Nucleophilic and electrophilic cyclization of -alkyne-substituted pyrrole derivatives: Synthesis of pyrrolopyrazinone, pyrrolotriazinone, and pyrrolooxazinone moieties.

Intramolecular nucleophilic and electrophilic cyclization of alkyne-substituted pyrrole esters is described. Efficient routes towards the synthesis of pyrrolopyrazinone, pyrrolotriazinone and pyrrolooxazinone have been developed. First, -alkyne-substituted pyrrole ester derivatives were synthesized. Introduction of various substituents into the alkyne functionality was accomplished by a copper-catalyzed cross-coupling reaction. Nucleophilic cyclization of -alkyne-substituted methyl 1-pyrrole-2-carboxylates with hydrazine afforded the 6--dig/6-dig cyclization products depending on the electronic nature of the substituents attached to the alkyne. On the other hand, cyclization of -alkyne-substituted methyl 1-pyrrole-2-carboxylates with iodine only resulted in the formation of the 6--dig cyclization product regardless of the substitution of the alkyne functionality.