Enantiodifferentiation of chiral hydroxy acids via19F NMR

Abstract

We present a high-resolution ¹⁹F NMR platform for the enantiodifferentiation of chiral hydroxy acids via a rapid three-component derivatization reaction between a ¹⁹F-labeled chiral amine, 2-formylphenylboronic acid, and the hydroxy acid analyte. The probe design includes two different fluorinated groups (–CF₃ and –OCF₃), allowing for detection using dual-site ¹⁹F readout. This dual-fluorine strategy markedly improves chiral resolution and minimizes signal overlap, a common limitation of conventional ¹H NMR approaches. The method simultaneously distinguishes up to ten chiral hydroxy acids within a single spectrum and allows accurate determination of enantiomeric excess, offering a versatile, efficient, and separation-free platform for the rapid chiral analysis of structurally diverse hydroxy acids.