Research group of Liu Qiang, associate professor of Tsinghua University: regioselective olefin isomerization controlled by cobalt catalytic kinetics

Isomerization of lead olefins is a very important reaction process in organic synthesis, and the selective control of the reaction is always the difficulty of this kind of reaction Generally, the regioselectivity of olefin isomerization is determined by the thermodynamic stability of the product In practical synthesis, the target product is not necessarily the most stable isomerization product in thermodynamics Therefore, it is of great significance to develop a kinetic controlled selective olefin isomerization reaction Recently, Liu Qiang group and Jiao Lei group of Tsinghua University have developed a kind of clamp type cobalt catalyst with easily controlled structure For the first time, the regioselective isomerization of 1,1-disubstituted alkenes has been systematically studied, and the products of internal alkenes with double bond migration to the less resistance end (j.am Chem SOC 2018, DOI: 10.1021 / JACS 8b01815) have been prepared with high efficiency and selectivity Introduction to the research group of Associate Professor Liu Qiang the research group of Associate Professor Liu Qiang was founded in 2015 At present, there are 1 postdoctoral and 3 doctoral students in the research group The research group focused on the challenge of homogeneous catalysis, based on the development of new reactions and catalysts in organometallic chemistry, and focused on the in-depth study of reaction mechanism by means of physical organic chemistry The rational design of catalyst and reaction is further guided by the understanding of reaction mechanism At present, the main research fields are the development of cheap metal catalysts and their application in the activation and transformation of small energy molecules At present, the research group is in the rising stage, and has been recruiting postdoctors and research assistants for a long time We warmly welcome students who are interested in organometallic chemistry, asymmetric synthesis, organic synthesis chemistry, homogeneous catalysis and polymer synthesis to join our research team (contact email: Qiang liu@mail.tsinghua.edu.cn) profile of Liu Qiang, associate professor, Center for basic molecular science, Tsinghua University, doctoral supervisor In 2003, he entered the school of chemistry and molecular science of Wuhan University and obtained his bachelor's degree in 2007 In the same year, he entered the research group of Professor Lei Aiwen of Wuhan University to study for a doctor's degree, and carried out research work in the research of transition metal catalyzed coupling reaction and related reaction mechanism, and obtained a doctor's degree in 2012 Subsequently, he won the support of Humboldt scholarship of Germany and joined Professor Matthias Beller's research group of Leibniz Catalysis Research Institute of Germany to carry out postdoctoral research His main research direction is the catalytic activation of C1 small molecule and its application in important industrial catalysis In June 2015, he joined the center for basic molecular science of Tsinghua University and started independent scientific research Dr Liu Qiang was awarded "top ten outstanding young people (students)" of Wuhan University in 2012 and "top ten academic stars" of Wuhan University in 2011 In 2010, he was invited by the Chinese delegation of outstanding doctors to attend the Nobel Prize winner conference in Lindau, Germany In 2015, he was selected into the 11th batch of "thousand talents plan" youth projects of the Central Organization Department, and won Thieme Chemistry Award in 2017 Research results: the isomerization of olefins is a very important process in organic synthesis This method can be used not only for the preparation of inner olefin products which are difficult to be synthesized directly by other methods, but also for the functionalization of the remote position of the initial carbon carbon double bond in the substrate molecule through the migration process of carbon carbon double bond, a highly reactive functional group, on the substrate As shown in Figure 1a, all olefin isomerization is a thermodynamically driven reaction Although researchers have developed a number of efficient catalytic systems for olefin isomerization, selectivity control is still the difficulty of such reactions For example, the isomerization of allyl alcohol (Fig 1b) is relatively easy to be controlled by thermodynamics As long as the migration of double bonds on the carbon chain is rapid and reversible, the main product of the reaction must be the more stable aldehydes in thermodynamics In practical synthesis, the target product of isomerization is not necessarily the most stable olefin isomer Therefore, the selective regulation of these reactions is more difficult For example, in the selective conversion of 1-olefin to 2-olefin (Fig 1c), the double bond may continue to migrate to other olefin isomers with similar energy In order to control the 2-site selectivity of the reaction, the catalyst must be able to distinguish the difference between 1-olefin and 2-olefin in the reaction activity and make the reaction activation energy Δ g ≠ 1 < Δ g ≠ 2 However, there are few reports about the catalyst which can effectively realize the selective regulation Recently, Liu Qiang group and Jiao Lei group of Tsinghua University have developed a kind of selective olefin isomerization reaction controlled by cobalt catalytic kinetics In this work, the isomerization of 1,1-disubstituted olefins has been studied systematically (Fig 1D) When there are two possible reaction sites a and B in the reaction substrate, the carbon carbon double bond can selectively migrate to the a-terminal with less steric hindrance In order to effectively control the selectivity of this kind of reaction, it is required that the catalyst used not only has high reaction activity, but also can accurately identify the small steric effect difference caused by the R group on the substrate, making the reaction activation energy Δ g ≠ 2 < Δ g ≠ 1, Δ g ≠ 3, which is undoubtedly more challenging Figure 1 Potential energy surfaces of several typical olefin isomerization reactions (source: J am Chem SOC 2018, DOI: 10.1021/jacs.8b01815) A kind of pincers cobalt catalyst system developed by the author can be applied to ring and chain 1, The isomerization of 1-disubstituted alkenes [Fig 2, Eq (1)] can also realize the efficient and highly selective isomerization of 1a to 2A [Fig 2, Eq (2)], which is the key step in the total synthesis of natural product minfiensine originally designed by the jiaolei group, while the traditional acid promoted isomerization of 1A mainly produces the product 3A (2a) with double bond migration to the other side : 3a =1:2.3）。 In addition, the selective conversion of 1-olefin to 2-olefin can be effectively controlled by introducing the substituent group R in the end olefin γ position [Fig 2, Eq (3)] Figure 2 Cobalt catalyzed regioselective olefin isomerization (source: J am Chem SOC 2018, DOI: 10.1021 / JACS 8b01815) Based on the experimental study, the author proposed the reaction mechanism of metal hydrogen transfer insertion / β - hydrogen elimination (Figure 3), in which the β - hydrogen elimination step determines the regioselectivity of isomerization Combined with DFT calculation, two possible transition structures (ts2a and ts2b) in the process of β - hydrogen elimination are analyzed In ts2b, there is a repulsion between the coordination pyridine group and the substituent group R of the substrate molecule, but this interaction does not exist in the dominant transition state ts2a, which explains how the ligand effect can realize the regioselective regulation of the reaction Figure 3 Olefin isomerization mechanism (source: J am Chem SOC 2018, DOI: 10.1021 / JACS 8b01815) This achievement was recently published in Journal of the American Chemical Society by Xufang Liu, Wei Zhang, Yujie Wang, Ze Xin Zhang, Leijiang * and Qiang Liu * After more than two years' efforts, this kind of high spin pincers cobalt complex developed by Liu Qiang's research group has realized the high efficient catalytic activation of small energy molecule amborane, which can be used for stereoselective transfer hydrogenation of alkynes and high selective preparation of (z) - alkenes and (e ）-Olefins; and chemically selective cyano transfer hydrogenation to synthesize primary amine, secondary amine and tertiary amine compounds with high selectivity; and regioselective olefin isomerization can also be realized to obtain internal olefin products with double bond migration to the side with less potential resistance 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.