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 CHF¹⁸ 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.