Cyanation With Ethyl(Ethoxymethylene) Cyanoacetate As Cyanating Agent

Aromatic nitriles exist widely in various natural products,pharmaceuticals and biologically active molecules.Moreover,aromatic nitriles are important synthesis intermediates in organic synthesis.Although many methods have been developed for the synthesis of aromatic nitriles,some of them suffer from the low efficacy and the use of toxic,expensive and unavailable cyanating agents.Therefore,the development of novel and efficient methods for preparing various important nitriles with high selectivity and yields by using inexpensive and safe cyanating agents is still highly desirable.In this thesis,ethyl(ethoxymethylene)cyanoacetate was systematically examined as a novel cyanating agent for the constructing a variety of aromatic nitriles,and some interesting results are obtained.(1)By using TBHP and air as the oxidants,an efficient copper(I)iodide mediated cyanation of aryl boronic acids and aryl iodides with ethyl(ethoxymethylene)cyanoacetate as cyanating agent has been developed.The reaction involves a C(sp2)-CN bond cleavage of ethyl(ethoxymethylene)cyanoacetate in the presence of oxidants and copper salt.The mechanistic studies showed that the cyanation reaction of boronic acids proceeds through the iodination of aryl boronic acids followed by cyanation of aryl iodides intermediates.This method was also characterized by wide substrate scope,high yields and high functional group tolerance.(2)The first Cu(OAc)2-mediated C-H cyanation reaction of(hetero)arenes with ethyl(ethoxymethylene)cyanoacetate as the cyanating agent has been successfully developed with molecular oxygen as a green oxidant.The desired monocyanated products could be obtained as the sole product in an excellent yield by controlling the amounts of ethyl(ethoxymethylene)cyanoacetate and shortening the reacting time,while the generation of dicyanated by-product was restrained.This paper expands the utilization of ethyl(ethoxymethylene)cyanoacetate and copper/oxygen system in organic synthesis,providing new methods for the synthesis of aromatic nitriles and enriching the content of organic chemistry and green chemistry.Therefore,this research has important theoretical and practical significance.