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.
Sakazaki et al. (Mon,) studied this question.