Electrochemical Activation of the C-X Bond on Demand: Access to the Atom Economic Group Transfer Reaction Triggered by Noncovalent Interaction.

Abstract

An atom economic method demonstrates the involvement of noncovalent interaction via hydrogen or halogen bonding interaction in triggering paired electrolysis for the group transfer reactions. Specifically, this method demonstrated the bromination of several aromatic and heteroaromatic compounds through the activation of the C(sp3)-Br bond of organic-bromo derivatives on demand. This electrochemical protocol is mild, and mostly no additional electrolyte is needed, which makes the workup process straightforward. Unlike the existing regioselective monobromination methods, this work utilizes a relatively small amount (1.2 equiv) of bromine surrogates that releases bromine on demand under the electrochemical condition and after completion of the reaction generates acetophenone as a useful byproduct. Green metrics indicate this protocol has a very good atom efficiency with an E-factor of 26.86 kg of waste/1 kg of product. In addition to the scale-up process, this strategy could be extended to the transfer of chlorine and thioaryl units. An extensive mechanistic study is accomplished to validate the hypothesis of noncovalent interaction using computational, spectroscopic, and cyclic voltammetry studies. Finally, the applicability of this newly developed nonbonding interaction to trigger paired electrolysis was extended to the chemoselective debromination of several dihalo organic compounds.