Nickel-Catalyzed C–S Cross-Coupling Enhanced by Mechanochemistry

We report a nickel-catalyzed cross-coupling between aryl (pseudo)halides and thiols under mechanochemical conditions. The reaction tolerated both alkyl and aryl thiols and required a lower catalyst loading than the same catalyst under homogeneous conditions (2.5 vs 5 mol %). Moreover, the reaction can be set up under air, greatly simplifying and shortening the reaction setup. Notably, trialkyl amines proved most efficient as a base under mechanochemical conditions. This class of bases has been rarely used in C–S cross-couplings before. The applicability of this system was demonstrated on numerous examples, including compounds relevant to materials science and pharmaceuticals. While mechanistic studies revealed that the reaction is mainly driven by thermal energy produced by the mixer mill, mechanical force appeared to accelerate the reaction, enabling otherwise unfeasible substrates. Using neat NMR and DSC techniques, it could be shown that the catalyst is initially deactivated by excess thiol, forming a mixture of nickel(hydrido)(thiolate) species. Upon reduction by zinc, the active catalyst is formed, able to engage in a Ni(0)/Ni(II) catalytic cycle.