title: Mechanism of Electrophilic Fluorination with Pd(IV): Fluoride Capture and Subsequent Oxidative Fluoride Transfer.
abstract: Electrophilic fluorinating reagents derived from fluoride are desirable for the synthesis of18F-labeled molecules for positron emission tomography (PET). Here, we study the mechanism by which a Pd(IV)-complex captures fluoride and subsequently transfers it to nucleophiles. The intermediate Pd(IV)-F is formed with high rates even at the nano- to micromolar fluoride concentrations typical for radiosyntheses with18F due to fast formation of an outer-sphere complex between fluoride and Pd(IV). The subsequent fluorine transfer from the Pd(IV)-F complex is proposed to proceed through an unusual SET/fluoride transfer/SET mechanism. The findings detailed in this manuscript provide a theoretical foundation suitable for addressing a more general approach for electrophilic fluorination with high specific activity18F PET imaging.
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, United States.
authors.forename: Jochen R
authors.initials: JR
authors.lastname: Brandt
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, United States.
authors.forename: Eunsung
authors.initials: E
authors.lastname: Lee
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, United States.
authors.forename: Gregory B
authors.initials: GB
authors.lastname: Boursalian
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, United States.
authors.forename: Tobias
authors.initials: T
authors.lastname: Ritter