Efficient Asymmetric Synthesis of Unnatural β-Amino Acids

Abstract

The simple and highly enantioselective methanolysis of cyclic meso-anhydrides mediated by cinchona alkaloids leads to a broad variety of dicarboxylic acid mono-methyl esters with up to 99% ee. From these products, unnatural N-protected β-amino esters can be obtained by means of Curtius degradation of the corresponding acyl azides. Subsequent cleavage of the protecting groups leads to the free β-amino acids in excellent yields. By enantiomer differentiating opening of racemic anhydrides, synthetically highly useful regioisomeric amino acid esters become readily available.