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

Abstract

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.