Copper-Catalyzed Regioselective Hydroamination and Dual Annulation of 2-Alkynyl Indole-3-carbonitriles: An Assembly of Functionalized Amino-Benzo[ <i>h</i> ]indolo[3,2- <i>c</i> ][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[<i>h</i>]indolo[3,2-<i>c</i>][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.