A Sequential Umpolung/Enzymatic Dynamic Kinetic Resolution Strategy for the Synthesis of γ‐Lactones. Issue 26 (24th April 2020)

• Record Type: Journal Article
• Authors: Maskeri, Mark A.; Schrader, Malte L.; Scheidt, Karl A.
• Is Part Of: Chemistry. Volume 26:Issue 26(2020)
• Page Start: 5794
• Page End: 5798
• Publication Date: 2020-04-24
• Subjects: chemoenzymatic catalysis -- ketoreductase enzyme -- N-heterocyclic carbene catalysis -- photoredox catalysis -- sequential catalysis; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.202000747
• Languages: English
• ISSNs: 0947-6539

Abstract

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. Abstract : Value guarantee : Herein we report the development of a two‐step‐one‐pot synthesis of γ‐lactones through the unification of a robust NHC‐catalyzed Stetter reaction with a ketoreductase‐catalyzed dynamic kinetic resolution, reduction, and cyclization. The process sets two stereogenic centers and provides rapid access to densely‐functionalized privileged heterocycles.