Electrochemically Driven, Ni-Catalyzed Aryl Amination: Scope, Mechanism, and Applications

Yu Kawamata, Julien C. Vantourout, David P. Hickey, Peng Bai, Longrui Chen, Qinglong Hou, Wenhua Qiao, Koushik Barman, Martin A. Edwards, Alberto F. Garrido-Castro, Justine N. Degruyter, Hugh Nakamura, Kyle Knouse, Chuanguang Qin, Khalyd J. Clay, Denghui Bao, Chao Li, Jeremy T. Starr, Carmen Garcia-Irizarry, Neal SachHenry S. White, Matthew Neurock, Shelley D. Minteer, Phil S. Baran

Research output: Contribution to journalArticlepeer-review

119 Scopus citations

Abstract

C-N cross-coupling is one of the most valuable and widespread transformations in organic synthesis. Largely dominated by Pd- and Cu-based catalytic systems, it has proven to be a staple transformation for those in both academia and industry. The current study presents the development and mechanistic understanding of an electrochemically driven, Ni-catalyzed method for achieving this reaction of high strategic importance. Through a series of electrochemical, computational, kinetic, and empirical experiments, the key mechanistic features of this reaction have been unraveled, leading to a second generation set of conditions that is applicable to a broad range of aryl halides and amine nucleophiles including complex examples on oligopeptides, medicinally relevant heterocycles, natural products, and sugars. Full disclosure of the current limitations and procedures for both batch and flow scale-ups (100 g) are also described.

Original languageEnglish (US)
Pages (from-to)6392-6402
Number of pages11
JournalJournal of the American Chemical Society
Volume141
Issue number15
DOIs
StatePublished - Apr 17 2019

Bibliographical note

Publisher Copyright:
© 2019 American Chemical Society.

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