Imine-based chiroptical sensing for analysis of chiral amines: from method design to synthetic application

Abstract

Imine-bond formation between a chiral amine analyte and 3-hydroxypyridine-2-carboxaldehyde (HCA) was used to create a fast and robust method for enantiopurity analysis. This approach showed good universality, and was applied to a variety of different classes of chiral amines. The sign of the measured CD signal was enantiospecific across the range of amines tested, allowing some confidence in absolute configuration determination. This technique was transitioned to an HPLC-CD detector to allow for rapid and automated sample introduction, while maintaining the level of accuracy noted for the standalone CD spectrophotometer. Finally, the enantiomeric purity of a series of crude reaction mixtures of synthetic amines produced by biocatalytic transamination was accurately determined using this approach.