Predictive chirality sensing via Schiff base formation

Abstract

Among the large number of chiroptical sensors that have been developed to date, few allow rational determination of the absolute configuration of chiral substrates together with quantitative ee analysis. We have prepared and tested stereodynamic N-aryl aminobenzaldehyde sensors that bind chiral amines via Schiff base formation. The covalent binding of the amine substrate generates a conformational bias in the chromophoric sensor moiety which results in characteristic CD signals. Computational analysis revealed that CD prediction of the sign of the Cotton effect and thus determination of the absolute configuration of the substrate becomes practical with a sterically crowded sensor design because the number of conformations to be considered is largely reduced and the chiroptical sensor response is less sensitive to conformational equilibria. The amplitude of the measured CD signal can be used for quantitative ee analysis of nonracemic amine samples with the help of a calibration curve.