Stereochemical analysis of d-glucopyranosyl-sulfoxides via a combined NMR, molecular modeling and X-ray crystallographic approach

Synthesis of Thiodisaccharide Sulfoxides and Sulfones – Determination of the Configuration of the Sulfur Stereocentre

“…For each experimentally determined conformer, a minimum energy structure was calculated using molecular mechanics (MM+), and from these structures, the orientation of each proton relative to the S=O bond was established. In agreement with our assignments, an R-glucosyl sulfoxide adopts, in the crystalline state, [19] an atomic arrangement similar to the syn φ/syn ψ conformation detected in solution for 8R. Thus, the syn φ/syn ψ conformation of 8R shows syn-axial interactions of the S=O group with 2Ј-H, 2-H, and 4-H, and the respective signals in the 1 H NMR spectrum should undergo the observed downfield shifts.…”

“…It was evident that the major product of the oxidation of 4 had the R configuration, as this particular diastereoisomer explains the upfield and downfield shifts shown in Table 1. Furthermore, consistent with the behaviour of common xylopyranosyl [18] and glucopyranosyl [19,20] sulfoxides, the 2-H signal vicinal to the S=O group is shifted further downfield in the R isomer of the thioglycoside sulfoxide than it is in the S isomer. Similarly, in the syn φ/anti ψ conformation of 8R, the C-3-3-H bond bisects the angle between the O-S bond and the lone-pair; thus, it lies in the deshielding zone of the S=O group and so the 3-H signal is also deshielded.…”

“…[17] The application of this procedure to a wide range of carbohydrates, including extremely complex and sensitive ones, has prompted the development of highly efficient reactions for the oxidation of thioglycosides and for the determination of the configuration of the sulfur atom. [18][19][20][21] In this paper, we describe the synthesis of S-oxide (i.e., sulfoxide) and S,S-dioxide (i.e., sulfone) derivatives of S-(1Ǟ3)-and S-(1Ǟ4)-linked thiodisaccharides. For the assignment of the configuration of sulfoxides, NMR methods, molecular modelling, and X-ray crystallography have been used.…”

Recent Progress in Application of Spectroscopic Methods for Assigning Absolute Configuration of Optically Active Sulfoxides

“…This model is consistent with the experimental data reported [14,15] where, in every instance, the sense of nonequivalence of the two groups on either side of sulfur are opposite and correlated to the sulfoxide AC. The same authors also showed that acid (S)-6 can be conveniently used for AC assignment of aryl and benzyl sulfoxides like 7e-g, and 8a-c [20], as well as complex galacto-sulfoxides [21], whose AC assignment was also subsequently confirmed by X-ray analysis [22]. (1)) was later used by Kagan and coworkers [16] to determine the enantiomeric purities of chiral sulfoxides obtained by enantioselective oxidation of sulfides [6c,d].…”

“…Knowing this configurational correlation, the AC of 1thiochroman-S-oxide (21) [40] and that of 1-thiochromanone-S-oxide (22) (Fig. (7)) [41] has been also assigned, simply empirically comparing their ECD spectra with the one of 18.…”