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.