title: Enantioselective radiosynthesis of positron emission tomography (PET) tracers containing [¹⁸F]fluorohydrins.
abstract: Herein, we describe an operationally straightforward radiosynthesis of a chiral transition metal fluoride catalyst, [(18)F](salen)CoF, and its use for late-stage enantioselective aliphatic radiofluorination. We demonstrate the utility of the method by preparing single enantiomer experimental and clinically validated PET tracers that contain base-sensitive functional groups, epimerizable stereocenters, and nitrogen-rich motifs. Unlike the conventional radiosyntheses of these targets with [(18)F]KF, labeling with (salen)CoF is possible in the last step and under exceptionally mild conditions. These results constitute a rare example of a nucleophilic radiofluorination using a transition metal fluoride and highlight the potential of such reagents to enhance traditional methods for labeling aliphatic hydrocarbons.
authors.affiliation: Department of Chemistry, Princeton University , Princeton, New Jersey 08544, United States.
authors.forename: Thomas J A
authors.initials: TJ
authors.lastname: Graham
authors.forename: R Frederick
authors.initials: RF
authors.lastname: Lambert
authors.forename: Karl
authors.initials: K
authors.lastname: Ploessl
authors.forename: Hank F
authors.initials: HF
authors.lastname: Kung
authors.forename: Abigail G
authors.initials: AG
authors.lastname: Doyle
mesh_terms: D003035:Cobalt / Q000737:chemistry; D005462:Fluorine Radioisotopes; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry*; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D049268:Positron-Emission Tomography; D013237:Stereoisomerism
chemical_list: D005462:Fluorine Radioisotopes; D006845:Hydrocarbons, Fluorinated; D009942:Organometallic Compounds; D003035:Cobalt