DFT Study On The Reaction Mechanisms Of Metal/nonmetal-catalyzed C-H Functionalization

Using density functional theory（DFT）the paper systematically studies the following three C-H activation/functionalization reactions:1)a DFT study on the reaction mechanism of Pd（OAc）₂-catalyzed trifluoroethylation of acetanilide:Role of additive CF₃COOH;2)Theoretical investigation on reaction mechanism of Pd（OAc）₂ catalyzed?-C（sp³）-H alkenylation of icolinamide（PA）-protected isoleucine methyl ester:the role of additive HFIP and O₂;3)Theoretical study on reaction mechanism of br?nsted acid ^pNO₂C₆H₄CO₂H catalyzed C（sp³）-H amination of 2-methylquinoline.In Chapter 1,Introduction of the research background and theoretical methods.In Chapter 2,At the level of M06 functional,using DFT method the mechanism of Pd（OAc）₂ catalyzed C（sp²）-H trifluoroethylation of acetanilide was studied.The calculated results indicate that in C-H activation,the proton abstraction ability of ligand CH₃COO^ˉis stronger than that of reaction substrate mesityl（trifluoroethyl）iodonium triflate 2a and free anion CF₃SO₃^ˉ.the two-step migration of CF₃CH₂-group is more favorable than the direct migration of CF₃CH₂-group.More importantly,the additive CF₃COOH can react with reaction substrate 2a to form a new active substrate mesityl（trifluoroethyl）iodonium trifluoroacetate 2a’.2a’can assist C-H activation by reduce rate-limiting free energy barrier of the catalytic reaction,causing that the rate-limiting step is changed from the migration insertion of CF₃CH₂-group to the C-H activation.These interesting findings and insights are valuable for exploring the detailed mechanism of transition-metal-catalyzed C-H trifluoroethylation,and understanding the role of additive in the C-H trifluoroethylation reactions.In Chapter 3,DFT method was used to study the reaction mechanism of Pd（OAc）₂catalyzed?-methyl C-H alkenylation of picolinamide（PA）-protected isoleucine methyl ester 1.The calculated results indicate in the migration insertion of alkyne 2a,compared to triplet O₂,singlet O₂ can oxidize Pd（II）intermediate to a Pd（IV）peroxide.The Pd（II）/Pd（IV）pathway can enhance the interaction between alkenyl C and C?,and reduces activation free energy barrier of the migration insertion of 2a.In addition,HFIP acts as a ligand to coordinate with the Pd center,which can increase the catalytic activity of the Pd center,further reduce the activation free energy barrier of the migration insertion of 2a,resulting that the rate-determining step is changed from the migrating insertion of alkyne 2a to the?-C-H activation.More importantly,the FIP^-ligand can act as a reducing agent,reducing Pd（IV）peroxide species to Pd（II）intermediate.In the process,FIP^-ligand is oxidized to hexafluoroacetone.We also exploreγ-methyl C-H andγ’-methylene C-H alkenylation of picolinamide（PA）-protected isoleucine methyl ester 1.By convention,γ-C-H orγ’-C-H activation is kinetically more favorable than?-C-H activation.However,the insertion of alkyne 2a into the Pd-Cγbond or the Pd-Cγ’bond has a large reaction energy barrier,causing that theγ-C-H or theγ’-C-H alkenylation is inhibited.Therefore,the migration insertion of2a controls the regioselectivity of the reaction.these interesting findings and insights are valuable for exploring the synthesis strategy about transition-metal-catalyzed C-H functionalization.In Chapter 4,The reaction mechanism of br?nsted acid ^pNO₂C₆H₄CO₂H catalyzed C-H amination of 2-methylquinoline benzyl was investigated using density functional theory（DFT）.The calculated results show that br?nsted acid ^pNO₂C₆H₄CO₂H can act as a proton shuttle,which can assist the proton transfer,reduce the activation free energy barrier of proton transfer.More importantly,the acidic strength of Br?nsted acid catalysts is major factor affecting their ability to assist proton transfer,and the stronger the acidity of the Br?nsted acid,the more favorable the reaction is（^pNO₂C₆H₄CO₂H>AcOH）.In addition,we also consider the effect of by-product H₂O in the C（sp³）-H amination of 2-methylquinoline.In summary,our theoretical study provides in-depth discussions of the detailed mechanism of the acidity of the Br?nsted acid catalyst for the C-H amination reaction of 2-methylquinoline.We hope that our present studies can provide guidance for the application of additives in the amination reactions.