Professor Wan Jieping's research group of Jiangxi Normal University: efficient synthesis of acyloxychromone and enaminone without catalyst

The lead alkenylamine ketones have a long history of application and research in organic synthesis chemistry Due to the Homo activation of amino group, these compounds have various reactive sites Although these compounds have been found and applied for a long time, their potential reactive modes and applications are far from being explored Professor Wan Jieping, School of chemistry and chemical engineering, Jiangxi Normal University, has been devoted to the synthesis of N, N - disubstituted enaminones Recently, Professor Wan Jieping's research group has developed the free radical cross coupling reaction without catalyst for the first time, and realized the efficient synthesis of 3-acyloxychromone and α - acyloxyenaminone (organic letters, DOI: 10.1021/acs.orglett.8b01536) 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 80 papers in org Lett., chem Commun., green chem., J org Chem., chemcatchem and other journals, and the papers have been cited more than 1700 times 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 Leading scientific research achievements: the efficient synthesis of acyloxychromone and enaminone without catalyst; the enaminone, as the representative of enaminone, has a variety of potential reaction activities Therefore, it is of great significance to study the organic reactions of these compounds as synthons in order to reveal the properties and applications of enamines and develop diversity oriented organic synthesis reactions Professor Wan Jieping's research group has long been devoted to exploring and developing the research on the characteristic transformation mode and related synthesis reaction of ketene compounds (review: chem Rec 2016, 16, 1164-1177; organic chemistry 2014, 34, 876-885), and systematically studied the carbon nitrogen bond functionalization of ketene compounds (J org Chem 2014, 79, 7232-7238; J org Chem 2016, 81, 6826-6831; org BIOMOL Chem 2016, 14, 6270-6273), carbon carbon double bond activation (chem Commun 2016, 52270-1273; green chem 2016, 18, 402-405; J org Chem 2014, 79, 9872-9877; chemcatchem 2015, 7, 1478-1482), based on the aromatization reaction of carbon carbon double bond block (chem Commun 2018, 54, 7475-7478; Org Lett 2016, 18, 6034-6037; J org Chem 2015, 80, 9028-9033) and direct coupling functionalization of alkenyl carbon hydrogen bonds (org Lett 2016, 18, 584-587; chemcatchem 2017, 9, 465-468; EUR J org Chem 2017, 4401-4404) On the basis of previous research, the group has recently realized the acylation of tertiary ketene in the absence of catalyst for the first time, and developed a simple synthesis method of 3-acyloxychromone and α - acyloxyketene Firstly, benzoyl peroxide (BPO) was used as the coupling reagent, and the third-order ketene amine was used as the model substrate to optimize the reaction conditions The results show that the target product can be obtained in excellent yield without catalyst, additive and ethanol (Table 1) Table 1 Optimization of reaction conditions (source: Organic letters) Then, the author investigated the substrate applicability of the synthesis of 3-acyloxychromone The results are shown in Table 2 O-hydroxyphenyleneamine ketone with different substituents in benzene ring and different peroxide arylformyl compounds show good compatibility A series of chromone derivatives were obtained in good to excellent yields It should be noted that the reaction effect of aliphatic acyl peroxides is not good under this condition Table 2 Substrate suitability test for the synthesis of 3-acyloxychromone (source: Organic letters) Based on the above results, the author has studied the suitability of the reaction of the third-order enaminones without o-hydroxy group As shown in Table 3, the oxidation reaction of N, N-disubstituted tertiary ketenes and benzoyl peroxide hydrocarbon bond gives α - acylated tertiary ketenes in ideal yield, which proves that the tertiary ketenes have good compatibility Table 3 Applicability of substrate for synthesis of α - acyl oxide tertiary ketamine (source: Organic letters) Because the reaction is easy to operate, the author has made a preliminary exploration on the amplification synthesis of the target product The results show that the model reaction still has a good yield after being amplified to gram level (Figure 1) Fig 1 Amplification synthesis of target products (source: Organic letters) in order to explore the possible reaction mechanism, the author conducted relevant control experiments Under the condition of no light, the reaction can still be carried out and the target product can be obtained with excellent yield, which shows that the reaction is not initiated by light At low temperature of - 20oC, the reaction was almost not carried out, which indicated that the reaction was initiated by heat In addition, the addition of tempo catcher can significantly inhibit the reaction, which proves that the reaction goes through a free radical process After the reaction of unsubstituted chromones with BPO, the target product can not be obtained, which shows that the reaction process is not the first chromone cyclization (Fig 2) Figure 2 Reaction mechanism research experiment (source: Organic letters) based on the results of control experiment, the author proposed the possible reaction mechanism First of all, carbamyl peroxide cleaves under the promotion of heat to produce acyloxyradicals, which are added with ketene to form 7 / 7 ', 7 / 7' and acyloxyradicals to form intermediate 8 When carboxylic acid is eliminated, hydrocarbon bond acyloxygenation product 5 can be obtained When o-hydroxyphenyleneamine ketone is used as the substrate, the cyclization of chromone is further carried out to obtain product 3 (Fig 3) Figure 3 Possible reaction mechanism (source: Organic letters) Summary: Professor Wan Jieping's research group has developed the first acylation reaction of the hydrocarbon bond of the third-order enaminones without catalysis The reaction was carried out by the thermal initiation of free radicals This method has the advantages of mild conditions, simple operation and good amplification effect It provides an effective way for the synthesis of 3-acyloxychromone and α - acyloxyenaminone Guo Yanhui, the master student of the research group, is the main author of this work 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.