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 Pyriproxyfen, the antifungal agent Bifonazole, the nonsteroidal anti-inflammatory drug Flurbiprofen, and the natural product Salicin 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.