Experimental and Theoretical Investigation of Competing β‑Heteroatom and Reductive Elimination in Nickel-Catalyzed Enone–Enyne Coupling

Nickel-catalyzed
domino coupling of enones and enynes proceeds
via competing β-heteroatom (β-X) and reductive elimination
pathways. Despite the importance of β-elimination and reductive
elimination in transition metal catalysis, the mechanistic basis for
β-X elimination remains underexplored, particularly in nickel
systems. In this study, we investigated a nickel-catalyzed domino
coupling of enones and enynes that proceeds through either β-X
elimination or reductive elimination depending on the substrate and
reaction conditions. To induce β-X elimination, particularly
β-O elimination, we introduced an OH group at the β-position
to suppress undesired β-H elimination for selective product
formation. The β-syn-OH elimination pathway
was experimentally verified, and reaction selectivity was found to
depend primarily on the substrate structure. Density functional theory
(DFT) calculations provided energetic profiles for β-O, β-H,
and reductive elimination pathways, supporting the observed selectivity
and clarifying the mechanistic trends. These findings establish a
mechanistic foundation for β-O elimination in nickel-catalyzed
reactions and highlight their strategic utility for selective C–C
bond formation. This work expands the synthetic potential of nickel-mediated
β-elimination and offers a framework for the design of new bond-forming
transformations.