Pan Yingming and Tang Haitao research groups of Guangxi Normal University: a new way to improve the selectivity of electron free oxidation of heck by alkylalkenes

Introduction: the birth of mizoroki Heck reaction set off the upsurge of transition metal / ligand catalytic system applied to organic synthesis However, since the birth of Heck reaction, the problem of regioselectivity of its electron free alkylalkenes has not been properly solved Although there are many reports about the highly branched chain selective Heck reaction, the research on the more complex highly straight chain selective Heck reaction has been slow (Fig 1) Figure 1 Different products of Heck reaction (source: angelw Chem Int ed.) highly dispersed metal catalyst can often bring superior reaction activity and selectivity In the field of heterogeneous catalysis, it seems to be an inevitable trend for the overall development of modern catalysis that the active center of transition metal catalyst is becoming smaller and smaller The advantages of homogeneous catalysis and heterogeneous catalysis can be effectively integrated by dispersing the metal catalytic center to the atomic level However, the field of homogeneous organic synthesis, which is most closely related to this, has not been "single atom" polished There are only a few reports on the application of "single atom" to solve the problem of organic synthesis Recently, pan Yingming and Tang Haitao of Guangxi Normal University reported a novel pre coordination / polymerization strategy, through which mononuclear Pd catalysts with atom level dispersion can be synthesized (Figure 2) Based on the porous organic polymers (POPs), the catalyst not only integrates the advantages of pore effect, electronic effect and discrete sites of the support materials, but also inherits the electronic effect and spatial effect of the ligands under homogeneous conditions Under the action of the catalyst, the highly regioselective electron free oxidation of alkenes by heck can be realized successfully Relevant research results were published in angelw Chem Int ed (DOI: 10.1002 / anie 201814493) Figure 2 Preparation of mononuclear Pd catalyst by pre coordination / polymerization strategy (source: angelw Chem Int ed.) Brief introduction of Professor Pan Yingming, State Key Laboratory of pharmaceutical resource chemistry and Drug Molecular Engineering jointly established by Guangxi Normal University, Ministry of science and technology, and "research team of natural active compounds and their analogues' synthesis and Pharmacology" Academic leader, Professor, doctoral supervisor He was selected by Thomson Reuters Group as "global high cited scientist", "winner of Mingde Teacher Award" and the second level candidate of Guangxi "one hundred thousand" talent project Reviewers of journals such as nat.commun., acsacatal., green chem., org Lett., chem Commun Editorial board of current cancer reports More than 90 SCI papers have been published in the academic journals at home and abroad, such as angelw Chem Int ed., green chem., org Lett., EUR J Med Chem., etc., with 2100 times of other SCI citations and more than 250 times of single SCI citations, it has obtained 20 authorized national invention patents, participated in the compilation of 4 teaching materials (including 2 Chinese and associate editors) and 3 English academic monographs It won one second prize (ranking first) and one third prize (ranking fourth) of Guangxi science and technology progress award, and one second prize (ranking second) and one third prize (ranking second) of Guangxi Natural Science Award The developed rosin chiral products have been applied and promoted in Guangxi Wuzhou rosin Co., Ltd., with a new output value of 250 million yuan and an export earning of 14.58 million US dollars He has been invited to make more than 20 academic reports in academic conferences and universities at home and abroad In the past five years, a number of high-quality graduate and undergraduate students have been trained, including one master's degree free to pursue a Ph.D degree from Peking University and four undergraduate's degree free to pursue a master's degree from Peking University Brief introduction to researcher Tang Haitao, researcher, bachelor's degree in Central South University, doctor's degree in Xiamen University In September 2017, he entered the National Key Laboratory of pharmaceutical resource chemistry and Drug Molecular Engineering jointly established by the provincial and Ministry of chemistry and Pharmacy College of Guangxi Normal University Mainly engaged in the research of green organic synthesis chemistry, developing new catalytic systems and new methods to provide green and new synthesis methods for the diversity synthesis of natural active compounds and their analogues (with drug core framework) At present, the emphasis is put on the development of new methods such as electroorganic synthesis to synthesize drug molecules and the development of new porous organic polymer catalytic system Since joining Guangxi Normal University for one year, he has published 9 Correspondents' papers in Angew Chem Int Ed., Green Chem., Org Lett., Chem.Commun., Adv Synth Catal and other JCR regional journals Some of the articles were selected as front cover (1 article) and inside back cover (1 article) Cutting edge scientific research achievements: a new way to improve the selectivity of the oxidation of alkenes to heck without electron bias Pan Yingming and Tang Haitao of Guangxi Normal University have done a series of innovative works in using heterogeneous catalysis strategy to focus on solving common problems that are difficult to solve in homogeneous catalysis (org Lett 2018, 20, 2494; chem Commin 2018, 54 , 8446; Org Lett 2018 , 20 , 7748 ）。 This series of work shows the advantages of p-doped porous organic polymer in catalytic regioselectivity and chemical selectivity, and proves the advantages of porous organic polymer as a single core catalyst carrier When p-doped pops is used as the support, the mononuclear metal catalyst with 100% metal dispersion can be effectively synthesized by traditional prepolymerization / coordination method However, this method only works when expensive p-doped POPs are used as carriers When the cheaper NHC ligands are used as carriers, some metal particles tend to aggregate to form larger nanoparticles in the same solvent In order to systematically study the catalytic system, the author first prepared PD metallized NHC doped pops (Pd / pop-9) according to the traditional prepolymerization / coordination method (Fig 3a) When Pd / pop-9 is used as catalyst to catalyze Heck reaction, different selective products will be obtained in each reaction even under the same conditions After careful investigation, the author concludes that the reason for this phenomenon may be that the polymerization of monomers leads to different coordination and chelation angles of coordination units (Fig 3a, isomer A-D), thus affecting the reaction results Figure 3 Synthesis mode of the two catalysts (source: angelw Chem Int ed.) According to the characterization results of the catalysts, the catalysts prepared under the classical prepolymerization / coordination conditions are mainly cluster catalyst Pd / pop-9 (Figure 4a) In order to avoid producing different isomers (A-D) in the monomer polymerization process, the author improved the synthesis method and took the lead in adopting a novel synthesis mode, in which the monomer replaces the initial prepolymerization / Coordination Synthesis mode through the prepolymerization / polymerization process (Fig 3b) This new strategy can fix the chelation angle of the catalytic system by the strong coordination between the transition metal and the ligand Even if polymerization occurs, this property will not change In addition, the coordination of N-heterocyclic carbene ligands can also be used to counteract the sharp increase of surface free energy when metals disperse into mononuclear particles, which can effectively prevent the aggregation of small clusters The HAADF-STEM image (Figure 4) also shows that the NHC doped catalyst PD @ pop-9 prepared by the pre coordination / polymerization strategy is a 100% atom level dispersed Pd catalyst with a Pd loading of 0.37% (determined by ICP-AES) In order to understand the coordination mode of PD and ligand, we have successfully separated the pre coordinated monomer S5 The 13 CNMR spectra of S5 provide evidence of metallization, and the peak at 162.01 ppm can be attributed to the coordination between the carbene carbon atom of S5 and PD The structure of S5 has been confirmed by X-ray structure analysis of single crystal The single crystal data clearly show the Pd-C coordination mode In addition, in order to further prove the correctness of the results, the author supplemented the coordination of the active units in the polymer by EXAFS characterization (Figure 5) The results obtained in the polymer are consistent with the single crystal data of monomer S5 In PD @ pop-9, no strong PD PD signal in FT spectrum was observed, indicating that PD cluster was removed in the process of coordination, leaving only mononuclear PD site TG curves of pop-9 and PD @ pop-9 show that the polymer can remain intact at temperatures up to 250 ℃ The results of nitrogen adsorption desorption analysis show that all polymers have graded pores, large pore volume and high surface area, which can be further confirmed by SEM images In addition, the catalyst was characterized by XPS The results show that PD exists in the form of PD 2 + Fig 4 A) Pd / pop-9, b) newly prepared PD @ pop-9, c) haddf-stem of used PD @ pop-9 (source: angel Chem Int ed.) Fig 5 EXAFS characterization data of PD @ pop-9 (source: angel Chem Int ed.) to study the influence of polymer internal structure on regioselective Heck reaction , the author synthesized a series of PD metallized NHC doped pops to screen the polymer carrier (Figure 6) The results show that when PD @ pop-9 is used as catalyst, the straight chain products can obtain excellent straight chain selectivity (LN: br = 100:1) Figure 6 Catalyst screening (source: angelw Chem Int ed.) is another highlight of the catalyst system PD @ pop-9 can be used at least 10 times without affecting regional selectivity and catalytic activity Stem images showed that PD @ pop-9 had obvious aggregation after the 10th use (Fig 4B and 4C) Another possible reason for the high regioselectivity and activity of the catalyst is that NHC ligands containing a large number of anions can maintain stable PKA The author selected various electron free alkylalkenes and arylborates as substrates to test and verify the catalytic effect of PD @ pop-9 (Figure 7) PD @ pop-9 promoted the formation of e-type straight chain products and could tolerate various functional groups For example, the substrate containing ketene, ether or ester can react smoothly and obtain the straight chain product in good yield Allyl ester can still obtain good yield and excellent selectivity Allylamine with double protection can also obtain straight chain products with excellent yield and selectivity under this catalytic system Figure 7 Substrate expansion (source: angelw Chem Int ed.) long chain aliphatic alkenes are usually the most representative and challenging substrates in Heck reactions due to the lack of induction and chelation In this study, the ratio of straight chain products to branched chain products was 100:1, and the total selectivity (R.R.) was 20:1 This is the best result of selective Heck reaction Therefore, this study also proves that the chelation of ligands and metal centers plays an important role in the catalytic system In order to further confirm the selectivity of the reaction, the author uses density functional theory (DFT) calculation to clarify the mechanism of PD catalyzed Heck reaction (Figure 8) In this paper, 1-butene is selected as the material for calculation and modeling, and the free energy results of four different products are compared DFT results show that a is the most stable product in thermodynamics, and the calculation ratio of different products based on Boltzmann distribution shows that a is the main product (96.63%).