A practical route to β2,3-amino acids with alkyl side chains

Enantiopure N(Boc)-β(3)-amino nitriles, valuable synthetic intermediates in the multistep homologation of α-amino acids, were alkylated using n-BuLi as base. Alkylations afforded easily separable, almost equimolecular mixtures of diastereomeric N(Boc)-protected syn and anti β(2,3)-amino nitriles. Suitable manipulations of both cyano and amino groups eventually led to enantiopure N- and/or C-protected β(2,3)-amino acids. For example, methanolysis using conc. HCl gas in MeOH, provides C-protected β(2,3) amino acids in excellent yields. This methodology is applied to the synthesis of a series N(Boc)-β(2,3)-dialkyl amino nitriles derived from l-phenylalanine, d-phenylalanine, l-valine and one C-protected β(2,3) amino acid. We demonstrate an efficient procedure for the preparation of anti and syn β(2,3)-amino acids with alkyl side chains, from α-amino acids in reasonable yields.