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Abstract Piano stool complexes have been studied over many years and found widespread applications in organic synthesis, catalysis, materials and drug development. We now report the first examples of quantitative chiroptical molecular recognition of chiral compounds through click‐like η⁶‐arene coordination with readily available half sandwich complexes. This conceptually new approach to chirality sensing is based on irreversible acetonitrile displacement of [Cp*Ru(CH₃CN)₃]PF₆by an aromatic target molecule, a process that is fast and complete within a few minutes at room temperature. The metal coordination coincides with characteristic circular dichroism inductions that can be easily correlated to the absolute configuration and enantiomeric ratio of the bound molecule. A relay assay that decouples the determination of the enantiomeric composition and of the total sample amount by a practical CD/UV measurement protocol was developed and successfully tested. The introduction of piano stool complexes to the chiroptical sensing realm is mechanistically unique and extends the scope of currently known methods with small‐molecule probes that require the presence of amino, alcohol, carboxylate or other privileged functional groups for binding of the target compound. A broad application range including pharmaceutically relevant multifunctional molecules and the use in chromatography‐free asymmetric reaction analysis are also demonstrated. 

The widespread occurrence and significance of chiral compounds does not only require new methods for their enantioselective synthesis but also efficient tools that allow rapid determination of the absolute configuration, enantiomeric composition and overall concentration of nonracemic mixtures. Although chiral analysis is a frequently encountered challenge in the chemical, environmental, materials and health sciences it is typically addressed with slow and laborious chromatographic or NMR spectroscopic techniques. We now show with almost 40 analytes representing 5 different compound classes, including mono-alcohols which are particularly challenging sensing targets, that this task can be solved very quickly by chiroptical sensing with a single, readily available arylisocyanate probe. The probe reacts smoothly and irreversibly with amino and alcohol groups when an organocatalyst is used at room temperature toward urea or carbamate products exhibiting characteristic UV and CD signals above 300 nm. The UV signal induction is not enantioselective and correlated to the total concentration of both enantiomers, the concomitant generation of a CD band allows determination of the enantiomeric composition from the same sample, and the sense of the induced Cotton effect reveals the absolute configuration by comparison with a reference. This approach eliminates complications that can arise when enantiomerically impure NMR derivatizing agents are used and it outperforms time-consuming HPLC protocols. The generation of distinct UV and CD signals at high wavelengths overcomes issues with insufficient resolution of overlapping signals often encountered with chiral NMR solvating agents that rely on weak binding forces. The broad solvent compatibility is another noteworthy and important characteristic of this assay. It addresses frequently encountered problems with insufficient solubility of polar analytes, for example pharmaceuticals, in standard mobile phase mixtures required for chiral HPLC analysis. We anticipate that the broad application spectrum, ruggedness and practicality of organocatalytic chiroptical sensing with aryliso(thio)cyanate probes together with the availability of automated CD multi-well plate readers carry exceptional promise to accelerate chiral compound development projects at reduced cost and with less waste production. 

Abstract Fluorinated oxindoles are frequently used building blocks in asymmetric synthesis and represent an important scaffold found in a variety of biologically relevant compounds. While it is understood that incorporation of fluorine atoms into organic molecules can improve their pharmacological properties, the impact on the configurational stability of chiral organofluorines is still underexplored. In this study, semipreparative HPLC enantioseparations of five oxindoles were carried out, and the resulting enantiomerically enriched solutions were used to investigate base promoted racemization kinetics at room temperature. It was found that incorporation of fluorine at the chiral center increases the configurational stability, while substitutions on the aromatic ring and at the lactam moiety also have significant effects on the rate of racemization, which generally follows reversible first‐order reaction kinetics.