A facile circular dichroism protocol for rapid determination of enantiomeric excess and concentration of chiral primary amines.
A protocol for the rapid determination of the absolute configuration and enantiomeric excess (ee) of alpha-chiral primary amines with potential applications in asymmetric reaction discovery has been developed. The protocol requires derivatization of alpha-chiral primary amines through condensation with pyridine carboxaldehyde to quantitatively yield the corresponding imine. The Cu(I) complex with 2,2'-bis (diphenylphosphino)-1,1'-dinaphthyl (BINAP--Cu(I)) with the imine yields a metal-to-ligand charge-transfer (MLCT) band in the visible region of the circular dichroism (CD) spectrum upon binding. Diastereomeric host-guest complexes give CD signals of the same signs but different amplitudes, allowing for differentiation of enantiomers. Processing the primary optical data from the CD spectrum with linear discriminant analysis (LDA) allows for the determination of the absolute configuration and identification of the amines, and processing with a supervised multilayer perceptron artificial neural network (MLP-ANN) allows for the simultaneous determination of the ee and concentration. The primary optical data necessary to determine the ee of unknown samples is obtained in two minutes per sample. To demonstrate the utility of the protocol in asymmetric reaction discovery, the ee values and concentrations for an asymmetric metal-catalyzed reaction are determined. The potential of the application of this protocol in high-throughput screening (HTS) of ee is discussed.
Nieto
Sonia
S
Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, TX 78712, USA.
Dragna
Justin M
JM
Anslyn
Eric V
EV
D000588:Amines / Q000737:chemistry*; D002384:Catalysis; D002942:Circular Dichroism; D057166:High-Throughput Screening Assays; D008024:Ligands; D008670:Metals / Q000737:chemistry*; D015394:Molecular Structure; D013237:Stereoisomerism
D000588:Amines; D008024:Ligands; D008670:Metals