Study On The Synthetic Methodology Of Constructing Indolizine And Amide Derivatives Under Metal-Free Conditions

As one of the structural units of heterocyclic compounds,N-Fused heterocyclic compounds are widely found in nature,and they have important applications in various fields.Indolizine compounds,as a class of nitrogen-containing aromatic heterocyclic compounds,are widely found in natural products and synthetic organic compounds.Through continuous research,it has been found that indolizine derivatives not only have good biological activity and are used as pharmaceutical intermediates,but also widely used in dyes,polymer materials and fluorescent probes.Since the first synthesis in the19th century,the synthetic methodology research of indolizine and its derivatives has attracted much attention.In this paper,a series of pyrrolo[3,4-a]indolizine-1,3（2H）-dione and 1,3-disubstituted indolizine derivatives were simply and efficiently constructed under metal-free conditions.Amide compounds are a very important class of compounds in organic chemistry.They contain amide bonds in many natural products,agricultural chemicals,synthetic products and polymers,and can also be used as potential synthetic precursors of drugs.The formation of amide bonds is one of the most common transformations in organic synthesis methodology.For many years,the synthesis and modification of amide compounds has never stopped.Although many strategies for the synthesis of amides have been reported,it is still necessary to develop more simpler and efficient methods.Therefore,in this paper,we propose a new method for the direct synthesis of amide derivatives using simple and readily available substrates under metal-free conditions.In the chapter 1,the introduction,biological activity,photophysical properties and latest synthesis research progress of indolizine compounds are summarized.In addition,the introduction,biological activity and synthesis progress of amide compounds are also reviewed.At the same time,the significance of the topic selection and the design ideas in this paper are proposed.In the chapter 2,transition-metal-free catalyzed[3+2]cycloadditions/oxidative aromatization three-component reactions for the successful direct construction of pyrrolo[3,4-a]indolizine-1,3（2H）-diones using pyridine/quinoline/isoquinoline,aromatic ketones and maleimide as substrates are reported.Compared with traditional methods,this method also has good yield and substrate universality under metal-free conditions.And through corresponding control experiments,a possible reaction mechanism is proposed.In the chapter 3,an I₂/TBHP-mediated[2+1+1+1]cycloadditions/oxidative aromatization reactions for the synthesis of 1,3-disubstituted indolizine derivatives using the one-pot cascade process have been developed.This method uses unfunctionalized pyridine/isoquinoline,aromatic ketone and TBHP as reaction substrates.Through the control experiments,TBHP was speculated to participate in this reaction as oxidant and reactant,and the reaction mechanism was studied.In the chapter 4,a series of amide compounds was directly constructed using caprylic hydrazide and amine as substrates under metal-free conditions.This method uses I₂ as the oxidant and toluene as the solvent,which has the characteristics of simple operation and environmental friendliness.