Mechanism Study On The Synthesis Of Oxa/N-Heterocycles Catalyzed By Lewis Acid Or N-Heterocyclic Carbenes

Heterocyclic compounds are very important products in organic chemistry,which play very important roles in the synthesis of natural products and the developing of new drugs.Of all the heterocyclic compounds,oxa-and aza-heterocycles are the most common types.In recent years,with the progress of synthesis methodology and structural analysis technology,more and more new synthetic strategies have been reported.Therefore,the synthesis of oxa-and azaheterocycles is becoming one of the hottest research fields.By using the density functional theory(DFT),conceptual density functional theory,the polarized continuum model(PCM),transition state theory(TST)and other methods,the systems involved in this paper have been studied in detail.On the basis of the appropriate method and basis sets,the potential energy surfaces have been obtained through structural optimization and frequency analysis.The reaction mechanism has been argued deeply using these data.The whole paper is divided into four parts:Chapter one: Research background.In this chapter,heterocyclic compounds,donoracceptor cyclopropanes(DAC),N-heterocyclic carbenes,H-shift and H-shuttles were briefly introduced.Also,the recent research advances on the reactions of DACs and aryl aldehydes catalyzed by Lewis acids and the synthesis of aza-heterocycles catalyzed by N-heterocyclic carbenes were listed.Chapter two: Theoretical basis and calculation methods.This chapter consists of the introductions of the development history of quantum chemistry,density functional theory(DFT)and conceptual density functional theory,transition state theory(TST),DFT-D correction and solvation effect models and so on.Chapter three: Mechanism study on the synthesis of indene derivatives and polycyclic lactolides from DAC and aryl aldehydes mediated by Ga Cl3 were performed.Aryl cyclopropanyl-1,1-di ester and benaldehyde was chosen as the reactants.The whole reaction process can be divided into three stages: the first stage is the DAC isomerization catalyzed by Ga Cl3,the second stage is the reaction of isomerized DAC and aromatic aldehyde to give indene derivatives,the third stage is the reaction between newly-formed indene derivatives and aromatic aldehydes to give polycyclic lactones.It is suggested by the calculations that the substitued DAC undergoes a synchronous H-migration and ring-opening process in the first stage.And in the second stage,the rate-determining step is the 1,2-elimination process giving water.In the third stage reaction,gallium chloride can react with water produced in the second stage and release hydrogen chloride,making an acidic condition which plays an important role for the reaction.From our theoretical calculations,it is shown that aromatic aldehydes can catalyze the reaction by involving in the dehydrate process in the second stage and the existence of acid is essential for the third stage,in which the newly-formed hydrogen chloride is the catalyst.Chapter four: Mechanism study on synthesis of 2,3-disubstituted indoles catalyzed by N-heterocyclic carbenes.Two kinds of NHCs(A-NHC and B-NHC)were selected as the model catalysts.Density functional theory(DFT)was applied to study the mechanism of this NHCs catalyzed reaction and the role of catalysts.Calculation results show that the reaction includes four steps:(i)the formation of key Breslow intermediates,(ii)the intramolecular 1,4-addition,(iii)the second 1,2-proton transferration,and(iv)the regeneration of NHC.In addition,the ratedetermining step of this reaction is the NHCs’ nucleophilic attack to imine carbon or β-carbon in the α,β-unsaturated ester,which also determines the types of intermediates formed(aza-breslow intermediates or deoxy-breslow intermediates).It is revealed that the direct 1,2-proton transfer is less favored than the DBU-H+ and water catalyzed proton-transfer(in the A-NHC case)or tBut OH catalyzed proton-transfer(in the B-NHC case).Through the analysis of NPA and conceptual density functional theory,it is found that the NHCs play very important roles in the umpolung of α,β-unsaturated ester as Lewis bases.