Study On The Synthesis Of N-Containing Heterocyclic Compounds Involved In Isothiocyanates

Phenanthridine and isoquinoline derivatives are two representative N-containing heterocyclic compounds.Natural alkaloids containing phenanthridine skeletons have specific biological activities.For example,chelerythrine has antibacterial and anti-inflammatory biological activity,and lycobetaine has anti-cancer biological activity.In addition,phenanthridine compounds have certain electrooptic activity.Isoquinoline and its derivatives are also widely found in natural products and drugs with antibacterial,analgesic,antihypertensive and other types of biological activity,such as typical berberine alkaloids,cytotoxic alkaloids quinocarcin.Given the increasing prevalence of these two kinds of nitrogen-containing compounds in medicine and other fields,the preparation of these two kinds of heterocyclic compounds by various organic synthetic methods would be of great value.Isothiocyanates are a class of important organic synthetic intermediates,which are widely used because of their many advantages such as ease of preparation and good stablity.Isothiocyanates are not only bioactive compounds,but also their applications for synthesis of nitrogen,sulfur-containing heterocyclic compounds in the fields of biomedicine and pesticides have marvelous potentiality.H-phosphite compounds are special phosphorus-containing reagents to synthesize various compounds furnishing phosphoryl groups.Phosphoyl radicals or phosphorus anions generated by H-phosphite compounds can be served as reactive groups involving tandem cyclization reactions.Diaryliodonium salts are often used as a highly efficient arylating agents.Aryl ions produced by the metal catalyzed can be used to form heterocyclic compounds via tandem cyclization reactions with nucleophilic substrates.Continuing interests in using isothiocyanates as the starting materials for the construction of heterocycles,a novel Mn(II)-promoted tandem reaction to synthesize 6-phosphorylated phenanthridines from 2-biaryl isothiocyanates and phosphine oxides under oxidant-free conditions is described.Substituted 6-phosphorylated phenanthridine derivatives(28 compounds)were synthesized via C-P/C-C tandem cyclization.Mchanistic experiments indicated that the reactions involved a non-radical pathway.The important thioamide intermediate of the reaction is obtained and confirmed by X-ray.Then,a copper-catalyzed tandem arylation-cyclization process to access 1-(arylthio)isoquinolines from isothiocyanates and diaryliodonium salts is described.It is the first general method to construct the potentially useful 1-(arylthio)isoquinoline derivatives(16 examples).Moreover,1-(methylthio)isoquinoline derivatives(9 examples)were also achieved successfully with MeOTf instead of diaryliodonium salts under metal-free conditions.Mechanistic studies revealed that these two processes proceed in different routes.In addition,the method was applied as a key step for the short synthesis of alkaloid rutaecarpine.