Construction of sterically congested oxindole derivatives <i>via</i> visible-light-induced radical-coupling
Yanling Shen, Ning Lei, Cong Lu, Dailin Xi, Xinxin Geng, Tao Pan, Zhishan Su, Ke Zheng
Abstract
The oxindole scaffold represents an important structural feature in many natural products and pharmaceutically relevant molecules. Herein, we report a visible-light-induced modular methodology for the synthesis of complex 3,3'-disubstituted oxindole derivatives. A library of valuable fluoroalkyl-containing highly sterically congested oxindole derivatives can be synthesized by a catalytic three-component radical coupling reaction under mild conditions (metal & photocatalyst free, >80 examples). This strategy shows high functional group tolerance and broad substrate compatibility (including a wide variety of terminal or non-terminal alkenes, conjugated dienes and enynes, and a broad array of polyfluoroalkyl iodide and oxindoles), which enables modular modification of complex drug-like compounds in one chemical step. The success of solar-driven transformation, large-scale synthesis, and the late-stage functionalization of bioactive molecules, as well as promising tumor-suppressing biological activities, highlights the potential for practical applications of this strategy. Mechanistic investigations, including a series of control experiments, UV-vis spectroscopy and DFT calculations, suggest that the reaction underwent a sequential two-step radical-coupling process and the photosensitive perfluoroalkyl benzyl iodides are key intermediates in the transformation.