Indolizidines, conformational analysis

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 overall structure contains an indolizidine or a quinolizidine attached to a cyclohexane, all forming a complex tricyclic system whose conformation has proved difficult to determine. The first two examples of these structures were cylindridnes A and B, whose structures were confirmed by X-ray analysis. These two molecules have a chlorine atom and are interconvertible through an aziridinium ion. At room temperature a solution of either of the two molecules will be found after six days to contain a mixture of 60% cylindricine A and 40% cylindricine B (Blackman et al., 1993). This equilibrium, however, occurs only with free bases at room temperature salts (picrates) are regarded as stable in solution. 

---