Electrooxidative C‐C Fragmentation of Aromatic Radical Cations for Cascade Benzylic Multifunctionalization
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.
Authors
- Wenying Ai (ORCID: https://orcid.org/0000-0001-5488-0048)
- L. Zhang
- Tianyi Xu (ORCID: https://orcid.org/0009-0003-6390-7005)
- Daixi Li (ORCID: https://orcid.org/0000-0001-7293-2008)
- Tao Shen (ORCID: https://orcid.org/0000-0002-2028-152X)
- Yexin Wang
- Ke‐Xin Liu
- Yu‐Rou Huang
- Kai‐Xuan Yang
- Shu‐Fan He
Institutions
- Shanghai Innovative Research Center of Traditional Chinese Medicine (CN)
- Zhengzhou University (CN)
- Henan University of Engineering (CN)
- Zhongshan Hospital of Xiamen University (CN)
- Huanghuai University (CN)
Publication Details
- Journal
- Angewandte Chemie International Edition
- Published
- 2026-02-09
- DOI
- https://doi.org/10.1002/anie.202522498
- Primary Topic
- Radical Photochemical Reactions
- Type
- article
- Field-Weighted Citation Impact
- 0.00