Chiral mono- and dicarbamates derived from ethyl (S)-lactate: convenient chiral solvating agents for the direct and efficient enantiodiscrimination of amino acid derivatives by 1H NMR spectroscopy

Abstract

New chiral solvating agents (CSAs) for NMR spectroscopy have been obtained from ethyl (S)-lactate, a very cheap commercially available product. By a sequence of simple chemical modifications of its functional groups, monocarbamoylated and dicarbamoylated derivatives were obtained, the potentialities of which as CSAs for NMR spectroscopy have been explored. Their ability to differentiate the resonances of enantiomeric mixtures of amino acids bearing a 3,5-dinitrobenzoyl moiety at the amino group and with the carboxyl function derivatized as methyl ester or amide has been probed. Almost every CSA was able to originate enantiodiscrimination in the ¹H NMR spectra, with (2S)-1-(3,5-dimethylphenylcarbamoyloxy)-2-(3,5-dinitrophenylcarbamoyloxy)propane (4) standing out for efficiency and versatility.

Fig. 1. Chemical structures of CSAs 1–6.

Fig. 2. Chemical structures of derivatives 7–13.

Scheme 1. Synthesis of CSAs 1–6: (a) Amberlyst-15H, MeOH; (b) 3,5-dinitrophenyl isocyanate, toluene at reflux.

Fig. 3. ¹H NMR (600 MHz, CDCl₃, 25 °C) spectral regions corresponding to 3,5-dinitrobenzoyl and NH_α protons of 7 (10 mM) in the presence of one equivalent of CSA.