Chemoselective Oxidation of Thiols with Oxoammonium Cations

• Published in: Journal of organic chemistry Vol. 88; no. 16; pp. 11392 - 11410
• Main Authors: Weierbach, Shayne M., Reynolds, Robert P., Stephens, Shannon M., Vlasakakis, Kostantinos V., Ritter, Ramsey T., White, Olivia M., Patel, Nishi H., Hayes, Eric C., Dunmire, Sydney, Lambert, Kyle M.
• Format: Journal Article
• Language: English
• Published: American Chemical Society 18.08.2023
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/acs.joc.2c01097

The oxidation of various aryl and aliphatic thiols with the commercially available and environmentally benign reagent Bobbitt’s salt (1) has been investigated. The reaction affords the corresponding disulfide products in good to excellent yields (71–99%) and can be accomplished in water, methanol, or acetonitrile solvent. Moreover, the process is highly chemoselective, tolerating traditionally oxidation-labile groups such as free amines and alcohols. Combined experimental and computational studies reveal that the oxidation takes place via a polar two-electron process with concomitant and unexpected deoxygenation of the oxoammonium cation through homolysis of the weak N–O bond, differing from prototypical radical-based thiol couplings. This unusual consumption of the oxidant has significant implications for the development of new nitroxide-based radical traps for probing S-centered radicals, the advancement of new electrochemical or catalytic processes involving nitroxide/oxoammonium salt redox couples, and applications to biological systems.