A Divergent Strategy for Site‐Selective Radical Disulfuration of Carboxylic Acids with Trisulfide‐1,1‐Dioxides

• Published in: Angewandte Chemie International Edition 2021-07, Vol.60 (28), p.15598-15605
• Main Authors: Wu, Zijun, Pratt, Derek A.
• Format: Article
• Language: English
• Subjects: alkyl radicals; Amides; Amino acids; Carboxylic acids; C−H functionalization; Decarboxylation; Dioxides; Direct conversion; disulfides; Divergence; homolytic substitution; photocatalysis; Selectivity; Substitution reactions; Substrates
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.202104595

The direct conversion of carboxylic acids into disulfides is described. The approach employs oxidative photocatalysis for base‐promoted decarboxylation of the substrate, which yields an alkyl radical that reacts with a trisulfide dioxide through homolytic substitution. The trisulfide dioxides are easily prepared by a newly described approach. 1°, 2°, and 3° carboxylic acids with varied substitution are good substrates, including amino acids and substrates with highly activated C−H bonds. Trisulfide dioxides are also used to achieve the γ‐C(sp3)−H disulfuration of amides through a radical relay sequence. In both reactions, the sulfonyl radical that results from substitution propagates the reaction. Factors governing the selectivity of substitution at S2 versus S3 of the trisulfide dioxides have been explored. Trisulfide‐1,1‐dioxides undergo rapid homolytic substitution with alkyl radicals. This has enabled the development of an oxidative photocatalytic approach for the direct conversion of carboxylic acids into disulfides as well as a related approach for the installation of a disulfide moiety by remote C−H functionalization.