Research group of Professor Yi Wenbin of Nanjing University of science and technology: new application of cf3so2cl -- promoting direct chlorination of alkenes and alkynes - trifluoromethylthiolation reaction

The bifunctional reaction of alkenes and alkynes with fluorine-containing groups is a hot topic in the field of organic fluorine chemistry Trifluoromethyl sulfur group is one of the most lipophilic fluorine-containing groups The introduction of this group into drug and pesticide molecules can change the molecular pharmacokinetics and physicochemical properties Therefore, how to effectively introduce trifluoromethyl sulfur group into drug and pesticide molecules has become a research hotspot in the field of organic fluorine chemistry in recent years Recently, Professor Yi Wenbin's research group of Nanjing University of science and technology and Professor Wei Zhang (Zhang Wei) of UMass Boston have successfully realized trifluoromethylsulfonyl chloride (cf3so2 CL) the new application of this classical reagent is to promote the direct chlorination of alkenes and alkynes to trifluoromethyl sulfurization This bifunctional reaction condition is mild and does not need additional chlorine source (DOI: 10.1021 / ACS Orglett 8b00581) Brief introduction of Yi Wenbin's research group there are 1 associate professor, 1 lecturer, 1 experimenter, 10 doctoral students and 5 Master's students in the research group of Yi Wenbin, School of chemical engineering, Nanjing University of science and technology The research group has long been committed to the basic research on the principle, design and application of fluorine-containing functional groups in the field of fine chemicals and medicine In recent years, the research direction is mainly focused on the reduction of trifluoromethylthiolation, and the relevant results are published in the journals of angelw Chem Int ed., etc., which to some extent accelerated the industrialization process of trifluoromethylthiolation Brief introduction of Professor Yi Wenbin, professor and doctoral supervisor of School of chemical engineering, Nanjing University of science and technology The research field is mainly organic fluorine chemistry In recent years, he has published more than 20 papers in the international famous journals such as angelw Chem Int ed., green chem., org Lett., adv synth Catalyst., etc as the corresponding author or the first author He has won one third prize of 2015 Jiangsu Science and Technology Progress Award (ranking first), and was selected as the young and middle-aged academic leader of Jiangsu University Blue project and the "six talent peaks" high-level talents of Jiangsu Province Cutting edge scientific research achievements: the new use of CF 3so2cl - to promote the direct chlorination of alkenes and alkynes - trifluoromethylthiolation of alkenes - trifluoromethylthiolation of alkenes is a very useful bifunctional reaction, because halogen atoms can be easily converted into amino, alkyl, alkenyl, alkoxy and other groups Billard group first reported the chlorination of Cyclohexene with trifluoromethyl thiol amide as SCF 3 source and HCl as chlorine source Then they reported a similar method with tmscl as chlorine source Trifluoromethylsulfonyl chloride (cf3so2cl) is a cheap and versatile industrial chemical Shibata group and Yi Wenbin group in Japan reported that this reagent was used in direct trifluoromethylsulfonation almost at the same time On the basis of this study, the author envisages that trifluoromethylsulfonyl chloride (cf3so2cl) can be developed as a direct chlorination trifluoromethylsulfonation reagent without other chlorine sources (Figure 1) Figure 1 The use of trifluoromethylsulfonyl chloride (CF 3so2 CL) (source: org Lett.) after preliminary study, the author optimized the reaction conditions with p-methylstyrene 1A as the model substrate (Figure 2) It was found that the type of solvent, the type of reducing agent and the amount of CF 3So 2Cl all had great influence on the yield of the reaction After a series of screening, the optimum reaction conditions were determined: the molar ratio of olefin to cf3so2cl and PPh3 was 1:2:3, DMF was the solvent, and the reaction yield could reach 90% at 90 ℃ for 4 hours Fig 2 The optimization of reaction conditions (source: org Lett.) substrate applicability study shows that (Fig 3), when there is electron donor group or electron acceptor group in styrene, the reaction can obtain the target product with a better yield, but the presence of electron acceptor group can significantly reduce the reaction yield, which is also one of the typical characteristics of electrophilic reaction The reaction applicability of ortho, meta substituted styrene, naphthalene ethylene, phenylpropene, allylphenyl (sulfide) ether, n-allylphthalic acid amine and other end olefin substrates was good, but only a small amount of products were detected for 1,2-stilbene and other non end olefin substrates, because this non end olefin substrate was not suitable for the reaction system It is worth noting that in the study of regioselectivity of the reaction, the author found that the styrene type substrate mainly produces the addition product of martensite, while the non styrene type substrate will produce more addition product of anti horse type Figure 3 Substrate development of chlorination trifluoromethylthiolation reaction of olefins (source: org Lett.) for electrophilic addition reaction, alkynes are generally more difficult than olefins Based on the successful reaction of alkenes, the author also studied the chlorination trifluoromethylthiolation of alkynes (Fig 4) Under the similar reaction system, the reaction time was extended to 8 h, and the addition product with e configuration could be obtained in medium or higher yield Similar to the reaction results of olefins, the end alkynes have good applicability, and the non end alkynes are not suitable for the system; the phenylacetylene substrate mainly generates the addition products of martensite, and the non phenylacetylene substrate more generates the addition products of anti martensite Figure 4 Substrate expansion of chlorination trifluoromethylthiolation of alkynes (source: org Lett.) later, the author further studied the mechanism of this reaction (Figure 5) The control experiment shows that when the reaction is carried out in argon and the solvent is ultra dry DMF, the yield of the reaction will be significantly reduced; and the fluorine spectrum trace of the reaction shows that there is the formation of trifluoromethylsulfonic acid (cf3so3h) in the reaction process Based on the catalytic report of trifluoroacetic acid on the electrophilic addition reaction, the mechanism of the electrophilic addition reaction based on trifluoromethane sulfonic acid was proposed However, the high regioselectivity of the martensitic products produced by styrene is due to the electron conjugation of the benzene ring and the bridged sulfonium ion when Cl - is introduced into intermediate I, while the non styrene alkenes have no good conjugation effect The R group leads Cl - to the carbon containing less substituents in I ', resulting in the anti horse addition products Fig 5 Control experiment and possible reaction mechanism (source: org Lett.) difluoromethylthio (scf2h) is the electronic isorow of Oh or NH, many molecules containing scf2h can effectively show biological activity The author successfully extended the reaction to chlorination difluoromethylthiolation of alkenes and alkynes with difluoromethylsulfonyl chloride (cf2hso2cl) (Fig 6) The result of the reaction is similar to that of chlorination trifluoromethylthiolation Figure 6 Chlorination difluoromethylthiolation of alkenes and alkynes (source: org Lett.) Yi Wenbin's research group developed a simple and effective method, using CF 3so2cl as a bifunctional reagent to chlorinate difluoromethylthiolation of alkenes and alkynes, reducing CF 3so2cl by PPH 3 to form CF 3 for electrophilic addition The hydrolysis product cf3so3h in the reaction system can be used as catalyst, and the reaction can be successfully extended to the chlorination difluoromethylthiolation of cf2hso2cl The main advantages of this new method are simple and efficient reaction process, good atomic economy and mild reaction conditions The research results were recently published on organizational letters (ASAP, DOI: 10.1021 / ACS Orglett 8b00581) Dr Jiang Lvqi, lecturer of Nanjing University of science and technology, and Dr Ding Tianqi, doctoral candidate, were the co first authors of the paper The research work has been strongly supported by the National Natural Science Foundation, Jiangsu Natural Science Foundation, Jiangsu blue project, Jiangsu "six talent peaks" and other projects Nowadays, people and scientific research have been paid more and more attention in the economic life China has ushered in the "node of science and technology explosion" Behind the progress of science and technology is the work of countless scientists In the field of chemistry, in the context of the pursuit of innovation driven, international cooperation has been strengthened, the influence of Returned Scholars in the field of R & D has become increasingly prominent, and many excellent research groups have emerged in China For this reason, CBG information adopts the 1 + X reporting mechanism CBG information, chembeango app, chembeango official microblog, CBG wechat subscription number and other platforms jointly launch the column of "people and scientific research", approach the domestic representative research group, pay attention to their research, listen to their stories, record their demeanor, and explore their scientific research spirit.