Cascade synthesis of indolizines and pyrrolo[1,2-]pyrazines from 2-formyl-1-propargylpyrroles

A straightforward synthesis of indolizines and pyrrolo[1,2- a ]pyrazines was performed through a cascade condensation/cyclization/aromatization reaction of substituted 2-formyl- N -propargylpyrroles with active methylene compounds such as nitromethane, alkyl malonates, methyl cyanoacetate and malononitrile. Under basic conditions, the reaction proceeded satisfactorily to provide the corresponding 6,7-disubstituted indolizines. The condensation of the pyrrolic analogues with ammonium acetate gave rise to pyrrolo[1,2- a ]pyrazines in high yields. N -Allenyl-2-formylpyrroles behaved as more reactive substrates than 2-formyl- N -propargylpyrroles, furnishing the expected indolizines in higher yields. Hence, an allenyl-containing intermediate was probably generated as the reactive species in the reaction mechanism of some N -propargyl pyrroles prior to the cyclization reaction. A cascade reaction of 2-formyl- N -propargylpyrroles or N -allenyl-2-formylpyrroles with active methylene compounds and ammonium acetate provides indolizines and pyrrolo[1,2- a ]pyrazines, respectively.