Electrochemical cascade of Knoevenagel condensation and reduction: Green strategy for intermolecular C(sp3)-C(sp3) bond formation

Abstract

An intermolecular C(sp3)-C(sp3) coupling of ketones with EWG-activated nitriles proceeding via a combination of Knoevenagel condensation of starting substrates and cathodic reduction of in situ formed alkene has been discovered. NH4OAc was used as the base and the electrolyte, the green solvent, aqueous EtOH, was applied as the media. High selectivity in C(sp3)-C(sp3) bond formation was achieved exclusively using available glassy carbon as the electrode material. The origin of an electrode’s ability to control the reaction outcome was disclosed. A hydrogen adsorption free energy (ΔGH*) far from 0, low HER overpotential (high absolute value), and high OER overpotential were proposed factors that make a glassy carbon ideal for cascade of Knoevenagel condensation and reduction. The reaction proceeds under mild conditions, does not require hydride-based reductants, and provides from moderate to good yields of the substituted nitriles.