A Palladium-Catalyzed Method for the Preparation of Indoles via the Fischer Indole Synthesis

• Published in: Journal of the American Chemical Society Vol. 121; no. 44; pp. 10251 - 10263
• Main Authors: Wagaw, Seble, Yang, Bryant H, Buchwald, Stephen L
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 10.11.1999; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Multidisciplinary; Physical Sciences; Science & Technology; MECHANISM; ANNULATION; ARYLATION; REGIOSELECTIVITY; INSIGHT; INDOLIZATION; HYDROFORMYLATION
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja992077x

A Pd-catalyzed method for the preparation of N-aryl benzophenone hydrazones 4 is described. The use of a Pd/BINAP-based catalyst provides hydrazones 4 in good yields. Using 0.1 mol % of a Pd/9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (Xantphos) catalyst, the desired hydrazones are produced in excellent yields. The N-aryl benzophenone hydrazones are converted to indole products via an in situ hydrolysis/Fischer cyclization protocol. A procedure that extends this methodology to the synthesis of N-alkylindoles via the intermediacy of N-aryl-N-alkyl benzophenone hydrazones is described. Additionally, the Pd-catalyzed preparation of diaryl benzophenone hydrazones, followed by a hydrolysis/Fischer cyclization protocol, affords N-arylindole products in good yields. This methodology provides a means for the preparation of a structurally diverse set of indoles from simple, (usually) commercially available precursors.