Studies On The Synthesis Of Nitrogen-Containing Compounds From Isocyanides Catalyzed By Transition Metals

Nitrogen-containing compounds widely exist in a variety of natural products and drug molecules,due to their important biological and pharmaceutical activities.Therefore,the synthesis and application of various nitrogen-containing compounds have been widely concerned by organic chemists and pharmaceutical scientists.In addition,isocyanides,as a kind of small molecules containing isocyano group,play an indispensable role in coordination chemistry,material chemistry,organic synthesis,etc.Isocyanides have a variety of reaction types,and can participate in multicomponent reactions,radical reactions,insertion reactions,etc.Among them,the reaction of isocyanides participating in the synthesis of nitrogen-containing compounds under the catalysis of transition metal has become one of the research focus in the field of isocyanides chemistry due to its advantages of high bonding efficiency,good reaction selectivity and convenient operation.Although the reaction of isocyanides under the action of transition metal has been widely reported,the research based on the application of vinyl isocyanides in organic synthesis,especially the reaction of isocyanides with 2,2,2-trifluorodiazoethane,is relatively few.Based on the development of the application of isocyanides in organic synthesis,this thesis focuses on the study of the homodimerization-cyclization of two vinyl isocyanides,the coupling cyclization of vinyl isocyanides and sulfonyl azides,the reaction of isocyanides and2,2,2-trifluorodiazoethane with terminal alkynes,activated methylene isocyanides or azomethine ylides and A~3coupling cyclization reaction of 2-isocyanobenzaldehyde.The specific studies are as follows:1.The homodimerization-cyclization reaction of two vinyl isocyanides was achieved for the first time under the catalysis of rhodium.In this reaction,a series of2-(isoquinolin-1-yl)oxazoles were constructed by continuous intramolecular cyclization of1,4-diazabutatriene,which was generated by the"head-to-head"coupling reaction of vinyl isocyanides as the key intermediate.The method is simple and efficient,constructing three new chemical bonds and two rings in one step.And a series of 2-(isoquinolin-1-yl)oxazoles,which are difficult to be prepared by conventional methods,are constructed.2.The 1-aminoisoquinoline and 6-aminophenanthridine containing sulfonamides were efficiently constructed in one step by the cascade cyclization reaction of vinyl isocyanides or2-isocyanobiphenyl with sulfonyl azides under the catalysis of rhodium.This method not only achieves the reaction between vinyl isocyanides and azides for the first time,but also lays a foundation for the further application of vinyl isocyanides or 2-isocyanobiphenyl in the synthesis of other nitrogen-containing heterocyclic compounds with important applications value.3.A series of trifluoroethyl-substituted 1-aza-1,3-enynes have been synthesized by the nucleophilic addition of alkynes to the key intermediate formed by the coupling reaction of aryl isocyanides with 2,2,2-trifluorodiazoethane in the presence of rhodium.This cascade reaction is easy to operate and the raw materials are easy to obtain.This method not only provides a novel synthesis strategy for the trifluoroethyl-substituted 1-aza-1,3-enynes,but also lays a foundation for the further application of the coupling reaction between isocyanides and 2,2,2-trifluorodiazoethane.4.A rhodium-catalyzed three-component reaction of isocyanides,2,2,2-trifluorodiazoethane and activated methylene isocyanides or azomethine ylides has been successfully achieved.In this reaction,the ketenimine intermediates generated by the coupling reaction of arylisocyanides with 2,2,2-trifluorodiazoethane undergo intermolecular[3+2]cyclization with activated methylene isocyanides or azomethine ylides and efficiently constructed trifluoroethyl-substituted imidazoles in a single step.This method provides a new idea for the further application of trifluoromethyl-substituted ketenimine intermediates in the synthesis of fluoroalkyl-substituted nitrogen-containing heterocyclic compounds.5.A series of alkynyl-substituted 3,4-dihydroquinazoline were constructed by the A~3coupling cyclization reaction of 2-isocyanobenzaldehyde with alkynes and amine catalyzed by copper.This method has the advantages of mild conditions,easy availability of raw materials and good tolerance of functional groups,which not only provides a simple and efficient synthesis method for 3,4-dihydroquinazoline,but also lays a solid foundation for the further application of 2-isocyanobenzaldehyde in the synthesis of other nitrogen-containing heterocyclic compounds.