Minisci-Type Reaction Enabled by Copper-Mediated Radical-Coupling: Photocatalytic C2-Selective C-H Bis(trifluoromethyl)carbinolation of Quinolines

Abstract

Herein, the C2-selective bis(trifluoromethyl)carbination of quinolines was accomplished, which is enabled by a rationally designed PCET/copper-mediated radical cross-coupling Minisci-type reaction. This synergistic strategy provides facile access to a broad range of previously inaccessible bis(trifluoromethyl)carbinolized quinolines by using readily available hexafluoroacetone hydrate instead of toxic gaseous hexafluoroacetone. The success of this transformation complements the reaction mode and extends the boundary for the classic Minisci-type reaction by surpassing the intrinsic challenge in the radical addition for the polarity-mismatched radical species with heteroarenes. Notable features of this method include operational simplicity, mild reaction conditions, excellent regioselectivity, and a broad functional group tolerance. A combination of experimental and theoretical studies was extensively conducted to investigate the reaction pathway.