Ferric chloride-catalyzed synthesis of indoles using the intramolecular amination of aryl bromides

Abstract

The great progress in the synthesis of heterocyclic compounds has been achieved due to the use of various transition metals as catalysts [1, 2]. Palladium catalysts are most often used among the transition metal catalysts for the synthesis of heterocyclic compounds [3-6]. However, despite the obvious advantages of such palladium catalysts, they also have a number of considerable disadvantages related to the high cost and toxicity of both palladium itself and the phosphine ligands often used in these reactions. The rapid recent development of methods using copper catalysts for various cross-coupling reactions can be attributed specifically to these disadvantages. Over the past decade, the "renewed" Ulmann reaction has become an important synthetic method for the creation of C–C and C-X bonds (X = N, O, S) [7]. However, iron catalysts are even more promising relative to cost and "green" chemistry. The feasibility of using such catalysts for cross-coupling reactions has recently been demonstrated [8-11]. The use of the bimetallic Fe/Cu catalyst system sometimes proves effective [12, 13]. Recently, Bonnamour and Bolm [14] have described the synthesis of 2-substituted benzoxazoles from the corresponding 2-haloacetanilides. The key step of this synthesis is intramolecular O-arylation using FeCl3–2,2,6,6tetramethylheptane-3,5-dione as the catalyst system. An additional example of a ferric chloride-catalyzed intramolecular O-arylation is the cyclization of methyl esters of 2-(2-bromophenyl)-3-oxopropionic acid, leading to the corresponding benzofurans [15]. In light of the advantages of using iron catalysts, we undertook a study of the feasibility of replacing copper catalysts in a synthetic strategy, which we previously employed for the preparation of N-substituted methyl esters of indole-3-carboxylic acids [16] and methyl esters of 1-aminoindole-3-carboxylic acids [17], with a catalyst containing ferric salts.