Angelw, Li Zhengming group and ye mengchun group, Nankai University: ligand promoted hydrofluorination of olefins catalyzed by iron

The author: jieyongtao, a doctoral student, is widely used in medicine, pesticide, material science and other fields According to statistics, about 30% - 40% of pesticide molecules and 20% - 25% of medicine molecules on the market contain fluorine atoms The hydrofluorination of alkenes has become an effective method for the preparation of fluorine-containing organic compounds due to the low cost and easy availability of alkenes The hydrofluorination of alkenes can be divided into proton acid induced hydrofluorination and transition metal induced hydrofluorination (Fig 1a) For the proton acid induced hydrofluorination reaction (Fig 1a, path I), due to the strong acid condition, there is the compatibility problem of functional groups In this context, transition metal induced hydrofluorination of the second kind has attracted more and more attention (Fig 1a, path II) In 2012, Boger group first reported the hydrofluorination of olefins mediated by Fe (III) / NaBH 4 (Fig 1b) (J am Chem SOC 2012, 134, 13588) The reaction has excellent functional compatibility and a wide range of substrates Various functional groups such as amino group, hydroxy group, carboxyl group and ester group can be compatible, and can be used for hydrofluorination of natural products containing olefins However, the reaction needs equivalent metal iron, which not only increases the reaction cost, but also causes a great environmental burden In order to obtain a more economical method, great efforts have been made to reduce the amount of metal used to achieve metal catalyzed hydrofluorination of olefins In 2013, Hiroya group realized hydrofluorination of olefins catalyzed by cobalt (org Lett 2013, 15, 5158) Then, in 2014, Gouverneur group realized the hydrofluorination of olefins catalyzed by palladium (angelw Chem Int ed 2014, 53, 4181) However, the hydrofluorination of olefins catalyzed by cheap metal iron has not been realized Fig 1 Hydrofluorination of unactivated olefins (source: angelw Chem Int ed.) recently, Li Zhengming and ye mengchun of the National Key Laboratory of elemental organic, Nankai University successfully realized the iron catalyzed hydrofluorination of olefins (Fig 1c) by designing a new reaction strategy Relevant research results were published in angelw Chem Int ed (DOI: 10.1002 / anie 201902607) The author conjectures that by using n-fluorobenzenesulfonylimide (NFSI) as the fluorine source, the electron deficient sulfonamide radical will be produced in the reaction process, which is easy to get an electron from metal iron and turn into sulfonamide anion, thus realizing the catalytic cycle of iron (Fig 2) Figure 2 Design of the reaction process (source: angelw Chem Int ed.) however, the initial condition screening was not successful The author investigated 16 kinds of common iron and found no product The author hopes to control the activity of metals by adding ligands to realize the hydrofluorination of olefins catalyzed by iron Firstly, nitrogen-containing ligands, organophosphine ligands and carbene ligands were investigated, but the target products were still not obtained Finally, the iron catalyzed hydrofluorination of olefins was successfully realized by using a group of amino bisphenol ligands The specific screening conditions are as follows (Fig 3): Fig 3 The screening of reaction conditions (source: angelw Chem Int ed.) substrate expansion shows that the reaction has relatively good activity for monosubstituted olefins, disubstituted olefins and trisubstituted olefins (Fig 3) And the reaction also has good functional group compatibility It is very compatible with ester group, ether, amide, aldehyde, ketone, hydroxyl group, heterocycle and bioactive molecules, and can be used to synthesize various fluorine-containing organic compounds The following are representative substrates: Figure 4 Substrate development (source: angel Chem Int ed.) This achievement was recently published in angel Chem Int ed under the title of "living promoted Fe (III) - catalyzed hydrofluorination of alkenes" The first author of this paper is Xie Yongtao, a doctoral student from the school of chemistry, Nankai University The authors of this paper are Yongtao Xie, Peng Wei sun, Yuxin Li, Siwei Wang, mengchun ye *, Zhengming Li *.