Premium
Copper‐Mediated Radiofluorination of Aryl Pinacolboronate Esters: A Straightforward Protocol by Using Pyridinium Sulfonates
Author(s) -
Antuganov Dmitrii,
Zykov Michail,
Timofeev Vasilii,
Timofeeva Ksenija,
Antuganova Yulija,
Orlovskaya Victoriya,
Fedorova Olga,
Krasikova Raisa
Publication year - 2019
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.201801514
Subject(s) - chemistry , pyridinium , trifluoromethanesulfonate , aryl , fluoride , nucleophile , combinatorial chemistry , sulfonate , pyridine , organic chemistry , catalysis , inorganic chemistry , alkyl , sodium
Radiofluorination of arylboronic acids pinacol esters (arylBPin) mediated by copper triflate pyridine complex is one of the more promising synthetic approaches for the direct introduction of nucleophilic [ 18 F]fluoride into non‐activated arenes and heteroarenes. However, the application of this method to the production of positron emission tomography (PET) radiotracers in automated synthesizers remains a challenging task. The choice of phase‐transfer catalyst (PTC) and corresponding base used for the generation of reactive [ 18 F]fluoride species has a profound impact on the efficiency of the 18 F‐fluorination process. Herein we report the development of a simple procedure involving trapping of the aqueous [ 18 F]fluoride on a weak anion‐exchange resin (WAX) and its release by elution with pyridinium sulfonate in dimethyl acetamide. Obtained reactive [ 18 F]fluoride was used as‐is in a copper‐catalyzed fluorination reaction employing pyridinium salt as both PTC and base. High radiochemical conversion rates (RCCs) achieved for a series of simple arylBPin substrates and 4‐[ 18 F]fluoro‐D,L‐phenylalanine demonstrate the efficiency of this novel 18 F‐processing approach. Notably, the proposed method obviates conventional azeotropic drying steps, solvents evaporation and/or changeover and can be implemented on commercial automated synthesizers.