Theoretical Study On The Lewis Base-Catalyzed [4+2] Cyclization Of Enals,[3+3] Cyclization Of Azomethine Imines

Besides the metal-organic catalysis and enzyme catalysis,the organocatalysis is the third kind of important pathway for asymmetric synthesis.Due to the advantages of mild reaction condition,high catalytic activity,low pollution and easy recycle,organocatalysis meets the requirements of green chemistry,so it has become a new research hotspot in the field of asymmetric reactions in recent years.If we can understand the mechanism of organic synthesis in essence,it will be of great help to design new synthetic routes,select suitable organic solvents and efficient catalysts.However,because of the limitations of experimental methods,it is still hard for chemists to understand the detailed reaction mechanism and the origin of stereoselectivity of such complex catalytic reactions.In this thesis,the mechanism,selectivity,and role of the catalyst of the three Lewis bases catalyzed reactions were studied at the molecular level using the density functional theory(DFT)method.The first chapter of this thesis sketched out the theoretical background,calculation methods,and several methods which were used to analyze the activaties of reactants.In addition,the related Lewis base organocatalysts had also been summarized briefly in this thesis.In the second,third,and fourth chapter,the DFT method was used to explore the three organocatalysis in theory.1.In the second chapter,the density functional theory(DFT)method was used to study the detailed mechanisms,origin of stereo-and chemo-selectivity,and role of catalyst for the [4 + 2] annulation reaction of enals with nitroalkenes catalyzed by N-heterocyclic carbene(NHC).The calculated results indicate that the most reasonable pathway of the reaction comprises seven steps.The addition of nitroalkenes on the Re or Si face of the enolate is identified to be the stereodetermining step.Moreover,the Gibbs free energy barrier of the reaction pathway leading to the RR configured product is the lowest,which is consistent with the experimental observations that the RR configuration is the main product.Furthermore,the analyses of global reactivity index(GRI),electrophilic and nucleophilic Parr functions of the reactants have been performed to explore the origin of the chemoselectivity and the role of catalyst NHC.2.In the third chapter,the mechanisms,chemo-and stereo-selectivity of PBu3-catalyzed intramolecular cyclization of N-allylic substituted ?-amino nitriles forming the functionalized pyrrolidines(5-endo-trig cyclization,Mechanism A)and its competing reaction generating another kind of pyrrolidines(5-exo-trig cyclization,Mechanism B)have been calculated with the DFT method.Several possible reaction pathways associated with four isomers(RR,SR,RS,and SS)of Mechanism A,and two isomers(R and S)of Mechanism B have been studied.The calculations show that the energy barriers of Mechanism A are significantly lower than those of Mechanism B,and the reaction pathway associated with the RS-configured product has the lowest energy barrier.The C–H???? interaction is confirmed to be responsible for the favorability of RS isomer via non-covalent interaction(NCI)analysis.Moreover,GRI analysis and natural population analysis(NPA)of the reactants are carried out to confirm catalyst PBu3 acts as a Lewis base to strengthen the nucleophilicity of the active sites in the reactants.3.In the fourth chapter,the DABCO-catalyzed [3 + 3] cyclization of 1,4-dithiane-2,5-diol and azomethine imines using the DFT method was studied.The reaction includes two consecutive stages:(1)the cleavage of 1,4-dithiane-2,5-diol forming mercaptoacetaldehyde,(2)the [3 + 3] cyclization of mercaptoacetaldehyde with the azomethine imines.In summary,double-methanol molecules mediated pathway followed by DABCO catalyzed [3 + 3] cyclization pathway is the most reasonable.The calculations are in consistent with the experimental observations that the reaction can carry out smoothly in the presence of catalyst DABCO and the absence of methanol,while it occurs more efficiently in the presence of both DABCO and methanol.The fifth chapter of this paper is the summary of the above work and the prospect for the future work.