Redox-Click Chemistry for Disulfide Formation from Thiols

The dynamic disulfide linkage plays a vital role in various biological processes as well as drugs and biomaterials. Oxidation of thiols is a widely utilized approach for disulfide synthesis; however, achieving both optimal reactivity and selectivity continues to pose a significant challenge. Here, we report the redox-click chemistry for disulfide formation from thiols by sulfonyl fluorides in both batch and flow-mode. Sulfuryl fluoride is a potent oxidant with exceptional selectivity toward thiols. This reaction's unique characteristics satisfy click chemistry's stringent criteria with its high thermodynamic driving force, simple reaction conditions, wide scope, quantitative yields, exceptional chemoselectivity, and non-chromatographic purification process. Furthermore, the redox click chemistry's ability to joining various modular thiol units was showcased in the synthesis of symmetrical, unsymmetrical and cyclic disulfides, poly(disulfide)s, and the in vivo disulfide cross-linked biomedical hydrogels.