Nickel-catalyzed Cyanation Of Pyridyl Groups Directed To C(sp~2)-H

Pyridine compounds as important skeleton structures are widely used in drugs,agrochemicals,dyes,agrochemicals,natural products and materials.2-Arylpyridine,2-arylquinoline and 1-arylisoquinoline are important fragments of medicines and natural products.The introduction of-CN groups into them can significantly change their pharmacological properties and biological activities.However,the process of introducing cyano groups into these small molecules using traditional methods has many disadvantages,such as high toxicity of cyanating reagents and the need for pre-functionalization of substrates.In recent years,transition metal-catalyzed C-H bond cyanation reaction has gradually become the main method,which can avoid the shortcomings of traditional methods and improve the atom utilization rate.The choice of cyanation reagent is the key point of the C-H bond cyanation reaction.Safe,stable,cheap,and high conversion cyanation reagents have become the current research hotspot.Through literature research and summarizing previous work,2-cyanoisothiazolidine 1,1-dioxide was designed and prepared as a new type of electrophilic cyanation reagent.Then,a nickel-catalyzed pyridyl-directed cyanation reaction was developed by using 2-cyanoisothiazolidine 1,1-dioxide(NCITD)as the cyanation reagent.The optimized system for pyridyl-directed C(sp~2)-H cyanation reaction was determined by screening the transition metal catalyst and its dosage,additive and its dosage,base and its dosage,reaction solvent and reaction temperature.35 Aromatic nitrile compounds were prepared under the optimal reaction system and their structures were characterized.Through controlled experiments,the reaction was proved to be an electrophilic ionic reaction,and the reaction mechanism was discussed.Finally,the strategy was used to synthesize a natural product menisporphine,which further proved the applicability of the synthetic method.