3-Azabicyclo nonanes conformation

The Aae values (at 60 MHz) observed for 3-azabicyclo[3.3.1]nonane and its Af-methyl derivative were 0.08 and 0.67 ppm respectively, a decrease of 0.5-0.6 ppm compared to the Aae values for the corresponding piperidines. On this evidence the conformations 15 and 16 were assigned to these compounds.37... 

The conformational equilibrium of A-methylpiperidine-m-2,6-fif2 favors conformer 40 with both deuteriums equatorial, with an equilibrium constant of 1.23.110 To the extent that the conformational preference in the protonated amine is much smaller and can be neglected, this IE also corresponds to a greater basicity of the conformer 41 with the deuteriums axial. Similarly the preferences of 3-azabicyclo[3.2.2]nonanes and (PhCHD)3N for conformers with H anti to the nitrogen lone pair implies a lower basicity for those conformers.111,112... 

Brough, RA., Gallagher, T., Thomas, P., Wonnacott, S., Baker, R., Abdul Malik, K.M., and Hursthouse, M.B. 1992. Synthesis and X-Ray crystal structure of 2-acetyl-9-azabicyclo[4.2.1]nonan-3-one. A conformationally locked s-cis analogue of anatoxin-a. J Chem Soc Chem Commun 1087-1089. 

The exo-2-methyl- and ethyl-substituted 3-benzyl-3-azabicyclo[3.3.1]-nonanes were shown to adopt the CC conformation in solution (from 13C-NMR data), while for the exo-2-isopropyl compound the CB conformation is predominant (106). 

There are significantly fewer data available on the conformational behavior of 3-oxa-7-azabicyclo[3.3.1]nonanes than for the 3,7-diaza compounds described above. 

Earlier references on the conformational behavior of azabicyclo[3.3.1]nonanes can be found in two previous reviews on the subject (1,2). 

In solution the endo-3 and exo-3 substituted compounds 233 and 234 adopt CB and CC conformations, respectively, according to 13C-NMR data (177). A variable temperature l3C-NMR study of 9-methyl-9-azabicyclo-[3.3.1]nonane has shown that the nitrogen inversion barrier is AG1 = 8.1 kcal mol"1 at — 90°C(178). For some other 9-heterobicyclo[3.3.1]nonanes studied using 13C-N M R data, the conformational behavior was shown to be governed by steric interactions (177-180). 

In recent years, a number of complexation agents have been developed that incorporate the bicyclo[3.3.1]nonane skeleton. In a series of publications, selective model receptors consisting of two substituted 3-azabicyclo [3.3.1]-nonane fragments interconnected with various aromatic bridges were described (231 -242 and references therein). The X-ray study of one of them (compound 277) revealed a chair-envelope conformation for the bicyclo[3.3.1]nonane fragments (231) a similar conformation was found in the monomeric compound 278 (231) and in the salts of compounds analogous to 277 (237,238). 

Nuclear Magnetic Resonance Spectroscopy.—As noted above, conformational analysis of bicyclo[3.3.1]nonanes is still a topic of considerable interest. A variable-temperature n.m.r. analysis now provides the first case in which the boat-chair-chair-boat equilibrium is directly observed in the amines (17) and (18). In a related case, re-examination of the acetal (19) suggests that the preferred conformation involves a chair carbocyclic ring and a boat heterocyclic ring. This conclusion was made by n.m.r. analysis, using lanthanide shift reagents, by a study of nuclear Overhauser effects, and by measurement of relaxation times of protons. Details have been reported for other 3-azabicyclo[3.3.1]nonanes, and the non-additivity of substituent effects on chemical shifts in 9-thiabicyclo[3.3.1]non-2-enes has been analysed. Both and n.m.r. data have been reported for a series of 9-borabicyclo[3.3.1]non-anes and their pyridine complexes. 

For bicyclo[3,3,l]nonane derivatives which are unsubstituted at positions 3 and 7, it has been shown in several cases that chair-chair conformations are preferred, although the cyclohexane rings are distinctly flattened with valence-angle increases (cc. 4°) beyond ideal tetrahedral values. However, derivatives with bulky endo substituents at positions 3 or 7 may adopt boat-chair conformations. Thus for 9-benzoyl-3a-bromo-9-azabicyclo[3,3,l]-nonan-2-one (74) and for the 2-hydroxy-analogue, it has been argued... 

The photoelectron spectrum of 9-(9-borabicyclo[3.3.1]nonyl)-9-azabicyclo-[3.3.1]nonane (46) shows two low-energy ionizations. Furthermore, cyclic voltametry suggests that the lifetime of the radical cation is short, which does not conform with expectation based upon Bredt s rule of kinetic stability. Mass spectral fragmentation patterns have been reported for compounds of types (47) and (48). ... 

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