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.