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Full Paper
New Highly Asymmetric Henry Reaction Catalyzed by CuII and a C1-Symmetric Aminopyridine Ligand, and Its Application to the Synthesis of Miconazole
Article first published online: 2 APR 2008
DOI: 10.1002/chem.200800069
Copyright © 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Additional Information
How to Cite
Blay, G., Domingo, L., Hernández-Olmos, V. and Pedro, J. (2008), New Highly Asymmetric Henry Reaction Catalyzed by CuII and a C1-Symmetric Aminopyridine Ligand, and Its Application to the Synthesis of Miconazole. Chemistry - A European Journal, 14: 4725–4730. doi: 10.1002/chem.200800069
Publication History
- Issue published online: 8 MAY 2008
- Article first published online: 2 APR 2008
- Manuscript Received: 14 JAN 2008
Funded by
- Ministerio de Educación y Ciencia. Grant Number: CTQ 2006-14199
- Generalitat Valenciana. Grant Number: GV 05/10
Keywords:
- aldol reaction;
- antifungal agents;
- asymmetric catalysis;
- copper;
- nucleophilic addition
Graphical Abstract
Enantioselective Henry reaction: A new copper(II) complex with a C1-symmetric chiral aminopyridine ligand catalyzes the asymmetric Henry reaction between nitroalkanes and a broad range of aldehydes (see scheme) to provide the expected nitroalkanols in high yields (up to 99 %) and excellent enantioselectivities (up to 98 %). The reaction has been applied to the enantioselective synthesis of miconazole.
Abstract
A new catalytic asymmetric Henry reaction has been developed that uses a C1-symmetric chiral aminopyridine ligand derived from camphor and picolylamine. A variety of aromatic, heteroaromatic, aliphatic, and unsaturated aldehydes react with nitromethane and other nitroalkanes in the presence of DIPEA (1.0 equiv), Cu(OAc)2⋅H2O (5 mol %), and an aminopyridine ligand (5 mol %) to give the expected products in high yields (up to 99 %), moderate-to-good diastereoselectivites (up to 82:18), and excellent enantioselectivities (up to 98 %). The reaction is air-tolerant and has been used in the synthesis of the antifungal agent miconazole.