Origin of Enantioselectivity in Benzotetramisole-Catalyzed Dynamic Kinetic Resolution of Azlactones

Density functional theory (DFT) calculations were performed to investigate the origins of enantioselectivity in benzotetramisole (BTM)-catalyzed dynamic kinetic resolution of azlactones. The transition states of the fast-reacting enantiomer are stabilized by electrostatic interactions between the amide carbonyl group and the acetate anion bound to the nucleophile. The chiral BTM catalyst confines the conformation of the a-carbon and the facial selectivity of the nucleophilic attack to promote such electrostatic attractions.