title: A broadly applicable [18F]trifluoromethylation of aryl and heteroaryl iodides for PET imaging.
abstract: Molecules labelled with the unnatural isotope fluorine-18 are used for positron emission tomography. Currently, this molecular imaging technology is not exploited at its full potential because many (18)F-labelled probes are inaccessible or notoriously difficult to produce. Typical challenges associated with (18)F radiochemistry are the short half-life of (18)F (<2 h), the use of sub-stoichiometric amounts of (18)F, relative to the precursor and other reagents, as well as the limited availability of parent (18)F sources of suitable reactivity ([(18)F]F(-) and [(18)F]F2). There is a high-priority demand for general methods allowing access to [(18)F]CF3-substituted molecules for application in pharmaceutical discovery programmes. We report the development of a process for the late-stage [(18)F]trifluoromethylation of (hetero)arenes from [(18)F]fluoride using commercially available reagents and (hetero)aryl iodides. This [(18)F]CuCF3-based protocol benefits from a large substrate scope and is characterized by its operational simplicity.
authors.affiliation: Imanova, Burlington Danes Building, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.
authors.forename: Mickael
authors.initials: M
authors.lastname: Huiban
authors.forename: Matthew
authors.initials: M
authors.lastname: Tredwell
authors.forename: Satoshi
authors.initials: S
authors.lastname: Mizuta
authors.forename: Zehong
authors.initials: Z
authors.lastname: Wan
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Zhang
authors.forename: Thomas Lee
authors.initials: TL
authors.lastname: Collier
authors.forename: Véronique
authors.initials: V
authors.lastname: Gouverneur
authors.forename: Jan
authors.initials: J
authors.lastname: Passchier
mesh_terms: D001555:Benzene Derivatives / Q000737:chemistry; D005462:Fluorine Radioisotopes / Q000737:chemistry*; D005473:Fluoxetine / Q000737:chemistry; D005485:Flutamide / Q000737:chemistry; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry*; D007462:Iodobenzenes / Q000737:chemistry*; D007553:Isotope Labeling / Q000379:methods; D009682:Magnetic Resonance Spectroscopy; D008745:Methylation; D057054:Molecular Imaging; D015394:Molecular Structure; D049268:Positron-Emission Tomography / Q000379:methods*
chemical_list: D001555:Benzene Derivatives; D005462:Fluorine Radioisotopes; D006845:Hydrocarbons, Fluorinated; D007462:Iodobenzenes; D005473:Fluoxetine; D005485:Flutamide