Theoretical Study Of Transition-metal Catalyzed New Coupling Reaction To Construction Carbon-carbon Bond

Transition metal catalyzed coupling reaction has become a new way to construct C-C bonds in organic chemical synthesis.Recently,due to the simple synthesis method,easy availability of raw materials,high atomic economy advantage,more attentions are focused on C-H activation,Alder-ene reaction of olefins and alkynes,trifluoromethylation reaction and cyclization of propargyl compounds by chemists.Theoretical calculations were carried out to study the energy,charge and structure of the intermediates and transition states,which could be used to further understand the mechanism,activity and selectivity of catalytic reactions.Also theoretical calculations have important guiding significance for expanding the type of substrate that is known to react and the development of new reactions and new reagents.In this thesis,the DFT method was used to study the mechnism of Ru-catalyzed C-H activation,Ru-catalyzed Alder-ene type alkene–alkyne coupling reaction,Cu?I?-catalyzed trifluoromethylation of aryl borate and Au-catalyzed cyclization of propargyl.This thesis mainly includes the following four parts:1.Density functional theory?DFT?calculation has been employed to elucidate the mechanism of the ruthenium-catalyzed direct arylation of C-H bonds in aromatic amides.In the initial procedure,coordination of the substrate,N-H bond cleavage,and carbonate exchange give the active catalytic species,which is the starting point in the catalytic cycle.The catalytic cycle includes electrophilic deprotonation by carbonate,oxidative addition of bromobenzene,reductive elimination to form a new aryl-aryl bond,proton transfer to release the product,and ligand exchange to regenerate active species.The ratedetermining step of this pathway was found to be oxidative addition of bromobenzene.These results are consistent with experimental observations.We also evaluated the ligand effect for this ruthenium-catalyzed arylation reaction using the triphenylphosphine ligand.The computational results suggest that the apparent activation free energy is 4.1 kcal/mol lower in the triphenylphosphine-assisted reaction?32.7 kcal/mol?than in the ligand-free reaction?36.8 kcal/mol?.Reported experimental results also show that addition of triphenylphosphine can increase the yield of products.2.Theoretical study of the mechanism of Ru-catalyzed Alder-ene type alkene–alkyne coupling reaction.A novel 1,5-H shift mechanism for this reaction was proposed by our group.The result shows that compared with the traditional cycloaddition-?-hydride elimination–reductive elimination route reported by Trost et al.,the pathway through a[3+2]oxidative cycloaddition and 1,5-H shift step is more favorable.Stereoselectivity of the product is also validated and the results shows that it is mainly controlled by the energy differences in both the oxidative cycloaddition and1,5-H shift step.The calculational results of the pathway proposed by Trost et al.shows that the rotation of the C-C?bond requires a higher activation energy,which is 5.3kcal/mol higher than that of the 1,5-hydrogen shift pathway.Therefore,the pathway proposed by Trost et al.is disadvantageous pathway.3.The mechanism for copper-catalyzed trifluoromethylation of aryl boronic acids by Togni's reagent was studied.Computational results suggest that the catalytic cycle proceeds with the transmetallation between phenylboronic acid and copper?I?species,which generats a phenylcopper?I?intermediate.Subsequent coordination of Togni's reagent and the electrophilic substitution of CF₃ group to phenyl group finally afford the trifluoromethylation product through a concerted five-membered ring transition state.The transmetallation process with an activation free energy of 21.7 kcal/mol is determined to be the rate-determining step of this reaction.Moreover,the reactivity of alkylboronic acid was also calculated and proven to be unfavorable due to the higher activation free energy of transmetallation process.4.A gold?I?-catalyzed propargyl-Claisen rearrangement/6-endo-trig tandem cyclization strategy for furopyran derivatives has been developed.Notably,ring strain acts as an indispensable factor to alter the regioselectivity from 5-exo trig to 6-endo-trig.The interplay of electronic and steric contributions to the transition states for 5-exo-trig and 6-endotrig cyclizations of theoretical models was also analyzed by DFT calculation,which provided results consistent with the experimental findings.The results indicate that the nucleophilic addition step of oxygen atom is the rate-determining step,and its activation energy is 30.2 kcal/mol,which controls the regioselectivity of the cyclization reaction.Ring strain and angle strain together affect the regioselectivity,while it is hardly affected by the electronic effects.