New highly asymmetric Henry reaction catalyzed by Cu(II) and a C(1)-symmetric aminopyridine ligand, and its application to the synthesis of miconazole.
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.
Blay
Gonzalo
G
Departament de Química Orgànica, Facultat de Química, Universitat de València, Burjassot (València), Spain. gonzalo.blay@uv.es
Domingo
Luis R
LR
Hernández-Olmos
Victor
V
Pedro
José R
JR
D015761:4-Aminopyridine / Q000737:chemistry*; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D008024:Ligands; D008825:Miconazole / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D013237:Stereoisomerism
D008024:Ligands; D003300:Copper; D008825:Miconazole; D015761:4-Aminopyridine