Brønsted acid- and Ni(ii)-catalyzed C–H oxidation/rearrangement of cyclotriveratrylenes (CTVs) to cyclic and acyclic quinones as potential anti-cancer agents

Abstract

This paper describes a simple and practical protocol for the direct synthesis of acyclic and cyclic quinone derivatives via an acid-promoted nickel(II)-catalyzed inner rim C–H oxidation of cyclotriveratrylene (CTV) and its analogues. The cyclic quinone derivatives resulted from trimethoxy-cyclotriveratrylene (TCTV) through C–C bond formation via intramolecular ipso substitution followed by subsequent anionic rearrangement containing stereo-vicinal quaternary centers. The DFT calculations strongly support the experimental findings and reveal the role of Brønsted acids in the C–H bond activation of CTV. All the newly synthesized compounds were screened for their in vitro anti-cancer activity using colorimetric SRB assay analysis. Among them, compounds 3a, 3d, 3h, 4a, 4b, 4c and 4e exhibited moderate anticancer activity against A549, HCT-116, PC-3, MDA-MB-231, HEK-293 and SW620 human cancer cell lines.