Pd(II)-Catalyzed [5+2] Cyclization of N-Triflyl Aryl Indoles and & alpha;,& gamma;-Substituted Allenoates: A Route to Indole-Fused Benzodiazepines

A Pd(II)-catalyzed [5 + 2] annulation between N-triflyl aryl indoles and & alpha;,& gamma;-substituted allenoatesfor the synthesis of indole-fused benzodiazepines is reported. Thisprotocol is highly efficient when N-acetylated valineamino acid and DMSO have been used as ligand and cosolvent, respectively.The substrate scope can be further extended to disubstituted allenoates.A reaction mechanism has been proposed based on the mechanistic studies.Mechanistically, the N-acetylated valine amino acidligand accelerates C-H activation of the C(sp(2))-Hbond. Consequent cyclopalladation leads to the formation of a six-memberedpalladacycle. Subsequent coordination and migratory insertion of anallenoate forms the possible eight-membered intermediate. Reductiveelimination followed by a [1,3]-H shift results in the indole-fusedbenzodiazepines.