Stereoisomeric chiral 2,9-diazabicyclo[4.4.0.]decane-3,10-diones as models of dipeptide grouping: Synthesis, X-ray, IR, NMR and cd studies

Abstract

Synthesis of the title optically active bicyclic dilactams I and II with cis- and trans-annelation of rings is described. The stereospecific synthesis started from (2R)-2-benzamido-2-(4-oxocyclohexyl)acetic acid ((-)-VI) whose absolute configuration was determined by chemical correlation with the known (2R)-2-amino-(4-hydroxyphenyl)acetic acid ((-)-IIIb). Relative configuration at the bridgehead atoms in I and II was assigned by 1H and 13C NMR spectroscopy and confirmed by X-ray diffraction analysis which showed the detailed conformation in crystal. According to the 1H NMR spectra in solution the trans-isomer II has the same configuration as in crystal whereas the cis-isomer I exists in two forms one of which is identical with that in crystal. This conformational analysis agrees also with the IR spectra, detecting an intramolecularly hydrogen-bonded conformation for IIbut no hydrogen bond for I. The CD spectra of both lactams were successfully interpreted using the exciton theory in the π-π region where it reflects the differences in the angles Φ and ψ (for I Φ = 110°, ψ = -143°; forII Φ = -145°, ψ = 162°). In the n-π transition region the interpretation was based on the quadrant rule and also inherent non-planarity of one of the amide groups in II.