Theoretical Studies On Mechanisms Of N-Heterocyclic Carbene/Phosphine-Catalyzed Cyclization And Palladiumcatalyzed C-H Activation Reaction

In recent decades,the theoretical computational chemistry,as a green research method,has received widespread attention from chemists in exploring the nature of chemical reactions.Quantum chemical methods,especially density functional theory?DFT?,are used in theoretical calculations to study the mechanism of organic catalytic reactions and to explore the origin of chemical selectivity.In this paper,N-heterocyclic carbene/phosphine-catalyzed cyclization and palladium-catalyzed C-H activation reactions are selected for theoretical computation study,and the mechanism of the reactions and origin selectivity are discussed and analyzed in depth.The research results reveal the essence of these three organic chemical reactions to people by theoretical computation study,and provide valuable theoretical guidance for designing similar reaction mechanisms and new organic catalysts.The first topic is theoretical study on the reaction mechanisms of N-heterocyclic carbene catalyzed[3+3]annulation of?,?-unsaturated esters and methyl ketimines.The second topic is a DFT study on the reaction mechanisms of phosphine-catalyzed[4+1]annulation of o-quinone methides with allenoates.The third topic is the theoretical study on the selective catalyst Pd activating allenic C-H bonds to synthesize[3]dendralenes.The first chapter of this thesis mainly introduces the basic knowledge of theoretical computational chemistry methods and commonly used research methods,and briefly describes the relevant background and research progress of N-heterocyclic carbene catalyzed organic reactions and phosphine-catalyzed organic chemical reactions,as well as the transition metal Pd catalyzed organic reactions.The second,third,and fourth chapters of this thesis mainly introduce the theoretical study on the mechanism and selectivity of N-heterocyclic carbene/triphenylphosphine/transition metal Pd?OAc?₂ catalyst-catalyzed organic reactions.The fifth chapter of this thesis is a conclusive summary of the research work on the three topics.The following is the corresponding research summary of three topics.1.Theoretical study on the reaction mechanisms of N-heterocyclic carbene catalyzed[3+3]annulation of?,?-unsaturated esters and methyl ketimines.The theoretical calculations reveal that the whole reaction consists of in six steps:N-heterocyclic carbene?NHC?catalyst attacks?,?-unsaturated esters,Michael addition,intramolecular[3,3]rearrangement,1,3-proton transfer,intramolecular cyclization reaction,catalyst leaving to form product.Among them,the intramolecular[3,3]rearrangement process determines the stereoselectivity of the reaction,and further induces the main product of the S-configuration.Additive DBU-H⁺plays an indispensable role in the 1,3-proton transfer process as a proton medium.In addition,the global reaction index?GRI?and the frontier molecular orbital?FMO?analyses show that NHC catalysts as Lewis bases can increase the nucleophilicity of?,?-unsaturated esters and reduce the FMO energy gap.2.A DFT study on the reaction mechanisms of phosphine-catalyzed[4+1]annulation of o-quinone methides with allenoates.Theoretical calculations reveal that the entire reaction process includes six steps:the adsorption process of allenyl ester with triphenylphosphine,the 1,4-proton transfer process,the Michael addition process,the 1,3-proton transfer process,the intramolecular cyclization process,catalyst departure and product formation.Among them,the Michael addition process and the intramolecular cyclization process determine the chirality of C7 and C4,respectively,and further induce the main products of the SS-configuration.Moreover,the cycloaddition process determines the stereoselectivity of the reaction.The analyses of the global reaction index?GRI?and the frontier molecular orbital?FMO?confirmed that the triphenylphosphine catalyst not only improved the nucleophilicity of the reactant allenoate,but also reduced the FMO energy gap.3.Theoretical study on the selective catalyst Pd activating allenic C-H bond to synthesize[3]dendralenes.Theoretical calculations reveal that the detailed reaction mechanism of selective catalyst Pd activating allenic C-H bond to synthesize[3]dendralenes includes five parts:the catalyst Pd coordinates with the reactant allene compound,allenic C-H activation,HOAc release,olefin insertion,?-hydride elimination.Similarly,the mechanism of potential competitive reactions also includes five parts.Moreover,the rate-determining step in both reactions is the olefin insertion process.The difference is the C-H bond activation process.In the main reaction,the selective catalyst Pd activates hydrogen on the allene compound C4 atom,while in the competitive reaction,the selective catalyst Pd?OAc?₂ activates methyl hydrogen of allene compound C1 atom.In competitive reactions,the energy barrier for C-H activation is as high as 19.2 kcal/mol,which is6.6 kcal/mol higher than that of the main reaction.In addition,the energy barrier of the rate-determining step of the competitive reaction is as high as 26.5 kcal/mol,which is3.6 kcal/mol higher than that of the main reaction,which indicates that the selective catalyst Pd is more inclined to activate hydrogen atom on C4 to form[3]dendralene product.