Chirality Sensing of N-Heterocycles via 19F NMR

Abstract

Methods to rapidly detect and differentiate chiral N-heterocyclic compounds become increasingly important owing to the widespread application of N-heterocycles in drug discovery and materials science. We herein report a 19F NMR-based chemosensing approach for the prompt enantioanalysis of various N-heterocycles, where the dynamic binding between the analytes and a chiral 19F-labeled palladium probe create characteristic 19F NMR signals assignable to each enantiomer. The open binding site of the probe allows the effective recognition of bulky analytes that are otherwise difficult to detect. The chirality center distal to the binding site is found sufficient for the probe to discriminate the stereoconfiguration of the analyte. The utility of the method in the screening of reaction conditions for the asymmetric synthesis of lansoprazole is demonstrated.