August 6, 2025

Friedel–Crafts chemistry. Part 64. Facile syntheses of fused azepinoindoles by Jourdan–Ullmann and Friedel–Crafts approaches

Key Points

Facile procedures were developed to synthesize a range of fused azepinoindoles from indole-2-acetic acids.
Indoleacetic acid was arylylated using aromatic halides to produce the required starting carboxylic acids.
The Friedel–Crafts cyclisations were catalyzed by AlCl3, TfOH, or PPA, yielding condensed indoles.
This methodology offers moderate to good yields, enhancing the synthesis of complex N-heterocycles.

Abstract

Facile and concise procedures for the construction of indole fused N-heterocyclic systems were described. A series of benzo-, pyrido-, thieno-, naphtho-fused azepinoindolones and indolo-azepinoquinolinones has been prepared starting from indol-2-acetic acids. The required starting carboxylic acids 3a–e were readily obtained by the N-arylations of indoleacetic acid 1 with various aromatic halides 2a–e. Subsequent carboxylic acids were esterified, followed by the addition of Grignard reagents to afford the corresponding indole-based alcohols 5a–e. The key step in this protocol is the Friedel–Crafts cyclisations of these precursors promoted by AlCl3/CH3NO2 or trifluoromethanesulfonic acid (TfOH) or polyphosphoric acid (PPA) catalysts to form the desired condensed indoles in moderate to good yields.

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