Highly enantioselective trapping of carboxylic oxonium ylides with imines for direct assembly of enantioenriched γ-butenolides

Abstract

Enantioenriched γ-butenolides are valuable structural cores in many pharmaceuticals and natural products, but their direct and catalytically asymmetric assembly remains rare. Here, we report an efficient, atom-economic synthetic strategy for enantioenriched γ-butenolides via a unique enantioselective reaction of cyclopropene carboxylic acids with imines under the synergistic catalysis of Rh2(esp)2/ chiral Brønsted acid system. The reaction involved trapping of carboxylic oxonium ylides, generated from cyclopropene carboxylic acids, which presented as the first asymmetric trapping reactive intermediate in the process. Subsequently, enantioenriched γ-butenolide derivatives were obtained in good-to-high yields (55-94%) with excellent stereoselectivities (up to >95:5 dr and up to 98:2 er) under mild conditions.