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.

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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

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article

Enantioconvergent Synthesis of α‐Fluoroalkyl Alcohols Enabled by Photocatalytic Radical Brook Rearrangement

Gang Zhou, Xiao Shen, Xiaoqian He, Yunhong Niu et al.
17 citations
Angewandte Chemie International Edition
Radical Photochemical Reactions
15.91
article

Enantioconvergent Synthesis of α‐Fluoroalkyl Alcohols Enabled by Photocatalytic Radical Brook Rearrangement

Gang Zhou, Xiao Shen, Xiaoqian He, Yunhong Niu, Chenyu Jin, Shanshan Liu, Siqi Deng
article en
17 citations

Abstract

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.

Angewandte Chemie International EditionVol. 64(30)
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)
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
Clean water and sanitation
Openalex Percentile: Top 1%
Radical Photochemical Reactions
15.91
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