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Catalytic enantioselective synthesis of α-chiral azaheteroaryl ethylamines by asymmetric protonation

Research output: Contribution to journalArticlepeer-review

Author(s)

Chao Xu, Calum Muir, Andrew Leach, Alan Kennedy, Allan J. B. Watson

School/Research organisations

Abstract

The direct enantioselective synthesis of chiral azaheteroaryl ethylamines from vinyl‐substituted N‐heterocycles and anilines is reported. A chiral phosphoric acid (CPA) catalyst promotes dearomatizing aza‐Michael addition to give a prochiral exocyclic aryl enamine, which undergoes asymmetric protonation upon rearomatization. The reaction accommodates a broad range of N‐heterocycles, nucleophiles, and substituents on the prochiral centre, generating the products in high enantioselectivity. DFT studies support a facile nucleophilic addition based on catalyst‐induced LUMO lowering, with site‐selective, rate‐limiting, intramolecular asymmetric proton transfer from the ion‐paired prochiral intermediate.
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Details

Original languageEnglish
JournalAngewandte Chemie International Edition
VolumeIn press
Early online date1 Aug 2018
DOIs
Publication statusE-pub ahead of print - 1 Aug 2018

    Research areas

  • Asymmetric catalysis, Brønsted acid, DFT, Heterocycles, Stereochemistry

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