Nickel-Catalyzed Deoxygenative Disulfuration of Alcohols to Access Unsymmetrical Disulfides

Abstract

Given the abundance of alcohol feedstocks and the significance of disulfides, we herein report a nickel-catalyzed direct deoxygenative disulfuration of alcohols with trisulfide dioxides to access a wide range of disulfide molecules without the cumbersome decoration of coupling partners. The use of readily available dicyclohexylcarbodiimide to form transient isoureas provides the activation of the high bond dissociation energy of the C−O bond, which facilitates the straightforward conversion of nonderivatized alcohols to forge a C−SS bond. Notably, this method obviates a preactivation multistep procedure and provides a catalytic turnover under exogenous ligand and base-free conditions, featuring a broad substrate scope and functional group compatibility. It thus offers a robust alternative to existing methods for the precise construction of versatile disulfide compounds from more abundant and commercially available substrates. The synthetic utility of the method was further showcased by successful gram-scale experiments and disulfuration of structurally complex pharmaceuticals.