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

Abstract

Nuclear magnetic resonance (NMR) is a powerful tool for the elucidation of chemical structure and chiral recognition. In the last decade, the number of probes, media, and experiments to analyze chiral environments has rapidly increased. The evaluation of chiral molecules and systems has become a routine task in almost all NMR laboratories, allowing for the determination of molecular connectivities and the construction of spatial relationships. Among the features that improve the chiral recognition abilities by NMR is the application of different nuclei. The simplicity of the multinuclear NMR spectra relative to 1H, the minimal influence of the experimental conditions, and the larger shift dispersion make these nuclei especially suitable for NMR analysis. Herein, the recent advances in multinuclear (19F, 31P, 13C, and 77Se) NMR spectroscopy for chiral recognition of organic compounds are presented. The review describes new chiral derivatizing agents and chiral solvating agents used for stereodiscrimination and the assignment of the absolute configuration of small organic compounds.

NMR chiral discrimination of chalcogen containing secondary alcohols

“…Furthermore, multinuclear NMR spectroscopy is an efficient alternative to overcome 1 H NMR limitations, such as overlap of signals, combined with broad and featureless spectra. Therefore, the 1 H NMR spectra of Naproxen ester derived from chalcogen containing secondary alcohol 1a is severely hampered due to the numerous scalar couplings.…”

“…77 Se and 125 Te NMR have great potential due to the characteristics of selenium and tellurium nuclei, such as a wide spectral window, 22 These great features can be witnessed by observing the 125 Te-{ 1 H} NMR spectra of Naproxen ester formed from chalcogen containing secondary alcohol 1h (Figure 1). Furthermore, multinuclear NMR spectroscopy is an efficient alternative to overcome 1 H NMR limitations, 23 such as overlap of signals, combined with broad and featureless spectra. Therefore, the 1 H NMR spectra of Naproxen ester derived from chalcogen containing secondary alcohol 1a is severely hampered due to the numerous scalar couplings.…”

Chalcogen‐Containing Diols: A Novel Chiral Derivatizing Agent for 77Se and 125Te NMR Chiral Recognition of Primary Amines

“…Alternatively, interest in the synthesis and application of chiral organochalcogen compounds has increased in recent years, in view of their versatility in asymmetric synthesis . However, the use of chalcogen ( 77 Se and 125 Te) NMR spectroscopy in chiral recognition is still in its infancy, particularly when compared to other nuclides, like 19 F and 31 P NMR . One of the major benefits of chalcogen nuclides is their ability to detect different structures, without the routine 1 H NMR difficulties, like signals overlapping, multiplicity and high sensitivity to the analysis conditions .…”

“…[10] However, the use of chalcogen ( 77 Se and 125 Te) NMR spectroscopy in chiral recognition is still in its infancy, particularly when compared to other nuclides, like 19 F and 31 P NMR. [11] One of the major benefits of chalcogen nuclides is their ability to detect different structures, without the routine 1 H NMR difficulties, like signals overlapping, multiplicity and high sensitivity to the analysis conditions. [12] Thus, the design of new strategic protocols for the assignment of the absolute configuration and determination of enantiomeric ratios involving new protocols, reagents and/or NMR pulse sequences is in constant development.…”

Stereospecific Assay of (R)- and (S)-Goitrin in Commercial Formulation of Radix Isatidis by Reversed Phase High-Performance Liquid Chromatography

“…Gas chromatography (GC) [18, 19], capillary electrophoresis (CE) [20, 21], and nuclear magnetic resonance spectroscopy (NMRS) [22, 23] also play important roles in the chiral recognition and analysis of enantiomers. Furthermore, the need for high-throughput and high-efficiency enantioseparation has led to the advancement of chiral screening techniques, such as supercritical fluid chromatography (SFC) [24, 25] and high-speed countercurrent chromatography (HSCCC) [26, 27].…”