Hu Jinbo research group of Shanghai Institute of organic chemistry has made new progress in the research of fluorinated heteroarylsulfones

Fluorine-containing organic compounds are widely used in functional materials, medicine, pesticide and so on Therefore, it is an important research direction to introduce fluorine atoms and fluorine-containing fragments into organic molecules efficiently and selectively Hu Jinbo, a researcher in the Key Laboratory of Shanghai Institute of organic chemistry, Chinese Academy of Sciences, has been committed to the study of the unique fluorine atom substitution effect (fluorine effect) in organic chemistry, and has made a series of achievements in selective fluoroalkylation and fluoroalkenylation based on fluorine-containing sulfur-containing reagents (chem Rev 2015, 115, 765) In recent years, they have carried out in-depth research on the various reactions of fluorine-containing heteroarylsulfones, developed new fluorine-containing reagents and synthesis methods, and provided new tools and ideas for the selective synthesis of fluorine-containing organic compounds In 2010, the team reported for the first time that difluoromethyl (2-pyridyl) sulfone (2-pyso2cf2h), a new reagent, was used to deoxidize aldehydes and ketones (org Lett 2010, 12, 1444) It was not only the first time to capture the intermediate of fluorinated sulphonates in the reaction, but also to develop a new fluoroalkylation reaction Thanks to the unique regulation of 2-pyridyl, a heteroaryl group, 2-pyso2cf2h has become an important reagent for the conversion of carbonyl compounds into dicyclohydroolefins and the preparation of oligofluoroalkylsulphonates with important value in drug development, which is called "Hu's reagent or Hu reagent" by peers at home and abroad In 2015, They also used the mono fluoroalkyl (2-pyridyl) reagents developed by our team to react with aldehydes, and developed a liquid-liquid extraction method for the efficient separation of CIS and trans isomers of mono fluoroalkenes through the kinetic resolution of intermediate containing fluorosulfites in the process of decomposition into alkenes For the first time, they realized the "traceless" chemical separation of CIS and trans isomers of mono fluoroalkenes (j.am.chem.soc 2015,
137 , 5199 ）。
On this basis, the team used the reaction characteristics of fluorine-containing heteroarylsulfone to study the controllable production of fluoroalkyl radicals from fluoroalkyl sulfone Using the mild reaction conditions catalyzed by visible light oxidation-reduction, they realized the single electron transfer reduction of sulfolane for the first time, and developed the fluoroalkyl (2-benzothiazolyl) sulfone and the fluoroalkyl (2-pyridyl) sulfone into a new practical fluoroalkyl radical precursor (angel Chem Int ed 2016, 55, 2743), which laid a foundation for the study of free radical fluoroalkylation of sulfolane The single electron transfer reduction of f-heteroarylsulfone was used for cross coupling fluoroalkylation (source: J am Chem SOC.) recently, the team successfully developed the first iron catalyzed high-efficiency difluoroalkylation of aromatics or heteroaromatics (J am Chem SOC 2018, 140, 880) using f-heteroarylsulfone reagents For many years, transition metal catalyzed fluoroalkylation has been a research hotspot in the field of transition metal participated fluoroalkylation In 1969, British and Japanese scientists first reported the trifluoromethylation and perfluoroalkylation of aryliodide with copper powder In recent ten years, palladium and nickel catalyzed fluoroalkylation have also been rising rapidly, but iron catalyzed direct fluoroalkylation of aromatics is rarely reported They used cheap and easily available Fe (ACAC) 3 as catalyst, TMEDA as ligand, and their original 2-pyso2cf2h reagent to successfully realize the efficient difluoromethylation of arylzinc Through preliminary mechanism verification experiments, they found that free radical trapping agents or single electron transfer inhibitors can prevent the difluoromethylation Based on this, they proposed a reaction mechanism for the formation of difluoromethyl iron species via difluoromethyl radicals This is also the first cross coupling fluoroalkylation of fluoro heteroarylsulfone via rif-s bond breaking under the catalysis of transition metal The above work was supported by the Ministry of science and technology of the people's Republic of China, the National Natural Science Foundation of the people's Republic of China, the Chinese Academy of Sciences and the Shanghai Municipal Science and Technology Commission.