N -(Difluoromethylthio)saccharin: Design, Synthesis, and Applications in Electrophilic Difluoromethylthiolation of Alkynes for the Construction of 4-Difluoromethylthiolated Isoxazoles
Abstract
A novel and highly electrophilic difluoromethylthiolating reagent, N -(difluoromethylthio)saccharin, which is easily synthesized from BnSCF 2 H 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.
Fields of Study & Subjects
Fluorine in Organic Chemistry
Sulfur-Based Synthesis Techniques
Synthesis and Characterization of Pyrroles
Publication details
- Journal / source
- The Journal of Organic Chemistry
- Publisher
- American Chemical Society (ACS)
- Volume
- 91
- Issue
- 14
- Pages
- 5091–5101
- Publication date
- 25 March 2026
- Language
- EN