Kinetic analysis of transmetalation at prototypical Nickel(II) catalyst species: rates, mechanisms, and implications for catalysis

Nickel-catalyzed cross-coupling reactions are of increasing importance in chemical synthesis. However, rate data for transmetalation at Ni^(II) is limited due to the difficulty of analyzing this step, hindering a priori reaction design. To address this limitation, a user-friendly method for analyzing transmetalation at Ni^(II) using NMR spectroscopy is reported. This approach is underpinned by the generation of an unsaturated coupling product that coordinates to Ni⁽⁰⁾, preventing comproportionation with remaining Ni^(II) and the generation of problematic Ni^(I) side products. This methodology was used to obtain rate data for transmetalation at 18 Ni^(II) complexes. Significant variation in the rate constant (k_obs) was observed, spanning at least 5 orders of magnitude. The most important factor in influencing k_obs was ligand choice, with weakly coordinating, monodentate ligands generally affording larger rate constants. The choice of halide (Cl, Br, I) had comparatively little effect, though the use of OTs and OTf resulted in modest rate enhancements. The mechanism of transmetalation at two representative complexes was examined through kinetic and computational studies, revealing differences in the rate-determining step. The foundational insight on transmetalation at Ni^(II) provided through the kinetic studies allowed guiding principles for reaction design to be developed.