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

Angew Chem Int Ed Engl. 2019 Sep 9;58(37):13149-13154. doi: 10.1002/anie.201907488. Epub 2019 Aug 9.


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.

Keywords: C−H activation; flow chemistry; fluorine; photochemistry; radiochemistry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Fluorine Radioisotopes / chemistry*
  • Halogenation
  • Hydrocarbons, Aromatic / chemical synthesis
  • Hydrocarbons, Aromatic / chemistry*
  • Methylation
  • Oxidation-Reduction
  • Positron-Emission Tomography / methods
  • Radiochemistry


  • Fluorine Radioisotopes
  • Hydrocarbons, Aromatic