Study On Trifluoromethylation Of 3-vinyl-2-siloxyindoles

Based on the unique spatial structure and electronic characteristics of trifluoromethyl group,it could bring important impacts on pharmacokinetics when introducing trifluoromethyl group into drug molecules,a great deal of works has been devoted to the methodological study of which with different structures of substrates as consequence.Indole molecules widely exist in nature and occupy an important position in the community of life science and pharmaceutical research and development.Introducing trifluoromethyl group into indole molecules could realize a great combination that merge the advantages of both,which could promote the discovery of innovative fluorine-containing drugs to give impetus to the development of life science.3-Vinyl-2-siloxyindoles compounds,which include the structural characteristics of silyl enol ether in the molecules,are a kind of easily prepared indole derivatives.Based on the trifluoromethylation method of silyl enol ether,the trifluoromethylation reaction of 3-vinyl-2-siloxyindoles could be explored by using efficiency trifluoromethylation reagent to establish an efficiency synthesis method of trifluoromethyl-containing indole derivatives,which is theoretically significant and has potential application value.Our research group has developed an electrophilic hypervalent iodine trifluoromethylation reagent ArICF₃X.On this basis,PhICF₃Cl was used as trifluoromethylation reagent to explore the vinylogous trifluoromethylation reaction of 3-vinyl-2-siloxyindole-type systematically.The main contents include:1.In the first chapter,on the basis of a brief summary of the synthesis and application of electrophilic trifluoromethylation reagents,the research progress of trifluoromethylation of silyl enol ether is emphatically summarized.2.In the second chapter,the topics basis and research strategy of this thesis are demonstrated.Based on the structural characteristics of the vinylogous silyl enol ether moieties of 3-vinyl-2-siloxyindole derivatives,a trifluoromethylation reaction research scheme was proposed to establish a synthesis method of trifluoromethyl substituted indole derivatives,including the selection of electrophilic trifluoromethylation reagents,the optimization of reaction conditions and the prospect of application scope of this synthesis strategy.3.In the third chapter,trifluoromethylation of 3-vinyl-2-siloxyindole was achieved by using PhICF₃Cl as the trifluoromethylation reagent without any additives and catalysts,which establish an efficient new synthesis method of CF₃-containing indole derivatives.3-Trifluoromethyl methylene-2-indolone derivatives were synthesized in 60%-85%yield through this mild,simple-operated reaction,and the good functional group tolerance provides a wide application range.Through this work,24 new compounds were synthesized and characterized by¹H NMR,¹³C NMR,¹⁹F NMR and HRMS respectively.