Catalytic Enantio- and Diastereoselective Aldol Reactions of Glycine-Derived Silicon Enolate with Aldehydes: An Efficient Approach to the Asymmetric Synthesis of anti-β-Hydroxy-α-Amino Acid Derivatives
Jun Kobayashi, Masayuki Nakamura, Yuichiro Mori, Yasuhiro Yamashita and Shu Kobayashi*
*Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo,
Bunkyo-ku, Tokyo 113-0033, Japan,
Email: skobayas
mol.f.u-tokyo.ac.jp
J. Kobayashi, M. Nakamura, Y. Mori, Y. Yamashita, S. Kobayashi, J. Am. Chem. Soc., 2004, 126, 9192-9193.
DOI: 10.1021/ja047597t
Abstract
An efficient method for the asymmetric synthesis of anti-β-hydroxy-α-amino acid derivatives is based on highly enantio- and diastereoselective aldol reactions of the silicon enolate derived from N-trifluoroacetylglycinate with aldehydes using a chiral zirconium catalyst.
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Details
The document describes a new synthetic protocol for the catalytic enantio- and diastereoselective aldol reactions of glycine-derived silicon enolate with aldehydes, developed by Jun Kobayashi and colleagues at the University of Tokyo. This method efficiently synthesizes anti-β-hydroxy-α-amino acid derivatives, which are important in various biologically active compounds. The researchers used a chiral zirconium catalyst to achieve high yields and selectivity. Initial experiments with benzaldehyde and different glycine-derived silicon enolates showed varying degrees of success, with the best results obtained using N-trifluoroacetylglycine-derived silicon enolate. The optimal conditions involved slow addition of the enolate and the use of toluene-tBuOMe as the solvent. The method was further tested with various aldehydes, consistently producing high yields and excellent enantioselectivity. The protocol was also applied to the efficient asymmetric synthesis of L-erythro-sphingosine, demonstrating its synthetic utility. This work represents the first example of enantioselective aldol reactions using silicon enolates from N-trifluoroacetyl-glycinate, offering a valuable approach for synthesizing complex molecules with β-hydroxy-α-amino carbonyl moieties. The research was supported by several Japanese scientific organizations and detailed experimental procedures are available online.
Key Words
α-Amino Acid Derivatives, Mukaiyama Aldol Addition
ID: J48-Y2004-1620
