Biomimetic Oxidation of Disulfides for the Synthesis of Sulfonyl Fluorides and Primary Sulfonamides Catalyzed by Copper/Lewis Acid

Abstract

Sulfonyl fluorides are valuable “click” handles in chemical probes, owing to their unique combination of reactivity and stability. Sulfonamides, acting as bioisosteres of amides, display significant biological activity and metabolic stability. Herein, we report a practical copper/Lewis acid relay catalytic system for the synthesis of sulfonyl fluorides and primary sulfonamides via biomimetic oxidation of disulfides, mediated by bromide ion. Benefiting from the mild reaction conditions and excellent selectivity, this protocol exhibits a broad substrate scope and is applicable to the synthesis of a variety of drug-like molecules. Notably, the successful incorporation of sulfonyl fluorides and ¹⁵N-labeled sulfonamides into peptides by selectively converting disulfide units underscores the versatility and potential of this methodology.