Mechanistic Investigations of Phenoxyimine–Cobalt(II)-Catalyzed C(sp2)–C(sp3) Suzuki–Miyaura Cross-Coupling

The mechanism of phenoxyimine (FI)-cobalt-catalyzed C(sp²)-C(sp³) Suzuki-Miyaura cross-coupling was studied using a combination of kinetic measurements and catalytic and stoichiometric experiments. A series of dimeric (FI)cobalt(II) bromide complexes, [(4-CF₃PhFI)CoBr]₂, [(4-OMePhFI)CoBr]₂, and [(2,6-diⁱPrPhFI)CoBr]₂, were isolated and characterized by ¹H and ¹⁹F NMR spectroscopies, solution and solid-state magnetic susceptibility, electron paramagnetic resonance (EPR) spectroscopy, X-ray crystallography, and diffusion-ordered NMR spectroscopy (DOSY). One complex, [(4-CF₃PhFI)CoBr]₂, was explored as a single-component precatalyst for C(sp²)-C(sp³) Suzuki-Miyaura cross-coupling. Addition of potassium methoxide to [(4-CF₃PhFI)CoBr]₂ generated the corresponding (FI)cobalt(II) methoxide complex as determined by ¹H and ¹⁹F NMR and EPR spectroscopies. These spectroscopic signatures were used to identify this compound as the resting state during catalytic C(sp²)-C(sp³) coupling. Variable time normalization analysis (VTNA) of in situ catalytic ¹⁹F NMR spectroscopic data was used to establish an experimental rate law that was first-order in a (FI)cobalt(II) precatalyst, zeroth-order in the alkyl halide, and first-order in an activated potassium methoxide-aryl boronate complex. These findings are consistent with turnover-limiting transmetalation that occurs prior to activation of the alkyl bromide electrophile. The involvement of boronate intermediates in transmetalation was corroborated by Hammett studies of electronically differentiated aryl boronic esters. Together, a cobalt(II)/cobalt(III) catalytic cycle was proposed that proceeds through a "boronate"-type mechanism.