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Updated: May 16, 2026

Synthesis of a Borylated Ibuprofen Derivative Through Suzuki Cross-Coupling and Alkene Boracarboxylation Reactions
Published on: November 30, 2022
Nickel-Catalyzed Cross-Coupling of Arylboronic Acids with Ethyl 3-Bromo-2,2-difluoropropanoate
Yuheng Xiao1, Kehan Zhou1, Xin Liu1
1Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, P. R. China.
Abstract:
The difluoromethylene group is a key fluorinated moiety in drug design, capable of providing desirable physicochemical properties and bioactivity. Despite this importance, very few methods have been reported for the one-step synthesis of β-difluoroaryl propionate derivatives, which are valuable potential drug intermediates. Therefore, this study developed a nickel-catalyzed cross-coupling reaction that employs ethyl 3-bromo-2,2-difluoropropanoate as a novel fluoroalkylating agent with arylboronic acids. The developed method enabled the efficient construction of β-difluoroaryl propionates under mild conditions, and showcased broad substrate scope coupled with exceptional functional group tolerance. Thus, this work offers a simple and efficient synthetic route to access these valuable fluorine-containing frameworks.
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