Co-catalyzed Pyridyl-directed Indole C2-H Cyanatio

As a unique and important nitrogen-containing heterocyclic compound,indole and its derivatives are widely present in many natural products and synthetic substances with unique activities,and play an important role in the pharmaceutical field,and the introduction of cyano into them can significantly improve their biological activity and pharmacological properties.With traditional methods,the introduction of cyano into(hetero)aromatic hydrocarbons requires prefunctionalized substrates and toxic metal cyanidation reagents.In the past two decades,the direct functionalization of C-H bonds catalyzed by transition metals has gradually become one of the reliable and practical methods for synthesizing(hetero)aryl nitrile,which can avoid these shortcomings and have a high atomic utilization rate.In the direct cyanation reaction of various transition metals catalyzed C-H bonds,finding a more economical,safe,efficient and green scheme has become a research hotspot.Through the investigation of previous literature and structural characteristics,N-cyano-2,2’-biphenylimide(NCBLD)was designed and synthesized as a new cyanation reagent.According to the principle of green,economic and environmental protection,the reusable and designable ionic liquid 1-butyl-3-acetylimidazole trifluoromethanesulfonimide salt([BAIM]NTf2)is used as the reaction solvent.Here,a strategy was developed for direct cyanation of indole C-H bonds at room temperature with pyridyl-guided N-cyano-2,2-biphenyldicarbonylimide as cyanation reagent,Cp*Co(CO)I2 as catalyst,AgNTf2 as cocatalyst,AgOAc as additive,[BAIM]NTf2 as solvent,and indole C-H bonds reacted for 24 h at room temperature.And 40(heterogeneous)aromatic nitrile compounds were synthesized and structurally characterized.Recycling experiments show that the catalytic system has good reusability and achieve green environmental protection.Through mechanism verification experiments,it was determined that the reaction was an electrophilic ionic reaction,and the precursor of the unnatural nucleobase fragment that appeared in remdesivir,a marketed drug for the treatment of COVID-19,was successfully synthesized by cyanation conversion.