Theoretical Studies On Lewis Acid Catalyzed Cyclization

Theoretical and computational chemistry has been playing an increasingly important role in studying the nature of chemical reactions since its birth.Theoretical and computational chemistry can not only reveal the mechanism of chemical reaction,but also study the structure and chemical properties of molecules in chemistry in detail,so as to guide experiments and design and synthesize some functional molecules.This article mainly uses Density Function Theory(DFT)method to explore the reaction mechanism of Lewis acid AgOTf/BF3 catalyzed cyclization reaction,and uses a variety of theoretical analysis methods(Global reactivity index,Parr function and Natural Population Analysis)specifically analyzes and explains the detailed mechanism,regioselectivity,and the role of catalysts in the cyclization reaction.These studies can provide instructive theoretical references for designing similar reactions and synthesizing more efficient catalysts.This article contains four chapters in total.The first chapter is the introduction,introducing theoretical and computational chemistry,different kinds of analytical methods and their applications in organic chemistry.In addition,the background of Lewis acid catalyst catalyzed cyclization is introduced,which includes two types of Lewis acid catalyzed reactions:metal ion-catalyzed cyclization reaction and organic small molecule catalyzed cyclization reaction.The research content of this article is based on this.The specific research content is carried out in Chapter 2 and Chapter 3.The second chapter uses density functional theory(DFT)to explore the theoretical study on the mechanism of silver(Ⅰ)catalyzing the cycloaddition reaction of orthoalkylene-benzaldehyde oxime and hexyne alcohol.Theoretical calculation results show that the entire catalytic cycle reaction process includes a total of eight processes:6endo cycloaddition process of silver-coordinated cyclopropyl-ethynyl-benzaldehydeoxime intermediate,intramolecular 1,4-proton transfer process,silver migration process,silver coordinated isoquinoline-N-oxide intermediate AgOTf catalyst reduction regeneration process,1,3-dipolar cycloaddition process,intramolecular dehydration process,N-O bond cleavage and ring opening process,and finally AgOTf catalyst reduction regeneration process in the silver coordinated Isoquinoline intermediate and product formation.After a series of theoretical calculations,we found that the first step of the 6-endo cycloaddition process is the decisive step of the entire catalytic reaction.The energy barrier of the critical step is 30.0 kcal/mol,which can happen at a temperature of 110℃.Then,we explored the role of the catalyst AgOTf in the entire catalytic cycle:(1)The Ag-π complex formed by the coordination of the AgOTf catalyst and the alkynyl group of the reactant ortho-alkylene-benzaldehyde oxime increases the electrophilicity of the alkynyl α-C and promotes the intramolecular 6-endo cycloaddition reaction happened.In addition,the AgOTf catalyst can also coordinate with the alkynyl group of the reactant hexyne alcohol to form an Ag-πcomplex to increase the nucleophilicity of α-C atoms and the electrophilicity of β-C atoms,thereby promoted its 1,3-dipolar cycloaddition reaction with the intermediate isoquinoline-N-oxide.(2)AgOTf catalyst takes part in the intramolecular dehydration reaction process as a dehydration medium.In addition,we have further studied the process of Au(I)catalysis.The calculation results show that the bond dissociation energy of the catalyst AuPPh3Cl is as high as 31.6 kcal/mol.At the same time,the Agπ complex formed by the coordination of AuPPh3+ with the alkynyl group of orthoalkylene-benzaldehyde oxime need to cross the energy barrier of 8.2 kcal/mol for intramolecular 6-endo cyclization,making such a reaction impossible.This also shows the characteristics of the Lewis acid catalyst AgOTf.The third chapter uses density functional theory(DFT)to explore the theoretical study of the cyclization reaction mechanism of 2-benzoylbenzaldehyde with aromatic hydrocarbons catalyzed by boron trifluoride(BF3)Theoretical calculation results show that the entire catalytic cycle reaction process includes a total of five processes:FriedelCrafts reaction,intramolecular 1,5-proton transfer process,intramolecular[BF3OH]departure process,[BF3OH]-assisted hydrogen atom departure process,and finally boron trifluoride(BF3)catalyst reduction regeneration process and product formation.We use natural population analysis to analyze the charges of the reactants and coordination complexes,and analyze the nucleophilic and electrophilic indicators of the reactants and coordination complexes using global reactivity index,and used frontier molecular orbital to react the reaction sites of the complex and the coordination complex were analyzed,which confirmed the role of boron trifluoride(BF3)in the reaction.The calculation results show that,the boron trifluoride(BF3)catalyst significantly improves the electrophilicity of the reactant in the chemical reaction and reduces the energy gap of the reaction.This prompted the reaction of boron trifluoride(BF3)to catalyze the synthesis of isobenzofuran compounds from 2benzoylbenzaldehyde.The fourth chapter is a summary of all theoretical calculations in this thesis.