RES-TOCSY: a simple approach to resolve overlapped 1H NMR spectra of enantiomers

Abstract

Chiral auxiliaries are used for the NMR spectroscopic study of enantiomers. Often the presence of impurities, overlap of peaks, line broadening and the multiplicity pattern restrict the chiral analysis in the 1D (1)H NMR spectrum. The present study introduces a simple 2D (1)H NMR experiment to unravel the overlapped spectrum. The experiment separates the spectra of enantiomers, thereby allowing the unambiguous assignment of all the coupled peaks and the measurement of enantiomeric excess (ee) from a single experiment even in combinatorial mixtures.

Insight into old and new pure shift nuclear magnetic resonance methods for enantiodiscrimination

“…It results in large error for ee when chemical shift between the enantiomers is very small. In such a situation, ω 1 ‐decoupled COSY experiment (see Figure b) and RES‐TOCSY experiment (see Figure c) can be employed for enantiodiscrimination studies. By using CLSRs or CSAs, accurate quantification of ee is possible for chiral compounds possessing different functional groups, for which errors from the 1D 1 H NMR spectra range in 2–5% .…”

“…The only difference between them is that, unlike in ω 1 ‐decoupled COSY experiment, RES‐TOCSY allows the resolution of multiple proton sites in ω 2 dimension. This was accomplished by appending spin lock just before the acquisition (see Figure c) to cause magnetization transfer to other protons in bonding network like in TOCSY experiment . One advantage of these experiments is that they require very small spectral width (15–25 Hz) in the indirect dimensions.…”

“…Selective refocusing block is a combination of selective and hard 180° pulses. Reproduced with permission from Lokesh et al…”

“…(a) 1D 1 H‐NMR spectrum of valine methyl ester hydrochloride in the presence of a chiral solvating agent; (b) 2D 1 H J ‐resolved spectrum and (c) 2D 1 H RES‐TOCSY spectrum with selective excitation of proton “b” recorded under identical conditions. Reproduced with permission from Lokesh et al…”

“…Use of these methodologies can avoid the effect of paramagnetic relaxation on line broadening at lower shift reagent concentration. Another advantage of RES‐TOCSY experiment lies in the assignment for the particular diastereomer straightforwardly due to TOCSY kind of block, which is informative in the assignment of absolute configuration …”