Highly Enantioselective Synthesis of γ-Carboxy-β-amino Acids via Desymmetric Alcoholysis of 3-Aminoglutaric Anhydrides

A highly enantioselective synthetic method of γ-carboxy-β-amino acids has been developed via the desymmetric alcoholysis of 3-aminoglutaric anhydrides. The asymmetric desymmetrization of <i>N</i>-trifluoroacetyl-<i>N</i>-acyl-3-aminoglutaric anhydrides with alcohols in the presence of bis-quinine-squaramide as a bifunctional organocatalyst afforded γ-carboxy-β-amino acids with up to 99% yield and 98% ee. These versatile compounds can be readily converted into various chiral derivatives. The practicality of this method was further demonstrated by its successful application in the synthesis of β-amino acid and β-amino lactone derivatives.