biostudies-literatureKawamata YDivision of ChemistryFoundation for the National Institutes of HealthNIGMS NIH HHS6392-6402https://www.ebi.ac.uk/biostudies/studies/S-EPMC6996791biostudies-literatureUnknown141(15)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.Journal of the American Chemical SocietyElectrochemically Driven, Ni-Catalyzed Aryl Amination: Scope, Mechanism, and Applications.PMC6996791GM-118176#1740656R35 GM118176Garcia-Irizarry CLi CClay KJNakamura HSach NChen LNeurock MVantourout JCWhite HSHickey DPQiao WKnouse KEdwards MABarman KGarrido-Castro AFBai PHou QMinteer SDBaran PSdeGruyter JNBao DKawamata YQin CStarr JTfalseElectrochemically Driven, Ni-Catalyzed Aryl Amination: Scope, Mechanism, and Applications.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.2019-01-01T00:00:00Z2019 Apr2024-11-21T00:51:53.314Z2020-10-29T14:13:47ZS-EPMC69967913090515110.1021/jacs.9b01886