Metal‐Free and NBS‐Mediated Direct Thiol‐Disulfide Exchange Reaction to Access Unsymmetrical Disulfides

• Published in: European journal of organic chemistry Vol. 26; no. 30
• Main Authors: Yang, Ke, Hu, Qingyue, Li, Qin, Liu, Junxiang, Li, Zheng‐Yi, Li, Bijin, Sun, Xiaoqiang
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 07.08.2023; Wiley Subscription Services, Inc
• Subjects: Amino acids; Chemistry; Chemistry, Organic; Disulfides; Functional groups; NBS; Physical Sciences; Room temperature; Science & Technology; Substrates; synthetic methods; thiols; disulfides; DESIGN; EFFICIENT SYNTHESIS; GENERATION; thiols; C-H FUNCTIONALIZATION; MICROWAVE-ASSISTED SYNTHESIS; synthetic methods; NBS; DISULFANES; FREE OXIDATION
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.202300394

A metal‐free and N‐Bromosuccinimide (NBS)‐mediated direct thiol‐disulfide exchange reaction at room temperature is developed. A variety of unsymmetrical disulfides have been prepared with good to excellent yields. Efficient late‐stage modification of amino acids and drugs demonstrates the utility of this strategy. In addition, easy to operate, broad substrate scope and good functional group tolerance further demonstrate that this reaction provides an essential complementary route to access unsymmetrical disulfides. A novel NBS‐mediated direct thiol‐disulfide exchange reaction has been described for the construction of various unsymmetrical disulfides at room temperature under metal‐free conditions. More than 30 examples of unsymmetrical disulfides were isolated in good yields (up to 93 %). Captopril, an angiotensin‐converting enzyme inhibitor, was able to form the corresponding unsymmetrical disulfide in 61 % yield.