Direct Organocatalytic Asymmetric Aldol Reactions of α-Amino Aldehydes: Expedient Syntheses of Highly Enantiomerically Enriched <i>a</i><i>nti</i>-β-Hydroxy-α-amino Acids

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.