is generated by steric
effects: bulky groups like adamantyl (CI0Hl5)in Structure 26 facilitate dissocia-
tion as indicated by the AH, data, bringing them again close to the class of phos-
phanes 22.
R
R
r;
Q-Pd-CN]

N
k R
26
N-Heterocyclic carbenes are compatible with metals in quite different oxidation
states and structural environments. They are easily accessible, easy to handle, ther-
mally fairly robust, structurally variable, and cheap. Functionalized, chelating,
water-soluble, chiral, and immobilized derivatives are now available [ 1211. The
latter are all the more important as catalyst leaching seems not to occur due to
the strong metal-ligand bonding. Numerous applications in important catalytic
processes have proven successful, particularly as compared with related metal-
phosphane catalysts. Examples are olefin metathesis, Heck-Suzuki and Stille
coupling, Grignard cross-coupling (Kurnada reaction), alkyne coupling, hydrofor-
mylation, olefin hydrogenation, and hydrosilylation, as well as several cyclization
reactions [121, 122, 1361.
A further advantage is the possible in situ generation of catalysts from simple
metal salts or complexes (e. g., Ni(OR)2, PdC12) and azolium salts. The nickel-
catalyzed Grignard cross-coupling of aryl chlorides at room temperature [ 1231
and the activation of aryl fluorides [ 1361 are convincing examples.

4.1.13 Rare Earth Catalysts

Rare earth organometallic chemistry and catalysis have been a “Sleeping Beauty”
for many decades (cf. Section 3.2.5). Only recently, ways of molecular activation
were discovered that set the scene for systematic studies in homogeneous cata-
lysis. In particular, the synthetic accessibility was greatly improved by virtue of
the “silylamide route” of Scheme 13 [ 1241. In contrast to the standard salt meta-
thesis reactions, this method merits the advantages that (1) noncoordinating sol-
vents can be used due to the precursors’ excellent solubility; (2) mild reaction con-
ditions can be applied (e. g., room temp.); (3) halide contaminations are excluded
and redox side reactions (at Ln) are rare; (4) product purification is easy (b.p.
HN(SiMeJ2: 125 “C; b. p. HN(SiHMe&: 93-99 “C); ( 5 ) base-free products of
Ln” and Ln”’ are obtained; (6) quantitative yields are obtained in many if not
most cases; and (7) mono- and bimetallic lanthanoid precursor compounds are
1370 4.I Homogeneous Catalysis - Quo vadis?

1-
or -N(SiHMe2)2
+
6+ 6-
H-L - Ln-CEC-R
-CP
-SnR3
-NR2
-P R2
-OR
-S R
-SeR
-TeR
-X(Ha I)
Scheme 13

easily available and can be tuned in terms of their reactivity by the right choice of
amide ligands (e. g., -N(SiMe3)2 vs. -N(SiHMe,),). Using this technique, cata-
lytically relevant rare earth complexes with salen (Structure 27), (substituted)
linked-indenyl (28), and sulfonamide ligands (29) have been made [124, 1251.

27 28 29

In spite of countless applications of rare earth activation in industrial heteroge-

neous catalysis, most soluble complexes have long been limited to more or less
stoichiometric reactions. An early example is the Kugun C-C coupling mediated
by samarium(I1) iodide [ 1261. Meanwhile, true catalytic reactions have become
available. Highlights are considered the organolanthanide-catalyzed hydroamina-
tion of olefins [ 1271, the living polymerization of polar and nonpolar monomers
[ 1281, and particularly the polymerization of methyl methacrylate [ 1291. In the
first case, lanthanocene catalysts of type 27 are employed [127].
High molecular weight polymers with a very narrow molecular weight distribu-
tion obtained via living polymerization were generated from methyl methacrylate
catalyzed by organolanthanoid alkyls and hydrides (Ln = Lu, Sm, Y), with ex-
cellent stereotacticity being another striking feature [ 1281. The product data are
 4.1.14 Orgunometullic Catalysts for Polymers 1371

fascinating to polymer chemists: M , > 500 X lo3,M J M , < lo5, syndiotacticity

> 95 %, with typical catalysts being the lanthanocenes 30 (syndiotactic polymers)
and the alkylytterbium(I1) complexes 31 (isotactic polymers, > 97 %); M , > 200
X lo3, M J M , = 1.1). High polymer yields are obtained throughout [128].

-G
30 R = H, CH3 31

The major advantage of the Periodic Table’s “footnotes” originates from (1) the
“lanthanoid’ contraction effect which makes the chemistry “tunable” according
to size and related properties (e. g., metal Lewis acidity, coordination number,
steric bulk); (2) their pronounced oxophilicity, “hardness”, and (tunable) size.
Their chemistry is ruled by simple principles such as ionic binding and HSAB
theory. For this reason, combinatorial chemistry could prove an avant-garde
tool for ligand fine-tuning. Supermolecular aspects such as dendrimer chemistry
[ 1291, immobilization [ 1301, and stacking host-guest interactions [ 1311 are at
the top of the synthetic chemist’s agenda. Organolanthanoid catalysis, however,
is still badly underestimated with regard to its potential.

4.1.14 Organometallic Catalysts for Polymers

In polymer chemistry, new C-C coupling products, such as COC materials
(cycloolefin copolymers) with special properties like high transparency and hard-
ness, appear possible through tailored organometallic catalysts (cf. Section 2.3.1).
The novel polyketones with their high melting points (>220 “ C ) have already
been mentioned above [66]. As a matter of fact, Ziegler-Natta catalysis remained
for a long time the only true organometallic catalysis in macromolecular chemis-
try. Once again, the area was revolutionized by the discovery that certain zircono-
cene derivatives (32) of stereorigid, C2-symmetrical structures catalyze the strictly
isotactic polymerization of propene. It must be emphasized that it was an interdis-
ciplinary effort that wrote this success story: Sinn observed the methylalumoxane
effect [68], Brintzinger designed and made the chiral zirconocene complexes [69],
and Kaminsky discovered the polymerization characteristics related to these struc-
tures [69, 701. At the same time, a strong industrial interest has pushed forward a
worldwide development in numerous laboratories since 1984. New perspectives
came along with novel structures such as 33 and 34 originating from a chemistry
that had not been popular previously. Special copolymers are at present the first-
priority goals in this area of catalysis. The first polymers based upon the new gen-
eration of metallocene-type catalysts have appeared on the market: Hostacen@
1372 4. I Homogeneous Cutalysis - Quo vudis?

(Hoechst), Exact’ (Exxon), and Affinity@(Dow). Some but not all expectations
have been fulfilled since the first edition of our book appeared (cf. Section
2.3.1 S ) .

X = CI, N(CH3)z
R2
32 33

X = N(CH3)z X = CI, N(CH&

34 35

Of particular “intelligence” are Waymouth’s unbridged zirconocene variants

36 and 37: They are “switchable” from isotactic to atactic block polymerization
due to their specific conformations. The oscillation between chiral and achiral
coordination geometries is the molecular basis for making novel thermoplastic
elastomeric polypropene, with the isotacticity depending on the temperature and
propene pressure (isotactic product content 6-28 %) [71 a]. This is an excellent
example of how a “gray-hair” type of organometallics fertilizes an applied area
of technology.
In spite of all the recent success in the metallocene area, the purely synthetic
part of the game has narrowed down to zirconium and hafnium. Little is known

36 37

t
isotactic block
t
atactic block

@ = growing polymer chain

 4.1.I 4 Organometallic Catalysts for Polymers 1373

on ansa-metallocenes of related metals like niobium and tantalum, in which fact a

loss of "synthetic culture" is seen. The imido complex 35 is one of the few such
examples [71 b].
In the near future, it is believed that a major part of macromolecular
chemistry will receive a strong impact from homogeneous organometallic cata-
lysis. Thus, poly-coupling reactions with redox-sensitive precursor compounds
to give polymers like 38 were discovered [72].

\ I
Fe

/ /
--/ 38 ($?: bonds formed by catalytic coupling

The coupling of alkynes, an old field of polymer chemistry, is on new tracks

resulting from defined metal-alkyl (39) and metal-carbene (40) catalysts [73,
741; previously simple metal halides (e. g. NbCIS) of unspecified active catalyst
structures were often employed. The polymer stereochemistry can be switched
from 100% trans (R = t-Bu) to 100% cis (R = C(CF3)*CH3) in the case of
the imido(carbene) complex 40 upon making poly(2,3-bistrifluoromethyl)nor-
bornadiene [74].

39 40
R = C(CF3)2CH3or C(CH&

As well as certain monomer syntheses, defined polymers can be made

through homogeneous catal sis, e. g., olefin metathesis (CdF Norsorex', Huls
8
Vestenamer', Hercules DCP ), special ring-opening metathesis (cf. Section 2.3.3),
CO/C,H, copolymerization (cf. Section 2.3.4), and other reactions (cf. Section
3.3.10.1).
Yet another era of organometallic polymer chemistry appears to arise from
new cationic nickel(I1)- and palladium(I1) complexes 41 of N,N-chelate (diimine)
ligands (cf. eq. (19)). According to Brookhardt et al., both the homo- and co-
polymerization of a-olefins proceed with activities that compare in the case of
1374 4.1 Homogeneous Catalysis - Quo vadis?

nickel with those commonly seen with metallocene catalysts. For the first time,
simple variation of pressure, temperature, and ligand substituents yields an eth-
ylene homopolymer whose structure varies from a highly branched, completely
amorphous to a linear, semi-crystalline, high-density material with a degree of
branching from 1 to 300 branches per 1000 carbons. As an alternative to 41,
the catalyst system (diimine)NiBr2 + methylalumoxane is equally suitable for
the polymerization of ethylene and higher a-olefins [90 a].

RI l+

k
41 a, b
The special brightness of the new catalysts comes from their ability to include
functionalized vinyl monomers which normally terminate polymerizations at
the oxophilic early transition-metal catalysts. On the other hand, late transition
metals most often dimerize or oligomerize olefins, especially nickel, due to the
preference of /3-hydride elimination. For this reason, ethylene-acrylate and
ethylene-vinyl acetate copolymers are exclusively manufactured by radical-type
processes, which often enough require high-pressure conditions. Palladium
complexes of type 41 allow the formation of high molecular weight random
copolymers; the acrylate co-monomer is equally distributed over all mole-
cular weights of the monomodal distribution. The branching amounts to ca.
100 branches/1000 carbon atoms, with the ester groups being predominantly
located at the ends of branches (eq. (20)). The slightly modified catalyst 42
adds the olefins in a reversible manner, while the intermediate 43 allows for the
chain growth, e. g., consecutive insertion of the ethylene into the Pd-C-alkyl
bond (cf. eq. (21)) [90b]. Brookhart’s work has opened a new possibility of
organometallic catalysis in macromolecular chemistry. DuPont has filed patents
in this area and expects commercialization [91].

CH-(CH& -CH -(CH),

CH2=CH2 I I
CH2 =CH-COpR’ I I
CHzCH2COzR’ CHs

R’ = alkyl functionalized polymer

 4.1.16 Final Closure 1375

chain growth to polymer

4.1.15 Catalyst Reactivation, Process,

and Reactor Technology
Only a small minority of organometallic reactions have cleared the hurdle to be-
come catalytic reality; in other words, catalyst reactivation under process condi-
tions is a relatively rare case. As a matter of fact, the famous Wacker/Hoechst
ethylene oxidation achieved verification as an industrial process only because
the problem of palladium reactivation, Pdo + Pd”, could be solved (cf. Section
2.4.1). Academic research has payed relatively little attention to this pivotal aspect
of catalysis. However, a number of useful metal-mediated reactions wind up in
thermodynamically stable bonding situations which are difficult to reactivate. Ex-
amples are the “early transition metals” when they extrude oxygen from ketones
to form C-C-coupled products and stable metal oxides; cf. the McMuny (Ti) and
the Kagan (Sm) coupling reactions. Only co-reactants of similar oxophilicity (and
price!) are suitable to establish catalytic cycles (cf. Section 3.2.12). In difficult
cases, electrochemical procedures should receive more attention because expen-
sive chemicals could thus be avoided. Without going into details here, it is the
basic, often inorganic, chemistry of a catalytic metal, its redox and coordination
chemistry, that warrant detailed study to help achieve catalytic versions.

4.1.16 Final Closure

Many questions raised in this “Epilogue” will certainly remain open problems for
the third edition of this book. On the other hand, there has never been such a
strong emphasis of organometallic chemistry on catalytic applications than at pre-
sent. More than ever before will collaborations “between the disciplines” prove
crucial for success - the problems left are, as ever, the more difficult ones. How-
ever, a much improved methodology is available these days, and the importance
of theory should be mentioned here. At the same time, large-scale sophisticated
organometallic preparations - for example, of metallocenes - are becoming stan-
dard in industry. It is now clear to many workers in the field that the philosophy of
the “roaring sixties” - to make each compound for its own sake and for the fun it
1376 4.1 Homogeneous Catalysis - Quo vadis?

gives - applies only for rare segments these days. It is all the more important to
intensify the collaboration of homogeneous catalysis with coordination and orga-
nometallic chemistry. Beyond that, theoretical chemistry, chemical kinetics, and
chemical engineering must be integrated and intensified in current research, not
least for the sake of an early assessment regarding the industrial feasibility of a
certain reagentheactiordmechanisdprocess combination.
We note that the problem of the much talked-about “gap” within heterogeneous
catalysis - namely how to perform structural investigations under realistic condi-
tions and to derive reliable conclusions therefrom for the working catalyst - will
remain central. Heterogeneous catalysis still has empirical status. In contrast,
homogeneous catalysis has its greatest potential in step-by-step improvements,
based on the possibility of examining (and understanding!) the molecular details
of mechanism(s) under true catalytic conditions. Unlike in heterogeneous cata-
lysis, an encyclopedic collection of catalysts and their efficiency (so-called “expert
systems” [94]) is thus not required to choose a homogeneous catalyst for a special
purpose.
It is generally observed that chemical companies include homogeneous cata-
lysis in their research and production. For example, Ciba-Geigy commercialized
their first organometallic homogeneous catalytic process (100 tons per year), the
synthesis of the herbicide Prosulfuron@ via the Pd(dba)2-catalyzed Matsuda
reaction of 3,3,3-trifluoropropene with an aryldiazonium salt [98].
Organometallic chemistry has become so central an interdisciplinary science
that the opportunities for it to serve in catalysis are a daily exciting challenge.
Let us hope that homogeneous and heterogeneous catalysis, as a modified, less
apodictic version of C. P. Snow’s “two cultures” [75], come to unification. The
recent Nobel Prize (2001) to Knowles, Sharpless, and Noyori unterlines the suc-
cesses of molecular organometallic catalysis in a convincing way. A 35-author
team [ 1371 of experts supports much of what has said in this book when they con-
sidered the future catalysis research needs of relevance to carbon management.
The chemical feedstock situation will greatly govern the catalytic sciences in
the near future, for sure.

References and Notes

[ I ] To be historically correct, there were earlier examples of metal-mediated homogeneous
catalysis. For example, the Hg2’-catalyzed hydration of acetylene to acetaldehyde
became an industrial process in 1912. There is an intermediate n-acetylene complex to
activate the substrate. The “lead chamber process” to make sulfuric acid (NO, catalysis)
is even older but does not involve metals or metal complexes as catalysts [134].
[ 2 ] The word “serendipity” was coined by Horace Walpole in a letter to Sir Horace Mann in
1754 and is based on the fairy tale about the adventures of “The Three Princes of Seren-
dip” (or Serendib, an ancient name for Ceylon, now known as Sri Lanka): R. M. Roberts,
Serendipity -Accidental Discoveries in Science, John Wiley, New York, 1989. The term
is now used for fortunate, totally unexpected discoveries - discoveries by accident and
sagacity.
 References and Notes 1377

[3] “Organometallic mixed catalysts” for ethylene polymerization, discovered (by serendip-
ity) when nickel-contaminated autoclaves were used to carry out an Aufiaureaktion (re-
action of A1(C2H5),with ethylene). The “nickel effect” lead to the zirconium-catalyzed
ethylene polymerization in Ziegler’s laboratory on October 26, 1953, see: F. M. MacMil-
Ian, The Chain Straighteners, The MacMillan Press Ltd., p. 62f., London, 1979.
E. Krause, A. von Grosse, Die Chemie der Metallorganischen Verbindungen, Gebriider
Borntraeger, Berlin, 1937; reprint by Dr. Martin Sandig oHG, Wiesbaden, 1965. Specific
treatments of organomagnesium (Grignard) and organoalkaline metal compounds are
older, for example: W. Runge, Organometallverbindungen, 1st ed., Wissenschaftliche
Verlagsgesellschaft mbH, Stuttgart, 1931; 2nd ed. 1944.
E. W. Abel, G. Wilkinson, F. G. A. Stone (Eds.), Comprehensive Organometallic Che-
mistry, 1st ed., Pergamon, Oxford, 1982; 2nd ed., 1995-1996.
[6] (a) J. Buckingham (Ed.), Dictionary of Organometallic Compounds, Vols. 1-3, Chap-
man and Hall, London, 1984; (b) B. J. Aylett, M. F. Lappert, P. L. Pauson (Eds.), Dic-
tionary of Organometallic Compounds, 2nd ed., Vols. 1-5, Chapman and Hall, London,
1995.
[7] Chemical Abstracts Service, December 2001.
[8] See, for example, J. Organomet. Chem. 1995, 500; published by Elsevier Science,
Amsterdam/Lausanne/Oxford.
[9] These journals were started in 1975 (Elsevier) and 1982 (American Chemical Society),
respectively.
[lo] (a) C. A. Tolman, Chem. Soc. Rev. 1972, 1, 337; (b) M. Tsutsui, R. Ugo (Eds.), Funda-
mental Research in Homogeneous Catalysis, Plenum, New York, 1977; (c) J. K. Kochi,
Organometallic Mechanisms and Catalysis, Academic Press, New York, 1978;
(d) J. Halpern, Pure Appl. Chem. 1983, 55, 99.
[ l l ] F. R. Hartley, Supported Metal Complexes. A New Generation of Catalysts, Reidel,
Dordrecht, 1985.
[I21 (a) W. A. Henmann, M. Elison, J. Fischer, Ch. Kocher, G. R. J. Artus, Angew. Chem.
1995, 107, 2602; Angew. Chem., Int. Ed. Engl. 1995, 34, 3005; (b) Hoechst AG (W.
A. Henmann, M. Elison, J. Fischer, Ch. Kocher), DE 4.447.066, 4.447.067, 4.447.068
(1994).
[13] U. Romano, A. Esposito, F. Maspero, C. Neri, M. G. Clerici, Chim. Ind. (Milan) 1990,
72, 610.
[I41 Review: S. L. Scott, J.-M. Basset, G. P. Niccolai, C. C. Santini, J.-P. Candy, Ch. Lecuyer,
F. Quignard, A. Choplin, New J. Chem. 1994, 18, 115.
[ 151 J.-M. Basset, personal communication to the editor (W. A. Henmann); Vth Kiinigsteid
Kreuth Conference on Organometallic Chemistry, KreuthBavaria, Oct. 3-6, 1995.
[ 161 D. Avnir, J. Blum, A. Rosenfeld, H. Schumann, H. Sertchook, S. Wernik, Abstracts 9th
Int. Symp. on Homogeneous Catalysis, Jerusalem, Israel, 1994, p. 144.
[17] G. Wulf, Angew. Chem. 1995, 107, 1958; Angew. Chem., Int. Ed. Engl. 1995, 34, 1812.
[ 181 G. A. Melson (Ed.), Coordination Chemistry of Macrocyclic Compounds, Plenum, New
York, 1979.
[ 191 G. Ertl, H. Knozinger, J. Weitkamp (Eds.), Handbook of Heterogeneous Catalysis, VCH,
Weinheim, 1997; especially Chapters 2.1.4, 2.3.5, 2.3.6, 4.9, 4.11, 5.3.3, 11.2.1, B/4.5,
B/4.15.
[20] D. E. De Vos, F. Thibault-Starzyk, P. P. Knops-Gerrits, R. F. Parton, P. A. Jacobs, Macro-
mol. Symp. 1994, 80, 157.
[21] I. T. Jarvith, J. Ribai, Science 1994, 266, 72.
[22] Cf. Ref. [19], Chapter 9.3.
[23] H. Vahrenkamp, Adv. Organomet. Chem. 1983, 22, 169.
[24] Recent monograph: G. Schmid (Eds.), Clusters and Colloids, VCH, Weinheim, 1994.
1378 4.1 Homogeneous Catal.ysis - Quo vadis?

[25] (a) H. Bonnemann, W. Brijoux, R. Brinkmann, E. Dinjus, T. Jouen, B. Korall, Angew.

Chem. 1991, 103, 1344; Angew. Chem., Int. Ed. Engl. 1991, 30, 1312; (b) H. Bonne-
mann, W. Brijoux, R. Brinkmann, R. Fretzen, T. Joussen, R. Koppler, B. Korall, P. Nei-
teler, J. Richter, J. Mol. Catal. 1994, 86, 129; (c) L. N. Lewis, J. Stein, K. A. Smith in:
Progress in Organosilicon Chemistry (Ed.: B. Marciniec, J. Chojonovski), Gordon and
Breach, Langhorne, 1995, p. 263; (d) T. J. Wehrli, A. Baiker, D. M. Monti, H. U. Blaser,
J. Mol. Catal. 1990, 61, 207; (e) Workshopon Bimetallic Effects in Chemistry, European
Science Foundation, Parma/Italy, April 26-29, 1995.
[26] (a) Ref. [19], Chapter 4; (b) J. H. Sinfelt, Bimetallic Catalysts - Discoveries, Concepts
and Applications, John Wiley, New York, 1983.
[27] J. R. Anderson, M. Boudart, Catalysis - Science and Technology, Springer, Berlin, 1981.
[28] (a) S. L. Stinson, Chem. Eng. News, Sept. 19, 1994, 33; (b) S. L. Stinson, ibid. Oct. 9,
1995, 44.
[29] C. Botteghi, S. Paganelli, A. Schionato, M. Marchetti, Chirality 1991, 3, 355.
[30] (a) L. S. Hegedus, Transition Metals in the Synthesis of Complex Organic Molecules,
University Science Books, Mill Valley 1994 (German translation published by VCH,
Weinheim, 1995); (b) D. Seebach, Angew. Chem. 1990, 102, 1363; Angew. Chem.,
Int. Ed. Engl. 1990, 29, 1320.
[3 I] H. Bmnner, W. Zettlmeier, Handbook of Enantioselective Catalysis, VCH, Weinheim,
1993.
[32] (a) Y. Onto, S. Imai, S. Niwa, J. Chem. Soc. Jpn. 1979, 1118; (b) H.-U. Blaser, H. P.
Jalett in: Heterogeneous Catalysis and Fine Chemicals, Vol. 111 (Ed.: M. Guisnet), Else-
vier, Amsterdam, 1993, p. 139; (c) B. Minder, T. Mallat, A. Baiker, G. Wang, T. Heinz,
A. Pfaltz, J. Catal. 1995, 154, 371; (d) K. E. Simons, G. Wang, T. Heinz, T. Giger,
T. Mallat, A. Pfaltz, A. Baiker, Tetrahedron: Asymmetry 1995, 6, 505.
[331 (a) R. Noyori, Science 1990,248, 1194; Chem. SOC. Rev. 1989,18, 187; (b) W. A. Herr-
mann, R. Eckl, unpublished results, 1996; (c) N. Sakai, S. Mano, K. Nozaki, H. Takaya,
J. Am. Chem. Soc. 1993,115, 7033; (d) N. Sakai, K. Nozaki, H. Takaya, J. Chem. Soc.,
Chem. Commun. 1994, 395; (e) T. Higashizima, N. Sakai, S. Mano, K. Nozaki,
H. Takaya, Tetrahedron Lett. 1994, 35, 2023; (f) T. Horiuchi, T. Ohta, K. Nozaki,
H. Takaya, J. Chem. Soc., Chem. Commun. 1996, 155; (g) T. Nanno, N. Sakai, K. No-
zaki, H. Takaya, Tetrahedron: Asymmetry 1995, 6, 2583.
[34] A. Togni, L. M. Venanzi, Angew. Chem. 1994, 106, 517; Angew. Chem., Int. Ed. Engl.
1994, 34, 497.
[35] (a) A. Pfaltz, Mod. Synth. Methods 1989, 5, 199; (b) see Section 3.1.7 of this book:
(c) T. Aratani, Pure Appl. Chem. 1985, 57, 1839; (d) M. P. Doyle, in: Catalytic Asym-
metric Synthesis (Ed.: I. Ojima), VCH Publishers, Weinheim, New York, 1993, p. 63.
[36] (a) E. N. Jacobsen, L. Deng, Y. Furukawa, E. Martinez, Pure Appl. Chem. 1994, SO,
4323; (b) E. N. Jacobsen in: Catalytic Asymmetric Synthesis (Ed.: I. Ojima), VCH,
New York 1993, pp. 159-202; (c) B. D. Brandes, E. N. Jacobsen, Tetrahedron Lett.
1995, 36, 5123; (d) B. D. Brandes, E. N. Jacobsen, J. Org. Chem. 1994, 59, 4378.
[37] (a) M. Kitamura, S. Suga, R. Noyori, J. Am. Chem. Soc. 1986, 108, 6071: (b) M. Kita-
mura, S. Okada, S. Suga, R. Noyori, ibid. 1989, 111, 4028; (c) K. Soai, T. Shibata,
H. Morioka, K. Choji, Nature 1993, 378, 767.
[38] (a) K. T. Wan, M. E. Davis, Nature (London) 1994, 370,449; I. T. Horvith, F. Jo6 (Eds.),
Aqueous Organometallic Chemistry and Catalysis, Kluwer Academic, Dordrecht, 1995;
(b) M. Sawamura, K. Kitayama, Y. Ito, Tetrahedron: Asymmetry 1993, 4, 1529.
[39] (a) E. J. Roskamp, S. F. Pedersen, J. Am. Chem. Soc. 1987, 109, 3152; ibid. 1987, 109,
6551; (b) J. B. Hartung, jr., S. F. Pedersen, ibid. 1989, I l l , 5468.
 References and Notes 1379

[40] (a) H. B. Kagan, J. L. Namy, Tetrahedron 1986, 42, 6573; (b) H. B. Kagan, New J.
Chem. 1990, 14, 453; (c) J. A. Soderquist, Aldrichim. Acta 1991, 24, 24; (d) G. A.
Molander, Chem. Rev. 1992, 92, 29.
[41] See, for example: H. B. Kagan, Bull. Soc. Chim. Fr: 1988, 846.
[42] J. D. Atwood, Mechanisms of Inorganic and Organometallic Reactions, BrooksJCole,
MontereyJCanada, 1985.
[43] (a) J. F. Waller, J. Mol. Catal. 1985, 31, 123; (b) G. W. Parshall, Organometallics 1987,
6, 687; (c) E. Drent, Pure Appl. Chem. 1990, 62, 661.
[44] (a) W. A. Henmann, Ch. BroBmer, K. Ofele, C.-P. Reisinger, T. Priermeier, M. Beller,
H. Fischer, Angew. Chem. 1995, 107, 1989; Angew. Che;., Int. Ed. Engl. 1995, 35,
1844; (b) M. Beller, H. Fischer, W. A. Henmann, K. Ofele, Ch. BroRmer, Angew.
Chem. 1995, 107, 1992; Angew. Chem., Int. Ed. Engl. 1995, 35, 1846; (c) J. J. Masters,
J. T. Link, L. B. Snyder, W. B. Young, S. J. Danishefsky, Angew. Chem. 1995,107, 1886;
Angew. Chem., Int. Ed. Engl. 1995, 35, 1723; (d) Review: K. C. Nicolaou, R. K. Guy,
Angew. Chem. 1995, 107, 2247; Angew. Chem., Int. Ed. Engl. 1995, 35, 2079.
See, for example: (a) T. Ziegler, Chem. Rev. 1991, 91, 651; (b) J. K. Labanowski, J. W.
Andzelm (Eds.), Density Functional Methods in Chemistry, Springer, New York, 1991;
(c) 0. D. Haberlein, N. Rosch, J. Phys. Chem. 1993, 4970; (d) N. Rosch, S. Kostlmeier,
H. Bock, W. A. Henmann, Organometallics 1996, 15, 1872; (e) G. Frenking in
B. Comils, W. A. Henmann, R. Schlogl, C.-H. Wong (Eds.), Catalysis from A to Z,
Wiley-VCH, Weinheim, 2000.
J. S. Giovannetti, Ch. M. Kelly, C. R. Landis, J. Am. Chem. Soc. 1993, 115, 4040.
(a) M. W. Balakos, S. S. C. Chuang, J. Catal. 1995, 151,253, 266; (b) R. M. Deshpande,
R. V. Chaudhari, Ind. Eng. Chem. Res. 1988, 27, 1996; (c) S. S. Divekar, R. M. Desh-
pande, R. V. Chaudhari, Catal. Lett. 1993, 21, 191.
R. V. Gholap, 0. M. Kut, J. R. Bourne, Ind. Eng. Chem. Res. 1992, 31, 1597, 2446.
BP Chemicals Ltd. (M. J. Baker, J. R. Dilworth, J. G. Glenn, N. Wheatley), EP 0.632.006
(1994).
D. Astruc, Electron Transfer and Radical Processes in Transition Metal Chemistry,
VCH, Weinheim, 1995.
G. W. Parshall, S. D. Ittel, Homogeneous Catalysis, 2nd ed., John Wiley, New York,
1992.
(a) K. Eller, H. Schwarz, Chem. Rev. 1991, 91, 1121; (c) B. S. Freiser, Acc. Chem. Res.
1994, 27, 353; (c) D. Schroder, H. Schwarz, Angew. Chem. 1995, 107, 2126; Angew.
Chem., Int. Ed. Engl. 1995, 34, 1973.
B. Brielbeck, E. Spika, M. Frede, E. Steckhan, BIOforum 1994, 17, 22.
(a) C. G. Hill, Activation and Functionalization of Alkanes, Wiley, New York, 1989;
(b) R. G. Bergman, ACS Adv. Chem. Ser: 1992, 230, 211; (c) R. H. Crabtree, Chem.
Rev. 1995, 95, 987.
Review: A. Behr, Angew. Chem. 1988, 100, 681; Angew. Chem., Int. Ed. Engl. 1988,
27, 661.
Monographs: (a) A. Behr, Carbon Dioxide Activation by Metal Complexes, VCH Wein-
heim, 1988; (b) W. Keim (Ed.), Catalysis in C,-Chemistry, D. Reidel, Dordrecht, 1983.
(a) R. G. Bergman, B. A. Arndtzen, Science 1995, 270, 1970; (b) P. L. Watson, G. W.
Parshall, Acc. Chem. Res. 1985, 18, 51; (c) M. Gozin, A. Weisman, Y. Ben-David,
D. Milstein, Nature 1993, 364, 699; see also: W. D. Jones, ihid. 1993, 364, 676;
(d) M. Gozin, M. Aizenberg, S.-Y. Liou, A. Weisman, J. Ben-David, D. Milstein, Nature
1994,370,42;(e) S.-Y. Liou, M. Gozin, D. Milstein, J. Am. Chem. Soc. 1995, 117, 9774;
(f) M. Hudlicky, Chemistry of Organic Fluorine Compounds, 2nd edition, p. 175ff,
Prentice-Hall, New York 1992; (g) M. Aizenberg, D. Milstein, Science 1994, 265,
359; (h) M. Aizenberg, D. Milstein, J. Am. Chem. Soc. 1995, 117, 8674;
1380 4.1 Homogeneous Catalysis - Quo vadis?

(i) J.-M. Basset, V. Dufaud, unpublished results 1995/95; (k) J. Corker, F. Lefevre,
Ch. LCcuyer, V. Dufaud, F. Quignard, A. Choplin, J. Evans, J.-M. Basset, Science
1996, 271, 966; (I) J.-M. Basset, V. Dufaud, FR. 9.508.552 (July 13, 1995).
[58] Ruhrchemie AG (B. Comils, W. Konkol, H. W. Bach, G. Dambkes, W. Gick, E. Wiebus,
H. Bahrmann), DE 3.415.968 (1984); EP 0.160.249 (1985).
[59] Argonne National Laboratory (J. W. Rathke, R. J. Klinger), US 5.198.589 (1994).
[60] R. G. Jessop, T. Ikariya, R. Noyori, Nature (London) 1994, 368, 23 1 ; ibid. 1995, 269,
1065; Chem. Rev. 1995, 95, 259. See also: W. Leitner, Angew. Chem. 1995, 107,
2391; Angew. Chem., Int. Ed. Engl. 1995, 34, 2187.
[61] (a) R. A. Sheldon, Top. Cum Chem. 1993, 164, 21; (b) R. A. Sheldon, CHEMTECH
1991, 566; (c) R. A. Sheldon, J. Dakka, Catal. Today 1994, 19, 215; (d) Hoechst AG
(W. A. Herrmann, W. Adam, R. W. Fischer, J. Lin, Ch. R. Saha-Moller, J. D. G. Correia),
DE 4.419.799 (1994); (e) W. A. Herrmann, W. Adam, J. Lin, Ch. R. Saha-Moller, R. W.
Fischer and J. D. G. Correia, Angew. Chem. 1994, 106, 2545; Angew. Chem. Int. Ed.
Engl. 1994, 33, 2475; (0W. Adam, W. A. Herrmann, Ch. R. Saha-Moller, M. Shimizu,
J. Mol. Catal. 1995, 97, 15.
[62] Monographs: (a) G. Strukul (Ed.), Catalytic Oxidations with Hydrogen Peroxide as
Oxidant, Kluwer Academic, Dordrecht, 1992; (b) L. I. Simandi, Catalytic Activation
of Dioxygen by Metal Complexes, Kluwer Academic, Dordrecht, 1992; (c) R. A. Shel-
don, J. K. Kochi, Metal-Catalyzed Oxidations of Organic Compounds, Academic
Press, London, 1981; (d) D. H. R. Barton, A. E. Martell, D. T. Sawyer (Eds.), The Acti-
vation of Dioxygen and Homonuclear Catalytic Oxidution, Plenum, New York, 1993.
[63] Review: W. A. Herrmann, J. Organomet. Chem. 1995,500, 149.
[64] See, for example: C. Botteghi, G. Del Ponte, M. Narchetti, S. Paganelli, J. Mol. Catal.
1994, 93, 1.
[65] (a) J.-L. Couturier, Ch. Paillet, M. Leconte, J.-M. Basset, K. Weiss, Angew. Chem. 1992,
104, 622; Angew. Chem., Int. Ed. Engl. 1992, 31, 628; (b) J.-L. Couturier, K. Tanaka,
M. Leconte, J.-M. Basset, Angew. Chem. 1993, 105, 99; Angew. Chem.,Int. Ed. Engl.
1993, 32, 112.
[66] (a) Shell (E. Drent), EP 121.965 (1984); Chem. A b s ~ 1985, 102, 46423; (b) E. Drent,
J. A. M. van Broekhoven, M. J. Doyle, J. Organomet. Chem. 1991, 417, 235;
(c) E. Drent, P. H. M. Budzelaar, Chem. Rev. 1996, 96, 663; (d) K. Nozaki, N. Sato,
H. Takaya, J. Am. Chem. Soc. 1995, 117, 9911; (e) E. Drent, P. Amoldy, P. H. M.
Budzelaar, J. Organomet. Chem. 1994, 475, 57.
[67] (a) BASF AG (G. Witzel et al.), DE 843.876 (1951); (b) B. Comils, H. Bahrmann,
Chem.-Ztg. 1980, 104, 39; (c) J. F. Knifton, Catal. Today 1993, 18, 355.
[68] H. Sinn, W. Kaminsky, Adv. Organornet. Chem. 1980, 18, 99, and references cited
therein.
[69] Reviews: (a) H.-H. Brintzinger, D. Fischer, R. Mulhaupt, B. Rieger, R. Waymouth,
Angew. Chem. 1995, 107, 1255; Angew. Chem., Int. Ed. Engl. 1995, 34, 143;
(b) H. Cherdron, M.-J. Brekner, F. Osan, Angew. Makromol. Chem. 1994, 223, 121;
(c) G. Fink, R. Mulhaupt, H.-H. Brintzinger (Eds.), Ziegler Catalysts, Springer, Berlin,
1995; (d) A. M. Thayer, Chem. Eng. News, 1995, Sept. 11, p. 15.
[70] (a) F. Kuber, New Scientist, Aug. 1993, 28; (b) F. Kuber, M. Aulbach, Chem. uns. Zeit
1994, 28, 197.
[71] (a) G. W. Coates, R. M. Waymouth, Science 1995, 267, 217; (b) W. A. Herrmann,
W. Baratta, E. Herdtweck, Angew. Chem. 1996, 108, 2098; Angew. Chem., Int. Ed.
Engl. 1996, 35, 1951.
[72] 0. Nuyken et al., unpublished results, 1995.
[73] (a) W. A. Herrmann, S. Bogdanovic, R. Poli, T. Priermeier, J. Am. Chem. Soc. 1994, 116,
4989; (b) S. Bogdanovic, Ph. D. Thesis, Technische Universitat Munchen, 1994.
 References and Notes 138 1

[74] R. R. Schrock, Pure Appl. Chem. 1994, 66, 1447.

[75] C. P. Snow, The Two Cultures: And a Second Look, Cambridge University Press,
London, 1959.
[76] (a) M. de Sousa Healy, A. J. Rest, Adv. Inorg. Radiochem. 1978, 21, 1; (b) J. Steinke,
D. C. Sherrington, I. R. Dunkin, Adv. Polym. Sci. 1995, 123, 81.
1771 E. Montflier, G. Fremy, Y. Castanet, A. Montreux, Angew. Chem. 1995, 107, 2450;
Angew. Chem., Int. Ed. Engl. 1995, 34, 2269.
1781 (a) R. A. Lemer, S. J. Benkovic, P. G. Schultz, Science 1991, 252, 659; (b) J. D. Stew-
art, L. J. Liotta, S. J. Benkovic, Acc. Chem. Res. 1993, 26, 396; (c) B. L. Iverson,
CHEMTECH 1995, 25 (June), 17; (d) E. Keinen, S. C. Sinha, D. Shabat, H. Itzhaky,
J.-L. Reymond, in Ref. 1161, p. 383.
[79] (a) M. T. Reetz, S.-H. Kyung, C. Bolm, T. Zierke, Chem. Ind. (London) 1986, 824;
(b) U.Koert, Nachr: Chem. Tech. Lab. (Weinheim) 1995,43, 1068.
[SO] G. Dyker, Angew. Chem. 1995, 107, 2407; Angew. Chem., Int. Ed. Engl. 1995, 34,
2223.
[81] E. Monflier, G. Fremy, Y. Castanet, A. Mortreux, Angew. Chem. 1995, 107, 2450;
Angew. Chem., Int. Ed. Engl. 1995, 34.
[82] P. G. Schultz, Angew. Chem. 1989, 101, 1336; Angew. Chem., Int. Ed. Engl. 1989,
28, 1283.
1831 M. T. Reetz, S. A. Quaker, Angew. Chem. 1995, 107, 2461; Angew. Chem., Int. Ed.
Engl. 1995, 34, 2240.
[84] (a) H. Konig, R. Rogi-Kohlenprath, H. Weber in Chiral Reactions in Heterogeneous
Catalysis (Eds.: G. Jannes, V. Dubois), Plenum, 1995, p. 135; (b) C. Exl, I. Francesconi,
H. Honig, R. Rogi-Kohlenprath, Preprints 8th Int. Symp. on the Relations between
Homogeneous and Heterogeneous Catalysis, Balatonfured, 1995.
1851 (a) J. M. Lehn, Angew. Chem. 1988, 100, 91; Angew. Chem., Int. Ed. Engl. 1988, 27,
89; (b) D. J. Cram, Angew. Chem. 1988,100, 1041; Angew. Chem., Int. Ed. Engl. 1988,
27, 1009.
[86] (a) C. J. Li, Tetrahedron Lett. 1995, 36, 517; (b) R. Sjoholm, R. Rairama, M. Ahonen,
J. Chem. Soc., Chem. Commun. 1994, 1217.
(871 P. Maitlis, H. Long, Z.-Q. Wang, M. L. Tumer, Ref. [16], p. 3.
I881 H. Heinemann, CHEMTECH 1971, I (3,286.
[89] A. Muller, H. Reuter, S. Dillinger, Angew. Chem. 1995, 107, 2505; Angew. Chem., Int.
Ed. Engl. 1995, 35, 2328.
[90] (a) L. K. Johnson, Ch. M. Killian, M. Brookhart, J. Am. Chem. Soc. 1995, 117, 6414;
(b) L. K. Johnson, S. Mecking, M. Brookhart, ibid. 1996, 118, 267.
1911 J. Haggin, Chem. Eng. News 1996, 74 (6), p. 6.
1921 W. A. Henmann (Ed.), Topics in Current Chemistry, Vol. 179, Springer, Berlin, 1996.
[93] B. Cornils, W. A. Henmann (Eds.), Aqueous-Phase Organometallic Catalysis, Wiley-
VCH, Weinheim, 1998.
[94] Cf. Ref. 1191, Section 2.5.
[95] Review: F. Agbosson, J.-F. Carpentier, A. Mortreux, Chem. Rev. 1995, 95, 2485.
[96] M. J. Cannarsa, Chem. Ind. 1996, 374.
1971 T. Shibata, K. Choji, H. Morioka, T. Hayase, K. Soai, J. Chem. SOC., Chem. Commun.
1996, 75 I .
[98] R. R. Bader, P. Baumeister, H.-U. Blaser, Chimia 1996,50,99; Ciba-Geigy AG (P. Bau-
meister, G. Seifert, H. Steiner), EP 584.043 (1992).
[99] (a) U.Bremberg, M. Larhed, C. Moberg, A. Hallberg, J. Org. Chem. 1999, 64, 1082;
(b) U. Bremberg, S. Lutsenko, N.-F. K. Kaiser, M. Larhed, A. Hallberg, C. Moberg,
Synthesis 2000, 1004.
1382 4.1 Homogeneous Catalysis - Quo vadis?

[IOO] N.-F.K. Kaiser, U. Bremberg, M. Larhed, Ch. Moberg, A. Hallberg, Angew. Chem.
2000,112, 3742;Angew. Chem., Int. Ed. 2000, 39, 3596.
[I011 H. Ihee, J. Cao, A. H. Zewail, Angew. Chern., Int. Ed. 2001, 40, 1334.
[I021 B. Jandeleit, D. J. Schaefer, T. S. Powers, H. W. Turner, W. H. Weinberg, Angew. Chem.
1999, 111; Angew. Chem., Int. Ed. 1999, 38, 2494.
[I031 F. Hollmann, A. Schmid, E. Steckhan, Angew. Chem. 2001, 113, 190; Angew. Chem.,
Int. Ed. 2001, 40, 169.
[104] W. A. Herrmann, J. P. Zoller, R. W. Fischer, J. Organomet. Chem. 1999, 579, 404.
[lo51 W. A. Herrmann, Th. Weskamp, J. P. Zoller, R. W. Fischer, J. Mol. Catal. A: Chemical
2000, 153, 49.
[lo61 (a) P. G. Jessop, T. Ikariya, R. Noyori, Chern. Rev. 1999,99, 475; (b) J. L. Kendall, D. A.
Canelas, J. L. Young, J. M. Defimore, Chem. Rev. 1999, 99, 543.
[I071 A. Furstner, D. Koch, K. Langemann, W. Leitner, C. Six, Angew. Chem. 1997, 109,
2.562; Angew. Chem., Int. Ed. Engl. 1997, 36, 2466.
11081 A. Fiirstner, Angew. Chem. 2000, 112, 3140; Angew. Chem., Int. Ed. 2000, 39, 3012.
[I091 P.G. Jessop, Y. Hsiao, T. Ikariya, R. Noyori, J. Am. Chem. Soc. 1996, 118, 344.
[110] W. Klaui, J. Bongards, G. J. ReiB, Angew. Chem. 2000, 112, 4077; Angew. Chem., Int.
Ed. 2000, 39, 3894.
[ 1 1 I] W. Leitner, Adv. Organomet. Chem. 2000, 14, 809.
11121 R. A. Brown, P. Pollet, E. McKoon, Ch. A. Eckert, Ch. L. Liotta, P. G. Jessop, J. Am.
Chem. Soc. 2001, 123, 1254.
[113] Short review: P. Wasserscheid, W. Keim, Angew. Chem. 2000, 112, 3926; Angew.
Chem., Int. Ed. 2000, 39, 3772.
[ 1141 See, for example: Solvent Innovation GmbH: http://www.solvent-innovation.com.
11151 (a) W.A. Herrmann, V.P. W. Bohm, J. Organomet. Chem. 1999, 572, 141; (b) L. Xu,
W. Chen, I. Xiao, Organometallics 2000, 19, 1123; (c) A. I. Carmichael, M. I. Earle,
I.D. Holberg, P.B. McCormac, K.R. Seddon, Org. Lett. 1999, 1, 997; (d) V.P. W.
Bohm, W. A. Henmann, Chern. Euc J . 2000, 6, 1017.
[ 1161 P. Wasserscheid, M. Eichmann, Proc. 3rd Int. Symp. Catal. In Multiphase Reactors,
Naples, 2000, pp. 249-261.
[117] (a) Ch. Dobler, G. Mehltretter, M. Beller, Angew. Chem. 1999, 111, 3211; Angew.
Chem. Int. Edit. Engl. 1999, 38, 3026; (b) Ch. Dobler, G. Mehltretter, U. Sundermeier,
M. Beller, J. Amec Chem. Soc. 2000, 122, 10289.
11181 S. L. Aeilts, D. R. Cefalo, P. J. Bonitatebus Jr., J. H. Houser, A. H. Hoveyda, R. R.
Schrock, Angew. Chem., Int. Ed. 2001, 40, 1452.
[ 1191 J. F. Hartwig et al., J. Am. Chem. Soc. 2000, 122, 9546.
11201 A. Togni et al., J. Am. Chem. SOC. 1997, 119, 10857; Lonza AG, EP 0.909.762.
11211 Reviews: (a) W.A. Herrmann, Ch. Kocher, Angew. Chem. 1997, 109, 2256; Angew.
Chem., Int. Ed. Engl. 1997, 36, 2162; (b) W. A. Henmann, Angew. Chem. 2002, in
press; Angew. Chem., Int. Ed. 2002, in press; (c) T. Weskamp, V. P. W. Bohm, W. A.
Henmann, J. Organomet. Chem. 2000, 600, 12; (d) W.A. Herrmann, T. Weskamp,
V. P. W. Bohm, Adv. Organomet. Chem. 2002, in press.
[ 1221 (a) T. Weskamp, F. J. Kohl, D. Gleich, W. A. Herrmann, Angew. Chem. 1999, 111, 2.573;
Angew. Chem., Int. Ed. 1999, 38, 2416; (b) M.S. Sanford, M. Ulman, R.H. Grubbs,
J. Amec Chem. Soc. 2001, 123, 749.
[I231 V. P. W. Bohm, T. Weskamp, Ch. W. K. Gstottmayr, W. A. Herrmann, Angew. Chem.
2000, 112, 1672; Angew. Chem., Int. Ed. 2000, 39, 1602.
[124] Review: R. Anwander, in Lanthanides: Chemistry and Use in Organic Synthesis
(Ed.: S . Kobayashi), Springer, Berlin, 1999, Vol. 2, pp. 1-62.
[I251 R. Anwander, 0. Runte, J. Eppinger, G. Gerstberger, E. Herdtweck, M. Spiegler,
J. Chem. SOC. Dalton Trans. 1998, 847.
 References and Notes 1383

[I261 (a) T. Skrydstrup, Angew. Chem. 1997,109, 355; Angew. Chem., Int. Ed. Engl. 1997,
36, 345; (b) H.B. Kagan, J.-L. Namy, in Ref. [124], pp. 155-198.
[I271 (a) M. A. Giardello, V. P. Conticelli, L. Brard, M. R. Gagne, T. J. Marks, J. Am. Chem.
SOC.1994, 116, 10241; (b) Y. Li, P.-F. Fu, T. J. Marks, Organometallics 1999, 13, 439.
[I281 (a) Review: J. Yasuda, in Ref. [124], pp. 25.5-283; (b) H. Yasuda, H. Yamamoto,
K. Yokota, S. Miyake, A. Nakamura, J. Am. Chem. SOC.1992, 114, 4908;
(c) H. Yasuda, E. Ihara, Advan. Polym. Sci. 1997, 133, 53.
[1291 J. M. J. Frkchet, M. Kawa, Chem. MuteK 1998, 10, 286.
[130] Reviews: (a) T.J. Marks, Ace. Chem. Res. 1992, 25, 57; (b) W.M.H. Sachtler,
Z. Zhang, Adv. Catal. 1993, 39, 129.
[ 131J C. Piguet, G. Bernardinelli, G. Hopfgartner, Chem. Rev. 1997, 97, 2005.
[132] H. W. Bohnen, B. Comils, Adv. Catul. 2002, in press.
[1331 Angew. Chem., Int. Ed. Engl. 1997, 36, 1431 and 2001, 40, 4422; Nature 1999, 401,
254 and 2000, 404, 982; Science 1998, 279, 1021.
[ 1341 Keyword “history of catalysis” in B. Comils, W. A. Herrmann, R. Schlogl, C.-H. Wong
(Eds.), Catalysis from A to Z, Wiley-VCH, Weinheim, 2000.
[135] W. A. Herrmann, M. Muhlhofer, T. Strassner, unpublished results 2001; Angew. Chem.
2002, in press (review article on N-heterocyclic carbenes in catalysis).
[136] V. P. W. Bohm, C. W. K. Gstottmayr, T. Weskamp, W. A. Herrmann, Angew. Chem., Int.
Ed. 2001, 40, 3387.
[137] H. Arakawa et al., Chem. Rev. 2001, 101, 953.
Index

A - via oxidation of hydrocarbons 9,

AS plant 122 106ff, 427, 525 ff, 535
AAA (acetic acid anhydride) acetic acid process
- in arene oxidations 440 - rhodium carbonyl catalyst 33
Abakavir 900 - via carbonylation 106
ab-initio calculations acetic anhydride
- in diene polymerizations 292 - by carbonylation 122, 124
- in hydrogenation of carbon - in oxidative carbonylation 169
dioxide 1197 - manufacture 116ff, 121
- in homogeneous catalysis 703 ff acetic anhydride process
ACAT inhibitor 577 - alkyl phosphines 120
acetaldehyde 407, 396 ff - block flow diagram 120
- as by-products in carbonylations 453 - electrochemical methods 120
- by ethylene oxidations 113 - extraction methods 120
- by homologation of methanol 1034ff - phenyl phosphines 120
- co-oxidations 281 - precipitation 120
- dialkyl acetals 430 - separation of catalyst and residues 120
- oxidation to acetic acid 106 - syngas stripping 120
- oxidations, ethylene-based 399 Acetica 129
- purification 280 acetone
acetaldehyde diacetal - carbonylation of methyl acetate 118
- in homologation of alcohols 1035 - a-picoline synthesis 12%
acetate anions - steady-state concentration 1 19
- in propyne carbonylation 3 18 - via propene 400
acetic acid (AA) - Wacker-type reaction product 402
- (2-pyrrolidone)-2-acetic acid 162 acetone cyanohydrine
- amidocarbonylation 162 - in alkyne-hydrocyanation 479 f
- as solvent in the Amoco process 546 acetophenone
- as terminal product in oxidations - by chloride-free oxidation 402
530 f - hydrogenation 681
- by oxidation of ethane 1234ff - in carbonylation of aryl-X-compounds
- by oxidation of methane 1236 149
- by carbonylation of methanol 18 - 4-isobutylacetophenone 149
- by homologation 141 - via autoxidations 443
- in alkyne carbonylations 316 acetox ybenzofuranes
- in arene-autoxidations 445 - via carbonylation of aryl-X-compounds
- in catalyzed chain reactions 531 151
- in paraffin oxidation processes 539 acetox ycarbazoles
- in propyne carbonylations 3 18 - via carbonylation of aryl-X-compounds
- propionic acid synthesis 1035 151
- purification 115 acetox yindoles
- via alkyne carbonylation 317 - via carbonylation of aryl-X-compounds
- via catalyzed oxidation of MEK 536 151
1386 Index

acetoxylations 402 - via oxidation of hydrocarbons 527

B-acetoxypropionic acid in oxidative - via uncatalyzed hydrocarbon
carbonylations 168 oxidations 528
acetyl chloride acrolein
- decomposition mechanism 119 - Diels-Alder reaction 9 13
acetyl iodide - oxidation of propane 1297
- decomposition to polyester acrylate esters
polyketones 119 - in alkyne carbonylations 316
- hydrolysis, in carbonylations 113 acrylic acid 10, 428
acetylcyanylation - by chloride-free oxidation of propene
- of aldehydes 485 402
acetylene - by oxidative carbonylations 166, 168 f
- alkynes 274 - synthesis 277f
- carbonylation 168, 318 acrylamine
- cyclization 683 - by biocatalysis 889
- cyclotetramerization 368, 1264 - by hydration 889
- gas-phase hydrosilylation 501 acrylonitrile
- in alkyne carbonylation 326 - cobalt-catalyzed hydrofotmylations 39
- in alkyne reactions 280, 282 - hydrocarboxylations 186
- in olefin oxidations 386 - a-picoline synthesis 1255
- in Pauson-Khand reaction 1241 - SOH10 process 1297 ff
- in polybutadiene manufacturing 3 10 - synthesis 282
- in polymerization 333 actinides
- insertion in hydrosilylations 499 - C-H activation 1231
- pyridine synthesis 1252 - Cp*,A,Me, 499
- trimerization 368 - organoactinide complexes in
acetylenecarboxylic esters 376 hydrosilylations 499
acetylenedicarboxylic esters activation barriers in hydrosilylations 493
- in alkyne-reactions 281 activators
acetylenes see alkynes - in catalyzed hydrocarbon oxidations
- in metathesis polymerizations 33 1 540
0-acetyl-(R)-mandelic acid as chiral - in hydrosilylations 496
auxiliary in oligomerizations 225 active species
acids see carboxylic acids, see also fatty - in arene oxidations 435 f, 437 ff
acids - in ethylene oligomerizations 249
achiral metallocenes 219 - in polymerizations 2 16
acid esters activity
- in hydrocarboxylations 188 - enzyme-like, in propyne carbonylation
Acid Optimization (AO) 107f 326
acid/H202/MT0 - in arene-autoxidations 445
- oxidation of 2-methylnaphthalene 434 - in polybutadiene manufacturing 309 f
acids - in polypropylene polymerization 222
- a-acylaminoacrylic acids 573 - of alkyne carbonylation catalysts
- 2-arylpropionic acid 186, 562, 559 317 f, 326
- 4-hydroxyphenylacetic acid 148 - of allylnickel catalysts 298
- in Pd catalyzed oxidative - of arene-oxidation catalysts 440
acetoxylations 41 I acyclic alkenes in metathesis reactions
- a,B-unsaturated acids 168 329 ff
- unsaturated, in liquid phase Acyclic Diene Metathesis see ADMET
oxidations 428 acyl chloride 161
- via carbonvlation of alkanes 191 acyl cleavage in hydrocarboxylations 183
 Index 1387

acyl complexes in hydrocarboxylations alcohols

183 - alkali fusion 427
acyl radicals - by asymmetric reduction 1142
- by aldehydes, in catalyzed oxidations - by Meenvein-Ponndorf-Verley
533 reaction 1003
- via radical carbonylations 192 - by oxazaborolidines 1142
acylamoinoacrylic acids - by reduction in biocatalysis 877ff
- asymmetric hydrogenations 573 - carbonylation 148
acylcobalt bond - formation, Shell process 74
- hydrolysis/alcoholysis 162 - homologation 1034 ff
acylcobalt complex - 4-hydroxybenzyl alcohol 148
- reaction in the hydroformylation - in alkyne carbonylations 326
cycle 46f - in synthesis of isocyanates 1215
acyloxy radicals in catalyzed chain - oxidation in biocatalysis 878, 959
reaction 534 - remote carbonylations 192
acylperoxy radicals alcoholysis in polyketone formation 350,
- as intermediates in aldehyde 353
oxidations 530 aldehydes
- in catalyzed chain reactions 534, - alkylation 947
538 - amm(0n)dehydrogenation 1301
acyltransfer reaction - as intermediates in parafin oxidations
- in template synthesis 924ff 539
AD (asymmetric dihydroxylation) - as promoters in the Amoco process
- mixtures in dihydroxylation of olefins 547
1153 - as redox-amphoteric precursors 3 1
adamantane - asymmetric hydrosilylations 498
- oxidation 960 - by carbonylation of alkanes 1230
additives - by photocleavage of diols 1074
- in arene-autoxidations 45 I - gold-aldol reaction 1144
adipic acid - hydrocyanations 485 f
- by oxidation of cyclohexanone 960 - in alkyne-reactions 282
- in oxidative carbonylations 170 - McMurry coupling 1093 ff.
adipic acid precursors 166 - olefination 1078ff
adiponitrile - oxidations 427, 533, 538, 959
- via butadiene hydrocyanations 48 1 ff - via carbonylation of alkanes 191
ADMET 329 aldol condensation in Aldox process 771
ADN aldol route 402
- in butadiene hydrocyanations 483 aldolases in biocatalyis 880
agglutinations 384 Aldox process 771
agostic interactions 715 ff Alfen process 243
AIBN in radical carbonylations aliphatic alcohols in oxidative
- air 192 carbonylations 171
- in dihydroxylation of olefins 1159 aliphatic aldehydes
- oxidant in aldehyde oxidations 400, - oxidation to carboxylic acids 427 ff
427 aliphatic carboxylic acids
Ajinomoto 39, 116 - via aliphatic aldehydes 427 ff
- L-Dopa process 903 aliphatic groups
?'-A1203 - carbonylations 190
- immobilization of hydrosilylation alkali metals
catalysts 500 - as cataysts in hydroaminations
- in oxidative carbonylations 174 516f
1388 Index

alkaline salts - by oxidative carbonylations 167

- carbonylation of methyl acetate alkoxy radicals in catalyzed chain
118 reactions 533
alkaloids alkoxycarbonylations 145, 150
- as chiral auxiliaries 1153 ff alkoxycarbonylpalladium species in
- cinchona 1153ff oxidative carbonylation 174
alkanes alkoxysilanes by asymmetric
- C-H activation 1071 ff, 1226 ff hydrosilylation 498
- carbonylation 1230 ff alkyl acrylates in hydrocarboxylation
- dimerization 1229 185
- in SOMC 667ff alkyl D-alkoxypropionates in oxidative
- oxidation 1232ff carbonylation 167
- transfer dehydrogenation 1230 alkyl hydroperoxides
alkanecarboxylic acids in carbonylations - in epoxidations 413 ff
189 - oxidant in epoxidations 424
alkanoic acides alkyl nitrites in oxidative carbonylation
- generation of carboxylic acids 143 165, 173, 175
- via hydrocarboxylations 185 alkyl peroxides
alkanoic acids see also carboxylic acids - in photooxidation 1070
alkenediones alkyl phosphines in acetic anhydride
- cyclopentadiene-cyclocondensations process 120
268 alkyl sarcosinates via amidocarbo-
alkene-insertions nylations 161 ff
- migratory, in hydrosilylation 493 alkylaluminium catalysts in ethylene
alkene isomerization in hydro- oligomerizations 240
carboxylations 184 alkylalurninium chloride derivatives in
alkenes (see also olefins) dimerizationslcodimerizations 254
- 1-alkenes 88 alkylaromatics in catalyzed hydrocarbon
- alkoxycarbonylations 1 83 oxidations 536
- amidations of 182 ff alkyl-aryl-ketones
- by asymmetric oligomerization 225 - asymmetric reductions 568
- dehydrogenative silylation 502 ff alkylation
- 2,2-dialkyl- 1-alkenes 37 - of aldehydes 947
- dicarboxylation 188 - of aryl halides 824
- esterification 182ff alkyldiphenylphosphine
- hydrocarboxylation 182 ff - deactivation of hydroformylation
- in hydroformylation 37 catalysts 60
- in metathesis reaction 329 alkylidenes in metathesis reactions 329,
- oxidative acetoxylations 406 ff 334
- oxidative carbonylations 166 ff alkylmetallocenium ions in
- rhodium complex catalyzed polymerizations 2 16 f
hydrosilylation 50 1 alkylperoxide radicals in catalyzed
- trans-silylation 88, 505 hydrocarbon oxidations 536
alkenylsilanes alkylphenols 242
- intermolecular hydrosilylations 495 alkylphosphines as ligands in the Shell
alkenylsuccinic anhydrides via a-olefin process 74
conversions 242 g-alkyl complex in hydrocyanations 470
alkenynes in silylcatbocyclizations - cotrimerization with carbon dioxide
507 1194
p-alkoxy esters - cyclodimerization 989 f
- via dialkoxycarbonylations 188 - cyclooligomerization 1252 ff
 Index 1389

- cyclopropanation 802 n-ally1 insertion mechanism

- cyclotrimerization 1261 ff - in butadiene polymerization 299, 301
- dehydrogenative silylations 502 ff - in diene polymerizations 292 f
- disubstituted 333 - in stereospecific polymerizations 288 f
- general properties 274f ally lation
- hydrocyanation 479 - by allyl-ally1 cross-coupling 1065
- hydrogenation 955 - of alkynes 967
- in cyclo-co-oligomerizations 375 allylic alcohols
- in cyclotrimerization 332 - asymmetric hydrogenation 558
- in hydroformylations 68 - epoxidations 415
- in metathesis reactions 332ff - in asymmetric epoxidation 420
- in propyne carbonylations 321 allylic amination
- internal, in metathesis reactions 336 - racemate catalyzed 575
- oligomerization 989 n-allylic complexes
- oxidation 958 - in butadiene hydrocyanation 482
- Pauson-Khand reaction 1241 allylic compounds in the oxirane
- polymerization 1055 technology 4 19
- reactions 274ff allylic derivatives
- silylations 503 - allyl-ally1 cross-coupling 1065
- silylative cyclocarbonylation 507 - isomerization 1121 f, 1125 f
- stannyl alkynes 480 u-ally1 insertion mechanism
- terminal 277, 329 - in butadiene polymerizations 294
alkynes - in stereospecific polymerizations 289
- 1,2 additions 275 allylneodymium complexes in butadiene
- allylation 967 polymerization 294
- carbonylation 3 16 f, 964 f allylnickel complexes in butadiene
- a-ketoalkynes, in hydrocyanations 48 1 polymerization 297 ff
alkynones 283 y’-allylnickel complexes in dimerizations
allenes and codimerizations 254
- carbonylation 965 allylnickel halides in butadiene
- hydrocyanation 484 polymerization 297 ff
- in cyclooligomerizations 379 allylnickel trifluoroacetate in 1,4-poly-
- oxidation 958 merization 303
allyl acetate allyltrimethylsilane in cycloolefin
- by propylene-acetoxylation 409 ff polymerizations 224
- in carbonylations of aryl-X- Alphabutol process 259 ff
compounds 148 - flow scheme 260
allyl alcohol aluminium
- activation energy for the - AKCJIs), 308
hydroformylation 54 - Al(i-Bu), 310
- asymmetric epoxidation 1140 - Al(i-Bu)H 310
- asymmetric hydrogenation 11 38 - Al(i-C4Hg)3 308
- by hydrogenation of butenal 757 - AIEt2CI 309
- hydroformylation 40, 54, 754 - alkylalumininium catalyst 306
- hydrogenation 750 - alkylaluminium halides 309
- in alkyne-isomerizations 283 - alkyls 243
- in Heck reaction 779 - [alumoxane-Me]-anion 2 16
allyl halides - as catalyst for PET production 550
- hydrodehalogenation 956 - chiral salenAl(II1) complexes 486
- hydrosilylations 498 - co-catalysts in polybutadiene
- in alkyne reactions 282 production 309
1390 Index

- ethylaluminium sesquichloride 309 ammonia

- in photocycloaddition 1068 - acrylonitril synthesis 1298 ff
- in polymerizations 216 - ammonium bisulfate 3 I6
- in Simmons-Smith reaction 803 - anhydrous 257
- ML,-Al(C,Hs), 499 - in amm(on)dehydration 1301
- oxide, BASF process 73 - a-picoline synthesis 1255
- R3Al 309 - synthesis 3
alumoxane - urea synthesis 1189
- ligand in butadiene polymerization 296 ammonium salts
alumoxane cocatalysts in polymerizations - in butadienelethylene codimerization
216 263
amides by hydrogenation of carbon - in phase-transfer catalysis 954 ff
dioxide 1202 ff amm(on)oxidation 1298 ff
amidations 182 ff Amoco process 460, 546
amidocarbonylation 145, 156 ff ampilicillin 895
- reaction mechanism 162 f anchoring see immobilization
amine ligands Anderson-Emmet-Kolbel mechanism
- cinchona alkaloids 1153 818
- IND 1155 Andrussow process 1298
- PHAL 1155 anhydrides in epoxy resin polymerizations
- phenanthroline 1220 383
- PYR 1155 anhydrous conditions in the carbonylation
amines of CH~OAC 113
- bifunctional in telomerizations 364 anilines
- by asymmetric hydrogenation of - by reduction of nitro arenes 954, 1090
imines 1145 - 2-haloanilines I5 1
- catalysts in epoxy resin - in carbonylations 15 1
polymerizations 383 - in Heck reaction 778
- in alkyne carbonylations 326 anisole in olefin polymerizations 2 13
- in epoxy resin polymerizations 383 ansa-ligand-synthesis 269
- in re-immobilizing ligands 686 ansa-metallocenes
amino acid derivatives by asymmetric - Group IV metallocene catalysts 213,
hydrogenations 573 267 ff
D-amino acids 893, 898 anthracene
amino acids by biocatalysis 891 ff - oxidation 435
p-amino acids via hydrocarboxylations antibodies in homogeneous catalysis
185 886, 936
P,y-amino acids via hydrocyanation of anti-insertion in butadiene polymerization
ansaturated nitrils 48 1 298
amino alcohols by oxyamination 1152, antiflammatory agents 148
1159 anti-Markovnikov addition
B-amino alcohols - in hydroboration 1003
- stereoselective synthesis 568 f - in hydrocarboxylation 184
aminoacylases in biocatalysis 89 1 - in hydroformylation 48, 50
B-aminoalkyl metals as intermediates in - in olefin hydrocyanation 470
hydroaminations 514 antimicrobial activity of propionic
B-aminoethyl complexes in acid 137
hydroaminations 5 15 antimony glycolate as catalyst in PET
aminomethylphosphonic acid in production 549
asymmetric epoxidations 423 anti-syn isomerizations
amm(on)dehydration 130 1 - in butadiene polymerization 292, 298
 Index 1391

- in cis- 1,4-polymerizations 303 - Grignard cross-coupling 824 f

- in trans- 1,4-polymerizations 300 f - Heck reaction 776ff
antitussives - hydrodehalogenation 956
- via glycidols, by asymmetric - Suzuki coupling 1276 ff
epoxidations 42 1 aryl triflates in Heck reaction 779
AOS (a-olefine sulfonates) 242 Arylon 460
API 461 arylpropionic acids
arachidonic ester by cyclopropanation - by asymmetric oxidation of (Rj-3-aryl-
796 1-butenes 562
aramides 460 - in carbonylations of aryl-X-compounds
a-aryl ketones 148
- asymmetric hydrogenation 568 - via hydrocarboxylations 185
Arbusov-like reactions 476 arylrhodium species
ARC0 40, 170, 413, 417 - deactivation of hydroformylation
- ethylurethane process 1090 ff catalysts 60
- glycidol process 1140 aspartame
arene coupling - via amidocarbonyIations 158
- by dimethyl phthalate 823 Asta Medica
- of benzene 823 - LHRH antagonist synthesis 898
arenes asymmetric see also chiral
- alkyl-substituted 443 - aldol reaction 1144
- Ar2PC3H7 61 - alkyne-nitrile cocyclization 1255 f
- ArC(0)OOH 449 - allylation 1065
- AKH2OOH 449 - allylic substitution 1146
- hydrogenation 955 - biocatalytic amidase 892 ff
- hydroxy-substituted 435 - carbocycle synthesis I295
- methoxy-substituted 435 - coupling of 2-naphthol 1072
- oxidation 433, 960f - cross-coupling 1145
- oxidative carbonylations 170 - cyclopropanation 798 ff
- rhenium catalyzed oxidation 439 - Diels-Alder reaction 913, 878ff, 1141,
aromatics see also arenes 1144
- carbonylations of aromatic - dihydroxylation 1 141, 1 1SO ff
compounds 147, 190 - ene reaction 1144
- dimines, as epoxy resin curing - epoxidation 1140
agents 383 - gold-aldol reaction 1144
aroyl chlorides - Grignard cross-coupling 824 f
- Blaser reaction 779 - Heck reaction 779f, 1146
Arrhenius activation energy - Henry reaction 993
- in hydroaminations 518 - hydroamination 1000 f
Arrhenius plot - hydroboration 1141
- dissociation energy of TPPTS 51 - hydrocyanation 1141
- hydroformylation of propene 53 - hydrogenation 1136 ff, 1145
aryl -boronic acids for Suzuki coupling - hydrolysis 875ff
1276 - hydrosilylation 998
aryl diazonium salts in Heck reaction - hydrovinylation 1166 f, 1 174 ff
778 - hydroxyamination 1159
aryl halides - isomerization 1125
- alkylation 824f - Michael reaction 994, 1141
- carbonylation 961 ff - reduction of carbonyl compounds
- cyanation 967 877, 904, 1142 ff
- dehalogenation 1005 - reductive amination 904
1392 Index

- synthesis and technical application Bayer 171, 310, 406

1132ff Baeyer-Villiger reaction 429, 530, 879
- synthesis in membrane reactors 947 ff Beckmann rearrangement 899
- synthesis with organozic compounds benzalactones
947 f - asymmetric hydrogenations 566
- transfer hydrogenation 1139, 1142 benzaldehydes
Atlantic Richfield see also ARC0 - by chloride-free oxidations 402
atom-transfer-chain catalysis 1056 ff - by oxidation of benzyl alcohol 959
atropic acid by carbonylation of - hydrocyanation 485
phenylacetylene 964 - in Co-catalyzed areneautoxidations
Aufbaureaktion in ethylene 449
oligomerizations 240 - in photochemical hydrosilylation SO2
autocatalysis - silylcyanylation 485
- by molecular recognition 929 f benzenes
autocatalytic cycle - 1,2,3-trimethoxy-5-methylbenzene
- carbonylation of ethylene 138 438
autoxidations of aromatic compounds - 1,2,4-trirnethylbenzene 332
443 ff - 1,3,5-trimethylbenzene 332
1-azaphospholenes in hydrovinylation - aryl-aryl coupling 823
1166ff - by cyclotrimerization of alkynes
azelaic acid in telomerizations 367 1261 f
azeotropes 119 - hydroxylation 960
aziridines - in arene oxidations 438
- by nitrenes 804 - metallation 822f
- carbonylation 966 - oxidation with MTO 434
- ring-opening 996 - via propyne trimerizations 332
azole antifungals 1160 benzoic acid esters by Rosenmund-
Tishchenko reaction 770
B benzoic acids in arene autoxidations 447
B(ChF5)3 benzonitrile
- cocatalyst in cyclopolymerizations - 2-phenylpyridine synthesis 1257
225 - by amm(on)oxidation of toluene
back biting reactions 1298
- in catalyzed chain reactions 534 benzoquinones
- in hydrocarbon oxidations 530f - chloride-free oxidants 402
Badische Anilin- & Sodafabrik AG - in dicarboxylations 188
see BASF - in oxidative carbonylations 174
baker’s yeast 877 benzothiophene
barbiturates - hydrodesulfurization 1 100f
- synthesis 282 - hydrogenation 1101 f
barium benzvalene
- anionic initiators 308 - in ROMP 330
Barker-Co/Mn/Br catalyst 443 benzyl acetates in Co-catalyzed arene-
Barton method 922 autoxidations 449
BASF 8, 88, 106, 278f, 316 benzyl alcohol
- alkynes 274 - by transfer hydrogenation 957
- synthesis of propionic acid 136ff - oxidation 959
- vitamin A production 40, 1079, 1124f benzyl halides
BASF process 66, 68, 69 ff, 82 f - carbonylation 754, 961
batch technology in alkylarene - Heck reaction 776ff
autoxidations 463 - hydrodehalogenation 956
 Index 1393

benzyldimethylamine as epoxy resin - in asymmetric isomerization 1125 f

curing agent 383 - in carbapeneme syntheses 576f
benzylic chlorides - in Heck reaction 779f
- carbonylation 153 BINAPHOS 472
benzylic radicals in autoxidation 447 BINAPO as ligand in enantioselective
benzylnixantphos 86 allylic substitutions 575
benzylperoxy radical BINAS 87
- elimination, in Co-catalyzed arene- BINOL
autoxidations 449 - as catalyst in glyoxylate-ene reactions
benzyltrialkylammonium salts in 575
carbonylations of aryl-X-compounds - as ligand in asymmetric nitroaldol
148 reaction 571
benzyl-X compounds - in olefin polymerization 977
- carbonylation 145 ff biocatalysis 872 ff
beta blockers 23 biodegradable polymers 983
- intermediates 570f biodegradation process 12
- via glycidols, by asymmetric biomimetic catalysis 1354 ff
epoxidation 42 1 biphasic systems 10
BF3 catalysts in I-decene - in the Shell process 245
oligomerizations 24 1 - RCWRP process 82
BHET - technology 264
- as intermediate in PET production biphenyls
548 - 4,4’-biphenyl 460
- by transesterification of DMT 549 - 2,2’-bis(dibenzophosphomethy1)-
bicyclo[2.2. Ilhept-2-ene 470 1- 1 ’-biphenyl 85
bicycloheptene - by aryl-aryl coupling 823
- hydrovinylation 1167 - by Suzuki coupling 1276ff
bidentate ligands 89 BIPHEP
- in carbonylations 129 - as ligand in asymmetric
- in hydrocarboxylations 185 hydrogenations 559, 562
biguanide derivatives in epoxy resin - asymmetric hydrogenation 1135,
polymerizations 383 1138f
bimetallic catalysts biphosphines
- amm(on)oxidation 1297 ff - ligands in alkyne carbonylation
- colloids 677, 682ff catalysts 3 17 f
- in amidocarbonylations 158 bipyridines
- in Heck reaction 780 - by 2-cyanopyridine and acetylene
- in hydrocarboxylations 185 1258
- in hydroformylation 763 - by dehydrodimerization of pyridine
- in Michael reaction 993 1258
BINAP 14, 23 BISBI 85f
- as ligand in asymmetric BISBIS 87
hydrogenations 559, 562, 565, bishydroxylation see dihydroxylation
573 f, 575, 578 bisindenyl systems in racemo-selective
- as ligand in prostaglandin synthesis synthesis 272
565 bismuth in oxidation of propene 1297
- as ligand in terpene syntheses 558 bisphenylphosphite complexes in trans-
- as ligand in the asymmetric naproxen 1,4-polymerizations 300
synthesis 559 bisphosphines
- in asymmetric hydrogenation 1 135, - containing P-N bonds 1022, 1023
1138f - containing P - 0 bonds 1021, 1023
1394 Index
bissilylation of unsaturated organic
compounds 49 1
bis-sulfonamides in the synthesis of chiral
secondary alcohols 567
bite angle 85
Blaser reaction 779
block polymers 988, 1074
BNPPA
- as ligand in (S)-ibuprofen and
(S)-naproxen synthesis 561
- in hydrocarboxylations 186
a-bond metathesis 506
boric acid in template synthesis 925
bornene
- hydrovinylation 1174
boron
- [ B u ~ N I B F ~151
- co-catalyst in asymmetric
hydrocyanations 472
- in carbonylations of aryl-X-
compounds 15 1
- in polymerizations 217, 219
- Ph,B/Ph3SnPh3BCN 483
- tetraalkylammonium borohydrides
475
- tetrakis(pentafluoropheny1)borate
- trifluoride-diethyl ether 309
- triphenylboron 483
- tris(pentafluoropheny1)borate 2 17
- tris(perfluoroary1)borate salts 270
Born-Oppenheimer appoximation 703
Boudouard equilibrium 814
BP Chemicals 9, 12, 33, 106f, 116, 122,
257
- homologation of alcohols 1042
- low-water technology 113 f
BR see polybutadiene rubber
Brassard's diene 993
Brefeldin A 579
Bridgestone Tire Co. 309
bromine
- alkali bromide 451
- as chain transfer agent in hydrocarbon
oxidations 540
- as free-radical source in the Amoco
process 546
- as promoters in the Amoco process
547
- co-catalyst 148
- Co(0Ac)Br 451
- CoBrz 451
- in carbonylations of aryl-X-compounds
149
- in Group IV metallocene catalysts 267
- 1-methylbenzyl bromide 149
- Mn(0Ac)Br 451
- NH4Br 451
- 2-phenylbenzyl bromide 267
bromine radicals 452
a-bromo ketones
- asymmetric hydroborations 5 , 68
bromobenzene
- carbonylation 153
- in carbonylations of aryl-X-compounds
146
Bucherer-Bergs condensation 876
building blocks
- benzoic 461
- polyimide 462
butadiene
- 1-phenylbuta- 1,3-diene 484
- 1,2-butadiene 310
- 1,3-butadiene 42, 159
- 1,2-polybutadiene 295 f
- 1,4-trans-poIybutadienes 286 f
- 2,3-dimethyl-l,3-butadiene 502
217 - 2,3-dimethylbutadiene 370
- ~'-cis-coordinated 303
- codimerization with ethylene 263
- coordination, in stereospecific
polymerizations 288, 293
- cyclodimerization 373
- cyclooligomerization 650, 772
- dimerization 362, 368
- hydrocarboxylation 186 ff
- hydrocyanation 481 ff, 484
- hydrodimerization 40, 364
- hydroformylation 42
- in amidocarbonylation 159
- in cyclodirnerization 368
- in cyclooligomerization 36 1, 370 ff
- in hydrosilylation with various organic
peroxides 502
- in polybutadiene manufacturing 3 10
- lactone synthesis 1191 ff
- manufacturing process 306
- oligomerization products 369
- oxidative carbonylations 170
- peroxides, in the manufacturing
process 306
- polymerization 295, 298, 75 1, 983
- telomerization 151, 187, 362
 Index 1395

butanal butyraldehydes see also butanal

- 4-hydroxybutanal 89 - technical oxidations of 43 1
- in rhodium-based processes 75, 89 butyrates
- manufacturing 64 - 3-methoxy-2-methylbutyrate 167
butane - by oxidative oxidations 167
- 1,4-bis(diphenylphosphino)butane butyrolactames
26 1 - via hydrocarboxylations 185
- oxidation process 525, 540 butyrolactones
butanediol 40, 89, 245 - via hydrocarboxylations 185
- as solvents in the SHOP process by-products 45 1
245 - carbonylation of methyl acetate 118
- by rhodium-catalyzed hydro- - chlorinated, in acetone manufacturing
formylation 40 40 1
butanes - chlorinated, in the Wacker-Hoechst
- azairidacyclobutane 521 process 399
- in hydrocarbon oxidations 525 - in arene oxidations 440
butanoic acid esters via hydro- - in butadiene hydrocyanations 482
carboxylations 186 - in carbonylations 113, 1 15
butanone - in commercial oxirane processes 418
- from l-butene/2-butene 401 - in epoxidations 414
- 3-chlorobutanone 401 - in hydroformylation 65, 90
butene - in propyne carbonylations 3 18
- 1,2-diacetoxy-3-butene 40 - in PVC production 555
- 1,4-diacetoxy-2-butene 40 - in technical aldehyde oxidations 431
- I-butene 241, 249, 259ff
- 2,3-dimethyl-2-butene 39, 255 ff, 264 C
- 2-butene 167, 261 f, 329 C2H,/Et,NH/LiNEt,/TMEDA as catalyst
- by ethylene dimerization 256, 259ff system in hydroaminations 5 18
- in dimerizations/codimerizations 255 C,-symmetric metallocenes in propylene
- in ethylene oligomerizations 24 1, 249 polymerizations 219 f
- in hydroamination 523 C&7PPh2
- in hydroformylation 39 - deactivation of hydroformylation
- in polyketone formations 355 ff catalysts 60
- in Wacker oxidation 402 ChOoxide
- isomerization 1120 - by MTO catalyzed oxidations 438
- oxidative carbonylation 167 caesium
- via propenes 264 - as catalyst in hydroaminations 516
butenol calixarenes
- 3-methyl-3-butenol 41 - by template synthesis 913
- rhodium-catalyzed hydroformylation - calix[4]arene monophosphites 89
41 - calix[4]arenes 87
butenyllithium in diene polymerizations - calix[6]arene phosphites 88
290 - phospha-calix[4]arenes 88
butyl nitrite CAMD 12
- in dicarboxylations 188 capnellene 1067
butylbenzoic acid ester N-(~-caprolactam)-2-acetic acid in
- via carbonylation of aryl-)<-compounds amidocarbonylations 162
150 c-caprolactam in amidocarbonylations
butynes 162
- 2-butyne 376 captopril by enzymatic hydrolysis 900 f
- butynediol 275 Car-Parinello method 7 10
1396 Index

carbanic acid carbon monoxide

- vinyl esters 279 carbon tetrachloride in
carbapenems in asymmetric syntheses 576 photoreduction 1072
carbene complexes carbonyl compounds
- in hydrofomylation 615 f - asymmetric hydrosilylation 494
- with rhodium compounds 1128 - by oxidation of olefinic compounds
carbene precursors 387 ff
- a-diazoesters 797 carbony lation
- ally1 diazoacetate 801 - alkyne carbonylations 323
- diazoacetamides 801 - by hydrogenations of carbinols 541
- diazomethane 795ff - catalyst stability 108
- diiodomethane 803 - catalyst systems 105
- ethyl diazoacetate 804 - catalyst-solution/product-separation
- vinyldiazomethane 797 115
carbenes - flow scheme 114
- chain mechanism 333 - iodine-promoted 140
- complex catalysts 338 - low water technology 107 ff
- in metathesis reactions 332 - mechanism 105
- in synthesis of carbocycles 1291 - of acetylene 277
- ions in carbonylations 189 - of alkanes 1230
- ligands 89 - of alkynes 274, 277, 279, 326, 964
- metal carbene complex 333 - of allylic and benzylic derivatives 145
- N-heterocyclic ligands 338, 1345 - of aromatic compounds 147
carbocycles - of aziridines 966
- by cyclooligomation of alkynes - of benzyl chloride 754
1252 ff - of dienes 965
- by diazoalkanes 1290ff - of fulvenes 965
- by McMuny coupling 1094 - of methanol 751
carbometalation see C-H activation - of oxiranes 965
carbon dioxide - of propyne 278
- as C, building block 1189 ff - photocatalysis 1066
- as solvent 611, 852ff - promoted catalyst systems 109
- cotrimerization with alkynes 1194 f - promotions 110
- cyclotrimerization with isoprene 1194 - reaction rate 11Off
- formic acid synthesis 1197 ff - stereoselective, benzylic bromides 149
- hydrogenation 613 carbosilanes
- in photocatalysis 1066 - silicon-containing dendrimers 495
- in water-gas shift reaction 1086ff carboxylic acids
- lactone synthesis 1191 f - by carbonylations 188
- photochemical reduction 1073 - by hydrocarboxylations 388
- polymerization with alkynes 1194 - by oxidation of alcohols 959
- under supercritical conditions 1196, - by oxidation of ketones 960
1201 f - cobalt salts 562
carbon monoxide see also syngas - 1,2-dicarboxylic acid 307
- as C1 building block 1189 - esters by oxidative carbonylation
- Fischer-Tropsch synthesis 808 ff 143 ff
- in electrocatalysis 1054 - in air oxidation reactions 182
- in homogeneous catalysis 1087 ff - in polybutadiene manufacturing 446
- in reduction of nitro arenes 954 - production 427
- Pauson-Khand reaction 1241 ff - 1,2,3-trimethyl-3-phenylindane-
- synthesis of isocyanates 1215 f 4',5-dicarboxylic acid 309
 Index 1397

- a,D-unsaturated 167 - in metal-doped systems 451

- unsaturated in alkyne carbonylations - in metathesis reactions 335
326 - in olefin hydrocyanations 473
carbyne complexes in olefin metathesis - in silicon compounds hydrosilylations
338 494
carnitine - in silylcarbonylations 506
- asymmetric synthesis 569 - in technical aldehyde oxidations 430
Carother’s equation 1275 - Karstedt’s catalyst type 495
D-carotin by McMurry coupling 1097 - lifetime in the UCC process 78
cascade reactions 1067 - M2+/3+ halogenide systems 45 1
- in carbonylations of aryl-X-compounds - M3(C0),2,in hydrosilylations 498
150 - manganese acetate bromide 452
CAT resins 383 f - monometallic 35
catalyst poisons 60 - Mo-V-AI-Cu oxides 428
- in telomerization processes 366 - organometallic homogeneous 386
- in the ADN process 482 - photoactivated 502
catalyst recycling 69 f, 173 - poisons, in arene-autoxidations 444,
- BASF process 72 447
catalyst separation - precursors, in epoxidations 414
- BASF process 72 - reactivity in carbonylations 108
- in ethylene oligomerizations 249 - recoverytseparation, in aldehyde
- in oxidative carbonylation 172 f oxidations 429
catalysts - Reppe 370
- activities 108, 363 - samarium-based, in aldehyde-
- anchored 7, 83 hydrocyanations 485
- catalyst losses 431 - S C C O ~423
- chirality-inducing 485 - separation 83
- chloride-free, in olefin oxidations - Shell catalyst 423
401 f - Speiers’ catalyst 495
- concentrations 56f, 430, 444 - stabilization 110
- deactivation, in asymmetric - synergistic systems 443
hydrocyanation 473 - thermally latent catalysts 383
- decomposinghecycling in arene - Ziegler 370
oxidations 440 f catalyst consumption number 888
- dehydrocoupling 503 catalyst design 1352
- for hydroformylation 34ff catalyst performance 1353
- Friedel-Crafts 3 catalytic cycle 5
- homogeneous, in hydrosilylations 495 - asymmetric hydroamination 1000f
- immobilized metal complexes 500 - asymmetric hydrosilylation 998 f
- in aldehyde oxidations 428 f - asymmetric Michael reaction 994
- in arene autoxidations 444 - carbonylation of ethylene 137 ff
- in arene oxidations 435, 439 - cyclotrimerization of butadiene and
- in asymmetric hydrosilylations 498 carbon dioxide 1193
- in butadiene hydrocyanation 482 - dihydroxylation of olefins 1152
- in carbonylations 105 - for methanol carbonylations 108
- in catalyzed hydrocarbon oxidations - Heck reaction 782f
540 - hydrodesulfurization 1102, 1 107
- in chloride-free oxidations 402 - hydroformylation of cyclohexene
- in cyanoolefin hydrocyanations 478 766
- in epoxy resin polymerizations 383 - hydroformylation of norbornene 769
- in liquid phase oxidations 444 - hydroformylation of olefins 729
1398 Index

- hydrogenation of carbon dioxide - in cyclooligomerization 370 f

1200 Celanese Chemicals 33, 75, 82, 106ff
- hydrovinylation of olefins 1040 cellulose acetates 106
- in cis- 1,4-polymerizations 302 - via acetic anhydrides 120
- in ethylene dimerizations 259 cephalexin 895
- in hydroaminations 519, 521 cephalosporin C 894, 896
- in hydrocarboxylations 183 cerium as catalyst in hydrocarbon
- in McMuny coupling 1098 oxidations 540
- in oxidative alkene acetoxylations 409 Cetrorelix 898
- isomerization of olefins 1123 CFK02
- of carbonylations 113 - in stereospecific polymerizations 287
- of chain reactions 532 CFC 13
- of co-carbonylations 125 CGC 271
- of cyclooligomerizations 376 ff - see Constraint Geometry Complexes
- of ethylene hydrocyanations 473 C-H activation 13
- of hydroaminations 5 14 ff - in olefin polymerization 978
- of hydrosilylations 497 - in photocatalysis 1071 f
- of olefin oxidations 389 - of alkanes 1226ff
- of polyketone formations 352 - oxidative methane carbonylation 131
- of propyne carbonylations 320, 325 f - Periana system 739
- of trans- 1,4-polyrnerizations 300 f - photochemical 190
- Rosenmund-Tishenko reaction 770 - Shilov system 737
- silylformylation of 1-alkynes 507 CH2[P(Ph)CH2CH2PEt2]2 86
- Suzuki coupling 1277 CH3CH2CH=CHCN
catalytic selectivity 91 - reaction inhibitor in the adiponitril
Catalytica Associates process 482
- chloride-free olefin oxidations 40 1 CHJ
- methylsulfate synthesis 1232 - carbonylation of methyl acetate 119
catechol in arene oxidations 438 - in carbonylations 104, 111 f
catenanes CH30Ac 112
- by self-assembling synthesis 929 - carbonylations 111, 113
- by template synthesis 913 - concentratin in carbonylations 109
Cativa process 107, 113 CH30H
CC see Celanese Chemicals - concentration in carbonylations 109
C-C bond formation - in carbonylations 104ff
- by arene coupling reactions 822ff chain end control in propylene
- by Heck reaction 775ff polymerization 2 19
- by McMuny coupling 1093ff chain lengths in catalyzed chain
- by photocatalysis 1065ff reactions 53 1 f
- in biocatalysis 880f chain propagation
- in stereospecific polymerizations 288 - in polyketone formations 354
C-C bond linking 285 - in uncatalyzed hydrocarbon
C-C cleavage 1237 oxidations 53 I
C-C coupling chain running in ethylene
- in carbonylations of aryl-X-compounds polymerizations 227
151 chain scissions in PET production
CdF-Chemie 339 549
CDT (cyclododecatriene) chain termination reactions
- by butadiene telomerization 369 - in catalyzed chain reactions 533
- cyclic, in cyclo-co-oligomerizations - in uncatalyzed hydrocarbon
378 oxidations 527
 hdex 1399

chain transfer in catalyzed hydrocarbon - cuc1, 394

oxidations 540 - lithium 394
Chalk-Hanod mechanism chloride ions in olefin oxidations 389
- in dehydrogenative silylations 503 chlorination in the Wacker-Hoechst
- in hydrosilylations 493 f process 399
Chaudhari chloroprene 1 125
- deactivation of hydroformylation chlorosilanes in McMuny coupling
catalysts 60 1096 f
- kinetics of hydroformylations 54 chloro keto esters
Chaulmoogric acid by hydrovinylation - asymmetric hydrogenations of 569
1174 chloro(a1lyl)neoymium in butadiene
chelate diphosphines polymerizations 294
- ligands in hydrocyanations 473 chloroaluminates 264
chelates 355 f chloroarenes
chemical engineering of poly- - methoxycarbonylations of 152
merizations 230 ff chloroethanol
Chemopetrol 243 - as main product in ethylene oxidation
chemoselectivity 394, 402
- in alkylarene autoxidations 464 - by-products in technical olefin
- in alkyne carbonylation 317 oxidations 402
- in polyketone formation 356f chlorohydrins
- of alkyne-silylformylation 507 - from higher a-olefins 402
Chichibabin reaction 1257 - optically active 402
chiral see asymmetric chloroplatinic acid in photochemically
chiral active center in propylene induced hydrosilylation 502
polymerization 2 19 chromium
chiral aldehydes 91 - as catalyst in hydrocarbon oxidations
chiral ally1 diphosphites 537 f
- ligands in hydrocyanations 476 - (C5H5)2Cr 22
chiral auxiliaries - chromate esters in catalyzed
- dihydroxylation of olefins 1153 hydrocarbon oxidations 537
- in cyclopropanation 802ff - colloids 682
- in Heck reaction 779f - Cr(C0)6 502
- phosphines 1014ff - dihydroxylation 1 149 f
chiral compounds - H2CT0-3 538
- zirconocene 225 - in aldehyde oxidation catalysts 432
chiral reagents in aldehyde hydro- - in water-gas shift reaction 1087
cyanations 486 f - photocatalytic diene hydrogenation
chirality of polyketones 357 1073
CHIRAPHOS - salen-Cr complexes 572
- as ligand in asymmetric chromium complexes in ethylene
hydrogenations 562, 573 trimerization 262 ff
- ligand in hydrocyanations 473 chrysanthemic acid in cyclopropanation
chloramphenicol 1160 798
chloroform by photoreduction of carbon chrysanthernic esters in pyrethroid
tetrachloride 1072 production 563
chlorhydrin route Cilastatin 563
- propene oxide production 412 - asymmetric synthesis of Cilastatin
chloride intermediate 564
- 3-chlorpropionyl chloride 166 - biocatalytic resolution 893
- by oxidative carbonylations 166 - by cyclopropanation 798
1400 Index

cinchona alkaloids Co/Br

- in asymmetric dihydroxylation 1 141 - catalyst system in arene autoxidations
- in dihydroxylation of olefins 1152 444
cinnamaldehyde by chloride-free Co/Mn
oxidations 402 - in arene autoxidations 458
cinnamic acid derivatives via dialkoxy- - reaction time in arene autoxidations
carbonylations 189 45 8
cinnamyl halides via carbonylation of Co/Mn/Br
aryl-X-compounds 151 - catalyst system in arene autoxidations
cis-hexaline by cocyclotrimerization 444,451,454
1263 - in naphthalene oxidations 461
fl-cis-hydride transfer 473 - synergistic catalyst system 443
cis-migration in ethylene oxidations 395 C 0 2 see also carbon dioxide
cis- 1,4-polymerization of butadiene - carbonylation of methyl acetate 118
301 ff, 303 - in polybutadiene manufacturing 306
cis- 1,4-polybutadiene - in telomerization processes 364
- hydrogenation 751 - production in carbonylation reactions
cis/trans-ratio 339 110
cis-trans polymerizations CO,(CO),(L)~ in hydroformylations 50
- equibinary 303 C O A C O ) ~ P B U ~57
)~
Cl/Cu ratio in acetaldehyde C02(CO)8
manufacturing 400 - catalyst in hydrocyanations 470
Clozilacon - high pressure 0x0 catalyst 51
- asymmetric synthesis 573 - in hydrocarboxylations 182 f
ClRh[P(CciHs)?I, 20 - in the hydroformylation cycle 45 f
cloud point 617 C02Rh2(C0)12 35
cluster Co3+in catalysis of co-oxidations 453 ff
- giant cluster catalysts 409 ff co-activators in hydrosilylations 496
- immobilization 677 ff coal
- in electrocatalysis 105 1 - gasification 10
- in Fischer-Tropsch synthesis 8 13 - hydrogenation 3
- in hydrogenation 680 cobalt
- rhodium-carbonyl, in - Co(acac), 295
silylcarbonylations 507 - Co3+acetate 448
CO 5 , 325, 507 - Co3+in arene oxidations 448
see also carbon monoxide - C02(C0)8 498
- addition in carbonylations 113 - CO~(CO)~ 502, 506
- co-catalyst in photochemical - Co2+/Co3+in anhydrous acid 451
hydrosilylations 502 - Co2+/Co3+systems 428
- efficiency in carbonylations 110 - (CO),,CoSiR3 503
- in alkene copolymerizations 344 - [Co(CO),(PR,),I 75
- in 0x0 processes 56 - [Co(CO),PR312 75
- in the hydroformylation cycle 45 - [CO(CO)~]- 146 f
- insertion 321, 349 - C O ~ ( C O ) I 502
~
- migratory insertion 348 - [Co(r3r2-CH,C,HIO)(r4-C4Hb)]295 f
- propyne carbonylation 321 - C O H ( X ) ~ L 498
~
- Shell process 75 - [Co(OAc),/Br] 450
CO insertion 321, 349 - CO(OAC), 454
- hydroformylation mechanism 50 - Co(0Ac)Br 451
- in carbonylations 104ff, 145 - Co(octoate), 295
Co process 13 - CoOH(C0)4 498
 Index 1401

- [co(s)(co),]+ 53 - RCH~CH~COCO(CO)T
- [CO~+(OAC)~/HB~] 452 - recovery, hydroformylation 63
- [HCo,(CO)IS] 53 - reduction of nitro arenes 954f
- [ L C O ( R C H ~ C ~ H ~ ~ ) ( C297
~H~)] - Shell process 75
- a-amidoalkanoylcobalt intermediate - template synthesis 927
162 - thermal latenet complexes 384
- alkyne nitrile cocyclization I256 f cobalt carbonyl
- as catalyst for PET production 550 - in arnidocarbonylations 156 f
- as catalyst in hydrocarbon oxidations cobalt carbonyl catalysts
535 - unmodified in hydroformylations 68
- as catalyst in the Witten process 545 cobalt carbonyl hydride 474
- as catalyst metal 32 - regenerative conversion 71
- as peroxide decomposer in catalyzed cobalt catalysts 90 f
oxidations 533 - alkylphosphine modified 58, 474
- BASF process, recovery of 72 - in amidocarbonylations 163
- bk(buteny1)cobalt complex 297 - in carbonylations 104, 146
- 2,2-biphenyl synthesis 1258 - in hydrocarboxylations 182
- carbonylation 961 - in hydroformylations 45 f, 5 1, 69
- carboxylic acids 309 - phosphine-modified in hydro-
- catalysts for polybutadiene production formylations SO, 57
309 - phosphine-modified in Shell process
- colloids 682 73
- cyclooligomerization of alkynes - recycling 70
1253f, 1262ff - unmodified in hydroformylations 53
- dicobalt octacarbonyl 279, 498 cobalt salts
- di-l-rnethylimidazole-bis-dirnethyl- - in butadiene/ethylene codimerization
dioximato-cobalt(II1) nitrate 384 263
- desulfurization 968 cobalt technology 75
- HCo(PR,), complexes 474 cobalt/manganese
- high-pressure process 67 - as catalyst system in TPA productions

- homologation of methanol 1040f 546

- hydrovinylation I 165 cobalt-based processes 69, 90
- in amidocarbonylations 162 - in hydroformylations 63
- in biocatalysis 889 cobaltcarbonyl/pyridine catalysts in
- in carbonylations 143, 146f hydrocarboxylations 185, 24 1
- in Fischer-Tropsch synthesis 809, 8 15 cobaltocenium salts 89
- in hydrocarboxylations 187 cobalthhodiurn catalysts in
- in hydrogen transfer reaction 1072 amidocarbonylations 158
- in liquid-phase oxidations of paraffin COC (cycloolefin copolymers) 223,
537 233, 265 ff
- in photocatalysis 1066 co-carbonylations 122 ff
- in Ziegler-Natta type catalysts 284, - catalytic cycle 125
289 f - methanol/methyl acetate mixture 122
- kinetics of hydroformylations 53 - promoter salt concentration 124
- naphthenate 309 - reaction course 122
- octanoate 295, 309 - reaction rate 122f
- olefin hydrosilylation catalysts 498 - single product process 125
- Pauson-Khand reaction 1241 ff - water-free conditions 124
- phosphine catalyst 33 co-cataly sts
- photoactivated catalysts 502 - in Aldox process 771
- polybutadienes 309 - in amrn(on)oxidation 1298 f
1402 Index

- in carbonylations 140 - in oxidative carbonylations 169

- in esterifications 183 Consortium fur Elektrochemische
- in Fischer-Tropsch synthesis 820 Industrie GmbH 386
- in homologation of alcohols 1035 Consortium fur Elektrochemische Industrie
- in hydroaminations 516 GmbH see also Wacker-Chemie
- in hydroformylation 767f constrained geometry catalysts (CGCs)
- in hydrovinylation 1165 - in ethylene polymerizations 2 19
- in metathesis reactions 334f - in technical polymerizations 235
- in olefin hydrocyanations 475 contact ion-pairing 112
- in oxidative carbonylations 165 continuous oxidation 463
- in polybutadiene manufacturing 309 convergent synthesis of Group IV
- in RIM technique 341 metallocene catalysts 267
- in the AMOCO MC process 443 co-oxidants in catalyzed hydrocarbon
- in the carbonylation of methyl acetate oxidations 540
117 co-oxidations
- synergistic in arene autoxidations 448 - in arene autoxidations 447
cocyclization of acetylene and nitriles - Co3+-catalysis 453 ff
1256 copolymerization
COD see also cyclooctadiene - of alkenes 213 ff, 344
- in butadiene telomerizations 369 - of carbon monoxide and olefins 1281
- in diene cyclooligomerizations 370 - of ethylenell-hexene 987
- product in BD cyclo-cooligomerizations - of MMAllactones 988
379 copolymerization parameters 2 18
codimerizations 253 ff copolymers 222 ff
- BD/alkynes 375 copper
coenzym Q from y-benzoquinones 436 - [CU~(OH)~CI] 397
collidines 1256 - CuC12 304, 554
CO insertion in deactivation of - Cu(I1) salt 172, 174, 347
hydroformylation catalysts 61 - Cu'+/Cu2+systems 428
co11oid s - acetylide catalysis 275
- in hydrogenation 680 - allylation of alkynes 967
- in immobilization 677 - as catalyst in PVC production 554
- in photoreduction 1073 - carbocyles by diazo compounds 1290
- in Suzuki coupling 1278 - chiral bisaxolidine-Cu complexes in
CoMn/Br/Zn ascatalyst system in arene asymmetric cyclopropanation 563
autoxidations 444 - chiral Schiff base/Cu complex 563
comonomers in technical polymerizations - chromite catalyst 366
235 - cupric chloride 389
n-complexes in olefin hydrocyanations - cupric salts as catalysts in hydrocarbon
413 oxidations 538
complexing in acetic anhydride process - cyclopropanation 794
120 - halides as promoters in alkyne
composite materials carbonylations 3 17
- manufacture of 384 - in photocyclization 1067
concentration profiles in biphasic - in water-gas shift reaction 1087
systems 749 - isomerization of olefins 1125
condensation polymerization 1275 - oxalate 401
conductive materials 333 - oxidative phenol coupling 826
cone angle in phosphine ligands 36 - oxychloride in ethylene oxidatin 398
conjugated dienes 284 - photooxychlorination 1070
- in hydrocyanation 482 - template synthesis 9 13
 Index 1403

copper chloride in alkyne-reactions 282 y3-crotyl-Rh in butadiene/ethylene

copper salts in oxidative carbonylations codimerizations 263
172, 174 crown ethers
coproduction of acetic acid and anhydride - by McMurry coupling 1097
in carbonylations 104 - by template synthesis 913
co-promoter - in cyanation of organic halides 968
- catalysts in carbonylations 108 - in phase-transfer catalysis 954 ff
CoRh(CO), 35 crystallization
Cossee - strain induced 308
- mechanism 714 CS2 in butadiene polymerization 295 ff
- stereospecific polymerizations 289 f C,,-symmetric metallocenes in
COT see also cyclooctatetraene polypropylene polymerizations 222
Coulson 522 cumene
coumarins by photocycloaddition I068 - in epoxidations 424
coupling - oxidation 961
- reductive, in cyclo-co-oligomerization cuminic acid in Co-catalyzed
reactions 379 co-oxidations 453
- Wittig 8 cupric chloride
coupling reactions see also Grignard, - in butanone manufacturing 401
Suzuki - in technical olefin oxidations 402
- alkenes/vinylsilanes 504 - in oxidations of olefinic compounds
- dehydrogenative 502 ff 402
- silylative couplings 504 curing agents
- Wurtz-coupling in hydrosilane - aromatic diamines 383
dehydrocouplings 506 - for epoxy resin polymerization 383
Cp&Me2 curing parameters in epoxy resin
- polycondensation initiator 505 polymerizations 383
Cp2ZrC12 Curtin-Hammett principle in cis-l,4-
- in ethylene polymerization 2 17 polymerizations 301
- in ethylene trimerization 262 C-X bond activation 145
- in propylene polymerization 219 - in carbonylations of aryl-X-compounds
Crabtree concept 147
- in dehydrogenative silylations 503 cyanation of organic halides 967 f
cracking processes 253 cyanides
cross-coupling see Suzuki reaction - trimethylsilyl cyanide 486
cross-coupling see also Grignard cross- cyanide-transfer in allene hydrocyanation
coupling 484
CrOJH2S04 cyanohydrins in aldehyde hydrocyanation
- stochiometric oxidant in arene 485
oxidations 433 cyanoolefins in hydrocyanations 478 f
cross over products in polyketone cyclic alkenes in metathesis reactions
formations 350 329 ff, 332
cross-metathesis 328 cyclic amines in hydroaminations 5 18
- cyclic/acyclic alkene 331 ff cyclic olefins in polymerizations 222
crotonaldehyde cyclization of alkynes 274
- 2-ethylcrotonaldehyde 129 cycloaddition by carbene fragments
- impurities in carbonylations 129 794 ff
crotonic acid cycloalkenes
- in oxidative carbonylation 168 - in oxidative carbonylations 167
crotyl-bis-triphenylphosphite complex in - in ring-opening polymerizations
trans- 1,4-polymerizations 300 329
1404 Index

cycloalkylphosphines as ligands in the - isomerization 1074

Shell process 74 cyclooctadienes (COD) 368 f
cyclocarbony lations cyclooctatetraene (COT) 368
- asymmetric 186 - ROMP 330
- of aryl-X-compounds 151 cyclooctene
cyclo-co-oligomerizations - metathetical polymer 339
- of 1,3-dienes 368ff, 374ff cyclooctane
- of 1,3-dienes and alkynes 375 ff - photochemical dehydrogenation
cyclodecadienes 368 f, 374 1071
cyclodecatrienes (CDT) 2 1, 369 cyclooctatetraene (COT) 368
- 1,5,9 cyclodecatriene 21, 379 - by cyclotetramerization of acetylene
- 1,5,9-cyclodecatriene-nickel 21 1264
- in cyclooligomerizations 379 cycloolefin polymers 224
- product in BD cyclo-co-oligo- cycloolefins
merizations 379 - in oxidative carbonylations 167
- via cyclo-co-dimerizations 375 - polymerization by metallocene
cyclodextrin complexes catalysts 223
- p-cyclodextrins 91 - technical polymerizations 230
- in hydrosilylations 496 cyclooligomerization
cyclodextrins - of alkynes 1252ff
- as colloid stabilizer 1073 - of butadiene 370ff, 772
- chiral stationary phase 226 - 1,3-dienes 368ff
- in hydroformylation 618 cy clopentadienes
cyclodimerization of alkynes 989 - cyclocondensations 268 f
cyclodimerization see also cyclo- - Diels-Alder reaction 9 13
oligomerization - hydrovinylation 1 169
cyclododecatrienes 368 - in olefin polymerizations 213
- 1,5,9-~yclododecatriene 369 cyclopentadienones in Pauson-Khand
cyclohexanone in ammoximation 422 reaction 1248
cyclohexadienes cyclopentadienyl as ligand in the Shell
- 1,3-~yclohexadiene 484, 1262 process 249
- in cyclo-co-oligomerizations 374 cyclopentanone derivatives via
- in hydrocyanations 484 carbonylation of aryl-X-compounds
cyclohexane 15 1
- C-H activation 1071 cyclopentanones
- oxidation 751, 960 - by diazo compounds 1290
cyclohexanol by photooxidation of - 3-hydroxycyclopentanone 565
cyclohexane 107 1 cyclopentenes
cyclohexanone - 1-vinyl- 1-cyclopentene 370
- by isomerization of cyclohexenol cyclopentenones
1074 - by Pauson-Khand reaction 1241
- by photooxidation of cyclohexane cyclopropanation
1071 - by electrocatalysis I052
- in L-lysine synthesis 899 - of alkynes 802
- oxidation 960 - of isobutene 798ff
cyclohexenes 422 - of styrene 798
- hydroformylation 48, 766 cyclopropanes by cyclopropanation of
- hydrogenation 682, 750 olefins 793ff
- in amidocarbonylations 159 cyclotetradimerization see cyclo-oligo-
- 4-vinyl-1-cyclohexene 159 merization cyclotetramerization of
cyclohexenol acetylene 1264
 Index 1405

cyclotrimerization - C-H activation 737ff

- of alkynes 332, 1252ff - dihydroxylation 1153
- of butadiene and carbon dioxide 1 191 - Heck reaction 721 ff
- of isoprene and carbon dioxide 1194 - in catalysts design 1352ff
- in hydroformylation 727ff
D - in hydrovinylation 1 181
DAB 461 - polymerization of olefins 713 ff
Daicel 171 f deprotonations in hydroaminations 5 14
Damkohler number 949 desulfurization under phase transfer
Danishefsky’s diene 991 conditions 968
Davison process for ethylene oxidation detergent alcohols 9 1
with chloride-free catalysts 401 deuterium labeling see isotope labeling
Davy Powergas dextromorphan via enamine hydro-
- rhodium-based 0x0 process 76 genations 575
Davy Process Technology 41 diacids via hydrocarboxylations I82
DCN in alkyne hydrocyanations 479 dialkyl carbonates
DCPB in cyclotrimerization of isoprene - by oxidative carbonylation 165, 171
and carbon dioxide 1194 dialkyl metallocenes in polymerizations
DCPD 340ff 216
DCPD see also dicyclopentadiene dialkyl oxalates
deactivation mechanism of hydro- - by heterogeneous catalyzed
formylations 60 processes 175
decanals 84 - oxidative carbonylation 165, 17 1,
decarboxylations of a$-carboxylic acids 174ff
388 diamine ligands in cyclopropanation
decenes 798
- 1-decene 54, 241 diamines in telomerization processes
- hydroformylation 54 364
- in ethylene trimerization 262 diastereoface selectivity in polypropylene
- oligomerization 24 1 polymerization 222
decobalting diastereoselectivity in dimetallocene
- by oxidation in the BASF process 69 synthesis 27 1
degree of polymerization 304 diazo compounds
DEGUSSA - in cyclopropanation 794ff
- BMA process 1298 - in olefination of aldehyds 1079 ff
- D-Cit synthesis 898f diazoalkanes
- epoxidation processes 422 - in carbocyclic synthesis 1290ff
- L-methionine process 891 f, 941 - in carbonylations of aryl-X-compounds
dehalogenation of organic halides 1005 147
deh y drodimerization - in olefination of aldehydes 1079 ff
- of hydrocarbons 1072 a-diazoketones
- of pyridine 1258 - in carbocycle synthesis 1290ff
dehydrogenation DIBAL in asymmetric hydrogenations to
- of alkanes 1071 secondary alcohols 567
- of cyclooctane 1071 dibenzenechromium 22
dehydrogenative coupling of dibenzyl ether in the Shell process 74
hydrosilanes 999 dibenzyl metallocenes in polymerizations
deltamethrin 799 f 216
dendrimers via hydrosilylations 495 dicarboxylations 188 ff
Denopamine 569 dicarboxylic acid via dicarboxylations
density functional theory 700, 706 ff 188
1406 Index

dichloroethan (DCE) in PVC production a-diimines in ethylene oligomerizations

553 f 250
dicyandiamides in epoxy resin diisobutene 90
polymerizations 383 - in ethenolysis 339
dicyclopentadiene (DCPD) in diketones in polyketone formation 349
hydroformylation 688 diltiazem
Diels-Alder reaction - by asymmetric dihydroxylation 1160
- by template synthesis 9 13 f - by biocatalysis 901
- in 1,4-polymerizations 304 Dimates 259
- of cyclopentadiene 263 dimerizations 253 ff
diene polymerization - in hydrocarboxylations 187
- LiR-catalyzed 290 - nonregioselective 256, 264
- organotitanium catalysts 294 - of alkanes 1229
- stereospecific 286, 288, 312 - regioselective 257, 264
dienes Dimersol process 256 f, 264
a,w-dienes 329 ff dimethylamine in DMF synthesis
- 1,3-dienes 169, 368 ff, 370 f, 502 1203 f
- 1,5-dienes 224 dimethyl carbonate
- by allyl-ally1 cross-coupling 1065 - via oxidative carbonylations 166,
- by Heck reaction 776ff 171 ff
- carbonylation 965 - via the nitrite route 173
- cyclodimerization 990 dimethyl malonate derivatives in
- hydrogenation 955 carbonylations of alkanes 191
- hydrovinylation 1168 f dimethyl succinate in polyketone
- in 1,4-hydrosilylations 502 formation 352
- in cyclo-co-oligomeiizations 368 ff dimethyl sulfate 171
- in metathesis reactions 329, 331 dimethyl adipate via hydrocarboxylations
- in oxidative carbonylations 169 188
- intramolecular metathesis 329, 362 dimethyl-2-butene- 1,4-dicarboxylate via
- methyl-substituted in cyclo- hydrocarboxylations 187
co-oligomerizations 37 I dimethyl-2-phenylsuccinate by oxidative
- photocatalytic hydrogenation 1073 carbonylations 166
- 1,2-polydiene 284 dimethylaluminium difluoride in
- polymerization 224 polymerizations 216
- stereoregular 284 dimethylcarbonate formation
dienones 283 - reaction mechanism 172
diesters dimethyldioxirane as stochiometric
- by oxidative carbonylation 167 oxidant in arene oxidations 436
- in polyketone formation 349 N,N-dimethylimidazolium iodide in
diethyl ketone 31 acetic anhydride process 127
- in ethylene copolymerizations 344 dimethylmetallocenes in one-pot
- in polyketone formation 352 synthesis 270 ff
diethylene glycol in PET production dimethylterephthalate see DMT
549 diols
diethylzinc 16 - by dihydroxylation 1149 ff
Difasol process 264 - photocleavage 1074
Diflufenican 150 DIOP in hydrosilylations 497
dihydroindols by cyclodimerization of diorganophosphino acid derivatives in the
alkynes and nitriles 1259 Shell process 245
dihydroxylation of olefins 1141, 1149 ff dioxane
dihydroxyphenylalanine see L-Dopa - carbonylation 142
 Index 1407

dioxirane Dow Chemicals 171, 173, 219, 265

- oxidation 438 - membrane process 692
DIPAMP 14 downstream operations 9 1
- as ligand in asymmetric D-oxynitrilase as chiral catalyst 485
hydrogenations 573 DPPB 40
diphenyl ether in the Shell process 74 DPPF
diphenyl isophthalate 461 - gold-aldol reaction 11 44
diphenyl sulfoxide in arnidocarbonylations - phenol coupling 827
161 drying column 116
diphenylenes 1264 DSC measurements 384
o-diphenylphosphinobenzoicacid in the DSM 88
Shell process 245 - a-amino acid synthesis 892
diphenylpyrimidine in dihydroxylation of - a-picoline synthesis 1255
olefins 1156 DUPHOS
diphosphine ligands 85, 87 - as ligand in asymmetric
diphosphite ligands in asymmetric hydrogenations 573
hydroformylations 43 - asymmetric hydrogenation of
diphosphites 88 imines 1138, 1145
DIPN 461 DuPont 88, 263, 344, 460, 468, 522
discontinuous operation in hydro- - adiponitrile process 1124
formylations 65 - Simmons-Smith reaction 803
disproportionation durene in autoxidations 456
- olefins 328 DVCB
- 2-pentene 328 - in diene cyclooligomerizations 370
di-t-butyl-peroxide in dicarboxylations - product in BD cyclo-co-oligo-
188 merizations 379
dithiocarbamate in electrocatalysis 1050 dynamic kinetic reactions in stereoselective
divinylbenzene in immobilization of hydrogenations 576
hydrosilylation catalysts 500 dynamic kinetic resolution in asymmetric
divinyldimethylbutadiene see DVCB syntheses 569
diynes 333
- in silylcabocyclizations 507 E
DMB (2,3-dimethylbutene) via Eastman Chemical Company 120 f
regioselective propene dimerizations Eastman Kodak 85, 122
257 ff Eastman process 120 ff
DMF by hydrogenation of carbon EBHP in commercial oxirane processes
dioxide 1203 f 417
DMT 460, 541 economic aspects of hydroformylations
- in autoxidations 443f 61
Dobanol 73 economic efficiency of Group 1V
dodecanoic acid metallocene catalysts 267
- via hydrocarboxylation 185 2-EH (2-ethyl hexanol) 4 1, 62
dodecene elastomers
- hydroformylation 36, 616 - in polymerizations 230f, 235
domino reaction 782, 1067 electrocatalysis 1046 ff
DOP 41 electrochemical methods in acetic
L-Dopa 14 anhydride process 120
- by biocatalysis 903 electron beam technique in epoxy resin
Dopamin by biocatalysis 903 polymerizations 384
double carbonylations 145 electron transfer 448, 453
- phase-transfer catalysis 961, 965 - in alkylarene autoxidations 455
1408 Index

- in catalyzed hydrocarbon oxidations EPDR by technical polymerizations 233

535 f EPM by technical polymerizations 233
- in Co-catalyzed arene autoxidations epoxidations
449 - agents 438
- mechanism in Co-catalyzed - asymmetric 421 ff
co-oxidations 453 - in membrane reactors 944
electronic parameter phosphine ligands - in photooxidation 1070
36 - of olefins 957
Elf Atochem 339 - shape-selective 422
elimination - stereospecific 414
- ,&elimination in butadienelethylene - with aqueous H202 424
codimerizations 263 epoxides
- reductive 402 - as intermediates 438
empirical rate law in hydroaminations - enantioselective ring-openings 572
518 - ring-opening of styrene oxide 996
emulsifiers in telomerization processes epoxy alcohols by photooxidation 1070
364 EPR by technical polymerizations 233
emulsion polymerization 1274 ergot alkaloids 1259
enamides in asymmetric hydrogenation Ercoli reaction-rate equation 5 1
1137 ESN in butadiene hydrocyanations 483
enamines by isomerization of ally1 amines Esomeprazole 577
1125f estenfication section in acetic anhydride
enantiofacial selection 1156 processes 120
enantiomeric excess in olefin esterification step in the Eastman
hydrocyanations 471 process 121
enantiomorphic site control in propylene esterifications 182ff
polymerization 219 - side reactions in aldehyde oxidations
enantioselection 557 43 1
enantioselectivities in hydrocyanations esters
476,486 - allylic 402,408
enantioselective see asymmetric - by hydrogenation of carbon dioxide
enediynes in cyclomerization 1263 1202
energy exporters 91 - by oxidative carbonylations 156
energy utilization 90 - chromate esters 537
enhancement factor 752f - 2,4-dicyano-2-methylbutanoicacid
Enichem 171 f, 310,422 esters 186
enoate reductase in biocatalysis 878 - homoallylic 407f
enol acetates in asymmetric - 3,8-nonadienoate ester 187
hydrogenation 1I37 - 4-pentanoic acid ester 188
enol ethers in alkyne-reactions 280 - a,@-unsaturated carboxylic acid esters
en01 ethers see also vinyl ethers 167
enols by alkyne reactions 280 - a$ unsaturated via chloride-free
enthalpies in cis- 1,4-polymerizations 303 oxidations 402
entropy barrier of propyne carbonylation EtZAlCI 297
kinetics 324 Et,AIOEt in ethylene oligomerizations
environmental impact 91 249
enterobactin by template synthesis 914 Et,NH/LiNEt,/TMEDA as catalyst system
enzymes 872ff in hydroaminations 5 16
EP rubber via polymerizations 213 Et3AIZC13 297
EPDM (ethylene propylene diene- ethane
monomer) 233, 263 - 1,2-bis(diphenylphosphino)ethane 152
 Index 1409

- 1,l -diacetoxyethane 118 - in alkoxycarbonylation 346

- 1 ,I-diacetoxyethane 128 - in Heck-type polymerization 779
- in the acetic anhydride process 128 - in the Wacker oxidation 386
- in the carbonylation of methyl acetate - in vapor phase oxidations 412
118 - insertion 349, 3.53ff
- oxidation 1234 - liquid phase reaction 168
ethanol - migratory insertion 348, 504
- 1-arylethanol 149 - oligomerization 240 ff, 7.5 1
- carbonylation of ethylene 138 - oxidation with CuCI, 396ff
- 2-chloroethanol 394, 402 - oxidative acetoxylation 406
- in carbonylations of aryl-X-compounds - oxidative carbonylation 169
149 - platinum-catalyzed hydrosilylations
- intermediates in carbonylations 142 493
- 1 -(4-isobutyIphenyl)ethanol 149 - photocycloaddition 1068
ethenolysis 329 - polymerization 643, 979
- of cycloalkanes 331 - reaction with palladium compounds
- of fatty oils and fatty esters 332 386ff, 389
- of isobutene 339 - trimerization 262 ff
ethinylations - uncatalyzed chain reaction with
- of alkynes 274 chlorine in PVC- production 555
- of aromatic compounds 276f - Wacker-oxidation 75 1
- of carbonyl compounds 275 ethylene glycol by oxidative
ethyl acetate by homologation of methyl carbonylation 174
acetate 1035 ethylene homopolymers via technical
Ethyl Corporation 240 polymerizations 233
ethyl iodide in carbonylations 139 f ethylene insertion 349, 3.53 ff
Ethyl process 243 f - in hydrosilylation 493
ethyl zinciodide 16 - in olefine hydrocyanations 474
ethylbenzene ethylene oligomerization mechanism 2.50
- autoxidation 443 ethylene polymerization 2 1.5
- in commercial oxirane processes ethylene waxes via technical
417 polymerizations 233
ethylbenzene hydroperoxide see EBHP ethylene/l-octene copolymers
417 - in ethylene polymerization 219
ethylbenzene route in commercial oxirane - in technical polymerization 236
processes 4 1 8 ethylene/l -olefine copolymers in technical
ethylene polymerization 233 f, 236
- a-picoline synthesis 125.5 ethylenekycloolefin copolymers by
- asymmetric hydrovinylations 562 technical polymerization 237
- carbonylations of 137, 142 ethylenelnorbomene in copolymerization
- copolymerizations of 226 227
- cross-metathesis 329 ethylenelpropene copolymerization 2 13
- dimerizationskodirnerizations 254, ethylene/propylene copolymers in technical
258, 773 polymerization 236
- double insertion 354 ethylenektyrene copolymers
- homopolymerizations 226 - by technical polymerization 237
- hydroamination 5 16, 522, 524 - via technical polymerization 233
- hydrocyanation 474 ethylene-bis-( 1-indeny1)titanium dichloride
- hydroformylation 61, 82, 316 in propylene polymerization 2 19
- hydrovinylation 1164 ff 2-ethylhexanal 43 1, 77 1
- in alkene copolymerization 344 2-ethylhexanol 14, 259
1410 Index

ethylidene - Dow membrane process 692f

- bridged oligomers 282 - in polybutadiene manufacturing 306
ethylidene diacetate - RCWRP hydroformylation process
- carbonylation of methyl acetate 11 8 609, 623
- in ethylene oxidation kinetics 393 - Shell higher olefins process 609
ethylidene norbornene fluorous biphasic system 635 ff
- in olefin polymerization 2 13 fluorinated acids via hydrocarboxylation
- via cyclopentadiene 263 185
ethyl succinonitrile see ESN fluorinated alcohols in asymmetric
ethylurethane 1090 f epoxidation 424
ethynylation under phase-transfer fluoro amino acids in amido-
conditions 966 carbonylation 158, 163
exotoxicity in RCH/RP process 8 1 fluoroolefines in hydroformylation and
extraction methods in acetic anhydride amidocarbonylation 157
process 120 forcefield method 703
Exxon 219 formaldehyde 275
- Aldox process 771 - amidocarbonylation 162
- Exxon process 69ff - condensation with propanal 316
- 2-vinylpyridine synthesis 1256
F formates as hydrogen donor 6 13
F(ChH4)-2,4-S03K 87 formic acid
fat hardening 3 - as telogen 367
Fe(COIS 18 - by hydrogenation of carbon dioxide
Felkin-Ahn model 995 613, 1196ff
Fenton 174, 345 - by oxidation of methane 1234
ferric chloride in oxidative carbonylations - in the catalyzed oxidation of MEK
170 534
ferric sulfate Formoterol 568
- chloride-free oxidants 402 y formylcrotyl acetat 8
- oxidant in chloride-free olefin free radical chain reactions
oxidations 40 1 - in arene autoxidation 447
ferrocene 22 - in catalyzed hydrocarbon oxidation
ferrocenyl phosphine ligands in 540
carbonylations of aryl-X-compounds free radicals
152 f - elimination in Co-catalyzed arene
ferricinium salt in electrocatalysis 1055 autoxidations 449
film variable hold-up (FVH) model 756 - in catalyzed oxidations of
Fischer-Tropsch reaction 5 alkylaromatics 536
- hydrocarbons 31 - in hydrocarbon-halogenation 552
- synthesis 5 , 253, 808ff - in the AMOCO MC process 443
fixation see immobilization - in hydrosilylation 491
fixed-bed processes in hydroformylation Friedel-Crafts acylation by Group IV
67 metallocene catalysts 267
flash-section in carbonylation reactors Friedel-Crafts compounds in technical
115 polymerization 235
Florfenicol via Sharpless fulvenes in carbonylation 965
epoxidations 569 fumaronitril in hydrocyanation of
flow scheme functionalized olefines 476
- acrylamide synthesis 890 functional olefines in polymerization 224
- DEGUSSA L-methionine process functionalities by heteroatoms in alkyne
891 f carboxylation catalysts 326
 Index 1411

furanes - colloids 683

- by photocyclization 1067
- 2-hydroxytetrahydrofuran 40
G Grignard cross-coupling of aryl
GABOB 1160
galanthamine by asymmetric synthesis
575
gasoline by Fischer-Tropsch synthesis
808
gas phase hydrosilylation of acetylene
501
gas phase process for dialkyl oxalates
175
gas recycle process 75 f, 77, 83
- BASF process 82
- in combination with liquid recycle
gem-diols in catalyzed hydrocarbon
oxidations 539
gene technology 906
General Electric 171
general salt-effect 1 12
- in acetic anhydride process 126
geometric chain-growth factor in the
Shell process 246
geraniol
- asymmetric hydrogenation 559
- regioselective epoxidation 420
geranylacetone 623
geranyldiethylamine by BINAP-Rh'
catalyzed isomerization 558
Gif system 1228, 1237
glass transition temperature 3 11
Glaxo Wellcome
- anti-HIV drug Abacavir 900
glutamic acid via amidocarbonylation
158
glutarates
- in hydroformylation 159
glycidol by asymmetric epoxidation 1140
glycidol derivatives via Sharpless
epoxidation of ally1 alcohol 571
glycidols as optically pure derivatives
42 1
glycol derivatives as by-products in
technical olefin oxidations 402
glycosidases in biocatalysis 88 1 f
glyoxylate in ene reactions 574
gold
- catalysts in alkene acetoxylations
- cluster 680
- electrocatalysis 1050
gold-aldol-reaction I144
grafting of organosiloxanyl radicals 501
halides 824f
Group IIIA-VIIIA as promoters in acetic
acid production 130
Group IV catalysts in olefin-
polymerizations 2 15 ff
Group IV metallocenes in industrial
productions 265 ff
Group IVA elements as catalyst stabilizers
and copromoters 128
Group V elements in acetic anhydride
process 127
77 Group VA elements as catalyst stabilizers
and copromoters 128
Group VIA elements as catalyst
stabilizers and copromoters 128
Group VIB carbonyls in carbonylations to
acetic anhydride 1 I6
Group VIII metals in carbonylations 104,
118
Group VIIVtransition metal in complex
combinations 157
greenhouse effect I189
Grubbs catalyst 338
Gulf Oil process 240, 243
H
H2 82
HJCO 82f, 120
H,Fe(CO), 18
H?02
- in epoxidation 415
- in olefin dihydroxylation 413
H202/CH3Re03as active species in arene
oxidation 435
H202/CH3Re03/AcOHas oxidant in
quinone formation 435 f
H2S 120
H,SO, in Pd-561 catalyzed oxidative
acetoxylation 41 1
H1PM~bVh040 as chloride-free oxidants
402
HiPMo6V6043as chloride-free oxidation
catalyst 40 1
hafnium in olefin polymerization 2 15
406 Halcon patents 116, 120 f, 1 18, 140,
413
1412 Index

halides - of aryl diazonium salts 776

- in carbonylation of aryl-X-compounds - of aryl halides 775f
147 - of aryl triflates 776
- in propyne carbonylation 321 - of vinyl halides 775 f
- transition metals 335 - under phase-transfer conditions 966
halocarbons in olefin polymerization 2 13 Heck-type reaction 147
halogen Hedione 578, 1243, 1249
- in oxidative carbonylations 165 hemilabile ligands 1 I67
- substituents in arene autoxidations 445 Henry reaction 993
halogenides in air oxidation reactions 45 1 Henry’s law 757
haloindanone - in ethylene oxidation kinetics 390,395
- Group IV metallocene catalysts 268 heptadienes
Hammett substitution coefficient in - cyclopolymerization 225
alkylarene autoxidations 455 - 4-trimethylsilyloxy- 1,6-heptadiene
Hartree-Fock method 704 f 225
Hatta number 749 heptane as solvent in Gulf Oil process
HBF4 in arene oxidations 436 243
HCl as reagent in hydrocarbon heptanols
halogenations 552 - 2-propylheptanol 42
HC104 in Pd-catalyzed oxidative - via aldol condensationhydrogenation
acetoxylations 4 11 42
HCo(C0)T heptenes
- in the hydroformylation cycle 45ff - hydroformylation 750
- kinetic\ of hydroformylation 52 - isomers in dimerizations 256
HCo(CO),PBuy 35, 57 - 3-methylheptenes 256
HCo(C0)4 10, 18, 35 heptyne in Pauson-Khand reaction 1243
- conversion into NaCo(C0)4 72 herbicides 150
- disintegration after hydroformy lation Hercules Inc. 341
69 f heteroaryl halides 150
- in hydrocarboxylations 183 heteroatom functionality in olefin
- in the hydroformylation cycle 45 ff metathesis 326, 332
- kinetics of hydroformylation 52 heterobifunctional ligands in
- recycled in BASF process 72 carbonylations 129
- re-integration 69 f heterocycles
HCol(CO), in the hydroformylation - by cyclooligomerization of alkynes
cycle 48 1252
HD-ocenol 688 - by hydroamination 1000
HDS see hydrodesulfurization - by McMurry coupling 1094
HDPE 19, 241 - hydrogenation 954 ff
HDPEhydrocarbons phase diagramm - in hydroaminations 518
232 - via carbonylation of aryl-X-compounds
heat transfer in polybutadiene 151
manufacturing 307 heterocyclic aromatic nitrogen as
heavy alkyl iodides as by-products in co-promoter in the Hoechst process
carbonylations I 13 122
heavy end products in acetic anhydride heterogeneous systems 3 ff
process 120 heterogeneous catalysts in SOH10
heavy ends carbonylation of methyl process 1298
acetate 118 heterogenization see immobilization
Heck reaction 21 heterogenized homogenous carbonylation
- in polymer chemistry 779 catalysts 129
 Index 1413

heteropoly acids high temperature processes in technical

- chloride-free oxidants 402
- in oxidation of alkynes 958
heteropolyoxo acids in chloride-free olefin
oxidations 40 1
heterovinyl compounds in alkyne reactions
282
hexaalkynylbenzenes 276
hexadienes
- copolymerization of 224
- cyclopolymerization 225
- hydrocyanation 484
- in butadiene/ethylene codimerization
263
- in diene cyclooligomerization 370
heteropoly acids
- chloride-free oxidants 402
- in oxidation of alkynes 958
heteropolyoxoacids in chloride-free olefin
oxidations 40 1
heterovinyl compounds in alkyne
reactions 282
hexaalkynylbenzenes 276
hexadienes
- copolymerization 224
- polymerizations 384
hexafluoroisopropyl in air oxidation
reactions 446
hexafluorophosphates as epoxy resin
polymerization initiators 385
hexanals
- 2-ethylhexanal 43 1
n-hexane
- in dimerizations/codimerizations 259
- in epoxidations 419
- in ethylene oligomerizations 241,
249
- in hydrosilylations with immobilized
metal-catalysts 498, 500
- in peroxide-initiated hydrosilylation
502
- in product distributions of hydro-
formylations 50
- isomers in dimerizations 256
- 2-methylhexenes 256
- via carbonylations 190
- via ethylene-trimerization 262 ff
hexanols
- by hydroformylation of 1-pentene
- 2-ethylhexanol 41, 62, 259
hexanones polymerizations 384
polymerizations 233, 236
HIV protease inhibitors 993
- asymmetric synthesis 572
- via glycidols by asymmetric
epoxidations 42 1
HLP via ethylene oligomerizations 249
HM(C0)2L in hydroformylations 58
HM(C0)4 57
Hoechst AG 9, 19, 116, 122, 389, 401,
406
homologation
- of acetic acid 141
- of alcohols 1034
homotopic coordination in propylene
polymerizations 219
Homer phosphines 1166, 1I76
hosvguest relation 91 1 ff
Hostinert 635
HPdCl(PPh3)2 in hydroesterifications
184
HRe04 by oxidation of CH3Re0(02)2
440
HRh(C0) in alkyne silylformylations
508
HRh(CO),(TPP) in hydroformylation
58 f
HRh(CO),(TPP), in hydroformylation
mechanism 48f, 58
HRh(CO),(TPPTS), in hydroformylation
51
HRh(C0)213 in carbonylations 110 f
HRh(C0)3 35
HRhC12 in butadiene/ethylene
codimerization 263
HSAB concept 976
/?-hydride transfer 473, 716
hydride transfer in ethylene oxidations
393
hydride- 1,2-shift
- in oxidative alkene acetoxylations
408
hydrides
- in Fischer-Tropsch synthesis 8 14
- in isomerization of olefins 1123 f
- in olefin polymerization 978 f
hydridocobalt carbonyls
- kinetics of hydroformylation 52
58 hydridocobalt complex reaction in the
- in alkyne silylformylations 508
hydriodic acid in carbonylations 109
1414 Index

hydroamination of olefins 1000 - anti-Markovnikov addition 48

hydroboration of olefins 1003 - mechanism 45f
hydrobromic acid in oxidative - modified catalysts 34ff, 45
carbonylations 140, 165 - di-ratio 31, 48, 53
hydrocarbons 525 - nonfunctionalized olefines 38
- by Fischer-Tropsch synthesis 808 ff - of a-olefines 242
- by Kolbel-Engelhardt synthesis 808 - of alkynes 41 f
- chlorinated in dimerizations 257 - of ally1 alcohol 754
- dehydrodimerization 1072 - of cyclohexene 766
- oxidation 960f - of 1-decene 688
- oxidation processes 106 - of dicyclopentadiene 688
hydrocarbonylations 182 ff, 3 18 - of diolefines 41 f
hydrocarboxylation 388 - of dodecenes 616
hydrochloric acid - of higher olefins 609, 616, 624
- in acetaldehyde manufacturing 400 - of norbornene 767f
- in alkyne reactions 282 - of I-octene 758
- in carbonylation of aryl-X-compounds - of special structures 34
149 - of unsaturated fatty acids 41 f
- in hydrocarboxylations 186 - photocatalysis I066
- in oxidative carbonylations 165 - polymer industry 62
hydrocyanations 468 ff - pressure-influence 56 f
- asymmetric 471 - propylene 13
hydrocyanic acid in alkyne reactions 282 - rate-determining step 50
hydrodehalogenation of aryl halides 956 f - reactors 66
hydrodesulfurization (HDS) of thiophenes - removal of heat 68
ll00ff - rhodium-catalyzed 84, 428
hydrodimerization see also telomerization - second generation 33
hydrodimerizations of olefines 361 ff - selectivity 48
hydroformylation technology 82 - separation of products and catalysts
hydroformylations 5 , 31, 386 68
- activation energy 53 - solvent-effects 53 ff
- aqueous biphasic system 68 - temperature-influence 55, 57
- aqueous phase 33 - third generation 33
- asymmetric 43ff, 91 - to linear aldehydes 32
- biphasic 90f - two-phase process 38
- catalytic cycle 45f - two-step process 56
- commercial applications 6 1 - unmodified systems 45
- discontinuous operation 65 - with re-immobilized ligands 685
- economic aspects 61 a-hydrogen abstraction
- exothermicity 84 - in alkylarene autoxidation 455
- first generation 33 - in metathesis reactions 334
- high-pressure operation 66 hydrogen cyanide
- homogeneous process 31, 38, 90 - by Andmssow process 1298
- hydrogenation 32 - DEGUSSA process 1298
- in membrane reactors 944f - DuPont adiponitrile process 1124
- in water-gas shift reaction 1086ff hydrogen in technical polymerizations
- influence of catalyst concentration 56 233
- influence of ligands 58 hydrogen hydrogen abstractions 530
- kinetics 51 ff - benzylic, in arene autoxidations 448
- low pressure 82 - in uncatalyzed hydrocarbon oxidations
- Markovnikov addition 48 528
 Index 1415

hydrogen bromide catalysis in arene- hydroperoxy radicals in uncatalyzed

air-oxidations 45 1
hydrogen chloride in oxidative
carbonylations 174
hydrogen peroxide
- in chloride-free oxidations
- in hydroxylation 1150 f
- in phase-transfer catalysis 957
hydrogen shift
- in ethylene dimerization 259
- in isomerization of olefins 1121 ff
hydrogen splitting 352
B-hydrogen transfer
- in ethylene trimerization 262
- in polypropylene polymerization
220
hydrogen transfer reaction
- of aldehydes 612 f
- of cyclooctane 1073
hydrogenation
- in membrane reactors 943 f
- of acetophenone 681
- of alkynes 955
- of arenes 955
- of aromatic compounds 682
- of benzothiophenes 1 100 ff
- of carbon dioxide 1196ff
- of coal 3
- of cyclohexene 682
- of dienes 955
- of heterocycles 954f
- ofhexene 997
- of 2-hexyne 685
- of living cells 1284
- of nitro arenes 954
- of olefins 954ff
- of thiophenes 1101 ff
- of a,B-unsaturated carbonyl
compounds 954 ff
hydrogenation activity in hydro-
formylation 57
hydrogenation of by-products in
hydroformylation 56
hydrogenolysis
- of benzothiophenes 1106 ff
- of thiophenes 1106 ff
hydrohalic acids in carbonylations
142
hydrolysis of phosphonate esters 920
hydroperoxide decomposition in
catalyzed chain reactions 532
oxidations 527, 528 ff
hydropyrans 4 1
hydropinones
- in alkyne-carbonylations 279
402 - in oxidative alkene-acetoxylations
406
hydrosilanes dehydrocoupling 505 ff
hydrosilylations
- asymmetric 494
- intermolecular 494 f
- of silicon compounds 491
- of styrenes 998
- of unsaturated polymers 494
hydrovinylation
- of 1,3-dienes 1168
- of bornene 1174
- of bicycloheptene 1167 f
- of olefins 1164 ff
- of styrene 1167
a-hydroxy acids 877
hydroxy carbonylations 145
a-hydroxyalkyl radicals in uncatalyzed
hydrocarbon oxidations 528 f
hydroxyamination of olefins 1159
p-hydroxybenzoic acid 460
hydroxydienones via arene oxidations
438
hydroxylation
- by monooxygenases 879
- of adamantane 960
- of benzene 960
- of cyclohexane 960
- of olefins 957ff
hypervalent iodo compounds in Heck
reaction 776
hypochlorite
- in epoxidation 958
- in hydroxylation 960
I
IBIS
- Naproxen route 903
Ibuprofen
- biocatalytic resolution 893, 901
- by asymmetric synthesis 475, 561
- by Grignard cross-coupling 825
- hydrovinylation route 1169
- in carbonylations of aryl-X-compounds
149
- via hydrocarboxylation 186
1416 Index

ICI 345 - Group IV metallocene catalysts 267 f

- 2,2'-bipyridyl synthesis 1258 - via carbonylation of aryl-X-compounds
- urethane synthesis 1217 151
Idemitsu Kosan Co. indene synthesis by Group IV metallocene
- chloride-free olefin oxidations 40 1 catalysts 268
IFP 259, 264 indenes 269
- RAM I1 process 674 - 4,7-alkyl-substituted indenes 268
IG Farben 443 - 4,7-dimethylindene 269
Imazapyr 150 - 2,4-substituted 272
imidazoles - Group IV metallocene catalysts 268
- as initiators 383 indenyl ligands in polypropylene
- catalysts in epoxy resin polymerizations polymerization 222
383 indenyl zirconium complexes in propylene
- in cycloaddition 1259 polymerization 222
imidazolines in butadiene/ethylene Indinavir by asymmetric synthesis 57 1
codimerizations 263 Indoles by McMurry coupling 1098
imidazolium salts 9 1 indolinyl carbamyl in hydroxylation
imidazols of olefins 1155 f
- 1,3-dialkylimidazolium chloride 263 industry
imines in asymmetric hydrogenation - oleochemical 332
569, 1145 - perfume industry 373
imines see also Schiff bases inert gas blanketing in polybutadiene
iminophosphines in ethylene manufacturing 306
oligomerizations 250 inhibitors of platinum catalysts in
Imipenem hydrosilylations 496
- in ethylene polymerization 563 initiation
- with metallocene/alumoxane catalysts - free-radical 344
217 - in arene autoxidations 447 f
immobilization see also re-immobilized - of polycondensations 505
catalysts, see also solid supporters, - of polyketone formations 349 f
see also SOMC - PdCOOMe' 350f
- by membrane reactors 942ff - PdH' 351
- colloids 677 initiators
- Fischer-Tropsch reaction 652 - carbomethoxide 350
- fixation 646 - in epoxy resin polymerizations 383,
- in biocatalysis 894 3 85
- in cyclooligomenzation 650 - olefin metathesis 337
- in epoxidation 652 - palladium methoxide 353
- in Heck reaction 777 insecticides 799
- in hydroformylation 649, 652 insertions
- in hydrogenation 649, 652 - CO 137, 321f
- in polymerization 651 ff - double ethylene 354
- in water-gas shift reaction 652 - in propylene polymerizations
- of homogenous catalysts 1345 220 f
- separation and recycling 602, 607 ff, - in propyne carbonylations 322
759 - of ethylene 353ff, 4747
Ind2ZrMe2 in dimethylmetallocene - of olefines 353ff
synthesis 270 - oxidative 379
indanones - propyne 321 f
- 2-alkylindanone 268 insertion reactions in ethylene
- 7-chloro-2-methyl- 1 -indanone 268 oxidations 391 ff
 Index 1417

Institut Frangais du Petrole see IFP - complexes in dehydrogenative

intermediates 45 1, 506 vinylsilane/silylation 503
- arene oxide intermediate 438 - electrocatalysis 1056
- epoxides 438 - hydrodesulfurizaion 1101 f
- in aldehyde oxidations 429f - hydrogenolysis of benzothiophene
- in alkyne silylformylations 507 1106 f
- in allene hydrocyanations 484 - immobilization 649
- in arene autoxidations 444, 449, 458 - in catalyzed carbonylations 116
- in asymmetric epoxidations 421 - in carbonylations of methanol 113
- in butadiene hydrocyanations 482 - [Ir(CH,(CO),I,] 1 13
- in cyanoolefin hydrocyanations 478 - [Ir(CH,CO)(CO),13] 1 13
- in cyclooligomerizations 376 ff - [Ir(CO)212]-l13
- in ethylene oxidations 390, 393 f - [II(PE~&(C~H,)~C~I 520
- in hydroaminations 515 - Ir(PEt3)2(H)(C7H,oNHPh)Cl52 1
- in hydrocarboxylations 183 - Ir(PEt3)2(H)(NHPh)CI 52 1
- in hydrocyanations 469 - Ir(PEt3)2Cl 520f
- in hydrosilylations 494, 498 - isomerization 967
- in oxidative acetoxylation 408 - low water-process 114
- in quinone formations 435 - transfer dehydrogenation of alkanes
- in the epoxide production 413 1230
- in uncatalyzed hydrocarbon oxidations - transfer hydrogenation 957
527 ff iridium catalysts in carbonylations 104
- metallacyclic 333 f iridium complexes in alkene/alkyne-
- Pd-Cu cluster 397 hydrosilylations 498
internal alkynes in linking with iron 18, 22
aldehydes 282 - a5 catalysts in hydroaminations 522
internal olefines via the Shell process - C-H activation 1227 ff
246 - (C5H5),Fe 22
intramolecular dialkoxycarbonylations - cluster 813
188 - [(CO),FeC(=O)OH] 18
intramolecular hydroaminations 518 - complexes in cyclo-co-oligo-
intramolecular ring-closing metathesis merizations 375
see RCM - complexes as aldehyde oxidations
inverse phase-transfer condition 956 catalysts 428
iodide as catalyst stabilizer 112 - cyclooligomerization of alkynes 1253
iodide salts in carbonylations 108, - desulfurization 968
ll0ff - electrocatalysis 1050f
iodine impurities in the acetic anhydride - [Fe(CO),I 2- 146
process 128 - Fe(CO)5 498, 502
ion-exchange resins 84 - Fe,(CO),, 503
ion-exchangers in acetic anhydride - ferric halide as catalyst in hydrocarbon-
processes 120 halogenations 553
ionic liquids 639 ff, 1362 ff - Fischer-Tropsch synthesis 813 f
iridium - hydroformylation 763
- as catalyst in hydroaminations 520ff - hydroxylation of benzene 960
- asymmetric hydrogenation of imines - immobilization 647
1145 - in asymmetric dihydroxylation 1141
- carbonylation chemistry 114 - in cyclopropanation 804
- cluster 681 ff - in photocatalysis 1066
- complexes in carbonylation of - in stereospecific diene polymerizations
olefines 140 312
1418 Index

- in water-gas shift reaction 1087ff isohexenes

- iron (11) complexes in cyclo-co- - by nonregioselective catalysts 259
oligomerizations 379 - via ethylene dimerization 259
- iron(I1) sulfate 280 isomerization of methyl formate 130
- iron(II1) sulfate 280 isomerizations in asymmetric hydro-
- photocleavage of diols 1074 cyanations 473 f
- photoisomerization 1062 ff, 1074 - anti-syn 290, 298ff
- photooxidation 1070 - cidtrans in polyketone formation 353
- reduction of nitro arenes 954 - in BASF vitamin-A synthesis 1124
- pentacarbonyl 279, 522 - in carbonylations 189
- photoactivated catalysts 502 - in DuPont adiponitrile process 1124
- porphyrin complexes 428 - in Grignard cross-coupling 825
iron catalysts in carbonylations of - in the Shell process 247
aryl-X-compounds 146 - metathetical cis-trans 329
iron salts - of alkynes 283
- in butadiene/ethylene codimerizations - of allylic alcohols 967
263 - of olefins 1119ff
- in oxidative carbonylations 174 - phosphine-catalyzed 283
iron-based catalysts in ethylene - trandcis in ethylene oxidations 391
oligomerizations 25 1 Isoniazid 150
IR-spectroscopy of rhodium isononanols 259
complexes 1 18 - by hydroformylation of octenes 36
iso-aldehydes 3 I isooctenes 259
isobutanal 13, 64 isophthalic acid via autoxidation 443
- RCHRP process 81 isoprene
isobutane in oxidations 41 7 - cyc looligornerizatio t i 372
isobutane route in commercial oxirane - in cyclo-co-oligomerizations 375
processes 4 1 8 - cyclotrimerization with carbon
isobutene dioxide 1194
- amm(on)oxidation 1298 - in diene cyclooligomerizations 370
- cyclopropanation 798 f - 1,4-insertion 293
- oxidations of 316 isopropenyl acetate by oxidation 407
isobutylbenzene in carbonylations of isopropyl in air oxidation reactions 446
aryl-X-compounds 149 isopropyl alcohol in the hydrogen
isobutylstyrene in asymmetric peroxide process 529
carbonylation 56 1 isoquinoline alkaloids by asymmetric
isobutyric acid 13 synthesis 575
- via carbonylations 190 isotactic polybutene 261
isochromanone via carbonylation of isotope effect
aryl-X-compounds 149 - in catalyzed oxidations of
isocoumarines via carbonylation of alkylaromatics 536
aryl-X-compounds 151 - in ethylene oxidation 393
isocy anates - in hydroaminations 520
- by reductive carbonylation 1090 isotope labeling
- in epoxy resin polymerizations - in amm(0n)dehydrogenation 1302
383 - in amm(on)oxidation 1299
isocyanoacetates by gold-aldol reaction - in asymmetric isomerization of
1I44 olefins 1126
isodecanol 42 - in carbonylation of aryl halides 963
isodecenes 259 - in electrocatalysis 1056
isoheptenes 259 - in Fischer-Tropsch synthesis 81 1 ff
 Zndex 1419

- in isomerization of olefins 1122 ff kinetic resolution

- in living cells 1289 - in biocatalysis 890ff
- in water-gas shift raction 1089 - of amino acids 891
- of cyclic ketones 879
J kinetics
Jacobsen epoxidation 1140 - carbonylation of methanol 751
Japanese Maruzen Oil Co. chloride-free - Heck reaction 784f
olefin oxidations 401 - hydroformylation of 1-heptene 750
- hydroformylation of 1-octene 758
K - hydroformylation of allylic alcohol
Karstedt’s catalyst 750
- in hydrosilylations 495 - hydroformylation of cyclohexene
- nickel equivalent, in dehydrogenative 766
silylations 503 - hydroformylation of diisobutene 750
KB in kinetics of hydroformylation 53 - hydroformylation of propene 750
Kellog-Synthol process 81 1 - hydrogenation of ally1 alcohol 750
ketene route in carbonylations 116 - hydrogenation of cis- 1,4-poly-
a-keto acids in reductive amination 904 butadiene 75 1
a-keto aldehydes by oxidation of alkynes - hydrogenation of cyclohexene 750
95 8 - in carbonylations 111
a-ketoamides via carbonylations 190 - in catalyzed chain reactions 526, 532
y-keto acids by carbonylation of alkynes - in Co-catalyzed arene autoxidations
964 449
ketones - in ethylene oxidations 390
- asymmetric hydroboration 566 f - in hydroaminations 520
- asymmetric hydrogenation 566 - in methoxycarbonylation of propyne
- asymmetric hydrosilylation 498 - in oxidations of hydrocarbons 526
- asymmetric reduction 877 - in SHOP process 751
- by 1,2 additions of alkynes 276 - in uncatalyzed chain reactions 526
- by carbonylation of alkyl halides - in Wacker-oxidation of ethylene 751
1068 - liquid-phase reaction 750 ff
- by oxidation of alcohols 959 - oligomerization of ethylene 751
- 1,3-diketones by chloride-free - of the Witten oxidation process 545
oxidations 402 - of aldehyde oxidations 429 ff
- ethinylation 275 - of allene hydrocyanations 484
- hydrocyanation 485 f - of arene autoxidations 454ff
- in asymmetric hydrogenation 570 - of carbonylations 111 ff
- kinetic resolution 879 - of catalytic olefin oxidations 389
- McMuny coupling 1093ff - of co-carbonylations 124
- Meenvein-Ponndorf-Verley reaction - of epoxidations 413 ff
1003 ff - of ethylene oxidations 391 ff
- oxidation 960 - of hydroaminations 518
- a,b-unsaturated ketone 276 - of olefin oxidations 389
- via alkyne-isomerization 283 - of Pd-catalyzed oxidative aceto-
ketoprofen in carbonylations of ary-X- xylations 409
compounds 149 - of poymerizations 216
Keulemans rule 39 - of propyne carbonylations 318
Kharasch reaction 387 - oxidation of cyclohexane 751
- ethylene-platinum complex 392 - polymerization of butadiene 751
- Kharasch complex 406 - reduction of nitro arenes 954
khellactone 1 160 Koch synthesis 130, 189, 427
1420 Index

Koch-Haaf reaction in carbonylations - in Michael reaction 993

189 - in Mukaijama aldol reaction 995
Kogasin process 808 - olefin dimerization 989 ff
Kolbe-Schmidt reaction 1 1 89 - olefin polymerization 978 ff
Kolbel-Engelhardt synthesis 808 - Oppenauer oxidation 1003 ff
Krupp-Uhde epoxidation processes 422 - organolanthanide complexes in
Kuhlmann process 69 hydrosilylations 499
- ring-opening metathesis polymerization
L 986 ff
1h-ratio 85, 87,91 - ring-opening of epoxides 996, 1005
- of phosphites 88f - shift reagents 996
La Roche 8 LAS (linear alkyl sulfates) 242
LABS (linear alkylbenzene sulfonates) Lazabemide 150
242 LCP (liquid crystal polymer) 460
lactames LCST (lower critical solution
- by addition of diazo compounds temperature) 232
1290 ff lead
- by carbonylation of aryl halides 962 - in aldehyde oxidation catalysts 432
- via hydrocyanation 481 leaving groups
lactones - in carbonylations of aryl-X-compounds
- by addition of diazo compounds 148
1290ff Lemakalin in asymmetric synthesis 572
- by carbonylation of alkynes 964 LEUPHOS in asymmetric Grignard
- by carbonylation of aryl halides 962 cross-coupling 825
- by 1,3-dienes and carbon dioxide levoflaxacin by industrial synthesis via
coupling 1191 ff propanediol 569
- by enzymatic resolution 901 Lewis acids
- copolymerization with MMA 988 - as epoxy resin curing agents 383
- ring-opening metathesis - in asymmetric hydroformylations 43
polymerization 986 ff - in butadiene hydrocyanations 482
- via carbonylation of alkanes 191 - in epoxy resin polymerizations 384
- via dialkoxycarbonylation 188 - in hydrovinylation 1 1 65
lanthanides - in olefin hydrocyanation 475
- (R)-BINOL-La 571 - in photocycloaddition 1068
- [(C,Me,),La(NHMe)(H,Me)I 519 - in reductive carbonylation 1216
- alkyne oligomerization 989 - in technical polymerizations 235
- as catalysts in hydroaminations 5 18 ff life cycles 10
- butadiene polymerization 983 ligand accelerated catalysis 1156
- C-H activation 978, 1231 - in hydrocarboxylations 185
- copolymerization 987ff - in technical polymerizations 235
- dehalogenation 1005 ligand development in hydro-
- Diels-Alder reaction 991 ff formylations 85
- Henry reaction 993 ligand effect in epoxidations 414
- hydroamination 1000ff ligand insertion in ethylene oxidations
- hydroboration 1003 394
- hydrogenation 997ff ligand tailoring in hydrocyanations 468,
- hydrosilylation 998 477
- in carbonylation of benzyl chloride ligand transfer oxidation 397
963 ligand tuning
- in Meenvein-Ponndorf-Verley - in butadiene telomerizations 369
reaction 1003 ff - in olefin oligomerizations 214
 Index 1421

ligands see also amines, phosphines, - phosphines 379

phosphites, P-N-ligands - phosphites 379
- n-acceptor, in hydrosilylations 496 - phosphonium salt 366
- alkoxy 419 - PPhi 410
- alkylperoxo 417 - steric interactions 474
- anionic 358 - tetravalent phosphonium salt 362
- bidentate I ,3-bis(diphenylphosphino) - thioethers 347
propane 346 - trivalent phosphine 362, 89
- bidentate dppp 346 limiting rates in catalyzed chain
- bidentate phosphanes in hydro- reactions 532
cyanations 475 limits
- bidentate in hydrocyanations 469 - catalyst composition, in alkylarene
- bidentate in propyne carbonylations autoxidations 458
326 - catalyst concentration, in alkylarene
- bidentate phosphine ligands 345 f autoxidations 458
- bidentate polyketone catalysis 352 ff linalool via regioselective epoxidations
- bipyridines 347 420
- bisoxazolines 347 linear a-olefine by ethylene
- CZHSSH 410 oligomerization 240 ff
- chelating 346f linear low-density polyethylene (LDPE)
- concentration in butadiene 218
telomerizations 363 linkers for immobilization of
- 1,2-dimethylcyclopentadienyI ligands hydrosilylation catalysts 500
222 LiOAc in carbonylations 109, 112
- imidazole 383 lipases in biocatalysis 873
- in asymmetric hydrocyanations 472 f liquid crystal polymer see LCP
- in asymmetric hydrogenations of amino liquid crystals via asymmetric
acids 573 epoxidations 578
- in butadiene hydrocyanations 483 liquid phase processes in oxidative
- in catalyzed hydrocarbon oxidations carbonylations 175
539 liquid recycle process 75 f, 77, 83
- in cyclooligomerizations 379 lithium 307
- in diene cyclooligomerizations 370 f - in diene polymerizations 290
- in diene polymerizations 290 - in stereospecific polymerizations 286
- in ethylene oxidations 391 - initiators in polybutadiene
- in ethylene/CO copolymerizations manufacturing 307
346 f - LiRh 118
- in hydrocyanations 468, 476 - LiBF, 112
- in hydroformylation 45, 58 - LiCF3SO3 112
- in hydrosilylations 496, 501 - LiCH, 121
- in metathesis reactions 334 - LiCHl 122
- in polypropylene polymerizations 222 - LiCH, 124
- monodentate 475 - LiCl, in ethylene oxidations 394
- monodentate phosphine 352 - LiI 112
- neutral bidentate 359 - LiI as catalyst in the Eastman process
- of Group IV metallocene catalysts 121
266 ff - LiI in carbonylation of methyl acetate
- of Pd catalyzed oxidative acetoxylations 118
410 - LiI in carbonylations 108, 170
- Ph3P 375 - polybutadiene 307
- phen 410 living cells 1283 ff
1422 Index

living polymerization mandelonitrile in aldehyde hydro-

- MMNlactone copolymerization 988 cyanations 485 f
- of lactones 986ff manganese
- of methyl methacrylates 983 ff - as catalyst in hydrocarbon oxidations
- of norbornene 1279 538
LLC 341 - as catalyst in enantioselective
LLDPE 218, 241, 261 f epoxidations 572
local density approximation (LDA) 707 - as peroxide-decomposer in catalyzed
Lonza oxidations 533
- asymmetric hydrogenation of - asymmetric epoxidation 958, 1140
imidazolone 1138 - C-H activation 969
- biocatalytic resolution 893 - carbonylation 965
- L-carnitine synthesis 903 - catalyst system, in arene autoxidations
long-term stability 83 444
loop reactor 73 - co-catalyst in arene autoxidations
low temperature chlorination (LTC) in PVC 45 1
production 554 - colloids 682
low temperature processes in technical - dihydroxylation 1149
polymerizations 233 - immobilization 648
low water A 0 process 112 - in aldehyde oxidations 429
low water technology in - in alkylarene autoxidations 456
carbonylations 107 ff - in carbonylations of alkanes 191
low waterhigh-LiI-catalyst system 109 - in catalyzed hydrocarbon oxidations
LPG (liquefied petroleum gas) 257 540
LPO process 12, 33, 63 f, 66 f, 75, 81, - in dicarboxylations 189
91 - in liquid-phase oxidations of paraffin
lubricant oils 537
- by technical polymerizations 230 - in synergetic autoxidations 452
- oxidative degradation 539 - in photocatalysis 1062, 1066
Luflexen 265 - manganese(II1) chiral Schiff’s base
lutidines 1257 complex 421
- manganesekmtacn catalyst 424
M - Mn(OAc), 189
M2+/3+halogenide-catalyst system in - Mn(OAc)2/HBr 452
arene autoxidations 45 1 - Mn(OAc)3 191
M3BN in butadiene hydrocyanations 482 - Mn(0Ac)Br 451 f
macrokinetics in hydroformylation 5 1 f - Mn/Br 444
macrolactones see lactones magnesium - Mn” 451
- bis(dihydrooxazo1e)-Mg(I1) complex - Mn2+/Mn3+systems 428
486 - Mn3+ 449f
- in olefin polymerization 981 - Mn3+ acetate 448, 456
- RMgX 17 - oxidation of hydrocarbons 960
maleic acid in a-olefine conversions 242 - synergetic co-catalyst in arene
- in hydrocyanations of functionalized autoxidations 450
olefines 476 manufacturing processes
malonic acid derivatives in alkyne - of acetaldehyde 400ff
reactions 282 - of acetone 400ff
- ethyl ester by Group IV metallocene - of agglutinations 384
catalysts 267 - of composite materials 384
mandelic acid as alternative chiral - of polymers 305
ligand 577 - of prepregs 384

MA0
- in ethylene oligomerizations 250
- in hydroaminations 516
- in hydrocarboxylations 184
- in hydrocyanations 481
- in hydroformylations 48
- in hydrosilylations 493
- in polymerizations 215
- Markovnikov-anti-Markovnikov-
product
mass transfer 88
- in hydroformylations 65f
MCM-41 423
McMuny coupling 1093 ff
MDPP as catalyst in asymmetric
hydrosilylations 499
mechanism
- amm(on)oxidation 1299
- arene oxide mechanism 436
- asymmetric hydroamination 999
- asymmetric hydrosilylation 999
- asymmetric Michael reaction 994
- carbonylations of aryl-X-compounds
145
- Chalk-Harrod mechanism 493
- C-H activation by SOMC 672
- cotrimerization of alkynes and carbon
dioxide 1195
- cyclotrimerization of butadiene and
carbon dioxide 1193
- dihydroxylation of olefins 1152
- electron transfer 453
- elimination in Co-catalyzed arene
autoxidations 449
- Fischer-Tropsch synthesis 81 1 ff
- Heck reaction 782ff
- heterolytic, in epoxidations 4 15
- homologation of alcohols 1040ff
- hydrodesulfurisation 1100
- hydroformylation of olefins 729
- hydrogenation of carbon dioxide
- hydrovinylation 1178 ff
- in dimerizationskodimerizations
254 ff
- isomerization of olefins 1121 ff
- membrane seperation 692
- metathesis 333
- of amidocarbonylations 157, 162 f
- of arene-autoxidations 447
- of cyclooligomerizations 376
- of epoxidations 413 ff
Index 1423
- of ethylene oligomerizations 250
- of ethylene/CO copolymerization
347 ff
- of hydrocyanations 469
- of isotactic polymerizations of
propene 220
- of olefin oxidations 389
- of oxidative alkene acetoxylation 407
- of Pd-catalyzed oxidative
acetoxylations 410
- of polymerizations 216
- of propyne carbonylations 320
- of the Shell process 248
- olefination of aldehydes 1082ff
- Pauson-Khand reaction 1247 ff
- photocyclization 1067 ff
- photoisomerization of pentene 1063
- polymerization of methyl
methacrylate 985
- polymerization of olefins 713 ff
- reductive carbonylation of nitro arenes
1218ff
- water-gas shift reaction 1087 ff
MeDuPHOS as ligand in asymmetric
hydrogenations 563
Meerwein-Ponndorf-Verley reaction
1003 ff
MEK (methyl ethyl ketone)
- catalyzed oxidation mechanism 534
- in catalyzed hydrocarbon oxidations
536
- in Co-catalyzed co-oxidations 453 f
membranes in selective gas permeation
333
membrane reactors in catalysis 942
membrane technology in ligand seperation
690
menadione 433
- industrial synthesis with C r 0 3 435
menthol
1200 - industrial synthesis via myrcene 558
- synthesis 15
- Takasago process 1125
menthyldiphenylphosphine see MDPP
MeOBIPHEP as ligand in enamide
hydrogenations 575
mercury
- as catalyst in PVC production 553
- C-H activation 1229
- dehydrodimerization 1072
- Hg2+ salts 280
1424 Index

- Hg;' salts 280 - of vinylsilanes 504

- HgC12 553 - termination step 335
- in oxidation of alkynes 958 methacrolein via formaldehyde 3 16
- mercury sulfate catalysis in methacrylates
vinylations 279 - ee in hydroformylations 45
- oxidation of methane 1232 - via alkyne carbonylations 3 16 ff
Mesembrine 575 methacrylic acid 13, 428
mesitylene methane
- by cyclotrimerization 1262 - Andrussow process 1298
- oxidations of 437 - carbonylation of methyl acetate 118
mesoscale methods 701 - oxidation 1234
metal carbonyls - oxidative carbonylation 131
- in carbonylations 136 - sulfonic acid, in propyne
- in electrocatalysis 1057 carbonylations 3 18
- in homologation 1034 methanol
- in Pauson-Khand reaction 1246f - co-carbonylation with methyl acetate
- photocatalysis 1062 122
metallacyclobutanes in cyclopropanation - concentration in aryl-X compound
797 carbonylations 146
metal complexes - condensation 253
- immobilized, hydrosilylation - homologation reaction 115, 1035
catalysts 500 - in carbonylation 9, 106, 110, 113, 114,
- peroxide-initiated, for hydrosilylations 116, 173, 346, 427, 525, 751
50 1 - in MTG process 764
- photo-initiated, for hydrosilylations - methyl acetate mixture in
50 1 carbonylations 124
metal salts in catalytic olefin oxidations methoxy group in propyne carbonylations
388 32 1
metallocenes methoxycarbonylation in the carbonylation
- 2-alkyl-4-aryl-substituted of bromobenzene 146
metallocenes 267 ff methoxyoctadiene via carbonylation of
- alumoxanes in polymerization 217, aryl-X-compounds 151
231 ff 6-methoxy-2-vinylnaphthalenein
- do complexes 359 hydrovinylation 1171
- Group IV metallocene catalysts methyl acetate
267ff, 506 - carbonylation 116 f
- in cyclooligomerization of alkynes - conversion 124
12.53ff - in the Eastman process 121
- in hydrosilane-dehydrocouplings 506 - promotion in carbonylations 108
- in polymerizations methyl acrylate in amidocarbonylations
- in polymerizations with M A 0 215 159
- isomenzation of olefins 1127 methyl benzoate as intermediate in the
- lanthanide 506 Witten process 545
metalloporphyrins as catalysts in arene methyl chloroformate in oxidative
oxidations 440 carbonylations 174
metathesis 328 ff methyl cinnamate by oxidative
- a-olefines 329 carbonylations 166 f
- cross-metathesis 328 methyl crotonate in alkyne carbonylations
- in the Shell process 247 3 18, 322
- initiation step 335 a-methyl-D-fructofuranoside as ligand in
- of acyclic alkynes 329 enantioselective hydrocyanations 478
 Index 1425

methyl ethyl ketone see MEK microkinetics in hydroformylations 5 1

methyl iodide microstructure
- in carbonylation 104, 107, 139 - metathesis-polymer 329
- purification in carbonylation 115 - of COC 224
- regeneration in co-carbonylations - of diene polymers 295
125 - of polymers 215
methyl ketones by oxidation of olefins - of polymethylenecyclopentane 225
95 8 - of polypropylene 220
methyl methacrylate see also MMA Milas reagent 1149
- in cycloolefin polymerizations 224 - in olefin dihydroxylations 413
- in hydroformylation 54 miscibility of solvents 610
- polymerization 983 ff Mitsubishi Chemical Industries 82, 88,
methyl propionate 243
- alkoxycarbonylation of ethylene 345 Mitsubishi process 84
- in polyketone formation 352 Mitsubishi Rayon 3 16
- synthesis 353 Mitsui Chemicals 265
methyl p-toluate as intermediate in PET MMA
production 54 1 - catalytic cycles 321 ff
methyl sulfate by oxidation of methane - via propyne carbonylation 326
1232 MO investigations
methyl-3-pentenoate 88 - alkyne carbonylation kinetics 322
- in hydroformylation 37 - in kinetic studies of ethylene
methyl-5-formalvalerate 37 oxidations 394
methylalumoxane 7 12, 720 Mobil
- see also M A 0 - MTG process 764
- in butadiene polymerization 294 modified catalysts in hydroformylation
- in hydrovinylation 1165 57
- in polymerizations 215 f m-OHCC6H4SO3Nain deactivation of
methylcarbapenem intermediate in hydroformylation catalysts 61
stereoselective synthesis 576 Moiseev reaction 386, 390, 392 f, 406 f
methylene- 1,3-cyclopentane in cycloolefin molecular dynamics 706, 710
polymerizations 224 molecular lock 930
methylene- y-lactones via alkyne- molecular mass distribution in technical
hydrocyanations 480 polymerizations 230 f
methylene diisocyanate 1091 molecular mechanics 703 ff
methyl-tert-butyl ether see MTBE molecular modeling
methyltrioxorhenium see MTO - in homogeneous catalysis 700ff
Metocene 265 - in hydrovinylation 118 1
Metolachlor by enantioselective imine molecular sieves in epoxidation processes
hydrogenation 569 422
Metton 341 molecular weight
MgC12 in oxidative carbonylations 166 - in polybutadiene manufacturing 309
MGN in butadiene hydrocyanations 483 - of polyketones 344, 347
MgO catalyst in the Shell process 246 - of rubber compounds and vulcanizates

mibefradil intermediates in asymmetric 311

synthesis 563
Michael addition 159, 993f
Michaelis-Menten-kinetics
- in epoxidations 414
- in Pd-561 catalyzed oxidative
acetoxylation 409
molecular weight distribution
- in olefin-oligomerizations 214, 308,
310f
- in 1,4-polymerizations 304
molecular weight regulation in 1,4-poly-
merizations 303 ff
1426 Index

molybdenum MTO (methyltnoxorhenium) 424 ff,

- alkylidene complexes 338 433
- amm(on)oxidation 1298 ff - Baeyer-Villiger oxidation 1309 ff
- carbene complex catalysts 338 - Diels-Alder reaction 1315 ff
- catalyst in epoxidations 419 - epoxidation of allylic alcohols
- catalyst in metathesis reactions 332 - in olefination of aldehydes 1080,
- dioxomolybdenum(V1) complex in 1314ff
epoxidations 414 - olefin metathesis 1315
- H3PM0120," 439 - oxidation of alkenes 1306
- H3PM~hV6040 as chloride-free catalyst - oxidation of anilines 1311
40 1 - oxidation of aromatic compounds
- hydrodesulfurization 1101 1309
- in epoxidations 413 - oxidation of dienes 1308
- in hydroformylation 767 ff - oxidation of sulfur compounds 1310 ff
- Mo(C0)6 414 - synthesis 1304ff
- Mo(V1) 419 MTO/H20,
- MoClS 334 - in naphthalene oxidations 434
- M003 413 Mukaijama aldol reaction 995
- olefination of aldehydes 1080 multifunctional catalysis 762
- photooxidation 1070 multienzyme systems 883
- trialkylammonium molybdate 34 1 muscarine 1294
Mond process 3, 17 muconic anhydrides in arene oxidations
monocarboxylic acids via 438
hydrocarboxylation 182 MVN in enantioselective hydrocyanations
monochloroacetaldehyde 399 477
monochloroacetic acid 106 myrcene in Vitamin-E synthesis 623
monoclonal antibodies see antibodies
monohydrosilanes by hydrosilylations N
498 di-column
monomer activation in polyketone - RCHRP process 81
formations 358 n/i-ratio
monomer conversion in polybutadiene - BASF process 82
manufacturing 3 10 - generation of carboxylic acids 143
monomeric styrene see SM - in hydroformylations 48, 50, 54, 56f,
monophenols 88 58 f
monophosphines 86 - RCHRP process 81
monosodium glutamate 39 - Shell process 74f, 85, 90
Monsanto NdK catalyst in the Shell process 246
- catalyst system 105, 117 N-acetyl-D-phenylalaninevia amido-
- high-water technology 113 f carbonylations 161
- Monsanto process 106ff, 128, 139f N-acetylglutamic acid 159
- technology in carbonylation 9, 14, N-acetylglycine from
107, 116, 121 paraformaldehyde 161
Monte Car10 methods 710 N-acyl-a-amino acids via amido-
Montedison's pilot plant 14, 148 carbonylations 156 ff
montmorillonit 185 NADH recycling 877
morpholines NAILS (non-aqueous-ionic-liquids) in
- N-methylmorpholine-N-oxide 578 butadiene/ethylene codimerizations
MTBE 263
- in the isobutane process 417 NaOAc in oxidative carbonylations 167
- production 316, 41 NAPHOS 85f

naphtha crackers 317, 340
naphtha fractions 116
naphthalenedicarboxylic acid 461
naphthalenes
- carboxylic acids by oxidative
carbonylation 170
- commercial production 446
- 2,6-/1,4-dicarboxynaphthalenes 446
- 2,6-dicarboxynaphthalenes 46 1
- 2,6-DIPN 461
- in oxidations with MTO 434f
- 6-methoxy-2-vinylnaphthalene 477
- 2,6-NDA 461
naphthenic naphthas for acetic acid
productions 539
naphthoic acid
- 6-hydroxy-2-naphthoic acid 460
naphthol
- asymmetric homo coupling 1072
- in photocycloaddition 1068
naphthol derivatives 460
- via carbonylation of aryl-X-
compounds 15 1
naphthoquinones in oxidations 433 f
naphthoxyacetoaldehyde in asymmetric
nitroaldol reaction 571
naphthylboronic acid by Group IV
metallocene catalysts 268
Naproxen 614
- biocatalytic resolution 890, 901
- by asymmetric hydrogenation 559 f,
1139
- in carbonylations of aryl-X-compounds
149
- synthesis of 475, 477
- (R)-naproxen-nitrile 478
- via enantioselective hydrocyanations
478
Natta’s law 56
Natta’s reaction rate equation 51
natural bite angle 91
- phosphine ligands 36
natural gas 116
Nazarov method in hydrocyanation of
aldehydes 485
NBS as reagent in hydrocarbon-
halogenation 552
n-butanal 14
- cost structure of processes 64
- production capacities 62
- RCWRP process 81
Index 1427
n-butene
- in dimerization 254ff
- RCHRP process 78
n-butyric acid via carbonylations 190
neodymium
- allylneodymium compounds 304
- catalysts for polybutadiene production
310
- in butadiene polymerization 293
- in Ziegler-Natta type catalysts 284f,
289 f
- neode~anoate/Al(i-Bu)~H 3 10
neohexene 339
neopentyl glycol 13
nerol in asymmetric hydrogenation 559
NH3/H202in epoxidations 422
N-heteroaromatic chlorides 153
nickel see also Raney nickel
- 7’-alkyl complexes, in olefin
hydrocyanations 475
- y3-allyl-q’-alkyl-Ni” complex 377
- (h3-allyl)NiCI2 catalyst 562
- c-ally1 nickel complexes 483
- allylnickel complexes 297
- allylnickel halides 297
- allylnickel(I1) complexes 287
- allylnickel cyanide complexes 476
- as catalyst in dimerizationd
co-dimerizations 258
- as catalyst in in olefin poly-
merizations 2 14
- as catalyst in stereospecific poly-
merizations 288
- as catalyst in the Shell process 245,
248
- as catalysts in hydrocyanations 471
- BINAP-Nio catalyst 567
- bis(butadiene)Ni” 378
- C12-allylnickelcomplexes 301
- carbonylation of ally1 halides 963 ff
- carbonylation of ethylene 137 ff
- carboxylate 309
- catalyst in alkyne carbonylations
317
- catalyst in butadiene telomerizations
369
- catalyst in the Eastman process 121
- catalyst system in
hydrocyanations 48 1
- catalyst of the Philipps process 258
- catalysts in telomerizations 361
1428 Index
- cationic complexes in dimerizations
254
- (C2H4)NiL2 474
- [ v ~ - ( C ~ H ~ ) C F K 303
O~I~
- chloride, carbonylation of ethylene
I37
- y4-cis-butadiene complex 301
- complexes in dehydrogenative
vinylsilane silylations 503
- concentration, SHOP process 246
- colloids 682
- cotrimerization of alkynes and carbon
dioxide 1 194 ff
- cyanation 968
- cyclooligomerization of alkynes
1253 ff
- dehydrocoupling catalysts 503
- dehydrodimerization of pyridine 1258
- n-ethylene-nickel complex 474
- EtNi(C,H,)CN 474
- Grignard cross-coupling 824
- hydride complex 137
- hydrocyanation 620
- hydrovinylation 1 165 ff
- in Aldox process 771
- in 1,4-butadiene polymerization 298
- in carbonylation catalysts 317
- in carbonylation reactions 116, 139,
146, 277
- in DMF synthesis 1203
- in epoxidation 958
- in ethylene oligomerizations 250
- in ethylene polymerizations 226
- in Heck reaction 780
- in hydrocarboxylations 182
- in hydrocyanations of functionalized
olefines 476
- in photocatalysis 1066
- in stereospecific polymerizations 287
- in Ziegler-Natta type catalysts 284,
289 f
- isomerization of olefins 1122 ff
- K2Ni(CN)4 344
- naphthenate/BF, 309
- NEt4PF6 304
- [Ni( 1,3-(CH&C3H3)(h4-1,4-
(CH3)2C4H4)1BF4 298
- [Ni(acac)*] 379
- [Ni(a~ac)~]-Al(OEt)Et,370
- [Ni2($-allyl),C1] 380
- NiBr2 250
- Ni[CDT] 370
- “i(C12His)llB(C,H,(CF,)2)4 304
- [Ni(C12Hls)]’ 302
- [Ni(CI2HIy)]O3SCF3/10-20 A1F3 305
- [Ni(Cl2HIy)]PF6 304
- [Ni(C3Hs)L2X]PF6 287
- [Ni(C,H5)XI2 287
- “i(y3,r2,r2-C12H1s>1 301
- [Ni(y3,h2,h2-C12HIY)IX 297
- [Ni(r3-C,H~)(P(OPh),),lPF, 300
- [Ni(r3-C3HS)I], 301
- [Ni(r3-C3Hs)L2]X 297
- [Ni($-C3HS)X], 297
- Ni(CN)2, in olefin hydrocyanations
473
- Ni(CN),/CO/KCN 278, 481
- Ni(CN)f 481
- Ni(C0)4 137ff
- Ni(COD)* 370, 476
- Ni” complexes in BD cyclooligo-
merizations 370
- Ni(I1) complexesMA0 182
- [NiCp(CH3)(h2-C4H6)] 298
- Ni(I1) diimine halides 226
- Ni2+/0 hydrosilylation catalysts 499
- Ni” in asymmetric hydrocyanations
56 1
- Ni” in olefin hydrocyanations 474
- NIL3 474f
- NiL4 in olefin hydrocyanations 473
- Ni(02CR),/BF3 301
- Ni[P(O-o-tolyl),], 476 ff, 484
- [Ni(y3-RC,Hs)(h4-C4H6)]+ 301
- Ni(I1) salt 298, 347
- Ni” templates 374
- phosphine complexes in hydro-
silylations 499
- phosphine complexes in carbonylations
of aryl-X-compounds 149
- polybutadiene 309 f
- polyfluoroaluminate 305
- polybutadienylnickel(I1) cation 301,
305
- RNiL2CN 478
- RNiL,CN 475
- salts in butadiene/ethylene
codimerization 263
- template synthesis 926
- tetracyanonickelate(0) 48 1
- tetrakis(ph0sphite)nickel complexes
474
 Index 1429

- tetrakis(tri-o-tolyl phosphite)nickel(O) Nomex 460

47 1 nonadienoates via hydrocarboxylations
- tetrakis(tri-p-tolyl phosphite)nickel(O) 187
478 nonanals 84
- tetrakisphosphite-nickel(0) 482 1,9-nonanedial 4 1
- trimerization catalyst 380 1,9-nonanediamine via telomerization
- zerovalent catalyst in cyclo-co- 367
dimerizations 2 I , 375 I ,9-nonanediol
Nicosulfuron 150 - in aqueous phase hydroformylation
Nifluminazid 150 40
niobium - via telomerizations 367
- cluster 817 nonanoic acid via carbonylation of aryl-X
- cyclooligomerization of alkynes 1253 compounds 151
Nippon Steel process for a-picoline nonenes 84
synthesis 1255 - in hydroformylation 42
Nippon Zeon Co. 339f nonylphenol in RIM technique 341
nitrenes norbornene
- in aziridines synthesis 804 - hydrocyanation by acetone cyanhydrin
- in reductive carbonylation 1218 ff 472
nitric acid - hydroformylation 767 ff
- in alkyne reactions 280 - in hydrocyanation 470f
nitriles - living polymerization 1279
- 2-aryl-2-propionitriles 477 - norbornene/tetracyclodecene
- 2-pentenenitrile 159 copolymers 224
- hydrolysis 876 - norbornylamine 521
- in alkyne hydrocyanations 479 - 7-oxanorbomene 338
- pyridine synthesis 1256ff - Pauson-Khand reaction 1242
- a$-unsaturated nitriles 479, 48 1 - photopolymerzation 1074
nitrite route for dimethyl carbonate 173 Norsorex 339
nitro arenes NR (natural rubber) 311
- reduction 954, 1090
- reductive carbonylation 1090 0
nitroaldol reaction see Henry reaction 0 - C coupling
nitrobenzene in reductive carbonylation - phenol coupling 826
1216ff octadienes
nitrogen - in amidocarbonylations 159
- in hydroaminations 5 13 ff - in octanol manufacturing 366
- in template synthesis 922 - 1,7-octadiene 367
nitromethane - via telomerization 364f, 367
- in asymmetric nitroaldol reaction 571 octadienols 41, 364 f
nitrotoluenes in autoxidation 447 octanoate in the Shell process 75
Nitto chemical Ind. octanols
- biocatalytic acrylamide process 889 - by telomerization of butadiene 619
N-methyl-2-pyrrolidone see NMP - in radical carbonylations 192
N-methylamine in amidocarbonylation - manufacture 366
161 octenal
N-methylimidazolium as co-promoter in - in butadiene telomerization 41, 366
the Hoechst Process 122 - 7-octenal 41, 366
NMP octenes
- in hydroformylation 624 - hydroformylation 42, 48, 54f, 86, 89,
- in propyne carbonylations 3 18 91, 758
1430 Index

- in ethylene oligomerizations 241 - in intermolecular hydroamination 520

- in hydrosilylations 498 - in metathesis 332
- isomerizations 84, 86, 1120 - in technical oligomerization 233
- isomers of dimerizations 256 - in technical polymerization 230
- 1-octene 48, 54f, 86, 89ff, 241, 498 - in telomerization 361 ff
- 2-octene 86 - insertion 348, 353ff
off-gases in technical aldehyde oxidations - isomerization 1119 ff
43 1 - isotactic copolymers with CO 357
olefination of aldehydes 1078 ff - metallocene-catalyzed 2 13
olefination see also Heck reaction - metathesis reactions 328, 334
- in hydroaminations 515 - migratory insertion in hydrosilylations
- in hydrocyanations 470, 474 499
a-olefins - oligomerization 978 ff
- in amidocarbonylation 158 - oligomerization by cationic nickel
- in copolymerization of ethylene 218 complexes 231 f, 256
- in co-oligomerization 245 - oxidation to carbonyl compounds 386,
- metathesis 329 388, 401 f
olefins 1, 182, 233, 230 - oxyamination 1150
- activated 277 - Pauson-Khand reaction 1241 ff
- as feedstock in Shell process 75 - petroleum-based process 32
- asymmetric cyclopropanations by - photoisomerization 1062 ff
dioazetates 563 - photooxidation 1070 ff
- asymmetric epoxidation 1140 ff - photooxychlorination 1070
- asymmetric hydrocyanation 56 1 - polymerization 978 ff
- asymmetric hydrogenation 1136 ff - syndiotactic copolymers with CO
- asymmetric hydrosilylation 498 357
- asymmetric hydrovinylation 562 - technical oxidations 402 ff
- atactic copolymers with CO 357 - terminal in chloride-free oxidations
- bisalkoxycarbonylation of 188 402
- by McMuny coupling 1093ff - unfunctionalized in asymmetric
- by methylene transfer reagents 1079 epoxidations 421
- by technical polymerization 231 ff oligomerization
- by transfer dehydrogenation of - of alkenes 213ff, 978ff
alkanes 1230 - of alkynes 989ff
- catalyzed polymerization 272 - of ethylene 751
- cyclopropanation 794 ff oligomerization processes 243 ff
- dihydroxylation 1141, 1149ff oligonucleotides 935
- epoxidation 957ff oligosaccharides 88 1 ff
- Heck reaction 775 olympiadane 934
- hydroamination 1000f Omeprazole 577
- hydrocyanation 470 one-pot synthesis
- hydroformylation 37, 48, 54, 86, 89, - for alkylrhenium oxide synthesis 440
91, 241, 687ff, 727ff, 766ff - in hydrocarboxylations 186
- hydrogenation 955 - in industrial productions 266
- hydrogenative dimerization 503 - of dimethylmetallocenes 270 ff
- hydrovinylation 1164ff Oppenauer oxidation 1003ff
- hydroxyamination 1159 Oppolzer’s sultam 796
- in dehydrogenative silylations 503 optically active hydrocarbons in
- in hydrocarboxylation 182 polymerizations 2 15
- in hydrodimerization 361 ff optically active monohydrosilyanes by
- in hydrosilylation 502 hydrosilylations 498
 Index 1431

organic halides - of arenes 960f

- in carbonylations of aryl-X-compounds - of cumenes 961
148 - of cyclohexane 751, 960
- in photocatalysis 1066ff - of hydrocarbons 960f
organoaluminium compounds in technical - of olefins 395ff, 402, 958
polymerizations 233 - of sulfides 960
organoammonium iodides as promoter- - propylene 10
salts in co-carbonylations 125 - saturated hydrocarbon oxidation
organophosphonium iodides as promoter- process 106
salts in co-carbonylations 125 - two-phase oxidations 428
organosiloxanyl radicals 501 oxidations see also epoxidations
orthoformates in oxidative carbonylations oxidative additions
167, 174 - deactivation of hydroformylation
ortho-metallation in deactivation of catalysts 61
hydroformylation catalysts 60 f - in hydroaminations 5 14 f
osmium - in hydrocyanations 470
- as catalyst in asymmetric oxidative carbonylation 164 ff, 166
aminohydroxylations 572 - intramolecular 167
- asymmetric cis-dihydroxylation 114 1 oxiranes
- dihydroxylation 1149 ff - carbonylation 965
- hydrodesulfurization 1 103 - synthesis of 4 12 ff
- OsHCl(CO)PPr, 498 0x0 catalysts
- 0 ~ 0 4 413, 428 - polymetallic 35
- photocatalytic C-H activation 1071 - unmodified for hydroformylations
Otsuka pharmaceutical industry 562 54 ff
oxalic acids 0x0 poisons in RCWRP process 81
- copper oxalate 399 0x0 products
- oxalate buffer in asymmetric - production capacities via various
epoxidations 424 processes 64
oxazaborolidine as catalyst in asymmetric 0x0 reactor in BASF process 70
reductions 568 0x0 synthesis see hydroformylation
oxazaphospholene-palladium complexes in oxonation see hydroformylation
carbonylations of aryl-X-compounds Oxone in epoxidation 958
149 oxyamination of olefins 11.50
oxazoline in cyclopropanation 795 oxyamination see also hydroxyamination
oxidants oxychlorination synthesis of DCE 553
- in aldehyde oxidations 428 oxygen
- in asymmetric epoxidations 424 - co-catalyst in peroxide-induced
- in catalytic olefin oxidations 388 hydrosilylations 502
- in ethylene oxidations 394 - formation in arene autoxidations
- in oxidative alkene acetoxylations 406 448
- stochiometric in arene oxidations 433 - in asymmetric dihydroxylations 578
oxidations - in C-H activation 1231
- in fluorous phase 636 - in olefin dihydroxylation 1151
- in gas phase 428 - in oxidation of cyclohexanone 960
- in liquid phase 428 - in photooxidation 1070ff
- in membrane reactors 943 - in polybutadiene manufacturing 306
- of alcohols 959 - in telomerization processes 363
- of aldehydes 429 oxygen transfer
- of alkynes 958 - in aldehyde oxidations 429
- of allenes 958 - in epoxidations 415 ff, 420
1432 Index

- in non-catalyzed hydrocarbon - cis-hydroxypalladate anion 394

oxidations 53 1 - immobilization 649
- intramolecular 41 9 - in alkyne carbonylation catalysts 3 17 f
- oxidant in aldehyde oxidations 427 - in alkyne hydrocyanations 479
ozone 129 - in alkyne reactions 281
ozonolysis 380 - in carbonylations 166 f, 170, 174 f,
190
P - in carbonylations of ary-X-compounds
palladium 146, 149, 151
- ( A C O ) ~ P ~ - - C H ~ C H + C H ~ C H ~ C H-H ~in complexes in olefin hydrocyanations
408 475
- acetate 347 - in d8-square-planar complexes 320,
- alkenyl species 324 348
- allylic substitution 620 - in dicarboxylations 188 f
- n-allylpalladium acatylacetonate 484 - in diphosphine complexes 348
- aryl-aryl coupling 822ff - in ethylene copolymerizations 345
- as carbonylation catalyst 140 - in ethylene oligomerizations 250
- as catalyst in asymmetric hydro- - in ethylene oxidations 394
cyanations 473 - in ethylene polymerizations 226
- as catalyst in chloride-free oxidations - in heterolytic hydrogen splitting 352
402 - in hydrocarboxylations 185 ff
- as catalyst in alkene acetoxylations - in hydroesterifications 184
406, 409 - in oxidative carbonylations 165 ff, 172
- as co-catalyst in naphthalene - in photocatalysis 1068
oxidations 46 1 - in the oxidation of olefinic compounds
- as dehydrocoupling catalyst 503 388
- as giant cluster catalyst 409ff - in the propyne carbonylation cycle
- as intermediate in oxidative 325 f
acetoxylations 408 - isomerization of olefins 112 1
- bipyridyl complexes 348 - L,Pd(R)X 347
- (S)-BNPPA-Pd2+catalyst 561 - L2PdX2 347
- carbon dioxide activation 1 191 - L2PdX2 354
- cluster 409, 678ff - [LZPdXlX 320
- colloids 682 - membranes 943ff
- chiral diphoshine complexes 471 - [(methyl-2-allyl)PdC1]2 151
- chloride-free catalysts 402 - methyl ketone synthesis 958
- chlorides 345, 386 palladium(0) 389
- ( P - C ~ HPdC12)2
~ 406 - 1 -palladium-2-carbomethoxypropene
- cluster intermediates in ethylene 324
oxidations 397 - 2-palladium- 1-carbomethoxypropene
- n-complexes in oxidative alkene 324
acetoxylations 406 f - palladium hetero-polyacid catalyst 402
- cyanides 345 - Pd(OAc)2-409
- cyclooligomerization of alkynes - [Pd(PPh,)2(CH,CN)2I2+ 353
1252ff, 1261ff - [ P ~ ~ ~ ~ L ~ I ( O A409ff
C)IXO
- cyclopropanation 795 ft' - [Pd.561L600601(PF6)60 409 ff
- Heck reaction 775 ff - [PdC12L2]complexes 185
- hydride species of 321 - [PdC14]2-393
- hydrodehalogenation 956 - pd0/2+ complexes in hydrosilylations
- hydrovinylation 116.5, 1 169 499
- B-hydroxyethylpalladium species 391 - Pd,(OAc): 409
 Index 1433

- Pd3(0Ac)h 409 - in oxidative carbonylations 170

- Pd clusters in alkene acetoxylations - 1,3-pentadiene 375
409 ff - 2,4-pentadiene- 1-carboxylate 170
- PdCl($-C,H,), 499 pentafluorostyrene via amido-
- PdClZ 402 carbonylations 157
- PdCOOMe' 350f n-pentanal
- Pd salts in olefin oxidations 387, 389 - by conversion of Raffinate 42
- phosphine complexes in propyne - from n-butene via the RCH/RP
carbonylations 3 18 process 78
- reaction with ethylene 386ff pentenes 253, 428
- reductive carbonylation 1090 - 5-(N,N-diisopropylamino)- 1-pentene
- ROMP 1281 224
- telomerization 1 192 ff - 2,3-dimethylpentenes 256
- tertiary phosphine complexes 345 - in amidocarbonylations 159
- tetrakis(tripheny1 phosphite)- - in cycloolefine polymerizations 224
palladium(0) 47 1 - in dimerizationskodimerizations 253,
PA0 (poly-a-olefines) 24 1 255
paraffins - in hydroformylation 58
- dehydrogenation 240 - in metathesis reactions 336
- in uncatalyzed oxidations 528 - isomers in dimerizations 256
- liquid phase oxidations 537 - methylpentenes 253, 256
- oxidation 427, 525f, 530, 535 - 1-pentene 58
- paraffin oxidation process 538 - 2-pentene 336
- wax cracking 240 - photoisomerization 1062
paraformaldehyde in amidocarbonylations - 2-PN (2-penetenenitril) 482
161 - 2,2,4-trimethyl-l -pentene 428
Pauson-Khand reaction 124 1 ff pentenoates via hydrocarboxylations
P-C bond cleavage in Heck reaction 187
784 ff peptide synthesis in biocatalysis 887
PCO) peracids
- in carbonylation 11.5 - as intermediates in uncatalyzed
- in hydroformylation 48, 50, 54ff oxidations 530
- in oxidative carbonylations 167 - in propene oxide manufacture 412
- in the Cativa process 114 - peracetic acid in aldehyde oxidations
- in the kinetics of hydroformylation 52 43 1
- rate-retarding effect in hydroformylation Periana system 739
56 permethrin 800
P(CO*) peroxide initiation
- in telomerization processes 364 - in hydrosilylations 501 ff
PE-HD by technical polymerizations - of metal complexes 501 ff
231 ff peroxides 129
pelargonic acid - in C-H activation 1228
- via carbonylations of aryl-X-compounds peroxodisulfate in C-H activation 1232
151 Perspex 316
- via hydrocarboxylations 187 PET production 460, 548
PE-LLD by technical polymerizations petroleum residues as source of synthesis
233 f gas 116
penicillin-(; 894 PH
pentadienes - in asymmetric epoxidations 423
- in cyclo-co-oligomerizations 375 - in ethylene oxidations 396 f
- in diene cyclooligomerizations 370 - in hydroformylations 68
1434 Index

phase transfer catalysis 10 phenylephedrine 569

- agents 954 phenyloxirane by epoxidation of
- allylation 966ff styrene 957
- by re-immobilized ligands 685 phenylthioacetylenes in regioselective
- carbonylation of organic halides 961 ff hydrosilylation 498
- cyanation 967ff Phillips catalysts 230
- desulfurization 968 Phillips process 258, 262
- ethynylation 966ff phorocantholide 877
- Heck reaction 966 phosgene 171
- hydrogenation 954 ff - as C, building block 1189
- hydrogenolysis 954 ff - syntheses of isocyanates 1214 ff
- in carbonylations of aryl-X-compounds phosphaimidazolines in hydro-
I48 vinylation 1168
- in homogeneous catalysis 953 ff phosphates in PET production 549
- in hydroformylation 56 phosphination nucleophilic 87
- isomerization 967 phosphines
- oxidation 957 - acetic anhydride process 120
- reduction 954 - as auxiliaries 1014ff
Ph-B-Glup 14 - as catalysts in hydroformylations
phenanthrene 36 f, 43. 48 ff
- in template synthesis 9 14 ff - as chiral catalysts in hydrosilylations
- oxidation 435 499
phenanthroline in reductive carbonylation - as trivalent ligands 362
1220 - 1-azaphospholene 1167
PHENAP 85 - bidentate ligands 1016ff
phenethyl alcohols by asymmetric transfer - BINAP 779f, 1125f, 1135, 1138
hydrogenation 567 - BIPHEP 1135, 1138
phenol - BISBIS 615
- 2,3,6-trimethylphenoI 435 - BPPFA 1135
- 2,6-di(t-butyl)-4-methylphenol 438 - chiral menthyl phosphines 1166
- 2,6-diisopropylpheno1 34 1 - DCPB 1194
- 2-halophenols 151 - DIPPB 780
- carbonylation 151 - DIPPP 780
- chlorophenols in halogenations 553 - DPPF 827
- hydroxylation of benzene 422 - DUPHOS 1138
- in arene oxidations 341, 435, 438 - in amidocarbonylations 161
- in Heck reaction 779 - in dimerization 254f
- oxidative coupling 826 - in olefin polymerizations 214
phenyl acetic acid by carbonylation of - in the carbonylation of methyl acetate
benzyl chloride 754, 961 118
phenylacetic acid derivatives in carbonyl- - in water-soluble complexes 37, 87ff
ations of aryl-X-compounds 148 - JOSIPHOS 1138
phenyl isocyanate by reductive - ligands in alkyne carbonylation
carbonylation 1090 f, 1215 ff, 1218 ff catalysts 318, 320, 324
phen ylacetylene - monodentate ligands 1015 ff
- carbonylation 964 - multidentate ligands 1024 ff
- cyclotrimerization 1262 - NORBOS 615
- in hydrosilylations 498f - phosphaimidazoline 1 168
- photocopolymerization 1074 - 2-pyridylphosphine 3 18 f, 320, 324,
phenylenediamines 460 326 f
phenylenes 1264 - recycling 1025
 Index 1435

- TADDOL-analogue I015 ff - in hydrosilylations 501

- tetradentates 86 phthalates 90, 259
- THREOPHOS 1177 phthalic acid anhydride (PTA) 460
- TOP0 617 - in olefin oligomerizations 241
- TPPDS 605, 614 phthalimidoalkynes in regioselective
- TPPMS 605, 613ff hydrocyanation 48 1
- TPPTS 605, 614 phyllodulcin 578
phosphites 88ff, 91, 379 picolinium iodides as co-promoter in the
- as ligands in hydrocyanation 475 Hoechst process 122
- in hydroformylation 37f piperidines in hydroaminations 522
- in PET production 549 plasticizers 90 f, 240
- stencally hindered 37 - for polyvinylchloride 362
phosphonic acid - hydroformylation 62
- ammonium salt$ 383 platinum 494
- imidazolium salts 383 - [PtC12(Et2NH)(CH2CH,NHEt,)] 5 15
- organophosphorus compounds 383 - as catalyst in asymmetric hydro-
phosphonites formylations 43
- in hydroformylations 88 - as catalyst in hydrocarboxylations
phosphonium halides 183
- as co-promoters in the Hoechst Process - as catalyst in hydroaminations 515
122 - as dehydrocoupling catalyst 503
- in butadiene/ethylene codimerizations - C-H activation 1231 ff
263 - cluster 678
- in oxidative carbonylations 172 - colloids 682
phosphorus 89 - d"'-Pt"'' complexes 495
- aiyl phosphites 379 - dx-Pt"" 495
- as tetravalent phosphonium salt 362 - electrocatalysis 1056
- chiral ally1 diphosphite 476 - H7PtC1, 495
- deactivation of hydroformylation - immobilization 649
catalysts 60 - in alkyne carbonylations 317
- [(HO,C),,PH],X compounds 463 - in alkyne reactions 281
- H3PM~hVh040, as chloride-free - in carbonylations of aryl-X-
catalyst 401 compounds 146
- in carbonylations of aryl-X-compounds - in ethylene-platinum complexes 387
152 - in hydrosilylations 492f, 495 f, 502
- in dimerizationskodimerizations 255, - in hydrovinylation 1184
2.57 - in olefin oxidations 387
- in hydroformylations 58 - in vinylations 279
- in telomerization processes 363 - in water-gas shift reaction 1087
- modified TPP ligand 59 - isomerization of olefins 1125
- P(i-C7H7), 58, 255 - K[PtC13(p-CZHd)] 387
- P(n-C?H7), 58 - Na,PtCI, 281
- P(z-C~H~X)I59 - Periana system 739
- P(cyclohexyl)3 255, 257 - platinudtin catalyst 44
- PEt, 59 - Pt2C14Lz 496
- [P(OMe),l 370 - PtClzL, 496
- P(OPh), 60 - Shilov system 737ff
- phospapalladacyclic catalysts 276 Plexiglass 3 I6
photo-initiation P-N ligands
- in carbonylations of ary1-X- - in Grignard cross-coupling 825
compounds 152 - in hydrovinylation 1166, 1169
1436 Index

PN polymer separation in polybutadiene

- monohydrocyanation of butadiene 482 manufacturing 307
- reaction inhibitor in the ADN process polymerization rate in polybutadiene
482 manufacturing 306
P(0J polymerizations
- in alkylarene autoxidations 456 - anionic 286
- in arene autoxidations 445 - cationic 384
- in commercial oxirane processes 417, - living 303
424 - Iiving in the alkyne-metathesis
polyalkenamers 339 333
polyamide polyesters via amido- - metathetical 335
carbonylations 159 - of alkenes 213 ff
polyamides 36 1 - of butadiene 284ff, 289
polyarylates 460 - of epoxy resins 383 ff
polybenzimidazole (PBI) 461 - of isoprene 284ff
polybutadiene rubber (BR) 305 f, 309, - 1,4-polymerization 284, 289, 303
31 1 - ring opening 329
pol ybutadienes - selective 359
- in butadiene polymerization 286 f, - stereospecific 21 9, 284 ff
295 polymers
- isomeric 284ff - polyacetylene-type 330
- neodymium catalyst 3 10 f - stereoregular 284, 3 12
- nickel catalyst 309 f poly(methylenecyc1opentane)
- stereoregular 285 microstructures 225
- syndiotactic 286 f, 295 f polynorbornene 339
polybutene terephthalate (PBT) 460 polypropy lenes
polycondensations 505 - atactic 219
polycyloalkenes 222 ff - hemiisotactic 222
polydienes - isoblock 222
- isotactic 284 - isotactic 219, 237
- syndiotactic 284 - microstructures 220
polydispersity 2 13 - stereoblock 222
- in butadiene polymerizations 295 - syndiotactic 219ff, 237
polyenes polysiloxanes 9 I
- in metathesis reactions 329 polyspiroketals 357
polyesters 36 1 polystyrenes
- ketones 119 - immobilization of hydrosilylation
- polymers 460 catalysts 500
polyethylene 5, 217 - syndiotactic 233, 237
polyethylene terephthalate see PET polyvinylpyridine as crosslinked
polyhalogenated aromatic acids 463 catalysts 129
polyhydrosilylation 494 porphyrins
pol yisoprenes - by self-assembling 932ff
- stereoregular 285 - in C-H activation 969, 1227ff
pol yketones - in cyclopropanation 802
- alternating 354ff - in oxidation 958
- synthesis 353 potassium
- via alkene copolymerization 344 ff - in Fischer-Tropsch synthesis 8 17
- via hydrocarboxylations 182 - template synthesis 913
poly-L-leucine in hydrocarboxylations PPh3 as ligands in propyne
I86 carbonylations 3 18
 Index 1437

precursor complex in the Shell process - VAM 406

248 - Wacker 386
prepregs 384 - Wacker-Hoechst 398
pressure in hydroformylations 55, 57 - Witten 443, 544f
P R h ratio - wood coking process 427
- in the BASF process 72, 82 processing problems in ethylene/CO
- in the RCHRP process 81 f copolymerization 345
Prilezhaev reaction 412, 415 product mixtures in oxidative
process technology carbonylations 167
- in carbonylations 107 product separation
- of co-carbonylations 122 - butadiene hydrodimerization 365
- of acetic anhydride processes 120 - extraction separation method 367
processes - in carbonylations of aryl-X-
- acetaldehyde 400ff compounds 153
- ACH 316 - in commercial oxirane processes 418
- ADN 482 - in presence of Group IV metallocene
- Amoco 443, 546 catalysts 267
- BASF 427 - in telomerizations 362
- biphasic 7 profenes
- butane oxidation 525 - via asymmetric carbonylation of
- commercial acetaldehyde 402 aromatic olefins 560
- continuous aldehyde oxidation 430 - via asymmetric syntheses 559
- ethylbenzene process 417 - via carbonylations of aryl-X-
- gas-phase polymerization 3 12 compounds 148 f
- Hoechst 9 promoters 475
- hydrocarbonylations 3 I8 - in butadiene hydrocyanations 483
- isobutane process 417 - in carbonylation of methyl acetate
- liquid phase oxidations 422, 443 118
- methanol carbonylation 525 - in carbonylations 110, 140, 112 f
- MMA 318 - in catalyzed hydrocarbon oxidations
- Monsanto 402, 427 540
- 1-octanol 362 - in hydroesterifications 185
- oxirane process 413, 417 - in metathesis reactions 335
- RGHRP 603ff - in oxidative carbonylations 165
- Reppe 317 - in the Amoco process 547
- resin injection 384 - in the Cativa process 114
- resin transfer molding 384 - in the Eastman process 121
- Showa-Denko gas-phase oxidation of - iodide salts 110
ethylene 402 - salts in co-carbonylations 124
- single-stage in acetaldehyde - salts in the methyl acetate
production 398 carbonylation 117
- solution polymerization 307 propanal 31, 89
- stereospecific emulsion - as by-product in acetaldehyde
polymerization 3 12 manufacture 400
- Telene 341 - condensation with formaldehyde 3 16
- Tennessee-Eastman 9 - 2-methyl-3-hydroxypropanal 89
- two-stage in acetaldehyde production - via hydroformylation 61
389, 398 Propanolol 569
- two-stage in 3-chlorobutanone propargyl alcohols 283, 507
production 401 propargylamines 275, 507
- Union Oil 10 propargylic acid esters 276
1438 Index

propene - in propyne carbonylation 324, 325

- dimerization 253ff - transition state 325
- direct epoxidation 424 PVC 41, 62, 90
- direct oxidation of 400 - for immobilization of hydrosilylation
- epoxidation 420 catalysts 500
- in hydroformylations 41, 52ff, 59, 63, pyran ring systems
69, 75ff, 82, 90 - by oxidative carbonylations 168
- in oxidative carbonylation 168 - 2-hydroxy-4-methyltetrahydropyran
- metathesis 328 41
- regioselective dimerization 82, 257 pyrethroid insecticide production 485
propene oxide p y ridin es
- commercial production 417, 422 - derivatives 463
propenehutene in codimerizations 256 - 2,s-dichloropyridine 150
PROPHOS as ligand in hydrocyanation - in acetaldehyde production 402
473 - in alkyne carbonylations 323 ff
propiconazole via asymmetric - in carbonylation of methyl acetate
hydrogenation of a-hydroxy ketone 118
569 - in hydrocarboxylations 185
propionic acid - ligands in propyne carbonylations
- as by-products in carbonylations 150, 318f
113, 116 pyridyls
- generation from acetic acid 141 - in alkyne carbonylation kinetics 322
- in ethylene copolymerization 344 - in propyne carbonylations 324ff
- in hydrocarboxylations 186 - 2-PyPPhz 318 f, 323 ff
- in the catalyzed oxidation of MEK - 2-pyridyl group 318
534 pyrophoric phosphine in carbonylations
- iodide 140 of aryl-X-compounds 152
- propionic acid anhydride 142, 136f, pyrrolidinones 48 1
279 pyrrolidins by hydrocyanation of
propy1ene ketoalkynes 48 1
- conversion with Pd-cluster catalysts pyrrolidones 162
41 1 pyrrols 172
- isospecific polymerization 266 - amidocarbonylation 162
- oxidation of 407 - 2,5-dimethylpyrrole 262
propyltrialkoxysilanes 9 1
propynes Q
- carbonylation process 278, 317 Q M N M calculations 701, 7 11, 7 18
- catalytic cycle of the carbonylation quantum size effects 678
325 f quinoid compounds in oxidative
- insertion 321 carbonylations 262
- insertion reaction in alkyne quinoline derivatives 463
carbonylation kinetics 323 quinolinones via carbonylation of aryl-X-
- methoxycarbonylation 3 18, 325 compounds 151
proton messenger quinone effect in polyketone formations
- co-catalysis in propyne carbonylations 35 1
320 quinones
- propyne carbonylation kinetics 324 - in oxidative alkene-acetoxylations
proton transfer in alkyne carbonylations 406
326 - in phenol coupling 826
protonolysis - 2-methyl- 1,4-naphthoquinone 433
- in polyketone formation 350 - via arene oxidations 433
 Index 1439

R - kinetics 54
racemic switches 569 - reaction mechanism 61
radical carbonylations 191 ff RCM (ring-closing metathesis)
radical chain demolition in autoxidations - metathesis reactions 332
of alkylaromatic compounds 454 - of octadiene 329
radical chain propagation in alkylarene reaction channel in butadiene
autoxidations 454 polymerizations 299
radical chain reaction in aldehyde reaction injection molding see RIM
oxidations 429 reaction mechanism
radical scavengers in arene autoxidations - acetylene insertions 499
447 - arene oxide 436
radicals - BD trimerization 378
- as promoters in the Amoco process 547 - butadiene hydrodimerizations 369
- in commercial oxirane processes 4 18, - electron transfer 453, 535
448 - elimination in Co-catalyzed arene
Raffinate-1 41 autoxidations 449
Raffinate-2 41 ff, 90 - enol reactions 534f, 540
Raney nickel 41 - free radical conversions 491
rapid screening techniques 91 - free radical pathway 536
rate constants - heterolytic in hydrosilylations 491
- in alkylarene autoxidations 455 f - hydroperoxide chain reactions 526
- in dimerizations 256 - in catalyzed chain reactions 531, 534
- in ethylene oxidations 390 - in ethylene oxidations 390
rate dependence - in hydroaminations 521
- in butadiene polymerizations 295 - in uncatalyzed hydrocarbon oxidations
- in trans- 1,4-polymerizations 300 f 530
rate determining steps - migratory olefin insertion 499
- in alkylarene autoxidations 456 - of aldehyde oxidations 429 ff, 437 ff
- in carbonylations 107 - of antimony-catalyzed poly-
- in cis-l,6polyrnerizations 302 condensations 549
- in Co-catalyzed arene autoxidations - of arene autoxidations 447
449 - of butadiene hydrocyanations 482
- in hydroaminations 520, 523 - of butadiene polymerizations 286 ff,
- in hydrocyanations 473, 475 296 ff
- in hydrosilylations, Chalk-Harrod - of carbonyl-group hydrosilylations
mechanism 493 498
- of epoxidations 414 - of catalysis by supported metal
- of ethylene oxidations 392ff complexes 501
rate enhancement in carbonylations 107, - of catalyzed hydrocarbon oxidations
111 535
rate equations - of cyclooligomerizations 376
- for ethylene oxidations 397 - of dehydrogenative hydrosilylations
- for propylene oxidations 395, 397 503
rate expressions for kinetics of - of epoxidations 4 13 ff
hydroformylation 52 - of ethylene hydrosilylation 496 f
rate model - of ethylene oxidations 394
- two parameters in hydroformylations - of hydroaminations 513 ff
53 - of hydrocarboxylations 183
raw-material costs 64 f - of hydrocyanations 469
RCWRP process 37, 65 f, 68, 78 ff, - of hydroformylation
SOff, 90 - of hydrosilane dehydrocouplings 506
1440 Index
- of hydrosilylations 491 f
- of isoprene polymerization 286 ff
- of oxidative alkene acetoxylation
407, 410
- of oxidative carbonylations 169
- of silylative couplings 504
- of stereospecific diene polymerizations
312
- pathways of dehydrogenative
silylations 503
- Russell Mechanism 527
- silyl migration mechanism 498
reaction rates 257, 474
- at low reaction water conditions
- co-carbonylations 122 f
- determining step in carbonylations
111
- in acetaldehyde manufacturing 400
- in aldehyde oxidations 430
- in alkylarene autoxidations 464
- in alkyne carbonylations 323
- in arene oxidations 435 f
- in butadiene/ethylene
codimerizations 263
- in carbonylations of aryl-X-
compounds 146
- in catalyzed chain reactions 532
- in cobalt-catalyzed hydrocarbon
oxidations 537
- in cyanoolefin hydrocyanations
- in dimerizations/codimerizations
259
- in hydroaminations 518, 522
- in hydrocyanations 468
- in hydroformylation 51
- in Mn-catalyzed hydrocarbon
oxidations 538
- in telomerization processes 364
- in uncatalyzed hydrocarbon
oxidations 527
- of alkylarene autoxidations 454
- of alkyne carbonylations 3 17
- of arene autoxidations 454
- of carboxylation 140
- of Co-catalyzed arene autoxidations
448
- of diene copolymerizations 370
- of epoxidations 414, 419
- of ethylene/CO copolymerization
- of hydroformylation 52
- of olefin oxidations 395 f
- of oxidative carbonylations 16
- of Pd catalyzed oxidative
acetoxylations 4 10 f
- of telomerizations 362
- with metal-doped catalyst systems 45 1
reactivity
- in trans- 1,4-polymerizations 300
- of allylnickel catalysts 298
- of durene in autoxidation reactions
456
reactors
- in arene-autoxidations 445
- plugflow in dimerizations 256
114 redox catalysts in catalyzed hydrocarbon
oxidations 539
reductive elimination
- in hydroaminations 5 14 f
- in hydrocyanations 470
- in hydroformylation mechanism 61
- in hydrosilylations 493
- of ethylene oxidations 392
regio modes in propyne carbonylations
321
regiocontrol in ethylene/CO
copolymerization 346
regioselectivity
- ansa-ligand-synthesis 270
- in hydroformylation 731 ff
- in alkyne carbonylations 317
478 - in alkyne hydroformylation 481
255, - in arene oxidations 438, 440
- in dimerizations and codimerizations
254
- in epoxidations 420
- in esterifications 183
- in ethylene/CO copolymerization 357
- in hydrocarboxylations 185 ff
- in hydrocyanations 468, 476
- in polypropylene polymerizations 222
- in propyne carbonylations 3 18, 321
- in silylative alkene/vinylsilane-
couplings 505
- of alkyne hydrocyanation 479f
- of alkyne silylformylations 507
- of the MTO/H202system 435
regiospecifity in propyne carbonylations
318
renewable resources
347 - carbohydrates 1271
- metathesis of oils and fats 1270
- oils and fats 1269
 Index 1441

- oleo chemistry 1268 - carbonylation of methyl acetate 118

- starch 1271 f - cationic complexes 508
reoxidants 165 - C-C coupling reaction 623
Reppe chemistry 3, 18, 136, 277, 317, - C-H activation 1229 ff
368, 370 - cluster 678, 813
- alkynes 274 - colloids 682
- carbonylations I64 - concentration in co-carbonylations
- catalyst in cyclooligomerizations 370 I24
- copolymerization 344 - concentration in hydroformylations 83
- reaction conditions 143 - cpRh(C2H5)SiR3 497
rhenium - cyanation 968
- as model for amm(on)oxidation - cyclooligomerization of alkynes 1253
1300ff - cyclopropanation 795, 800 ff
- [CH3ReO3] 433 - d*-complexes 5 , 496f
- [CH3Re0,] 436 - dehydrogenation of alkanes 1071
- CH,Re0(02)2 440 - [(diene)Rh(m-Cl),] 497
- electrocatalysis 1057 - [(diene)Rh(m-OSiMe,)], 497
- [H(ReO,)] 438 - dimerization of ethylene 773
- [H4Re2OI3] 437ff - high pressure 0x0 catalyst 51
- HRe04 440 - hydrodehalogenation 956
- [HORe0(02)2 H20] 437ff - hydrodesulfurization 1102, 1105 ff
- in photocatalysis 1062 - hydroformylation 608, 728 ff
- inorganic rhenium oxides 433 - hydrogen transfer reaction 1073
- olefination of aldehydes 1080 - hydrogenation 955 ff
- oxidation of ketones 960 - hydrogenation of carbon dioxide
- perrhenic acid 437f 1197ff, 1199ff
- [ReO,]' moiety in arene oxidations - hydrogenolysis of benzothiophene
436 f 1106
- Re207 440, 433, 436 - hydrovinylation 1 170 ff
- ReO, 433f, 436 - immobilization 648
- ReVII complex, in arene oxidations - immobilized complexes in hydro-
436 silylations 501
rhodium 13, 15, 23, 35, 87,109ff, 190 - in butadienelethylene codimerizations
- acetic anhydride process 126 f 263
- [AcORh(CO)I,L] 112 - in carbonyl complexes 345
- as catalyst in hydroformylations 68 - in carbonylations 104ff
- as catalyst in carbonylations 104, 107, - in carbonylations of aryl-X-compounds
111, 114, 116 146
- as catalyst in asymmetric hydro- - in carbonylations, rate of oxidation
genations 569 llOff
- as catalyst in hydroaminations 522 - in catalyzed hydroformylation 86
- as catalyst in the Eastman process 121 - in ethylene carbonylations 139
- as catalyst in WGSR 109, 111 - in Fischer-Tropsch synthesis 81 3
- as TPP-modified catalyst 37 - in homologation of alcohols 1036ff
- asymmetric hydrogenation 1138, 1145 - in hydroformylations 37, 49 f, 51, 68,
- BASF process 82 89
- BINAP-Rh+ catalyst 558 ff - in kinetic studies of hydroformylations
- carbocycles by diazo compounds 1125 54
- carbonyl clusters, phosphido-bridged - in methyl acetate carbonylations 122
60 - in phosphine modified hydro-
- carbonylation complex 1 17 formylation 48f, 53
1442 Index

- in stereospecific diene poly- - unmodified, in the hydroformylation

merizations 3 12 cycle 45f
- in two-phase hydroformylation 87 - water-soluble complexes 78
- in water-gas shift reaction 1087ff - zwitterionic complexes 508
- isomerization of allylic alcohols 967 RhGne-Poulenc 12, 14
- isomerization of olefins 1121 ff - vitamin A production 40
- ligand-modified catalysts 90 RIM 340f
- methyl ketone synthesis 958 ring opening metathesis (ROM) 331
- Monsanto catalyst system 117 ring opening metathesis polymerization
- oxidative methane carbonylation 131 (ROMP)
- Ph,PCH2NMe2-modified 89 - initiators 338
- phosphine catalyst 33 - of benzvalene 330
- recovery in acetic anhydride - of cycloalkenes 334
processes 120 - of cyclooctatetraene 330
- rhodium iodides 1 12, 117, 140 - of cyclopentene 340
- recovery 624 - of endo-dicyclopentadiene 340
- [Rh'( (-)-BINAP)COD]' 15 - of norbornene 339
- RC(O)Rh(CO)(TPP), 50 - of unfunctionalized monomers 336,
- RCWRP process 81 13, 330ff
- RCORh(C0)2(TPP)2 54 rubidium as catalyst in hydroaminations
- RCORh(CO),(TPP) 54 516
- Rh(PPh&(pip)21PFh 523 Ruhrchemie process 69, 73
- R M 122 ruthenium 494
- RhI,(CO),(L), 111 - acetate complexes 279
- RhI3 108 - acetylene polymers 279
- Rh[(S)-BINAP]+BF,- 579 - as carbonylation catalysts 140, 190
- Rh"-(R,R)-MeDuPHOS 563 - as catalyst in hydroaminations 522
- Rhl+/'+ complexes in hydrosilylations - asymmetric coupling of 2-naphthol
496 f 1072
- RhCl(PPh3)3 506 - asymmetric hydrogenation 1136 ff
- [Rh(CzH,+C1]2 523 - BINAP-RU~' 573
- [Rh(C2H,)(PPh,),(acetone)]PF6- 523 - BINAP-RU,' catalyst 559
- [Rh(CH,)(CO)2(I)J 104 - (S)-BINAP-Ru catalyst 569
- [Rh(CH,CO)(CO),(I),I- 104 - carbene complex catalysts 338
- [Rh(CO),I*]- 104 ff, 110 ff - carbonylations 279
- [Rh(CO),I,]- 110 - catalyst in metathesis reactions 332
- [Rh(cod)2]+BF4- 497 - catalyst in the Eastman process 121
- [Rh(COD)Cl], 506 - C-H activation 1229
- Rh(1) complexes 276 - colloids 682
- [Rh(nbd)C1212 54 - cyclooctadienylruthenium halides 279
- [RhC1(C2H4)pip,] 523 - dihydroxylation 1149
- [RhCl(CO),], 506 - homologation of alcohols 1035
- Rh(1)-species, in carbonylations 113 - HRu,(CO),, 506
- Rh(II1)-species, in carbonylations - hydrodesulfurization 1102, 1105 ff
113 - hydroformylation 763, 768
- Rh-TPP complexes 68 - hydrogenation 759, 1201
- salts in olefin oxidations 387 - in cyclopropanation 805
- transfer dehydrogenation of alkanes - in Fischer-Tropsch synthesis 8 14 ff
1230 - in stereospecific diene polymerizations
- triphenylphosphine modified 54 312
- triphenylphosphine oxide 36 - in water-gas shift reaction 1087ff
 Index 1443

- living polymerization 1279 - in arene autoxidations 445, 458

- metathesis initiators 338 - in arene oxidations 436
- methyl ketone synthesis 958 - in butadiene hydrocyanations 483
- oxidation of alcohols 959 - in dimerizationslcodimerizations 253
- photoactivated catalysts 502 - in epoxidations 415
- photocatalytic C-H activation 1071 - in ethylene dimerizations 259
- photoisomerization 1062 - in hydrocarboxylations 184 f
- recovery 759 - in hydrocyanations 475
- reduction of nitro arenes 954 - in oligomerization processes 240, 243
- Rosenmund-Tishchenko reaction 770 - in oxidative carbonylations 169, 171
- (R)-tol-BINAP-Ru 577 - in Pd catalyzed oxidative
- Ru(C0)3(PPh3)2 498, 502 acetoxylations 409 f
- Ru(NH3)4(0H)C12 522 - in polypropylene polymerization 222
- Ru2+-(R)-MeOBIPHEPcatalyst 562 - of alkyne carbonylation catalysts
- RU,+-(S)-HS-BINAP 562 3 17 f, 326
- R u ~ ( C O ) 498,
~ ~ 503, 506 - of diene copolymerizations 370
- RuCI,(PPh3)3 498 - of propyne carbonylation 320
- RuClJHCI 339 - of technical aldehyde oxidations 431
- RuH2(Hz)z(PCy,), 503 - of telomerizations 362
- RuX,[(R)-/(S)-BINAP] catalyst 575 selectivity study in kinetics of hydro-
- salts, in olefin oxidations 387 formylations 53
se1enium
S - ARC0 ethylurethane process 1090
saccharides in hydrocyanations of - H202/PhSe(0)OH 428
functionalized olefines 477 - reduction of nitro arenes 1089 ff
salicylaldehydes i n hydrocyanation of - water-gas shift reaction 1089 ff
aldehydes 486 self-association 87
salicylaldimin ligands in nickel complexes self organization 928 ff
227 semiempirical calculations 703
SAPC 13, 38, 84, 91 seperation of catalyst 10
sarcosinates sertraline preparation 567
- as special surfactants 161 Sharpless epoxidations 415, 1140ff
- via amidocarbonylations 16 1 Sharpless oxidation in prostaglandin
sarcosines 13 syntheses 565
SBR (styrene butadiene rubber) 3 11 Sharpless reagent in aldehyde-
S C C O ~91 hydrocyanations 485 f
- as catalyst in epoxidations 423 Sheldon oxygen transfer in epoxidations
Schiff bases in cyclopropanation 798 415
Schulz-Flory-distribution 23 I Shell 57, 89f
- in oligomerization processes 243 - Aldox process 771
- in the Shell process 246 - asymmetric epoxidations 42 1
D-scission reaction - epoxide production 4 I3
- in catalyzed chain reactions 531, 533 - higher olefins process 609
- in uncatalyzed hydrocarbon oxidations Shell Higher Olefins Process see SHOP
527f, 531 Shell process lOf, 14, 33, 73 ff
sebacinic acid in oxidative carbonylations - flow diagram 74
170 - formation of alcohols 74
selectivity - fresh cobalt 75
- alkyne carbonylation kinetics 324 - separation of products and catalysts 74
- cis-trans 290, 294, 299, 303 - side products 75
- for DCE in PVC production 556 - side reactions 74
1444 Index

Shell Research Company 245, 318 siloxanes

Shilov system 737 - in hydrosilylations 494f
SHOP (Shell Higher Olefin Process) 116, - in silylative alkene/vinylsilane-
226, 240, 245ff, 339, 345 couplings 505
Sic& in synthesis of polybutadienes 308 silver
p-Si-elimination in silylative alkene/ - carbonylation of ethylene 139
vinylsilane couplings 504 - catalyst in ethylene oxidation 412
side products in oxidative carbonylations - in self-assembling synthesis 928
167, 170 a-silyl esters via hydroesterifications 508
side reactions p-silyl esters via hydrocarboxylations 508
- carbonylation of methyl acetate 118 ff silyl migration in dehydrogenative
- in alkylarene autoxidations 458 silylations 503
- in arene autoxidations 458 silylations
- in carbonylation processes 138, 142 - dehydrogenative 498 ff, 502 ff
- in Co-catalyzed co-oxidations 453 silylcyanation
- in ethylene dimerizations 259 - enantioselective in aldehyde hydro-
- in hydroaminations 523 cyanation 486
- in hydroformylations 91 - of aldehydes 485 f
- in hydrosilylations 493, 499 silylolefin conversions 504
- of PET production 549 Simmons-Smith reaction 803
sigma-complexes in olefin hydro- single site catalysts
cyanations 473 - by zirconocene in polymerizations 2 16
silacarbosilanes by hydrosilylation - for stereospecific butadiene
polymerization 495 polymerization 297
silanes 999 - in stereospecific diene polymerizations
- by McMurry coupling 1096 312
- in dehydrogenative silylations 503 SIPSY’s asymmetric epoxidation of ally1
- in hydrosilylations 494 alcohols 421, 1140
- in silylative alkene/vinylsilane- sixantphos 86
couplings 505 SLPC 13, 38, 84
silazanes in dehydrogenative couplings SM (styrene monomer) in commercial
506 oxirane processes 4 17
silica in immobilization of hydrosilylation SnCI2
catalysts 500 - co-catalyst in asymmeric hydro-
silicates formylations 43
- titanium substituted 422 - in hydrocarboxylations 185
silicium sodium phosphate in telomerization
- [(CH,),SiCI] 440 processes 364
- Me,Si(Me,Cp)(WuNH) 272 sol-gel method 91 f, 501
- Ph2SiClz 423 solid-liquid phase transfer in
- Sic& 308 carbonylations of aryl-X-compounds
silicon 1 50
- HSiR3 in hydrosilylations 492 solvents 310, 424
- in radical carbonylations 192 - in arene-autoxidations 445
- (Me,Si),SiH 192 - in carbonylations 107
- organosilicon reagents in - in catalyzed hydrocarbon oxidations
hydrosilylations 493 539
- poly(viny1)organosiloxanes by - in epoxidations 414
hydrosilylations 494 - in ethylene/CO copolymerization 347
- silicon rubber 494 - in hydroaminations 522
- triphenylsilylgroup 480 - in hydroformylation 53ff
 Index 1445

- in olefin hydrocyanations 475 stereospecifity

- in olefin polymerizations 214 - in epoxidations 415
- in oxidative carbonylations 165 - in polybutadiene manufacturing 309 f
- in polybutadiene manufacturing 306 - in propylene polymerization 2 19
- in polyketone formations 354 - polybutadienes 308
- in polymerizations 226 steric effects in arene oxidations 436
- in telomerization processes 364f stochiometric oxidants
- in the Shell process 245 - CO(OAC)~ 449
- in uncatalyzed hydrocarbon oxidations - dimethyldioxirane 436
530 Strecker synthesis 39, 163, 486
- propyne carbonylation 321 styrenes
solvolysis in hydrosilylations 494 - asymmetric aminohydroxylations 573
Sonogashira reaction 276 - asymmetric epoxidation 424
space-time yields - bisalkoxycarbonylations I88 f
- acetic anhydride process 126 f - dehydrogenative silylations 503
- in alkylarene autoxidations 463 - hydrocyanation 475, 478
- in oxidative carbonylations 172 f - hydroformylation 43, 89
Speiers catalyst in hydrosilylations 495 - in ethylene polymerizations 219
n-stacking 914, 931 - migratory insertion in silylative
stannyl alkynes in hydrocyanations 480 couplings 504
steady-state concentration - oxidations 453
- acetone I19 styrene/PdC12 complex in oxidative
- of rhodium in carbonylations 113 carbonylations 166
steady-state regime in oxidative alkene substituents
acetoxylations 409 - electron withdrawing 85
steam cracking 73 - influence in arene autoxidations 447
stereochemistry in ethylene oxidations substrates in hydroformylations 38
394 succinates
stereocontrol - by oxidations 167
- in ethylene/CO copolymerization 346 - by oxidative carbonylations 167
- in hydrocyanations 471 - 2,3-dimethylsuccinate 167
stereoregulation - via dicarboxylations 188
- in stereospecific polymerizations 288 succinonitrile via amidocarbonylations
- mechanism of 290f 161
- polybutadienes 285 sulfolane in telomerization processes
- polyisoprenes 285 364 f
- polymers 284 sulfonated ylides in ethylene
stereoselectivity oligomerizations 249
- alkyne hydroformylation 481 sulfonates
- in carbonylations 146 - in carbonylations of aryl-X-
- in epoxidations 420 compounds 147
- in ethylene/CO copolymerization - in propyne carbonylations 3 18
357 sulfones in epoxy resin
- in hydrocyanations 468ff, 477 polymerizations 384
- in hydroformylation 733 sulfonic acid salt in telomerization
- in metathesis reactions 332 processes 366
- in olefin hydrocyanations 475 sulfoxides as chiral auxiliaries 577
- in propene polymerization 7 17 superacids in carbonylations 189
- in silylative alkene/vinylsilane- supercritical fluids 9 1, 423
couplings 505 surface-active agents 240
- of alkyne silylformylations 507 - via amidocarbonylations 159, 163
1446 Index
Suzuki coupling 1276
- Group IV metallocene catalysts 268
synergistic co-catalysts 118
synergistic effects 35
- in butadiene hydrocyanation 483
- in catalyzed autoxidations 452f
syngas 12, see also carbon monoxide
- technologies 10, 106, 116
syngas stripping
- in the acetic anhydride process 120
T tetraenes 329
tantalum metallacycles 338
taxogenes 36 1
taxol 1160
taxol-intermediates via 0s-catalyzed
asymmetric aminohydroxylation 572
TBA in commercial oxirane
processes 41 7
TBHP
- epoxidation mechanism 416
- in asymmetric epoxidations 421
- in chloride-free oxidations 402
- in commercial oxirane processes
- in the oxirane technology 413, 419
- oxidant in epoxidations 422f
TBHPNO(acac)2 in epoxidations 420
Tebbe reagent 1079
tert-butylethylene in regiospecific
hydrocyanation 476
telechelics by technical polymerizations
235 f
Telene 341
telogenes 361 f
telomerizations of olefines 361 ff
temperature range
- in aldehyde oxidations 429
- in arene oxidations 435
- in polybutadiene manufacturing 3 10
- of epoxidations 414
- of hydroformylations 54f, 57
terephthalic acid 106, 459
- by the AMOCO MC process 443
- manufacturing 453
- production by air oxidation 451
- via autoxidation 443
terephthalic acid (TPA) in PET
production 541
terminal alkenes in hydrocyanation 475
termination reactions in cyclooligo-
menzations 380
termination steps of polyketone
formation 349 f
termonomer in technical poly-
merizations 233 f
terpolymerization in ethylene/CO
copolymerizations 356
terpolymers by ethylene/propene/CO
terpolymerization 344
tert-butyl hydroperoxide see TBHP
tertiary alcohols in uncatalyzed
hydrocarbon oxidations 528
tetrafluoroborates as epoxy resin
polymerization initiators 385
tetraglycidyl diaminodiphenylmethane
384
tetralones via carbonylation of ary1-X-
compounds 15 1
thermodynamics in ethylene oxidations
390
thermoplastic materials via technical
polymerizations 233, 344, 460
thioesters in alkyne carbonylations 326
417 thiols in alkyne carbonylations 326
thixanphos 86
three column process 1I5
three-phase process in hydroformylation
65
tin
- as catalyst for PET production 550
- cyclooligomerization of lactones 9 15
- in allyl-ally1 cross-coupling 1065
- in esterifications 183
- in hydroformylation 763
- in photocyclization 1067
- in photocycloaddition 1069
- Ph3B/Ph3SnPh3BCN 483
- R3SnX, in butadiene hydrocyanation
483
- Sn(CH&, 440
- SnCl, 334
- tetraalkyltin 440
- trialkyltin hydride 341
- WCl&4e4Sn 336
- WOC14/Me4Sn 336
titanium
- allyltitanium complexes 294 f
- as catalyst for PET production 550
- as construction material 400
- asymmetric hydrogenation of
imines 1145
 Index 1447

- asymmetric epoxidations 1140 TMSCN in aldehyde hydrocyanations

- CGCs 271 486 f
- (Cp),TiC12 423 tmtacn 424
- [(L-Dipt(Ti)OPr'),] 486 TOFs
- in butadiene polymerizations 294, - in carbonylations 153, 190
308 - in hydrocyanations 475
- in olefin polymerizations 215, 714 Tolman's rule
- in template synthesis 914 - in cis- 1,4-polymerizations 301
- in Ziegler-Natta type catalysts 284 f, p-tolualdehyde
289 f - as intermediate in the Witten process
- isomerization of olefins 1124 545
- McMuny coupling 1093 toluenes
- metallacycles 338 - autoxidation 454 ff, 458
- photooxidation 1070 - 4-chlorotoluene 458
- salen-titanium alkoxide complex 486 - derivatives in arene autoxidations 445,
- Tebbe reagent 1079 45 8
- Ti(IV) Schiff bases 486 - in alkylarene autoxidations 455
- Ti-A1 systems in cyclooligomerizations - 4-methoxytoluene 458
370 - reaction rates of substituted toluenes
- Ti(CH2Ph),1 in butadiene poly- 456
merizations 294 p-toluenesulfonic acid in carbonylations
- Ti(CH,Ph), in butadiene poly- 140
merizations 294 TONS
- Ti(OAc), 428 - in arene oxidations 440
- Ti(OC2Hs)13 308 - in butadiene polymerizations 295
- Ti(OEt)I,/TiCI,/AlEt, 308 - in carbonylations 153, 190
- Ti(o-iPr), 272 - in cyclooligomerizations 370, 379
- Ti(OPr'), 486 - in dicarboxylations 188
- Ti(OR),Cl 308 - in ethylene polymerization 226 f
- Ti(OR)31 308 - in ethylene/CO copolymerization 346
- Ti-BINOL catalyst 575 - in hydroaminations 5 16, 5 18, 522 f
- TiC1, 486 - in hydrocarboxylations 186
- TiCl4A2/AlR, 308 - in hydrocyanations 475
- TiC14/R,,A1I3.,,/AlR3 308 - of ethylene oligomerizations 250
- TiI, 308 - of Group IV metallocene catalysts 268
- Ti'"/Si02 413, 417f TPP (triphenylphosphine) 36, 84, 89
- TiO, catalyst 418 - in hydroformylations 51, 54, 58, 83
- titanium iodide 304 - in the BASF process 82
- titanium(1V)silsesquioxanes 423 - in the UCC process 77
- titanium(1V)tartrate 42 1 TPPMS 41
titanium complexes in ethylene TPPO 36, 84
dimerizations 259 TPPTS 87, 91
titanium tetrabutoxid 261 - deactivation of hydroformylation
titanium tetrabutyl cster in ethylene catalysts 60
dimerizations 259 - in butadiene hydrocyanations 483
titanocyclopentane in ethylene - in carbonylations of aryl-X-compounds
dimerizations 259 153
TMEDA - in rhodium-based processes 76
- in amidocarbonylations 161 - in the hydroformylation mechanism
- in hydroaminations 516 51
TMSCl in arene oxidations 440 - RCWRP process 81
1448 Index

trans-effect in ethylene oxidation kinetics triphenyl phosphite 140

392 - ligand in hydroformylation 60
trans-l,4-polymerization of butadiene triphenylphosphine see also TPP
300 f - in ethylene oligomerizations 249
transalkylation in the Ethyl process 244 f - in hydrocarboxylations 185
transformations in polyketone formation - modified catalysts in hydroformylations
354 51
transition states 322 - monosulfonate see TPPMS
- diastereotopic 2 19 triphenylphosphinoxide 36
- in butadiene polymerizations 297 ff TS-1 as catalyst in epoxidations 422
- in cis- 1,4-polymerizations 30 1 tungsten
- in hydroaminations 5 19 f - as catalyst in metathesis reactions
- in polyketone formation 356 329
- in propyne carbonylations 325 - in epoxidations 413
transmetallations 266 - sodium tungstate 423
transport phenomena in hydroformylation - WC14(OC6H3-Br2-2,6)/u4Pb 336
kinetics 52, 56 - WC16 334
transvinylation 395 - WCl&tAlCI2/EtOH 336
tri(rn-sulfonatopheny1)phosphine see - WClme4Sn 336
TPPTS - WClah2SiH2 336
trialkylaluminium in ethylene - WO3 413
dimerizations 259 - WOC14 334
tribenzyltitanium halides in butadiene - WOC14/Me4Sn 336
polymerizations 294 turnover numbers see TONS
tri-n-butylmethylphosphonium iodide in Twaron 460
the acetic anhydride process 127 two-phase carbonylation methodology
tri-n-butylphosphine as ligand in the Shell 148
process 74 two-hase processes
tricyclohexylphosphine in carbonylations - in butadiene/ethylene codimerizations
of aryl-X-compounds 152 263
triethylorthoformiate in asymmetric - in hydroformylation 65
hydroformylation 56 I
triethylaluminium 26 1 U
triethylamine concentration in Ube 171
telomerization processes 364 - Upirex synthesis 823
triethylorthoformate in dicarboxylations UCC process 76ff
188 - gas recycle and product streams 76ff
triflates in carbonylations of aryl-X- - liquid recycle 77f
compounds 147 - productkatalyst separation 76
trifluoromethansulfonic acid as catalyst - raw materials 78
in PTADMT production 547 Ullmann coupling 823
trifluoroprene ultrafiltration
- in dehydrogenative silylations 503 - in catalyst separation 690
- via amidocarbonylations 157 - membranes 949
trimethylsilicium chloride see TMSCI ultrahigh molecular mass polyethylenes
trimethylsilyl cyanide in benzaldehyde by technical polymerizations 19, 230
hydrocyanation 486 ultralow-density polyethylenes 2 19
trimethylsilylethylene in regiospecific undecene in hydrocarboxylation 185
hydrocyanations 476 Union Carbide Corporation 33, 41, 43,
N,N,N-trimethyltriazacyclononane 75, 82, 174, 525
see tmtacn Union Oil 345
 Index 1449

Unoxol 10, 42 vinyl alcohols

unsaturated acids by oxidative - in cycloolefin polymerizations 224
carbonylations 168 vinyl compounds
unsaturated carboxylic acid derivates 145 - in alkyne reactions 282
unsaturated ketones vinyl ethers
- by 1,4-additions of alkynes 276 - in alkyne reactions 280
- by carbonylation of allenes 96.5 viny larenes
UOP 129 - hydrocyanations 476
Upirex synthesis 823 vinylations 279 ff
ureas as catalysts in epoxy resin - of alkynes 274
polymerizations 383 vinylchloride monomer (VCM) in PVC
urethanes 1090 ff production 553
vinylcyclohexadienes in dienelalkyne
V cyclo-co-trimerization 376
valeraldehydes in technical oxidations vinylcyclohexane in polybutadiene
43 1 manufacturing 3 10
valinol as chiral reagent in aldehyde vinylcyclohexene see VCH
hydrocyanations 486 vinyl cyclopentenes in diene cyclooligo-
VAM (vinyl acetate) 106, 406 merizations 370
vanadium vinylethylene diacetate 8
- as catalyst in epoxidations 413, 415, vinylic halides
419 - in carbonylations of aryl-X-
- as catalyst in polymerizations 213 compounds 146
- H1PM~6V6040, as chloride-free vinyl naphthalene
catalyst 401 - in hydroformylation 45
- phosphomolybdovanadic hetero- vin ylsilanes
polyacid 394 - dehydrogenative silylations 503
- photooxidation 1070 - in alkene hydrosilylations 497
- polymerization 230 - metathesis reactions 504
- reduction of nitro arenes 954 - migratory insertion in silylative
- vanadium (V) 416, 419 couplings 504
- VC12R 214 - self-disproportionations 504
- VCI,/AIBu', viscosity index improvers via technical
- V205 413 polymerizations 233
VCH (vinylcyclohexene) vitamin-A by BASF synthesis 1124
- in diene cyclooligomerizations 370
- product in BD cyclo-co-oligo- W
merizations 379 Wacker-Chemie 9, 280, 389
- via telomerization 370 - butanone manufacturing 401
- catalyst in polymerizations 213 - oxidation of ethylene 751
VC14/AICI(C2H5)2/anisole as catalyst in Wacker oxidations 407
polymerizations 2 I3 Wacker reaction 388, 402
vinyl acetate see also VAM Wacker-Hoechst process 398
- by ethylenehcetic acid co-oxidation waste
406 - in alkyne carbonylations 316
- hydrocyanation 476 - in carbonylation processes 318
- manufacture 386, 427 water as inhibitor in catalyzed
- via akaline acetate in oxidative hydrocarbon oxidations 539
acetoxylations 407 - in alkyne carbonylations 326
vinyl acetate monomer in carbonylations - in arene autoxidations 445
106 - in carbonylation processes 108, 141
1450 Index

- in dicarboxylations 188 - immobilization of hydrosilylation

- in oxidative carbonylations 165 ff, catalysts 501
168, 174f - titanium substituted in epoxidation
- in polybutadiene manufacturing 306 processes 422
water concentration Zeonex 339
- in carbonylations 110 Ziegler 3, 20, 231, 259, 286
- in co-carbonylations 124 Ziegler catalysts in cyclooligo-
water-gas shift reaction (WGSR) 1086 ff merizations 370
waxes by technical polymerizations 230 Ziegler system in hydrosilylations 499
WCl6/EtAlCl2/EtOH as disproportionation Ziegler-Natta catalysts 213, 230
catalyst 328 - in butadiene polymerizations 295
weight distribution 330 - in 1,4-polymerizations 301, 304f
WGSR (water-gas shift reaction) 109 ff, - in stereospecific diene polymerizations
111, 115, 138, 352 312
- catalytic cycle 109 - in technical polymerizations 2 16,
- rate-determining step 110 233, 235
- rhodium-catalyzed 1 11 Ziegler-Natta polymerisation 2 1
Wilke reaction 21 Ziegler-Natta-type catalysts 284
Wilkinson catalyst Ziegler’s Mischkatalysatoren 20
- hydrogenation of carbon dioxide 1197 Ziegler-type catalysts
- in hydrosilane dehydrocouplings 505 - in butadienelethylene
- in hydrosilylations 494 codimerization 263
- in photochemical hydrosilylations 502 - in dimerizationslcodimerizations 257
Wilkinson rhodium-based 0x0 process 76 zinc
Witten process 443, 541 f - in alkylation of aldehydes 947
Wurtz-coupling 506 - in self-assembling 932
- in template synthesis 918 ff
X - in water-gas shift reaction 1086
xanthphos 86 f - Simmons-Smith reaction 803
- 2,7-bis(S03Na)-xantphos 87 zirconium
- derivatives 87 as promoter in catalyzed hydrocarbon
xanthphos compounds in hydro- oxidations 537
cyanations 475 biphenolate dichlorides 272
xylenes C2H,(4,7-Me21nd)2ZrMe2 27 1
- amm(on)oxidation 1298 CH2(3-tBuInd)2ZrMe2 27 1
- o-xylene 462 co-catalysts in naphthalene oxidations
p-xylene 46 1
- autoxidation of 443 ff compounds in technical poly-
- in DMT productionn 541 merizations 233
- in PET productions 541 in cycloolefine polymerizations 224
- in TPA productions 546f in olefin polymerizations 215, 219
- oxidations to p-toluic acid 443 [Me2Si(Flu)2]ZrC12 219
1,2-xylyl dichloride via carbonylations of r~c-Me~Si(2-Me-4-Ph-Ind)~ZrC1~ 267
aryl-X-compounds 149 Z ~ ( O A C )as
~ ,catalyst-additive 45 1
ZrO(OAc), 537
Y zirconocene/methylalumoxane catalysts in
Yoneda in carbonylations 189 polymerization of cyclic olefines 215,
222
Z zirconocenes
Zeise’s salt in ethylene oxidations 392 - biphenolate derivatives 272
zeolites - chiral compounds 225