Yan Xiaoyu group, Renmin University of China: ruthenium catalyzed o-site selective hydrogen deuterium exchange reaction of benzene ring

Lead deuterium labeled compounds have important application value in organic reaction mechanism analysis, analysis and test, material science, life science and medicine Isotope dilution mass spectrometry (IDMS) based on deuterium labeled compounds has been widely used in quantitative analysis It has the advantages of fast, accurate, high sensitivity and good repeatability due to its small matrix effect In order to avoid the interference of other isotopes in the substance to be measured, isotope dilution mass spectrometry usually needs to mark three or more deuterium atoms in the internal standard of the substance to be measured In recent years, the selectivity and multi site deuterium reactions of compounds have been the focus of chemists Recently, Yan Xiaoyu's group of Renmin University of China successfully realized the deuterium generation of benzene ring with ruthenium as catalyst The related results were recently published in org Lett (DOI: 10.1021 / ACS Orglett 9b03955) Yan Xiaoyu's research group was founded in 2016 At present, there are 9 people in the group, including 5 doctoral students and 4 master's students The research direction of the research group is organometallic chemistry, main group element chemistry and organic synthesis methodology Profile of Associate Professor Yan Xiaoyu Associate Professor Yan Xiaoyu graduated from Tsinghua University in 2008 with a bachelor's degree and obtained a doctor's degree from Tsinghua University in 2013 During that time, he visited and studied in the research group of Takahashi professor of Hokkaido University and Bertrand professor of the University of California, riverside From 2014 to 2016, as a Humboldt scholar, he worked as a postdoctoral researcher at the University of welzburg, Germany, and his co tutor was Professor Braunschweig He joined Renmin University of China in 2016 and was employed as an associate professor Frontier research achievements: ruthenium catalyzes the o-site selective hydrogen deuterium exchange reaction of benzene ring to introduce C-D bond into specific molecular structure, which can be realized either by chemical synthesis of deuterium containing raw materials or by hydrogen deuterium exchange There is no doubt that the second method is more efficient, but it requires higher selectivity Previously, a large number of studies have realized the hydrogen deuterium exchange reaction in the ortho position of the benzene ring by Using Ru, IR, PD, Rh (Fig 1a) However, the selective deuterium reaction between benzene rings is quite challenging Until recently, researchers used U-shaped template as the locating group to realize palladium catalyzed selective deuterium exchange reaction between benzene rings (Fig 1b) Since frost and Ackermann reported that Ru catalyzed the functionalization of benzene rings in 2011, Ru has always been a research hotspot Through the study of reaction mechanism, it is now agreed that the functionalization of benzene rings is realized through the free radical process (Fig 1c) However, there is no deuterium radical in the reaction system, so the hydrogen deuterium exchange reaction can not be realized through the ruthenium catalytic reaction mechanism of the radical By adding electron rich ligands to change the electronic density of the active intermediate, the hydrogen deuterium exchange reaction between benzene rings guided by nitrogen heterocycles can be realized through the electrophilic substitution process Fig 1 At the beginning of the study on metal catalyzed selective hydrogen deuterium exchange reaction of aromatic ring (source: org Lett.), the author optimized the relevant conditions with 4-methylphenylpyrazole as the substrate Through the selection of reaction conditions, it was found that the high efficiency H / D exchange of benzene ring was successfully realized in D 4-acod with dichlorobis 4-methylisopropylphenylruthenium as catalyst, triphenylphosphine as ligand and silver acetate as additive At the same time, the high deuterium substitution rate of benzene ring was also achieved in its neighborhood Figure 2 Optimization of reaction conditions (source: org Lett.) after determining the best reaction conditions, the author began to study the applicability of the substrate First, we studied the substrate with pyrazole as the guiding group (Fig 3) The substituents with higher steric resistance and the electron absorbing groups can reduce the deuterium substitution rate The substituents on pyrazol ring have little effect on the deuterization rate of benzene ring Fig 3 pyrazole as the guiding group to realize the hydrogen deuterium exchange reaction in the adjacent position (source: org Lett.), then the author further studied the reaction strategy with pyridine and other azaaromatic rings as the guiding group (Fig 4, FIG 5), and also realized the hydrogen deuterium exchange reaction in the adjacent position in the benzene ring Fig 4 pyridine as the guiding group to realize the hydrogen deuterium exchange reaction in the adjacent position (source: org Lett.) Fig 5 other azaaromatic rings as the guiding group to realize the hydrogen deuterium exchange reaction in the adjacent position (source: org Lett.) Summary: in this study, ruthenium catalyzed hydrogen deuterium exchange reaction of benzene ring was successfully realized The applicability of the reaction substrate was studied It was found that this method was suitable for a variety of guiding groups and maintained a high deuterium substitution rate The mechanism of this reaction is different from that of Ru catalyzed intermodal functionalization reported in the past Instead of the usual free radical mechanism, it realizes the intermodal H / D exchange through the S-AR process, which provides another possible reaction way for the realization of Ru catalyzed intermodal functionalization 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 website, chembeangoapp, chembeango official micro blog, CBG information wechat subscription number and other platforms jointly launch the column of "people and scientific research", approach the representative research groups in China, pay attention to their research, listen to their stories, record their demeanor, and explore their scientific research spirit.