Constructing Phenanthridine Derivatives With Isonitrile Through Radical Cascade Reaction

Radical cascade reaction shows significant advantages of the aspect of atom economy, the effectiveness of the synthetic efficiency and environment friendliness. Now, it’s a vital research frontier of organic synthesis. The exceptional reactivity of the functional group of isocyanide provides a powerful driving force and broad space for development of related radical cascade reaction. In recent years, aryl isonitriles, which could directly construct phenanthridine derivatives by a radical cascade reaction, have attracted much attention in the synthetic community. The phenanthridine core is an important substructure present in many natural products with different biological activities, such as antibacterial, antitumoral, antiviral and antileukemic. On the other hand, it also has a wide application in the field of material chemistry owe to its rigid structure.In this paper, we, inspired by the widely application prospect of phenanthridine derivatives and the achievement of our group’s work on free radical functionalization reaction, did some research about radical cascade reaction based on isocyanide. The thesis consists of the following contents:Part 1, the preparation of 6-alkylthiophenanthridines. A concise metal-free method for synthesizing 6-alkylthiophenanthridines from 2-isocyanobiaryls and disulfides proceeding through thiolation of isocyanides and intramolecular radical aromatic cyclization is found. This process involves S-S/C(sp2)-H bond cleavage and C-S/C-C bond formation. This reation obtain the desired products in up to 95% yields with high regioselectivity by metal-free approach.Part 2, the preparation of 6-Amidophenanthridines. A metal-free cyclization reaction of 2-isocyanobiphenyls with amide derivatives by using tert-butyl peroxybenzoate (TBPB) as oxidant was developed, which provided an access to pharmacologically interesting 6-amidophenanthridine compounds. The reactions proceeded through a sequence of functionalization of the C(sp3)-H bond adjacent to the nitrogen atom and intramolecular radical aromatic cyclization with good chemistry yields.