Copper-Catalyzed Regioselective Hydroamination and Dual Annulation of 2‑Alkynyl Indole-3-carbonitriles: An Assembly of Functionalized Amino-Benzo[h]indolo[3,2‑c][1,6]naphthyridines

Presented herein are the copper-catalyzed regioselective hydroamination and successive dual annulation of 2-alkynyl indole-3-carbonitriles. The reaction shows a general approach for the versatile synthesis of amino-benzo[h]indolo[3,2-c][1,6]naphthyridines under mild conditions. The hydroamination process is highly regioselective; the nucleophilic attack preferentially occurs at the alkyne functional group over the cyano (-CN) group. The transformation shows a broad substrate scope with wide functional group variation on alkyne, late-stage modification, postsynthetic transformation, absolute atom economy, and ease of scalability. Control experiments provide substantive evidence supporting the proposed mechanism.