Difluorocarbene-derived rapid late-stage trifluoromethylation of 5-iodotriazoles for the synthesis of 18F-labeled radiotracers

Difluorocarbene has emerged as a valuable intermediate to synthesize fluorides. However, difluorocarbene-derived synthesis of 19F/18F-trifluoromethyl triazoles has not been explored. Herein, we reported the Cu(I)-promoted difluorocarbene-derived 19F/18F-trifluoromethylation of iodotriazoles using KF/K18F 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 18F-trifluoromethylation of iodotriazoles. This work provides a practical synthetic methodology for the development of triazole drugs and 18F-radiotracers for positron emission tomography. Cu(I)-promoted difluorocarbene-derived rapid late-stage trifluoromethylation and [18F]trifluoromethylation of iodotriazoles was used to prepare a series of 5–19F/18F-trifluoromethyl-1,2,3-triazoles in good yields with high functional group compatibility. The resulting18F-trifluoromethylated derivatives of bioactive molecules may be useful as 18F-labeled radiotracers for PET imaging. [Display omitted]