Electrochemical Umpolung of Bromide: Transition-Metal-Free Bromination of Indole C–H Bond

Abstract

A facile and sustainable electrochemical umpolung of bromide ion protocol was developed under mild reaction conditions. Transition metal catalysts and exogenous chemical oxidants were obviated for the bromination of C–H bond. Notably, graphite rod, which is commercially available at supermarkets and is inexpensive, was employed as the electrode material. This operationally easy and environmentally friendly approach accomplished the synthesis of 3-bromoindole in excellent yield and regioselectivity.

Electrochemical Dearomative Dihydroxylation and Hydroxycyclization of Indoles

“…Note: Most of the dihydroxyindolines are obtained as a mixture of trans and cis diastereoisomers. The 13 C NMR signals of C2 and C3 are deshielded (downfield) of approximately 5 ppm for the trans isomer in comparison to the cis isomer. The 1 H NMR signal of the proton at C2 is deshielded (downfield) of approximately 0.2 ppm for the trans isomer in comparison to the cis isomer.…”

“…[7e] In contrast to the direct anodic oxidation of the indole nucleus, we very recently performed an indirect electrochemical dearomatization of indole derivatives (Scheme 2). Recognising that, like several other arenes and unsaturated substrates, [12] 3-unsubsituted indoles 3 could be halogenated into 4 or 5 by electrolysis in presence of halides, [13] we achieved the MgBr 2 -mediated conversion of tryptophol, tryptamine and tryptophan derivatives 6 into bromofuranoindolines and bromopyrroloindolines 7 without the need of an additional electrolyte. [14] In this process, MgBr 2 is presumably oxidized at the anode into an electrophilic bromine reagent which could react with the indole nucleus to form bromonium ion B which is then intramolecularly intercepted by the oxygen or nitrogen nucleophile on the C3-substituent to deliver 7.…”

“…Therefore, decreasing the load of MgBr 2 from one equivalent to 0.25 equivalent led to an increase of the yield to 60% (entry 11). Conducting, the electrolysis in potentiostatic conditions (entries [12][13][14] instead of galvanostatic conditions led to an improved yield (71%) at a constant potential of 5 V between the two electrodes (entry 13). Finally, a slight increase of the yield to 74% could be obtained, as a 4:1 diastereoisomeric ratio in favour of the cis diastereoisomer, with a higher concentration of water (entry 15).…”

Recent Update on Transition Metal‐Free C(sp2)−H Bond Halogenation in (Hetero) Arenes

“…Bromination of indole in electrochemical pathway has also been accomplished [78] by Chen et al . using graphite electrodes.…”

“…Bromination of indole in electrochemical pathway has also been accomplished [78] by Chen et al using graphite electrodes. Ammonium salts of bromide have been utilized as bromine source without any external oxidant.…”