Mechanistic Dichotomy: Cu(II)- and Enzyme-Catalyzed Aldol Reaction

Significance

This is a nice mechanistic follow-up comparing the Shair group’s previously reported catalytic asymmetric thioester aldol reaction to the enzymatic mechanism (M. Shair and co-workers J. Am. Chem. Soc. 2005, 127, 7284-7285). Kinetics, kinetic isotope effects (both deuterium and ¹³C), and crossover experiments were performed and it was concluded that the two systems react under distinct mechanisms. The Cu(II)-catalyzed reaction undergoes the aldol reaction followed by decarboxylation while the enzymatic version undergoes decarboxylation to form the enolate, which then acts in the aldol reaction.