A novel and eco-friendly electrochemical activation of trifluoromethyl thianthrenium triflate(TT-CF_(3)^(+)OTf^(-))for trifluoromethylation of imidazole-fused heteroaromatic compounds was established.This method involves the direct electrolysis of TT-CF_(3)^(+)OTf^(-)without the requirement of external oxidants or catalysts,aligning with the principles of green chemistry.A wide range of imidazole-fused heteroaromatic compounds including imidazo[1,2-a]pyridines and benzo[d]imidazo[2,1-b]thiazoles have been successfully trifluoromethylated using this technique,exhibiting excellent compatibility with various functional groups and a broad substrate scope.Moreover,the method's applicability for one-pot sequential reactions enables the reduction of waste and resource consumption by eliminating the need for intermediate purification steps.
Iodomethane is usually used as an electrophilic methylation reagent.Herein,we report its use as a C1 organocatalyst for the aerobic ortho-selective trifluoromethylation of pyridines in the absence of a transition metal.Trifluoroacetic acid(TFA)was employed as an inexpensive,readily available trifluoromethyl source.The reaction efficiently produced a variety of trifluoromethylation products,with good functional group compatibility.Pyridine-containing drug molecules could also be selectively trifluoromethylated for late-stage functionalizations.Mechanistic studies showed that iodomethane selectively reacted with the pyridine starting material,rather than the pyridine product,to generate the corresponding N-methylpyridinium iodide.The decarboxylation of trifluoroacetic acid produced a trifluoromethyl anion,which added to the methylpyridinium iodide,and the subsequent aerobic rearomatization led to the generation of the ortho-trifluoromethylated product.
Difluorocarbene has emerged as a valuable intermediate to synthesize fluorides.However,difluorocarbene-derived synthesis of^(19)F/^(18)F-trifluoromethyl triazoles has not been explored.Herein,we reported the Cu(I)-promoted difluorocarbene-derived^(19)F/^(18)F-trifluoromethylation of iodotriazoles using KF/K^(18)F as the fluorine source.This approach rapidly generated a wide range of 5-trifluoromethyl-1,2,3-triazoles in good yields showing high functional group compatibility.The reaction was effective for late-stage functionalization of bioactive molecules and^(18)F-trifluoromethylation of iodotriazoles.This work provides a practical synthetic methodology for the development of triazole drugs and^(18)F-radiotracers for positron emission tomography.
