EXPLORING THE POTENTIAL-ENERGY HYPERSURFACES FOR THE TRIPLE SYMMETRICAL INVERSION IN 3-AZABICYCLO[3.3.1]NONAN-9-ONE AND ITS N-METHYL DERIVATIVE

The potential energy hypersurfaces for the triple inversion, from chai r to boat and alpha to beta conformations, are explored theoretically, by using the quantum semiempirical method AM 1, in 3-azabicyclo[3.3.1 ]nonan-9-one and its N-methyl derivative. Both compounds are precursor s of rigid analogues of the potential of gamma-butyric acid receptor a ntagonists (GABA(B)). It is found that the chair-chair a conformer is by far the most stable structure for the non-methylated compound. In c ontrast, N-methylation changes the conformational preference to the be ta-structure, the chair-chair beta conformer being the most stable. Th e inversion barriers are calculated to be relatively low, so that the conformers must be found in thermodynamic equilibrium. The theoretical results compare well with the available experimental results.