Wan Xiaobing group and Bao Xiaoguang group of Suzhou University: one pot construction of full substituted 1,2,4-triazole by [3 + 2] cycloaddition of cyanylide and diazonium salt catalyzed by copper

Lead organic nitriles can react with diazo compounds to obtain nitrile ylides easily and quickly, and [3 + 2] cycloaddition with alkenes can construct a variety of five membered nitrogen heterocyclic frameworks However, there are few reports about the intermolecular capture reaction of nitrile ylide Recently, Professor Wan Xiaobing and Professor Bao Xiaoguang from the Department of materials and chemical engineering of Suzhou University have made a new breakthrough in the study of the formation capture series reaction of nitrile ylide They have successfully used aryl diazonium salt to capture nitrile ylide and realized one pot construction of all substituted 1,2,4-triazole It is worth noting that these 1,2,4-triazoles are difficult to synthesize by traditional methods (org Lett., DOI: 10.1021/acs.orglett 8b02172) Brief introduction to Professor Wan Xiaobing, professor and doctoral supervisor of materials and Chemical Engineering Department of Suzhou University He graduated from the school of chemistry and chemical engineering of Nanjing University with a bachelor's degree in 1997 and a master's degree in chemistry and chemical engineering of Nanjing University in 2001 In 2005, he received his Ph.D from Shanghai Institute of organic chemistry, Chinese Academy of Sciences In 2005, he entered the research group of Shi Zhangjie, School of chemistry and molecular engineering, Peking University to carry out postdoctoral research In 2007, he joined Suzhou University and worked as an associate professor In 2012, he was hired as a researcher, and in 2014, he was selected as a doctoral supervisor In 2014, as a Humboldt fund scholar, he went to RWTH Aachen University of technology in Germany for academic exchanges Professor Wan has been committed to the research work of free radical chemistry and carbene chemistry, and has published dozens of papers in international first-class research journals such as J am Chem SOC., angel Chem Int ed., org Lett., J org Chem., chem Commun., chem EUR J., adv synth Cat., etc., which has been widely concerned and cited by peers at home and abroad (nearly a thousand times cited) 12 Chinese invention patents have been applied for and 4 have been authorized Brief introduction to Professor Bao Xiaoguang, Professor of materials and Chemical Engineering Department of Suzhou University In July 2002, he graduated from school of chemistry and chemical engineering, Shanghai Jiaotong University with a bachelor's degree; in July 2007, he graduated from Shanghai Institute of medicine, Chinese Academy of Sciences with a doctor's degree From August 2007 to August 2010, he was engaged in postdoctoral research in the Department of chemistry of Ohio State University; from September 2010 to August 2012, he continued to be engaged in postdoctoral research in the Department of chemistry of North Texas University; from August 2012, he worked in the Department of materials and chemistry of Suzhou University Professor Bao Xiaoguang has been devoted to the research of computational chemistry and physical organic chemistry At present, more than 20 research papers have been published, some of which are published in the journals of proc Natl Acad SCI USA, J am Chem SOC., angel Chem Int ed., chem SCI He has won the excellent scholarship award of the president of the Chinese Academy of Sciences and the special scholarship award of Liu Yongling of the Chinese Academy of Sciences Leading scientific research achievements: copper catalyzed one pot method of [3 + 2] cycloaddition of cyanylide and diazonium salt to construct all substituted 1,2,4-triazole cyanylide is widely used in the construction of a variety of heterocyclic compounds as a practical and easy to obtain 1,3-dipoles The nucleophilic substitution reaction between organic nitriles and diazo compounds can easily obtain the intermediate of nitrile ylide, and then the intramolecular cycloaddition reaction can be carried out to construct a variety of nitrogen-containing heterocyclic compounds However, there are few intermolecular capture reactions of nitrile ylide In 2014, Liu Ruixiong's research group of National Tsinghua University in Taiwan completed the 1,2-oxidation aromatization of organic nitriles through the nucleophilic attack of pyridine oxide on ylide nitriles Recently, Wan Xiaobing's research group also reported that copper catalysed the three-component series reaction of capturing nitrile ylide by carboxylic acid to synthesize asymmetric glycine ester derivatives As far as the authors know, the cycloaddition of [3 + 2] between molecules by triple bond capture of nitrile ylide has not yet been realized Recently, our group, under the catalysis of copper, carried out the intermolecular [3 + 2] cycloaddition reaction with the in-situ nitrile ylide through the cheap and easily available diazonium salt reagent as the substrate, and realized the one pot method to construct the fully substituted 1,2,4-triazole skeleton The related work was published on the recent organic letters (org Lett., DOI: 10.1021/acs.org lett 8b02172) Fig 1 Transformation of nitrile ylide (source: org Lett.) under the condition of CuBr as catalyst and Li 2CO3 as base, the author determined that aryldiazonium salt, diazonium ester and organic nitrile can generate [3 + 2] cycloaddition reaction in high yield to obtain 1,2,4-triazole Under this optimal condition, the research group explored the universality of the reaction substrate It can be seen from Fig 2 that various substituted aryldiazonium salts can participate in the reaction well, especially the electron donor group It can be seen from Fig 3 that a variety of functional groups can be introduced into diazo ester substrate without great impact on the reaction, especially the introduction of carbon carbon double bond, which provides more possibilities for further transformation of target compounds Figure 4 shows the substrate applicability of organic nitriles, which are also well compatible with carbon carbon double bonds When Cinnamonitrile is used as the substrate, the single crystal diffraction pattern of the target compound can be obtained to confirm the structure of 1,2,4-triazole Fig 2 Substrate development of aryl diazonium salt of fluoborate (source: org Lett.) Fig 3 Substrate development of diazonium ester (source: org Lett.) Fig 4 Substrate development of organic nitrile (source: org Lett.) as shown in Fig 5 Isotope labeling experiment shows that N in target triazole product The atom comes from aromatic diazonium salt, not diazonium ester Under the condition of template reaction, the author added 4-tert-butyl styrene to the reaction and successfully detected the formation of a small amount of cyclopropanized products, which indicated that there might be carbene intermediate process in the reaction process A small amount of amidation product 8 was isolated by the analysis of by-products, which indicated that the reaction process produced nitrile ylide Later, Professor Bao Xiaoguang of Suzhou University provided theoretical calculation support to further verify that the reaction went through the process of intermolecular [3 + 2] cycloaddition (Figure 6) Figure 5 Mechanism experimental study (source: org Lett.) Figure 6 Theoretical calculation study (source: org Lett.) through experimental and theoretical calculation study, the author proposed possible reaction mechanism Firstly, copper catalyzes the denitrification of diazo ester to produce copper carbene, then nucleophilic reaction with organic nitriles to form the intermediate of cyanylide, and then coordinated intermolecular [3 + 2] cycloaddition with aryl diazonium salt to further dehydroaromatize under the action of alkali to obtain the final product Figure 7 Possible reaction process (source: org Lett.) the above results are published on org Lett (DOI: 10.1021/acs.org lett 8b02172) The experimental part of the work is mainly completed by Li Huihuang, a doctoral student of Suzhou University, and the theoretical calculation part is completed by Wu Xueli of Suzhou University The research work has been supported by the construction project of Jiangsu University's advantageous disciplines and the National Natural Science Foundation Review of previous reports: Professor Wan Xiaobing's research group of Suzhou University: sulfonamide capture secondary amide ylide strategy applied to the synthesis of n-sulfonamidine derivatives People and scientific research are increasingly valued in the economic life of scientific and technological elements Today, China has ushered in the "node of scientific and technological 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.