Li Gang group, Fujian Institute of physical architecture, Chinese Academy of Sciences: Rh (I) catalyses the chemical selective C-H carboxylation of aromatic rings with CO2 participation

The C-H bond carboxylation of aromatic compounds catalyzed by transition metals, in which CO 2 is involved, has shown a good development potential due to its high efficiency, green and atomic economy However, due to the inherent chemical inertness of CO2 and the limited affinity of C-H bond activated intermediates, there are very limited reports on the selective activation of C-H bond by transition metal catalysis (from C-H bond to C-C bond) Similar reactions have been reported, and many substrates are limited to some aromatic compounds with specific structures containing acid C-H bonds (PKA DMSO < 32.5) Recently, the research group of Li Gang, the State Key Laboratory of structural chemistry and the Key Laboratory of coal to ethylene glycol and related technologies of Fujian Institute of structure chemistry, has realized the carboxylation of inert aromatic C-H bond in 2-arylaniline compounds with CO 2 as the catalyst, using amino group as the guide group Relevant research results were published in org Lett (DOI: 10.1021/acs.orglett.9b01105) Li Gang, research group of researcher Li Gang, Fujian Institute of material structure, Chinese Academy of Sciences, was founded in December 2013 The main research directions of the research group are: (1) the research of new efficient and economic organic synthesis methodology; (2) the exploration of novel and efficient natural product total synthesis strategy; (3) the total synthesis of natural products with important biological activities, the synthesis of drugs and organic functional materials There are 4 staff members, 1 postdoctoral student, 4 doctoral students and 5 Master students (including joint training students) in the research group The research group recruits postdoctoral students and other researchers all the year round We welcome young people who love organic chemistry to join us For detailed recruitment information, please refer to the website: http://www.fjirsm.cas.cn/li'u group / Introduction to researcher Li Gang, researcher, doctoral supervisor In 2005, he graduated from China University of science and technology In 2009, he graduated from the University of Wisconsin Madison with a doctor's degree From 2009 to 2013, he successively engaged in postdoctoral research at Emory University and the Scripps Research Institute The research results were published in nature, nature catalyst, nature Commission indications, Journal of the American Chemical Society, angelwandtechie International Edition, organicletters and other magazines In December 2013, he was introduced to Fujian Institute of material structure of Chinese Academy of Sciences with high-level talents and served as a researcher and project leader Selected into the 10th batch of national "thousand talents plan" youth projects in 2013, automatically selected into the "hundred talents plan" of Chinese Academy of Sciences, and the "hundred talents plan" of high-level entrepreneurship and innovation talents in Fujian Province Leading scientific research achievements: Rh (I) catalyzes the chemical selective C-H carboxylation of aromatic rings in which CO 2 participates In 2011, Iwasawa group used Rh (I) as catalyst and pyridine as guide group to realize the carboxylation of non acid C-H bond However, the activity of the catalyst (scheme 1a) is changed by the use of active and combustible methylaluminum reagent Recently, Li Gang group of Fujian Institute of physical composition used CO2 as a C1 synthon to realize Rh (II) - catalyzed, site-selective C-H bond activation / direct carboxylation of aromatic rings (scheme 1b) In addition, although Xi changjuan's group reported that the carboxylation of electron rich 2-arylaniline substrate (scheme 1c) was realized through the electrophilic ring closing reaction of isocyanate intermediate under the effect of equivalent methylation reagent, the yield of electron poor substrate was very low Up to now, endoacylation of electron rich and electron poor 2-arylaniline substrates has been achieved by transition metal catalyzed C-H bond activation using CO 2 as the C1 synthon One of the important reasons that has not been reported is that the amines of aniline derivatives usually react with CO 2 to form urea derivatives (C-N bond) ）Therefore, it is very difficult to realize the C-H bond activation / carboxylation of chemically selective aromatic rings (C-C bond formation) In view of the above reasons, it is still a great challenge to realize the carboxylation of C-H bonds of aniline derivatives with CO2 as catalyst In this paper, we have successfully carried out the carboxylation of C-H bond of inert aromatic in 2-arylaniline compounds with CO 2 participation in redox neutral conditions (scheme 1D) using transition metal Rh (I) as catalyst (source: org Lett.) firstly, the author used 2-phenylaniline as raw material, and optimized the reaction conditions at a atmospheric pressure of CO2 (Table 1) The experimental results show that [RhCl (COD)] 2 has an obvious promoting effect on the reaction system; at the same time, when the ligand L4 is added to the system, the reaction yield is significantly improved In this paper, the reaction conditions of ligand, alkali and temperature were compared carefully After the optimal reaction conditions were determined, the separation yield of target product 2A could reach 83% (entry 21) (source: org Lett.) next, the author explored the substrate applicability of the reaction (scheme2) The results show that the R H (I) - catalyzed carboxylation of C-H bond with CO 2 has good substrate applicability Under the optimal reaction conditions, the substrates with electron donor or electron acceptor at different positions of benzene ring can give medium to excellent separation yield It is worth mentioning that the reaction has good applicability (2c, 2O, 2k and 2n) to the substrate containing electron withdrawing substituents, which is different from the reported carboxylation method similar to the substrate (source: org Lett.) in addition, in order to further highlight the universality of the method, the author extended the range of substrates to aromatic systems containing electron deficient pyridine, furan, thiophene and indole heterocycles The experimental results show that the catalyst system has good applicability in a series of carboxylation reactions of heterocyclic aromatic C-H bonds (scheme 3) (source: org Lett.) finally, the mechanism of the reaction was preliminarily explored (scheme 4) First, the use of 13 CO 2 confirmed that the carbonyl of the product was from the gas CO 2 (scheme 4a) At the same time, when 1A - D 5 was used as the substrate, obvious D / H exchange was observed in the product, indicating that the activation of C − H bond in the reaction was reversible (scheme 4b) When the reaction was not completed, the author observed the formation of urea 5 and BOC amine 6 (scheme 4C); while when compound 5 or 6 was used to react under the optimal conditions, the yield of 2a was significantly reduced, indicating that compound 5 or 6 was not the intermediate of the reaction (scheme 4D), but was a non-target chemical selective by-product affecting the reaction efficiency The author thinks that by-products 5 and 6 need to be decomposed into a real substrate 1A activated by hydrocarbon bond at high temperature, so that the reaction can continue, so the formation of by-products hinders the efficient process of the reaction, and explains that the reaction must be carried out at high temperature to some extent (source: org Lett.) through the deuterium generation experiment and control experiment, the author proposed a possible catalytic cycle mechanism (scheme 5) for the reaction First, the intermediate B was obtained by oxidation addition and reduction elimination of Rh (I) species and substrate Then, the intermediate B and CO2 are nucleophilic adducted to get intermediate C Finally, the intermediate C was treated by internal amidation to obtain the product, and Rh (I) species was released to continue the catalytic reaction (source: org Lett.) Summary: the carboxylation of inert aromatic C-H bonds in 2-arylaniline compounds with CO 2 as a catalyst and amino group as a guide group was realized The reaction system is simple, does not need to add redox agent or equivalent organometallic reagent, and can be completed under a atmospheric pressure of CO2 This study has brought new ideas and new catalytic systems to the utilization of CO2 in the field of C-H bond activation These results were published in org Lett (DOI: 10.1021/acs.orglett.9b01105) The research work has been greatly supported by the national "youth thousand talents plan", the National Natural Science Foundation, the Fujian hundred talents plan, the Fujian Natural Science Foundation and the postdoctoral innovative talents plan 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.