<i>N</i> -(Difluoromethylthio)saccharin: Design, Synthesis, and Applications in Electrophilic Difluoromethylthiolation of Alkynes for the Construction of 4-Difluoromethylthiolated Isoxazoles

A novel and highly electrophilic difluoromethylthiolating reagent, <i>N</i>-(difluoromethylthio)saccharin, which is easily synthesized from BnSCF₂H and the silver salt of saccharin, was developed. With this reagent, we disclose a practical and straightforward approach to access 4-difluoromethylthiolated isoxazoles via direct oxidifluoromethylthiolation of alkynes under mild reaction conditions. This protocol exhibits a broad substrate scope and good functional group compatibility and can be applied to late-stage difluoromethylthiolation of alkynes derived from natural products and pharmaceuticals. Mechanistic studies revealed that the reaction occurred via an electrophilic reaction pathway.