The Research On In Situ Trapping Of Ketoaldehyde Intermediates To Construct 6/7/8 Membered Heterocycles Based On I₂/DMSO System

Nitrogen-containing heterocyclic compounds are a class of extremely important organic small molecular structures,which are widely used in various fields,such as medicine,dyes,and optoelectronic materials,and have become an indispensable part of human life.Therefore,developing an efficient,green and atomic-economic path to construct nitrogen-containing heterocyclic compounds has great significance.In the study of new organic reaction design,the in situ-captured strategy of active intermediates is based on the metastable structure generated in the reaction process,and through the in situ-captured of other molecular fragments,the bonding reaction forms expected or unexpected structure.The design principle of this strategy provides an important way for the generation of new molecular frameworks,the occurrence of new bonding methods and the development of new reactions,which has become one of the most important tools in the field of heterocyclic synthesis.In the past ten years,our research group has realized a series of achievements in the synthesis of novel nitrogen-containing heterocyclic compounds based on in situ-captured of aryl ketoaldehyde mediated by I₂/DMSO combination reagent.The research topic of this paper is to further expand the research on the in-depth construction level of I₂/DMSO combination reagent mediated heterocyclic synthesis toolbox,to improve and enrich the synthesis space of the system,and to build nitrogen-containing heterocyclic molecular libraries with diverse structures,novel skeletons in high performance.This paper takes multi-component reaction as the core strategy.Starting from the ketoaldehyde intermediate,a series of elegant multi-nitrogen fused heterocycles,medium-sized seven membered rings,eight membered rings were constructed via intermolecular cascade cyclization,double C（sp³）-H ammoniation,intermolecular bicyciization and smaii molecule self-assembly,which further enriches the capture strategy of active intermediates in I₂/DMSO combination reagent system.Specifically,it is mainly divided into the following parts:In the first chapter,the development of modern organic synthesis,the requirements and challenges,the concept of capture strategy of active intermediates and the research status are briefly introduced.The capture strategy of active intermediates in I₂/DMSO combination reagent system and its applications in organic synthesis are summarized in detail.Finally,the paper puts forward the idea of establishing the topic.In the second chapter,based on the principle of one pot multi-component intermolecular cascade cyclization,we constructed 2,3-diaroyl quinolines using methyl ketones,aromatic amines and enaminones as substrates.The quinoline containing 1,4-dicarbonyl skeleton can be directly functionalized by hydrazine hydrate in one pot without separation and purification to construct nitrogen-containing quinolinopyridazine derivatives.This reaction provided a new route for the synthesis of cyclic 1,4-dicarbonyl skeleton and its application in one pot.In the third chapter,based on the reaction principle of double C（sp³）-H ammoniation,we used methyl ketones,aromatic amine and cyanamide as substrates to construct star molecular skeleton 2,4-diamino-1,3,5-triazine derivatives via intermolecular condensation and ammoniation.The method used easily available cyanamide as ammonia source,which provided a new example for the green and efficient synthesis of triazines.In the fourth chapter,based on the principle of intermolecular bicyclization/ring-opening reaction,using aromatic acetylene,aromatic amine and water as substrates to construct nitrogen-containing eight-membered ring skeleton via breaking the aromatic acetylene carbon-carbon triple bond.This reaction reported for the first time that aryl acetylene was involved in the synthesis of heterocycles as a two-carbon synthon in the form of cleavage.In the fifth chapter,on the basis of the previous chapter,based on the principle of intermolecular continuous/ring-opening reaction,using methyl ketone,aromatic amine,dimethyl sulfoxide and water as substrates to construct quinazolinone through the breaking of methyl ketone carbon-carbon bonds.This reaction cleverly re-sewed and assembled the one-carbon synthon produced by the cleavage of the C-S bond in DMSO,the acyl source and carbonyl source produced by the cleavage of the methyl ketone carbon-carbon bond to the target molecular structure.In the sixth chapter,based on the principle of multi-component small molecule self-assembly,we employed methyl ketones,phenylhydrazine,and ethyl acetoacetate as substrates to construct oxa seven-membered ring oxepin through five-component reaction.This reaction realized the direct construction of C-O bond between ethyl acetoacetate molecules for the first time,and provided a simple and efficient multi-component reaction path for the synthesis of medium-sized rings.The seventh chapter summarized all the work of the doctoral dissertation,and put forward prospects for further enriching the capture of in situ intermediates under the I₂/DMSO system.