Metal-, Photocatalyst-, Light- and Electrochemical-Free C-3 Trifluoromethylation of Quinoxalin-2(1H)-ones, Imidazo[1,2-a]pyridines and 2H-Indazoles

We report an efficient protocol for the synthesis of 3-trifluoromethylquinoxalin-2(1H)-ones, 3-trifluoromethylimidazo[1,2-a]pyridines and 3-(trifluoromethyl)-2H-indazoles under metal-, photocatalyst-, light- and electrochemical-free conditions. The combination of Langlois' reagent (sodium triflinate) with the oxidant (NH4)(2)S2O8 in DMSO: H2O (10 : 1) works as an efficient reagent system to promote this free radical trifluoromethylation reaction. The trifluoromethyl radical generated by the oxidation of sodium triflinate with (NH4)(2)S2O8 attacks on to the C-3 position of quinoxalin-2(1H)-ones, imidazo[1,2-a]pyridines and 2H-indazoles; and the excess SO4 center dot- completes the reaction furnishing their respective 3-trifluoromethyl derivatives in very good to excellent yields. Radical scavenging experiments with (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO), butylated hydroxy toluene (BHT), and 1,1-diphenylethylene also prove the participation of radical.

Automated summary

An efficient protocol for the synthesis of various trifluoromethylated compounds under metal-, photocatalyst-, light- and electrochemical-free conditions was reported. This protocol involves the use of Langlois' reagent in combination with an oxidant to promote the free radical trifluoromethylation reaction, resulting in high yields. Radical scavenging experiments confirmed the involvement of radicals in the reaction.