Mechanisms of Nickel-Catalyzed Coupling Reactions and Applications in Alkene Functionalization

Abstract

Conspectus Nickel complexes exhibit distinct properties from other group 10 metals, including a small nuclear radius, high paring energy, low electronegativity, and low redox potentials. These properties enable Ni catalysts to accommodate and stabilize paramagnetic intermediates, access radical pathways, and undergo slow β-H elimination. Our research program investigates how each of these fundamental attributes impact the catalytic properties of Ni, in particular in the context of alkene functionalization. Alkenes are versatile functional groups, but stereoselective carbofunctionalization reactions of alkenes have been underdeveloped. This challenge may derive from the difficulty of controlling selectivity via traditional two-electron migratory insertion pathways. Ni catalysts could lead to different stereodetermining steps via radical mechanisms, allowing access to molecular scaffolds that are otherwise difficult to prepare. For example, an asymmetric alkene diarylation reaction developed by our group relies upon the radical properties of Ni­(III) intermediates to control the enantioselectivity and give access to a library of chiral α,α,β-triarylethane molecules with biological activity. Mechanistic studies on a two-component reductive 1,2-difunctionalization reaction have shed light on the origin of the cross-electrophile selectivity, as C sp2 and C sp3 electrophiles are independently activated at Ni­(I) via two-electron and radical pathways, respectively. Catalyst reduction has been identified to be the turnover-limiting step in this system. A closer investigation of the radical formation step using a (Xantphos)­Ni­(I)Ar model complex reveals that Ni­(I) initiates radical formation via a concerted halogen-abstraction pathway. The low redox potentials of Ni have allowed us to develop a reductive, trans-selective diene cyclization, wherein a classic two-electron mechanism operates on a Ni­(I)/Ni­(III) platform, accounting for the chemo- and stereoselectivity. This reaction has found applications in the efficient synthesis of pharmaceutically relevant molecules, such as 3,4-dimethylgababutin. The tendency of Ni to undergo one-electron redox processes prompted us to explore dinuclear Ni-mediated bond formations. These studies provide insight into Ni–Ni bonding and how two metal centers react cooperatively to promote C–C, C–X, and N–N bond forming reductive elimination. Finally, isolation of β-agostic Ni and Pd complexes has allowed for X-ray and neutron diffraction characterization of these highly reactive molecules. The bonding parameters serve as unambiguous evidence for β-agostic interactions and help rationalize the slower β-H elimination at Ni relative to Pd. Overall, our research has elucidated the fundamental properties of Ni complexes in several contexts. Greater mechanistic understanding facilitates catalyst design and helps rationalize the reactivity and selectivity in Ni-catalyzed alkene functionalization reactions.

NiH-Catalyzed Reductive Hydrocarbonation of Enol Esters and Ethers

“…Next, we performed a low-temperature (10 K) X-band electron paramagnetic resonance (EPR) experiment to analyze the reaction mixture after different reaction times. [51][52][53] The [54][55][56][57] Although we obtained some convincing experimental data, it is still difficult to clearly understand the reaction mechanism. In particular, we could not clarify the fundamentals of the change in valence states of nickel during the reaction process.…”

Nickel‐CatalyzedDicarbofunctionalization of Alkenes†

“…On the other hand, the renaissance of nickel catalysis provides extensive chemical space in cross‐coupling reactions recently, [ 27‐35 ] not only because nickel serves as a low‐cost and earth‐abundant alternative to noble metals, but also because nickel catalysis features intriguing chemistry leading to distinct reactivities. Compared with the traditional palladium catalyst, nickel possesses unique properties, such as different readily accessible oxidation states ranging from Ni(0) to Ni(IV), smaller radius, lower electronegativity, and lower reduction potential.…”

Nickel-catalyzed reductive coupling of homoenolates and their higher homologues with unactivated alkyl bromides

“…6 ). Ni 0 oxidatively adds cyclic anhydride 1 giving a Ni II species ( I ) 71 – 74 . Next, decarbonylation of I with loss of CO forms the primary C(sp 3 )-Ni bond 75 in II .…”