Direct Deoxyfluorination of Alcohols with KF as the Fluorine Source
Jun Xu, Chao Peng, Bolin Yao, Hua-Jian Xu* and Qiang Xie*
*Hefei University of Technology, Hefei 230009; University of
Science and Technology of China, Hefei 230001, P. R. China,
Email: hjxu
hfut.edu.cn, xieqiang1980ustc.edu.cn
J. Xu, C. Peng, B. Yao, H.-J. Xu, Q. Xie, J. Org. Chem., 2022, 87, 6471-6478.
DOI: 10.1021/acs.joc.2c00388
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Abstract
In situ generation of highly active CF3SO2F enables a deoxyfluorination of alcohols with KF as the fluorine source. This mild and fast reaction tolerates diverse functionalities, including halogen, nitro, ketone, ester, alkene, and alkyne.
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proposed mechanism
Details
This document details a method for the direct deoxyfluorination of alcohols using potassium fluoride (KF) as the fluorine source. The process involves the in situ generation of highly active CF3SO2F, which facilitates the transformation of alcohols into triflates, followed by their replacement with a fluorine anion. This method is notable for its mild conditions, short reaction time, and broad substrate scope, making it an excellent choice for constructing C−F bonds. The introduction of C−F bonds into organic molecules enhances their chemical, physical, and biological properties, which is significant in pharmaceuticals, agrochemicals, and materials discovery. The method tolerates diverse functionalities and is highly selective, particularly against elimination reactions. It is also operationally simple and scalable, demonstrating high efficiency and compatibility with various functional groups and complex bioactive molecules. The study highlights the potential of this method for late-stage modification of drug-like molecules and natural products, providing a valuable tool for synthetic chemistry. The research was supported by the National Natural Science Foundation of China and other institutions, with no competing financial interests declared by the authors.
Key Words
alkyl fluorides, benzyl fluorides
ID: J42-Y2022
