Catalytic Cross Dehydrogenative Coupling And Bicyclization Reaction In The Construction Of N,S-Heterocycles

This paper consists of six parts.In the first part,C-S bond-forming reactions,cross dehydrogenative coupling reactions and bicyclization reactions were described.Among them,C-S bond-forming reactions included the construction of metal-catalyzed intramolecular/intermolecular C-S bonds and metal-free intramolecular/intermolecular C-S bonds.After that,the recent research progress on the construction of C-C,C-N,C-O,C-S and C-P bonds were presented by using cross dehydrogenation coupling reactions under metal-free condition.The last bicyclization reactions including intramolecular,two-component and multi-component were summaried,which had been extensively applied in the construction of carbocycles,N-heterocycles,O-heterocycles,N,O-heterocycles,N,S-heterocycles.On the basis of the above research literature,the topics basis,meaning and novelty as well as research methods for the synthesis of N,S-heterocycles were put forward.In the second part,a new cross dehydrogenation coupling under metal-free condition was developed,enabling it to construct the intramolecular C-S bond.Using triethylammonium thiolates derived from isatins and a-thiocyanatoacetophenones as starting materials and I₂ as a catalyst,the reactions in 1,4-dioxane solvent led to efficient formation of benzo[b]thiophenes with simultaneous realization of the construction of C?sp2?-S bond under metal-free conditions.Substituents on the aryl group of triethylammonium thiolates were well compatible.During which,the electron-donating substituents would favor the reaction progress as compared with electron-withdrawing counterparts.Controlled experiments indecated that the reaction process involved I₂/O₂-mediated free radical mechanism.In the third part,a new I₂/DMSO-mediated cross dehydrogenation coupling reaction for constructing intermolecular C-S bond was described.By employing the above-mentioned triethylammonium thiolates to react with indoles under theI₂/DMSO-mediate conditions,3-sulfenylindoles were regioselectively synthesized with excellent yields with simultaneous realization of the construction of intermolecular C-S bond.When rich electron pyrroles as a replacement of indoles were used to expand the reaction scope,the reaction proceeded smoothly to access the corresponding sulfenylpyrroles with excellent yield.Substituents on the pyrrole ring may control the sulfenylation of its position.Controlled experiments confirmed that the reaction involved a electrophilic substitution process,rather than a free radical mechanism.In the fourth part,a new I₂/O₂-mediated cross dehydrogenation coupling reaction for forming intermolecular N-S bond was developed.I₂/O₂-Mediated reaction between triethylammonium thiolates and aryl hydrazines efficiently delieveredfunctionalized 1,2,3-thiadiazoles.Substituents of triethylammonium thiolates and aryl hydrazines did not hamper the reaction progress.Among them,aryl hydrazines bearing electron-neutral substituents led to the slightly higher yields than that of electron-donating and electron-withdrawing counterparts.Controlled experiments showed that the reaction involved an I₂/O₂-mediated free radical mechanism.On the basis of these observations,a reasonable reaction mechanism was proposed,which involved the in situ formation of hydrazone,the formation and cleavage of S-I bond and free radical coupling.In the fifth part,a new bicyclization reaction of triethylammonium thiolates was described.We continued to use triethylammonium thiolates as reaction substrate andemployed them to react with aliphatic hydrazines,enabling an unexpected cascade bicyclization process,rather than a free radical mechanism described in the previous section,to obtain a series of pyrazole[3,4-c]pyridines with high chemoselectivity and regioselectivity.Based on the literature survey and our experimental results,a reasonable mechanism was proposed,which involved intermolecular proton exchange,tautomerization,selective nucleophilic addition and so on.It was worth mentioning that aliphatic hydrazines with no hydrogen bonding acceptor moieties were not suitable for this bicyclization reaction.In the sixth part,the experimental dates were conducted.The structures of all the products were confirmed by IR,1H and 13C NMR and HRMS characterization,some of which were confirmed by single-crystal X-ray diffraction.Additionally,the spectrum of the representative compounds were provied.