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

Abstract

A series of water‐soluble sulfonated calix[4]resorcinarenes with L‐proline, cis‐4‐hydroxy‐d‐ and ‐L‐proline, trans‐4‐hydroxy‐L‐proline and trans‐3‐hydroxy‐L‐proline are evaluated as chiral NMR solvating agents. The changes in chemical shifts and enantiomeric discrimination in the 1H NMR spectra of a variety of phenyl‐ and pyridyl‐containing compounds are reported. Substrates associate by insertion of the phenyl or pyridyl ring into the cavity of the calix[4]resorcinarene. Series of compounds with methylbenzylamine and benzyl alcohol units are among those examined. For many compounds, the calix[4]resorcinarenes with the hydroxyproline groups are more effective chiral NMR solvating agents than the corresponding proline derivative. The trans‐4‐ and trans‐3‐hydroxy‐L‐proline derivatives are especially effective as chiral NMR solvating agents. Enantiomeric discrimination in the 1H NMR spectra is often large enough to facilitate the analysis of enantiomeric purity.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Binding abilities of a chiral calix[4]resorcinarene: a polarimetric investigation on a complex case of study

“…Similar derivatives have also been studied as hydrogelators [22–23]. Moreover, water soluble chiral calix[4]resorcinarenes have been recently designed and used as chiral shift reagents for NMR applications [24–27]. …”

“…The host CAP was designed in analogy with a sulfonated chiral calix[4]resorcinarene (CAPS, Fig. 1) already known from the literature as NMR shift reagent able to perform chiral recognition [24–27]. Guests 1 – 12 were selected for their diverse structural features.…”

A water‐soluble calix[4]resorcinarene with L‐pipecolinic acid groups as a chiral NMR solvating agent

“…The most broadly applicable water‐soluble chiral NMR discriminating agents are underivatized cyclodextrins and certain cyclodextrin derivatives 4–21. A series of water‐soluble calix[4]resorcinarenes ( 1 , 2 , 3 , 4 , 5 , 6 ) are useful reagents for the enantiomeric discrimination of aromatic‐containing compounds 22–31…”

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 .…”

“…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. [23][24][25][26][27][28][29][30][31][32] Favorable association usually occurs with mono-or ortho-substituted phenyl rings or with monoor 2,3-disubstituted naphthyl rings. [26] One advantage of our system is that the derivatizing agent is achiral so that kinetic resolution of the enantiomers and loss of configuration in the derivatization step is not a concern.…”