11 C-Cyanation of Aryl Fluorides via Nickel and Lithium Chloride-Mediated C-F Bond Activation
Zhouen Zhang1, Takashi Niwa1,2, Kenji Watanabe1
1Laboratory for Chemical Biology, RIKEN Center for Biosystems Dynamics Research (BDR), 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe, 650-0047, Japan.
Abstract:
Aryl fluorides are expected to be useful as radiolabeling precursors due to their chemical stability and ready availability. However, direct radiolabeling via carbon-fluorine (C-F) bond cleavage is a challenging issue due to its significant inertness. Herein, we report a two-phase radiosynthetic method for the ipso-11 C-cyanation of aryl fluorides to obtain [11 C]aryl nitriles via nickel-mediated C-F bond activation. We also established a practical protocol that avoids the use of a glovebox, except for the initial preparation of a nickel/phosphine mixture, rendering the method applicable for general PET centers. This method enabled the efficient synthesis of diverse [11 C]aryl nitriles from the corresponding aryl fluorides, including pharmaceutical drugs. Stoichiometric reactions and theoretical studies indicated a significant promotion effect of lithium chloride on the oxidative addition, affording an aryl(chloro)nickel(II) complex, which serves as a precursor for rapid 11 C-cyanation.
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