The twist angle approach to the stereoselectivity in reduction of ketones

Abstract

Semiempirical MO calculations show that the π* orbital of the carbonyl carbon of asymmetric ketones deviates from orthogonality. These small deviations, measured by twist angles, are used to predict the configurations of the diastereoisomeric alcohols formed on reduction of the ketones with complex metal hydrides. The method is particularly suitable for predicting the changes in stereoselectivity when the carbonyl compound is substituted. This is illustrated by a number of examples of reduction of substituted rigid polycyclic ketones. It is proposed that a nucleophile approaches a carbonyl group preferentially from the side of obtuse angle with respect to the O—C bond. The twists incorporate the electronic nature of the substitent and help to understand the steric effect. The application of the twist angle approach to other reactions is briefly mentioned.