Preparation Of Functionalized Nitriles By Oxidative C-H And C-C Activation Reactions

Nitriles are important organic compounds containing cyano groups,which are widely used in many fields such as biologies,medicines,pesticides,materials and daily chemicals.In addition,cyano groups are very valuable in organic synthesis,and it can be easily converted into various meritorious functional groups and heterocycles,such as amines,aldehydes,amides,carboxylic acids or tetrazolium.The traditional cyanide reagents used in the preparation of nitriles are mainly metal cyanide salts.For example,cuprous cyanide was used as cyanide reagent in the Rosenmund-von Braun and Sandmeyer reaction.When metal cyanide salt was used as the source of cyano group,it is easy to produce highly volatile and highly toxic HCN gas,which brings great danger in storage and transportation.Meanwhile,the generated metal salt waste will cause environmental pollution problems,which greatly restricts the wide application of these reactions.In recent years,in order to develop green and safe nitrification reactions,organic cyanide reagents have received extensive attention.In this paper,the inexpensive,easy-to-obtain,green and non-toxicα-cyano ester was used as the source of cyano groups,and functionalized nitriles were constructed by using C-H activation and C-C activation under oxidative conditions.The specific work is as follows:(1)Using ethyl cyanoacetate as the cyanating reagent,in an oxygen atmosphere,through the synergistic effect of ligands,copper salts,and co-oxidants,Acetylene nitriles were synthesized by the cleavage of the C-CN bond and the C(sp)-H activation functionalization of the terminal alkyne.A series of terminal alkyne substrates were expanded under optimal conditions to verify their applicability and explored the reaction mechanism.And under optimal conditions,the direct cyanation of aryl halides,aryl boronic acid and alkenyl halides was well realized.(2)Under the conditions of ligand,copper catalyst and oxidant,in a nitrogen atmosphere,the sp~2 carbon of the diaryl olefin was cross-coupled with the sp~3 carbon of theα-cyano ester to obtain 2,2,4,4-Four-substituted-3-butenenitriles.Meanwhile,the sp~3 carbon ofα-methylstyrene was cross-coupled with the sp~3 carbon ofα-cyano ester to obtain 2,2,4-trisubstituted-3-pentenenitrile.New compounds containing alkenyl,ester and cyanide groups were obtained by activating and coupling C-H and C-H bonds of the two substrates to construct C-C bonds.Subsequently,a series of substrates were expanded under optimal conditions to verify their applicability,and the mechanism of the reaction was explored through free radical capture and free radical Clock experiments.(3)Based on the discovery of the synthesis of ethyl oxanilide from aniline and ethyl cyanoacetate,in an oxygen atmosphere,under the synergistic effect of ligands,copper catalysts,and co-oxidants,ethyl cyanoacetate was acylated and oxidized to achieve C2 and C3 positions of the indole heterocycle are bifunctional(cyano and oxoester).Subsequently,a series of substrates were expanded to verify their applicability under optimal conditions.Then we also discovered that in this reaction system,a pyridine ring-directed aromatic C-H cyanation reaction was discovered,and there is still space for further improvement in the yield.But it provides a novel idea for us to explore the use of cyanoesters to realize the C-H activated functionalization of aromatics.Generally,we selectedα-cyano ester as the cyanation reagent,and through condition screening and optimization,using oxidation,C-H activation and C-C activation as means,and we realized the functionalization of alkynes,aryl halides,aryl boronic acids,alkenes and heterocycles.We had developed a series of green and efficient nitrification reactions,which reflected its potential synthetic value.