Theoretical Insight into C(sp3)-F Bond Activations and Origins of Chemo- and Regioselectivities of "Tunable" Nickel-Mediated/-Catalyzed Couplings of 2-Trifluoromethy1-1-alkenes with Alkynes

The mechanisms and chemo- and regioselectivities of divergent (Ni(cod)(2)/PCy3)-mediated/-catalyzed C(sp(3))-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 beta-F(C(sp(3))) 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 AIMe(3)). 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(sp(3))-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 sigma bond heavily influences the generation of alkyne hydrosilylation complexes. In addition, the weak Ni center dot center dot center dot Zn interaction impedes the rate determining C(sp(3))-F oxidative addition leading to 9 and eventually provides regioselective product 8, while the strong Ni center dot center dot center dot Al interaction promotes the evolution of the initially formed 8 further into 9.