INTERMOLECULAR H-1-H-1 2-DIMENSIONAL NUCLEAR OVERHAUSER ENHANCEMENTS IN THE CHARACTERIZATION OF A RATIONALLY DESIGNED CHIRAL RECOGNITION SYSTEM

Chiral stationary phases (CSPs) for liquid chromatography derived from N-(acyl)proline-3,5-dimethylanilides separate the enantiomers of N-(3 ,5-dinitrobenzoyl)-alpha-amino esters and amides with high levels of s electivity. These CSPs have been used to assemble a large body of chro matographic data which indirectly supports the validity of the mechani stic rationale originally used in the design of these CSPs. We herein report H-1 and C-13 chemical shift data obtained when the (S)-enantiom er of chiral solvating agent (CSA) 3, a soluble analogue of the select or used in CSP (S)-1, acts on each of the enantiomers of the dimethyla mide of N-(3,5-dinitrobenzoyl)leucine, 2. The changes in chemical shif t in the mixture of (S)-2 and (S)-3 support the existence of those int eractions thought to be essential to chiral recognition in this system . In addition, significant intermolecular NOESY enhancements are obser ved in this mixture. These NOE data are consistent with the structure expected for the more stable diastereomeric adsorbate formed between ( S)-2 and the (S)-proline-derived CSP 1. No intermolecular NOEs are obs erved for corresponding mixtures of the chiral solvating agent (S)-3 a nd (R)-2, the enantiomer least retained on (S)-CSP 1.