Study On The Fluoroalkyl Carbene Transfer Reaction Based On O-trifluoromethylbenzenesulfonylhydrazon

In recent decades,organofluorine compounds have received increasing attention mainly due to their extensive use in the chemical industry,especially in medicinal and agricultural chemistry.However,naturally occurring fluorine-containing organic compounds are rare and occur only as metabolites in a few microorganisms and marine organisms,so they are mainly obtained by chemical synthesis.Since the first preparation of CF3CHN2 by Gilman et al in 1943,fluoroalkyl diazos have become versatile fluorine-containing building blocks in organic synthesis,and related research on synthesis and transformation has increased year by year.As attractive precursors for functionalized syntheses,fluoroalkyl diazo compounds can act as a 1,3-dipole or release nitrogen gas to form carbene that participate in the reaction in the presence of light,heat,or transition metals.They have shown remarkable activity in the synthesis of heterocyclic compounds,cyclopropanation,X-H insertion,and cross-coupling reactions.However,the volatile,explosive,and difficult-to-store natural properties of fluoroalkyl diazos make them challenging to use.In addition,the distinctive chemical properties that fluorine atoms contribute to diazo compounds do not appear to be fully explored.Therefore,it is of great significance for fluorine chemistry and chemical industry to develop safe and stable fluoroalkyl diazo precursors,find their novel reactivity,and establish efficient synthesis and conversion system.Our research group has been devoted to the study of carbene chemistry of sulfonylhydrazones and fluorine chemistry.In our investigations,we have found that fluoroalkyl ketones can be readily and efficiently converted to sulfonylhydrazones,which serve as precursors for fluoroalkyl diazo compounds.This basis enables the conversion of fluoroalkyl ketones,which are difficult to manipulate.Building on this foundation,this thesis explores the new reactions with fluoroalkyl carbene based on N-triftosylhydrazones derived from fluoroalkyl ketones.Through this effort,we aim to expand the frontiers of fluoroalkylcarbene chemistry.Specific research includes the following three main aspects.1.We have developed a novel carbene strategy for the controllable hydrodefluorination of fluoroalkyl ketones,and successfully achieved selective(deutero)hydrodefluorination of diverse fluoroalkyl ketones with(deuterated)water in Rh catalyzed manner.The development of this strategy provides a convenient and direct method to obtain various partially fluorinated ketone compounds.The practicality of this strategy was confirmed by the modular synthesis of various hydrogenated and deuterated fluoroalkyl carbonyl homologues of biologically active molecules.2.Inspired by the hydrodefluorination reaction,we developed a tandem defluorinative vinylation and rearrangement reaction of fluoroalkyl N-triftosylhydrazones.This strategy has led to the successful defluorinative carboimination of fluoroalkyl ketones.Remarkably,our work represents the first instance of defluorinative bifunctionalization of fluoroalkyl ketones,thus offering valuable insights for the functionalization of C-F bonds.Theoretical calculations have shown that silver serves as both a catalyst in carbene reaction and as a Lewis acid,promoting the aza-Claisen rearrangement reaction.3.We development an innovative asymmetric one-carbon insertion reaction of fluoroalkyl carbene with indole,which breaks through the prevailing substrate limitation that carbene precursors must have leaving groups.Remarkably,we have achieved the conversion of two-dimensional heteroaromatic structures into three-dimensional heterocycles through one-carbon insertion.The convenient synthesis of drug analogues demonstrates the promising practical utility of this method.The specificity of this reaction towards α-CF3-carbenes also highlights the significant impact of fluorinated groups on the reactivity of organic molecules.