Sulfur(VI)-containing functional groups, such as sulfonamides, sulfinates and sulfonyl fluorides, are ubiquitous in pharmaceuticals, where they confer unique physicochemical properties that enhance metabolic stability, solubility and bioactivity across diverse therapeutic areas. Despite their prevalence, synthetic access to alkyl-sulfur(VI) derivatives remains fragmented, often requiring multi-step sequences from scarce precursors or harsh conditions that limit functional-group tolerance and scalability. Here we report a unified platform that enables divergent synthesis of alkyl-sulfur(VI) compounds from abundant, unactivated feedstocks including ketones, alcohols, amines and other structurally complex molecules. Central to this method is the use of alkyl hydrazines (or their sulfonylated derivatives) as practical radical precursors. Upon simple thermal activation, these hydrazines undergo efficient homolysis to generate alkyl radicals under mild and operationally simple conditions, without the need for photocatalysts, expensive metals or reagents and elaborate setups. Over 70 sulfur-containing molecules are synthesized, including direct functionalization of complex natural products without resorting to protecting group chemistry.

Wang, S., Cagan, D.A., Tsien, J. et al. Highly chemoselective access to alkyl-sulfur compounds via N₂ extrusion of alkyl hydrazines.
Nat. Chem. (2026). https://doi.org/10.1038/s41557-026-02212-8

https://doi.org/10.1038/s41557-026-02212-8