Professor Wang Baiquan, Nankai University Research Group: Cp * CO (III) catalyzes the regioselective synthesis of cyclopentyl [b] carbazole derivatives by the double C-H functionalization of 1 - (2-pyridyl) indole and diacetylene

Lead carbazole skeleton is widely found in natural products and drug molecules Many molecules containing carbazole units have antitumor, antimalarial and antifungal effects, and also have a certain relieving effect on hypertension Therefore, it is of great significance to develop efficient construction methods of carbazole skeleton In the past decade, transition metal catalyzed C-H bond functionalization has been developed rapidly Due to its high atomic economy and step economy, C-H bond functionalization has been widely used in the construction of various carbon carbon and carbon heterobonds Transition metal catalyzed activation of multiple C-H bonds has also been widely reported, but most of them are catalyzed by noble metals (PD, Rh, IR, etc.) As a representative of cheap metals, there are few reports about the activation of multiple C-H bonds by Co Recently, Professor Wang Baiquan's research group of Nankai University has made a breakthrough in this aspect Under the catalysis of Cp * CO (III), the indole substrate containing pyridine guiding group reacts with 1,6-diyne with intermolecular and intramolecular properties, realizing the activation of double C-H bond and the construction of new carbazole framework Relevant research results were published in org Lett (DOI: 10.1021/acs.orglett.8b03438) Brief introduction to Professor Wang Baiquan's research group: Professor Wang Baiquan has 1 Professor, 1 associate professor, 5 doctoral students, 10 master's students, relying on the National Key Laboratory of organic elements of Nankai University and the national "2011 Tianjin chemical industry collaborative innovation center" The current research work of our group includes: 1) organometallic chemistry activated by C-H bond Through step-by-step and quantitative reactions, the key reaction intermediates were separated and identified, and the reaction mechanism of transition metal catalyzed C-H bond activation was studied Based on the understanding of the reaction mechanism, a new and efficient transition metal catalyzed C-H bond activation and conversion reaction was designed and developed 2) Design, synthesis and catalytic polymerization of transition metal polymerization catalyst This paper focuses on the design and synthesis of transition metal compounds based on anion N-heterocyclic carbene ligands, studies their catalytic performance in coordination polymerization, active radical polymerization, ring opening metathesis polymerization and other polymerization reactions, and develops high-efficiency polymerization catalysts with independent intellectual property rights Prof Wang Baiquan, professor and doctoral supervisor of School of chemistry, Nankai University, now vice president of School of chemistry, Nankai University In 1990, 1993 and 1996, he received bachelor's degree, master's degree and doctor's degree from Nankai University respectively, and his tutor was Professor Zhou Xiuzhong He stayed in the Department of chemistry of Nankai University in July 1996 and has been a lecturer, professor and doctoral supervisor ever since From March to December 1997, he worked as a visiting scholar in the Department of chemistry of the Chinese University of Hong Kong, under the guidance of academician Xie Zuowei From September 1999 to August 2000, he went to the University of Texas at Austin for postdoctoral research under the guidance of Professor J J lagowski Mainly engaged in Organometallic Chemistry and homogeneous catalysis He has published more than 170 papers included in SCI and authorized 11 Chinese invention patents In 1998, he won the second prize of the Ministry of education for scientific and technological progress In 2004, it was selected into the "new century talent support plan" of the Ministry of education He served as a member of the 29th and 30th Chemical Education Committee of the Chinese chemical society, and a member of the University Chemistry Curriculum Teaching Steering Committee of the Ministry of education Leading scientific research achievements: the research team of Wang Baiquan, Professor of Nankai University, has done a series of innovative works in the field of transition metal catalyzed multiple C-H bond activation (j.am.chem.soc 2012, 134, 16163; org Lett 2016, 18, 2483; Org Lett 2016 , 18 , 2816; Org Lett 2016 , 18 , 5066; Chem Commun 2017 , 53 , 6343; Chem Commun 2018 , 54 , 9147 ）。 A series of fused ring compounds were synthesized by the activation of multiple C-H bonds catalyzed by transition metals These molecules have potential applications in medicine and materials Previously, it has been reported that under the catalysis of PD or Rh, aryl halides or boric acid substrates react with diacetylene to synthesize carbon ring framework Professor Wang Baiquan's research group adopts the strategy of oriented group and uses relatively low-cost CO as catalyst to construct carbazole framework through the reaction of indole substrate containing pyridine oriented group and diacetylene (Figure 1) This method has the advantages of simple reaction conditions, good functional group compatibility, wide range of substrate application, high yield, good regional selectivity, and the removal of guiding group Fig 1 The transition metal catalyzed construction of carbon ring framework in which diyne is involved (source: org Lett.) the author optimized the reaction conditions with 2-pyridyldindole (1L) and 1,6-diyne (2a) as standard substrates (Fig 2) The results show that 96% of the target product can be obtained by reacting 1L and 2A at 110 ˚ C for 24 hours with Cp * CO (CO) I2 as catalyst, cuoac as oxidant and HFIP as solvent Figure 2 Optimization of reaction conditions (source: org Lett.) under the optimal conditions, the author inspected the application scope of substrate (Figure 3) When the substituents of 4, 5 and 6 positions of indole are introduced, both the substituents of electron donor and electron acceptor can produce good to excellent yields (74-99%) However, when the substituents, such as methyl, are introduced into the 7-position of indole, the yield of the reaction decreases The author speculates that the introduction of the substituents at 7-position of indole may affect the coplanarity of pyridine and indole, thus affecting the guiding ability of N atom Next, the author expanded the substrate of diyne, and introduced phenyl, heterocyclic (such as thiophene group) or alkyl group with electron absorption or electron supply into the alkyne end of diyne to obtain medium to excellent yield (52-88%) In addition to diesters, ethyl acetoacetate and diketones (such as acetylacetone, damidone, 1,3-indenedione) are also very adaptable to the reaction, among which damidone, 1,3-indenedione can also obtain spiro compounds The yield of n-ts as chain substituent is 71% Asymmetric diyne can produce two isomers with high yield Fig 3 Substrate development (source: org Lett.) in order to prove the practicability of the reaction, the author also carried out gram level preparation, 1 l of 3.0 mmol and 2 a of 3.2 mmol reacted to generate 3la, with the yield up to 85% (FIG 4A) Furthermore, the author derived the product 3la, and the guide group of 3la can be removed under mild conditions At the same time, the ester group is hydrolyzed and decarboxylated to obtain cyclopentyl [b] carbazole-2-carboxylic acid compound 4 (Fig 4b) Figure 4 Gram level preparation and derivatization (source: org Lett.) in order to better understand the mechanism of this reaction, the author conducted in-depth research The experimental data show that the C-H bond fracture in the system is reversible The results of parallel KIE experiments show that the fracture of C-H bond is not a critical step (Fig 5) In addition, the control experiment was carried out to try to use pyridine indole substrate to react with monopyne, but the reaction could not happen, indicating that the intramolecular characteristics of diyne contributed to the reaction The author directly uses indole without guiding group to react with diacetylene, and the reaction does not take place, indicating that guiding group is very important in the reaction system (Fig 6) Figure 5 H / D exchange experiment and parallel KIE experiment (source: org Lett.) Figure 6 Control experiment (source: org Lett.) based on the above research, the author proposed the possible mechanism of the reaction (Figure 7) Cp * CO (CO) I 2 forms the active cobalt intermediate I under the action of cuoac; then I coordinates with N atom on 1A pyridine to generate ortho C-H bond activation to form the five membered ring cobalt intermediate II; the two alkyne units of 2A coordinate with II to form the intermediate III; next one alkyne is inserted into the c-co bond of III to form the seven membered ring intermediate IV Because of the weak bidentate coordination of alkynes, cobalt is selectively close to one end of the bridge chain when alkynes are inserted; pyridine ligand dissociation occurs in intermediate IV, and then the C-H bond at position 3 of indole is further activated to form intermediate V; the second alkyne is inserted into c-co bond of V to form intermediate VI; the target product 3a is obtained by its generation reduction elimination, and the monovalent cobalt produced at the same time is controlled by cuoac The active cobalt intermediate I is formed by oxidation and then enters the next catalytic cycle Figure 7 The possible mechanism of the reaction (source: org Lett.) was published on org Lett (DOI: 10.1021/acs.org lett 8b03438) The first author of the paper is Li Qiuyun, a doctoral student of Nankai University, and the corresponding author is Wang Baiquan, a professor of Nankai University The above research work was supported by National Natural Science Foundation of China (no.21672108) and Tianjin Natural Science Foundation (no.16jczdjc31700) 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, chembeangoapp, 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.