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

Authors

Zi-Meng Li, State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200032, China
Zhang-Jian Li, a State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200032, China; b College of Chemistry and Materials Science, Sichuan Normal University,Chengdu 610068,China
Anat Milo, Department of Chemistry, Ben-Gurion University of the Negev, Beer-Sheva 841051, Israel
Ping Fang, State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200032, ChinaFollow
Tian-Sheng Mei, State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200032, ChinaFollow

Corresponding Author

Ping Fang(pfang@sioc.ac.cn); Tian-Sheng Mei(mei7900@sioc.ac.cn)

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

DOI Link

https://doi.org/10.61558/2993-074X.3435

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