Copper-catalyzed Synthesis Of N-Heterocycles From Diazo-compounds

Nitrogen-containing heterocyclic compounds are ubiquitous in natural products,bioactive molecules,drugs and material molecules,which has elicited significant interests in chemistry and material science.In this thesis,we developed the coppercatalyzed synthesis of heterocycles from diazo-compounds,which can be divided into the following two sections:i)We have developed a copper-catalyzed ring-opening reaction of fluoroalkylsubstituted isoxazoles.On the basis of our previous work with diazo-compounds,a series of fluoroalkyl-substituted enaminones were obtained in high yields from readily available fluoroalkyl isoxazoles with the aid of a copper/diamine catalytic system.Fluoroalkyl-substituted enaminones were converted to fluoroalkyl substituted pyrazoles.Such compounds are effective COX-2 inhibitors,including marketed drugs celecoxib,deracoxib,SC-560.Finally,we proposed the reductive ring-opening reaction proceeds via an electron transfer pathway.ii)We developed a tandem cyclization reaction of diazoacetonitrile and oaminophenyl acetylene for the synthesis of C-2 cyanomethylindole compounds in one step.Notable features of this method are as follows: It does not require any cyanide salt and is highly regioselective and tolerant of a diversity of functionalities.Furthemore,the cyano group can be converted into many other functional groups,providing an entry to functionalized indoles.Finally,we have conducted a preliminary study on the reaction mechanism.