Metal-Free Oxidative Fluorination of Phenols with [18F]Fluoride


  • The authors thank the EPSRC (to Z.G., M.T., M.H.), the CRUK (to Z.G., M.T.), GSK (to M.H.), the A*STAR NSS Overseas Ph.D. Scholarship (to Y.H.L.), the K. C. Wong Education Foundation (to L.L.), and Advion BioSystems for generous funding, Dr. John M. Brown FRS for discussions and Dr. Oscar Lozano for technical assistance.


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The radiochemical synthesis of [18F]4-fluorophenols is based on phenol umpolung under oxidative conditions and direct nucleophilic fluorination with [18F]fluoride (see scheme, TBAF=tetra-n-butylammonium fluoride, TFA=trifluoroacetic acid). Readily available O-unprotected 4-tert-butyl phenols are used as precursors in this one-pot protocol. The reaction is completed in less than 30 minutes at room temperature and can be performed using standard or microfluidic technology.