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

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

doi:10.1021/ol026721f

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

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

Authors

David M Casper¹, James R Burgeson, Joel M Esken, Gregory M Ferrence, Shawn R Hitchcock

Affiliation

¹ Department of Chemistry, Illinois State University, Normal, Illinois 61790-4160, USA.

PMID: 12375932
DOI: 10.1021/ol026721f

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aldehydes / chemistry*
Ephedrine / chemistry*
Magnetic Resonance Spectroscopy
Molecular Structure
Oxazines / chemistry*
Stereoisomerism

Substances

3,4,5,6-tetrahydro-2H-1,3,4-oxadiazin-2-one
Aldehydes
Oxazines
3-hydroxybutanal
Ephedrine