Synergistic catalytic synthesis of chiral γ-butenolides by trapping carboxylic oxonium ylides with enones and isatins

Abstract

Enantioenriched γ-butenolides constitute the structural core of many natural products and biologically active molecules, but their direct and atom-economical asymmetric assembly from simple starting materials remains quite limited. Here, we describe a facile and atom-efficient synthesis of enantioenriched α-aryl-γ-butenolides from cyclopropenyl carboxylic acid and electrondeficient olefins or isatins. The reaction proceeds via carboxylic acid insertion of carbenoid initiated by an achiral rhodium salt, followed by chiral Lewis acid-mediated enantioselective trapping of the resulting carboxylic oxonium ylides with enones and isatins. Various enantioenriched γ-butenolides were obtained in high yields (up to 99%) with excellent stereoselectivities (up to >19:1 dr and up to 96% ee) under mild conditions by low catalyst loading (S/C = 200). The potential application of these methods was demonstrated by the gram-scale synthesis of γ-butenolides and their further transformations into other bioactive molecules.