Enantioconvergent Synthesis of α‐Fluoroalkyl Alcohols Enabled by Photocatalytic Radical Brook Rearrangement
While radical Brook rearrangement has emerged as a powerful strategy in modern organic synthesis, enantioselective cross coupling involving radical Brook rearrangement remains unexplored. Herein, we report a photocatalytic radical Brook rearrangement followed by cross-coupling with aryl/heteroaryl bromides, enabling the enantioconvergent construction of chiral α-fluoroalkyl alcohols. Key to this transformation is a radical relay process involving sequential generation of aryl cation radicals, alkoxy radicals, and carbon-centered radicals through Brook rearrangement. The reaction exhibits exceptional scope (>40 examples), outstanding enantiocontrol (up to 99% ee), and broad functional group tolerance. The synthetic utility is demonstrated through formal syntheses of bioactive Odanacatib and LX-1031, along with diverse downstream derivatizations.
Authors
- Gang Zhou (ORCID: https://orcid.org/0000-0003-4988-0814)
- Xiao Shen (ORCID: https://orcid.org/0000-0002-8675-1213)
- Xiaoqian He
- Yunhong Niu
- Chenyu Jin
- Shanshan Liu (ORCID: https://orcid.org/0000-0002-8446-7235)
- Siqi Deng (ORCID: https://orcid.org/0000-0002-4239-5843)
Institutions
- Wuhan University (CN)
- City University of Hong Kong, Shenzhen Research Institute (CN)
- EarthTech International (United States) (US)
- Hubei University (CN)
- Wuhan Institute of Technology (CN)
Publication Details
- Journal
- Angewandte Chemie International Edition
- Published
- 2025-05-14
- DOI
- https://doi.org/10.1002/anie.202507789
- Citations
- 17
- Primary Topic
- Radical Photochemical Reactions
- Type
- article
- Field-Weighted Citation Impact
- 15.91
Funders
- National Natural Science Foundation of China
- China Postdoctoral Science Foundation
- Wuhan University
- Southern University of Science and Technology
- Basic and Applied Basic Research Foundation of Guangdong Province