Diastereoselective-Controllable Construction Of Five-Membered Heterocycles Through Transition Metal-Catalyzed[3+2]-Cyclization

Five membered heterocyclic frameworks are common in natural products and drug molecules.Therefore,it is of great significance to explore and develop efficient strategies for the constructions of five membered heterocyclics.In this paper,two kinds of catalyzed controllable strategies were developed,namely palladium(0)/scandium(Ⅲ)catalyzed controllable diastereoselective[3+2]-cyclization to construct five membered heterocyclic compounds and gold(Ⅰ)/silver(Ⅰ)catalyzed controllable diastereoselective[3+2]-cyclization to construct five membered heterocyclic compounds.This paper can be divided into four chapters:The first chapter is the introduction,which mainly introduces the natural products and drug molecules containing five membered heterocyclic frameworks,and summarizes three different methods of[3+2]-cyclization/cyclization to construct five membered heterocyclic derivatives,as well as the research progress of catalyst controlled cyclization/cycloaddition.Based on this result,the significance and design ideas of this paper are elaborated.In the second chapter,the design scheme,optimization process,reaction substrate synthesis steps,substrates scope,gram-synthesisreaction,transformations of the corresponding cycloadducts and results of Pd(0)/Sc(Ⅲ)catalyzed controlled diastereoselective[3+2]-cycliaddition of styryl ethylene oxide diester and endosulfonimide to construct five membered heterocyclic derivatives were introduced.The optimal reaction conditions were determined as follows:at room temperature,Sc(OTf)3 was used as catalyst,CH2Cl2 was used as solvent,reaction time was 36 hours at room temperature,and 26 H-H trans-tricyclooxazolidine derivatives were obtained in moderate to excellent yields(33-95%);At room temperature,12 H-H cis-tricyclohoxazolidoles were obtained by using Pd(PPh3)4 as catalyst,CH2Cl2 as solvent and room temperature reaction for 4 hours.At the same time,the reaction mechanism was speculated,and the corresponding compounds were characterized by NMR and HRMS.The relative configuration of the desired products was confirmed by single crystal XRD.In the third chapter,the Au(Ⅰ)/Ag(Ⅰ)catalyzed asymmetric selective[3+2]-cyclization of indoleimine and 2-alkynylstyrenone to construct five membered heterocyclic derivatives was introduced,including the design scheme,optimization process,synthesis steps,substrates scope and the transformations of coprresponding cycloadducts.The optimal reaction conditions were determined as follows:AuPPh3NTf2 was used as catalyst,triethylamine was used as basic environmental source,MeCN was used as solvent,the reaction time was 12 hours at room temperature without light and oxygen,and 32 derivatives were obtained in moderate to excellent yields(58-98%);Using MeTA-Au/AgSbF6 as catalyst,triethylamine as basic environmental source,CH2Cl2 as solvent,13 derivatives were synthesized in moderate to excellent yields(46-92%)at room temperature in the dark under Ar atmosphere for 12 hours.The related compounds were characterized by NMR and HRMS.The relative configuration of the target product was confirmed by single crystal XRD.The fourth chapter summarizes the research content of this paper.In this paper,transition metal catalyzed controlled diastereoselective[3+2]-cyclization reaction was used to construct five membered heterocyclic derivatives.The reaction conditions were mild,the stereoselectivity was high,the substrate application was wide,and the reaction yield was high.This work enriches the synthesis methods of five membered heterocyclic frameworks and provides a new idea for the efficient construction of diastereoselective heterocyclic compounds.