Nickel-Catalyzed Cross-Coupling of Functionalized Difluoromethyl Bromides and Chlorides with Aryl Boronic Acids: A General Method for Difluoroalkylated Arenes†
Yu-Lan Xiao
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032 (China)
Search for more papers by this authorWen-Hao Guo
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032 (China)
Search for more papers by this authorGuo-Zhen He
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032 (China)
Search for more papers by this authorQiang Pan
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032 (China)
Search for more papers by this authorCorresponding Author
Prof. Dr. Xingang Zhang
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032 (China)
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032 (China)Search for more papers by this authorYu-Lan Xiao
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032 (China)
Search for more papers by this authorWen-Hao Guo
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032 (China)
Search for more papers by this authorGuo-Zhen He
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032 (China)
Search for more papers by this authorQiang Pan
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032 (China)
Search for more papers by this authorCorresponding Author
Prof. Dr. Xingang Zhang
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032 (China)
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032 (China)Search for more papers by this authorThis work was financially supported by the National Basic Research Program of China (973 Program) (No. 2012CB821600), the NSFC (21172242 and 21332010), and SIOC.
Graphical Abstract
Simple and easy: The first example of a nickel-catalyzed difluoroalkylation of aryl boronic acids with functionalized difluoromethyl bromides and chlorides has been developed. This cross-coupling process features a broad substrate scope, a cheap catalyst, and excellent functional-group compatibility.
Abstract
Transition-metal-catalyzed difluoroalkylation of aromatics remains challenging despite the importance of difluoroalkylated arenes in medicinal chemistry. Herein, the first successful example of nickel-catalyzed difluoroalkylation of aryl boronic acids is described. The reaction allows access to a variety of functionalized difluoromethyl bromides and chlorides, and paves the way to highly cost-efficient synthesis of a wide range of difluoroalkylated arenes. The notable features of this protocol are its high generality, excellent functional-group compatibility, low-cost nickel-catalyst, and practicality for gram-scale production, thus providing a facile method for applications in drug discovery and development.
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