Phosphated cyclodextrins as water-soluble chiral NMR solvating agents for cationic compounds.

Cira Mollings Puentes,Thomas J Wenzel

doi:10.3762/bjoc.13.6

Abstract

The utility of phosphated α-, β- and γ-cyclodextrins as water-soluble chiral NMR solvating agents for cationic substrates is described. Two sets of phosphated cyclodextrins, one with degrees of substitution in the 2–6 range, the other with degrees of substitution in the 6–10 range, are examined. Results with 33 water-soluble cationic substrates are reported. We also explored the possibility that the addition of paramagnetic lanthanide ions such as praseodymium(III) and ytterbium(III) further enhances the enantiomeric differentiation in the NMR spectra. The chiral differentiation with the phosphated cyclodextrins is compared to prior results obtained with anionic carboxymethylated cyclodextrins. There are a number of examples where a larger differentiation is observed with the phosphated cyclodextrins.

Highlights

Chiral NMR solvating agents are commonly used for determining enantiomeric purity
Previous studies [21,31,32] and observations made with the P-CDs indicate that host–guest complexes through insertion of the aryl ring into the cavity of the CDs occur which is supported by NMR measurements
In the NMR spectra the resonances of the P-CD H3 and H5 protons, which are located inside the CD cavity, are perturbed to lower frequencies in the spectra due to shielding of these protons by the inserted aryl ring

Summary

Introduction

Chiral NMR solvating agents are commonly used for determining enantiomeric purity. In some cases, these compounds cause reproducible perturbations in chemical shifts that can be used in the assignment of the absolute stereochemistry [1,2,3,4,5,6,7]. Since chiral solvating agents associate with the compound being studied through non-covalent interactions, they are easy to use and involve merely mixing the reagent with the compound in an NMR tube. Cyclodextrins (CDs), which are cyclic oligosaccharides containing D-glucose units, represent an important and versatile class of chiral NMR solvating agents (Figure 1). The most common representatives are α-, β- and γ-CD, which contain six, seven and eight glucose rings, respectively. The secondary hydroxy groups at the 2 and 3-posi-

Methods

Results

Conclusion