Difluorocarbene-Enabled\nTrifluoromethylation and Cyclization\nfor the Synthesis of 3‑(Trifluoromethyl)‑4<i>H</i>‑pyrans

A three-component annulation reaction and trifluoromethylation\nfor the construction of 3-(trifluoromethyl)-4<i>H</i>-pyrans\nusing β-CF<sub>3</sub>-1,3-enynes, BrCF<sub>2</sub>CO<sub>2</sub>Et, and sulfoxonium ylides as readily available substrates has been\ndeveloped. This metal-free process involves two C–F bond cleavages\nof β-CF<sub>3</sub>-1,3-enynes and a CF<sub>3</sub> group generated <i>in situ</i> from BrCF<sub>2</sub>CO<sub>2</sub>Et. This method\nis applicable to the late-stage modification of pharmaceutically active\nmolecules.