Abstract
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 a-aryl-a-cyanoacetates, which can be reduced to high-value-added α-aryl-β-amino acids. The cross-coupling reaction of electron-deficient aryl bromides with a-cyanoacetates achieves 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.
Graphical Abstract
Keywords
organic electrosynthesis; nickel-catalysis; paired electrolysis; alpha-arylation; DFT calculation
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Publication Date
2024-05-28
Online Available Date
2023-11-21
Revised Date
2023-11-12
Received Date
2023-08-27
Recommended Citation
Zi-Meng Li, Zhang-Jian Li, Anat Milo, Ping Fang, Tian-Sheng Mei.
Nickel-Catalyzed α-Arylation of α-Cyanoacetates Enabled by Electrochemistry[J]. Journal of Electrochemistry,
2024
,
30(5): 2313004.
DOI: 10.61558/2993-074X.3435
Available at:
https://jelectrochem.xmu.edu.cn/journal/vol30/iss5/2
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