A stereoselective synthesis of the (2R, 3S)- and (2S, 3R)-3-amino-2-hydroxybutyric acid derivatives, the key components of a renin inhibitor and bestatin.

The title synthesis was achieved by featuring the [2+2]-cycloaddition reaction of benzyloxyketene with a chiral imine derived from methyl (R)- or (S)-mandelate, alcoholysis of the formed 3,4-cis disubstituted β-lactam under acidic conditions, and reductive removal obtained by the [2+2]-cycloaddition reaction employing achiral and chiral imines derived from benzylamine, p-anisidine, di-panisylmethylamine, and (S)-l-phenylethylamine were also reported. Stereoselectivity of the [2+2]-cycloaddition reaction could be explained by the initial formation of a zwitter-ionic intermediate and its subsequent conrotatory ring closure.