Chiral Discrimination of Organothiols via ¹⁹F NMR and a Multicomponent Reaction

This study aims to develop a sensitive and precise method for determining chiral thiols using an efficient multicomponent reaction. This innovative approach leverages the coupling of ¹⁹F-labeled chiral amines, <i>o</i>-phthalaldehyde, and targeted thiol analytes to rapidly generate diastereoisomeric isoindole derivatives. These derivatives exhibit distinctive ¹⁹F NMR signals, providing valuable insights for chiral discrimination. The introduction of chiral amines bearing dual ¹⁹F labels enables dual-site detection, significantly enhancing the system's resolving capabilities. The superior resolving power of this methodology is demonstrated through the simultaneous chiral discrimination of eight chiral thiols, showcasing its potential for analyzing complex samples in biological studies and pharmaceutical development.