Density Functional Theory Insights Into Ruthenium‐Catalyzed Alkene–Alkyne Cross‐Coupling: Mechanism, Regioselectivity, and Catalyst Effects

ABSTRACT Direct cyclometalation of two unsaturated bonds at a transition metal center constitutes a highly efficient strategy for carbon–carbon cross‐coupling. In this work, density functional theory calculations were performed to delineate the detailed reaction mechanism of ruthenium‐catalyzed direct alkene–alkyne coupling for diene synthesis. Computational results reveal that the reaction proceeds via three elementary steps: concerted cyclometalation, β‐hydride elimination, and reductive elimination, with the initial cyclometalation step serving as both the rate‐determining and regioselectivity‐controlling step. Under standard reaction conditions, the branched diene is the major product, whereas the more stable linear diene is a minor isomer; however, this regioselectivity is significantly modulated by ligand architecture and substrate substituent effects. Calculations demonstrate that replacing the pentamethylcyclopentadienyl ligand with the unsubstituted cyclopentadienyl ligand, or introducing alkyl substituents on the alkene substrate, can invert the selectivity, switching the major product from branched to linear diene. Furthermore, investigations into catalyst structure–reactivity relationships reveal that ligand structure plays a dominant role, because the presence of a cyclooctatetraene ligand results in a substantial reduction in catalytic activity, whereas the formal charge of the Ru center exerts only a secondary influence. The present computational findings not only rationalize existing experimental observations but also provide deeper mechanistic insights into the origins of regioselectivity and reactivity in this class of transformations.