Quinolizidines nitrogen inversion

The different conformations of indolo[2,3-a]quinolizidines play an important role in predicting the thermodynamically more stable epimer (see below). The indolo[2,3-a]quinolizidine system can exist in three main conformations one C/D trans ring juncture (conformation a) and two C/D cis ring junctures (conformations b and c). These are in equilibrium by nitrogen inversion and cw-decalin type ring interconversion. Ring C is considered to be in a half chair conformation and ring D in a chair conformation, Scheme (16) [40]. 

Because of the possibility of nitrogen inversion, cis- and frans-fused indolizidine have no separate chemical identity. However, conformational analysis of the indolizidine and quinolizidine systems suggests that the trans is significantly more stable than the cis conformation. A value for the energy difference of 2.4 kcal mole-1 has been obtained, compared with ca. 0.3 kcal mole-1 for hydrindane.276,277... 

The X-ray data available suggest that some alkaloids have a different conformation in solution than in crystal form (41). The presence of a nitrogen atom, capable of inversion, ensures certain conformational mobility of quinolizidine molecules, and the reaction conditions should be considered in establishing their... 

The quinolizidine system in monomeric C15 alkaloids in some cases is susceptible to inversion of the ring junction, which is accompanied by inversion of the relative configuration of C-7. Protonation of the nitrogen atom, quaternization, or V-oxide formation are the conditions which cause such transformations. 

Inversion of quinolizidine system from trans to cis in monomethiodides can occur in the AB or A B ring, corresponding to the nitrogen atom, which becomes quaternary. Structures of this type are represented by thiobinupharidine monomethiodides 36 and 37 (43). In the dimethiodides the inversion was ob-... 

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