A General Copper‐Mediated Nucleophilic 18F Fluorination of Arenes |
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| Authors: | Dr. Matthew Tredwell Dr. Sean M. Preshlock Nicholas J. Taylor Dr. Stefan Gruber Dr. Mickael Huiban Dr. Jan Passchier Dr. Joël Mercier Dr. Christophe Génicot Prof. Véronique Gouverneur |
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| Affiliation: | 1. Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA (UK);2. Imanova, Burlington Danes Building Imperial College, London Hammersmith Hospital, Du Cane Road, London W12 0NN (UK);3. Global Chemistry, UCB Medicines, UCB Biopharma, 1420 Braine‐L'Alleud (Belgium) |
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| Abstract: | Molecules labeled with fluorine‐18 are used as radiotracers for positron emission tomography. An important challenge is the labeling of arenes not amenable to aromatic nucleophilic substitution (SNAr) with [18F]F?. In the ideal case, the 18F fluorination of these substrates would be performed through reaction of [18F]KF with shelf‐stable readily available precursors using a broadly applicable method suitable for automation. Herein, we describe the realization of these requirements with the production of 18F arenes from pinacol‐derived aryl boronic esters (arylBPin) upon treatment with [18F]KF/K222 and [Cu(OTf)2(py)4] (OTf=trifluoromethanesulfonate, py=pyridine). This method tolerates electron‐poor and electron‐rich arenes and various functional groups, and allows access to 6‐[18F]fluoro‐L ‐DOPA, 6‐[18F]fluoro‐m‐tyrosine, and the translocator protein (TSPO) PET ligand [18F]DAA1106. |
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| Keywords: | aryl boronic esters copper fluorination fluorine‐18 positron emission tomography |
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