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New Highly Asymmetric Henry Reaction Catalyzed by Cu II and a C 1 ‐Symmetric Aminopyridine Ligand, and Its Application to the Synthesis of Miconazole
Author(s) -
Blay Gonzalo,
Domingo Luis R.,
HernándezOlmos Victor,
Pedro José R.
Publication year - 2008
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200800069
Subject(s) - nitromethane , 2 aminopyridine , ligand (biochemistry) , chemistry , catalysis , nitroaldol reaction , medicinal chemistry , miconazole , enantioselective synthesis , combinatorial chemistry , organic chemistry , antifungal , receptor , dermatology , medicine , biochemistry
A new catalytic asymmetric Henry reaction has been developed that uses a C 1 ‐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 ⋅ H 2 O (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.