Enantiopure O-Ethyl Phenylphosphonothioic Acid: A Solvating Agent for the Determination of Enantiomeric Excesses

An improved method, which is highly reproducible, was developed for the enantioseparation of racemic O-ethyl phenylphosphonothioic acid (1a) with brucine by introducing seeding to a supersaturated solution of the diastereomeric salt mixture. The present method gave both diastereomeric salts in high yields with a diastereomeric ratio of >99.5:0.5 upon choosing the crystallization solvent (MeOH for the (R)-1a salt and MeOH/H2O for the (S)-1a salt). The enantiopure acid 1a showed a good chirality recognition ability for not only strong bases, such as amines and amino alcohols, but also weakly basic alcohols and was applicable as a solvating agent to the H-1 NMR determination of the enantiomeric excess of chiral amines, amino alcohols, and alcohols, including aliphatic substrates. (C) 2014 Wiley Periodicals, Inc.