Enantioselective, Chromatography-Free Synthesis of β 3 -Amino Acids with Natural and Unnatural Side Chains

beta(3)-Amino acids are key components of some pharmaceuticals, excellent surrogates for metabolically labile alpha-amino acids, and building blocks for chiral heterocycles. Unfortunately they are not easily accessible in enantiomerically pure form, especially when possessing unnatural side chains. A flexible, chromatography-free process for the synthesis of enantiopure beta(3)-amino acids possessing natural and unnatural side chains is described. The procedure uses inexpensive starting materials and reagents and offers a good alternative to the hazardous and expensive Arndt-Eistert homologation of enantiopure a-amino acids. Its utility has been demonstrated with the preparative scale synthesis of two valuable beta(3)-amino acids possessing unnatural side chains.