Mechanism and selectivity control of trifluoromethylation of free radicals
Free radical trifluoromethylation plays an important role in organic synthesis, especially under the conditions of copper/photocatalysis, the reaction shows unique activity and selectivity. In depth study of its reaction mechanism and selectivity control strategy is of great significance to expand the application scope of trifluoromethylation reaction and realize precise organic synthesis.
In the copper catalyzed free radical trifluoromethylation reaction, copper salt is used as catalyst to realize the generation and transfer of trifluoromethyl free radical through redox cycle. In the reaction process, copper (I) salt and trifluoromethylation reagent were oxidized and added to form copper (III) - trifluoromethyl intermediate, and then the intermediate was cracked to release trifluoromethyl radical. The free radical reacts with the substrate molecule to form a carbon trifluoromethyl free radical intermediate. Finally, the catalytic cycle is completed by the reduction of copper (II) salt. By adjusting the type of copper salts, ligand structure and reaction conditions, the selectivity of the reaction can be effectively controlled, and the trifluoromethylation of different substrates can be achieved.
The photo catalytic free radical trifluoromethylation reaction uses the electron hole pairs generated after the photo catalyst absorbs photons to initiate the formation of trifluoromethyl free radicals. Under visible light irradiation, the photocatalyst is excited, and the electrons generated will reduce the trifluoromethylation reagent to trifluoromethyl free radicals, while the holes will oxidize the substrate molecules to form free radical cations. By reasonably designing the structure of photocatalyst and selecting appropriate reaction solvent, the reaction selectivity can be controlled. In addition, the introduction of guiding groups or the use of chiral catalysts can also achieve enantioselective or regioselective free radical trifluoromethylation, which provides a new method for the synthesis of chiral trifluoromethyl compounds. With the in-depth study of the reaction mechanism and selectivity control of free radical trifluoromethylation, the reaction will play a greater role in the field of organic synthesis.