Study On Iodine-mediated Oxidative Cyclization Reactions For The Construction Of Six-membered Nitrogen Heterocycles

Six-membered nitrogen heterocycles exhibit important applications in chemistry,biology,materials,medicine,etc.For a long time,the construction and functionalization of six-membered nitrogen heterocycles has been a hot spot in scientific community.With the development of economy and society,environmental problems are becoming increasingly prominent.The development of green synthetic methods featuring high step and atom efficiency by converting naturally abundant amines into value-added functional six-membered nitrogen heterocycles gradually becomes the concern of scientists.The utilization frequence of iodine by researchers is increasing due to the abundant availability,unique catalytic performance,and easily handling characteristics of iodine reagents.Based on long-term research of the construction of nitrogen-containing heterocycles by our research group,it would be very meaningful to explore the use of iodine catalysts to construct six-membered nitrogen-containing heterocycles through iodine catalysed cyclization reaction under oxidative conditions.This artical mainly contains the following two aspects of research content:Part 1.In this chapter,we introduce a method for synthesizing iodo-indoquinoline by direct cyclization of elemental iodine,serving as both reactant and catalyst,together with 2-aminobenzyl alcohol and indole.Under the O₂/DMSO system,through mild oxidation,regeneration of elemental iodine is realized,thereby greatly improving the reaction efficiency.The developed reaction has the advantages of high substrate compatibility,good regioselectivity,high step-and atom-efficiency,and no need for any metal catalyst.This synthetic method provides the possibilities of further preparing the indoloquinoline with structural diversities.Part 2.A new iodide-mediated three-component annulation reaction of secondary anilines,cyclohexanones and elemental sulfur is demonstrated,which allows access to various phenothiazines with the merits of formation of multiple chemical bonds in one single operation,high step-and atom-efficiency,readily available feedstocks and catalyst system,good substrate and functional group compability.The developed chemistry capable of constructing novel phenothiazines with structural diversities offers a significant basis for further applications.Briefly,in the research work of this thesis,C–C bond,C–N bond or C–S bond can be efficiently constructed in one-step via iodine-mediated oxidation cyclization strategy,providing effective synthetic method for constructing polycyclic iodoindoloquinolines and phenothiazines compounds.This method enriches organic synthetic methodology connotation of iodine-mediated oxidation cyclization reaction,bringing new solution to the construction of six-membered nitrogen heterocyclic skeleton.