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Updated: Aug 22, 2025
A Two-Step Protocol for Umpolung Functionalization of Ketones Via Enolonium Species
Published on: August 16, 2018
Synthesis of push-pull-activated ynol ethers and their evaluation in the bioorthogonal hydroamination reaction
Dahye Kang1,2, Conrad Wahl1, Justin Kim1,2
1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA. Justin_Kim@dfci.harvard.edu.
Abstract:
A new class of push-pull-activated alkynes featuring di- and trifluorinated ynol ethers was synthesized. The difluorinated ynol ether exhibited an optimal balance of stability and reactivity, displaying a substantially improved half-life in the presence of aqueous thiols over the previously reported 1-haloalkyne analogs while reacting just as fast in the hydroamination reaction with N,N-diethylhydroxylamine. The trifluorinated ynol ether reacted significantly faster, exhibiting a second order rate constant of 0.56 M-1 s-1 in methanol, but it proved too unstable toward thiols. These fluorinated ynol ethers further demonstrate the importance of the hyperconjugation-rehybridization effect in activating alkynes and demonstrate how substituent effects can both activate and stabilize alkynes for bioorthogonal reactivity.
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