Insights into the Origins of Configurational Stability of Axially Chiral Biaryl Amines with an Intramolecular N−H−N Hydrogen Bond

Abstract

Configurationally stable chiral biaryl amines with an intramolecular N-H-N hydrogen bond have been developed. The barriers for racemization are in the range of 19.3-28.2 kcal/mol, which corresponds to the half-lives of racemization of the enantiomers in the range of 7 s to 2 years at 20 degrees C. Enantiomers of some of these compounds were separable by HPLC with chiral stationary phases. The biaryl amines are supposed to have a conformation similar to that of a binaphthyl skeleton, which was indicated by an X-ray crystal analysis of a biaryl amine. The N-H appears at 11.1-13.3 ppm in their (1)H NMR spectrum in CDCl(3), indicating strong hydrogen bonding. Biaryl amines with an extremely strong intramolecular N-H-N hydrogen bond (delta(NH) approximately 13 ppm) were assumed to undergo racemization without cleavage of an N-H-N hydrogen bond, while those with a mediumly strong N-H-N hydrogen bond (delta(NH) approximately 11 ppm) are assumed to undergo racemization via cleavage of an N-H-N hydrogen bond. Hydrogen/deuterium exchange of a chiral biaryl amine was found to proceed without any trace of racemization.