High-throughput screening of α-chiral-primary amines to determine yield and enantiomeric excess

A novel screening protocol was developed using a combination of a fluorescent indicator displacement assay and a circular dichroism (CD) active Fe(II) complex to determine concentration and enantiomeric excess (ee) of α-chiral amines, respectively. The analyte concentration is quantified with a pre-formed non-fluorescent imine, where transimination with the chiral amine results in displacement of the fluorophore 2-naphthylamine. After discerning the concentration of amine via fluorescence in a wellplate reader, the analyte is then incorporated into a three-component octahedral Fe(II) assembly for ee determination using an EKKO CD plate-reader. With these two assays, both the ee and yield of asymmetric transformations of 192 samples could be determined with acceptable errors in under fifteen minutes (not counting the preparation time). This combined speed and accuracy provides an attractive solution to overcoming analytical bottlenecks when creating α-chiral amines.