Double Annulation Of Two Different Isocyanides As An Efficient Access To Trifluoromethylated Indoles Derivatives

Fluorinated organic compounds have been widely used in medicine,pesticide and materials due to their high chemical stability,excellent biological activity and temperature resistance.However,the number of natural fluorinated organic compounds is relatively little,its source mainly depends on artificial synthesis.Therefore,the synthesis methodology of fluorinated organic compounds is one of the hot fields.At present,metal catalyzed fluorine-containing reagents have been successfully introduced into organic molecules.In addition,due to the special reactivity of isocyanides,the well-known multicomponent Ugi and Passerini reaction of isocyanides have been developed for the construction of many organic compounds.However,the chemoselective annulation of two different isocyanides has seldom been explored,probably because of the readiness of homodimerization or polymerization of isocyanides.Our research group has been devoted to the research of isocyanides for a decade.Combined with the stable characteristics of metallized isocyanide carbon anion,the tandem reaction of?-trifluoromethylated isocyanides with?-acylaryl isocyanides catalyzed by silver-promoted was designed for the first time in this paper.It provides a new and efficient protocol for the introduction of fluorine atoms into heterocyclic compounds.The thesis consists of two parts:?1?Using Ag₂CO₃ as a promoter,the cross-cycloaddition of trifluoromethylated isocyanides with another isocyanides was developed,and trifluoromethylated oxadiazino[3,2-a]indoles were efficiently synthesized in a single operation.?2?The mechanism of the reaction was explored by control experiments,which showed that the reaction was initiated by the deprotonation of trifluoromethyl isocyanides to form isocyanide silver complex,and followed by nucleophilic attack on the carbon atom of?-arylaryl isocyanides.Then it undergoes the double annulation,isomerization and oxygen transfer cascade.In this thesis,a new bimolecular cross heterocyclization reaction of isocyanides has been developed,which provides a rapid,efficient and high atom-economic method for the synthesis of trifluoromethylated oxadiazino[3,2-a]indoles.