Applying asymmetric-waveform alternating current in nickel-catalyzed asymmetric reductive cross-coupling.

Abstract

Asymmetric waveform alternating current electrocatalysis (asym. AC-eChem) is introduced as a powerful and versatile platform that overcomes key limitations in electrochemical reductive cross-coupling chemistry. By precisely tuning electrode materials, forward / reverse current magnitude, duty ratio, and frequencies, asym. AC-eChem effectively addresses challenges associated with traditional direct current (DC) methods, such as cathodic over-reduction and anodic metal salt deposition. Through nickel-catalyzed asymmetric reductive cross-coupling, this method enables the dialkylation of alkynes with two non-activated alkyl halides, which are traditionally challenging substrates due to their difficult reduction properties and similar reduction potentials, while also providing precise control over chemo-, regio-, E/Z-, and enantio-selectivities. It efficiently produces axially chiral compounds, including deuterated methyl and ethyl derivatives with pharmaceutical relevance. Furthermore, the resulting products can be readily transformed into phosphine ligands, which exhibit exceptional performance in palladium-catalyzed asymmetric allylation reactions. The scalability and industrial viability of this strategy are demonstrated through a custom-designed flow electrochemical system. Overall, this protocol establishes asymmetric waveform AC electrocatalysis as a transformative method for advancing electrochemical reductive cross-coupling.