This article focuses on the development of an aromatic amination reaction using CuI and CsOAc and its application to total syntheses of nitrogen-containing cyclic natural products. The reaction conditions present several unprecedented features that have not been observed in conventional palladium-catalyzed systems, including high functional group compatibility (e.g., N-alloc-and sp²-Br are retained) and applicability for highly hindered substrates. The utility of this reaction has been fully demonstrated through total syntheses of duocarmycins, yatakemycin, and PDE-II.