Exploring the Chiral Match–Mismatch Effect in the Chiral Discrimination of Nitriles

Abstract

This study tackles the challenge of enantiodifferentiation of nitrile compounds, which is typically difficult to resolve using nuclear magnetic resonance (NMR) due to the significant distance between the chiral center and the nitrogen atom involved in molecular interactions. We have developed novel chiral ¹⁹F-labeled probes, each featuring two chiral centers, to exploit the “match–mismatch” effect, thereby enhancing enantiodiscrimination. This strategy effectively differentiates chiral analytes with quaternary chiral carbon centers as well as those with similar substituents at the chiral center. Our approach not only provides a novel method for precise probe performance optimization but also offers a rapid and efficient technique for screening reaction conditions in asymmetric synthesis.