Late‐Stage ¹⁸F‐Difluoromethyl Labeling of N‐Heteroaromatics with High Molar Activity for PET Imaging

Abstract

Abstract Despite a growing interest in CHF 2 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.