Copper-Mediated Trifluoromethylation

Currently, organic chemists and medicinal chemists have been paying much attention to the introduction of fluorine atom(s) or fluorine-containing groups into potentially biologically active molecules because their introduction could bring about remarkable and profound changes in physical, chemical, and biological properties of the compounds. In addition, naturally occurring organofluorine compounds are infrequent, so the development of new synthetic methods for introduction of fluorine atom(s) or fluorine-containing groups is needed. The transition-metal-catalyzed direct trifluoromethylation of carbon-hydrogen bond or heteroatom-hydrogen bond is an efficient method to achieve this goal. In this thesis, trifluoromethylation of different substrates with nucleophilic trifluoromethylation reagent (Me3SiCF3) were studied.PartⅠ:The copper-mediated trifluoromethylation of nitrogen -hydrogen of secondary amine was studied. It was a pity that the major product was hydrazine.PartⅡ:The copper-mediated trifluoromethylation of aryl diazonium tetrafluoroborate was studied. We chose 4-nitrobenzenediazonium tetrafluoroborate as the model substrate. The GC yield of 1-nitro-4-(trifluoromethyl)benzene increased to 35% when Cul was used as the catalyst in DMF. However, in other conditions, the yields were during trace to 18%. The products included nitrobenzene,1-iodo-4-nitrobenzene and azo compound.PartⅢ:An improved copper-mediated oxidative trifluoromethylation of terminal alkynes was developed. The optimal reaction conditions were established as follows: 2.0 equiv of CuCl,2.0 equiv of phen,2.0 equiv of tBuOK,2.0 equiv of Ag2CO3,2.0 equiv of Me3SiCF3, and 1.0 equiv of terminal alkyne in DMF at room temperature. Then oxygen was tested for the oxidative trifluoromethylation of alkynes instead of expensive Ag2CO3. The isolated yields of the trifluoromethylated alkynes with the use of oxygen in the presence of 4 A powdered molecular sieves were similar to those obtained with Ag2CO3.