(Phenoxyimine)nickel-Catalyzed C(sp<sup>2</sup>)–C(sp<sup>3</sup>) Suzuki–Miyaura Cross-Coupling: Evidence for a Recovering Radical Chain Mechanism
L. Reginald Mills, Eric M. Simmons, Heejun Lee, Eva Nester, Junho Kim, Steven R. Wisniewski, Matthew V. Pecoraro, Paul J. Chirik
Abstract
Phenoxyimine (FI)–nickel(II)(2-tolyl)(DMAP) compounds were synthesized and evaluated as precatalysts for the C(sp 2 )–C(sp 3 ) Suzuki–Miyaura cross coupling of (hetero)arylboronic acids with alkyl bromides. With 5 mol % of the optimal (Me OMe FI)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(sp 2 )–C(sp 3 ) 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(sp 2 )–C(sp 3 ) reductive elimination, bromine atom abstraction from C(sp 3 )–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.