Heterocyclic compounds with bridgehead nitrogen atoms. Part 7. The synthesis of pyrrolo[2,1,5-cd]indolizines ([2,2,3]cyclazines) and pyrazino[2,1,6-cd]pyrrolizines (6-aza[2,2,3]cyclazines) from 3H-pyrrolizine

Abstract

3H-Pyrrolizine reacts with NN-dimethylformamide and phosphoryl chloride to give a 3-(NN-dimethylaminomethylene)-3H,5H-pyrrolizinium salt (2), isolated as the perchlorate, which can be further converted, with NN-dimethyithioformamide and acetic anhydride, into 3,5-bis-(NN-dimethylaminomethylene)-3H,5H-pyrrolizinium perchlorate (8). The conjugate base of the salt (2) reacts with dimethyl but-2-yne-1,4-dioate to give dimethyl pyrrolo[2,1,5-cd]indolizine-5,6-dicarboxylate. The salt (8) reacts with nitromethane, in the presence of base, to give 6-nitropyrrolo[2,1,5-cd]indolizine (9a) and with ammonia to give pyrazino[2,1,6-cd]pyrrolizine (10a). Electrophilic substitution reactions of (9a) and (10a), and a nucleophilic substitution of (10a), are described.