Theoretical and spectroscopic studies on the conformational equilibrium of 9-oxabispidines in solution

Abstract

Abstract The conformational behavior of N,N-dimethyl-9-oxabispidine and four 2-endo-substituted 9-oxabispidines (3,7-diaza-9-oxabicyclo[3.3.1]nonanes) in solution was investigated by theoretical and spectroscopic methods. The electronic energies of all conformers were calculated on the B3LYP/TZVP level of theory and solvent effects were taken into account by the continuum solvent model COSMO. Only two conformers, the double chair form A1 (both N–R exo) and the boat–chair form B2 (Nchair–R exo, Nboat–R endo), were of energetic relevance (ΔE ⩽ 18.2 kJ mol−1), with the former one strongly dominating (A1:B2 ⩾ 98:2 at room temperature), independent of the existence or nature of the 2-endo-substituent. Compared to the corresponding bispidines, the dominance of the double chair conformers A1 was more pronounced in the 9-oxabispidines, presumably due to stronger N,O-repulsions in their boat–chair conformers B2. 1H NMR studies on 21 2-endo-substituted 9-oxabispidines, using the 3J coupling constants of the exo-methylene protons with the neighboring bridgehead protons as conformational probes, gave no evidence on a noticeable population of the boat–chair conformers B in solution, which is good agreement with the calculations. In addition, the experimentally determined proton shifts of two 2-endo-substituted 9-oxabispidines matched excellently with those calculated for their double chair conformers A1.