Studies On The Synthesis Of Difluoromethylated Nitrogen Heterocycles From Functionalized Isocyanides And Difluorocarbene

Considering the broad application of difluoromethylated nitrogen heterocycles in the fields of pharmacology and agrochemistry,the development of efficient methods for their preparation would be desirable.At present,the synthesis strategies of difluoromethylated nitrogen heterocycles mainly include deoxyfluorination of nitrogen heterocyclic aldehydes,difluorination of nitrogen heterocycles benzylic C-H bonds,transformation of other fluoroalkyl nitrogen heterocycles,difluoromethylation of nitrogen heterocycles,cyclization of difluoromethylated building blocks and difluoromethylation/cyclization of chain substrates.However,most of these synthesis methods require the use of transition metal,acid or base catalysts and the pre-synthesis of nitrogen heterocycles or difluoromethylated substrates.Therefore,it is necessary to develop efficient,metal-free and general synthesis strategies for difluoromethylated nitrogen heterocycles.This thesis is divided into four chapters:Chapter One: Research background and topic selectionIn this chapter,the significance of difluoromethylated nitrogen heterocycles and the existing synthesis methods,the reaction types of difluorocarbene and the synthesis and transformation of ketenimines involved in isocyanides are briefly reviewed,and the basis of this thesis is described.Chapter Two: Synthesis of difluoromethylated pyridines by isocyanides and difluorocarbeneThis chapter describes the tandem cyclization of various functionalized isocyanides and difluorocarbene under metal-free conditions.This domino reaction provides a new and efficient method for the synthesis of difluoromethylated pyridines.We have also developed a method to access tetrafluoroethylated pyridines.These reactions can incorporate the difluoromethyl group simultaneously into a nitrogen heterocyclic ring construction in one step from simple and easily available raw materials.This new domino reaction features many advantages such as high step economy,broad substrate scope,good functional group compatibility,no metal catalyst and operational simplicity.This chapter provides the synthesis methods of functionalized isocyanides and difluoromethylated nitrogen heterocycles,the analysis of the structural characterization data of the synthesized compoundsChapter Three: Synthesis of other difluoromethylated nitrogen heterocycles by isocyanides and difluorocarbeneThis chapter describes the tandem cyclization of various functionalized isocyanides and difluorocarbene under metal-free conditions.This domino reaction provides a new and efficient method for the synthesis of difluoromethylated quinolines,isoquinolinse,carbolines and other nitrogen heterocycles.This reaction not only achieved the first synthesis of aryl-substituted difluoroketenimine intermediate involving arylisocyanide,but also found the first6π-electrocyclization reaction involving this intermediate.This chapter provides the synthesis methods of functionalized isocyanides and difluoromethylated nitrogen heterocycles,the analysis of the structural characterization data of the synthesized compoundsChapter Four: summary and prospectThis chapter summarizes the work content of this thesis,and makes plans for the later work,hoping to achieve the synthesis of different fluoroalkyl nitrogen heterocycles by changing different fluorocarbene.