A Versatile C–H Halogenation Strategy for Indole Derivatives under Electrochemical Catalyst‐ and Oxidant‐Free Conditions

Abstract

Halogenated indoles are essential structural motifs in bioactive natural products. Reported herein is an economical and scalable electrochemical protocol for regioselective 3C–H halogenation of indole derivatives. This strategy provides access to a host of 3‐iodo‐, 3‐bromo‐, 3‐chloro‐, and 3‐thiocyanoindole derivatives under mild conditions using inexpensive (pseudo)halide salts as the sole reagent. The optimized conditions do not require any supplementary electrolyte salts.

A low-cost electrochemical thio- and selenocyanation strategy for electron-rich arenes under catalyst- and oxidant-free conditions

“…Adopting electron as "reagent" in place of stoichiometric amounts of oxidants or reductants, electrosynthesis has been recognized as an eco-friendly synthetic tool. 22,23 As part of our continuous works on electrochemical (pseudo)halogenation reactions, 24 herein we present an efficient, low-cost, catalyst-and oxidantfree approach for thio-and selenocyanation of electron-rich arenes using thio-or selenocyanate salts as the sole reagent under mild electrochemical condition (Scheme 1f).…”

Electrochemical 1,2‐Diarylation of Alkenes Enabled by Direct Dual C–H Functionalizations of Electron‐Rich Aromatic Hydrocarbons

“…A cross diarylation between 1‐methyl‐1 H ‐indole 2 a and 3‐iodo‐1 H ‐indole 2 v showed that indole 2 v was not a suitable substrate to execute the reaction [Eq (6)]. The results suggest that the diarylation process does not includes oxidation of iodide [14] …”

“…T he results suggest that the diarylation process does not includes oxidation of iodide. [14] Notably,c ompetitive cross reactions in Table 2s howed that 1-dimethyl-1H-indole 2a was more reactive than electron-deficient methyl 1-methyl-1H-indole-7-carboxylate 2g or 1-methyl-1H-indole-6-carbonitrile 2l (3aag/3 aga, 3aal/ 3ala), suggesting that the main process of the final indole trapping step may not include the radical addition. To verify the results,the kinetic isotope effect (KIE) experiments of 3deuterated 1-methy-1H-lindole (2a-1D)a nd 1-methy-1Hlindole 2a,r espectively were carried out:asmall KIE value (k H /k D = 1.27) was observed, which support ae lectrophilic reaction rather than ah ydrogen atom abstraction (radical) process in the final indole trapping step (Supporting Information, Figure S11).…”

Dearomatization Reactions of Indoles to Access 3D Indoline Structures

“…It is known that 3-unsubsituted indoles could be halogenated into 3-haloindoles by electrolysis in the presence of halides. 53 It inspired us to generate in situ an electrophilic bromine reagent via the anodic oxidation of a bromide salt which could react with the indole nucleus to form bromonium ion XXVIII and could be intercepted with an internal or external nucleophile. We identify that such a process could be achieved with MgBr 2 in an undivided cell with a graphite anode and a platinum-plated cathode with a constant cell potential of 5 V in a mixture of acetonitrile and water at room temperature without the need of an additional electrolyte (Scheme 19).…”