Chen Qingyun, academician team of Shanghai Institute of organic Sciences, made progress in fluoroalkylation reagents derived from tetrafluoroethylene - β - sulfolactone

Cheap and efficient fluoroalkylation reagents have always been the research focus of organic fluorine chemistry Tetrafluoroethylene - β - sulfolactone, which is prepared by the reaction of tetrafluoroethylene (f 2C = CF 2) and sulfur trioxide (so 3), is one of the key raw materials for the manufacture of commercial Nafion ® ion exchange membrane The advantages of easy scale preparation and low price make all kinds of fluoroalkylation reagents developed from tetrafluoroethylene - β - sulfolactone derivatives have strong practicability and potential industrial application foundation In order to solve the problem of chromic acid pollution in chromium plating industry, Chen Qingyun, a Key Laboratory of Shanghai Institute of organic chemistry, Chinese Academy of Sciences, carried out the research on the synthesis of perfluorosulfonic acid from tetrafluoroethylene, and finally successfully developed the chromium fog inhibitor f-53b (ClCF 2 (CF 2) 5 OCF 2 CF 2 so 3 K) A unique synthesis method of fluorine-containing c-o-c-s bond intermediates has been developed On this basis, the fluoroalkylation reagents and methods derived from raw materials, intermediates, products and by-products are rich and colorful (chin J org Chem 2001, 21, 805) Among them, a series of practical and efficient trifluoromethylation reagents, difluoromethylation reagents and Difluorocarbene reagents have been developed based on the key raw material tetrafluoroethylene - β - sulfolactone (Fig 1, J fluorine chem 1995, 72, 241; tetrahedron 2013, 69, 10955; coord Chem Rev 2014, 261, 28) The representative fluorosulfonyldifluoroacetate (FSO 2cf 2CO 2me) is a widely used, efficient and cheap trifluoromethylation reagent (Chen reagent), through which the first case of catalytic trifluoromethylation of organic halogenated compounds (J.Chem SOC., chem Comm 1989, 705) was realized On this basis, the team has recently developed a new generation of trifluoromethylation reagent, copper (o 2ccf 2SO 2f) 2, to achieve trifluoromethylation of aryl halides in excellent yields under more mild conditions (RSC adv 2016, 6, 50250) However, many of the trifluoromethylation reagents derived from tetrafluoroethylene - β - sulfolactone are nucleophilic trifluoromethyl sources In the application process, the by-product sulfur dioxide may affect the reaction, but also bring environmental pollution problems, which is not conducive to the application and promotion of the reagents How to avoid or even use the by-product sulfur dioxide while realizing the efficient trifluoromethylation is the basis for the further application of such reagents Figure 1 Representative sources of fluoroalkylation reagents derived from tetrafluoroethylene - β - sulonolactone: in order to solve the above-mentioned challenges, Chen Qingyun's team plans to adopt the oxidation free radical reaction strategy , transform the nucleophilic trifluoromethyl species into the free radical trifluoromethyl species, then react with olefins to generate a new free radical a, further capture the by-product sulfur dioxide to obtain the intermediate B, and finally combine with the electrophilic fluorination reagent, so that the important alkylsulfonylfluoro compounds can be obtained at the same time of trifluoromethylation (Fig 2) Fig 2 Design source of trifluoromethylation of olefin oxidation free radicals: after a lot of efforts and experiments, the team of Shanghai Institute of organic chemistry, Chinese Academy of Sciences, synthesized silver fluosulfonyldifluoroacetate (Ag (O 2 CCF 2 SO 2 F)) by reacting with FSO 2 CF 2 CO 2 h and Ag 2 Co 3 -Under the action of NFSI, two important fluorine-containing functional groups, trifluoromethyl group and fluorosulfonyl group, were introduced into the molecule to realize trifluoromethyl fluorosulfonylation of non activated olefins (Fig 2, angel Chem Int ed 2017, 56, 15432; Chinese patent cn201710978989.7) The preliminary mechanism study also verified the oxidation free radical reaction strategy In this strategy, the application of a series of trifluoromethylation reagents derived from tetrafluoroethylene - β - sulfolactone is extended to the free radical trifluoromethylation reaction for the first time, and the by-product sulfur dioxide produced in the reaction is fully utilized to transform into an important sulfonylfluorogroup The reagent is cheap, easy to obtain, mild and efficient, and has strong universality It is expected to be used in the research and development of new fluorine-containing drugs in the future Figure 3 Preparation of Ag (O 2 CCF 2 SO 2 F) reagent and oxidative free radical trifluoromethylation of olefins Source: Shanghai Institute of organic chemistry, Chinese Academy of Sciences The above research work was mainly completed by Liu Chao, associate researcher, master student Liu Yong'an, Dr Wu Hao, Dr Zhao Gang, etc., and was supported by NSFC, Ministry of science and technology, Chinese Academy of Sciences and Shanghai Science and Technology Commission Paper link: http://onlinelibrary.wiley.com/doi/10.1002/anie.201709663/abstract introduction of academician Chen Qingyun: http://sourcedb.sioc.cas.cn/cn/expert/yxyjhx/200906/t20090621_.html introduction of academician Chen Qingyun and associate researcher Liu Chao: http://sourcedb.sioc.cas.cn/expert/fyjy/201303/t201304_.html associate researcher Liu Chao