TY - JOUR

T1 - Effect of Pyridine Addition on the Efficiency of Copper-Mediated Radiofluorination of Aryl Pinacol Boronates

AU - Antuganov, Dmitrii

AU - Zykov, Michail

AU - Timofeeva, Ksenija

AU - Antuganova, Yulija

AU - Orlovskaya, Victoriya

AU - Krasikova, Raisa

PY - 2017/9/4

Y1 - 2017/9/4

N2 - 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.

AB - 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.

KW - copper mediated radiofluorination

KW - pinacol esters of arylboronic acids

KW - positron emission tomography

KW - pyridine

KW - [F]fluoride

KW - copper mediated radiofluorination · [18F]fluoride · pinacol esters of arylboronic acids · positron emission tomography · pyridine

UR - http://www.scopus.com/inward/record.url?scp=85040365553&partnerID=8YFLogxK

U2 - 10.1002/slct.201701628

DO - 10.1002/slct.201701628

M3 - Article

AN - SCOPUS:85040365553

VL - 2

SP - 7909

EP - 7912

JO - ChemistrySelect

JF - ChemistrySelect

SN - 2365-6549

IS - 26

ER -