Direct Synthesis\nof <i>N</i>‑Fused\nIndoles Enabled by Copper-Catalyzed Aerobic Oxygenative Rearrangement

<i>N</i>-Fused indoles are typical <i>N</i>-heterocycles, which are extensively found in natural products\nand\nbioactive molecules. Despite their importance, the synthesis of N-fused\nindoles has not yet been fully developed. Herein, we report a direct,\ngeneral unified copper-catalyzed aerobic oxygenative skeletal rearrangement\nstrategy using readily available cyclic indole substrates, which provides\na practical synthetic platform for the rapid construction of a wide\narray of N-fused indole scaffolds. This open-flask method features\nmild reaction conditions, high chemoselectivity, and a broad substrate\nscope (over 90 examples). The scaled-up synthesis and versatile transformations\nof the products using various nucleophiles demonstrated the scalability\nand utility of this protocol. Mechanistic studies revealed that, by\ninvolving a unique single-electron transfer (SET)-induced aerobic\noxygenation mechanism, the reaction of tetrahydro-γ-carbolines\nproceeded via a formal 1,3-migration rearrangement, while that of\ntetrahydrocarbazoles proceeded by a Witkop–Winterfeldt/C–C\ncleavage cascade.