Trifluoromethylation Of 8-aminoquinoline Derivatives Catalyzed By Iridium

Trifluoromethyl（TFM）could change the stability and biological properties of molecules significantly due to its electron-withdrawing effect and fat solubility,therefore,arenes and heteroaromatics with TFM have been widely used in the synthesis of medicines and pesticides.Traditional methods for synthesis of trifluoromethylated compounds often used toxic fluorine reagents,with harsh reaction conditions,and poor compatibility of functional groups.In recent years,transition-metal-catalyzed direct C-H trifluoromethylation has become a hotspot due to the mild reaction conditions,preclusion of pre-activation for substances and atom economy.Herein,a novel iridium-catalyzed direct trifluoromethylation method has been developed by using Ruppert’Reagent（TMSCF₃）as trifluoromethylating reagent.8-Acylaminoquinolines containing amides as directing group were designed as the substrates according to the characteristics of transition-metal-catalyzed direct C-H trifluoromethylation.Sixteen 8-aroylaminoquinolines were synthesized by using improved method of amidation of aryl carboxylic acids and 8-aminoquinoline.The improved method obtained the desired product in high yield under a simple work-up operation.Furthermore,four 8-alkyl acylaminoquinolines were synthesized by condensation of anhydride with 8-aminoquinoline.An IrCl₃-catalyzed trifluoromethylation system using TMSCF₃ as trifluoromethylating reagent,8-amidoquinolines as substrates was developed.After the screening of reaction conditions,the optimized reaction conditions employed IrCl₃（10mol%）as catalyst,TMSCF₃/KF（3 mmol）as trifluoromethylating reagent,PIDA（3mmol）as oxidant,1,2-DCE（5 mL）as solvent and TFA（1 mmol）as addition stirred at room temperature for 18 h.Twenty 7-trifluoromethylquinolines had synthesized through optimum reaction system and all the compounds have been characterized.