Asymmetric titanium-catalysed Michael addition of O-benzylhydroxylamine to αβ-unsaturated carbonyl compounds: synthesis of β-amino acid precursors

Abstract

A new titanium-catalysed Michael type addition of O-benzylhydroxylamine to αβ-unsaturated N-acylated 1,3-oxazolidinones giving β-amino acid precursors has been developed. The reaction is catalysed by TiX2–TADDOLate and TiCl2–BINOLate complexes and good conversions with enantiomeric excesses up to 42% were obtained with the application of 10 mol% of the catalyst. In order to determine the absolute stereochemistry of the enriched enantiomer one of the products, 3-(3-benzyloxyaminobutanoyl)-1,3-oxazolidin-2-one, was converted into methyl 3-benzoylaminobutanoate. Based on the absolute stereochemistry of the Michael type addition product the mechanism for the addition step is discussed, as well as the structure of the active intermediate.