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

Yenice I., Basceken S., BALCI M.

BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY, vol.13, pp.825-834, 2017 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 13
  • Publication Date: 2017
  • Doi Number: 10.3762/bjoc.13.83
  • Journal Name: BEILSTEIN JOURNAL OF ORGANIC CHEMISTRY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.825-834
  • Keywords: alkyne cyclization, pyrrole, pyrrolooxazinone, pyrrolopyrazinone, pyrrolotriazinone, DESIGN, INHIBITORS, PYRAZINONE, CONTINUUM, BINDING
  • Middle East Technical University Affiliated: Yes

Abstract

Intramolecular nucleophilic and electrophilic cyclization of N-alkyne-substituted pyrrole esters is described. Efficient routes towards the synthesis of pyrrolopyrazinone, pyrrolotriazinone and pyrrolooxazinone have been developed. First, N-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 N-alkyne-substituted methyl 1H-pyrrole-2carboxylates with hydrazine afforded the 6-exo-dig/6-endo-dig cyclization products depending on the electronic nature of the substituents attached to the alkyne. On the other hand, cyclization of N-alkyne-substituted methyl 1H-pyrrole-2-carboxylates with iodine only resulted in the formation of the 6-endo-dig cyclization product regardless of the substitution of the alkyne functionality.