A Fluorinated Cyclorhodium Probe Enables Separation-Free 19F NMR Enantiodifferentiation of Chiral Amines and Nitriles

Abstract

Separation-free determination of enantiomeric composition is valuable for the rapid evaluation of chiral nitrogen-containing compounds, but chromatographic analysis is often substrate-specific and may require tailored conditions. Here, we report probe 4, a cyclorhodium(III) complex bearing a CF3 reporter designed to convert analyte coordination into well-resolved 19F NMR readouts. The design integrates a rigid Rh(III)-centered cyclometalated scaffold, a compact trifluoromethyl reporter, and an accessible coordination site for nitrogen donors. Direct mixing with amino alcohols, primary amines, or nitriles gives new 19F resonances under slow exchange on the NMR time scale. The probe resolves a broad amine panel with Rs values of up to 92.4 and extends to weakly coordinating nitriles bearing ester, amide, acid, cyclic, and quaternary stereocenter motifs. Five-component amine and six-component nitrile mixtures were resolved in a single NMR tube. Direct crude-product analysis of copper-catalyzed asymmetric decarboxylative cyanation gives ee values consistent with those of chiral HPLC. This Rh(III)-centered 19F NMR platform combines broad nitrogen donor compatibility, spectral simplicity, multiplex readout, and quantitative ee analysis.