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DOI: 10.1055/s-2008-1042749
Synthesis of Chiral Pyridyl Alcohols by Cyclotrimerization
Contributor(s):Victor Snieckus, Wei GanLeibniz-Institut für Katalyse e.V. an der Universität Rostock and ChiroBlock GmbH, Wolfen, Germany; DSM Nutritional Products Ltd., Basel, Switzerland
Synthesis of Chiral Pyridyl Alcohols Using a Two-Step Catalytic Approach
Synthesis 2008, 69-74
Publication History
Publication Date:
21 February 2008 (online)
Key words
asymmetric synthesis - cyclotrimerization - pyridines
Significance
Reported is a synthesis of chiral pyridyl alcohols by a two-step reaction. In the first step, catalyst (R,R)-A leads to the S-enantiomers while (S,S)-A results in the formation of the R-enantiomers. The enantiomeric excess of O-trimethylsilylcyanohydrins B was retained in the final products after Co-catalyzed cyclotrimerization and desilylation.
Comment
Chiral pyridyl alcohols have seen applications as catalysts and ligands in asymmetric reactions such as the epoxidation of allylic alcohols (J. M. Hawkins, K. B. Sharpless Tetrahedron Lett. 1987, 28, 2825), the nucleophilic addition of dialkylzinc reagents to aldehydes (M. Ishizaki, O. Hoshino Tetrahedron: Asymmetry 1994, 5, 1901), and have served as key intermediates for drugs, for example (R,S)-mefloquine. The standard access to chiral pyridyl alcohols includes hydrogenation of pyridyl acetones (C.-Y. Chen et al. Org. Lett. 2003, 5, 5039) and resolution of racemic pyridyl alcohols (C.-Y. Mazet et al. Org. Lett. 2006, 8, 1879). The Co-catalyzed cyclotrimerization of chiral cyanohydrin approach was reported previously (G. Chelucci et al. Tetrahedron: Asymmetry 1994, 5, 1973) with disadvantages of a three-step preparation of cyanohydrin precursors and high temperature (120 ºC) reaction conditions.