A General Copper-Mediated Nucleophilic F-18 Fluorination of Arenes

作者：Tredwell, Matthew; Preshlock, Sean M.; Taylor, Nicholas J.; Gruber, Stefan; Huiban, Mickael; Passchier, Jan; Mercier, Joel; Genicot, Christophe; Gouverneur, Veronique^*

来源：Angewandte Chemie - International Edition, 2014, 53(30): 7751-7755.

DOI：10.1002/anie.201404436

• aryl boronic esters
• copper
• fluorination
• fluorine-18
• positron emission tomography

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 [F-18]F-. In the ideal case, the F-18 fluorination of these substrates would be performed through reaction of [F-18]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 F-18 arenes from pinacol-derived aryl boronic esters (arylBPin) upon treatment with [F-18]KF/K-222 and [Cu(OTf)(2)(py)(4)] (OTf = trifluoromethane-sulfonate, py = pyridine). This method tolerates electron-poor and electron-rich arenes and various functional groups, and allows access to 6-[F-18] fluoro-l-DOPA, 6-[F-18] fluoro-m-tyrosine, and the translocator protein (TSPO) PET ligand [F-18]DAA1106.

• 出版日期2014-7-21