Probing the Mode of Asymmetric Induction of Biginelli Reaction Using Proline Ester Salts

Abstract

Described are the studies on the mechanism of the asymmetric Biginelli reaction using proline ester salt catalyst to explain the enantioselectivity of the 3,4-dihydropyrimidin-2(1H)-one (DHPM) formation. Of the three possible activation methods by the catalyst that could provide asymmetric induction we revealed that the steric environment of the chiral enamine formed by the condensation of beta-keto ester with the catalyst is most responsible for the enantioselectivity. This assumption is supported by experiments with the N-methylated catalyst, and the combination sets of L- or D-proline ester catalyst with racemic or chiral BINOL-derived phosphoric acid as counter acid. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)