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.

镍催化的烯酮与烯炔多米诺偶联反应可通过竞争的β-杂原子（β-X）消除与还原消除路径进行。尽管β消除与还原消除在过渡金属催化领域具有重要意义，但β-X消除的机制基础仍未得到充分探索，尤其是在镍催化体系中。本研究针对镍催化的烯酮与烯炔多米诺偶联反应展开探究，该反应可根据底物与反应条件的差异，分别经由β-X消除或还原消除路径进行。为诱导β-X消除（尤其是β-O消除），我们在β位引入羟基（OH），以抑制非目标的β-H消除过程，从而实现产物的选择性生成。实验验证了β-顺式羟基消除路径，且反应选择性主要取决于底物结构。密度泛函理论（Density functional theory, DFT）计算给出了β-O、β-H消除与还原消除路径的能垒分布，佐证了实验观测到的选择性，并阐明了相关机制趋势。本研究成果为镍催化反应中的β-O消除奠定了机制基础，并凸显了其在选择性C-C键形成中的战略应用价值。本工作拓展了镍介导β消除反应的合成潜能，并为新型成键转化反应的设计提供了理论框架。