Determination of the Absolute Configuration of Amines and α-Amino Acids by 1H NMR of (R)-O-Aryllactic Acid Amides

(R)-O-Aryllactic acid (ROAL) amides derived from alpha-chiral primary amines and alpha-amino acid esters show different chemical shifts in (1)H NMR spectroscopy (300 MHz) depending on their configuration. Molecular mechanics, semiempirical calculations, and (1)H NMR studies suggest that, in solution, these amides prefer an ap-Z conformation with the C(alpha)OAr and C=O groups close to anti-periplanar as in the case of mandelic acid amides. The proposed conformational preference is different from that of the ROAL esters (C(alpha)H and C=O groups in a syn-periplanar conformation). The conformational model for ROAL amides allows the absolute configuration assignment of primary amines and alpha-amino acid esters according to the relative position of the aryl group and the substituents on the amine moiety, and also their enantiomeric composition.