迈向一类结构新颖的手性助剂的开发：基于(1R,2S)-麻黄碱的3,4,5,6-四氢-2H-1,3,4-恶二嗪-2-酮的非对映选择性羟醛反应。

Toward the development of a structurally novel class of chiral auxiliaries: diastereoselective aldol reactions of a (1R,2S)-ephedrine-based 3,4,5,6-tetrahydro-2H-1,3,4-oxadiazin-2-one.

作者信息

Casper David M, Burgeson James R, Esken Joel M, Ferrence Gregory M, Hitchcock Shawn R

机构信息

Department of Chemistry, Illinois State University, Normal, Illinois 61790-4160, USA.

出版信息

Org Lett. 2002 Oct 17;4(21):3739-42. doi: 10.1021/ol026721f.

DOI:10.1021/ol026721f

PMID:12375932

Abstract

[reaction: see text] Asymmetric aldol addition reactions have been conducted with (1R,2S)-ephedrine-derived 3,4,5,6-tetrahydro-2H-1,3,4-oxadiazin-2-one (2). Diastereoselectivities range from 75:25 to 99:1 for the formation of the crude non-Evans syn adducts 8a-h. The facial selectivity of the enolate is directed by the stereogenic N(4)-methyl substituent. Aldol adduct 8a is readily cleaved by acid hydrolysis to afford (2S,3S)-3-hydroxy-2-methyl-3-phenylpropionic acid (9) in >95% ee.

摘要

[反应：见正文] 已使用（1R，2S）-麻黄碱衍生的3,4,5,6-四氢-2H-1,3,4-恶二嗪-2-酮（2）进行不对称羟醛加成反应。粗制非埃文斯顺式加合物8a-h的形成的非对映选择性范围为75:25至99:1。烯醇盐的面选择性由手性N（4）-甲基取代基引导。羟醛加合物8a很容易通过酸水解裂解，以>95%的ee值得到（2S，3S）-3-羟基-2-甲基-3-苯基丙酸（9）。