Electrochemically Enabled C3-Formylation and -Acylation of Indoles with Aldehydes

Abstract

Reported herein is an effective strategy for oxidative cross-coupling of indoles with various aldehydes. The strategy is based on a two-step transformation via a well-known Mannich-type reaction and a C–N bond cleavage for carbonyl introduction. The key stepthe C–N bond cleavage of the Mannich productwas enabled by electrochemistry. This strategy (with over 40 examples) ensures excellent functional-group tolerance as well as late-stage functionalization of pharmaceutical molecules.

Graphene oxide–iridium nanocatalyst for the transformation of benzylic alcohols into carbonyl compounds

“…Aromatic aldehydes or ketones are widely used in various elds, such as biological, pharmaceutical, chemical, and materials sciences. [1][2][3][4][5] A large number of aromatic carbonyl compounds are consumed by certain industries, for example, the global consumption of benzaldehyde is around 7000 tons per year and that of vanillin is estimated to be 12000 tons per year. Therefore, a great effort has been dedicated to developing highly selective and reliable approaches to prepare aromatic aldehydes or ketones in modern synthetic chemistry.…”

C3‐Formylation of Indoles in Continuous Flow

“…Tetrabutylammonium iodide (Bu 4 NI), potassium iodide (KI), and iodine (I 2 ) have been used as catalysts to address these shortcomings, but short reaction time could not be achieved. [9][10][11][12][13][14][15] Recently, an electrochemical C3-formylation method based on a two-step transformation via a Mannichtype reaction and C N bond cleavage has been reported, 16 but a long reaction time of over 12 h is required to obtain good yields.…”

Electrochemical Iodoamination of Indoles Using Unactivated Amines

“…In recent years, electrochemical generation of N-centered radicals has drawn much interest, and several efficient protocols have been developed. ,, The halogen-mediated amination of double bonds via an electron-driven process has also developed well. ,, Furthermore, the electrochemical halogenation of indoles is a known process . As part of our continuing pursuit of the discovery of new electrochemical methods, herein, we report an environmentally friendly electrochemical dual functionalization of indole derivatives with the formation of C–N and C–I bonds in one step. The N-centered radical intermediates were demonstrated as key intermediates in this process.…”