This article was published as part of the

2009 Metalorganic frameworks issue

Reviewing the latest developments across the interdisciplinary area of
metalorganic frameworks from an academic and industrial perspective
Guest Editors Jeffrey Long and Omar Yaghi
Please take a look at the issue 5 table of contents to access
the other reviews.
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View Article Online / Journal Homepage / Table of Contents for this issue
Enantioselective catalysis with homochiral metalorganic frameworksw
Liqing Ma, Carter Abney and Wenbin Lin*
Received 24th October 2008
First published as an Advance Article on the web 23rd February 2009
DOI: 10.1039/b807083k
This tutorial review presents recent developments of homochiral metalorganic frameworks
(MOFs) in enantioselective catalysis. Following a brief introduction of the basic concepts and
potential virtues of MOFs in catalysis, we summarize three distinct strategies that have been
utilized to synthesize homochiral MOFs. Framework stability and accessibility of the open
channels to reagents are then addressed. We nally survey recent successful examples of
catalytically active homochiral MOFs based on three approaches, namely, homochiral MOFs
with achiral catalytic sites, incorporation of asymmetric catalysts directly into the framework, and
post-synthetic modication of homochiral MOFs. Although still in their infancy, homochiral
MOFs have clearly demonstrated their utility in heterogeneous asymmetric catalysis, and a bright
future is foreseen for the development of practically useful homochiral MOFs in the production
of optically pure organic molecules.
Introduction
Metalorganic frameworks (MOFs), also known as coordina-
tion polymers, are hybrid solids with innite network structures
built from organic bridging ligands and inorganic connecting
points.
15
MOFs can be constructed from designer building
blocks to impart unique properties for a wide range of potential
applications including nonlinear optics,
6
gas storage,
710
sensing,
11
and catalysis.
1215
One of the most extraordinary
features of MOFs is their ability to possess unprecedentedly
high porosity. Depending on the size of ligands and inorganic
connecting points and network connectivity, the porosity of
MOFs can be readily tuned to aord open channels and pores
with dimensions of several angstroms to several nanometres.
The ability to incorporate functional groups into porous
MOFs makes them excellent candidates as heterogeneous
catalysts. The well-dened pores and channels in MOFs have
the potential to endow them with the size- and shape-selective
catalysis that is the hallmark of zeolites. The diversity of
zeolites, however, is rather limited due to the use of exclusively
SiO
4
/AlO
4
tetrahedral building units. The resulting 3D frame-
works of zeolites are microporous with channels/cavities of up
to 1.0 nm, and as a result, the catalytic applications of zeolites
are restricted to relatively small organic molecules (typically
no larger than xylenes). In contrast, MOFs can be built from
an innite number of building blocks to allow for a systematic
ne-tuning of their properties. Furthermore, the mild synthetic
conditions typically employed for MOF synthesis allow direct
incorporation of a variety of delicate functionalities into the
framework structures. For example, either enantiopure
chiral ligands or their metal complexes can be incorporated
directly into the frameworks of MOFs to lead to ecient
asymmetric catalysts. Such a process would not be possible
with zeolites or other microporous crystalline oxide-based
materials because of the harsh conditions typically used for
their synthesis (e.g., calcination at high temperatures to
remove organic templates).
Department of Chemistry, CB#3290, University of North Carolina,
Chapel Hill, NC, 27599, USA. E-mail: wlin@unc.edu;
Fax: +1-919-962-2388; Tel: +1-919-962-6320
w Part of the metalorganic frameworks themed issue.
Liqing Ma
Liqing Ma obtained his PhD
degree from Case Western
Reserve University in 2006
under the supervision of
Prof. John D. Protasiewicz.
Currently he is a Postdoctoral
Associate with Prof. Wenbin
Lin at the University of North
Carolina at Chapel Hill. His
current research focuses on de-
veloping porous metalorganic
frameworks for gas storage,
chiral separation, and hetero-
geneous catalysis.
Carter W. Abney
Carter W. Abney obtained his
BS degree from the University
of Wisconsin at Madison in
2007. He is currently a PhD
student at the University of
North Carolina at Chapel Hill
under the guidance of Prof.
Wenbin Lin. His research
emphasis is on the development
of novel homochiral metal
organic frameworks and their
catalytic applications.
1248 | Chem. Soc. Rev., 2009, 38, 12481256 This journal is c The Royal Society of Chemistry 2009
TUTORIAL REVIEW www.rsc.org/csr | Chemical Society Reviews
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In spite of the great potential for MOFs in heterogeneous
catalysis, very few of them have been explored for catalytic
applications. This is in part due to the relative thermal and
hydrolytic instability of MOFs as compared to zeolites.
Furthermore, it remains a great challenge to engineer very
strong Lewis acid or Brnsted acid sites in MOFs. These two
limitations make it dicult for MOFs to nd applications in
many of the processes that are currently catalyzed by zeolites
(such as hydrocracking of crude oil).
Two very dierent strategies have been utilized to synthesize
catalytically active MOFs. In the rst approach, the
metal-connecting points with unsaturated coordination
environments are utilized as catalytically active sites. The
metal-connecting points in MOFs typically have coordinated
water or other solvent molecules that can be readily removed
without distorting the framework structures. Such accessible,
coordinatively unsaturated metal centers can be used to catalyze
organic reactions (Scheme 1). In the second approach, catalytic
sites are incorporated directly into the bridging ligands used to
construct MOFs (Scheme 2). Although more synthetically
demanding, the second approach is much more versatile and
allows for the incorporation of a wide variety of catalysts.
Compared to the limited number of MOFs that have been
used as achiral catalysts, even fewer examples have been
reported for application in asymmetric catalysis, despite the
great importance of heterogeneous asymmetric catalysis in the
production of enantiomerically pure products. The scarcity of
MOF-based heterogeneous asymmetric catalysts is directly
related to the diculty of designing porous MOFs with open
channels that are several nanometres in dimension. Such large
open channels are essential for asymmetric catalytic reactions
because of the need to transport organic substrates and
products that are typically quite sizeable.
In the present review, we briey introduce the basic concepts
of catalysis with MOFs and describe the general strategies for
the synthesis of homochiral MOFs. We then survey recent
examples of homochiral MOFs that have been examined for
heterogeneous asymmetric catalysis.
Strategies for homochiral MOF synthesis
Homochiral MOFs with built-in catalytic sites are necessary for
enantioselective reactions, and thus far three distinct strategies
have been used for their construction. In the rst approach,
homochiral MOFs are prepared fromtotally achiral components
via self-resolution during crystal growth. Such a strategy would
oer the greatest advantage as it does not use chiral components
which often require laborious synthesis and are typically
expensive. Although numerous claims of such self-resolution of
homochiral MOFs have been made, almost all of these MOFs
are in fact racemic because their bulk samples contain both
enantiomorphs (opposite handedness) of MOFs. Aoyama and
coworkers reported the rst example of obtaining a homochiral
MOF Cd(apd)(NO
3
)
2
H
2
OEtOH, 1, based on achiral Cd
2+
centers and 5-(9-anthracenyl)pyrimidine (apd) bridging ligand.
16
1 crystallizes in the chiral space group P2
1
, with chirality arising
from a pyrimidine-Cd
2+
helical array (Fig. 1). Crystals of 1 were
observed to grow radially from the rst appearing nucleus,
suggesting the possibility of seeding the growth of homochiral
1 in the bulk. By using solid-state circular dichroism spectro-
scopy, they convincingly demonstrated the seed-induced
synthesis of homochiral 1 from totally achiral components.
Zheng and coworkers recently demonstrated the synthesis
of homochiral MOFs from totally achiral components by
Scheme 1 Coordinatively unsaturated metal connecting points as
active catalytic sites.
Scheme 2 Incorporation of active catalytic sites into the bridging
ligands of MOFs.
Fig. 1 Structure of 1 showing two hydrogen-bonded helices. Wenbin Lin
Wenbin Lin is a professor of
chemistry and pharmacy at the
University of North Carolina at
Chapel Hill. His research
focuses on designing novel
molecular and supramolecular
systems and hybrid nano-
materials for applications in
chemical and life sciences. He
has published B150 papers in
several research areas.
This journal is c The Royal Society of Chemistry 2009 Chem. Soc. Rev., 2009, 38, 12481256 | 1249
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chemically manipulating the statistical uctuation of enantio-
meric pair formation.
17
The kinetics of [{Cu(succinate)-
(4,4
0
-bipyridine)}
n
](4H
2
O)
n
(2) crystallization were retarded
when ammonia was added to the mixture as a competing
ligand, resulting in the formation of fewer parent crystals.
Careful tuning of ammonia concentrations and solvent
evaporation rates led to the growth of a single cluster of
homochiral 2. This elegant chiral symmetry breaking strategy
obviates the use of a seed crystal, but the handedness of the
MOF crystals cannot be known a priori.
In the second approach, bulk homochiral MOFs are
synthesized from achiral metal connecting points and bridging
ligands under chiral inuence. Rosseinsky and coworkers
utilized enantiomerically pure 1,2-propanediol as a chiral
template (co-ligand) to synthesize homochiral MOFs
from 1,3,5-benzenetricarboxylate (btc) and M(NO
3
)
2
6H
2
O
(M = Ni, Co).
18,19
Enantiopure 1,2-propanediol chelates to
the metal centre, allowing the stereochemistry of the metal
to control the absolute helicity of the growing polymeric
structure and to determine the nature of interpenetration.
Morris and coworkers recently utilized ionic liquids with chiral
anions to induce spontaneous crystallization of homochiral
MOFs of the same enantiomorph.
20
Using the chiral ionic
liquid 1-butyl-3-methylimidazolium L-aspartate (BMIm-L-asp)
as the reaction medium, homochiral (BMIm)
2
[Ni(btc-H)
2
(H
2
O)
2
]
(3) was obtained (Fig. 2). Although containing neither chiral
ligands nor chiral anions, 3 crystallizes in the chiral space
group P4
1
2
1
2. Analysis of 10 randomly selected crystals of 3
by single-crystal X-ray determination veried the enantio-
morphic purity. Chiral induction was further supported by
the fact that substitution of L-aspartate with D-aspartate
yielded crystals of 3 with the opposite chirality and that
removal of chiral anions in the ionic liquid resulted in an
achiral MOF (BMIm)
2
[Ni
3
(btc-H)
4
(H
2
O)
2
].
More recently, Bu and coworkers further advanced the
concept of chiral inuence and successfully used sub-
stoichiometric amounts of a chiral spectator to amplify the
chiral induction of homochiral MOFs from achiral bulking
blocks.
21
Utilizing small amounts of the alkaloids
()-cinchonidine or (+)-cinchonine, enantomorphically pure,
homochiral MOFs such as (Me
2
NH
2
)[In(thb)
2
]xDMF (4)
were grown from achiral precursors (H
2
thb refers to thiophenen-
2,5-dicarboxylic acid). As expected, crystals of opposite
chirality were obtained when they were grown in the presence
of ()-cinchonidine or (+)-cinchonine. The resulting crystals
were found to be racemic twins when no chiral alkaloid was used.
The third approach to homochiral MOF construction is to
use readily available chiral linker ligands as the building
blocks. This approach not only provides the most reliable
means for homochiral MOF synthesis, but also allows the
synthetic elaboration of the chiral bridging ligands to impart
desirable functionalities for asymmetric catalysis. Indeed, all
of the homochiral MOFs examined for asymmetric catalysis so
far were prepared via this third strategy. Any of the chiral
auxiliaries used for homogeneous asymmetric catalysis can, in
principle, be elaborated to contain functionally orthogonal
groups to bridge metal centres and form homochiral MOFs.
For example, Lin et al. have extensively functionalized
1,1
0
-binaphthyl-derived chiral auxiliaries, such as 1,1
0
-bi-
naphthalene-2,2
0
-diol (BINOL) and, 2,2
0
-bis(diphenylphosphino)-
1,1
0
-binaphthyl (BINAP), with exo-bidentate or exo-multidentate
bridging ligands to construct a variety of homochiral
MOFs.
2224
The 1,1
0
-binaphthyl framework is of particular
interest because of the ability to selectively functionalize
the dierent positions (e.g. 2,2
0
-, 3,3
0
-, 4,4
0
-, 5,5
0
-, 6,6
0
-,
and 7,7
0
-positions as well as several combinations of them)
with a variety of groups such as pyridyl, carboxyl, and
phosphonic acid (Scheme 3). Furthermore, these functional
groups can be installed on the 1,1
0
-binaphthyl framework via
dierent linkers to aord chiral bridging ligands of the same
geometry but varied lengths. Such ligand families are of great
importance in constructing homochiral MOFs with tunable
porosity and pore and channel sizes.
Framework stability and reagent-accessible channels
For a homochiral MOF to function as an eective hetero-
geneous asymmetric catalyst, it needs to maintain its frame-
work structure during the catalytic reaction, as well as sustain
the open channels to allow rapid transport of the reagents and
the products. Chiral MOFs with large open channels (typically
larger than 1.5 nm) are desired due to the large size of
prochiral substrates and the resulting chiral products.
Unfortunately, MOFs with large open channels tend to
undergo signicant framework distortion upon the removal
of solvent molecules, aording materials that exhibit very
Fig. 2 Perspective view of 3 along the a axis showing the two helices
with the same handedness running through both a and b axes.
Scheme 3 Examples of BINOL-derives chiral ligands used by the Lin
group.
1250 | Chem. Soc. Rev., 2009, 38, 12481256 This journal is c The Royal Society of Chemistry 2009
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dierent powder X-ray diraction (PXRD) patterns than
those of the pristine solids. These MOFs also typically exhibit
lower surface areas than those calculated from single crystal
structure data. It is thus important to demonstrate the frame-
work stability of homochiral MOFs during the catalytic
reactions and to prove the accessibility of their open channels
to large organic molecules.
In order to demonstrate framework stability of homochiral
MOFs, Wu and Lin synthesized a 1D homochiral MOF
[Cd(L
1
)
2
(ClO
4
)
2
]11EtOH6H
2
O, 5, built from the elongated
di-pyridyl ligand L
1
and Cd(ClO
4
)
2
.
25
The pristine crystals lost
crystallinity upon removal of the included solvent molecules as
judged by PXRD. However, the crystallinity was readily
restored when the amorphous material was exposed to a
solvent vapour. More importantly, the homochiral MOF
remained crystalline and underwent a single-crystal-to-single-
crystal transformation during the solvent exchange process
(Fig. 3). These results indicate that the framework distortion
does not negatively impact the accessibility of solvent mole-
cules to the open channels and that the homochiral framework
structure should be maintained under typical heterogeneous
asymmetric catalytic conditions where a solvent is involved.
More recently, Lin and co-workers reported homochiral
MOFs based on a BINOL-derived tetra-carboxylate bridging
ligand L
2
.
26
The resulting 3D MOF [Cu
2
(L
2
)(H
2
O)
2
](DEF)
12

(H
2
O)
16
, 6, possesses large channels of 3.2 nm running through
the b axis (Fig. 4), and represents the rst example of a
mesoporous homochiral MOF. Interestingly, this system
exhibits catenation isomerism that is not only controlled by
the chirality of the bridging ligand but also inuenced by the
solvent used to grow the MOF crystals. When the crystals
were grown in dimethylformamide (DMF), the enantiopure
ligand L
2
gave a noninterpenetrating structure, while the
racemic L
2
yielded a 2-fold interpenetrated MOF 7 (Fig. 4).
However, both enantiopure and racemic L
2
yielded
non-interpenetrating structures when the crystals were grown
from diethylformamide (DEF). The non-interpenetrating
framework 6 has a remarkable solvent accessible void space
of B85% as calculated by PLATON, whereas the 2-fold
interpenetrated framework 7 has a smaller void space of
B70% and possess smaller open channels of 1.4 0.7 nm.
As a result of the very open structures, the frameworks of both
6 and 7 severely distorted when the solvent molecules were
removed and exhibited surface areas much smaller than those
calculated fromsingle crystal data. In spite of such evacuation-
induced framework distortion, 6 readily took up 103 wt%
(dye/framework) of the nano-sized dye molecule Brilliant Blue
R-250, with dimensions of B1.8 2.2 nm. In contrast, 7 took
up only 10.6 wt% of Brilliant Blue R-250 under the same
conditions, presumably via surface adsorption. The resulting
dye-incorporated solids exhibited the same PXRD patterns as
pristine 6 and 7. These results conclusively demonstrate the
maintenance of open channels in these frameworks and the
accessibility of the open channels to nano-sized molecules in
solution.
Recent examples of enantioselective catalysis with
homochiral MOFs
Several strategies have been used to construct catalytically
active homochiral MOFs. Earlier attempts focused on
examining the activities of achiral catalytic sties that were
incorporated into the homochiral MOFs.
13,27
Enantio-
selectivities of such systems arise from the remote inuence
by chiral environments of the open channels, and to date,
disappointingly low ees were obtained with this approach.
Later eorts were directed toward designing homochiral
Fig. 3 Schematic illustration of reversible single crystal to single
crystal transformations of 5.
Fig. 4 (a) A view of the [Cu
2
(O
2
CR)
4
] paddle-wheels in 6 and their
connectivity with R-L
2
. (b) Space lling model of [R-L
2
Cu
2
] (6) viewed
down the b axis, showing open channels of 3.2 nm at the greatest
point. (c) The largest channels of 3.2 nm can be described as helices
running through both a and b axes. (d) Two-fold interpenetrating
structures of [rac-L
2
Cu
2
] (7).
This journal is c The Royal Society of Chemistry 2009 Chem. Soc. Rev., 2009, 38, 12481256 | 1251
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MOFs with bridging ligands that contain chiral functional
groups exploitable for asymmetric catalysis based on two
distinct approaches. In the precatalyst approach, bridging
ligands containing asymmetric catalytic sites are linked with
metal-connecting points to generate homochiral MOFs. In an
alternative and complementary post-synthetic modication
approach, homochiral MOFs are constructed with chiral
bridging ligands that contain secondary and orthogonal
functionalities. The secondary functional groups are then
converted into catalytic sites via post-synthetic modication.
Although the precatalyst approach provides a versatile
method for synthesizing a wide range of catalytically active
homochiral MOFs, it is not compatible with some of the less
stable Lewis acid and late transition metal catalysts. The
post-synthetic modication approach overcomes this limita-
tion and expands the range of heterogeneous asymmetric
catalysts based on homochiral MOFs.
Achiral catalytic sites within homochiral MOFs
Kim et al. reported the rst example of asymmetric catalysis
with a homochiral MOF based on an enantiopure
tartaric acid-derived bridging ligand L
4
, and the Zn
3
(m
3
-O)-
(carboxylate)
6
secondary building unit (SBU). Homochiral
[Zn
3
(m
3
-O)(L
4
-H)
6
]2H
3
O12H
2
O (8) was synthesized under
solvothermal conditions (Scheme 4).
27
Three zinc ions are held
together by six carboxylate groups and a m
3
-oxygen to form
the enantiopure trinuclear SBU (Fig. 5). Each of the SBUs
possesses six pyridyl groups, with two of them protonated and
three of them involved in coordination with zinc ions. The
Zn
3
(m
3
-O)(carboxylate)
6
SBUs are linked by the L
4
ligands to
generate 2D layers with a hexagonal topology. The resulting
MOF has large (B13.4 A

) chiral 1D channels along the c axis

and an estimated void space of B47%. The remaining
pyridine is exposed in the channels of 8 and endows the
MOF with its catalytic properties.
Compound 8 catalyzed the transesterication between an
aromatic ester (A) and ethanol to aord ethyl acetate in 77%
yield after reacting in carbon tetrachloride for 55 h (Scheme 5).
Under similar conditions, a very modest enantiomeric excess
(ee) of B8% was observed when 8 was used to catalyze the
transesterication of A with racemic 1-phenyl-2-propanol.
Lin et al. prepared a series of homochiral MOFs
[Ln(L
3
-H
2
)(L
3
-H
3
)(H
2
O)
4
]xH
2
O (9) based on lanthanide
phosphonate and examined their activities as Lewis acid
catalysts by taking advantage of the lanthanide metal-
connecting points (Fig. 6).
28
Unfortunately, negligible ees
were observed in several Lewis acid catalyzed reactions
including cyanosilylation of aldehydes and ring opening of
meso-carboxylic anhydrides. These results illustrate the challenge
in designing highly enantioselective MOF catalysts via remote
inuence by chiral environments of the open channels.
Incorporation of asymmetric catalysts directly into the
framework
A more reliable route to designing homochiral MOFs with
asymmetric catalytic activity is to utilize bridging ligands that
contain ready-to-use catalysts. As chiral metal complexes have
been widely used for enantioselective organic transformations
under homogeneous conditions, their incorporation into
bridging ligands can directly impart asymmetric catalytic
activities to the resulting MOFs.
Lin and coworkers have designed BINAP based homochiral
bridging ligands (L
5
and L
6
) with ruthenium complexes
incorporated in the scaold. Such diphosphoric acid substi-
tuted ligands were reacted with zirconium tetra-tert-butyloxide
to yield chiral porous hybrid solids 10 and 11 (Scheme 6).
23
With the imbedded Ru(BINAP)(diamine)Cl
2
precatalysts, 10
and 11 showed excellent enantioselectivity for the asymmetric
hydrogenation of aromatic ketones (up to 99.2% ee). These
catalysts were readily recycled by centrifugation, and could be
reused up to 10 times without signicant loss of activity or
enantioselectivity. Analogous zirconium phosphonates con-
taining Ru(BINAP)(DMF)
2
Cl
2
moieties were also prepared
and used for asymmetric hydrogenation of b-keto esters.
29
Scheme 4 Synthesis of homochiral MOF 8.
Fig. 5 1D equilateral triangular shape channel along the c axis of 8,
with a size of 13.4 A

(left); coordination environment or metal centres

of 8, showing the catalytic centre and the chiral pocket (right).
Scheme 5 Transesterication reactions catalyzed by 8.
Fig. 6 Perspective view of 9 along the a axis, showing lamellar
structure. Dierent colours illustrate dierent lamellae.
1252 | Chem. Soc. Rev., 2009, 38, 12481256 This journal is c The Royal Society of Chemistry 2009
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These zirconium phosphonate-based solids are amorphous,
however, and dicult to characterize in molecular details.
Hupp and coworkers reported a homochiral MOF
constructed from the chiral (salen) Mn ligand L
7
, biphenyl-
4,4
0
-dicarboxylic acid (H
2
bpdc), and Zn
2+
ions (Scheme 7).
The framework [Zn
2
(bpdc)
2
L
7
]10DMF8H
2
O (12) was
obtained under solvothermal conditions, showing a twofold
interpenetrating 3D network with 57% solvent accessible
volume (Fig. 7).
15
The channels in the a and c directions
possess dimensions of 6.2 6.2 A

and 6.2 15.7 A

, respec-
tively. Due to the diagonal displacement of the network, all
Mn
III
sites are accessible to the channels (Fig. 8).
Compound 12 was examined for asymmetric olen
epoxidation reactions and eectively catalyzed the epoxidation
of 2,2-dimethyl-2H-chromene to result in the desired product
in 71% yield and 82% ee (Scheme 8). 12 has a higher activity
than the homogeneous counterpart, albeit with slightly lower
enantioselectivity. Unlike related homogeneous epoxidation
catalysts, which are highly active for only a few minutes, 12
maintained its activity throughout a three hour reaction
period. Additionally, 12 was recycled and reused three times,
displaying only a slight decrease in activity and no loss in
enantioselectivity.
Based on an approach developed by the Lin group, Tanaka
and coworkers used 5,5
0
-dicarboxy-substituted BINOL as a
bridging ligand (L
8
) to react with copper nitrate under
solvothermal conditions (Scheme 9).
30
The resulting 2D
innite framework [Cu
2
(L
8
)
2
(H
2
O)
2
]MeOHH
2
O (13) con-
tains copper paddle-wheels as SBUs and are stacked along
the b axis with an interlayer CuCu distance of 15.6 A

(Fig. 8).
The water molecules terminating the copper paddle-wheels
were removed upon heating, allowing the exposed copper
centres to function as Lewis acid catalytic reaction centres.
To test the catalytic activity of framework 8, the asymmetric
ring-opening of epoxides with amines was examined
(Scheme 10). Following 48 h of reacting at 25 1C in toluene,
a maximum 54% yield with 45% enantiomeric excess was
obtained. The catalyst was recovered by ltration and recycled
without detrimental aect to the reactivity and enantio-
selectivity. Interestingly, enantioselectivity and reactivity both
Scheme 6 Asymmetric hydrogenation of aromatic ketones catalyzed
by homochiral hybrid solids 10 and 11.
Scheme 7 Chiral bridging ligand L
7
with (salen) Mn complex and the
achiral bridging ligand H
2
bpdc.
Fig. 7 Schematic representation of open channels and catalytic active
sites within the two-fold interpenetrating framework of 12.
Fig. 8 Stacking patterns of a 2D grid of 13 as viewed along the c axis.
Scheme 8 Asymmetric epoxidation catalyzed by 12.
Scheme 9 Schematic representation of the synthesis of 13 and the
connectivity of L
8
and the copper paddle wheels.
Scheme 10 Asymmetric ring-opening reaction of epoxide with amine
catalyzed by 13.
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improved under solvent-free conditions. Control experiments
indicated that (S)-BINOL itself is not catalytically active. To
date, the mechanism of this catalytic reaction remains unclear.
Post-synthetic modication of homochiral MOFs
Lin and co-workers pioneered the post-synthetic route to
catalytically active homochiral MOFs by utilizing orthogonal
functionalities within the backbones of BINOL-derived
bridging ligands. For example, 3D homochiral MOF
[Cd
3
(L
9
)
3
Cl
6
]4DMF6MeOH3H
2
O (14) was synthesized via
slow vapour diusion of diethyl ether into a mixture of L
9
and
CdCl
2
in DMF/MeOH.
24
Through the linkage of 1D zigzag
[Cd(m-Cl)
2
]
n
SBUs with the L
9
ligands via pyridine coordina-
tion, the 3D framework showed the largest channel opening of
1.6 1.8 nm running along the a axis (Scheme 11 and Fig. 9).
The permanent porosity of 14 was characterized by CO
2
adsorption experiments that showed a surface area of
601 m
2
g
1
. Despite the use of such an elongated ligand, frame-
work catenation was prevented due to the 1D zigzag Cd chain.
Further analysis of the framework 14 reveals that two-thirds
of the orthogonal hydroxyl groups are inaccessible due to tight
pairing of L
9
ligands by hydrogen-bonding and p p stacking
interactions, but the remaining third are oriented into the
channels and readily react with Ti(O
i
Pr)
4
to form a chiral
catalytic species and thus functionalize the MOF (Fig. 10). The
resulting Ti-BINOLate species are capable of catalyzing the
diethylzinc addition to aldehydes with high ees up to 93%
(Table 1), which is comparable to the homogeneous analogue
(94%). The absence of catalytic activity in the supernatant of
the 14 and Ti(O
i
Pr)
4
mixture illustrated the heterogeneous
nature of this porous solid. To conrm that the aldehydes are
accessing the active Ti sites located within the interior of the
framework, a series of aldehydes with sizes from 0.8 nm to
2.0 nm were tested. The data showed that larger aldehydes
gave lower conversions, which further demonstrates that
catalytic conversion happened inside the crystal channels,
and veries the heterogeneous nature of 14.
It is well-established that dierent anions used in the crystal
growth may direct the growth of dierent MOF structures.
For example, the reaction of CdCl
2
with L
9
aorded
[Cd(m-Cl)
2
]
n
SBUs resulting in the formation of a MOF with
large open channels. In contrast, the MOFs formed by
Cd(NO
3
)
2
and Cd(ClO
4
)
2
with L
9
adopted two dierent
Scheme 11 Schematic representation of the synthesis of 14, and its
3D network showing zigzag chains of [Cd(m-Cl)
2
]
n
along the a axis.
Fig. 9 (a) Space-lling model of 14 as viewed down the a axis,
showing the large 1D chiral channels (1.6 1.8 nm). (b) Schematic
representation of the active (BINOLate)Ti(O
i
Pr)
2
catalytic sites in the
open channels of 14.
Fig. 10 (a) The 2D square grid in 15. (b) Schematic representation of
the 3D framework of 15. (c) Schematic representation of the inter-
penetration of mutually perpendicular 2D grids in 16. (d) Schematic
representation of steric congestion around the chiral dihydroxyl group
of L
9
(orange sphere) arising from the interpenetration of mutually
perpendicular 2D grids in 16.
Table 1 Ti(IV)-catalyzed ZnEt
2
additions to aromatic aldehydes
Ar
BINOL/Ti(O
i
Pr)
4
14Ti
Conv.(%) ee(%) Conv.(%) ee(%)
1-Naph 499 94 499 93
Ph 499 88 499 83
4-Cl-Ph 499 86 499 80
3-Br-Ph 499 84 499 80
4
0
-G
0
OPh 499 80 499 88
4
0
-G
1
0
OPh 499 75 73 77
4
0
-G
1
OPh 499 78 63 81
4
0
-G
2
0
OPh 95 67 0
1254 | Chem. Soc. Rev., 2009, 38, 12481256 This journal is c The Royal Society of Chemistry 2009
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homochiral structures, [Cd
3
(L
9
)
4
(NO
3
)
6
]7MeOH5H
2
O (15)
and [Cd(L
9
)
5
(ClO
4
)
2
]DMF4MeOH3H
2
O (16), respectively,
12
with both networks containing 2D grids as shown at Fig. 10a.
In 15 the grids are stacked in layers, interconnected by 1D
polymeric chains (green zigzag line at Fig. 10b), and possess
large channels with dimensions of 13.5 13.5 A

along the
c axis. However, framework 16 was constructed solely by 2D
grids and displays a 2-fold interpenetrating pattern (Fig. 10c)
to result in 12 15 A

1D channels.
When activated by Ti(O
i
Pr)
4
, framework 15 showed very
good enantioselectivity (up to 90% ee) in the diethylzinc
addition to aromatic aldehydes. Surprisingly, framework 16
showed no activity at all under the same reaction conditions.
Further examination revealed the interpenetration pattern
adopted by 16 brought dihydroxyl groups from one 2D
grid within close proximity of the the Cd(py)
2
(H
2
O)
2
moiety
in the other 2D grid (Fig. 11d). The Cd(py)
2
(H
2
O)
2
moiety sterically prohibits the Ti(O
i
Pr)
4
from reacting with
the dihydroxyl groups and prevents formation of the active
Ti-BINOLate species. It is this subtle structural dierence that
leads to completely dierent catalytic reactivity of the two
frameworks.
Rosseinsky and coworkers recently reported a microporous
MOF that can aord Brnsted acid sites after post-synthetic
modication.
31,32
The open framework [Cu(L-asp)
2
(bipy)]
2HClH
2
O (17) was obtained by a solvothermal reaction of
Cu(L-asp)3H
2
O with 4,4
0
-bipyridine (bipy) in H
2
O and
MeOH, followed by protonation with HCl. As evidenced by
powder X-ray diraction, 17 bears a very similar structure to
its Ni counterpart framework, which contains 1D channels of
size 4.3 3.2 A

running through the b axis (Fig. 11). When a

longer ligand 1,2-bis(4-pyridyl)-ethane (bpe) was used, frame-
work 17b with larger 1D channels of 8.6 3.2 A

was obtained.
The resulting Brnsted acid sites were used to catalyze the
methanolysis of cis-2,3-epoxybutane (Scheme 12). Both 17 and
17b showed some enantioselectivity, however, in all test reac-
tions moderate yields (3265%) and very low ees (up to 17%)
were obtained. Nevertheless, their heterogeneous nature was
evidenced by the inactive ltered supernatant. No conversion
was observed for attempted methanolysis of the bulkier
epoxide (2,3-epoxypropyl)-benzene, suggesting catalysis does
occur mostly in the channels and pores rather than on the
external surfaces.
Conclusions
This review summarized the developments of homochiral
MOFs for applications in heterogeneous asymmetric catalysis.
The various synthetic techniques used in homochiral MOF
formation were discussed and their ability to maintain frame-
work structure during solvent exchange and to take up
nanosized dye molecules was analyzed. Finally, recent exam-
ples of MOFs used in asymmetric catalysis were reviewed.
Although inferior to zeolites in thermal or hydrolytic stability,
MOFs possess extensive tunability, highly regular catalytic
sites, and homochirality and thus represent a unique oppor-
tunity to design MOF-based heterogeneous asymmetric
catalysts. Homochiral MOFs have a bright future in the
asymmetric catalytic synthesis of important optically pure
organic molecules.
Acknowledgements
We thank NSF for nancial support.
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