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Updated: May 27, 2025

Facile Preparation of 2Z,4E-Dienamides by the Olefination of Electron-deficient Alkenes with Allyl Acetate
Published on: June 21, 2017
Use of Aldehyde-Alkyne-Amine Couplings to Generate Medicinal Chemistry-Relevant Linkers
Andrew McGown1, Vesna Vetma2, Damien Crepin1
1Sussex Drug Discovery Centre, School of Life Sciences, University of Sussex, Falmer BN1 9QJ, U.K.
Abstract:
Copper catalyzed aldehyde-alkyne-amine (A3) couplings lead to multifunctional, racemic, propargylic amines, many on a multigram scale. As part of an industrial collaboration, a selection of linkers was purified by chiral HPLC to afford single enantiomers, the absolute configuration of which was determined by vibrational circular dichroism (vCD). To show medicinal chemistry applications, selected linkers were further derivatized into potential cellular probes and (+)-JQ1 containing PROTACs (proteolysis targeting chimeras), which degraded their target protein BRD4.
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