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

A three-component annulation reaction and trifluoromethylation for the construction of 3-(trifluoromethyl)-4H-pyrans using β-CF₃-1,3-enynes, BrCF₂CO₂Et, and sulfoxonium ylides as readily available substrates has been developed. This metal-free process involves two C-F bond cleavages of β-CF₃-1,3-enynes and a CF₃ group generated in situ from BrCF₂CO₂Et. This method is applicable to the late-stage modification of pharmaceutically active molecules.