康 · 学术 | Reaction of the Day No. 1209

转自：康龙化成

(Phenoxyimine)nickel-CatalyzedC(sp2)–C(sp3) 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, and Paul J. Chirik*

Department of Chemistry, PrincetonUniversity, Princeton, New Jersey 08544, United States;

Chemical Process Development, BristolMyers Squibb Company, New Brunswick, New Jersey 08903, United States;

—J. Am. Chem. Soc.,2024, 146, 14, 10124.

Recommended by Xuemei Yao_ MC3

ABSTRACT: Phenoxyimine(FI)–nickel(II)(2-tolyl)(DMAP) compounds were synthesized and evaluated as precatalysts forthe 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, thescope of the cross-coupling reaction was established and included a variety of(hetero)arylboronicacids and alkyl bromides (>50 examples, 33–97% yield). A β-hydrideelimination–reductive elimination sequence from reaction with potassium isopropoxide base, yielding a potassium (FI)nickel(0)ate, was identified as a catalystactivation pathway that is responsible for halogen atom abstraction from thealkyl bromide. A combination of NMR and EPR spectroscopies identified(FI)nickel(II)–aryl complexes as the resting state during catalysis with noevidence for long-lived organic radical or odd-electron nickel intermediates.These data establish that the radical chain is short-lived and undergoes faciletermination 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 formationwas proportional to the concentration of the (FI)nickel(II)–aryl resting statethat captures the alkyl radical for chain propagation. The proposed mechanisminvolves two key and concurrently operating catalytic cycles; the firstinvolving a nickel(I/II/III) radical propagation cycle consisting of radicalcapture at (FI)nickel(II)–aryl, C(sp2)–C(sp3) reductive elimination, bromineatom abstraction from C(sp3)–Br, and transmetalation; andthe second involving an off-cycle catalyst recovery process by slow(FI)nickel(II)–aryl → (FI)nickel(0)ate conversion for nickel(I) regeneration.

Nickel-CatalyzedC(sp2)−C(sp3) Suzuki−Miyaura Cross-Coupling

Substrate Scope

Prof.PaulJ. Chirik and co-worker havereportedthesynthesis of Phenoxyimine nickel(II) aryl complexes and shown it to be effective precatalysts forC(sp2)−C(sp3) Suzuki−Miyaura cross coupling between (hetero)aryl boronic acid nucleophiles and alkyl halideelectrophiles. The scope of the reaction is broad, the precatalysts areair-stable and compatible with aryl boronic acid nucleophiles and a host ofcommon organic functional groups, which is a distinct advantage overstate-of-the-art cobalt or iron precatalysts.These studies demonstrate that phenoxyimines area privileged class of chelates for supporting first-row transition metalcatalysts for C(sp2)−C(sp3) Suzuki−Miyaura cross coupling.

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