Synthesis Of Phenanthridines By Radical Cyclization Of 2-Isocyanobiphenyls

Phenanthridines are important structural motifs in the fields of organic and pharmaceutical chemistry. These heterocycles not only show biological activities such as antitumor, antileukemic, antiviral, and antifungal properties, but have excellent optical and electronic properties in the fields of functional materials. Therefore, it is of interest to prepare phenanthridines. However, the traditional synthesis methods of phenanthridines have some disadvantages including harsh conditions, multiple steps, difficulty to obtain the raw materials, poor yield, and so on. Herein, the synthesis of 6-arylthiophenanthridines and 6-trichloromethylphenanthridines via a radical addition-cyclization of 2-isocyanobiphenyls were described.1) According to literature records, using 2-bromoanilines and phenylboronic acids as starting materials,2-isocyanobiphenyls were synthesized via Suzuki coupling, formylation and amide dehydration.2) Isocyanide is a kind of very active organic compounds similar to CO molecule. Also, isocyanide is a good free radical acceptor. We have developed the TBPB-promoted phenanthridinylation of simple thiol sources with 2-isocyanobiphenyls. A radical pathway was proposed and evidenced for the reaction mechanism. The functional group, such as acetyl, ester, cyano, tert-butyl, fluorine and chlorine were all tolerated well, and the desired products were obtained in moderate yields. This represents a practical approach to access 6-arylthiophenanthridines.3) Trichloromethyl group is an attractive backbone which is widely utilized as a useful synthetic precursor to give corresponding methyl, gem-dichloromethyl, trifluoromethyl, carboxyl, ester group, oxazoles etc.. An BPO-promoted addition-cyclization reaction between 2-isocyanobiphenyls and inexpensive carbon tetrachloride is developed for the synthesis of 6-trichloromethylphenanthridines. A radical pathway was proposed and evidenced for the reaction mechanism. From 6-trichloromethylphenanthridines diverse 6-carbon substituted phenanthridines, such as methyl, carboxy, trifluoromethyl and benzimidazolyl, were easily prepared.