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

Işıl Yenice,Metin Balci,Sinan Basceken

doi:10.3762/bjoc.13.83

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-2-carboxylates 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.

Highlights

Pyrrole has a great range of applications in organic synthesis because of its occurrence in many active natural products, synthetic pharmaceuticals, and optoelectronic materials [1,2]
Substituted alkyne derivatives 10a and 10b were synthesized according to the literature
We demonstrate for the first time the concept of the cyclization of N-alkyne-substituted pyrrole esters 7 (Figure 3) to provide a practical access to design pyrrolopyrazinone, pyrrolotriazinone, and pyrrolooxazinone derivatives

Summary

Introduction

Pyrrole has a great range of applications in organic synthesis because of its occurrence in many active natural products, synthetic pharmaceuticals, and optoelectronic materials [1,2].

Results

Conclusion