Synthesis and axial chirality of an enantiopure aminodibenzazepinone

A route for the synthesis of (S,S)-7-amino-5-methyl-5H-dibenzo[b,d]azepin-6(7H)-one hydrochloride is disclosed. The synthesis includes a Friedel–Crafts alkylation to form the seven-membered ring and a highly efficient classical resolution. Additional studies on the enantiopure material showed the amine to be highly resistant to racemization, which led us to investigate the unexpected stability. We propose that the inherent axial chirality contained in the dibenzazepinone works to produce an interesting chirality transfer mechanism, which accounts for the observed robustness of the stereocenter. This previously unrecognized stereochemical element exists within this specific class of molecules, and they should be drawn in a manner which displays the axial chirality.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide

(S,S)-7-Amino-5-methyl-5H-dibenzo[b,d]azepin-6(7H)-one (2S,3S)-2,3-bis(4-methylbenzoyloxy)succinate hydrateC35H34N2O10[α]D23=-22.5 (c 1.07, DMSO)Source of chirality: (+)-di-p-toluoyl tartaric acidAbsolute configuration: (S,S)

(S)-7-Amino-5-methyl-5H-dibenzo[b,d]azepin-6(7H)-oneC15H14N2O[α]D23=-160.0 (c 0.96, MeOH)Source of chirality: (+)-di-p-toluoyl tartaric acidAbsolute configuration: (S,S)

(S)-7-Amino-5-methyl-5H-dibenzo[b,d]azepin-6(7H)-one hydrochlorideC15H15N2OCl[α]D23=-90.6 (c 0.97, water)Source of chirality: (+)-di-p-toluoyl tartaric acidAbsolute configuration: (S,S)