Angelw. Chem. Int. ed.: Ackermann's team realized electrochemical C-H / N-H activation by water-resistant cobalt catalyst at room temperature

C-H activation is widely used in natural product chemistry, pharmaceutical industry, material science and other fields In the past, precious metal catalysts, such as palladium, iridium, ruthenium and rhodium, were used in C-H conversion Recently, researchers have turned their attention to the rich, cheap and low toxic 3D alkali metals Among them, cobalt catalysis has been proved to have a powerful function in the functionalization of C-H bond, especially the economic synthesis of heterocycles through the functionalization step of C-H / N-H However, this kind of cyclization of C-H / N-H alkynes requires high temperature and chemical equivalent toxic metals as oxidants, which limits it to some extent In 2017, Lutz Ackermann's team at the University of Gottingen in Germany realized C-H oxidation of aromatics and olefins at room temperature using electrochemical cobalt Catalysis (J am Chem SOC., 2017, 139, 18452) The reaction has high chemical, position and non enantioselectivity Under extremely mild reaction conditions, it can realize the oxidation of C-H (click to see) Recently, the Ackermann team combined electrochemistry with cobalt catalyzed C-H / N-H activation to realize the cyclization of C-H / N-H alkynes at room temperature for the first time The reaction has the following characteristics: (I) unprecedented electrochemical C-H / N-H activation / cyclization; (II) Isoquinolinone can be synthesized without the use of toxic metal oxidants; (III) the electrochemical C-H activation process has water resistance; (I V) the continuous electric power can realize the C-H functionalization catalyzed by cobalt at room temperature; (V) the molar equivalent of the reaction substrate is similar, with atomic economy Recently, related papers were published online at angelw Chem Int ed., and the first author was Cong Tian, a doctoral student Fig 1 Source of C-H / N-H activation catalyzed by electrochemical cobalt at room temperature: angelw Chem Int ed firstly, the reaction conditions for functionalization of electrochemical C-H / N-H were screened (Fig 2) The reaction of benzamide 1a and phenylacetonitrile 2a was carried out in a diaphragm free cell containing platinum plate cathode and reticulated glassy carbon (RVC) anode The results show that the yield of Isoquinolinone can reach 76% with CO (OAC) 2 ＜ 4H 2O as catalyst, naopiv as base and H 2O / MeOH (1:1) as reaction solvent at 23 ℃ for 16 hours The importance of cobalt catalyst, carboxylate additive and current was confirmed in the control experiment The experimental results also show that other C-H activated catalysts, including manganese, copper, nickel, iron, ruthenium, gold, platinum, iridium, rhodium and palladium, have no effect on these reactions Figure 2 Source of condition optimization: after angelw Chem Int ed had the best reaction condition, the author expanded the reaction substrate The extended results of amide substrate 1 are shown in Figure 3 It can be seen that benzamide, heterocyclic amide and unsaturated amide with different substituents can all be compatible with such electrochemical C-H / N-H functional reactions The expansion results of alkyne 2 are shown in Fig 4 The functional groups such as cyclohexyl, alkyl chloride and ester group can tolerate such reaction conditions Fig 3 Source of amide substrate expansion: angelw Chem Int ed Fig 4 Source of alkyne substrate expansion: angelw Chem Int ed in order to study the mechanism of the reaction, the author designed a series of mechanism research experiments, including competition experiment, isotope labeling experiment, KIE study, voltammetric analysis, etc., and gave a credible mechanism of catalytic cycle (Fig 5) Firstly, activated cobalt (III) carboxylate component 5 was formed by anodizing Then, carboxylic acid assisted C-H activation to obtain intermediate 6, which migrated and inserted with 2 to form cobalt (III) cyclo 7 Next, 7 is converted to target product 3 through β - H elimination and / or reduction elimination, and assumed cobalt (I) component 8 Finally, cobalt (I) component was converted into cobalt (III) component by anodization Figure 5 Possible reaction mechanism source: angelw Chem Int ed conclusion: Ackermann group reported the first cyclization of Alkynes by C-H / het-h activation catalyzed by electrochemical transition metals at room temperature Mild reaction conditions, no need of toxic metal oxidants and water resistance are the highlights of the new achievements Paper link: http://onlinelibrary.willey.com/doi/10.1002/anie.201712647/full the Ackermann group: http://www.ackermann.chemie.uni-goettingen.de/professor Lutz Ackermann