Chiral NMR discrimination of pyrrolidines using (18-crown-6)-2,3,11,12-tetracarboxylic acid

Abstract

The compound (18-crown-6)-2,3,11,12-tetracarboxylic acid is shown to be an effective chiral NMR solvating agent for determining the enantiomeric excess of chiral pyrrolidines. Enantiomeric discrimination is observed in both the 1H and 13C NMR spectra. The neutral amine is mixed with the crown ether in an NMR tube and a neutralization reaction between the two produces the corresponding ammonium and carboxylate ions. An association of these ions accounts for the chiral recognition. Pyrrolidines with one or two substituent groups α to the nitrogen atom are not inhibited from binding to the crown ether. Chiral discrimination was observed in the NMR spectra of pyrrolidines that have a stereogenic center α or β to the nitrogen atom. Dibasic substrates are likely converted to their diprotonated form in the presence of the crown ether, and both ammonium sites appear to associate with the crown ether moiety.