Diastereoselective Radical Cyclization of Imine and Olefin: Rapid Access to 1,2,3,4-Tetrahydroquinoline Scaffolds
Herein, we developed an intramolecular radical cyclization reaction between imines (or aldehydes) and olefins using Hantzsch ester as the reductant to enable the efficient and diastereoselective synthesis of 1,2,3,4-tetrahydroquinoline scaffolds with a high medicinal value. Deuteration experiments indicated that the radical intermediate abstracts a hydrogen atom directly from the 4 position of the Hantzsch ester, thereby ruling out the possibility of an anionic intermediate formation via the radical crossover pathway. A fast synthesis of BRD4 degraders and the elucidation of their cellular and enzymatic activities demonstrate the practicality of this method.
Authors
- Suping Zhang (ORCID: https://orcid.org/0000-0003-0564-895X)
- Gogu V. Surendra Babu
- Yuguo Wang (ORCID: https://orcid.org/0000-0003-2407-8112)
- Haihui Huang (ORCID: https://orcid.org/0000-0002-6546-969X)
- Mingliang Wang
- Guoqin Xia (ORCID: https://orcid.org/0000-0001-7666-9550)
- Pengli Zhang (ORCID: https://orcid.org/0000-0001-6065-4557)
- Weiguo Cao (ORCID: https://orcid.org/0000-0002-6482-2877)
- Jia Li (ORCID: https://orcid.org/0000-0002-1648-1465)
- Tingxuan Zeng (ORCID: https://orcid.org/0000-0003-4698-1601)
Institutions
- Guangzhou University of Chinese Medicine (CN)
- Nanjing University of Chinese Medicine (CN)
- Chinese Academy of Sciences (CN)
- Shanghai Institute of Materia Medica (CN)
- University of Chinese Academy of Sciences (CN)
Publication Details
- Journal
- Organic Letters
- Published
- 2025-05-06
- DOI
- https://doi.org/10.1021/acs.orglett.5c01242
- Citations
- 3
- Primary Topic
- Radical Photochemical Reactions
- Type
- article
- Field-Weighted Citation Impact
- 2.81
Funders
- National Natural Science Foundation of China
- Zhongshan Science and Technology Bureau