The differentiation of diastereomers by 13C NMR spectroscopy

Abstract 13C shifts are reported for diastereomers with halogen, oxygen and amino substituents which are mainly at vicinal chiral centres. The conformer populations underlying the 13C shift analysis can be verified by chemical means, such as change of temperature, solvent polarity (with dihalides), solvent hydrogen bonding capacity (with diols), deprotonation (with diacids) and by molecular mechanics calculations. The latter provide the basis for configurational and conformational assignments with a series of ephedrine derivatives. In accordance with the 13C shift observations, it is found that ephedrine derivatives predominate in conformations with a gauche O and N substituent arrangement, even in cases where hydrogen bonds are absent.