Regioselective, unconventional pictet-spengler cyclization strategy toward the synthesis of benzimidazole-linked imidazoquinoxalines on a soluble polymer support

Chih Hau Chen, Jaren Kuo, Gorakh S. Yellol, Chung-Ming Sun*

*Corresponding author for this work

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

A novel strategy for an unconventional Pictet-Spengler reaction has been developed for the regioselective cyclization of the imidazole ring system at the C2 position. The developed strategy was utilized to develop a diversity-oriented parallel synthesis for bis(heterocyclic) skeletal novel analogs of benzimidazole-linked imidazoquinoxalines on a soluble polymer support under microwave conditions. Condensation of polymer-immobilized o-phenylenediamines with 4-fluoro-3-nitrobenzoic acid followed by nucleophilic aromatic substitution with an imidazole motif affords bis(heterocyclic) skeletal precursors for the Pictet-Spengler reaction. The unconventional Pictet-Spengler cyclization with various aldehydes was achieved regioselectively at the C2 position of the imidazole ring to furnish rare imidazole-fused quinoxaline skeletons. During the Pictet-Spengler cyclization, aldehydes bearing electron-donating groups afford 4,5-dihydro-imidazoquinoxalines, which then auto-aromatize into benzimidazole-linked imidazo[1,2-a]quinoxalines. However, interestingly, aldehydes bearing electron-withdrawing groups directly provide aromatized imidazo[1,2-a]quinoxalines, which unexpectedly afford novel benzimidazole-linked 4-methoxy-4,5-dihydro-imidazo[1,2-a]quinoxalines after polymer cleavage.

Original languageEnglish
Pages (from-to)1557-1565
Number of pages9
JournalChemistry - An Asian Journal
Volume6
Issue number6
DOIs
StatePublished - 6 Jun 2011

Keywords

  • diversity-oriented synthesis
  • heterocycles
  • microwave chemistry
  • Pictet-Spengler cyclization
  • solid-phase synthesis

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