Site‐Selective Electrochemical Benzylic C−H Amination

• Published in: Angewandte Chemie International Edition Vol. 60; no. 6; pp. 2943 - 2947
• Main Authors: Hou, Zhong‐Wei, Liu, Ding‐Jin, Xiong, Peng, Lai, Xiao‐Li, Song, Jinshuai, Xu, Hai‐Chao
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 08.02.2021; Wiley Subscription Services, Inc
• Edition: International ed. in English
• Subjects: Alkylbenzenes; Amination; Amines; Catalysts; Chemistry; Chemistry, Multidisciplinary; Cross coupling; cross-dehydrogenative coupling; C−H amination; C−H functionalization; Electrochemistry; Hydrogen evolution; Oxidants; Oxidation; Oxidizing agents; Physical Sciences; Science & Technology; Selectivity; Substrates; ELECTROSYNTHESIS; H functionalization; H amination; ELECTRON-TRANSFER; electrochemistry; HETEROCYCLES; BONDS; oxidation; C− ACCESS; cross-dehydrogenative coupling; C−H functionalization; C−H amination
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.202013478

C−H/N‐H cross‐coupling is an ideal strategy to synthesize various amines but remains challenging owing to the requirement for sacrificial chemical oxidants and the difficulty in controlling the regio‐ and chemo‐selectivity. Herein we report a site‐selective electrochemical amination reaction that can convert benzylic C−H bonds into C‐N linkages via H2 evolution without need for external oxidants or metal catalysts. The synthetic strategy involves anodic cleavage of benzylic C−H to form a carbocation intermediate, which is then trapped with an amine nucleophile leading to C−N bond formation. Key to the success is to include HFIP as a co‐solvent to modulate the oxidation potentials of the alkylbenzene substrate and the aminated product to avoid overoxidation of the latter. An electrooxidative C−H/N−H cross‐coupling reaction with excellent site selectivity for benzylic positions is presented. The electrochemical C−H amination reaction employs easily available starting materials and proceeds under mild conditions without need for transition‐metal catalysts and external chemical oxidants.