Palladium(?) Acetate Catalyzed C-C Bond-Formation For Synthesis Of Isoindigos

The bisindole-2-one skeleton is an important structural framework found not only in natural products but also in a number of synthetic bioactive compounds.Additionally,bisindol-2-ones have important applications in the synthesis of material.Transition-metal-catalyzed C-H functionalization and C-C bond formation process is undoubtedly a powerful tool for the construction of N-containing heterocycles.Here,we have disclosed an unprecedented approach for the construction of a series of?E?-bisindole-2-ones from the diarylbut-2-ynediamides via a palladium?II?-catalyzed intramolecular C-H functionalization and C-C bond-formation protocol.The method is practically useful and operationally convenient to perform.The reaction features extremely mild reaction conditions,room temperature,green oxidant.Through optimize the reaction conditions we concluded that 10 mol%of Pd?OAc?₂ as catalyst,air as the oxidant and 2 equivalents of NaOAc as additive in DMF at room temperature.We also investigate the generality of this newly established protocol.A variety of diarylbut-2-ynediamides were investigated under the optimized conditions.We also used our method realizing the synthesis of isoindigo and meisoindigo which are two important pharmaceutical agents found to offer effective treatment for chronic myeloid leukemia.Based on the k_H/k_D value of the kinetic experiment for electronic effect study and competitive experiment we tentatively postulated two possible mechanistic pathways for this domino reaction.