Synthesis of Indolo[2,3/3,2-c]quinoline through Complementary PIDA/BF₃·OEt₂ as Well as Pd(0)-Mediated Intramolecular Cyclization of Isomeric N-((Aryl)-N-(phenylsulfonyl)indolyl)methylbenzenesulfonamides

Abstract

Herein, a straightforward facile synthesis of indolo[2,3-c]quinoline analogues was reported from 2-arylamino(phenylsulfonyl)methylindoles involving PIDA/BF3·OEt2-mediated intramolecular dehydrogenative coupling (IDC) as a key step. Even though isomeric 3-arylamino(phenylsulfonyl)methylindoles, upon interaction with PIDA/BF3·OEt2, led to complications, synthesis of the indolo[3,2-c]quinoline framework could be easily achieved from N-(2-iodoaryl)-N-indolylmethylbenzenesulfonamide by employing a Pd(0)-mediated intramolecular cyclization reaction. Under identical conditions, synthesis of indolo[2,3-c]quinolines was also accomplished from the respective N-(2-iodoaryl)-N-indolylmethylbenzenesulfonamides. The SRB assay of fluorine-bound indoloquinolines displayed nanomolar-level cytotoxicity against a nonsmall lung cancer cell line, NCI-H460.