Difluorocarbene-Enabled Trifluoromethylation and Cyclization for the Synthesis of 3-(Trifluoromethyl)-4H-pyrans

Abstract

A three-component annulation reaction and trifluoromethylation for the construction of 3-(trifluoromethyl)-4H-pyrans using β-CF 3 -1,3-enynes, BrCF 2 CO 2 Et, and sulfoxonium ylides as readily available substrates has been developed. This metal-free process involves two C−F bond cleavages of β-CF 3 -1,3-enynes and a CF 3 group generated in situ from BrCF 2 CO 2 Et. This method is applicable to the late-stage modification of pharmaceutically active molecules.