Calix[4]arene, calix[4]resorcarene, and cyclodextrin derivatives and their lanthanide complexes as chiral NMR shift reagents

Abstract

Calix[4]arenes, calix[4]resorcarenes, and anionic cyclodextrin derivatives were examined as chiral NMR solvating agents. The calix[4]arenes were prepared by attachment of amino acids through the hydroxyl groups of the phenol rings. Chloroform-, methanol-, and water-soluble derivatives were prepared and tested with a range of substrates. Chloroform-soluble chiral calix[4]resorcarenes were prepared by attachment of chiral primary and secondary amines and examined in NMR applications with a variety of substrates. Sulfated and carboxymethylated beta-cyclodextrin are effective at causing enantiomeric discrimination in the (1)H NMR spectra of organic cations. Lanthanide ions associate at the carboxymethyl groups and cause sizeable shifts and enhancements in enantiomeric discrimination in the spectra of organic cations. The enhancements caused by the lanthanide ion are large enough that much lower concentrations of the cyclodextrin can be used as compared to conventional analyses.

Carboxymethylated cyclodextrins and their complexes with Pr(III) and Yb(III) as water‐soluble chiral NMR solvating agents for cationic compounds

“…[30][31][32]35 A similar finding occurs with most of the substrates examined herein. Ion pairing interactions between the cation and anionic carboxymethyl groups presumably are important in enhancing the distinction between the enantiomers that occurs for the carboxymethylated cyclodextrins compared with the native cyclodextrins.…”

“…In prior studies with commercially available CDCM derivatives, Dy(III), a lanthanide ion that produces large changes in chemical shifts with more broadening usually was needed to cause significant enough enhancements in enantiomeric discrimination. 30,31 With our CDCM-Ind derivatives, which have substantially higher DS than commercially available varieties, Pr(III) and Yb(III) could be used and produced significant enhancements in enantiomeric discrimination without causing too much line broadening. 35 Using an ion such as Eu(III), which is common with organic-soluble lanthanide shift reagents, is usually not as feasible with carboxymethylated cyclodextrins because the changes in chemical shifts are too small.…”

“…The highly substituted CDCM-Ind derivatives used in this report (DS 5 8-11) produce larger enantiomeric discrimination than commercially available carboxymethylated cyclodextrins with lower degrees of substitution (DS 5 2 for b-cyclodextrin), the use of which was described in earlier reports. 30,31 In prior reports with CDCM derivatives with lower DS, dysprosium(III), a lanthanide known for causing large perturbations in chemical shifts with much greater broadening, was usually needed to get sufficient alterations of the spectra. 30,31 In this report, using CDCM with higher DS, paramagnetic praseodymium(III) or ytterbium(III) ions can be added to CDCM-substrate mixtures and cause substantial changes in chemical shifts without significant broadening.…”

Carboxymethylated cyclodextrin derivatives as chiral NMR discriminating agents

“…[15][16][17][18] In particular, commercially available sulfated or carboxymethylated derivatives can be used for this purpose. 24,25 The sulfate and carboxymethylate moieties also provide binding sites for paramagnetic lanthanide ions, and addition of appropriate lanthanide ions to the systems often enhances the enantiomeric discrimination in the NMR spectrum. 24,25 Trends in the association of native and carboxymethylated a-, b-, and c-cyclodextrins with cationic pheniramine 1, chlorpheniramine 2, and brompheniramine 3 ( Fig.…”

Phosphated cyclodextrins as water-soluble chiral NMR solvating agents for cationic compounds

“…CDs with anionic carboxymethyl [21–32] (CM-CD, Fig. 1), sulfate [29–30 33–35], sulfobutylether [22–24 36–37] and thiocarboxymethyl [38] groups also have been studied as chiral NMR solvating agents. The general findings of these studies are that anionic CDs are more effective chiral NMR solvating agents for cationic substrates than neutral native CDs.…”