Assignment of the Absolute Configuration of α-Chiral Carboxylic Acids by 1H NMR Spectroscopy

Abstract
The prediction of the absolute configuration of α-chiral carboxylic acids from the 1H NMR spectra of their esters with (R)- and (S)-ethyl 2-hydroxy-2-(9-anthryl) acetate [(R)- and (S)-9-AHA, 5] is discussed. Low-temperature NMR experiments, MM, semiempirical, and aromatic shielding effect calculations allowed the identification of the main conformers and showed that, in all esters studied, conformer ap is the most stable. A simple model for the assignment of the absolute configuration from NMR data is presented, and its reliability is corroborated with acids 6 − 31 of known absolute configuration. In addition to 5, other auxiliary reagents with open (32 − 38) and cyclic (39 − 42) structures have also been studied. trans-(+)- and (−)-2-phenyl-1-cyclohexanol (41) was found to be particularly efficient and produced ΔδRS values similar to those of 5.