(Phenoxyimine)nickel-Catalyzed C(sp2)–C(sp3) Suzuki–Miyaura Cross-Coupling: Evidence for a Recovering Radical Chain Mechanism

Phenoxyimine (FI)–nickel­(II)­(2-tolyl)­(DMAP) compounds were synthesized and evaluated as precatalysts for the C­(sp2)–C­(sp3) Suzuki–Miyaura cross coupling of (hetero)­arylboronic acids with alkyl bromides. With 5 mol % of the optimal (MeOMeFI)­Ni­(Aryl)­(DMAP) precatalyst, the scope of the cross-coupling reaction was established and included a variety of (hetero)­arylboronic acids and alkyl bromides (>50 examples, 33–97% yield). A β-hydride elimination–reductive elimination sequence from reaction with potassium isopropoxide base, yielding a potassium (FI)­nickel(0)­ate, was identified as a catalyst activation pathway that is responsible for halogen atom abstraction from the alkyl bromide. A combination of NMR and EPR spectroscopies identified (FI)­nickel­(II)–aryl complexes as the resting state during catalysis with no evidence for long-lived organic radical or odd-electron nickel intermediates. These data establish that the radical chain is short-lived and undergoes facile termination and also support a “recovering radical chain” process whereby the (FI)­nickel­(II)–aryl compound continually (re)­initiates the radical chain. Kinetic studies established that the rate of C­(sp2)–C­(sp3) product formation was proportional to the concentration of the (FI)­nickel­(II)–aryl resting state that captures the alkyl radical for chain propagation. The proposed mechanism involves two key and concurrently operating catalytic cycles; the first involving a nickel­(I/II/III) radical propagation cycle consisting of radical capture at (FI)­nickel­(II)–aryl, C­(sp2)–C­(sp3) reductive elimination, bromine atom abstraction from C­(sp3)–Br, and transmetalation; and the second involving an off-cycle catalyst recovery process by slow (FI)­nickel­(II)–aryl → (FI)­nickel(0)­ate conversion for nickel­(I) regeneration.