Synthesis of N-acyl sulfenamides via copper catalysis and their use as S-sulfenylating reagents of thiols

Sulfur-heteroatom bonds such as S-S and S-N are found in a variety of natural products and often play important roles in biological processes. Despite their widespread applications, the synthesis of sulfenamides, which feature S-N bonds that may be cleaved under mild conditions, remains underdeveloped. Here, we report a method for synthesis of N-acyl sulfenamides via copper-catalyzed nitrene-mediated S-amidation reaction of thiols with dioxazolones. This method is efficient, convenient, and broadly applicable. Moreover, the resulting N-acetyl sulfenamides are highly effective S-sulfenylation reagents for the synthesis of unsymmetrical disulfides under mild conditions. The S-sulfenylation protocol enables facile access to sterically demanding disulfides that are difficult to synthesize by other means. Sulfenamides are organosulfur reagents that feature labile S-N bonds and have potential applications in chemical synthesis. Here, the authors report the preparation of N-acyl sulfenamides via copper-catalyzed S-amidation of thiols with dioxazolones; These N-acyl sulfenamides can be used to prepare unsymmetrical disulfides via reaction with thiols.

Automated summary

This study reports a method for the synthesis of N-acyl sulfenamides via copper-catalyzed S-amidation of thiols with dioxazolones. This method is efficient, convenient, and broadly applicable. The resulting N-acetyl sulfenamides can be used as highly effective S-sulfenylation reagents and enable the synthesis of sterically demanding disulfides that are difficult to prepare by other means.