Theoretical Insights into the Ni ⁽⁰⁾ ‐Catalyzed Asymmetric Hydroalkylation of Phenylbutadiene and Acetophenone: Mechanism, Selectivity, and Ligand Effect

Transition-metal-catalyzed hydroalkylation of enols/enolates with unsaturated hydrocarbons enables the functionalization via C─C and C-heteroatom bond formation. In this work, the reaction mechanisms of Ni⁽⁰⁾-catalyzed asymmetric hydroalkylation of phenylbutadiene and acetophenone are systematically investigated using density functional theory (DFT) calculations. The Ni⁽⁰⁾/Ni^(II) catalytic cycle comprises oxidative addition, proton transfer, and the C(sp³)─C(sp³) bond formation via reductive elimination. The rate-determining oxidative addition step proceeds via a concerted ligand-to-ligand hydrogen transfer (LLHT) mechanism, bypassing an unstable Ni^(II)-hydride intermediate. Proton transfer occurs via a ligand exchange with the enolate group within the acetophenone, and the regioselectivity arises from the preferential C(sp³)-C(sp³) bond formation via reductive elimination at the methyl-adjacent carbon in the acetophenone. Furthermore, the electron population analysis on the rate-determining transition state demonstrates that charge transfer from the Ni⁽⁰⁾-ligand moiety to the ─O⁺H σ* and ─C═C─π* antibonding orbitals facilitates the weakening of the ─O⁺H bond and η²-coordination of ─C═C─ bond in phenylbutadiene with the nickel center, enabling the LLHT mechanism. Additionally, the influence of ligand on the reactivity of Ni⁽⁰⁾-catalyzed asymmetric hydroalkylation is also explored, and the steric contour maps of percent buried volume (%Vbur) analysis confirm that the bulky ligands increase the %Vbur and enhance catalytic performance.