NHC-Copper Mediated Ligand-Directed Radiofluorination of Aryl Halides

[18F]-labeled aryl fluorides are widely used as radiotracers
for positron emission tomography (PET) imaging. Aryl halides (ArX)
are particularly attractive precursors to these radiotracers, as they
are readily available, inexpensive, and stable. However, to date,
the direct preparation of [18F]-aryl fluorides from aryl
halides remains limited to SNAr reactions between highly
activated ArX substrates and K18F. This report describes
an aryl halide radiofluorination reaction in which the C­(sp2)–18F bond is formed
via a copper-mediated pathway. Copper N-heterocyclic
carbene complexes serve as mediators for this transformation, using
aryl halide substrates with directing groups at the ortho position. This reaction is applied to the radiofluorination of electronically
diverse aryl halide derivatives, including the bioactive molecules
vismodegib and PH089.