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

Abstract

In this work, a novel chiral diol containing a chalcogen was developed for the 77Se and 125Te NMR chiral recognition of racemic primary amines. The enantiopure chiral derivatizing agents were synthesized from a readily available and versatile (S)‐solketal reagent. The synthesis was performed in three steps with satisfactory yields. The chiral derivatizing agents containing selenium or tellurium nuclides were evaluated for effective NMR chiral discrimination of racemic primary amines by a simple three component chiral derivatization protocol through the modified James‐Bull method. The split 77Se and 125Te NMR signals are well‐distinguishable and greater than 1H NMR signals. The Nuclear Overhauser Spectroscopy (NOESY) NMR 2D analysis and semi‐empirical method suggest a conformational preference of diastereoisomers, that provide information of the absolute configuration using selenium and tellurium chiral derivatizing agents.

Selenium‐NMR Spectroscopy in Organic Synthesis: From Structural Characterization Toward New Investigations

“…Selenium element has proven to be a suitable nuclide in NMR spectroscopy in studies on stability, [40] reactivity, [41,42] chirality, [43,44,45,46,47,48] polymers, [49,50,51] coordination chemistry, [52,53,54,55] and bio-based experiments. [56,57,58,59] The great potential of 77 Se NMR experiments can be attributed to selenium-77 isotope properties, as spin ( 1 = 2 ), natural abundance (7.63%), no quadrupolar moment, magnetogyric ratio (5.12 × 10 7 rad.s À 1 .T À 1 ) and negligible nuclear Overhauser effect (nOe).…”

Recognition in the Domain of Molecular Chirality: From Noncovalent Interactions to Separation of Enantiomers

“…Recently, Silva et al described chiral discrimination and assignment of the absolute configuration of primary amines based on a three-component NMR derivatization protocol, involving a racemic primary amine such as 74, 2formylphenyl-boronic acid (75), and enantiopure (R)-3-(phenylchalcogen)-1,2-propanediols 76 and 77, as CDAs, in CDCl 3 at 25 °C (Figure 78a). 989 In the NMR analysis, the observed chemical shift differences of 1 H a and 1 H b of the diastereomeric adducts 78 were 0.015 ppm (7.5 Hz) and 0.044 ppm (22 Hz), respectively (500 MHz frequency) (Figure 78b). For the hydrogen 1 H b , it was possible to measure the integrals without signals overlapping, whereas 1 H a was affected by the multiplicity of the signals.…”

“…The main advantage of chalcogen nuclides is their ability to detect different structures without the difficulties encountered in 1 H NMR, like overlapping signals, multiplicity, and high sensitivity to the analysis conditions. Recently, Silva et al described chiral discrimination and assignment of the absolute configuration of primary amines based on a three-component NMR derivatization protocol, involving a racemic primary amine such as 74 , 2-formylphenyl-boronic acid ( 75 ), and enantiopure ( R )-3-(phenylchalcogen)-1,2-propanediols 76 and 77 , as CDAs, in CDCl 3 at 25 °C (Figure a) . In the NMR analysis, the observed chemical shift differences of 1 H a and 1 H b of the diastereomeric adducts 78 were 0.015 ppm (7.5 Hz) and 0.044 ppm (22 Hz), respectively (500 MHz frequency) (Figure b).…”

“…(a) Derivatization of racemic primary amine 74 with CDA 76 and 77 by the three-component reaction; (b) 1 H and (c) 77 Se-{1H} NMR spectra of diastereomeric mixtures of adducts 78 ; (d) 125 Te-{1H} NMR spectrum of diastereomeric mixtures of adducts 79 . Adapted with permission from ref . Copyright 2019 John Wiley and Sons.…”

Application of aromatic amide‐derived atropisomers as chiral solvating agents for discrimination of optically active mandelic acid derivatives in 1H nuclear magnetic resonance spectroscopy

“…Various chiral derivatizing agents (CDAs), chiral solvating agents (CSAs), or chiral shift reagents (CSRs) have been developed and used in NMR spectroscopy for chiral analysis. [ 13–16 ] For the CDA method, the enantiomers of a chiral compound should be derivatized before the NMR analysis, leading to obvious inconvenience. In contrast, the CSA or CSR method could overcome the above disadvantage.…”