Practical and modular construction of benzo[c]phenanthridine compounds

Here, we describe a general and modular strategy for the rapid assembly of benzo[c]phenanthridine (BCP) derivatives using homogeneous gold catalysis. Notably, in contrast to traditional methods based on the specially preformed substrates that have an inherent preference for the formation of this class of compounds with limited flexibility, this protocol is achieved via a selectively intramolecular cascade of a diazo-tethered alkyne and subsequently an intermolecular cyclization with a nitrile to facilitate the successive C-N and C-C bonds formation. This methodology uses readily available nitriles as the nitrogen source to deliver the products in good yield with excellent functional group compatibility. A preliminary anti-tumor activity study of these generated products exhibits high anticancer potency against five tumor cell lines, including HeLa, Mel624, SW-480, 8505C, LAN-1. Besides, we report a catalyst-controlled intermolecular cycloaddition/intramolecular insertion of the substrate with a fulvene to provide fused polycarbocycles containing a seven-membered ring. [graphic not available: see fulltext]