Acetate Facilitated Nickel Catalyzed Coupling of Aryl Chlorides and Alkyl Thiols

We report a mild, fast, and convenient catalytic system for the coupling of aryl chlorides with primary, secondary, as well as previously challenging tertiary alkyl thiols using an air-stable nickel(II) precatayst in combination with the low-cost base potassium acetate at room temperature. This catalytic system tolerates a variety of functional groups and enables the generation of thioethers for a wide range of substrates, including pharmaceutical compounds in excellent yields. Chemoselective functionalization of disubstituted substrates was demonstrated. Kinetic and NMR studies, as well as DFT computations support a Ni(0)/Ni(II) catalytic cycle and identify the oxidative addition product as the resting state. Acetate coordination and subsequent acetate facilitated formation of a thiolate complex via internal deprotonation play a key role in the catalytic cycle.

Automated summary

We present a catalytic system that allows for mild and fast coupling of aryl chlorides with primary, secondary, and previously challenging tertiary alkyl thiols using an air-stable nickel(II) precatayst in combination with cost-effective potassium acetate as a base at room temperature. This system exhibits excellent tolerance towards various functional groups and yields thioethers in high yields, including pharmaceutical compounds. The chemoselective functionalization of disubstituted substrates is successfully demonstrated.