Theoretical Elucidation on the Regio-, Diastereo-, and Enantio-Selectivities of Chiral Primary–Tertiary Diamine Catalyst for Asymmetric Direct Aldol Reactions of Aliphatic Ketones

The asymmetric direct aldol reactions of aliphatic ketones (acetone, butanone, and cyclohexanone) with 4-nitrobenzaldehyde catalyzed by a chiral primary–tertiary diamine catalyst (trans-<i>N</i>,<i>N</i>-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 (<i>S</i>)-enantiomer and that butanone prefers the branched <i>syn</i>-selective product, while cyclohexanone yields predominantly the opposite <i>anti</i>-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