Indolo quinolizine alkaloid synthesis

Ortho lithiation of 2-substituted indoles occurs readily, but fragmentation to an alkynylanilide may occur in some instances. The use of a 2-pyridyl group to facilitate the 3-lithiation of an indole was recently used in a synthesis of some indolo[2,3-a]quinolizine alkaloids an example is the synthesis of flavopereirine (22 Scheme 29). 

Several other groups have made use of the Smith indole synthesis, and a summary of this work is shown in Table 1. Gribble and cowoikers prepared 2-(2-pyridinyl)indoles en route to syntheses of several zwitterionic indolo[2,3-fl] quinolizine alkaloids (Entry 1) [13], and Husson and Hashimoto synthesized a derivative of the alkaloid goni-omitine via a Smith indole synthesis (Entry 2) [14]. Henegar and Hunt reported a very convenient synthesis of 2-trifluoromethylindole (Entry 3) [15], in which TMEDA was found to be necessary. Two bis-indoles were prepared in low yield (Entry 4), bnt this approach failed for n = 1 [16], The bridged indole shown in Entry 5 was synthesized following acid-catalyzed cyclization of the initially formed indole [17]. 

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