A novel and highly electrophilic difluoromethylthiolating reagent, N-(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.
Fu et al. (2026) studied this question.