Electrochemical cascade of Knoevenagel condensation and reduction: a 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 the starting substrates and cathodic reduction of an in situ-formed alkene has been discovered. NH₄OAc was used as the base and the electrolyte, and a green solvent, aqueous EtOH, was applied as the medium. A high selectivity of C(sp³)–C(sp³) bond formation was achieved 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 (ΔG_H*) far from 0, low HER overpotential (high absolute value), and high OER overpotential were proposed factors that make glassy carbon ideal for the cascade of Knoevenagel condensation and reduction. The reaction proceeds under mild conditions, does not require hydride-based reductants, and provides moderate to good yields of the substituted nitriles.