Solvent-Induced Chirality Switching in the Enantioseparation of Hydroxycarboxylic Acids with a Quaternary Stereogenic Center

The enantiomer separation of three isomeric hydroxycarboxylic acids with a quaternary stereogenic center via diastereomeric salt formation with (1<i>R</i>,2<i>S</i>)-2-amino-1,2-diphenylethanol was demonstrated. Racemic acid <b>1,</b> with a quaternary chiral center at the β-position, was separated with nearly ideal efficiency. The stereochemistry of acids <b>2</b> and <b>3</b> incorporated in the less-soluble salts was reversed depending on the recrystallization solvents, and both enantiomers were accessible. The mechanism of this chirality switching was discussed based on the crystal structures of the less-soluble diastereomeric salts; the solvation of the salt with an alcohol molecule changed the hydrogen-bonding network and its stability.