In Situ Generated Azomethine Ylides To Construct Heterocyclic Structures Via Cycloaddition Strategy

Heterocycles are basic skeletons presented in a wide variety of biomolecules,natural products and drugs,which play significant physiological role in living organisms.Statistics show that nearly one third of selling drugs are heterocyclic compounds,whose potential value in drug discovery and economy have attracted substantial attention.Hence significant progress have been developed to synthesize heterocycles.As a kind of crucial methods for the rapid construction of cyclic compounds,cyclic addition reaction has been widely concerned and studied.The 1,3-dipole cycloaddition of azomethine ylide,one of the most common nitrogen-containing 1,3-dipoles,could achieve the efficient construction of monocyclic and polycyclic frameworks,which not only meets the objective requirements of modern synthesis,but also effectively promoted the development of new reactions and new methods for the synthesis of heterocyclic compounds.This dissertation focuses on the biologically active compounds pyrrolazine and pyrrolo[2,1-a]isoquinoline,investigates the novel strategies for the synthesis of 2,3-dihydro-1H-pyrrolizines and three kinds of poly-substituted pyrrole[2,1-a]isoquinolines as well as their probable reaction mechanisms.In addition,this strategy was extended to the concise total synthesis of the lamellarin core and lamellarin G trimethyl ether.The main contents are listed as follows:In chapter 1,we outlined the preparation of azomethine ylide and its applications in azo-heterocycles synthesis.On this basis,we put forword the research topics.In chapter 2,we report the use of acrylates to capture the azomethine ylides generated in situ from arylglyoxal and pyrrolidine to develop a new reaction for the acid-mediated N-H/?,?-C(sp3)-H trifunctionalization of pyrrolidine in one-pot.Based on the control experiments and previous reports from the literature,we have proposed a possible mechanism for this reaction.In chapter 3,on the basis of preliminary work,we developed a cycloaddition reaction for the construction of two types of substituted pyrrolo[2,1-a]isoquinolines via the capture of azomethine ylides generated in situ from 1,2,3,4-tetrahydroisoquinoline and arylglyoxal.This methodology was further extended to the three-step synthesis of natural products lamellarin core and lamellarin G trimethyl ether.In chapter 4,based on our fundamental work of in situ generation of arylglyoxal from methyl ketones,we developed a molecular iodine mediated formal[2+1+1+1]cycloaddition from methyl ketones and 1,2,3,4-tetrahydroisoquinoline for the construction of polysubstituted pyrrolo[2,1-a]isoquinolines.