Toward the Development of a Structurally Novel Class of Chiral Auxiliaries: Diastereoselective Aldol Reactions of a (1<i>R</i>,2<i>S</i>)-Ephedrine-Based 3,4,5,6-Tetrahydro-2<i>H</i>-1,3,4-oxadiazin-2-one

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.