Application of a ¹H δ‐resolved 2D NMR experiment to the visualization of enantiomers in chiral environment, using sample spatial encoding and selective echoes

Abstract

We present the application of a 2D broadband homodecoupled proton NMR experiment to the visualization of enantiomers. In a chiral environment, the existence of diastereoisomeric intermolecular interactions can yield-generally slight-variations of proton chemical shifts from one enantiomer to another. We show that this approach, which relies on a spatial encoding of the NMR sample, is particularly well suited to the analysis of enantiomeric mixtures, since it allows, within one single 2D experiment, to detect subtle chemical shift differences between enantiomers, even in the presence of several couplings. This sequence, which uses semiselective radio-frequency (rf) pulses combined to a z-field gradient pulse, produces different selective echoes in various parts of the sample. The resulting homonuclear decoupling provides an original delta-resolved spectrum along the diagonal of the 2D map where it becomes possible to probe the chiral differentiation process through every proton site where the resulting variation in the chemical shift is detectable. We discuss the advantages and drawbacks of this approach, regarding other experiments which provide homodecoupled proton spectra. This methodology is applied to the observation of enantiomers of (1) ( +/- )2-methyl-isoborneol coordinated to europium (III) tris[3-(trifluoromethyl-hydroxymethylene)-(+)-camphorate] in isotropic solution, and (2) ( +/- )3-butyn-2-ol dissolved in a chiral liquid-crystal solvent, in order to show the robustness of this pulse sequence for a wide range of chiral samples.

Broadband 13C‐Homodecoupled Heteronuclear Single‐Quantum Correlation Nuclear Magnetic Resonance

“…Moreover, the selective irradiation of the full bandwidth (30 kHz) generates signals with pure phases, making it www.chemphyschem.org possible to record spectra in a phase-sensitive manner. Identical observations have been made by Giraud et al [7] in the 1 H dresolved experiment, which highlights the robustness of this kind of experiments.…”

“…[6] More recently, this approach has been successfully extended by Giraud and co-workers to obtain 1 H d-resolved 2D NMR spectra. [7] These spatial encoding methods present similarities with ultrafast 2D NMR techniques whose success is constantly increasing.…”

Application of selective F1 decoupled 1H NMR for enantiomer resolution and accurate measurement of enantiomeric excess at low chiral substrate/auxiliary concentration

“…It is also well known that the enantiomeric discrimination depends on relative solute/chiral auxiliary concentration [8]. Generally the multiplets for both the enantiomers get resolved at higher concentration of the auxiliary.…”

“…Nowadays chiral-HPLC and capillary electrophoretic methods are routinely employed for enantiomeric analysis [3,4]. However, NMR spectroscopy continues to one of the very powerful and efficient analytical tools not only for chiral discrimination but also for the accurate measurement of enantiomeric excess [1,[6][7][8]. The NMR spectroscopy is intrinsically blind to differentiate enantiomers unless the intermolecular diastereomeric interactions are imposed with enantiomerically pure additives such as chiral solvating agents (CSAs), chiral derivatizing agents (CDAs) or chiral lanthanide shift reagents (CLSRs).…”

Simultaneously Enhancing Spectral Resolution and Sensitivity in Heteronuclear Correlation NMR Spectroscopy

“…It is routine to suppress heteronuclear couplings (J XH ) by broadband decoupling, [3][4][5][6][7] but only recently have experimental methods for homonuclear broadband decoupling become practical. These "pure shift" or "chemical-shift resolved" or "d-resolved" methods [8][9][10][11][12][13][14][15][16][17][18][19] can give resolution improvements approaching an order of magnitude, far in excess of any gains to be realistically expected from increases in the static magnetic field. However, all of these methods suffer to a greater or lesser extent from reduced sensitivity compared to conventional measurements.…”