Synthesis of Difluoromethyl Thioethers from Difluoromethyl Trimethylsilane and Organothiocyanates Generated In Situ

A copper-CF2 H complex generated in situ from copper thiocyanate and TMSCF2 H smoothly converts organothiocyanates into valuable difluoromethyl thioethers. This reaction step can be combined with several thiocyanation methods to one-pot protocols, allowing late-stage difluoromethylthiolations of widely available alkyl halides and arenediazonium salts. This strategy enables the introduction of difluoromethylthio groups-a largely unexplored substituent with highly promising properties-into drug-like molecules.