Mechanically driven stainless steel-initiated activation of S–H bonds to construct disulfides

Abstract

Disulfides are important scaffolds in biologically active molecules and pharmaceuticals; however, their traditional synthesis method relies on costly precious metals, toxic solvents, oxidants, and harsh reaction conditions. Herein, we report a mechanochemical strategy enabling solvent-, oxidant-, catalyst-, and auxiliary abrasive-free construction of disulfides via stainless steel-induced S–H activation. Stainless steel nanoparticles (SS NPs) generated during ball milling facilitated efficient oxidative coupling of thiols under ambient conditions, achieving 41–99.9% yields within 30–90 minutes. The mechanistic studies confirmed the synergistic radical-mediated pathway dominated by iron species, effectively suppressing over-oxidation. This green approach eliminated environmental burdens while offering broad substrate tolerance, advancing sustainable disulfide synthesis for pharmaceutical and material applications.