Zinc-Promoted Reductive Disulfuration of Sulfonated Alcohols with Glycosyl Thiosulfonates To Access Unsymmetrical Glycosyl Alkyl Disulfides

Abstract Given the abundance of alcohol feedstocks and the significance of glycosyl disulfides as glycomimetics in drug design, we herein report a Zn-mediated reductive disulfuration of alkyl sulfonates with glycosyl thiosulfonates or N-(thioglycoside)succinimides as sulfurating reagents, providing an unprecedented and efficient route to diverse unsymmetrical glycosyl alkyl disulfides over the corresponding glycosyl sulfides. Notably, this method proceeds under mild reaction conditions without requiring any exogenous ligands or bases, featuring a broad substrate scope, excellent functional group compatibility, and high yields. Furthermore, the practicality of this method is demonstrated by its suitability for large-scale synthesis and its potential for late-stage glycodiversification of complex bioactive molecules.