Xu, C, Muir, CW, Leach, AG, Kennedy, AR and Watson, AJB (2018) Catalytic Enantioselective Synthesis of α-Chiral Azaheteroaryl Ethylamines by Asymmetric Protonation. Angewandte Chemie International Edition. ISSN 1521-3773

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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.

Item Type:	Article
Uncontrolled Keywords:	03 Chemical Sciences
Subjects:	Q Science > QD Chemistry R Medicine > RM Therapeutics. Pharmacology
Divisions:	Pharmacy & Biomolecular Sciences
Publisher:	Wiley
Related URLs:	Author
Date Deposited:	14 Aug 2018 10:45
Last Modified:	04 Sep 2021 10:14
DOI or ID number:	10.1002/anie.201806956
URI:	https://researchonline.ljmu.ac.uk/id/eprint/9088

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