RESUMEN
Nuclear magnetic resonance (NMR) spectroscopy has long been utilized as a classic method for chiral discrimination of enantiomers. However, its sensitivity limitations have hindered the detection of analytes at low concentrations. In this study, we present our efforts to overcome this challenge by employing chiral NMR probes that are labeled with a significant number of chemically equivalent 19F atoms. Specifically, we have designed and synthesized three chiral palladium pincer complexes, all of which are labeled with nonafluoro-tert-butoxy groups to enhance detectability. The recognition of enantiomers with the probe induces distinct changes in microenvironments, resulting in differential perturbations on the chemical shift of the 19F atoms in proximity. This method is applicable to the enantiodifferentiation of various amines, amino alcohols, and amino acid esters. The abundance of 19F atoms enables the detection of chiral analytes at low concentrations, which is otherwise challenging to achieve through traditional 1H NMR-based analysis. Two of the probes are constructed with asymmetric pincer ligands with structurally varied sidearms, allowing for facile manipulation of the chiral binding pocket. The C2 symmetrical probe possesses 36 equivalent 19F atoms, enabling the determination of enantiocomposition of samples with concentrations in the low micromolar range.
RESUMEN
Chirality is a ubiquitous phenomenon in nature, serving as a foundation for a variety of life activities on earth. Separation-free methods that rapidly and accurately distinguish chiral analytes in complex systems are highly demanded in fields ranging from drug quality control to the screening of privileged chiral catalysts. However, in situ enantidifferentiation methods possessing resolution and tunability that are comparable to those achieved by chiral high-performance liquid chromatography are rare. Herein, we report a Lewis pair-based system for enantioanalysis via recognition-enabled "chromatographic" 19F NMR spectroscopy. The construction of Lewis pairs renders the detecting system not only enhanced affinity to chiral analytes but also superior and tunable resolving capability. Using this strategy, as many as 16 chiral analytes are simultaneously resolved without need for separation, thus opening new avenues for the development of precise and real-time detection methods that are robust enough for dealing with complex real-world samples.