biostudies-literatureBai ZNational Natural Science Foundation of ChinaNational Natural Science Foundation of China (National Science Foundation of China)6445https://www.ebi.ac.uk/biostudies/studies/S-EPMC9616856biostudies-literatureUnknown13(1)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 oNature communicationsSynthesis of N-acyl sulfenamides via copper catalysis and their use as S-sulfenylating reagents of thiols.PMC961685621901127Hu YHe GYang PChen GChu XBai ZWang HZhu SfalseSynthesis 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 o2022-01-01T00:00:00Z2022 Oct2025-04-04T09:42:21.96Z2025-04-04T09:42:21.96ZS-EPMC96168563630740810.1038/s41467-022-34223-7