Ultrafast Click Chemistry with Fluorosydnones

Angew Chem Int Ed Engl. 2016 Sep 19;55(39):12073-7. doi: 10.1002/anie.201606495. Epub 2016 Aug 25.

Abstract

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 Pd(II) 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 10(4) 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 [(18) F]Selectfluor.

Keywords: click chemistry; electrophilic fluorination; fluorine-18; kinetics; radiolabeling.

Publication types

  • Research Support, Non-U.S. Gov't