Theoretical Investigation on the Mechanism of 1,4-Michael Additions of Malononitrile to Unsaturated Aryl Ketones Catalyzed by Cinchona Alkaloid

초록

The mechanism of Michael addition of malononitrile to cinnamylideneacetophenones catalyzed by cinchona organocatalysts was investigated at the ONIOM(B3LYP/ 6-31++G**:HF/STO-3G) level. The computational results indicate that reaction proceeds through a dual activation mechanism, in which ketone substrates could be activated by generating reactive iminium ion intermediates through primary amine group of cinchona catalysts in the presence of TFA. The tertiary amine in quinidine could work as a Lewis base to promote the activation of malononitrile and deprotonation. The overall reaction involves three stages: (i) the formation of iminium ion intermediates; (ii) the addition of iminium ion to malononitrile; (iii) the regeneration of catalyst by hydrolysis. The steric repulsion between the phenyl group attached to the carbonyl group in the ketone and the quinuclidine ring of cinchona alkaloid plays an important role for the control of stereoselectivity. These results are in agreement with experimental observations.