A Simple ¹³C NMR Method for the Discrimination of Complex Mixtures of Stereoisomers: All Eight Stereoisomers of α‐Tocopherol Resolved

Abstract

A simple one-dimensional (13)C NMR method is presented to discriminate between stereoisomers of organic compounds with more than one chiral center. By means of this method it is possible to discriminate between all eight stereoisomers of α-tocopherol. To achieve this the chiral solvating agent (S)-(+)-1-(9-anthryl)-2,2,2-trifluoroethanol and the compound of interest were dissolved in high concentrations in chloroform-d, and the nuclear magnetic resonance (NMR) spectrum was recorded at a low temperature. The individual stereoisomers of α-tocopherol were assigned by spikes of the reference compounds. The method was also applied to six other representative examples.

Recent Advances in Multinuclear NMR Spectroscopy for Chiral Recognition of Organic Compounds

“…This strategy becomes more attractive mainly when the 1 H-NMR spectra demonstrate broad multiplets and small chemical shift differences between the stereoisomers. As a result, Lankhorst et al presented a simple 13 C-NMR methodology for the discrimination of a complex mixture of α-tocopherol stereoisomers [ 75 ]. The traditional methods employed to perform this discrimination, such as gas and liquid chromatography, require multiple steps to prepare the sample and obtain the ideal conditions.…”

One-Dimensional 13C NMR Is a Simple and Highly Quantitative Method for Enantiodiscrimination

“…Very recently, we have shown that one important advantage of 1D 13 C NMR is the extremely high resolution that can be obtained, which led to the discrimination of all eight stereoisomers (four diastereomeric pairs of enantiomers) of the three-chiral-carbon containing α-tocopherol (Vitamin E). We could assign all eight stereoisomers, and 0.75% of a minor stereoisomer could be detected in a sample of pure RRR α-tocopherol in an NMR experiment of 30 min (256 scans) [ 13 ]. The use of multinuclear NMR for enantiodiscrimination has been reviewed recently [ 14 ].…”

Discrimination of stereoisomers by one‐dimensional 13C NMR: All 16 stereoisomers of 4‐hydroxy‐α‐tocopherol resolved

“…We previously demonstrated that all eight stereoisomers of α-tocopherol, which contains three chiral centers, could be identified by means of one-dimensional (1D) 13 C NMR. [1] In the present contribution, we show that the superior resolution of 1D 13 C NMR even allows for the discrimination between all 16 stereoisomers of a compound with four chiral centers: 4-hydroxy-α-tocopherol (1; Figure 1).…”

“…For general information on experimental procedures, see ref. [1] Purities given were measured by quantitative 1 H NMR, unless otherwise noted.…”

“…A recent comprehensive review on the use of CSAs for chiral analysis was published by Balzano et al [6] and on NMR methods for differentiation of chiral compounds in general by Wenzel. [7] 1D 13 C NMR is not applied frequently for the analysis of mixtures of stereoisomers, [1,[8][9][10][11][12] and further examples can be found in a recent review on multinuclear NMR spectroscopy for chiral recognition by Silva [13] and in the reviews mentioned above. [6,7] The main reason is the fact that 13 C NMR is much less sensitive than 1 H NMR.…”