Deuterium labelling to extract local stereochemical information by VCD spectroscopy in the C–D stretching region: a case study of sugars

Abstract

Stereochemical elucidation of molecules with multiple chiral centers is difficult. Even with VCD spectroscopy, excluding all but one diastereomeric structural candidate is challenging because the stereochemical inversion of one chiral center among many centers does not always result in noticeable differences in their VCD spectra. This work demonstrates that the introduction of a suitable VCD chromophore with absorption in the 2300–1900 cm⁻¹ region can be used for extracting local stereochemical information and for the stereochemical assignment of the C-1 position of various sugars as a case study. Through studies on a series of epimeric pairs of monosaccharides and their derivatives, we found that the introduction of one –OCD₃ group to each C-1 position produced almost mirror-image VCD patterns in the 2300–1900 cm⁻¹ region depending on the C-1 stereochemistry irrespective of the other molecular moieties. This work also shows that comparison of the observed VCD signals and the calculated ones enables the stereochemical assignment of a chiral center in the vicinity of the chromophore. This study provides a proof of concept that the use of a VCD chromophore in the 2300–1900 cm⁻¹ region enables the analysis of selected stereochemistry of suitable molecular systems. Further studies on this concept should lead to the development of a method useful for the structural elucidation of other types of complex molecules.