Origins of enantioselectivity in catalytic asymmetric synthesis

The catalytic application of organometallic compounds in organic synthesis dates back over 50 years but their use in asymmetric synthesis is much more recent. The most favourable examples rival or exceed the power of enzymes in specific cases, and several procedures are working on a large scale in industry [1]. 

The chapter concentrates on those reactions where the mechanism is at least partly understood, for a wholly pragmatic reason speculative comments on the origin of enantioselection are hardly justified if the catalytic pathway is ill-defined. 

The resting state of the catalytic reaction is a dynamic equilibrium (much faster than the addition of Hj under enantioselective conditions) between a solvate complex (the reaction is normally run in methanol) and the two possible diastereomeric enamide complexes in which the pro-R or pro-S 

The ligand can be any of a range of chelate chiral ligands with the asymmetric centre in the backbone or exceptionally at phosphorus 

In the several cases where it has been established, the less favoured of the two enamide diastereomers has the same configuration as the preferred hydrogenation product, assuming cis-delivery of H2 via rhodium. Thus, 

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Brown, J.M., Guity, P.J. and Wienand, A. (1993) Origins of enantioselectivity in catalytic asymmetric synthesis, in Principles of Molecular Recognition (eds A.D. Buckingham, A.C. Legon and S.M. Roberts), Chapman and Hall, Glasgow. 

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