Copper-catalyzed enantioselective synthesis of γ-butenolides via radical diversification of allenoic acid.

Han, Bingxu; Nie, Zaicheng; Ye, Changqing; Bao, Hongli · Nat Commun · 2025

basic_science · Level V

Where this comes from

Abstract

Chiral γ-butenolides, which are widely prevalent in natural products and pharmaceuticals, necessitate synthetic methods that precisely control both stereochemistry and substituent diversity. In this study, we report a Cu/PyBim-catalyzed asymmetric lactonization of 2,3-allenoic acids initiated by sulfonyl or phosphonyl radicals. This strategy facilitates the direct construction of enantioenriched γ-butenolides featuring modular endocyclic double bond substituents, thereby circumventing the traditional reliance on prefunctionalized substrates. Synthetic applications of the obtained chiral γ-butenolide are emphasized and mechanistic experiments are investigated.