The rise of the transition-metal-mediated and/or catalyzed
radiofluorination reactions has led us to investigate possibilities
for the improvement of the radiolabeling yields of pinacol
esters of arylboronic acids (arylBPin) in the presence of Cu(OTf)2
(py)4. Addition of small amounts pyridine to the reaction
medium with DMF as a solvent and [18F]F/K222Cs+complex as
[18F]fluoride source was shown to have a significant positive
effect on the radiofluorination yields. The effect was investigated
in depth using 4-biphenylboronic acid pinacol ester as
a model compound, with up to 20% increase in radiochemical
conversion observed at optimized conditions. Maximum effect
was observed at pyridine-to-catalyst ratio of 30:1. The findings
were applied to a representative electron-rich ring systems that
are traditionally difficult or impossible to radiolabel with
nucleophilic fluoride, leading to products such as 2-[18F]
fluoroanisole and protected 4-L-[18F]fluorophenylalanine. Given
the ever-present pressure to develop new methods for
introduction of fluorine-18 into various substrates to facilitate
easy and robust production of clinically-relevant radiotracers
for PET imaging we believe our findings can be of significant
practical interest for radiofluorination of ortho-substituted
substrates in particular.