Cyanomethylation Of Copper - Catalyzed Aryl - Tetrahydroisoquinoline

The cross-dehydrogenative coupling reaction of aryl tetrahydroisoquinolines and acetonitrile was developed, which focused on the activation of C-H bond and forming C-C bond via exploring a certain oxidation system containing copper salt. We used copper salt CuCl2 as the catalyst, 2,2,6,6-tetramethyl-1-piperidinyloxy free radical as the oxidant, caesium carbonate, which is of relatively weak basicity, as the base to realize the cyanomethylation at the C-1 position of N-aryl tetrahydroquinolines successfully, and acteonitrile served as the coupling partner and the solvent. It has good yields and a broad substrate scope. Both common electron-donating groups and electron-withdrawing groups in the N-aromatic rings are compatible. And the substituents on the N atom could be some heterocyclic groups and ring-fused groups. We investigated the mechanism by GC, and we found that 2,2,6,6-tetramethylpiperidin-1-ol could be generated in the process.Ultimately we thought that under the action of the copper salt and the base acetonitrile could yield the nucleophile, cyanomethyl anion, to couple with the imine cation, which generated from the oxidation of aryl tetrahydroisoquinolines with the copper salt and 2,2,6,6-tetramethyl-1-piperidinyloxy free radical. That acetonitrile was used as the pronucleophile to couple with tetrahydroisoquinolines was reported for the first time.