Nickel-Catalyzed α-Arylation of α-Cyanoacetates Enabled by Electrochemistry

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Corresponding Author(s)

Ping Fang(;
Tian-Sheng Mei(


β-Amino acids have a wide range of applications in the field of pharmaceuticals. Utilizing a combination strategy of nickel catalysis and paired electrolysis, a catalytic α-arylation protocol of carbonyl compounds has been developed. This protocol affords various α-aryl-α-cyanoacetates, which can be reduced to high-value-added α-aryl-β-amino acids. The cross-coupling reaction of electron-deficient aryl bromides with α-cyanoacetates yields the expected products with good yields and functional group compatibility under mild conditions. Excessive electron-richness in initial aryl bromides facilitates the self-coupling of desired products. DFT calculations confirm that the presence of electron-rich aryl substitutions decreases the reduction potentials of the product anions, making them more susceptible to oxidation at the anode. Based on electroanalyses and mechanistic studies, it is proposed that the enolate intermediate, rather than the radical intermediate, participates in the catalytic cycle.

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Organic electrosynthesis, Nickel-catalysis, Paired electrolysis, α-arylation, DFT calculation

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