Circular dichroism of heterocyclohexan-4-onic systems. Part I-optically active N-(α-phenethyl)-derivatives of 4-piperidone, nortropinone and norpseudopelletierine

New optically active 4-piperidonic compounds possessing an asymmetric group lying in the symmetry plane of the ring were prepared and characterized. Although the carbonyl chromophore is situated 4 σ-bonds away from the asymmetric group, it was nonetheless strongly enough perturbed to exhibit a n → π^* Cotton effect. N-Epimeric methiodides (4 and 5) of the tropanic system were prepared and found to undergo easy equilibration in aqueous solution. The possible mechanisms of asymmetric perturbation are discussed and their relative importance assessed by comparing the CD data obtained for the bases 1-3 and the methiodides 4 and 5. The conformer populations, their Cotton effect signs and amplitudes, as predicted by Octant Rule and theoretical considerations, were confirmed by CD, assisted by a suitable NMR technique. In the quaternary compounds the epimer having the asymmetric group in the axial position, gave rise as predicted to the strongest Cotton effect, an observation which, if proved general, will allow the assignment of N-stereochemistry by CD.