Late‐Stage 18F‐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 CHF¹⁸F into druglike compounds. Herein described is a photoredox flow reaction for ¹⁸F‐difluoromethylation of N‐heteroaromatics that are widely used in medicinal chemistry. Following the two‐step synthesis for a new ¹⁸F‐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.