Photoredox-Catalyzed Modular Synthesis of ε-Lactams via Acrylamides Cyclization Enabled by Radical-Polar Crossover-Mediated Carbanion Trapping
A photocatalytic strategy for the direct synthesis of naphtho-fused ε-lactams from acrylamides is reported. This protocol leverages visible-light-induced single-electron-transfer oxidation of acrylamides to radical cations, followed by intramolecular electrophilic aromatic substitution and subsequent functionalization with external electrophiles. This methodology facilitates the one-step construction of functionalized ε-lactam derivatives with atom and step-economy. Notably, it demonstrates good compatibility with alternative electrophiles, including allyl bromide and aryl aldehydes, and further supports downstream product derivatization, thereby underscoring its significant potential for application in the synthesis of complex molecules. Mechanistic studies confirm a radical pathway involving 1,5-hydrogen atom transfer and carbanion intermediates, presenting a novel approach to lactam scaffolds.
Authors
- Fanyuanhang Yang
- Weiping Su
- Denghui Ma
- Zheng Liu (ORCID: https://orcid.org/0000-0002-4252-4617)
- Ying Xu (ORCID: https://orcid.org/0000-0002-2401-7718)
- Yan Gao
- Jing Zhang (ORCID: https://orcid.org/0000-0003-3064-7625)
- Haoran Huang (ORCID: https://orcid.org/0000-0002-6124-3175)
Institutions
- Ningbo University of Technology (CN)
- Chinese Academy of Sciences (CN)
- ShanghaiTech University (CN)
- Fujian Institute of Research on the Structure of Matter (CN)
Publication Details
- Journal
- Organic Letters
- Published
- 2026-02-25
- DOI
- https://doi.org/10.1021/acs.orglett.6c00053
- Primary Topic
- Radical Photochemical Reactions
- Type
- article
- Field-Weighted Citation Impact
- 0.00