Poor enantioselectivity of the direct aldol reaction catalyzed by (S,S)-proline dipeptide:: A density functional study

Density functional theory calculations were performed to study the stereo-controlling step of the direct aldol reaction between acetone and 4-nitrobenzaldehyde catalyzed by (S,S)-proline dipeptide. Four transition state structures have been determined using B3LYP functional with the 6-31G* basis set, corresponding to the anti and syn arrangements of the methylene moiety with respect to the carbonyl group in enamine intermediate, and to the si and re attacks to the aldehyde carbonyl carbon, respectively. Solvent effects of DMSO on the stereo-controlling step were investigated with Onsager model. The energy results of the transition states reveal the origin of poor enantioselectivity for the reaction. (C) 2007 Wiley Periodicals, Inc.