Aryne Induced Dearomatization Reaction Of 1-Fluoroisoquinolines

Aromatic compounds are widely present in nature,and dearomatization reactions can make them highly functionalized and construct three-dimensional molecules.As an important organic synthesis intermediate,benzyne provides an efficient pathway for the dearomatization reactions.In this thesis,a new method for the dearomatization of 1-fluoroisoquinoline compounds initiated by benzyne is developed.This thesis first introduces benzyne and dearomatization reactions,including the traditional types of dearomatization reactions,dearomatization reactions of various aromatic compounds,and dearomatization reactions initiated by benzyne.Dearomatization of indole,aromatic amine,phenolic compounds,pyridine,pyrrole,and furan are systematically reviewed.The dearomatization reactions induced by benzyne is also reviewed,followed by description of the basis for the selection of the topic of this thesis.Secondly,the preparation of 1-fluoroisoquinoline and other substrates is described.1-Fluoroisoquinoline compounds were prepared from isoquinolines in three steps through oxidation,chlorination and fluorination.The preparation methods of other substrates are introduced one by one.Subsequently,the dearomatization reaction of 1-fluoroisoquinolines initiated by benzyne was discussed.We used 1-fluoroisoquinoline and Kobayashia benzyne precursor as the raw materials,optiming the reaction temperature,solvent,base and material ratio obtain the optimal reaction conditions.Under the optimal reaction conditions,we studied the general applicability of the reaction substrates,and obtained dearomatization products mostly in good yields.In addition,the using 4-haloquinolines as the substrates also achieved the dearomatization of quinolines.When 2-fluoropyridine reacts with benzyne under our optimal conditions,after dearomatization of pyridine,a cycloaddition product from[4+2]reaction of 2-pyridone with benzyne is obtained.Then the mechanism of the reaction was verified and a possible reaction mechanism was proposed.Finally,the unreported compounds were confirmed by spectroscopies,including 1H NMR,13C NMR,19F NMR and high resolution mass spectrometry.Based on the concept of "green chemistry",this reaction uses water as the proton source to perform dearomatization reaction initiated by benzyne,which provides a new path for the development of dearomatization reactions.