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. 2020 Sep 18;10(57):34605-34611.
doi: 10.1039/d0ra06312f. eCollection 2020 Sep 16.

Azaheterocyclic diphenylmethanol chiral solvating agents for the NMR chiral discrimination of alpha-substituted carboxylic acids

Gao-Wei Li  1   2 , Xiao-Juan Wang  1 , Dan-Dan Cui  1 , Yu-Fei Zhang  1 , Rong-Yao Xu  1 , Shuai-Hua Shi  1 , Lan-Tao Liu  1 , Min-Can Wang  2 , Hong-Min Liu  2 , Xin-Xiang Lei  3
Affiliations

Azaheterocyclic diphenylmethanol chiral solvating agents for the NMR chiral discrimination of alpha-substituted carboxylic acids

Gao-Wei Li et al. RSC Adv. .

Abstract

A series of small-membered heterocycle probes, so-called azaheterocycle-containing diphenylmethanol chiral solvating agents (CSAs), have been developed for NMR enantiodiscrimination. These chiral sensors were readily synthesized were inexpensive and efficiently used for the chiral analysis of alpha-substituted carboxylic acids. The sensing method was operationally simple and the processing was straightforward. Notably, we propose (S)-aziridinyl diphenylmethanol as a promising CSA, which has excellent chiral discriminating properties and offers multiple detectable possibilities pertaining to the 1H NMR signals of diagnostic split protons (including 25 examples, up to 0.194 ppm, 77.6 Hz). Its ability to detect the molecular recognition of fluorinated carboxylic acids were further investigated, with a good level of discrimination via the 19F NMR spectroscopic analysis. In addition, an accurate enantiomeric excess (ee) analysis of the p-methoxyl-mandelic acid with different optical compositions have been calculated based on the integration of well-separated proton signals.

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Conflict of interest statement

There are no conflicts to declare.

Figures

Fig. 1
Fig. 1. Chiral aza-heterocycle-containing diphenylmethanols 1–4.
Fig. 2
Fig. 2. Part of the 1H NMR spectra of (rac)-4-MeO-MA in the presence of different molar amounts of (S)-aziridinyl diphenylmethanol 1.
Fig. 3
Fig. 3. Job plots of (S)-aziridinyl diphenylmethanol 1 with (R)-4-MeO-MA and (S)-4-MeO-MA. Δδ stands for the chemical shift change of the α-H proton of (R)- and (S)-4-MeO-MA in the presence of (S)-aziridinyl diphenylmethanol 1. X stands for the molar fraction of the (S)-aziridinyl diphenylmethanol 1 (X = [(S)-aziridinyl diphenylmethanol 1]/[(S)-aziridinyl diphenylmethanol 1] + [4-MeO-MA]). The total concentration is 10 mM in CDCl3.
Fig. 4
Fig. 4. (a) Selected regions of the 1H NMR spectra of different optical purities 4-MeO-MA samples (ee% = R% − S%) with (S)-aziridinyl diphenylcarbinol 1 in CDCl3; (b) linear correlation between ee values determined by gravimetry (Y) and values were defined in terms of (R)-4-MeO-MA (X), R2 = correlation coefficient.
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