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.
[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.
Casper
David M
DM
Department of Chemistry, Illinois State University, Normal, Illinois 61790-4160, USA.
Burgeson
James R
JR
Esken
Joel M
JM
Ferrence
Gregory M
GM
Hitchcock
Shawn R
SR
D000447:Aldehydes / Q000737:chemistry*; D004809:Ephedrine / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010078:Oxazines / Q000737:chemistry*; D013237:Stereoisomerism
C467771:3,4,5,6-tetrahydro-2H-1,3,4-oxadiazin-2-one; D000447:Aldehydes; D010078:Oxazines; C116609:3-hydroxybutanal; D004809:Ephedrine