(R)- or (S)-bi-2-naphthol assisted, L-proline catalyzed direct aldol reaction

Chiral Bronsted acids (R)- and (S)-BINOL were employed as additives in the classic L-proline catalyzed direct aldol reaction. Eighteen substrates were tested with 0.5 mol % (R)-BINOL loading and 1 mol % of (S)-BINOL loading, and the enantioselectivity was improved from 72% ee without additive to 98% ee. In the proposed transition state, the chiral Bronsted acid promoted the reaction through hydrogen bonding, which not only activated the carbonyl group but also stabilized the transition state. (c) 2006 Elsevier Ltd. All rights reserved.