9.29 – Enantioselective Synthesis

Computational chemistry can help in the design of more efficient processes for transition metal-catalyzed asymmetric synthesis. The basis for enantioselectivity is the energy difference between transition states leading to R and S products, and this can be estimated by standard methods, often based in density functional theory (DFT). Special attention has to be paid to mechanistic nuances, which are illustrated by selected examples, and to conformational search techniques, that are briefly reviewed. Although not directly related to energy profiles, the application of molecular descriptors to enantioselectivity is briefly discussed. The main part of the contribution consists of the presentation of the results obtained by different authors on the computational study of enantioselective catalysis. Many of the topics chosen have an important practical impact, but the main reason for their selection has been the diversity of problems and methods. Computational results on enantioselectivity for the following processes are discussed: rhodium-catalyzed hydrogenation, osmium-catalyzed dihydroxylation, zinc-catalyzed alkylation, copper-catalyzed cyclopropanation, and vanadium-catalyzed sulfoxidation.