Water‐soluble calix[4]resorcinarenes as chiral NMR solvating agents for bicyclic aromatic compounds

Abstract

Water-soluble calix[4]resorcinarenes with proline, 3-hydroxyproline, and 4-hydroxyproline substituent groups are evaluated as chiral NMR solvating agents on a series of bicyclic aromatic compounds with naphthyl, indole, dihydroindole, and indane rings. The substrates interact with the calixresorcinarene through insertion of the aromatic ring into the cavity. Most of the substrates are analyzed as cationic species, although one anionic species is analyzed. All of the substrates exhibit enantiomeric discrimination in the 1H-NMR spectrum with one or more of the calixresorcinarenes. In most cases, the hydroxyproline derivatives are more effective at causing enantiodifferentiation than the corresponding proline derivative. Presumably, the hydroxyl group on the proline moieties is involved in interactions with the substituent groups of the substrate that are important in creating chiral recognition. The enantiomeric discrimination in the 1H-NMR spectrum is large enough for many resonances to permit the analysis of enantiomeric purity.

An Edge Selection Mechanism for Chirally Selective Solubilization of Binaphthyl Atropisomeric Guests by Cholate and Deoxycholate Micelles

“…) were performed with higher concentrations of bile aggregates (e.g., 80 mM). Placing the naphthyl guest in a hydrophobic pocket is self‐consistent with the chemical shift perturbations observed in Figures and , since upfield changes in chemical shifts are associated with increasing hydrophobicity of the local binding environment …”

“…Placing the naphthyl guest in a hydrophobic pocket is self-consistent with the chemical shift perturbations observed in Figures 3 and 4, since upfield changes in chemical shifts are associated with increasing hydrophobicity of the local binding environment. 37 Any individual 2D-NOE spectrum in Figures 6 and 7 provides 18 intermolecular NOE signals (six for each methyl, noting again that some weak Me 21 NOE cross-peaks in Figs. 6 and 7 are not contoured).…”

Water‐Soluble Calix[4]resorcinarenes with Hydroxyproline Groups as Chiral NMR Solvating Agents for Phenyl‐ and Pyridyl‐Containing Compounds

“…Changes in the chemical shifts are quite comparable for SCR-Pro and SCR-t3L, slightly larger with SCR-c4L, and larger still for SCR-t4L. The enhanced enantiomeric discrimination with SCR-t4L is more likely the result of differential interactions of the proline hydroxy group rather than the larger perturbations in chemical shifts, because, as already noted herein and from previous studies, [28][29][30] larger shifts with the different calix[4]-resorcinarenes often do not correlate with enhancements in enantiomeric discrimination. Substantial enantiomeric discrimination of the Hm and Hp resonances only occurs in the presence of SCR-t4L.…”

“…In this and other studies using these calix [4]resorcinarenes as chiral NMR discriminating agents, larger changes in the chemical shifts of the resonances of the substrate are often accompanied by greater broadening. [26][27][28][29][30] The best calix [4]resorcinarene is the one that produces adequate changes in chemical shifts with suitable enantiomeric discrimination and acceptable levels of broadening. As seen by the spectra in Figure 3, SCR-Pro is the best reagent for 20.…”

Chiral discrimination of aliphatic amines and amino alcohols using NMR spectroscopy

“…We have devised an alternative procedure for the analysis of 2–10 that relies on derivatizing the amine with naphtho[2,3‐ c ]furan‐1,3‐dione (Scheme ) to form an amide and using water‐soluble calix[4]resorcinarenes ( 11–13 ) for the NMR analysis. Compounds 11–13 form cavities and are effective water‐soluble chiral NMR solvating agents for substrates with aromatic rings that are relatively free of steric hindrance . Favorable association usually occurs with mono‐ or ortho ‐substituted phenyl rings or with mono‐ or 2,3‐disubstituted naphthyl rings .…”