Theoretical Insight into C(sp³)–F Bond Activations and Origins of Chemo- and Regioselectivities of “Tunable” Nickel-Mediated/-Catalyzed Couplings of 2‑Trifluoromethyl-1-alkenes with Alkynes

The mechanisms and chemo- and regioselectivities of divergent (Ni­(cod)₂/PCy₃)-mediated/-catalyzed C­(sp³)–F bond activation of 2-trifluoromethyl-1-alkenes (1) with alkynes (2) were investigated by density functional theory (DFT) calculations. The nickel-mediated/-catalyzed reaction involves sequential ligand exchange, alkene coordination, oxidative cyclization (1 + Ni(0) + 2), and first β-F­(C­(sp³)) elimination to give a common and requisite alkenylnickel­(II) species, which bifurcates into either stoichiometric defluorinative [3 + 2] cycloaddition product 3 or catalytic defluorinative coupling products (nonmethylated 5, monomethylated 8, or trimethylated 9) depending on the absence and presence of additional reagents (Et₃SiH, ZnMe₂, and AlMe₃). The Et₃SiH-induced formation of 5 is found to be a result of facile metathesis relative to the 5-endo insertion leading to 3. Because of the presence of an F→Zn/Al interaction, ZnMe₂/AlMe₃ brings the methyl into defluorinative coupling products. In the stoichiometric reaction, the chemoselectivity of 3 over C­(sp³)–F oxidative addition product originates from the presence of the electron-withdrawing −CF₃ group. Under the Et₃SiH-involved catalytic environment, the chemoselectivity of the formation of 5 can be explained as follows: (i) the formation of an Et₃Si–H oxidative addition product is thermodynamically infeasible and (ii) the large steric hindrance as well as the weak Ni–Si σ bond heavily influences the generation of alkyne hydrosilylation complexes. In addition, the weak Ni···Zn interaction impedes the rate-determining C­(sp³)–F oxidative addition leading to 9 and eventually provides regioselective product 8, while the strong Ni···Al interaction promotes the evolution of the initially formed 8 further into 9.