Research group of Professor Wan Jieping of Jiangxi Normal University: cutting off carbon carbon bond to synthesize α - keto ester in the atmosphere of photocatalytic air

Lead carbon carbon bond is one of the most stable chemical bonds in nature It is of great significance to develop organic reactions based on direct activation or functionalization of carbon carbon bond In the existing carbon carbon bond conversion models, it is a common strategy to activate carbon carbon bond by noble metal catalysis with high catalytic activity, oxidation of strong oxidant and / or structural modification of substrate When the target carbon carbon bond conversion is realized by modifying the substrate structure, the precondition is that the modification process is simple and the modified substrate is stable enough As a typical push-pull electronic structure compound, the carbon carbon double bond of alkenylamine ketones is activated by the electron withdrawing and electron supplying groups at both ends, which not only shows good stability, but also has potential carbon carbon bond conversion activity Recently, the research group of Professor Wan Jieping, School of chemistry and chemical engineering, Jiangxi Normal University realized the method of photocatalytic synthesis of α - keto ester without any transition metal catalyst for the first time through the key transformation of C-C bond breaking of alkenyl amine ketone Relevant research results were published in green chemistry (DOI: 10.1039 / c9gc01357a) Prof Wan Jieping, Professor of Jiangxi Normal University, doctoral supervisor In 2010, he graduated from the Department of chemistry of Zhejiang University and obtained his Ph.D from Professor Pan Yuanjiang In the same year, he entered the school of chemistry and chemical engineering of Jiangxi Normal University and began to work independently He was supported by the Sino German Science Center of the National Natural Science Foundation of China and engaged in cooperative research in the research group of Professor Dieter Enders of Aachen University of technology from September 2011 to August 2012 He was promoted to associate professor in 2012, doctoral supervisor in 2016 and professor in 2017 Since his independent work, he has published more than 90 papers in the journals of org Lett., chem Commun., green chem., J org Chem., chemcatchem, etc., which have been cited more than 2100 times, and 5 papers have been selected into ESI high cited papers successively As a representative of Chinese doctoral students, he participated in the Nobel laureate conference in Lindau, Germany (2010) and won Thieme Chemistry Journal Award (2014) The main research interests are the research and development of high-efficiency multifunctional platform synthons, green catalysis and synthesis methods based on biomass, diversity oriented synthesis, etc Cutting edge scientific research achievements: photocatalytic synthesis of α - keto ester α - keto ester by cutting off carbon carbon bond in air atmosphere is a highly functional organic compound, whose structure has been widely reported as organic synthesis block and key segment of active molecule of biological drugs Therefore, the synthesis of α - ketoesters has been an important part of organic synthesis The traditional synthesis methods of α - keto ester include esterification of α - keto acid / acyl chloride, oxidation of α - hydroxy / halogenated ester, acyl c-h-bond esterification of α - oxaldehyde, coupling of aryl boric acid and cyano ester, and catalytic tandem c-h-bond oxygen functionalization esterification of methyl ketone Although many synthesis methods have been known, the transformation modes involved in the reactions are not abundant in nature, and some of them have some problems, such as the need for noble metal catalysis, the harsh reaction conditions and / or the difficult to store substrates Therefore, it is still necessary to develop new transformation methods for the synthesis of α - ketoesters Professor Jiao Ning's research group of Peking University has reported the pioneering work of α - keto ester synthesis by copper catalyzed carbon carbon single bond breaking and alcohol reaction in 1,3-diketone structure However, the synthesis of α - keto ester by completely breaking carbon carbon bond has not been reported Based on the basis of the research of the research team on the carbon carbon double bond cutting of ketene (J org Chem 2019, 84, 1064; chem Commun 2016, 52, 1270; green chem 2016, 18, 402; chem Asian J 2016, 11, 2092; chemcatchem 2015, 7, 1478; J org Chem 2014, 79, 9872) Recently, the research group of Professor Wan Jieping of Jiangxi Normal University revealed the new application of substrate structure modification in the field of inert chemical bond conversion by photocatalytic synthesis of α - keto ester under the carbon carbon fracture mode of ketene ketone without transition metal In the optimization stage, the reaction conditions were optimized by using ketene 1a and ethanol 2A as substrates (Table 1) The best reaction conditions were selected by examining reaction medium, photocatalyst and additives The results show that the highest yield can be obtained by using 1 mol% of Rose Bengal and acetic acid as additives Table 1 Optimization of reaction conditions (source: Green chem.) then, under the optimized conditions, the author studied the substrate range of the reaction First, different ketene substrates were used to react with ethanol The results are shown in Table 2 The aryleneamines show a high degree of compatibility for this reaction The benzene ring, naphthalene ring and aromatic heterocyclic functionalized ketene amine substituted by common functional group can all participate in the reaction smoothly, and the target product can be generated in good to excellent yield In addition, it is worth mentioning that the enone derived from the natural product 16 dehydropregnolone acetate can also react with ethanol to obtain the natural product 3R modified by α - keto ester in 45% yield Table 2 application scope of ketene (source: Green chem.) then, in order to further investigate the application scope of the synthesis method, the author used different alcohols and ketene 1a to react As shown in the results in Table 3, the reaction shows general compatibility for the first and second alcohol substrates All kinds of straight chain alcohols, branched alcohols, cycloalcohols and aromatic (heterocyclic) functionalized alcohol substrates react with ketene, and the target products are obtained in good to excellent yields In addition, the biomass compound ethyl lactate can also be used as alcohol substrate to participate in the reaction to obtain the corresponding product 3aq It is worth mentioning that when the substrate containing more than one hydroxyl group, such as phenol alcohol, glycol and triol, is used for the reaction, the results show excellent chemical selectivity, and the reaction only takes place on one alcohol hydroxyl group (3ar-3at), which proves that the synthesis method has a unique selective advantage This kind of chemical selectivity has not been reported in the literature Table 3 application scope of alcohol substrate (source: Green chem.) based on the full investigation of the substrate scope, the author has studied the possible derivative application of the reaction (Figure 1) By simply adding o-phenylenediamine in the reaction system, quinoxalinone 5 was successfully synthesized and the reaction effect was good These results further confirm the advantages of this method in the synthesis of various organic small molecules Figure 1 Study on the derivative synthesis of quinoxalone (source: Green chem.) later, in order to verify the possible reaction mechanism, the author conducted a series of control experiments (Figure 2) Free radical trapper experiment indicated that the reaction experienced a free radical process The realization of isotope labeling in the atmosphere of 18O2 confirmed that oxygen in the air was the oxidant and carbonyl oxygen source of the reaction; α - aldehydes and ketones and α - ketoacids were used as substrates for the reaction respectively, suggesting that both were not intermediates of the reaction; meanwhile, the competitive reaction of primary alcohol and secondary alcohol confirmed that the steric hindrance on the alcohol substrate had a significant inhibitory effect on the reaction In addition, the fluorescence quenching experiments show that ketene has no quenching effect on the photocatalyst, so oxygen in the air is a possible quenching agent, which directly initiates the reaction with the excited photocatalyst Fig 2 control experiment (source: Green chem.) based on the above reaction results, the author proposed the possible reaction mechanism (Fig 3) First of all, Rb becomes excited state RB * under the condition of light The catalyst intermediate reacts with oxygen to produce singlet reactive oxygen species The latter reacts with double bonds in the structure of ketene to form peroxycycline intermediate a The intermediate B is formed by the formation of N-O bond and the ring opening of a is promoted by proton; the intermediate C is obtained by the combination of a and water, and the target product 3 and by-product D are generated by the decomposition of the intermediate D is easily oxidized to DMF under the reaction conditions Fig 3 possible reaction mechanism (source: Green chem.) summary the author first realized the method of completely breaking carbon carbon bond to synthesize α - keto ester without transition metal by using the characteristic structure of alkenylamine ketone compounds The reaction can be carried out efficiently under the catalysis of 1 mol% RB photocatalyst and air atmosphere, which is highly versatile for the first and second alcohol reactions Especially, for the polyhydroxy substrates such as phenol alcohol, diol and triol, the reaction showed excellent chemical selectivity of monoalcohol hydroxyl The results provide a new method with high atom economy and practicability for the synthesis of α - keto ester This achievement was recently published on Green Chemistry (green chem 2019, DOI: 10.1039 / c9gc01357a) The author of the paper is Qing Yu, Yang Zhang, Jie Ping Wan The above work was supported by NSFC (21562025, 21861019) Review of previous reports: Professor Wan Jieping's research group of Jiangxi Normal University: synthesis of Isoflavones by aromatization of C-H bond based on transient and recyclable halogenation process Today, science and technology elements are increasingly valued in 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.