A Sequential Umpolung/Enzymatic Dynamic Kinetic Resolution Strategy for the Synthesis of γ-Lactones

Abstract

Combining biological and small-molecule catalysts under a chemoenzymatic manifold presents a series of significant advantages to the synthetic community. We report herein the successful development of a two-step/single flask synthesis of γ-lactones through the merger of Umpolung catalysis with a ketoreductase-catalyzed dynamic kinetic resolution, reduction, and cyclization. This combined approach delivers highly enantio- and diastereoenriched heterocycles and demonstrates the feasibility of integrating NHC catalysis with enzymatic processes.

Keywords: N-heterocyclic carbene catalysis; chemoenzymatic catalysis; ketoreductase enzyme; photoredox catalysis; sequential catalysis.