Relay Catalysis of Bismuth Trichloride and Byproduct Hydrogen Bromide Enables the Synthesis of Carbazole and Benzo[α]carbazoles from Indoles and α‐Bromoacetaldehyde Acetals

Abstract

Benzo[a]carbazoles were synthesized from 2-phenylindoles and a-bromoacetaldehyde using bismuth trichloride as a catalyst. The reaction was triggered by a bismuth trichloride-catalyzed Friedel-Crafts alkylation of these two precursors, which provided a tryptaldehyde intermediate that underwent intramolecular olefination to form the final product. Interestingly, the HBr byproduct generated in the upstream step of the reaction catalyzed the following downstream reaction steps, thus creating a byproduct-participated relay catalytic process. Motivated by this mechanism, we developed a three-component reaction of indole, abromoacetaldehyde acetal, and 1,3-dicarbonyl compounds. This study offers a straightforward method for synthesizing substituted carbazoles.

Modular Synthesis of Bicyclic and Tricyclic (Aza‐) Arenes from Nucleophilic (Aza‐)Arenes with Electrophilic Side Arms via [4+2] Annulation Reactions

“…Recently, we have found that, in the presence of a Brønsted acid, tryptaldehyde can act as a 1,4‐donor‐acceptor molecule to react with a β ‐ketoester in the manner of [4+2] annulation to form carbazoles . Inspired by this reactivity, we tried to establish a molecular library of all‐carbon 1,4‐nucleophilic‐electrophile molecules for enriching the product diversity of the third [4+2] annulation model, and make it be practically useful for the construction of fused six‐membered rings.…”

Recent synthetic strategies for the construction of functionalized carbazoles and their heterocyclic motifs enabled by Lewis acids

“…Given the abundance of readily accessible simple indoles and the wide range of commercially available aryl ketones 50 , the suggested catalytic technique is a potential way for the synthesis of carbazole libraries with a high degree of diversity (Scheme 35). 122,123…”

Recent Studies of Bifunctionalization of Simple Indoles

“…In 2019, the Verma group [1m] reviewed the synthesis of carbazoles from indoles (2015–2019). The Gu group [4a,b] utilized α‐ bromoacetaldehyde acetal as the key reagent in the indole‐mediated benzo[ α ]carbazoles [4b] . During the Bi(OTf) 3 ‐catalyzed three‐component reactions[4a], the Friedel‐Crafts alkylation and hydrolysis generated aldehyde intermediates.…”