Assignment of the Absolute Configuration of β-Chiral Primary Alcohols by NMR:  Scope and Limitations

The prediction of the absolute configuration of β-chiral primary alcohols from the 1 H NMR spectra of their esters with ( R )- and ( S )-9-anthrylmethoxyacetic acids (9-AMA, 3 ) is discussed. Low-temperature NMR experiments, MM, semiempirical, ab initio, and aromatic shielding effect calculations allowed the identification of the main conformers and showed that, in all alcohols for which the calculated Δ E ag (CVff) is in the range of 0.7−1.5 kcal/mol, conformer a / a is the most stable. A simple model for the assignment of the absolute configuration from NMR data is presented and its reliability corroborated with alcohols ( 8 − 20 ) of known configuration. Nevertheless, cyclic alcohols 21 − 23 have much higher Δ E ag values (2.2−3.1 kcal/mol) due to their different conformational composition, and their absolute configuration cannot be reliably predicted by this method.