ACS catalyst: ruthenium catalyzed decarboxylation of aromatics

In recent years, directed group assisted transition metal catalyzed C-H acylation of aromatic hydrocarbons with various acyl compounds has been fully developed Because of its high efficiency and environmental protection, palladium catalyzed decarboxylation of α - carbonyl carboxylic acids has become one of the efficient methods to construct aromatic ketones In contrast, the C-H acylation of aromatics is still limited and challenging Recently, ruthenium catalyzed σ - activation has been used to realize the intermodal C-H functionalization of aromatics Among them, the ortho ring ruthenization affects the aromatic ring by electrons and promotes the sulfonation, alkylation, halogenation, nitration and difluoroalkylation of ruthenium carbon bond This method avoids the use of complex template substrates / ligands or additional transient media, and uses cheap ruthenium as catalyst to promote remote C-H functionalization In spite of the above advantages, many new functional groups have not been introduced into the intermediate sites of aromatics Inspired by ruthenium catalyzed C-H functionalization, recently, Professor Wang Guanwu's research group of University of science and technology of China reported for the first time the selective decarboxylation of aromatics and α - oxocarboxylic acid catalyzed by ruthenium (scheme 1) Relevant articles were published on ACS catalyst (DOI: 10.1021 / acscalal 8b03695) (source: ACS catalyst.) at the beginning of the study, the author used 2-phenylpyridine (1a) as the model substrate and phenylglyoxylate (2a) as the acylation reagent to explore the feasibility of the reaction (Table 1) In the presence of Ru 3 (CO) 12, the target intermediate acylation product 3AA can be obtained in 27% yield The yield of the reaction can be increased to 48% by adding oxidant Na 2S 2O 8 After that, the author investigated a variety of additives, such as d-camphorsulfonic acid (d-csa), trifluoroacetic acid (TFA) and p-toluenesulfonic acid (PTSA), and found that the addition of d-csa made the separation yield further improved It is gratifying to note that the highest yield is 72% when tbme is added as a co solvent The reason may be that tbme is beneficial to the dissolution of reaction mixture or the formation of active catalytic intermediates The control experiment shows that Ru 3 (CO) 12 and Ag 2CO 3 are necessary for the reaction (source: ACS catalyst.) after establishing the optimal reaction conditions, the author investigated the substrate range and functional group tolerance (scheme 2) of 2-aryl heterocycle 1 The intermediate acylation products (3AA - 3la) can be obtained in medium to good yields from p-aryl pyridines with various electron donor or electron acceptor substituents The aryl pyridines with fluorinated substituents at the o-and m-sites are also suitable substrates (3 Ma, 3 Na) In addition, the target product (3PA - 3ra) can also be obtained from pyridine with substituent in 47-66% yield Other guiding groups (such as pyrimidinyl, pyrazolyl) and bioactive purine derivatives can also be compatible with the reaction, and the corresponding product (3sa - 3YA) can be obtained in medium or above yield (source: ACS catalyst.) later, the author used a variety of α - carbonyl carboxylic acids (2B - 2W) to react with 1a to further study the universality of the reaction (scheme 3) Phenylglyoxylic acid with electron rich and electron deficient substituents has a wide range of tolerance, and the required intermediate acylation product (3AB - 3an) is obtained in a medium to good yield The corresponding product (3AO - 3ar) can also be obtained successfully from the disubstituted phenylglyoxylic acid, and the yield is 60% - 76% More importantly, naphthyl or heteroarylglyoxylic acid is also a suitable substrate, although the yield of the product is slightly lower (source: ACS catalyst.) then, based on the above results and related literature, the author proposed a reasonable mechanism (scheme 6) First, 1a and Ru3 (CO) 12 are reversible ortho ruthenization to form active ruthenium ring intermediate I, which is electrophilic attacked with benzoyl radical 4 at the opposite position of Ru-C bond to form intermediate II 4 is produced by decarboxylation of 2 under the action of Na 2S 2O 8 and Ag 2CO 3 Subsequently, II was deprotonated by oxidation of Ag 2CO 3 and / or Na 2S 2O 8 to obtain ruthenium ring intermediate III Finally, III and 1A were protonated and ligand exchanged to release the required intermediate 3AA, and the intermediate I was regenerated to complete the catalytic cycle (source: ACS catalyst.) Summary: Professor Wang Guanwu's research group first developed ruthenium catalyzed intercarboxylation site selective C-H acylation of aromatics with Ru 3 (CO) 12 as catalyst and α - carbonyl carboxylic acid as acylation source This method is characterized by a wide range of substrates, good tolerance of functional groups and high regional selectivity This work expands the existing functionalization methods of ruthenium catalyzed C-H and provides a new strategy for regioselective m-acylation.