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 α-chiral primary amines and α-amino acid esters show different chemical shifts in ¹H NMR spectroscopy (300 MHz) depending on their configuration. Molecular mechanics, semiempirical calculations, and ¹H NMR studies suggest that, in solution, these amides prefer an ap-Z conformation with the C_αOAr 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_αH and CO groups in a syn-periplanar conformation). The conformational model for ROAL amides allows the absolute configuration assignment of primary amines and α-amino acid esters according to the relative position of the aryl group and the substituents on the amine moiety, and also their enantiomeric composition.