TfOH-Catalyzed Cascade C-H/N-H Chemo-/Regioselective Annulation of Indole-2-carboxamides with Benzoquinones for the Construction of Anticancer Tetracyclic Indolo[2,3- c ]quinolinones.

An efficient TfOH-catalyzed cascade C-H/N-H annulation of indole-2-carboxamides with benzoquinones has been developed for the synthesis of tetracyclic indolo[2,3- c ]quinolinones. This reaction exhibits excellent chemo-/regioselectivity, achieving functionalization of the C-3 of indole and N-H of the amide moiety to form the new C-C and C-N bonds. Various expected products were synthesized from readily available starting materials in good to high yields with a wide substrate scope and good functional group tolerance. Among all synthetic products, 3d showed the most potent cytotoxicity toward the 4T1 cancer cell line with an IC 50 value of 0.62 ± 0.05 μM. In vivo study demonstrated that 3d remarkably suppressed 4T1 xenograft tumor growth without body weight loss.