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

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.