para-Selective, Direct C(sp2)-H Alkylation of Electron-Deficient Arenes by the Electroreduction Process

Pufan Ni; Lei Yang; Jiasheng Yang; Ruihua Cheng; Weiping Zhu; Yueyue Ma; Jinxing Ye

doi:10.1021/acs.joc.2c02412

para-Selective, Direct C(sp²)-H Alkylation of Electron-Deficient Arenes by the Electroreduction Process

J Org Chem. 2023 May 5;88(9):5248-5253. doi: 10.1021/acs.joc.2c02412. Epub 2023 Apr 6.

Authors

Pufan Ni¹, Lei Yang¹, Jiasheng Yang¹, Ruihua Cheng², Weiping Zhu³, Yueyue Ma², Jinxing Ye^{1

2}

Affiliations

¹ Engineering Research Centre of Pharmaceutical Process Chemistry, Ministry of Education; Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, China.
² School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China.
³ State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, PR China.

PMID: 37023248
DOI: 10.1021/acs.joc.2c02412

Abstract

Direct para-selective C(sp²)-H alkylation of electron-deficient arenes based on the electroreduction-enabled radical addition of alkyl bromides has been developed under mild conditions. In the absence of any metals and redox agents, the simple electrolysis system tolerates a variety of primary, secondary, and tertiary alkyl bromides and behaves as an important complement to the directed alkylation of the C(sp²)-H bond and the classic Friedel-Crafts alkylation. This electroreduction process provides a more straightforward, environmentally benign, and effective alkylation method for electron-deficient arenes.