Dearomative difunctionalization of arenes via highly selective radical relay reactions†

Abstract

Dearomatization of arenes emerges as a reliable strategy for crafting intricate 3D polycyclic frameworks. Nonetheless, the development of an efficient method for dearomatization across diverse arenes remains a formidable challenge, particularly in the case of unactivated benzene. In this study, we present a facile dearomative difunctionalization approach for unactivated arenes through a highly selective radical relay reaction. The reaction operates under mild conditions, devoid of metals, photocatalysts, and additives. This method exhibits a broad substrate scope and exceptional functional group tolerance, successfully transforming various aromatics, including inert naphthalene and benzene rings, indoles, pyrroles, benzofuran, and thiophene. Bioactivity assessments reveal a significant inhibitory effect of the synthesized complex polycyclic frameworks on HCT 116 cancer cells, with subsequent mouse experiments providing compelling evidence of its feasibility.