A three-component Fischer indole synthesis.
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 approximately 20 h to complete: 3 h for metalloimine formation, 15 h for the Fischer indole reaction and 2 h for isolation and purification.
Simoneau
Christopher A
CA
Baker Laboratory, Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, USA.
Ganem
Bruce
B
D002264:Carboxylic Acids / Q000737:chemistry; D002625:Chemistry, Organic / Q000295:instrumentation / Q000379:methods; D006834:Hydrazines / Q000737:chemistry; D006835:Hydrazones / Q000737:chemistry; D007202:Indicators and Reagents; D007211:Indoles / Q000138:chemical synthesis*; D009570:Nitriles / Q000737:chemistry; D009942:Organometallic Compounds / Q000737:chemistry
D002264:Carboxylic Acids; D006834:Hydrazines; D006835:Hydrazones; D007202:Indicators and Reagents; D007211:Indoles; D009570:Nitriles; D009942:Organometallic Compounds