title: A general copper-mediated nucleophilic 18F fluorination of arenes.
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 [(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/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-[(18)F]fluoro-L-DOPA, 6-[(18)F]fluoro-m-tyrosine, and the translocator protein (TSPO) PET ligand [(18)F]DAA1106.
authors.affiliation: Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford OX1 3TA (UK).
authors.forename: Matthew
authors.initials: M
authors.lastname: Tredwell
authors.forename: Sean M
authors.initials: SM
authors.lastname: Preshlock
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Taylor
authors.forename: Stefan
authors.initials: S
authors.lastname: Gruber
authors.forename: Mickael
authors.initials: M
authors.lastname: Huiban
authors.forename: Jan
authors.initials: J
authors.lastname: Passchier
authors.forename: Joël
authors.initials: J
authors.lastname: Mercier
authors.forename: Christophe
authors.initials: C
authors.lastname: Génicot
authors.forename: Véronique
authors.initials: V
authors.lastname: Gouverneur
mesh_terms: D003300:Copper / Q000737:chemistry*; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D054879:Halogenation / Q000502:physiology*; D015394:Molecular Structure; D049268:Positron-Emission Tomography / Q000379:methods*
chemical_list: D005462:Fluorine Radioisotopes; D003300:Copper
keywords: aryl boronic esters; copper; fluorination; fluorine-18; positron emission tomography