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This perspective details advances made in the field of Ni-catalyzed C–N bond formation. The use of this Earth abundant metal to decorate amines, amides, lactams, and heterocycles enables direct access to a variety of biologically active and industrially relevant compounds in a sustainable manner. Herein, different strategies that leverage the propensity of Ni to facilitate both one- and two-electron processes will be surveyed. The first part of this Perspective focuses on strategies that facilitate C–N couplings at room temperature by accessing oxidized Ni(III) intermediates. In this context, advances in photochemical, electrochemical, and chemically mediated processes will be analyzed. A special emphasis has been put on providing a comprehensive explanation of the different mechanistic avenues that have been proposed to facilitate these chemistries; either Ni(I/III) self-sustained cycles or Ni(0/II/III) photochemically mediated pathways. The second part of this Perspective details the ligand designs that also enable access to this reactivity via a two-electron Ni(0/II) mechanism. Finally, we discuss our thoughts on possible future directions of the field. 

Abstract This study presents a Ni‐photoredox method for indoleN‐arylation, broadening the range of substrates to include indoles with unprotected C3‐positions and base‐sensitive groups. Through detailed mechanistic inquiries, a Ni(I/III) mechanism was uncovered, distinct from those commonly proposed for Ni‐catalyzed amine, thiol, and alcohol arylation, as well as from the Ni(0/II/III) cycle identified for amide arylation under almost identical conditions. The key finding is the formation of a Ni(I) intermediate bearing the indole nucleophile as a ligand prior to oxidative addition, which is rare for Ni‐photoredox carbon‐heteroatom coupling and has a profound impact on the reaction kinetics and scope. The pre‐coordination of indole renders a more electron‐rich Ni(I) intermediate, which broadens the scope by enabling fast reactivity even with challenging electron‐rich aryl bromide substrates. Thus, this work highlights the often‐overlooked influence of X‐type ligands on Ni oxidative addition rates and illustrates yet another mechanistic divergence in Ni‐photoredox C‐heteroatom couplings. 

Abstract This work demonstrates the dominance of a Ni(0/II/III) cycle for Ni‐photoredox amide arylation, which contrasts with other Ni‐photoredox C‐heteroatom couplings that operate via Ni(I/III) self‐sustained cycles. The kinetic data gathered when using different Ni precatalysts supports an initial Ni(0)‐mediated oxidative addition into the aryl bromide. Using NiCl₂as the precatalyst resulted in an observable induction period, which was found to arise from a photochemical activation event to generate Ni(0) and to be prolonged by unproductive comproportionation between the Ni(II) precatalyst and the in situ generated Ni(0) active species. Ligand exchange after oxidative addition yields a Ni(II) aryl amido complex, which was identified as the catalyst resting state for the reaction. Stoichiometric experiments showed that oxidation of this Ni(II) aryl amido intermediate was required to yield functionalized amide products. The kinetic data presented supports a rate‐limiting photochemically‐mediated Ni(II/III) oxidation to enable C−N reductive elimination. An alternative Ni(I/III) self‐sustained manifold was discarded based on EPR and kinetic measurements. The mechanistic insights uncovered herein will inform the community on how subtle changes in Ni‐photoredox reaction conditions may impact the reaction pathway, and have enabled us to include aryl chlorides as coupling partners and to reduce the Ni loading by 20‐fold without any reactivity loss.