Theoretical Study On Asymmetric Reaction Mechanism Of Intramolecular Amine Nucleophiles Catalyzed By Chiral Phosphoric Acid

Chiral molecules are closely related to human live and life.Efficient and highly selective synthesis of optically pure chiral molecules has always been one of the goals pursued by synthetic chemistry.Asymmetric catalysis has become one of the most efficient strategies for creating chiral molecules due to its unique chiral proliferation advantage.Asymmetric reactions catalyzed by small organic molecules,as a core type of asymmetric catalysis,have been greatly developed in the past two decades.Among them,chiral phosphoric acid is one of the common organic small molecule catalysts,and the asymmetric reactions that it participating is developing rapidly,and its catalytic reaction mechanism as well as selectivity control factors have received extensive attention.for chiral phosphoric acid catalyzed intramolecular nucleophilic reaction of amine,there are still a series of reaction mechanisms and stereoselectivity problems in the asymmetric reactions,which make the rational design of new catalysts and reactions difficult,hinder the further development of this field,and urgently need theoretical research.Based on this,in this thesis,the selective synthesis of axial chiral indole catalyzed by chiral phosphoric acid and the asymmetric dearomatization of homopropargylamine catalyzed by chiral phosphoric acid were systematically studied,revealing the reaction mechanism and chiral Sexual Control Model.The thesis consisted of four chapters,the brief introduction of each chapters is as follows:Chapter 1:Introduction.This chapter briefly introduces the research background and progress of the Br?nsted acid-catalyzed alkynamide reaction,the chiral phosphoric acid-catalyzed asymmetric dearomatization reaction,as well as the quantum theory of density functional theory,transition state theory,commonly used calculation software,methods and basis sets.Chapter 2:Study on the reaction mechanism and stereoselectivity of alkyneamides to synthesize axially chiral indole catalyzed by chiral phosphoric acid.The research in this chapter shows that alkynamides undergo a novel synergistic intramolecular nucleophilic substitution step under the action of a chiral phosphoric acid catalyst,which follows the S_NVσmechanism.Calculations indicate that the reaction is first initiated by the hydrophosphoryloxylation step of alkynamides to generate the enamide intermediate,which is different from the classical ionic mechanism.At the same time,the coordinated intramolecular nucleophilic substitution step is also the stereoselective determinant of the reaction,and its selectivity comes from the steric repulsion between the reaction substrate and the catalyst.Chapter 3:Mechanism and stereoselectivity of chiral phosphoric acid-catalyzed asymmetric dearomatization of homopropargylamines to synthesize central chiral fused polycyclic ketenes.The research in this chapter shows that homopropargylamine has a chemical phenomenon of chirality transfer under the action of chiral phosphoric acid catalyst,and the central chirality of the product is controlled by the axial chiral methylene o-quinonemethyl intermediate activated in the reaction,delivered by sequential intramolecular nucleophilic addition.The source of the stereoselectivity of the reaction was investigated,and it was elucidated that chiral phosphoric acid acts as a bifunctional catalyst,which is coordinated by non-covalent interactions such as hydrogen bonding and steric hindrance.Chapter 4:Summary and outlook.In this chapter,the research contents of this thesis were summarized,the research progress we have made were illustrated and directions for further in-depth research were also pointed out.