Investigation On Trifluoromethylation And Annulation Of Enamines

The synthesis of complex organic functional molecules from readily available raw materials has always been the goal of organic synthesis chemistry.Enamines and their derivatives are important organic compounds that are widely found in natural products and drug molecules.As organic synthons,enamines have the advantages of easy to prepare and active chemical property,which are important raw materials for the synthesis of various nitrogen compounds.The ?-C of the enamine is electronegative which can achieve the halogenation,arylation,thiolation,and amination through nucleophilic and oxidative processes,thereby building multifunctional olefins.On the other hand,enamines are also useful materials for various nitro-containing heterocycles such as pyrroles,indoles,quinolines,pyrazoles,oxazoles by cyclizing with unsaturated compounds.Based on the above background and the accumulation of our group,this thesis focused on the electron-depleted enamines and developed new methods for constructing more complex organic functional molecules by employing readily available reagents.The results are as follows:Firstly,we realized the direct ?-C-H trifluoromethylation of enamines by employing cheap and stable Langlois reagent(sodium trifluoromethanesulfinate)as the trifluoromethyl radical source and TBHP as oxidant.The reaction conditions are mild and have a good tolerance for moisture and air.Noteworthily,the reaction can specifically produce the E-isomer.Mechanism studies have demonstrated that the reaction proceeds through a free radical process.The final products can be used as the raw materials for the synthesis of ?-amino acids having good potential for practical application.Secondly,we developed a new methodology for the synthesis of 1,5-disubstituted and 1,4,5-trisubstituted 1,2,3-triazoles via the oxidative cyclization of enamines and N-tosylhydrazine under the TBAI/KI-TBHP oxidation system.Compared with the traditional methods,the raw materials of this method are more cheap and easy to obtain and avoids the use of organic azide.The mechanism studies verified that the reaction went through a amino exchange process.It is noteworthy that the product are precursors of a kind of anti-influenza virus drug,and a series of potential drug molecules containing fluorine substituents were synthesized by this method and their anti-H3N2 virus activity was tested,demonstrating the practical application value of the reaction.