Angewandte
Chemie
Homogeneous Catalysis
Homo- or heterobimetallic complexes have enormous
potential to revolutionize asymmetric catalysis. They can
activate both components of a bimolecular reaction simulta-
neously,overcome entropy barriers associated with bringing
the two reagents together,minimize the energy barrier that
arises from solvent–shell rearrangements during the reaction,
and recognize prochiral faces or groups within the reagents
through predetermination of the reaction trajectory.
In Situ Formation of a Heterobimetallic Chiral
[(Salen)TiIV]/[(Salen)VV] Catalyst for the
Asymmetric Addition of TMSCNto
Benzaldehyde**
Yuri N. Belokon,* Michael North, Victor I. Maleev,
Nikolay V. Voskoboev, Margarita A. Moskalenko,
Alexander S. Peregudov, Andrey V. Dmitriev,
Nikolai S. Ikonnikov, and Henri B. Kagan*
Belokonꢀ,North and co-workers have developed an
IV
efficient catalyst based on dinuclear,chiral [{(salen)Ti
-
(m-O)}2] precatalysts for the asymmetric addition of trime-
thylsilyl cyanide to aldehydes.[7] Kinetic studies indicated that
two TiIV complexes were involved in the rate-limiting step of
this reaction.[8] Subsequently,monomeric chiral ionic [(sale-
The wide potential of molecules with multiple (multidentate)
Lewis acid sites that bind and chemically activate small
organic molecules has been recognized for some time.[1] Quite
recently,several groups made significant progress towards the
design and use of chiral homo- and heterobimetallic com-
plexes for asymmetric catalysis,with particularly important
contributions reported by Shibasaki et al.[2] and Trost et al.[3]
The former group developed an effective chiral bimetallic
catalyst based on an alkali metal/lanthanoid complex for
asymmetric Michael addition reactions,whereas the latter
group elaborated on dinuclear zinc complexes of a chiral
pentadentate ligand for asymmetric Henry and aldol con-
densation reactions. In the case of the asymmetric opening of
epoxides catalyzed by chiral [(salen)Co] complexes (salen =
N,Nꢀ-bis(salicylaldehydo)ethylenediamine),[4] the reaction
involved two separate chiral salen–metal species in the rate-
limiting step of the reaction,and subsequently,very efficient
oligomeric catalysts were developed based on this principle.[5]
It is reasonable to propose that many other established
catalysts may operate via unrecognized polymetallic inter-
mediates lying on the reaction coordinate; a large number of
nonlinear effects observed in asymmetric catalytic reactions
seem to indicate such a possibility.[6]
n)VV(O)]+EtOSO3 complexes were shown to be even more
ꢀ
enantioselective in the same reaction,although the rate was
almost two orders of magnitude slower than that with the
analogous TiIV catalysts.[9] Kinetic studies indicated that two
cationic VV complexes were again involved in the rate-
limiting step of the reaction.[9a]
Based on these results,we thought that a mixed-metal
complex derived from TiIV and VV might form an even better
catalyst,which would exhibit the asymmetric induction
associated with VV complexes and the faster rates of reaction
associated with TiIV catalysts. Furthermore,we considered
complexes derived from enantiomeric ligands to study the
interactions between the complexes,as mixed species could
give rise to anomalies with respect to the independent metal
catalysts. Herein,we report the performance of mixtures of
[{((R,R)-salen)TiIV(m-O)}2] or [{((S,S)-salen)TiIV(m-O)}2],and
ionic [((S,S)-salen)VV(O)]+EtOSO3
or [((R,R)-salen)-
ꢀ
VV(O)]+EtOSO3ꢀ in the asymmetric addition of trimethylsilyl
cyanide to benzaldehyde at different molar ratios of
Ti/V.
The [{((R,R)-salen)TiIV(m-O)}2] 1a (or [{((S,S)-salen)-
TiIV(m-O)}2], 1b),and [(( R,R)-salen)VV(O)]+EtOSO3 2a
ꢀ
(or [((S,S)-salen)VV(O)]+EtOSO3ꢀ, 2b) catalysts (Scheme 1)
were synthesized as described previously.[9b] The asymmetric
addition of trimethylsilyl cyanide to benzaldehyde
(Scheme 1) was catalyzed by 1a or 2a to give (S)-O-
(trimethylsilyl)mandelonitrile (80 and 90% ee,respec-
tively).[7,9] Use of 1b or 2b similarly led to (R)-O-(trimethyl-
silyl)mandelonitrile.
[*] Prof. Dr. Y. N. Belokon, Dr. V. I. Maleev, Dr. M. A. Moskalenko,
Prof. Dr. A. S. Peregudov, A. V. Dmitriev, Dr. N. S. Ikonnikov
A. N. Nesmeyanov Institute of Organo-Element Compounds
Russian Academyof Sciences
Vavilov 28, 119991 Moscow (Russian Federation)
Fax: (+95)135-5085
E-mail: yubel@ineos.ac.ru
Use of a mixture of 1b and 2a as a catalyst in the reaction
at a 1:1 molar ratio of Ti/V may be expected to result in:
1) Completely racemic product if a fast exchange of ligands
between the two metal centers takes place. 2) Almost
exclusive (R)-mandelonitrile formation at this ratio (and up
to a 1:4 molar ratio of Ti/V) if 1b and 2a were independent.
Above a 1:4 molar ratio of Ti/V,the enantiomeric excess of
the product would decrease and at a 1:11 ratio of Ti/V,
racemic product would be formed (see Figure 1,curve a).
Accordingly,exclusive formation of ( S)-mandelonitrile would
be observed if a 1:1 mixture of 1a and 2b were used as a
catalyst. 3) Formation of a mixed complex with novel catalytic
properties,which could not be predicted in advance.
Prof. Dr. H. B. Kagan
Institut de Chimie MolØculaire et des MatØriaux d’Orsay,
Laboratoire de Synthse AsymØtrique (UMR 8075)
UniversitØ de Paris-Sud
Bâtiment 420, 91405 OrsayCedex (France)
Fax: (+33)169-157-895
E-mail: kagan@icmo.u-psud.fr
Prof. M. North
Department of Chemistry, King’s College
Strand, WC2R 2LS London (UK)
N. V. Voskoboev
Higher Chemical College, Russian Academyof Sciences
Miusskaya pl. 9, 125047 Moscow (Russian Federation)
[**] We thank the Russian Foundation for Basic Research (Project
Nos. 02-03-32091 and 03-03-06461) and the EU (Descartes Prize
research fund) for financial support of this work. TMSCN=trime-
thylsilyl cyanide.
As the [(salen)Ti] catalyst is almost two orders of
magnitude faster than the [(salen)V]+ catalyst,one could
expect the Ti catalyst to determine the absolute configuration
Angew. Chem. Int. Ed. 2004, 43, 4085 –4089
DOI: 10.1002/anie.200454031
ꢀ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4085