(R)- or (S)-Bi-2-naphthol assisted, l-proline catalyzed direct aldol reaction

Chiral Brønsted 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 Brønsted acid promoted the reaction through hydrogen bonding, which not only activated the carbonyl group but also stabilized the transition state.

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(4R)-Hydroxy-4-(1′-anthranyl)-butan-2-oneC18H16O2Ee = 86%[α]D25=-53.9 (c 0.2, CHCl3)Absolute configuration: RSource of chirality: asymmetric synthesis