A Convenient Synthesis of 8-Substituted Indolizines as Precursors to 5-Substituted Cycl{3.2.2}azine Derivatives

Article abstract of DOI:10.1002/jhet.5570340511

The synthesis of 8-substituted indolizines is described via a two step process in which a 1,4-diketone, containing a tert-butyl group, is cyclocondensed with a trialkylsilyl protected pyrrole to provide 5,8-disubstituted indolizines in higher yields than the identical reaction with unprotected pyrrole. Cleavage of the tertbutyl group from the indolizine 5-position, by treatment with 85% phosphoric acid, provides 8-substituted indolizines in good yields. Treatment of 8-substituted indolizines with dimethyl acetylenedicarboxylate, in the presence of palladium-on-carbon, provides novel 5-substituted cycl{3.2.2} derivatives.