A General Copper‐Mediated Nucleophilic 18 F Fluorination of Arenes

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 (S N Ar) with [ 18 F]F − . In the ideal case, the 18 F fluorination of these substrates would be performed...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2014-07, Vol.53 (30), p.7751-7755
Main Authors: Tredwell, Matthew, Preshlock, Sean M., Taylor, Nicholas J., Gruber, Stefan, Huiban, Mickael, Passchier, Jan, Mercier, Joël, Génicot, Christophe, Gouverneur, Véronique
Format: Article
Language:English
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Summary: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 (S N Ar) with [ 18 F]F − . In the ideal case, the 18 F fluorination of these substrates would be performed through reaction of [ 18 F]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 18 F arenes from pinacol‐derived aryl boronic esters (arylBPin) upon treatment with [ 18 F]KF/K 222 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‐[ 18 F]fluoro‐ L ‐DOPA, 6‐[ 18 F]fluoro‐ m ‐tyrosine, and the translocator protein (TSPO) PET ligand [ 18 F]DAA1106.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201404436