Electrochemical Oxidative Clean Halogenation Using HX/NaX with Hydrogen Evolution

Abstract

Organic halides (R-X) are prevalent structural motifs in pharmaceutical molecules and key building blocks for the synthesis of fine chemicals. Although a number of routes are available in the literature for the synthesis of organic halides, these methods often require stoichiometric additives or oxidants, metal catalysts, leaving or directing groups, or toxic halogenating agents. In addition, the necessity of employing different, often tailor-made, catalytic systems for each type of substrate also limits the applicability of these methods. Herein, we report a clean halogenation by electrochemical oxidation with NaX/HX. A series of organic halides were prepared under metal catalyst-and exogenousoxidant-free reaction conditions. It is worth noting that this reaction has a broad substrate scope; various heteroarenes, arenes, alkenes, alkynes, and even aliphatic hydrocarbons could be applied. Most importantly, the reaction could also be performed on a 200-mmol scale with the same efficiency (86%, 50.9 g pure product).

Electrochemical Dearomative Dihydroxylation and Hydroxycyclization of Indoles

“…[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).…”

Electrochemical Synthesis of 3‐Bromoimidazo[1,2‐a]pyridines Directly from 2‐Aminopyridines and alpha‐Bromoketones

“…Based on the mechanistic investigations above and the reported works,,, a plausible mechanism is proposed and shown in Scheme . Condensation of 2‐aminopyridine with 2‐bromoacetophenone produces imidazo[1,2‐a]pyridine derivative 6 .…”

“…[4] To date, the preparation of these halogenated compounds has been generally accomplished in two steps: the build-up of the imidazo [1,2-a]pyridine core and the halogenation. [5] Nevertheless, the existing few methods for one pot direct synthesis of 3-halogensubstituted imidazo[1,2-a]pyridines suffered from one or more disadvantages, such as limited substrate scope, [6a] the involvement of transition-metal, [6c,d] elevated temperature [6b-d] or microwave conditions. [6b] From the viewpoint of green and stepeconomic strategy, development of direct synthesis of 3halogen-substituted imidazo[1,2-a]pyridines under mild conditions is still desirable.…”

Recent Advances in Electrochemical Chalcogen (S/Se)‐Functionalization of Organic Molecules

“…In recent years, several reactions have been conducted through electrosynthesis, such as alkyne functionalization, alkene functionalization, cascade cyclisation, C−H activation, and halogenation . Unstable reactive intermediates, e. g., radical ions (anions or cations), can be readily obtained by anodic oxidation or cathodic reduction, and can be stabilized at low temperature or reacted directly with other substrates via nucleophilic substitution, electrophilic substitution or radical reactions, providing acidic or basic species.…”