Sharpless and Dong Jiajia work together to open the new gate of click chemistry of sufex: the ever reactive sulfonylimidazolium salt

Since 2001 Nobel Prize winner Karl Barry Sharpless put forward the concept of "click chemistry", click chemistry has been widely used in the fields of chemistry, chemistry, biology and materials (http://www.chembergo.com/news/art? Id = 6144) Click chemistry is characterized by modular assembly of organic synthons, and useful properties are explored through heteroatom links Focusing on the reaction with strong thermodynamic driving force and consistent and controllable path is the inherent requirement of click chemistry development Among them, the most representative is copper (I) - catalyzed azide alkyne cycloaddition (cuaac) Figure 1 Cuaac in 2014, the Sharpless team of Scripps Institute met a new generation of "stars" in click chemistry: sulfur (VI) fluoride exchange (safex) Through the fringe acid base reactivity of svi-f functional group represented by sulfonylfluoride, it can achieve efficient and reliable linkage Since then, sufex chemistry has started a prairie fire A series of interesting discoveries have been made due to the special reactivity between the sufex compounds and the targets of small molecules, biomacromolecules and polymer molecules Sulfuryl fluoride (so 2F 2) gas is a thousand ton industrial product, which is widely used as fumigant to control termites In the presence of triethylamine or borax buffer, so 2F 2 can react selectively with a series of phenols at room temperature to quantitatively form aryl fluorosulfate (Fig 2, top) The discovery of so 2F 2 makes the sufex reaction widely used in the synthesis of polysulfate and polycarbonate The product fluorosulfate can covalently modify the protein side chain, so it becomes a powerful tool to study the protein function in complex biological environment Ar-oso2f, the intermediate of fluorination reaction between so 2F 2 and phenol, is a kind of haloid compound which can be used to construct C sp2-c and C sp2-n bonds In addition, so 2F 2 can also be used for the preparation of bis (fluorosulfonyl) imine anion, which is an expensive compound for the production of lithium-ion battery electrode materials Fig 2 The source of sufex reaction in which so 2F 2 and sulfonylimidazolium salts are involved: angel Chem Int ed although so 2F 2 has ideal reactivity and selectivity in sufex reaction, it faces several challenges as a laboratory reagent First of all, the operation of this toxic gas is difficult; second, the reaction effect of so 2F 2 with secondary amine is poor, the substrate is limited and the conditions are complex; third, so 2F 2 can not react with primary amine smoothly In view of the above limitations, it is very important to develop alternative reagents that are easy to obtain, easy to use and can realize the sulfonation of amines In May 2016, Sharpless signed a contract with Shanghai Institute of organic chemistry, Chinese Academy of Sciences to become a distinguished professor In July 2017, Professor Sharpless cooperated with Dong Jiajia, a researcher in the Key Laboratory of organic fluorine chemistry, and Dr Wu Peng of Scripps Research Institute to make a new breakthrough in the study of sufex reaction, that is to say, the anion fluoride salt [HF 2 -] can be used as a more efficient catalyst to promote sufex reaction and to synthesize polysulfate or polysulfonate polymer materials Relevant achievements were published in nature Chemistry (nat.chem 2017, 9, 1083) Recently, Professor Sharpless and researcher Dong Jiajia jointly published a paper again, which reported the strong ability of sulfonyl imidazolium salts in the preparation of sulfonates and sulfonamides It should be emphasized that such reagents can react efficiently with primary amines and secondary amines to form corresponding sulfonamides without using alkali This feature improves the click chemistry of sofex and greatly widens the application scope of substrate (Figure 2, bottom) Relevant papers were received by angelw Chem Int ed at the end of 2017 The papers are jointly as Guo Taijie, Meng Genyi and Zhan xiongjie In the early stage of the study, the author carried out the synthesis of sulfonylimidazolium salts So 2F 2 reacts with 2-methylimidazole to form 2-1 through sufex The use of inorganic base Na 2CO 3 is the key to realize this transformation 2-1 does not need to be separated, but directly converted to 3-1 under the action of Ch 2Cl2 and meotf (Fig 3a) The synthesis process of 3-1 is simple, and it can easily realize the preparation at the level of 100 grams The product is white powder (Fig 3b) In addition, the data of thermal stability, half-life in water and long-term stability of 3-1 were tested to determine whether it can be stored and used for a long time Fig 3.3-1: synthesis, characterization and stability test source: angelw Chem Int ed with a new sulfonyl fluoride transfer reagent, the author uses it as a source of so 2F 2 to react with various phenols and heterocyclic aryl hydroxides As shown in Fig 4, the yield of fluorosulfonate can reach good to excellent when reacting at room temperature for 1 hour; the substrate with potential resistance, the substrate containing electron absorption or electron supply can be compatible with such reactions It was also found that the reactivity of 3-1 with primary and secondary amines was much better than that of so 2F 2 It can be seen from Figure 5 that compared with the reaction of so 2F 2, the reaction of 3-1 with secondary amine does not need to add organic base, and the reaction time is short, the yield is high, and the substrate is widely used On the other hand, the primary amines which can not be reacted by so 2F 2, 3-1, also show good reactivity It can be seen from Fig 6 that a variety of anilines or aliphatic primary amines can be converted into NH sulfamoyl fluoride under the action of 3-1, which is rarely reported in the literature; however, if the equivalent of 3-1 is increased and tea is added at the same time, difluorosulfonylation products (such as 10-1) can be obtained It is worth mentioning that 3-1 preferentially reacts with amino group in the presence of amino group and phenolic hydroxyl group to form product 9-6, which is opposite to the selectivity of so 2F 2 Figure 4.3-1 reaction source with phenol: angelw Chem Int ed figure 5.3-1 reaction source with secondary amine: angelw Chem Int ed figure 6.3-1 reaction source with primary amine: angelw Chem Int ed summary: Sharpless and Dong Jiajia team developed a new type of f-so 2 + donor, sulfonyl fluoride imidazolium salt (3-1 ）This reagent shows extraordinary reactivity, selectivity and scope of application, which opens a new door for the click chemistry of sufex Paper link: http://onlinelibrary.wiley.com/doi/10.1002/anie.201712429/abstract key experiment of organic fluorine chemistry Karl Barry Sharpless research group: http://www.fluorinelab.ac.cn/ketizu.jsp? Name = Karl% 20barry% 20sharpless key experiment of organic fluorine chemistry Dong Jiajia research group: http://www.fluorinelab.ac.cn/ketizu.jsp? Name =% E8% 91% A3% E4% BD% B3% E5% AE% B6 Dong Jiajia researcher and Professor Sharpless source: Key Laboratory of organic fluorine chemistry