Ultrafast Click Chemistry with Fluorosydnones

• Published in: Angewandte Chemie (International ed.) Vol. 55; no. 39; pp. 12073 - 12077
• Main Authors: Liu, Hui, Audisio, Davide, Plougastel, Lucie, Decuypere, Elodie, Buisson, David-Alexandre, Koniev, Oleksandr, Kolodych, Sergii, Wagner, Alain, Elhabiri, Mourad, Krzyczmonik, Anna, Forsback, Sarita, Solin, Olof, Gouverneur, Véronique, Taran, Frédéric
• Format: Journal Article
• Language: English
• Published: WEINHEIM Blackwell Publishing Ltd 19.09.2016; Wiley; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Alkynes; Chemical reactions; Chemical synthesis; Chemistry; Chemistry, Multidisciplinary; click chemistry; Cycloaddition; Dipoles; electrophilic fluorination; Fluorination; fluorine-18; Kinetics; Physical Sciences; Pyrazoles; radiolabeling; Radiolabelling; Rate constants; Science & Technology; CELLS; COMPLEX; click chemistry; radiolabeling; REDUCTIVE ELIMINATION; SYDNONE; CYCLOADDITION; fluorine-18; PD; electrophilic fluorination; FLUORINE; COPPER-FREE; kinetics
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201606495

We report the synthesis and reactivity of 4‐fluorosydnones, a unique class of mesoionic dipoles displaying exquisite reactivity towards both copper‐catalyzed and strain‐promoted cycloaddition reactions with alkynes. Synthetic access to these new mesoionic compounds was granted by electrophilic fluorination of σ‐sydnone PdII precursors in the presence of Selectfluor. Their reactions with terminal and cyclic alkynes were found to proceed very rapidly and selectively, affording 5‐fluoro‐1,4‐pyrazoles with bimolecular rate constants up to 104 m−1 s−1, surpassing those documented in the literature with cycloalkynes. Kinetic studies were carried out to unravel the mechanism of the reaction, and the value of 4‐fluorosydnones was further highlighted by successful radiolabeling with [18F]Selectfluor. Fast and fluorious: Fluorosydnones are extremely reactive towards copper‐catalyzed cycloaddition reactions with terminal alkynes and copper‐free reactions with cycloalkynes. These highly reactive clickable reagents were prepared by electrophilic fluorination of sydnone PdII precursors in the presence of Selectfluor.