Synthesis and Cytotoxic Evaluation of N-Aroylureas through Rhodium(III)-Catalyzed C−H Functionalization of Indolines with Isocyanates

The rhodium(III)-catalyzed C−H amidation and subsequent C−N bond formation reaction of indolines with aryl and alkyl isocyanates at room temperature are reported. These transformations allow the generation of N-aroylurea functionality at the C7-position of indolines, which is known as a crucial scaffold found in biologically active molecules. In addition, the synthesis of pyrroloindolidione derivatives is also described through sequential C6-amidation reaction and intramolecular cyclization of C7-amidated indolines. All synthesized products were evaluated for in vitro cytotoxic effect against human prostate adenocarcinoma cells (DU145), human breast cancer cells (MCF-7), and triple negative human breast cancer cells (MDA-MB-231), respectively. Notably, compounds 4 d and 4 e with linear alkyl side chains were found to be highly cytotoxic, which is comparable to that of anticancer doxorubicin and cisplatin as positive controls. (Figure presented.).