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A three-component Fischer indole synthesis

Nature Protocols volume 3, pages 1249–1252 (2008)Cite this article

Abstract

This protocol describes a three-component approach to multiply-substituted indoles from nitriles, organometallic reagents and arylhydrazine hydrochloride salts. The condensation of organolithium or Grignard reagents with nitriles produces metalloimines, which under acidic conditions and in the presence of arylhydrazines lead to arylhydrazones, the starting materials for the Fischer indole reaction. Combining this approach with the Fischer indole reaction produces indoles in an efficient, one-pot process. The procedure takes ∼20 h to complete: 3 h for metalloimine formation, 15 h for the Fischer indole reaction and 2 h for isolation and purification.

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Author notes

  1. Christopher A Simoneau

    Present address: Present address: Novomer Inc., 950 Danby Road Suite 198, Ithaca, New York 14850, USA.,

Authors and Affiliations

  1. Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University, Ithaca, 14853, New York, USA

    Christopher A Simoneau & Bruce Ganem

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  1. Christopher A Simoneau
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  2. Bruce Ganem
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Correspondence to Bruce Ganem.

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Simoneau, C., Ganem, B. A three-component Fischer indole synthesis. Nat Protoc 3, 1249–1252 (2008). https://doi.org/10.1038/nprot.2008.94

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