Enantioconvergent Synthesis of α‐Fluoroalkyl Alcohols Enabled by Photocatalytic Radical Brook Rearrangement
Yunhong Niu, Chenyu Jin, Xiaoqian He, Siqi Deng, Gang Zhou, Shanshan Liu, Xiao Shen
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.