The Rh(III)-catalyzed site-selective C-H alkylation of azobenzenes with internal olefins, such as maleimides, maleates and fumarates, followed by reductive intramolecular cyclization is described. A cationic rhodium catalyst in the presence of acetic acid additive in DCE solvent was found to be the optimal catalytic system for the synthesis of ortho-alkylated azobenzenes, which smoothly underwent the annulation reaction leading to the formation of C3-functionalized oxindoles in the presence of zinc powder and acetic acid. Actually, oxindole scaffold has been recognized as a ubiquitous heterocycle found in various natural compounds and synthetic products with medicinal applications. Particularly noteworthy was the resulting 1-amino-indolic framework, which represents a biologically important scaffold found in various synthetic molecules. Thus, the synthesized oxindoles have been screened cytotoxicity against human prostate adenocarcinoma cell lines (LNCaP), human breast cancer cell lines (MCF-7), human ovarian cancer cell lines (SKOV3), human lung carcinoma cell lines (A459) and human renal adenocarcinoma cell lines (786-O). With a rational design based on C-H alkylation and subsequent annulation process, we herein reported efficient access to the construction of oxindoles through Rh(III)-catalyzed site-selective alkylation of azobenzenes and internal olefins, such as maleimides, maleates and fumarates, followed by reductive intramolecular cyclization. The formed oxindole framework could be also an important architecture towards the development of novel bioactive molecules. Notably, some synthesized products were found to display potent anti-tumor activity.

Synthesis of oxindole derivatives via C-H alkylation and intramolecular cyclization: Access to Hit compound for anti-tumor agent

2019 Spring National Meeting

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