Cu-Catalyzed Radical Cyclization Of Cycloketone Oxime Esters And Vinyl Azide

Nitrogen-containing heterocycles,especially phenanthridine derivatives and quinoxaline derivatives had been applied extensively in pharmaceuticals,materials and organic synthesis.And because phenanthridine derivatives and quinoxaline derivatives can be used as drugs or prodrugs.Phenanthridine is a recurring motif in natural products and medicine,which exhibits antileukemic,anticancer,antivirus,antibacterial and antifungal activities.Quinoxaline can be used as intermediate for the synthesis of anti-tuberculosis drug pyrazinamide.Quinoxaline compounds possessed extensive pharmacological activity in treatment of obesity,antitumor etc.Therefore,many reporters about the efficient preparation methods of phenanthridine and quinoxaline derivatives have emerged,the exploration of efficient and selective preparation methods for phenanthridine and quinoxaline derivatives is of great significance.Cyanides is one of the core functional groups in organic synthesis,and cyanoalkyl moieties are of wide appearance in modern pharmaceuticals and bioactive compounds.For example,the introduction of cyanide groups can change the physical and chemical properties of molecules.In addition,the cyanide group is also an important synthetic intermediate,which can be converted into many other important functional groups through simple chemical reactions,such as carboxylic acid through hydrolysis,amine through reduction,etc.However,cyanoalkyl is traditionally prepared using inorganic cyanides and alkyl halides,both are inevitable problems.Inorganic cyanides are highly toxic.Many inorganic cyanides will release hydrogen cyanide when heated or reacted with acids or in the air.Preparation of alkyl halides will add many steps and costs.Thus,the effective synthesis of organic cyanides has attracted considerable attention,and various methods have been developed for the preparation of organic cyanides,but most of them are aromatic nitriles instead of alkyl nitriles.In this article,we have developed an efficient method of radical cyclization of cycloketone oxime esters and vinyl azides using accessible and inexpensive Cu(II)catalyst.Using this uncomplicated method,we were able to synthesize cyanoalkyl-substituted phenanthridine and quinoxaline derivatives from readily available and safe starting materials under mild conditions.