Development and application of indole-2,3-epoxide surrogates

Takumi Abe, Koji Yamada, Takahide Nishi

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)


C3-Nucleophilic substitution of indoles has been limited because the transformation requires an umpolung of the C3 position of indoles. Among the indole derivatives, indole-2,3-epoxides could be potentially be used as C3-electrophilic reagents due to the electrophilic nature of the C2 and C3 positions. However, their use as C3 electrophilic reagents has not been possible so far due to their instability. We describe a novel and bench stable surrogate of indole-2,3-epoxide, 2-hydroxyindoline-3-triethylammonium bromide (HITAB), which was found to be a convenient reagent for formal C3-electrophilic reactions of indoles with nucleophiles. By taking advantage of the nucleophilic character of the oxygen of the 2-hydroxyindoline, interrupted retro-Claisen and interrupted Feist-Bénary reactions with 1,3-dicarbonyl compounds, one-pot formation of furodiindolines from 3-substituted indoles were achieved. Furthermore, we developed a novel cascade reaction of the indole-2,3-epoxide surrogate with 7-carbolines to access multiheterocyclic compounds containing both isotryptamines and pyrimido[1,6-a] indoles. This reaction utilizes the in situ formation of a bulky quaternary ammonium salt via ammonium exchange, which undergoes Hofmann elimination/vinylogous Mannich/retro-Mannich/cyclization cascade sequences. The synthetic potential of the ammonium salts was demonstrated by the short synthesis of cryptolepine, iheyamine A, racemocine B derivative, and neocryptolepine derivative.

Original languageEnglish
Pages (from-to)597-607
Number of pages11
JournalYuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry
Issue number6
Publication statusPublished - Jun 1 2020
Externally publishedYes


  • 3-epoxide surrogate
  • Ammonium salts
  • Cascade reaction
  • Indole alkaloids
  • Indole-2
  • Umpolung

ASJC Scopus subject areas

  • Organic Chemistry


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