Formation Of Functionalized2H-Azirines Through PhIO-Mediated Trifluoroethoxylation And Azirination Of Enamines

2H-Azirines, the smallest unsaturated nitrogen heterocycles, represent a highlyvaluable class of compounds found in several natural products which were isolatedfrom streptomyces aureus. They were found to exhibit a broad range of antibioticactivities. More importantly, they are the valuable precursors in many usefultransformations. In another aspect, fluorinated functional groups are also the keystructural units in various pharmaceuticals. The synthesis of compounds withbioactive azirine moiety and the exploration on compounds with fluorinatedfunctional groups have attracted more and more attention from organic chemists inrecent years. In this thesis, we described a novel method for the synthesis offluorinated2H-azirines.Nowadays, hypervalent iodine(III) reagents have been widely applied to buildC–C, C–O and C–N bonds, leading to the construction of various heterocycles. Thisthesis mainly covers the exploration of a new synthetic route to2H-azirines fromα-unsubstituted enamines, which includes the following aspects:1. Based on the results from both literature and our previous research, a novelapproach to synthesize2H-azirines through reactions between α-unsubstitutedenamines and PhIO in trifluoroethanol (TFE) was developed.2. A variety of α-unsubstituded enamines were converted into2-triflouroethoxyl-2H-azirines under the optimal reaction conditions. The impact ofdifferent substituted groups on the outcome of the reaction was studied.3. We also switched TFE to other alcohols, such as methanol and t-butyl alcohol,to continue to explore the scope and limitation of this reaction.4. The application of the methodology was explored by efficiently transforming2-triflouroethoxyl-2H-azirine into isoxazole compound via intramolecular ringexpansion.5. Based on an important intermediate being captured and the results fromprevious literature, a reasonable mechanistic pathway was postulated.