A convenient method for the determination of the absolute configuration of chiral amines.
A highly useful methodology that allows the determination of the absolute configuration of aliphatic and aromatic chiral amines based on the rationalization of stereoselective three-point interactions during chromatography on a rationally designed chiral stationary phase and conformational analysis of the elutes was developed. This approach is based on the broadly accepted chiral recognition mechanism of the Whelk-O 1 CSP and requires a facile derivatization of the amine and the determination of the lowest energy conformation of the corresponding t-Boc- or Z-derived carbamates. The absolute configuration determined by employing chiral structure activity relationships in HPLC analysis was verified by single-crystal X-ray analysis or studies with carbamoyl derivatives of amines of known configuration. The general validity and applicability of this methodology was demonstrated by analysis of seven carbamates derived from aliphatic and aromatic amines. Due to its simplicity and time-efficiency, i.e., ease of derivatization of amines and fast HPLC method development, this approach can be considered a useful supplement to established techniques such as NMR spectroscopy.
Wolf
Christian
C
Department of Chemistry, Georgetown University, Washington, D.C. 20057, USA. cw27@georgetown.edu
Pranatharthiharan
Lakshmi
L
Volpe
Emily C
EC