Skeletal Transformation of Benzene Rings to Indoles via Arylthianthrenium Salts Strategy

Herein, we describe a method employing an arylthianthrenium salts strategy for the direct skeletal transformation of the benzene rings commonly found in drugs into indoles via two consecutive site-selective C-H functionalizations. This method features a broad substrate scope and is applicable for the late-stage skeletal transformation of pharmaceuticals. For example, the insect growth regulator <i>Pyriproxyfen</i>, the antifungal agent <i>Bifonazole</i>, the nonsteroidal anti-inflammatory drug <i>Flurbiprofen</i>, and the natural product <i>Salicin</i> can all be rapidly transformed into the desired indole derivatives. As for the mechanistic studies, DFT calculations demonstrated that the nitrogen insertion proceeds through a reductive elimination involving an eight-membered ring intermediate, rather than a nitrene pathway.