Palladium-catalyzed Domino Coupling Cyclization Of 1,6-diynes With Aryl Halide

Many of nitrogen-containing heterocyclic compound is widely applicable at Molecular Biology, organic synthetic chemistry, medical chemistry, pesticide chemical. So it may be extremely significant using Domino reaction to synthesis the benzo[f]isoindole Core.In this paper, the domino reaction was investigated to benzo[f]isoindole Core via the aromatic C-H activation of 1,6-diynes with different aryl halides.The palladium catalyzed domino cyclization of 1,6-diynes to afford the benzo[f]isoindole Core with high yield was controlled by ortho-aromatic C-H functionalization. For example, substrate (a,b,c,d,e) was reacted with different aryl halides (1.2 equiv) in the presence of 2 mol % of palladium(II) catalyst and 4 mol % of Ph3P with of (n-Bu)3N (1.2 equiv) as an additive in DMF at 130°C. According to the results, we found electronic effect is great influence at domino cyclization of the yield. If the substituent of the benzene has electron-withdrawing group, Synthesis of the heterocyclic compounds with lower yields. In contrast, If the substituent of the benzene has electron-donating group, the production of the heterocyclic compounds with higher yields.In this paper, the reaction of by 1,6-diynes with different aryl halides(R-C6H4Br: R = p-COOCH₃,p-COCH₃,p-COOC₂H₅,p-Cl,p-CN,p-CHO,p-CH₃,α-naphthalenylBr)etc, it affords 25 fused heterocyclic compounds.This paper, fused polycyclic heterocycles such as benzo[f]isoindole and its derivatives were gained efficiently through Domino C-C bond formations. It would provided the good method for synthesis of many natural products, formation of the complicated structure, and preparation of the optics activity and the biological activity matters.