Paired electrolysis-enabled nickel-catalyzed enantioselective reductive cross-coupling between α-chloroesters and aryl bromides

Abstract

Electrochemical asymmetric catalysis has emerged as a sustainable and promising approach to the production of chiral compounds and the utilization of both the anode and cathode as working electrodes would provide a unique approach for organic synthesis. However, precise matching of the rate and electric potential of anodic oxidation and cathodic reduction make such idealized electrolysis difficult to achieve. Herein, asymmetric cross-coupling between α-chloroesters and aryl bromides is probed as a model reaction, wherein alkyl radicals are generated from the α-chloroesters through a sequential oxidative electron transfer process at the anode, while the nickel catalyst is reduced to a lower oxidation state at the cathode. Radical clock studies, cyclic voltammetry analysis, and electron paramagnetic resonance experiments support the synergistic involvement of anodic and cathodic redox events. This electrolytic method provides an alternative avenue for asymmetric catalysis that could find significant utility in organic synthesis.

Nickel-Catalyzed Enantioselective Electrochemical Reductive Cross-Coupling of Aryl Aziridines with Alkenyl Bromides

“…complicates the scalability of the processes. Second, the control of stereochemistry still represents a significant challenge and, despite a few examples, most nickel-catalyzed electrochemically mediated processes deliver the corresponding products in racemic form (Scheme A, bottom). Notably, Reisman’s group has reported a Ni-catalyzed enantioselective cross-coupling of benzylic chlorides and alkenyl bromides using zinc as a sacrificial anode (Scheme B)…”

Electroreductively Induced Radicals for Organic Synthesis

“…In order to achieve more efficient and selective molecular syntheses, electrochemical processes can be designed as a combination of two simultaneous desirable half-reactions, oxidation and reduction. Therefore, paired electrolysis can be considered as the gold standard for two desirable progressions on both electrodes [ 106 , 107 ]. On the other hand, there should be more advances made in asymmetric electrochemical radical reductive transformation [ 86 , 108 ].…”

Asymmetric Organic Electrochemistry Catalyzed by Transition Metals

“…In 2022, Mei and co-workers reported a reduction crosscoupling reaction under paired electrolysis conditions (Scheme 12d). 41 In this study, bromide anions were oxidized to bromide radicals at the anode, then bromide radicals rapidly abstract hydrogen from the silane. The resulting silyl radical can abstract the chlorine atom from the α-carbonyl chloride to generate an electrophilic alkyl radical species.…”