Photocatalytic Trifluoromethylation Of 2H-indazole In Ionic Liquid

Indazole and its derivatives are one of the important nitrogen-containing heterocyclic compounds and are commonly found in a variety of biologically active compounds and drugs as important structural motifs.The introduction of trifluoromethyl into 2H-indazole core through C-H activation can significantly improve its biological and pharmacological activities,increasing its molecular diversity and application value.However,in the conventional trifluoromethylation method,not only harsh reaction conditions but also expensive transition metal catalysts and oxidants are required.To solve the above problem,a strategy of metal-and oxidant-free activation of trifluoromethylation using photocatalytic C-H bonding was developed.In recent years,ionic liquids have become a hot research topic as green and recyclable solvents instead of traditional toxic organic solvents for organocatalytic reactions,and have been successfully applied in a variety of catalytic reactions.Therefore,the application of ionic liquids to trifluoromethylation can make the reaction with green and recyclable properties.On this basis,a stable and efficient trifluoromethylation reagent TT-CF3+OTf-was selected as the trifluoromethyl source by optimizing the conditions,and a strategy was developed for the direct trifluoromethylation of C-H bonds of indazole by photocatalytic irradiation with eosin Y at room temperature under blue light in a solvent with a 2:1 ratio of ionic liquid 1-butyl-3-methylimidazole bis(trifluoromethanesulfonyl)imide([BMIM]NTf2)to water.And 31 2H-indazoles were successfully trifluoromethylated and structurally characterized.Through controlled experiments,it was demonstrated that the reaction proceeds through a free radical mechanism.The ionic liquid solvent was also subjected to recovery cycle experiments to demonstrate the recoverability of the solvent.Finally,the strategy was used to synthesize a highly selective ligand for estrogen receptor β and the drug granisetron,further demonstrating its usefulness in organic synthesis.