Investigations Of The Reaction Mechanisms And Origin Of Selectivity In Synthesizing Allene And Quinoline Derivatives Catalyzed By Chiral Phosphoric Acid

Axially chiral allene and quinoline structures are widely observed in natural products and pharmaceutical active molecules,and have an important positions in functional material modules,asymmetric catalytic reactions and other fields.Due to their unique structural features,their synthetic strategies and reaction modes deserve more investigation.Chiral phosphoric acid as an outstanding organocatalyst with its double hydrogen bonding activation can be used for asymmetrical catalytic synthesis of allene and quinoline derivatives,but the reaction mechanisms and the origins and influencing factors of selectivity still need to be studied in depth.In this thesis,the reaction mechanisms have been explored by modeling the reactions of chiral phosphoric acid catalyzed synthesis of axially chiral allene and quinoline derivatives,and the origins of selectivity in these reactions have been discussed by analytical methods such as quantum theory of atoms in molecules(QTAIM)and independent gradient model(IGM).The thesis is mainly divided into four chapters as follows:Chapter 1: Research background.This chapter briefly introduced some important concepts of asymmetry,the origin and important catalysts of organic asymmetric catalysis,the research progress in the synthesis of allene and quinoline derivatives,and the purpose and significance of this chosen topic in this thesis.Chapter 2: Theoretical basis and computational methods.This chapter briefly introduced the basic principles of density functional theory(DFT)and the dispersion and solvation models used for correction,transition state theory,and the main theoretical analysis methods,including conceptual density functional theory,surface electrostatic potential analysis,quantum theory of atoms in molecules(QTAIM),various methods for visualizing non-covalent interactions,distortion/interaction analysis and energy decomposition analysis.Chapter 3: Theoretical study of the synthesis of axially chiral allene derivatives by catalysis of chiral phosphoric acid.In this chapter,the reaction of racemic indolesubstituted alkynyl alcohol and phenylindole catalyzed by chiral phosphoric acid to synthesize axially chiral allene derivatives has been modeled.Structure optimization was carried out based on the Minnesota monohybrid functional M06-2X,using 6-31G(d,p)basis set and the density-based implicit solvent model SMD,the single-point energy calculations were performed at Def2-TZVP basis set,leading to a detailed study of mechanisms for the generation of different products and different reaction modes.The calculation results indicated that the reaction started with a dehydration activation process of alkynyl alcohol promoted by chiral phosphoric acid,followed by the electrophilic attack of phenylindole to produce the axially chiral allene derivatives.By comparing the different reaction modes through QTAIM and independent gradient model(IGM)analysis,it can be found that weak interactions between the catalyst and substrates in the transition states determine the enantioselectivity.Chapter 4: Theoretical study of the synthesis of axially chiral C2-arylquinolines derivatives by asymmetric catalysis of chiral phosphoric acid.This chapter calculated the reaction mechanisms of chiral phosphoric acid-catalyzed synthesis of axially chiral C2-arylquinolines derivatives from alkynylnaphthalenes and carbonyl-substituted anilines via allene intermediate.Structure optimizations were performed employing M06-2X-D3/6-31G(d,p)theory level and SMD solvent model,and single-point energy of optimized structures were calculated under Def2-TZVP basis set.The reaction starts with the isomeric activation of alkynylnaphthalene catalyzed by chiral phosphoric acid transforming it into the key allene intermediate,followed by the electrophilic attack of aniline and intramolecular cyclization to produce axially chiral C2-arylquinoline derivatives.The important role of weak interactions in the reaction processes for enantioselectivity was investigated by QTAIM and independent gradient model based on Hirshfeld partition(IGMH)analyses.In the distortion/interaction and energy decomposition analyses,the distortion energy represented by steric effect and the interaction energy represented by activation provided conformational restriction and substrate activation,respectively,which gave us a deeper understanding of the origin for enantioselectivity.This thesis hopes to provide a deeper understanding of the catalytic mechanisms of chiral phosphoric acid through the study of the reaction mechanisms and origin of selectivity in the synthesizing allene and quinoline derivatives catalyzed by chiral phosphoric acid,and to contribute theoretical perspectives for structural design and catalytic applications of chiral phosphoric acid.