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

Abstract

The mechanisms and chemo-and regioselectivities of divergent (Ni(cod) 2 /PCy 3 )-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 β-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 (Et 3 SiH, ZnMe 2 , and AlMe 3 ). The Et 3 SiH-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, ZnMe 2 /AlMe 3 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 −CF 3 group. Under the Et 3 SiH-involved catalytic environment, the chemoselectivity of the formation of 5 can be explained as follows: (i) the formation of an Et 3 Si−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 ratedetermining C(sp 3 )−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.

Picking One out of Three: Selective Single C−F Activation in Trifluoromethyl Groups

“…Transmetallation with Et 3 SiH (formation of Et 3 SiF) and reductive elimination, lead to the regeneration of Ni 0 catalyst. A recent DFT study by Liu and Bi is in agreement with this reaction pathway . It should be noted that in the absence of Et 3 SiH, the intermediate alkenylnickel(II) fluoride complex cyclises in a 5‐ endo ‐trig fashion to yield fluorinated cyclopentadienes …”

“…Ar ecent DFT study by Liu and Bi is in agreement with this reactionp athway. [25] It should be noted that in the absence of Et 3 SiH, the intermediate alkenylnickel(II) fluoridec omplex cyclises in a5 -endo-trig fashion to yield fluorinated cyclopentadienes. [26] Trifluoromethylated diazo compounds have been successfully employed in single CÀFa ctivation reactions.…”

DFT Studies on Ni-Mediated C–F Cleavage for the Synthesis of Cyclopentadiene Derivatives

“…Therefore, the combined processes of the β -fluorine elimination and the 5- endo insertion can be viewed as the rate-determining step because the endergonicity of the β -fluorine elimination process contributes to the overall rate-determining barrier. This finding is consistent with the recent DFT study by Bi's group (Zhang et al, 2017 ), in which the 5- endo insertion transition state is also the rate-determining for the whole Ni-mediated reaction.…”

Transition‐Metal‐Mediated and ‐Catalyzed C−F Bond Activation by Fluorine Elimination

“…Thegroup of Bi and Liu calculated the energy barriers for two major possible routes for the first C À Fb ond cleavage from nickelacyclopropanes F,w hich we have observed experimentally,t oi ntermediates D (Figure 1). [17] Although the overall energy barrier was 37.6 kcal mol À1 in the oxidative addition-alkyne insertion route,t he overall energy barrier in the oxidative cyclization-b-fluorine elimination route was calculated to be lower (only 19.5 kcal mol À1 ). Thus,t hese results indicate that b-fluorine elimination readily proceeds as expected.…”