PhIO/Et₃N·3HF-Mediated Formation Of Fluorinated 2H-Azirines Via Reaction Of Enamines

2H-Azirines,a class of highly strain and reactive molecules with a C=N bond incorporated into a three-membered ring,represent a highly valuable class of compounds found in several natural products.They were found to exhibit a broad range of antibiotic activities.Besides,they are also the useful synthons in many transformations.In another aspect,fluorine functional group is also the key structural unit in various pharmaceuticals.The synthesis of compounds with bioactive2H-azirine moiety and the exploration on compounds with fluorinated functional groups have attracted more and more attention from organic chemists in recent years.In this thesis,we focused on develop a novel method for the synthesis of fluorinated2H-azirines.Nowadays,hypervalent iodine?III?reagents have made remarkable progress in building C-C,C-O and C-N bonds,leading to the construction of various heterocycles.Among them,difluoroiodoarenes?ArIF₂?,bearing two fluorine atoms,have been widely used in synthetic applications.It has also been well documented that the combined use of PhIO and amine·HF complex could generate PhIF₂ in situ and the use of such oxidative system could be applied to fluorination reactions.This thesis mainly covers the study of a new synthetic route to 2H-azirines from?-unsubstituted enamines,which includes the following aspects:1.Based on the results from both literature and our previous research,a novel approach to synthesize fluorinated 2H-azirines through reactions of?-unsubstituted enamines in the presence of PhIO and Et₃N·3HF was developed.2.A variety of?-unsubstituted enamines containing a carbonyl group were converted into 2-fluorinated-2H-azirines under optimal conditions.The impact of different substituted groups on the outcome of the reaction was studied.3.In order to broad the reaction scope and investigate whether a carbonyl group is necessary for this reaction or not,we also synthesized?-unsubstituted enamines bearing a cyano and nitro group.Disappointingly,no desired products can be abtained using these substrates under the optimal reaction conditions.4.The application of the methodology was explored by efficiently transforming2-fluorinated-2H-azirine into isoxazole compound via intramolecular ring expansion under the FeCl₂ catalyst.5.Based on the control experimental results and the results from previous literature,a reasonable mechanistic pathway was postulated,which the enamine substrate first underwent the?-fluorination to form the?-fluorinated enamine derivative followed bytheintramolecularazirinationreactionleadingtothedesired2-fluorinated-2H-azirine product.