Theoretical Study On The Coupling Reaction Mechanism Of Nickel-catalyzed C(sp~3)-F Bond Activation

Transition-metal catalyzed organic reactions possess extensive applications due to their specific properties including high reactivity,high selectivity as well as excellent furnctional group compatibility.Among these transformations,transition-metal-mediated C-F bond activation has occupied a significant research area,establishing new synthetic methodologies.During the past few years,striking developments have been made on the C-F bond activaiton of aryl,vinyl,and allyl fluorides.In contrast,the C-F activation of the trifuloromethyl group remains a great challenge,which might be attributed not only to the high bond dissociation energies of the C?sp³?-F bond but also to the strong shielding effect of the three F atoms.Usually,the C?sp³?-F bond is broken by the oxidative addition using transitional-metal catalyst in low valence,in which,however,the harsh reaction conditions are required.This,to a certain extent,limited the application of the methodlology.Alternatively,under the milder conditions,the cleavage of the C?sp³?-F bond can be achieved by the?-fluorine elimination,which is considered as a much more reasonable method.So far,the related selectivity control is not only challenging to experimental chemists but attracts extensive attention of theoretical chemists.Therefore,theoretical studies are of great significance on exploring the intrinsic reasons behind the reactions.In this dissertation,the mechanisms,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,the oxidative cyclization?1+Ni?0?+2?,and first?-F?C?sp³??elimination to give a common and requisite alkenylnickel???species,which bifurcates into either stoichiometric defluorinative[3+2]cycloaddition product 3 or catalytic defluorinative coupling products?no-methylated 5,mono-methylated 8 or triply-methylated 9?depending on the absence and presence of additional reagents?Et₃SiH,ZnMe₂ or 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 follow:?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?-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 8further into 9.