Kai‐Xuan Yang, Shu‐Fan He, Yu-Rou Huang, Tianyi Xu, Yexin Wang, Ke‐Xin Liu, L. Zhang, Wenying Ai, Daixi Li, Tao Shen
Oxygen, nitrogen, and halogen-containing functional groups are ubiquitous in complex small molecules. The installation of multiple carbon-heteroatom bonds by the simultaneous functionalization of contiguous C-H/C-C bonds in a selective fashion is highly desirable in polymers degradation, skeletal editing, and petroleum cracking. However, achieving simultaneous, multi-site functionalization of relatively inert C-C/C-H bonds with precise control over site-, regio-, and oxidation-state selectivity remains challenging, particularly due to competing overoxidation and decomposition. Here we report the electrooxidative selective C-C fragmentation of aromatic radical cations for cascade benzylic di- and trifunctionalization in simple alkylarenes by iterative dehydrogenation and oxygenation. Central to our approach is the controlled formation of olefin intermediates in situ at a rate carefully balanced to prevent polymerization and overoxidation. This strategy provides efficient access to diverse, high-value di- or trifunctionalized products, including di- and triacetates, 2-oxazolines, 1,2-dibromoethanes, 1,3-dibromo-2-ols, and 2-(bromomethyl)oxiranes via controlled 4-electron, 6-electron, or 10-electron oxidation events. Notably, the selective synthesis of di- versus trifunctionalization products is readily controlled through judicious choice of acids and nucleophiles.