Carboxylation of hydrazone with CO2 catalyzed by ruthenium

Carbon dioxide (CO2) has become an ideal source of C1 due to its high abundance, low cost, low toxicity, renewable and other characteristics In many chemical transformations involving carbon dioxide, the synthesis of carboxylic acids by the formation of C-C bonds has an important application prospect Martin and he liangnian group of Nankai University reported the reduction carboxylation of benzyl (pseudo) halides and CO 2 Catalyzed by transition metals (scheme1a) However, ruthenium catalyzed CO 2 carboxylation is rare Recently, Yu Dagang research group of Sichuan University, Li Chaojun research group of McGill University and Lanzhou University in Canada, and Lan Yu research group of Chongqing University reported the ruthenium catalyzed carboxylation of hydrazone and CO 2 under mild conditions (scheme1b) The reaction is characterized by good functional group tolerance, high selectivity, wide substrate range and good expansibility This paper is entitled "ruthenium catalyzed dumping carboxylation of hydrazones with CO2" and published on chem SCI (DOI: 10.1039 / c8sc01299g) Polarity reversal is a strategy to give new reactivity to common functional groups by reversing their inherent polarity Recently, Sato, radosevich and Zhang Wenzhen group of Dalian University of technology have developed the reaction of imides and their derivatives without transition metal participation with CO 2 through carboxylation to produce α - amino acids In 2015, the Chengjiang research group of Changzhou University reported the alkali promoted carboxylation of Shapiro type n-toluenesulphonylhydrazone to generate acrylic acid (scheme 1b) However, it has not been reported that aryl acetic acid can be produced by breaking the C = n double bond in the catalytic system The author considers whether this problem can be solved by using transition metal catalysts with different reaction mechanisms Recently, Li Chaojun's research group has developed ruthenium catalyzed polarity reversal reaction of carbonyl compounds, in which carbonyl is used as carbon anion equivalent Considering that hydrazone is easy to be prepared from carbonyl compounds, this new strategy is expected to provide a more efficient and sustainable way for the synthesis of phenylacetic acid However, ruthenium catalyzed carboxylation of hydrazone derivatives also faces some challenges, such as the reduction of Wolff Kishner catalyzed by ruthenium under mild reaction conditions, or the formation of acridine by hydrazone in the reaction; in addition, alkali promoted Shapiro type carboxylation can also occur (source: chem SCI.) in view of the above challenges, the author began to study the carboxylation reaction of benzaldehyde hydrazone 1A with CO 2 Many diphosphonic ligands were found to promote the reaction, among which dppf was the best (entries 1-3) The reason may be that the ruthenium complexes formed in situ by dppf have higher nucleophilic property Then the author screened a variety of bases and found that CS 2CO 3 was the best (entries 3-6) CSF, as an additive, can effectively improve the yield of the reaction (entry 12), which may be due to the enhancement of nucleophilic properties of fluoride anion as a strong hydrogen bond receptor The importance of ruthenium catalysts, ligands and CO 2 (entries 9, 10, 12, 13) was also confirmed by control experiments (source: chem SCI.) after obtaining the optimal reaction conditions, the author investigated the substrate range of aldehydrazone (Table 2) Most of aldehydrazones can be prepared by the corresponding aldehydes in one step without purification Therefore, from the practical point of view, the reaction system has significant advantages Phenylacetic acid derivatives can be obtained from the substrates with electron donor and electron acceptor groups in medium yield It is worth noting that various functional groups such as fluorine (2b), chlorine (2C and 2L), nitro (2n) and cyano (2O) are compatible with the reaction (source: chem SCI.) in view of the structure of α - substituted phenylacetic acid existing in a large number of bioactive molecules, the author continues to investigate whether ketazone can carry out such reactions (Table 3) It is found that the diphenyl acetic acid 4A can be successfully obtained in 72% or 86% yield by adjusting the reaction conditions slightly In addition, the substrate with different substituents (including fluorine, chlorine and methoxy) can obtain the desired product (4B – 4h) in medium to good yield In addition to benzophenone hydrazone, the products of α - alkylphenylacetic acid can also be obtained by the simple and easily obtained ketone hydrazone 3I and 3j (source: chem SCI.) on the basis of preliminary mechanism research and relevant literature, the author proposes a possible mechanism to explain such changes As shown in Figure 2, catalyst a exchanges ligands with hydrazone and CS 2CO 3 to obtain complex B, which then undergoes two steps of deprotonation to produce complex D A six membered Ru ring e was formed by the addition of CO 2 and D in coordination with [4 + 2] ring Then E releases N2 (the driving force of the reaction) and carries out protonation ligand exchange, converts it into the target product and generates active catalyst B (path-a); or, intermediate f can also be obtained by isomerization, carbonization and carbon dioxide insertion of intermediate D (path-b) Finally, the author proves that path-a is more advantageous than path-b by DFT calculation (source: chem SCI.) conclusion: Yu Dagang group, Li Chaojun group and Lan Yu group have achieved the first time of ruthenium catalyzed carboxylation of hydrazone and CO 2 under mild conditions, and prepared important aryl acetic acid compounds The only by-product of the reaction is N2, which has the characteristics of high atomic efficiency In addition to aldehyde hydrazone, all kinds of ketone hydrazone which did not react with other active electrophilic reagents before also showed high reactivity and selectivity in this reaction.