Single-Atom Nickel-Catalyzed C–H Amidation of Pyridine and Quinoline N-Oxides

Abstract A single-atom nickel catalyst (Ni-N-C-700) was developed for the efficient direct amidation of quinoline N-oxides with dioxazolones, providing a broad range of 2-acetamidoquinoline N-oxide derivatives. Two one-pot synthetic routes starting from commercially available quinoline were also designed, enabling the flexible preparation of both 2-acetamidoquinoline N-oxides and the pharmaceutically relevant 2-aminoquinoline scaffolds. The single-atom nickel catalyst showed good stability, recyclability, and operational simplicity, while EXAFS analysis revealed a well-defined Ni–N4 coordination environment. A hot filtration experiment confirmed the heterogeneous nature of the catalytic system. This work provides a practical approach to the 2-acetamidoquinoline N-oxide and further illustrates the utility of heterogeneous nickel catalysis in C–H functionalization reactions.