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

preprint
submitted on 26.02.2019, 19:16 and posted on 28.02.2019, 17:13 by Yu Kawamata, Julien 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 W. Knouse, Chuanguang Qin, Khalyd J. Clay, Denghui Bao, Chao Li, Jeremy T. Starr, Carmen N. Garcia-Irizarry, Neal Sach, Henry S. White, Matthew Neurock, Shelley D. Minteer, Phil Baran

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 as well as procedures for both batch and flow scale-ups (100 gram) are also described.

Funding

NIH (GM-118176)

History

Email Address of Submitting Author

pbaran@scripps.edu

Institution

The Scripps Research Institute

Country

USA

ORCID For Submitting Author

0000-0001-9193-9053

Declaration of Conflict of Interest

no conflict

Exports