Tunable Site Selectivity and Chemo- and Regioselectivity: Diversification of Indole Alkaloid Privileged Scaffolds Enabled by λ-Iodane-Mediated Cross-Nucleophile Coupling Cascade.

Amidst nature's repertoire of small molecule architectures, indole alkaloid-derived privileged scaffolds continuously support innovation in bioactive compound discovery and propel fragment-based drug design. Herein, we realized a metal-free, site-selective, and chemo- and regioselective cross-nucleophile coupling cascade of pluripotent indole-enamine-aniline intermediates by use of λ-iodane-mediated umpolung chemistry. The protocol is applicable toward the divergent synthesis of valuable benzo[]indolo[3,2-][2,6]naphthyridines and azepino[4,5-]indoles, which are very important privileged scaffolds in communesin-, peroforamidine-, and iboga-type alkaloids. The control experiments and theoretical calculations provide insights into the reaction mechanism and the site-selectivity of umpolung induced by λ-iodane.