Open Access19F- and 18F-arene deoxyfluorination via organic photoredox-catalysed polarity-reversed nucleophilic aromatic substitution
Author(s) -
Nicholas Tay,
Wei Chen,
Alison Levens,
Vincent A. Pistritto,
Zeng Huang,
Zhanhong Wu,
Zibo Li,
David A. Nicewicz
Publication year - 2020
Publication title -
nature catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 14.33
H-Index - 65
ISSN - 2520-1158
DOI - 10.1038/s41929-020-0495-0
Subject(s) - nucleophilic aromatic substitution , chemistry , nucleophilic substitution , electrophilic aromatic substitution , nucleophile , combinatorial chemistry , fluorine , radical nucleophilic aromatic substitution , substitution reaction , organic chemistry , catalysis
Nucleophilic aromatic substitution (S N Ar) is routinely used to install 19 F - and 18 F - in aromatic molecules, but is typically limited to electron-deficient arenes due to kinetic barriers associated with C-F bond formation. Here we demonstrate that a polarity-reversed photoredox-catalysed arene deoxyfluorination operating via cation radical-accelerated nucleophilic aromatic substitution (CRA-S N Ar) enables the fluorination of electron-rich arenes with 19 F - and 18 F - under mild conditions, thus complementing the traditional arene polarity requirements necessary for S N Ar-based fluorination. The utility of our radiofluorination strategy is highlighted by short reaction times, compatibility with multiple nucleofuges, and high radiofluorination yields, especially that of an important cancer positron emission tomography (PET) agent [ 18 F]5-fluorouracil ([ 18 F]FU). Taken together, our fluorination approach enables the development of fluorinated and radiofluorinated compounds that can be difficult to access by classical S N Ar strategies, with the potential for use in the synthesis and discovery of PET radiopharmaceuticals.