Photoinduced regio- and stereoselective C(sp2)–H fluoromethylthiolation of enamides

Abstract

Vinyl fluoromethyl thioethers are widely employed as pivotal intermediates in organic synthesis and deemed as promising scaffolds in drug candidates. Herein, we report a general and concise strategy for the stereoselective fluoromethylthiolation of enamides, enabling the modular assembly of vinyl di-/trifluoromethyl thioethers from bench-stable fluoromethylthiolating reagents. This mild protocol exhibits broad functional group compatibility, as demonstrated by over 40 examples, including enamides derived from bioactive molecules. Furthermore, the utility of this method is highlighted through the late-stage modification of the approved probenecid drug and a series of synthetic applications. Mechanistic investigations, including control experiments, Stern–Volmer quenching, and light on–off experiments, elucidate the photoredox radical reaction pathway.