Nickel catalyzed C–S cross coupling of sterically hindered substrates enabled by flexible bidentate phosphines

Due to the smaller size of nickel compared to palladium, the C–S cross-coupling of sterically challenging aryl electrophiles with alkyl thiols under nickel catalysis remained elusive. Herein, we report the nickel-catalyzed cross-coupling of alkyl thiols with aryl triflates bearing functional groups in ortho -position relative to the leaving group using Ni(cod) 2 /DPEphos (L1) or dppbz (L2) as the catalytic system. For substrates featuring non-coordinating ortho -substituents, the reaction operates under mild conditions using L1, while for electrophiles bearing coordinating groups, the ligand L2 and elevated temperatures are required. The synthetic utility could be demonstrated on numerous examples, including biologically relevant compounds, and on larger scale. Instead of Ni(cod) 2 , more cost-efficient Ni(OAc) 2 can also be employed in the presence of zinc as reductant. Furthermore, insights into the reaction mechanism were obtained by competition experiments, isolation of organometallic intermediates and computations.