¹⁸F‑Difluoromethyl(ene) Motifs via Oxidative Fluorodecarboxylation with [¹⁸F]Fluoride

Herein, we report that α-fluorocarboxylic acids undergo manganese-mediated oxidative ¹⁸F-fluorodecarboxylation with [¹⁸F]-fluoride affording biologically relevant ¹⁸F-difluoromethyl(ene)-containing molecules. This no-carrier added process provides a solution to a known challenge in radiochemistry and expands the radiochemical space available for positron emission tomography (PET) ligand discovery. Scalability on a fully automated radiosynthetic platform is exemplified with the production of [¹⁸F]4,4-difluoropiperidine that, we demonstrate, is amenable to postlabeling functionalization including N-heteroarylation and amide as well as sulfonamide bond formation (Figure Presented).