Enantiotopic-group differentiation. Catalytic asymmetric ring-opening of prochiral cyclic acid anhydrides with methanol, using cinchona alkaloids

Abstract

Asymmetric ring-opening of prochiral acid anhydrides (1) with methanol has been achieved by a catalytic quantity of cinchona alkaloids (2). The product, the optically active half-ester (3), has been subjected to functional-group-selective reduction to give the optically active lactones (5). The reaction rate of the ring-opening and the extent of selectivity are dependent on the nature of the reaction medium, the polarity of solvent, and substrate concentration. By selecting the reaction conditions, an enantiometric excess of up to 70% has been obtained. The kinetic isotope effect and other mechanistic investigations suggest that the reaction proceeds via general-base catalysis by the quinuclidine moiety of the base (2), and that the relative configuration of the C-9 hydroxy group with respect to the C-8 quinuclidine amino function determines the selectivity of the reaction.