ACS catalyst: Professor Zhai Hongbin's research group reports on the synthesis of 3-acylquinoline derivatives by trifunctionalization of diene catalyzed by cobalt

Due to the high reactivity and rich chemical properties of two vertical carbon carbon double bonds, the dienes have become valuable precursors in organic synthesis Alkynes and alkenes are widely used in transition metal catalyzed C-H activation reactions to synthesize various heterocyclic compounds efficiently and economically In contrast, the preparation of highly functionalized molecules from dienes still needs further development At present, there are many reports about the method of allylation of arenes by C-H functionalization catalyzed by transition metal assisted by guiding group, most of which are the single functionalization of olefins by heck type or hydrogenated aromatization to provide substituted olefins or allylated benzamide (scheme 1a), or the heterocyclic compounds are obtained by the bifunctionalization of alkenes（ Scheme 1b ）。 However, the trifunctional reaction of diene catalyzed by transition metal assisted by bidentate guiding group has not been reported (source: ACS Catalysis) oxygen molecule is a green and sustainable oxidant, and it is also an ideal oxygen source for the construction of oxygen-containing compounds Although transition metal catalyzed oxidation of oxygen molecules has been greatly developed, it is still rare to synthesize oxygen-containing compounds by guiding group assisted C-H bond functionalization in series Recently, Zhai Hongbin, Professor of Shenzhen Graduate School of Peking University, reported the method of forming 3-acylquinoline derivatives by cobalt catalyzed trifunctionalization of diene in oxygen atmosphere Relevant articles were published on ACS catalyst (DOI: 10.1021 / acscalal 8b01720) under the title of "trifunctionalization of allenes via cobalt catalyzed MHP assisted C-H bond functionalization and molecular oxygen activation" At the beginning of the study, the author used 20 mol% CO (OAC) 2.4h 2O as catalyst, 2 equivalent Ag 2CO 3 and O 2 as oxidant, n '- methyl-n' - (2-pyridyl) benzoylhydrazide 1a and propadienyl benzene 2A as substrate, reacted in TFE at 60 ℃ for 16 hours, and obtained ketone 3AA and alcohol 4AA in 44% and 34% yield respectively; then DMP was used directly at room temperature The yield of ketone 3AA was 75% (Table 1, entry 1) Subsequently, the author screened the reaction conditions, and other cobalt catalysts and silver salts would reduce the reaction efficiency (entries 3-9) The results of solvent screening showed that EtOH was the best solvent, and the yield of the product was 80% (entries 10-12) In addition, the control experiment showed that the reaction did not take place without co (OAC) 2.4h 2O, Ag 2CO 3 or O 2 (source: ACS Catalysis) then, under the optimal reaction conditions, the author investigated the application scope of hydrazide (Table 2) Benzohydrazide derivatives with electron donor (such as methyl, tert butyl, methoxy, etc.) or electron acceptor (such as halogen, trifluoromethyl, acetyl, etc.) can react smoothly, and the cyclized product (3ba - 3PA) can be obtained in good yield The intermediate substituted benzoylhydrazide can produce the cyclized product (3qa - 3sa) in high yield, but the regioselectivity of the reaction depends to a certain extent on the steric effect of the substituent (source: ACS Catalysis) next, the author investigated the scope of application of diene derivatives (Table 3) The diene derivatives with electron donor or electron acceptor on the benzene ring are compatible with the reaction conditions (3AB - 3AK) When 2-naphthyl (2G) or phenylethyl (2L) is used to replace the phenyl part, the corresponding diene can still obtain acylquinoline derivatives (3aG, 3Al) in good yield (source: ACS catalyst) in order to further understand the mechanism of this reaction, the author has carried out a control experiment and isotope tracing experiment (scheme 2) Firstly, compound 7 can not form product 3AA under standard reaction conditions, which indicates that compound 7 is not the intermediate of the reaction (scheme 2a) When argon was used instead of oxygen, no product 3AA or 4AA was formed Using EtOH / h 218o (3:1) as the co solvent, only the normal 3AA / 4AA was produced, and no 18O was detected in the product This means that the oxygen atom of carbonyl or hydroxyl in 3AA / 4AA may be derived from oxygen rather than water or EtOH (schemes 2B and 2C) In addition, if the reaction stopped after 1 hour, scheme 2D could be detected by HRMS Therefore, the author speculated that the compound 3AA / 4AA should be derived from the intermediate 6 (source: ACS catalyst) based on mechanism experiments and related literature reports, the author proposed a reasonable mechanism for the series reaction (scheme 3) Firstly, Ag 2CO 3 oxidizes CO (II) to CO (III), and hydrazide 1 is coordinated with CO (III), then C-H activation is carried out to produce a Then, B was obtained by the coordination of diene 2 with CO (III) center The C-C double bond with small steric hindrance was inserted into the c-co bond to form a compound C containing a seven membered ring of CO, which was reduced to compound 5 and low CO (I) On the one hand, intermediate 5 can be rearranged by 1,3-h to get compound 7; on the other hand, intermediate 5 reacts with active peroxy radical species (CO (I) and oxygen molecules to form intermediate 8, which is formed by tautomerization to form intermediate 9 Free radical intermediate 9 is oxidized to imine 10, which is protonated and demetallized to obtain peroxides 6 and CO (II) Peroxides 6 were converted into compounds 3 and 4 by elimination and reduction respectively Finally, CO (II) is oxidized by Ag 2CO 3 to form active CO (III) species and enter the next catalytic cycle (source: ACS Catalysis) Summary: Professor Zhai Hongbin's research group has established a new method for the synthesis of 3-acylquinoline derivatives through the trifunctionalization of diene catalyzed by cobalt The reaction mainly undergoes the process of C-H bond functionalization / cyclization / oxygen activation of benzoylhydrazide This method has the characteristics of wide range of substrates and good regioselectivity, and can obtain a variety of 3-acylquinoline derivatives in high yield Prof Zhai Hongbin, Professor of Shenzhen Graduate School of Peking University He received his bachelor's degree in Applied Chemistry from Peking University in 1985, his master's degree in analytical chemistry from Peking Union Medical College in 1988, and his doctor's degree in organic chemistry from Ohio State University in 1995 He was engaged in postdoctoral research at Ohio State University and the University of California, Berkeley from 1996 to 2000 2000-2010 Professor, Shanghai Institute of organic chemistry, Chinese Academy of Sciences From 2010 to 2015, he served as a professor and director of the State Key Laboratory of functional organic molecular chemistry in Lanzhou University, and joined the school of chemical biology and biotechnology in Shenzhen Graduate School of Peking University in 2015 The research direction of the research group is total synthesis of natural products, heterocyclic chemistry and pharmaceutical chemistry, organic synthesis methodology.