Quinolizidine methiodide

Methylation of indolizidine gave a mixture of trans and cis fused methiodides (19) and (20), the structures of which have been substantiated by a comparison of the NMR spectra with those of the corresponding quinolizidine methiodides. 

These changes of stereochemistry in C1S Nuphar methiodides are detectable in their l3C-NMR spectra when the fra/w-quinolizidine system is retained, para-... 

C-6 and one of the protons on C-17 and, on the other, creation of an H-H 1,3-diaxial interaction between protons on C-8 or C-8 and one of the protons on C-17. A new 8-syn-diaxial interaction between C-6 and C-8 (A B trans and A B cis) or between C-6 and C-8 (AB trans) was observed. As a stereochemical consequence of this interaction, the distance between the two quinolizidine rings decreases. The tetrahydrothiophene ring adopts a conformation between an envelope and a half-chair. Such stereochemistry in thiobinupharidine methiodide (34) was confirmed by X-ray single-crystal measurements (46). 

Different changes are observed when quaternization causes inversion of the quinolizidine ring from trans to cis, as is observed in the case of nupharidine (which is an N-oxide) (32) and deoxynupharidine methiodide (71) (41, 69). In such cases the tertiary carbon atoms in the 3 position (C-4, C-10) with respect to the new N+—O" or N+—C bonds exhibit a paramagnetic shift, and the secondary carbon atom (C-6) exhibits a diamagnetic shift in comparison with similar carbon atoms in the free base. 

Quaternization of the nitrogen atom is the first step of the classical Hofmann degradation of quinolizidines, a reaction that is still widely practised <82JOC5i4l, 82AP(315)273, 84TL5169>. As an example, the degradation of deoxynupharidine methiodide (140) and its 7-epi derivative (141) <83H(20)1773,84JST(ll6)l> is summarized in Scheme 19. 

Pyrolysis of tetrahydroprotoberberine methiodides is reported to yield, in addition to the expected iV-demethylation product, 13-methyl tetrahydroprotoberberine via migration of the 7V-methyl group to C-13. This rearranged product possesses a rm -quinolizidine system with the 13-methyl group occupying the axial position. (For the base-catalyzed rearrangement of iV-methyltetrahydroprotoberberine salts to spirobenzylisoquinolines, see Sec. 25.2.7.)... 

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