Application Of TMSCF₃ In N-Trifluoromethylation And Oxidation Trifluoromethylation Of Methylarene

Fluorinated organic molecules have an enhanced lipophilicityand membrane permeability, and an elevated electronegativity andoxidation resistance, which are responsible for their increasedmetabolic stability and bioavailability compared to their nonfluorinated analogues. But the fact there have only 13 cases of fluorinated organic molecules were found in nature make the introduction of fluorine atom or fluorine fragment become a hot research subject in organic chemistry.Trifluoromethyl is the most prevalentperfluoroalkyl function group. Recent years have witnessed a rapid development of strategies for the incorporation of CF₃ into various organic structures. Generally, there are three pathway for incorporation of CF₃:nucleophilic trifluoromethylation, electrophilic trifluoromethylation and radical trifluoromethylation. Among these research, most of efforts was focused on constructing C-CF₃ bonds via direct trifluoromethylation of various C-H bonds. However, the trifluoromethylation of heteroatoms was mainly focused on the sulfer atom and the oxygen atom, it is safe to say that N-trifluoromethylation are still rather rare and scarcely studied.1. We summarizes and elaborates the trifluoromethylation methods for the C-CF₃, N-CF₃ and the O-CF₃.2. We used the insitu generated electrophilic acyclic aryl?trifluoromethyl?iodonium compounds [PhICF₃]⁺ to realize the direct trifluoromethylation of N-H ketimines by simply mixing PhI?OAc?₂, nucleophilic Ruppert Prakash reagent ?TMSCF₃? and KF. The simple execution, mild conditions, and good yields, make the protocol very attractive for practical applications in the connection of nitrogen atom and CF₃ directly. And above all, this is the first research on the N-trifluoromethylation based on the acyclic electrophilic hypervalent iodine reagent.3. We have aslo explored the application of Togni-2 reagent [1-?Trifluoromethyl?-1,2-benziodoxol-3?1H?-one] for the direct N-Trifluoromethylation. We still choosed the N-H ketimines as the nitrogen source after the detailed screening on the N-containing compounds. Finally, We successfully achieved the Cu-catalyzed N-trifluoromethylation reaction and synthesised a set of N-trifluoromethylated ketimines.4. We have developed a direct oxidation of benzylic sp³ C-H bond by using cheap copper salts as the catalyst and molecular oxygen as the ultimate oxidant under ligand-free and additive-free conditions. Additionally, a well combination of oxidations of heterobenzylic methylenes with trifluoromethylation in one-pot was realized to synthesize a set of trifluoromethylazinylketols which are valuable synthon in organic chemistry.