A total conformational analysis of diastereomeric esters and calculation of their conformational shielding models

A total conformational analysis of diastereomeric esters was performed and the conformational shielding models (CSM) of the esters necessary for the NMR spectroscopic stereochemical assignment of carboxylic acids or alcohols were calculated. The esters of (R)-2-butanol and both enantiomers of O-methylphenylacetic acid (MPA), 2-phenoxypropanoic, 2-(2-formylphenoxy)propanoic, 2-methoxy-3-phenyl-propanoic and 2-methoxy-2-methyl-3-phenylpropanoic acids were investigated. The calculation method used was DFT B3LYP/6-31+G∗ (at the highest level in the optimization cascade). The Boltzmann weighting of individual conformers, covering an energy range of 2 kcal/mol, was used to evaluate the ring current effects of the aromatic group on the basis of a classical Pople point-dipole model describing anisotropy. The results afforded a CSM for the pairs of diastereomeric esters. The calculated CSM coincides with an empirical CSM of MPA and 2-phenoxycarboxylic acid esters and is in accordance with the experimental stereochemical results obtained for 2-methoxy-3-phenylpropanoic acid esters. The low values observed for the differential shieldings (ΔδRS) of 2-methoxy-2-methyl-3-phenylpropanoic acid esters were confirmed by their complex conformational equilibrium.