Palladium (II) Catalyzes The CH Activation-directed Cyanation Reaction

The introduction of-CN group into aromatic rings of pharmaceuticals,agrochemicals and natural products can significantly improve their properties.In addition,-CN group can also be converted into other valuable functional groups such as carboxyl group,aminomethyl and aminoformoxyl.Therefore,cyanidation reaction of introducing the cyano functional groups is important in organic chemistry.In early years,cyanation reaction existed some drawbacks,including high toxic reaction reagent andtheharshreactionconditionsandsoon.Inrecentdecades,transition-metal-catalyzed cyanation reaction was an appealing strategy via functionalization of C-H activation approach.It can avoid the disadvantages of traditional methods,and enhance atomic utilization.In this paper,single-and bidentate-chelation direct Pd?II?-catalyzed aromatics cyanidation reaction system is respectively developed.First,24 N-?naphthalen-1-yl?picolinamide derivatives as substrates containing-picolinamido functional groups were designed and synthesized by literature research.A novel cyanidation reaction system of these substrates was developed by optimizing the reaction conditions such as the kind and amount of catalysts,oxidants,solvents,cyanide reagents and reaction temperature.The optimized reaction conditions were N-?naphthalen-1-yl?picolinamide derivatives as substrates,benzoyl nitrile as a cyanating agent,Pd?OAc?₂ as catalyst,Cu?TFA?₂ as oxidant and DMAc as solvent.23naphthalene nitrile compounds were synthesized under the optimal conditions,10 of which were new compounds.The reaction system is easy to process;the reaction conditions are not polluted and have a good group tolerance.Then,25 substrates containing-imidazolyl functional groups were designed and synthesized.The cyanidation reaction conditions were optimized by screening catalysts,the amount of catalyst,oxidants,solvents and reaction temperature.A novel cyanidation reaction system of 2-arylbenzimidazoles as substrate,K₄Fe?CN?₆ as cyanating agent,Pd?OAc?₂ as catalyst,Cu?OAc?₂ as oxidant and DMAc as solvent was developed.20benzonitrile compounds were synthesized by this reaction system,19 of which were not reported.The catalytic system has the advantages of simple operation,high atomic utilization rate and a wide range of applications.