Water-Soluble Calix[4]Resorcinarenes as Chiral NMR Solvating Agents for Bicyclic Aromatic Compounds

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 H-1-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 H-1-NMR spectrum is large enough for many resonances to permit the analysis of enantiomeric purity. Chirality 21:911-921, 2009. (C) 2009 Wiley-Liss, Inc.