Theoretical elucidation on the regio-, diastereo-, and enantio-selectivities of chiral primary-tertiary diamine catalyst for asymmetric direct aldol reactions of aliphatic ketones

J Phys Chem A. 2012 Jul 5;116(26):7082-8. doi: 10.1021/jp2124873. Epub 2012 Jun 21.

Abstract

The asymmetric direct aldol reactions of aliphatic ketones (acetone, butanone, and cyclohexanone) with 4-nitrobenzaldehyde catalyzed by a chiral primary-tertiary diamine catalyst (trans-N,N-dimethyl diaminocyclohexane) have been investigated by performing density functional theory calculations to rationalize the experimentally observed stereoselectivities. Focused on the crucial C-C bond-forming steps, we located several low-lying transition states and predicted their relative stabilities. The calculated results demonstrate that the catalytic direct aldol reactions of acetone favors the (S)-enantiomer and that butanone prefers the branched syn-selective product, while cyclohexanone yields predominantly the opposite anti-selective product. The theoretical results are in good agreement with the experimental findings and provide a reasonable explanation for the high enantioselectivity and diastereoselectivity, as well as regioselectivity, of the aldol reactions under consideration.