General Method for Selective C(sp2)–H Trifluoromethylation of Enamides via Visible Light Dual Photoredox/Nickel Catalysis

Abstract

Fluoroalkylated enamides are pivotal intermediates and drug-forming scaffolds in organic synthesis. Herein, we report a visible-light-promoted photoredox/nickel protocol for the (E)-β-trifluoromethylation of N-vinyl secondary enamides using sodium trifluoromethanesulfinate. This newly developed protocol allows for facile and divergent access to various stereodefined β-CF3 in high yields and excellent stereoselectivity from readily available starting materials. We also report a one-step synthesis of the pyrimidine derivative trifluorothymine, the purine nucleoside analogue 5-(trifluoromethyl)uridine, and the antiviral drug trifluridine to demonstrate synthetic utility. Mechanistic investigations, including radical-trapping experiments and control experiments, reveal the radical nature of the reaction.