Study On The Green Synthesis Of Fused N-heterocycles Under The Catalysis Of Coppre Or Rhodium Catalyst

This dissertation aims to develop highly efficient and green synthetic methods for the preparation of some fused N-heterocyclic compounds.The dissertation is divided into the following five chapters:Chapter 1:IntroductionIn this chapter,the advent and development of green chemistry,the basic principles and evaluation indexes of green chemistry,the basic strategies and research fields of green synthetic chemistry,the significance of fused N-heterocycles including indoles,benzo[a]carbazoles and imidazo[1,2-a]pyridines,and the applications of copper-or rhodium-catalyzed synthesis in green synthetic chemistry were briefly introduced.Chapter 2:Highly selective synthesis of 3-cyano-1H-indoles,9H-pyrimido[4,5-b]indoles and 9H-pyrido[2,3-b]indoles.In ths chapter,a novel and selective synthetic method for the preparation of several indole derivatives via copper-catalyzed one-pot multi-component cascade reactions of 1-brolo-2-(2,2-dibromovinyl)benzenes with aldehydes and aqueous ammonia was disclosed.It turned out that the concentration of ammonia,the molar ratio of reagents and the structural feature of the aldehyde substrates serve as keyfactors in controlling the selective formation of 3-cyano-1H-indoles,9g-pyrimido[4,5-b]indoles,or 9H-pyrido[2,3-b]indoles.Compared with literature methods,this method has the advantages such as readily available starting materials,mild reaction conditions,and divergent reaction patterns toward different products with easily tunable selectivity.Chapter 3:Efficient synthesis of 3-cyano-1H-indoles and their 2'-deoxyribonucleoside derivativesIn this chapter,an efficient and economical method for the preparation of 3-cyano-1H-indoles via copper-catalyzed domino reactions of 2-(2-bromophenyl)acetonitriles with aldehydes and aqueous ammonia is presented.Mechanically,the formation of 3-cyano-1H-indoles involves a one-pot cascade procedure consisting of an aldol-type condensation,a copper-catalyzed amination,and an intramolecular Michael addition followed by a dehydrogenative aromatization.The main advantages of this new method include simple operation procedure,high efficiency and good atom-economy.Moreover,the indole products thus obtained were found to be ready substrates for the preparation of indole 2'-deoxyribonucleosides through an unprecedented and highly practical glycosylation procedure,in which the required C-N bond formation and toluoyl protecting group removal were accomplished efficiently in one pot.In addition,the in vitro anticancer activities against several cancer cell lines of these indole 2'-deoxyribonucleosides were evaluated,and some valuable lead compounds were identified.Finally,by using Atom Economy,Reaction Mass Efficiency,Environmental Factors,Mass Intensity and Environmental Quotient as the criteria,the greenness of the synthetic methods for the preparation of 3-cyano-1H-indoles and their 2'-deoxyribonucleoside derivatives was evaluated.The corresponding results showed that it could partially meet the requirements of green synthetic chemistry.Chapter 4:Efficient synthesis of diversely substituted benzo[a]carbazole derivativesIn this chapter,a novel synthetic approach toward diversely substituted benzo[a]carbazoles through Rh(?)-catalyzed inert C(sp2)-H bond carbenoid insertion,intramolecular aldol-type condensation and aromatization of 2-arylindoles,3-carbaldehyde-2-arylindoles or 3-carbonitrile-2-arylindoles with ?-diazo carbonyl compounds has been established.To our knowledge,this is the first example in which the NH unit of indole is used as a directing group for an intramolecular C(sp2)-H bond functionalization to give benzo[a]carbazole derivatives.Compared with literature methods,this new method showed advantages such as simple starting materials,high efficiency and good atom-economy.By using Atom Economy,Reaction Mass Efficiency,Environmental Factors,Mass Intensity and Environmental Quotient as the criteria,the greenness of this novel synthetic method was evaluated.The corresponding results showed that it could partially meet the requirements of green synthetic chemistry.Chapter 5:Novel and efficient synthesis of naphtho[1',2':4,5]imidazo[1,2-a]pyridinesIn this part,a Rh(?)-catalyzed cascade reaction of 2-arylimidazo[1,2-a]pyridines or 3-carbaldehyde-2-arylimidazo[1,2-a]pyridines with ?-diazo carbonyl compounds was disclosed.It turned out that in the presence of Rh(?)catalyst 2-arylimidazo[1,2-a]pyridine derivatives could undergo inert C(sp2)-H bond carbenoid insertion,aldol-type condensation and aromatization with ?-diazo carbonyl compounds to afford diversely substituted naphtho[1',2':4,5]imidazo[1,2-a]pyridine with high efficiency and good selectivity.Compared with literature methods,this novel method has advantages such as readily available starting materials,high atom-economy,excellent selectivity and simple procedure.By using Atom Economy,Reaction Mass Efficiency,Environmental Factors,Mass Intensity and Environmental Quotient as the criteria,the greenness of this method was evaluated.The results showed that this method could partially meet the requirements of green synthetic chemistry.In conclusion,under the guidance of the concept of green chemistry,novel and green methods for the green synthesis of some fused N-heterocycles have been developed in this dissertation.By using these methods,a series of fused N-heterocyclic compounds with potential applications were synthesized.It is expected that the results presented in this dissertation will help to pave the way toward the industrial scale green preparation of related fine chemicals.