Highly Chemoselective Access to Alkyl-Sulfur Compounds via N2 Extrusion of Alkyl Hydrazines

Sulfur(VI)-containing functional groups, such as sulfonamides, sulfinates, and sulfonyl fluorides, are ubiquitous in pharmaceuticals, conferring unique physicochemical properties that enhance metabolic stability, solubility, and bioactivity across diverse therapeutic areas. Despite their prevalence-appearing in over 300 FDA-approved drugs and rising to 20% of new approvals in 2024-synthetic access to alkyl S(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 S(VI) 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, readily prepared via conventional transformations from these feedstocks. Upon simple thermal activation, these hydrazines undergo efficient homolysis to generate alkyl radicals under exceptionally mild and operationally simple conditions, without the need for photocatalysts, expensive metals or reagents, and elaborate setups. The remarkable chemoselectivity of these transformations is exemplified through the synthesis of over 70 sulfur-containing molecules, including direct functionalization of complex natural products without resorting to protecting group chemistry.