The introduction of fluorine atoms into organic molecules significantly changes their physical, chemical, and biological properties, and thus fluorinated compounds have found widespread applications in pharmaceuticals, agrochemicals as well as materials. Currently about 25% pharmaceuticals and 30% agrochemicals contain fluorine atoms. In addition, 18F-labeled organic compounds are clinically used as contrast agents for positron emission tomography.

    However, to date only a small number of natural occurring organic molecules contain fluorine, while most of fluorinated compounds have to be synthesized. Hence, the carbon – fluorine bond formation has become an important topic in organic synthesis.

    There are mainly two types of carbon – fluorine bonds, C(sp2)–F and C(sp3)–F bonds。Two types of methods are typically used for the C(sp3)–F bond formation: nucleophilic fluorination and electrophilic fluorination. As a comparison, the third method, radical fluorination, is not well understood and its synthetic value is yet to be uncovered.

    In the course of their investigation on catalytic Hunsdiecker reactions, the Chaozhong Li group at Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, discovered that, with the use of AgNO3 as the catalyst and Selectfluor as the fluorine source, aliphatic carboxylic acids underwent efficient decarboxylative fluorination in aqueous solution at room temperature to 65 oC to give the corresponding alkyl fluorides (J. Am. Chem. Soc. 2012, 134, 10401–10404).They then proposed for the first time the concept of “transition metal-assisted fluorine atom transfer” and the corresponding Ag(III)-mediated reaction mechanism.

    On the basis of the above results, the Li group further conducted radical aminofluorination (J. Am. Chem. Soc. 2013, 135, 4640–4643) and phosphonofluorination (J. Am. Chem. Soc. 2013, 135, 14082–14085) of unactivated alkenes. These reactions were performed in aqueous media under mild conditions with broad substrate scope and excellent regioselectivity and functional group compatibility. The results not only broaden the scope of radical fluorination, but also provide further support to the proposal of “silver-assisted fluorine atom transfer”. It is expected that silver-catalyzed radical fluorination reactions will play an important role in the synthesis of fluorinated organic molecules and fluoropolymers. The research in this area continues in the Li group.

    The above project was supported by the NSFC, MOST, STCSM and SIOC.

Proposed mechanism of radical phosphonofluorination and aminofluorination of unactivated alkenes.(Imaged by LI Chaozhong @ SIOC)