NMR Spectroscopic Determination of Enantiomeric Excess Using Small Prochiral Molecules

The use of chiral auxiliaries, which derivatize enantiomers to diastereomers, is an established technique for NMR spectroscopic analysis of chirality and enantiomeric excess (<i>ee</i>). Here we report that some small prochiral molecules exhibit <i>ee</i>-dependent splitting of ¹H NMR signals at room temperature based on acid/base interactions with chiral analytes, especially when either a chiral or prochiral acid contains a phenoxy group at the α-position of the carboxylic acid. As a representative case, the benzylamine (<b>BA</b>)/2-phenoxylpropionic acid (<b>PPA</b>) complex was comprehensively investigated by using various methods. Notably, X-ray crystallographic analysis shows that there are multipoint interactions in the <b>BA</b>/<b>PPA</b> complex, implying that “fixing” of molecular conformation is critical for efficient intermolecular transfer of magnetic anisotropy. Our results suggest that a wide range of prochiral molecules are available for NMR determination of <i>ee</i> when intermolecular interactions between prochiral molecules and chiral analytes are adequately designed