A Universal 19F NMR Probe for Enantiomeric Discrimination of Primary, Secondary, and Tertiary Amines

Chiral amines are fundamental building blocks in pharmaceuticals and bioactive molecules, necessitating fast and reliable enantiomeric analysis. However, developing a single probe capable of effectively distinguishing primary, secondary, and particularly tertiary amines remains challenging due to their diverse steric and electronic characteristics. Herein, we report a novel 19F-labeled palladium-based probe bearing a strategically positioned trifluoromethyl group away from the coordination site to minimize steric hindrance. This structural design enables broad applicability across all three classes of amines, producing well-resolved 19F NMR signals that directly correlate with their absolute configurations. The method allows rapid, derivatization-free determination of enantiomeric excess and demonstrates a strong potential for application in pharmaceutical analysis and high-throughput screening.