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Updated: May 4, 2026

Facile Preparation of 2Z,4E-Dienamides by the Olefination of Electron-deficient Alkenes with Allyl Acetate
Published on: June 21, 2017
Mechanistically Guided Functionalization of α,α-Disubstituted Alkenyl Amides Enabled by a Conformationally Flexible
Al Vicente Riano D Lisboa1, Phornphan Yongpanich1,2, Shijia Li3
1Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
Abstract:
In this work, we demonstrate that directing group flexibility plays a decisive role in overcoming reactivity barriers in PdII-catalyzed alkene functionalization. Kinetic, organometallic, and DFT studies reveal that employing the rigid 8-aminoquinoline (AQ) auxiliary in α,α-disubstituted substrates leads to high activation barriers for a rate-determining protonation transition state arising from geometric distortion. Guided by these insights, we show that judicious tuning of the directing group can minimize energetic penalties with the use of a flexible 2-pyridylmethylamine (PM) auxiliary. This mechanistically informed approach led to a 115-fold rate increase for the model α,α-dimethyl substrate and broadens the scope to sterically encumbered alkenes, including α-spiro(hetero)cyclic systems, with tolerance for diverse N-H and C-H nucleophiles. Furthermore, we demonstrate that the mechanistic framework developed for hydroamination extends to other difunctionalization reactions such as carboamination and cyclopropanation. This work expands access to structurally complex and lipophilic scaffolds from readily available alkenes.
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