Synthesis of N-CF3 Amides and Ureas from N-CF3 Secondary Amines and Acyl Chlorides.

A general and traditional strategy for the construction of N-CF3 secondary amines/ureas from N-CF3 secondary amines via conventional amide bond formation is developed. This protocol exhibits broad functional group compatibility, straightforward execution, and operates under mild reaction conditions. RCO-OTf was generated in situ in the presence of acyl chlorides and AgOTf as a high reactive intermediate. Three drug-like N-CF3 amide derivatives, Leflunomide, Phenacetin and Flutolanil, were successfully synthesized, which demonstrated the ability to form N-CF3 derivatives using N-CF3 secondary amines as building blocks.