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Cu‐Mediated Radiofluorination of Aryl Pinacolboronate Esters: Alcohols as Solvents with Application to 6‐L‐[ 18 F]FDOPA Synthesis
Author(s) -
Orlovskaya Viktoriya,
Fedorova Olga,
Kuznetsova Olga,
Krasikova Raisa
Publication year - 2020
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.202001198
Subject(s) - chemistry , trifluoromethanesulfonate , alcohol , yield (engineering) , pinacol , aryl , catalysis , solvent , combinatorial chemistry , fluoride , tetramethylethylenediamine , substrate (aquarium) , organic chemistry , medicinal chemistry , inorganic chemistry , materials science , alkyl , oceanography , metallurgy , geology
Cu‐mediated radiofluorination of arylboronic acid pinacol esters (ArylBPin) using Cu(OTf) 2 (Py) 4 complex is a useful approach for the introduction of [ 18 F]fluorine into non‐activated arenes and heteroarenes. Owing to the complexity of the mechanism and wide variation in substrate reactivity the choice of reaction conditions must be made individually for every precursor. Careful selection of phase‐transfer catalysts also plays a role, as Cu‐catalyst and ArylBPin precursors are known to be unstable in basic conditions. Using tetrabutylammonium triflate alcohol solution for elution of [ 18 F]fluoride from ion‐exchange cartridge and employing same alcohol as a co‐solvent in the following labelling step, we have developed a general protocol resulting in >80 % fluorination efficiency of ArylBPin precursors for 4‐[ 18 F]fluoro‐D,L‐phenylalanine and 6‐L‐[ 18 F]FDOPA. Radiofluorination in neat alcohol was particularly effective for the synthesis of 6‐L‐[ 18 F]FDOPA, allowing for substantial increase of yield and decrease of synthesis time compared to current methods (activity yield 14.5 ± 0.5 %, 70 min synthesis time).