Enantioconvergent Synthesis of α‐Fluoroalkyl Alcohols Enabled by Photocatalytic Radical Brook Rearrangement
Year: 2025
Type: article
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.
Authors: Yunhong Niu, Chenyu Jin, Xiaoqian He, Shenna Deng, Gang Zhou, Shanshan Liu, Xiao Shen
Institution: Wuhan University
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: bronze
Funders: National Natural Science Foundation of China, China Postdoctoral Science Foundation, Wuhan University, Southern University of Science and Technology, National Key Research and Development Program of China, Shenzhen Science and Technology Innovation Program, Basic and Applied Basic Research Foundation of Guangdong Province
OpenAlex ID: W4410370948