Silver-Catalyzed Direct Synthesis of Trifluoromethylated Enaminopyridines and Isoquinolinones Employing Trifluorodiazoethane

This Letter reports a Ag-catalyzed three-component approach for the N-alkenylation of 2-aminopyridines employing aldehydes and trifluorodiazoethane. Unlike the known reactions of trifluorodiazoethane with imines, which generate Mannich adducts, aziridines, or triazolines depending on the substrates and conditions, this reaction, after Mannich addition, proceeds via a carbene formation and 1,2-aryl migration sequence to afford (E)-enaminopyridines. This surprising selectivity, which is effective for a wide range of aldehydes and 2-aminopyridines, has been subsequently explored to access trifluoromethylated isoquinolinones.