Theoretical Investigation on Asymmetric Cyanation of Activated Olefins with Ethyl Cyanoformate Catalyzed by Titanium Catalyst

초록

The mechanism and the origin of selectivity of asymmetric cyanation of activated olefins with ethyl cyanoformate catalyzed by a Ti(IV)-complex catalyst have been investigated by DFT and ONIOM methods. The calculations indicate that the reaction proceeds through a dual activation mechanism, in which TiIV acts as Lewis acid to activate the olefin substrates while the tertiary amine in cinchona alkaloid works as a Lewis base to promote the activation and isomerization of HCN. The overall reaction involves two stages: (i) the formation of C-C bond; (ii) the transfer of H atom and the regeneration of catalyst. The first step is predicted to be the rate-determining step and selectivity-controlling step with an energy barrier of 7.9 kcal mol-1. The large steric hindrance from 3,3’-biphenol, combining with the quinoline fragment of cinchona alkaloid and the orientation of hydrogen bonding of iPrOH, play a key role in controlling the stereoselectivity, which is in good agreement with experimental observations.