Assignment of the absolute configuration of α-chiral carboxylic acids by 1H NMR spectroscopy

The prediction of the absolute configuration of a-chiral carboxylic acids from the H-1 NMR spectra of their esters with (R)- and (S)-ethyl 2-hydroxy-2-(9-anthryl) acetate [(R)- and (S)-g-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 crp 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 Delta delta(RS) values similar to those of 5.