| Nitrogen-containing heterocyclic frameworks are widely present in various natural products,bioactive active molecules,and organic functional material molecules,which play an indispensable role in the fields of drug development,materials,life sciences and so on.Therefore,exploring new ways to construct various nitrogen heterocyclic structures has always been an important research topic in organic synthesis.Based on the new requirements of the development of modern organic synthesis,it is expected to explore and establish new reactions and new methods with readily available starting materials,high atomic economy,simple and safe operation,environmental friendliness,low energy consumption and high conversion rate,which can improve the synthesis efficiency from the source and reduce the negative impact of the synthesis process.These challenging problems in modern organic synthesis have further promoted the innovation of organic synthesis concepts,and some more efficient synthesis strategies have emerged.Among them,the tandem cyclization strategy can realize ring construction by continuously formation of multiple chemical bonds in one pot,which eliminates the steps of separation and purification of intermediates and greatly improves the reaction efficiency.Among the many synthetic methods for constructing nitrogen heterocycles,it is undoubtedly the most suitable strategy to meet the core requirements of ideal synthesis.Oxidation systems are the most basic type of reaction systems in organic synthesis,and it is of universal significance for the study of tandem cyclization reactions in oxidation systems.However,some unintended processes such as oxidative cracking and over-oxidation are prone to occur in this type of system,which it is more challenging for us to rational design of novel tandem cyclization reactions.We hope that on the basis of the principle of self-organized reaction proposed by our group,by logically combining some fragmented organic unit reactions such as substitution reaction,addition reaction,elimination reaction,rearrangement reaction,coupling reaction and name reaction,etc.,and based on the principle of self-ordered transformation of organic unit reactions.we can finally achieve the goal of rational design of novel tandem cyclization reactions in oxidation systems.Through this,we can not only establish new reactions,provide simple and efficient new methods for the synthesis of some important physiological active nitrogen heterocycles,but also can reveal new reaction mechanisms and discover more new reaction models.In this thesis,we focused on the construction of nitrogen-containing heterocycles by rational design of tandem cyclization reactions under the oxidation systems such as Cu/air,K2S2O8 and I2/DMSO.Five novel tandem cyclization reactions were designed to complete the efficient synthesis of nitrogen heterocyclic structures such as 2-(1,3,4-oxadiazol-2-yl)anilines.Specifically,it mainly includes the following seven chapters:In chapter 1,on the basis of detailed literature research and analysis,we firstly introduced the challenging topics in modern organic synthesis and the principle and significance of self-organized reactions,then summarized the relevant research progress of tandem cyclization reactions in oxidation systems,and put forward the research ideas and work to be expanded according to the existing blind and blank points.In chapter 2,in the system of air oxidation catalyzed by copper,a simple and efficient method has been developed for the synthesis of 2-(1,3,4-oxadiazol-2-yl)aniline derivatives from easy available isatins and hydrazides.This tandem cyclization reaction integrated consecutive condensation,base-promoted ring-opening and the key copper-catalyzed decarboxylative coupling sequences.The use of copper-catalyzed decarboxylation coupling strategy to achieve the construction of intramolecular C-O bonds in this synthesis method is still rarely reported.This strategy also provides new ideas for the synthesis of other heterocyclic compounds.In chapter 3,in the system of air oxidation catalyzed by copper,we have successfully developed a practical domino protocol for the synthesis of potentially valuable quinazoline derivatives from simple and readily available 2-bromoaldehydes,benzylamines,and sodium azide via the integration of continuous condensation,copper-catalyzed SNAr,Cu/O2 synergistic catalytic oxidation,intramolecular denitrification and cyclization sequences.In this reaction,the ortho-functionalized aryl azide intermediate was generated in situ,followed by a process of oxidative amination of sp3 C-H bond,the intramolecular C-N bond could be constructed directly.This strategy avoids the use of pre-prepared aryl azide substrates.In chapter 4,on the basis of chapter 3,and by utilizing the dual reaction characteristics of sodium azide,we have developed a copper catalyzed aerobic multicomponent tandem cyclization reaction for the efficient synthesis of 1H-[1,2,3]triazolo[4,5-c]quinoline derivatives from commercially available 2-bromobenzaldehydes,aryl methyl ketones,and sodium azide.This tandem cyclization reaction integrated consecutive Aldo condensation,[3+2]oxidative cycloaddition,copper-catalyzed SNAr,and denitrogenation cyclization sequences in one-pot.In chapter 5,a K2S2O8 mediated four-component oxidative tandem cyclization reaction has been developed for the synthesis of potentially valuable 4-methylpyrimidine derivatives by using simple methyl ketone,hydrazine hydrochloride and DMSO as starting materials.This elegant domino process integrated continuous sp3 C-H olefination,Pummerer reaction,Michael addition,condensation cyclization,elimination,isomerization sequences.Notably,DMSO was an essential component as well as the solvent.Two molecules of DMSO served as the source of the methyl unit and the methine unit to participate in this tandem annullation reaction.This strategy provides a novel example for the construction of heterocyclic compounds by using DMSO as a dual synthon.In chapter 6,in the oxidation system of I2/DMSO,we have developed a tandem annulation/ring-opening reaction for the synthesis of(E)-3-(2-acyl-1H-benzo[d]imidazol-4-yl)acrylaldehyde derivatives from simple and readily available methyl ketone and 8-aminoquinoline based on Komblum oxidation as the key node.The reaction process integrated consecutive iodination,Kornblum oxidation,condensation cyclization and C-N cleavage sequences.The acrylaldehyde functional group in products is valuable and can be used for further synthetic derivatization.In chapter 7,the summery of this thesis and the outlook of future work were given. |
