α-氨基醛的直接有机催化不对称羟醛反应：高效合成对映体高度富集的反式-β-羟基-α-氨基酸

Direct organocatalytic asymmetric aldol reactions of alpha-amino aldehydes: expedient syntheses of highly enantiomerically enriched anti-beta-hydroxy-alpha-amino acids.

作者信息

Thayumanavan Rajeswari, Tanaka Fujie, Barbas III Carlos F

机构信息

Department of Chemistry and Molecular Biology and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.

出版信息

Org Lett. 2004 Sep 30;6(20):3541-4. doi: 10.1021/ol0485417.

DOI:10.1021/ol0485417

PMID:15387543

Abstract

[reaction: see text] A simple and efficient method for the synthesis of highly enantiomerically enriched beta-hydroxy-alpha-amino acid derivatives has been developed. Direct asymmetric aldol reactions of a glycine aldehyde (aminoacetaldehyde) derivative have been performed under organocatalysis using l-proline or (S)-5-pyrrolidine-2-yl-1H-tetrazole. The reactions afforded anti-beta-hydroxy-alpha-amino aldehydes in good yield with high diastereoselectivity (dr up to >100:1) and high enantioselectivity (up to >99.5% ee), which were easily transformed into beta-hydroxy-alpha-amino acid derivatives.

摘要

[反应：见正文] 已开发出一种简单有效的方法来合成高度对映体富集的β-羟基-α-氨基酸衍生物。甘氨酸醛（氨基乙醛）衍生物的直接不对称羟醛反应已在有机催化下使用L-脯氨酸或（S）-5-吡咯烷-2-基-1H-四唑进行。反应以良好的产率、高非对映选择性（dr高达>100:1）和高对映选择性（高达>99.5% ee）得到反式β-羟基-α-氨基醛，这些醛很容易转化为β-羟基-α-氨基酸衍生物。