Catalytic enantioselective synthesis of α-chiral azaheteroaryl ethylamines by asymmetric protonation
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.
Citation
Xu , C , Muir , C , Leach , A , Kennedy , A & Watson , A J B 2018 , ' Catalytic enantioselective synthesis of α-chiral azaheteroaryl ethylamines by asymmetric protonation ' , Angewandte Chemie International Edition , vol. In press . https://doi.org/10.1002/anie.201806956
Publication
Angewandte Chemie International Edition
Status
Peer reviewed
ISSN
1433-7851Type
Journal article
Description
The authors thank the Leverhulme Trust for funding (C.X.; RPG-2015- 308) and GSK for a PhD studentship (C.W.M.). The authors thank the EPSRC UK National Mass Spectrometry Facility at Swansea University for analyses.Collections
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