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Shashi Bhushan1 and Kuppuswamy Vijayakumaran2 1 Gerchem Labs (India) Pvt. Ltd., Hyderabad 700 001, India. (e-mail: gerchem@hd2.dot.net.in) 2 Chimique Laboratories (India) Ltd., Alathur 603 110 (TN) India. (e-mail: kvjkum@eth.net)
INTRODUCTION C-C bond formation lies at the heart of organic chemistry and in this context biaryl coupling occupies a prominent place, particularly with important applications to natural products synthesis. Oxidative phenolic coupling is an area that has been actively pursued with synthetic and biosynthetic implications. Transition metal ions such as Fe(III) are well known to catalyze aerobic oxidative biaryl coupling. There is continued interest in this field one of the objectives being the discovery of efficient catalytic systems which will perform under mild conditions, avoiding (or minimizing) the formation of unwanted side products such as quinones. In 1994, Noji et al1 introduced a copper-derived complex viz. CuCl(OH).TMEDA2 as catalyst for oxidative coupling of beta-naphthols1,3 based on the previously reported ability of Cu(I)-amine complexes to catalyze the oxidative coupling of acetylenes and active methine compounds (Glaser-Hay coupling). NOVEL Cu-BASED CATALYST FOR AEROBIC COUPLING CuCl(OH).TMEDA is a stable, free flowing solid, soluble in chlorinated solvents, ethanol, diethylether, methanol and THF. It is sparingly soluble in acetone, benzene, toluene and other non-polar solvents. The reactions are usually carried out in dichloromethane or chloroform under aerobic conditions (air or oxygen). The catalyst is formulated as CuCl(OH).TMEDA and in some references a dimeric structure 1 is also depicted.4
H3C N Cu N H3C CH3 O H H3C CH3 H O Cu N CH3 H3C N 2 Cl CH3 ++
-2This article presents selected applications of CuCl(OH).TMEDA in biaryl coupling reactions and inter alia some recent reports on Glaser-Hay acetylenic coupling with particular reference to diyne-bridged chiral binaphthol oligomers, macrocycles and porphyrins.
R1 R1
OH OH
R1
OH
R2
2 (a-e)
SCHEME- I
3 (a-e)
R1 H H OCH3 H
R2 H CH3 H COOCH3
Oxidant
Temp. (oC) 0 RT RT RT
Yield (%) 90 92 96 99
O2 O2 O2 O2
-3Nakajima and coworkers also compared the efficacy of CuCl(OH).TMEDA with classical Glaser-Hay coupling catalysts derived from Cu(I) and Cu(II) salts (in conjunction with TMEDA) in the oxidative coupling of 2-naphthol. They found CuCl(OH).TMEDA to be much superior, enabling an efficient catalytic oxidative coupling of 2-naphthols which could be applied to a large-scale synthesis of binaphthols.3 Not surprisingly, 2-methoxynaphthalene itself did not undergo oxidative coupling under these conditions. Ng et al5,6 took advantage of CuCl(OH).TMEDA to synthesize 4,4'-dibromo-1,1'-bi-2-naphthol 5 through the oxidative coupling of 4-bromo-2-naphthol 4 in 90% yield (Scheme II). The 4,4'-dibromo-1,1'-bi-2naphthol 5 thus prepared was resolved, converted to chiral oligo-1,1'-bi-2-naphthalene molecules through Glaser-Hay acetylenic coupling (see further, II.2.).
Br Br
OH OH
Br
4
SCHEME-II
I.2 SYNTHESIS OF "CYCLO-BINOLS" Lipshutz et al7,8 developed a modular approach to tethered non-racemic cyclo-BINOLS 7 by the use of CuCl(OH).TMEDA on chiral 6 to give 7 in 90-95% isolated yield. The level of chiral induction due to the chiral acetal auxiliary in the crucial biaryl coupling-cyclization step is quite high, attaining a diastereomeric excess (de) of 90% (Scheme III).
R1 O O O O OH OH R1
6 7 (R1=H)
CuCl(OH).TMEDA (8 mol%) O2, CH2Cl2
R1 O O O O
R
OH OH R1
-4In this intramolecular biaryl coupling, use of concentrations greater than 0.001M led to increasing amounts of polymeric materials. Syringe pump addition, however, allowed for a final working concentration of 0.01M. Noteworthy is the comment by the authors that salts of other metal ions commonly used in this kind of coupling process, such as Fe(III), are required in stoichiometric amounts, besides leading to inferior yields in the biaryl coupling step.7 The cyclo-BINOL 7 (useful as a chiral ligand) was obtained as a separable diastereomeric mixture.
CuCl(OH).TMEDA (1 mol%)
OH
OH OH
air, CH2Cl2, 24 h
Br
8
SCHEME-IV
Villemin and coworkers9 commented that bromination of binol itself depends on the purity of the substrate. Where binol is prepared by oxidative coupling of beta-naphthol using iron(III) chloride in stoichiometric amount, several recrystallizations are needed to remove all the iron salts before the bromination step. Indeed, traces of iron(III) chloride catalyze the bromination reaction and thus induce the formation of unwanted byproducts. In this instance, use of just 1% CuCl(OH).TMEDA serves admirably to obtain the desired 6,6'-dibromo-binol in excellent yields. As an alternative route to 11, these authors tried the oxidative coupling of dialkyl 6hydroxynaphthylphosphonate 10 using 5% CuCl(OH).TMEDA to give 11 (Scheme V).9 In spite of the use of dioxygen instead of air, they could not realize yields higher than 25% (R=C2H5) and 60% [R=CH(CH3)2]. They explained these relatively lower yields based on mechanistic considerations of the oxidative coupling reaction. Besides, they also surmised that the reactivity of the Cu-complex might be reduced due to complexation with the phosphonate substituent.
CuCl(OH).TMEDA (5 mol%)
OH
OH OH
10
SCHEME-V
11
[Cu(OH).TMEDA]2Cl2
B(OH)2 R1 NH R2 N N N R2
R1
12
13
14
SCHEME-VI
This catalytic coupling process of for preparing N-arylimidazoles10 is a considerable improvement over previous reports which used p-tolyllead triacetate and catalytic Cu(OAc)2 at 90oC, or arylboronic acids and more than equimolar quantities of Cu(OAc)2 and a tertiary amine (triethylamine or pyridine).
-6-
CH3O
OH O
CH3O
O O
CH3O OR
CH3
CH3 OR OR
(R = -CH2OCH3)
CH3O
CH3 O CH3O O
17 SCHEME-VII
-7-
CuCl.TMEDA, O2
C CH
(CH3)3Si
Si(CH3)3
19
SCHEME-VIII
-8-
CH3O
(R)-(+)-20 n=2, (R,R)-(+)-21 (20%) n=3, (R,R,R)-(+)-22 (30%) n=4, (R,R,R,R)-(+)-23 (10%) SCHEME-IX
-9-
(CH2)4
EtN
OCH3
CH3O
NEt
(CH2)4
24
(CH2)4 (CH2)4 O
O C2H5N NC2H5
25 SCHEME-X
-10-
N R C C N Zn
N C C H N
CuCl.TMEDA
N R C C N Zn
N C C N
CH2Cl2 , O2
N
26 [R = Si(n-C6H13)]
N
27
SCHEME-XI
Recently, Maya et al reported the synthesis of exclusively linearly conjugated phthalocyanine dimers through homo-coupling reaction of the ethynyl precursors under Glaser-Hay conditions in the presence of molecular sieves.22
-11-
SUMMARY
CuCl(OH).TMEDA is an efficient catalyst for achieving oxidative biaryl coupling reactions. The salient features are: ! ! ! ! The reagent is fairly stable, easily handled and soluble in common organic solvents. The reaction conditions are mild and many functional groups are tolerated. The requirement of catalyst can be as low as 1% (mol) and yields are generally high. The reaction is amenable for scale-up.
CONCLUSION
CuCl(OH).TMEDA is a useful addition to the existing choice of reagents which effect catalytic oxidative coupling reactions. There is ample scope for enlarging the utility domain of this reagent.
-12-
18 Anderson H.L.; Inorg. Chem., 33, 972 (1994). 19 Anderson H.L.; Martin S.J.; Bradley D.D.C., Angew. Chem. Int. Ed. Engl., 33, 655 (1994). 20 Taylor P.N.; Huuskonen J.; Rumbles G.; Aplin R.T.; Williams E.; Anderson H.L., Chem. Commun., 909 (1998). 21 Wilson G.S.; Anderson H.L., Chem. Commun., 1539 (1999). 22 Maya E.M.; Vazquez P.; Torres T.; Gobbi L.; Diederich F.; Pyo S,; Echegoyen L., J. Org. Chem., 65, 823 (2000).
ACKNOWLEDGEMENT
The authors thank Prof. K.K. Balasubramanian (Department of Chemistry, Indian Institute of Technology, Madras) for useful suggestions and constant encouragement.
Name
Di-Micron-hydroxo-bis-[N,N,N',N'-tetramethyl-ethylenediamine)copper(II)]chloride
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