Late-Stage (18) F-Difluoromethyl Labeling of N-Heteroaromatics with High Molar Activity for PET Imaging.

Despite a growing interest in CHF2 in medicinal chemistry, there is a lack of efficient methods for the insertion of CHF(18) F into druglike compounds. Herein described is a photoredox flow reaction for (18) F-difluoromethylation of N-heteroaromatics that are widely used in medicinal chemistry. Following the two-step synthesis for a new (18) F-difluoromethylation reagent, the photoredox reaction is completed within two minutes and proceeds by C-H activation, circumventing the need for pre-functionalization of the substrate. The method is operationally simple and affords straightforward access to radiolabeled N-heteroaromatics with high molar activity suitable for biological in vivo studies and clinical application.