Transition Metal-Catalyzed Cyanation Of (Hetero) Aryl/Alkenyl Halides And Diazoarenes With Acetonitriles As A Cyano Source

As a long-term research interest in our group,we focused on developing green and inexpensive organic nitriles as a source of“CN”.In recent years,we developed two types of copper-catalyzed systems to realize the possibility of acetonitrile as a green cyanide source for the cyanation of arenes bearing directing groups,simple arenes,aromatic halides and alkynes.Acetonitrile as a slow dosage cyanide source could solve the problem of using other metal cyanide to cause the catalyst to deactivate.On the other hand,these reactions had certain limitations:1)high temperature was required;the C-CN bond of acetonitrile could not be activated at low temperatures by using a copper catalyst;2)the reaction time was long(48hours or 72 hours).In view of these problems,we attempted to design a new catalyst system and an organic slow-release cyanide source to achieve the cyanation of various aromatic hydrocarbons under mild conditions by using acetonitrile as a cyano source.We first studied palladium-catalyzed cyanation of aryl/alkenyl halides and diazo aromatic hydrocarbon by the use of 2-(2,2,6,6-tetramethylpiperidin-1-yl)acetonitrile as a CN source under mild conditions.Notably,we have designed this metal-free(piperidin-1-yl)acetonitrile used as a organic cyanide reagent for Pd-catalyzed aryl/alkenyl halides and diazo aromatics under acidic and basic conditions.These reactions were easy to handle and had a broad substrate scope.This strategy have also been successfully applied to the synthesis of 1-oxo-1,3-dihydroisobenzofuran-5-carbonitrile scaffold as a drug precursor.In the second part of this dissertation,we achieved the cyanation of nickel-catalyzed aryl halides(including F,Cl,Br and I)using acetonitrile as a source of cyanide under mild conditions.This work showed some excellent advantages:(1)acetonitrile is successful in using as CN source under the mild conditions by the catalysis of nickel.In particular,aryl iodides can be cyanated smoothly with acetonitrile at 50 ~oC;(2)aryl fluorides without electron-withdrawing groups are quite inert,and we first successfully realized the cyanation of aryl fluorides which have broad application value in the fields of biology and medicine.Therefore,our method provides an effective way for the conversion of aryl fluorides;(3)aryl chlorides,the cheapest and readily available ones in aryl halides,were smoothly converted into industrially synthetic aryl nitriles;(4)these reactions had a wide substrate scope.In particular,various types of unprotected hydroxyl and amino groups,other electron-donating and-withdrawing groups were well compatible.We also extended the application of this method to the synthesis of drug molecules and the conversion of functional groups.We synthesized a series of bioactive compunds such as diethoxy binaphthalene dicarbonitrile,letrozole,citalopram etravirine,NNRTI and achieved the bioactive transformation of 2-cyanoindole and citalopram under mild reaction conditions.