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

Seble Wagaw,† Bryant H. Yang,‡ and Stephen L. Buchwald*
Contribution from the Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
J. Am. Chem. Soc., 1999, 121 (44), pp 10251–10263
DOI: 10.1021/ja992077x
Publication Date (Web): October 22, 1999
Copyright © 1999 American Chemical Society
†

 Current address:  Abbott Laboratories, North Chicago, IL.

,
‡

 Current address:  BASF Bioresearch Corp., Worcester, MA.

,
*

In papers with more than one author, the asterisk indicates the name of the author to whom inquiries about the paper should be addressed.

Abstract

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.

View: Full Text HTML | Hi-Res PDF

Tools

History

  • Published In Issue November 10, 1999
  • Received June 18, 1999

Recommend & Share

Related Content

Other ACS content by these authors: