Difluoromethoxide Is a Strong Leaving Group in the Photoredox Deoxyradiofluorination of 2-Phenylpyridines.

A 2-phenyl-3-difluoromethoxy-pyridinyl moiety features in potent phosphodiesterase 4D inhibitors that are considered to be candidate radiotracers for positron emission tomography if they are labeled with fluorine-18. Fluorine-18 could be installed as desired at the 3'-phenyl position with acridinium-mediated photoredox radiodeoxyfluorination in homologues bearing variously substituted 3'-aryloxy groups. However, a distal 3-difluoromethoxide (-OCHF 2 ) group strongly competes as a leaving group, especially when an electron-deficient aryloxy group is present at position 3'. A yield of up to 50% may occur without observable 19 F for 18 F exchange.