Mechanistic Insights from Reaction Progress Kinetic Analysis of the Polypeptide-Catalyzed Epoxidation of Chalcone

Reaction progress kinetic analysis of the poly(l)-leucine (PLL)-catalyzed epoxidation of substituted chalcones 1a−1c helps to refine an earlier mechanistic proposal by demonstrating that the reaction proceeds via reversible addition of chalcone to a PLL-bound hydroperoxide, forming a fleeting hydroperoxy enolate species. Observation of an induction period offers an alternate rationalization for effects formerly attributed to substrate inhibition. Previous clues about the origin of enantioselectivity in this system are supported by this work.