Research group of Professor Yi Wenbin of Nanjing University of science and technology: new application of sulfonyl chloride direct chlorination sulfurization of Alkynes

Lead vinyl sulfide is a common intermediate in organic synthesis and material chemistry Many natural products and bioactive compounds also contain vinyl sulfide Among them, β - haloalkenyl sulfide is of great significance, because the halogen part can be converted into a variety of alkenyl sulfide Recently, Professor Yi Wenbin's research group of Nanjing University of science and technology has successfully realized the new use of sulfonyl chloride, a classical reagent, direct chlorination sulfurization of alkynes The bifunctional reaction conditions are mild and no additional chlorine source is required Relevant research results were published in org Lett (DOI: 10.1021/acs.orglett.8b02929) Professor Yi Wenbin's cutting-edge scientific research achievements: the new use of sulfonyl chloride direct chlorination sulfurization of alkynes the traditional method for the synthesis of β - haloalkenyl sulfide is realized by the addition reaction of thiohalide and alkyne Modena and Benati reported the bifunctional reactions of thiochloride and thiobromine on alkynes Nishihara's team reported the regioselective and stereoselective bifunctional reactions of thiochloride to alkynes catalyzed by palladium and iron However, the disadvantages of the sulfur halides used in these reactions are obvious: on the one hand, the sulfur halides are very unstable, and are generally synthesized from smelly mercaptans or highly toxic chlorine or bromine; on the other hand, the types of sulfur halides are very limited, which greatly reduces the attraction of this reaction Sulfonyl chloride, as a cheap material on the market, has been widely used as a protective group and a leaving group formed by sulfinylation, sulfonation, chlorosulfonylation reagent or C-C bond Before that, Professor Yi Wenbin's research team developed the chlorination trifluoromethyl sulfonyl chloride to olefins and alkynes This time, they developed the common sulfonyl chloride as the bifunctional reagent of chlorination sulfurization Figure 1 Optimization of reaction conditions (source: org Lett.) after preliminary study, the author optimized the reaction conditions with p-methylphenylacetylene 1a and benzenesulfonyl chloride 2A as model substrates (Figure 1) It is found that copper salt has a good catalytic effect on the reaction, of which CuCl has the best effect; the type of solvent and the reaction temperature will have a great impact on the reaction yield After a series of screening, the author determined the best reaction conditions: the molar ratio of alkyne, benzenesulfonyl chloride and PPH 3 is 1:2:4, 10% CuCl is the catalyst, DMF is the solvent, the reaction time is 4 hours at 85 ℃, the reaction yield can reach 85% Figure 2 Alkyne substrate development (source: org Lett.) next, the author will react a series of phenylacetylene containing electron donor groups (methyl, n-butyl and phenyl) and electron acceptor groups (halogen, trifluoromethyl, cyano, nitro and ester) with 2a to obtain a product with medium to excellent yield (Figure 2) Non phenylacetylene alkynes and aliphatic alkynes were also successfully obtained Fig 3 Further development of internal alkyne substrate (source: org Lett.), the author found that in addition to terminal alkynes, internal alkyne is also suitable for this reaction (Fig 3) The yield of symmetric internal alkyne reaction is good, but asymmetric internal alkyne may produce two isomers with opposite addition mode Figure 4 Control experiment (source: org Lett.) later, the author conducted control experiment (Figure 4) According to previous reports, benzene sulfonyl chloride will generate benzene sulfur chloride under the reduction of PPH 3, and the control experiment also shows that CuCl has a catalytic effect on the addition of benzene sulfur chloride; the addition of free radical catcher tempo not only inhibits the reaction but also captures benzene sulfur radicals, indicating that the reaction may be carried out through the free radical pathway When CuBr and Cui are used in the reaction, the corresponding brominated / iodized products can also be detected by GC-MS, indicating that copper catalyst may not only be the free radical initiator of the reaction, but also play a more important role Figure 5 Reaction mechanism (source: org Lett.) based on the results of control experiments, the author proposed the reaction mechanism (Figure 5) Firstly, sulfonyl chloride is reduced to thionyl chloride 11 by PPH 3, 11 and CuCl undergo a single electron transfer to form a free radical 15 CuCl 2 formed by the triple bond of CuCl 2 and alkynes forms an intermediate 16, which may control the regioselectivity of the reaction Based on DFT theory, the author calculated the energy of reaction intermediates by prbe and BLYP to prove the effect of CuCl2 on regioselectivity (Fig 6) Then, the free radical 15 reacts with the intermediate 16 to form 17, which is converted into the trans addition product (E) - 4 and completes the CuCl cycle Figure 6 Intermediate energy calculated based on DFT (source: org Lett.) the author uses cheap and various sulfonylchloride for chlorination sulfurization of alkynes, which provides an important supplementary method for the synthesis of β - haloalkenyl sulfide The mild conditions, good tolerance of functional groups and low price of raw materials show that the synthesis method has a certain application prospect The research results were recently published in org Lett (DOI: 10.1021 / ACS Orglett 8b02929) Liang Shuai, Ph.D student and Jiang Luqi, Ph.D., lecturer, School of chemical engineering, Nanjing University of science and technology, are the co first authors of this 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 Review of previous reports: Professor Yi Wenbin, Nanjing University of science and technology research group: the new use of sodium trifluoroethylsulfite -- promoting direct electrophilic trifluoroethylsulphonation reaction in the absence of metal; Professor Yi Wenbin, Nanjing University of science and technology research group: the new use of CF 3so2cl -- promoting direct chlorination of alkenes and alkynes - trifluoroethylsulphonation reaction 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, chembeangoapp, 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.