Professor Mo Dongliang and Professor Su Guifa of Guangxi Normal University: selective synthesis of polysubstituted pyridines and isoxazolines by n-alkenyl-o, β - unsaturated nitrones catalyzed by iron

Introduction: the concept of "diversity oriented synthesis" (DOS) was put forward by Professor Schreiber of Harvard University in 2000 That is to say, starting from a single starting material, a simple and easy method is used to synthesize a variety of structural compounds, and then biological screening is carried out for them In diversity oriented synthesis, the control of reaction selectivity is an important and challenging research topic, and it is also the key to achieve diversity oriented synthesis At present, reaction selectivity can be controlled by substrate, reagent, solvent and catalyst, among which catalyst is one of the most attractive strategies Iron is one of the most abundant metal elements on the earth Its selectivity as a catalyst in organic synthesis is still very challenging Therefore, it is of great value to explore the synthesis of organic compounds with various structures from a single raw material with iron as catalyst to control the selectivity of the reaction On the basis of previous research, Professor Mo Dongliang and Professor Su Guifa's research group of Guangxi Normal University have realized the selective synthesis of polysubstituted pyridine and isoxazoline compounds by using iron catalyst (green chem 2018, DOI: 10.1039 / c8gc00630j) Prof Mo Dongliang's project team was established in November 2014 At present, there are 1 doctoral student, 7 master students and 5 undergraduate students in the research group The research group mainly relies on the State Key Laboratory of pharmaceutical resource chemistry and Drug Molecular Engineering jointly established by the Ministry of Guangxi Normal University The research group is mainly engaged in the research of organic synthesis methodology and the design of nitrogen-containing heterocyclic bioactive small molecules, including the application of high valent iodine reagent, the strategy of metal catalytic selective n − O bond breaking, the design of series reaction involving alkenylnitrones and asymmetric catalysis Prof Mo Dongliang, professor and doctoral supervisor of Guangxi Normal University In 2006, he graduated from the school of chemistry of Nankai University; in 2011, he received his Ph.D from Shanghai Institute of organic chemistry, Chinese Academy of Sciences, under academician Dai Lixin and researcher Hou Xuelong; from 2011 to 2014, he was engaged in post doctoral research in Chicago Campus of Illinois State University in the United States In September 2014, Li Jiang scholars were introduced to the school of chemistry and pharmacy of Guangxi Normal University as professors and doctoral supervisors of Guangxi Normal University In November 2014, he was selected into the "hundred talents plan" of Guangxi universities to introduce overseas high-level talents In 2016, he won Thieme Chemistry Journals award, Guangxi Science Fund for Distinguished Young Scholars, and in 2017, he was selected into the "thousand young and middle-aged backbone teachers" cultivation plan of Guangxi universities He is mainly engaged in the design of organic synthesis methodology and bioactive small molecules, and the research on the construction of skeleton diverse nitrogen heterocyclic compounds with alkenylnitrone, high valent iodine compounds and N − O bond breaking strategy As the first author or corresponding author, he has published more than 30 SCI papers in many famous international chemical journals, such as angelw Chem Int ed., green chem., adv synth Catalyst., org Lett., org Chem Front., J org Chem., and many papers have been selected as cover and hot topics At present, he has presided over 2 research projects sponsored by the National Natural Science Foundation of China, 2 projects sponsored by the Guangxi Natural Science Foundation, and many other research projects funded by the State Key Laboratory Leading scientific research achievements: selective synthesis of tetrasubstituted pyridine and 3,5-disubstituted isoxazoline derivatives by n-alkenyl-λ, β - unsaturated nitrones catalyzed by iron as 1,3-dipoles has been widely used in organic synthesis and the total synthesis of complex natural products Professor Mo Dongliang and Professor Su Guifa's research group are mainly engaged in the application research of nitrones in organic synthesis, and have developed a series of new series strategies of n-arylnitrones for cycloaddition and rearrangement (green chem 2017, 19, 5761; J org Chem 2017, 82, 502) and further revealed the unique chemical properties of n-alkenylnitrones in traditional organic reactions (adv synth Catalyst 2017, 359, 3545; J org Chem 2017, 82, 6417) Recently, Professor Mo Dongliang's research group has developed a new method of controlling reaction selectivity with mild and cheap iron catalyst, that is, the selective synthesis of tetrasubstituted pyridine and 3,5-disubstituted isoxazoline with n-alkenyl-o, β - unsaturated nitrone catalyzed by iron (Figure 1) Fig 1 Selective Synthesis of polysubstituted pyridine and isoxazoline (source: greenchem 2018, DOI: 10.1039 / c8gc00630j) Firstly, the author found that the tetrasubstituted pyridine compounds can be generated by reaction of n-alkenyl or β - unsaturated nitrone at 80 ℃ with 20 mol% ferric chloride as catalyst, isopropanol as solvent and 3 Å molecular sieve as additive The results of substrate expansion show that (Fig 2): different functional groups and heterocyclic substituents can be compatible on different positions of symmetric and asymmetric nitrones; in addition, for the n-alkenyl part, no matter it is chain like double substitution or ring-like n -The regioselectivity of cyclization showed that nitrone with electron donor group was propitious to form pyridine compound Fig 2 synthesis of tetrasubstituted pyridine compounds (source: greenchem 2018, DOI: 10.1039 / c8gc00630j) Secondly, the author further found that n-alkenyl-α, β - unsaturated nitrones can selectively generate 3,5-disubstituted isoxazoline compounds under the action of ferric chloride and 1,10-phenanthroline ligands The reaction has good applicability for different substituent groups on nitrone aromatic ring, especially heterocyclic substituent of nitrone, which can obtain double heterocyclic compounds in good yield (Fig 3) Fig 3 synthesis of isoxazoline compounds (source: GreenChem 2018, DOI: 10.1039/C8GC00630J) starting from isoxazoline compound 3A obtained by the above method, the author has synthesized a new kind of chiral dinitrogen ligand L6 in four steps in 37% yield Further research shows that: when the diazo ligand L6 combines with the iron catalyst to catalyze n-alkenyl-α, β - unsaturated nitrone, pyridine compounds are mainly obtained; when the copper acetate and the chiral diazo ligand L6 are used as catalysts, pyridine epoxy compounds with a yield of 40% and an EE value of 10% can be obtained (Figure 4) Fig 4 synthesis and application of dinitrogen ligands (source: greenchem 2018, DOI: 10.1039 / c8gc00630j) Finally, according to the relevant experimental results and the related literature of n − O bond breaking, the author proposed the possible reaction mechanism of n-alkenyl-nitrone forming polysubstituted pyridine and isoxazoline in the presence of iron (III) catalyst (Fig 5): nitrone 1 and iron (III) coordinate to form intermediate a, The intermediate B was obtained by intramolecular cyclization of a, followed by n − O bond cleavage to form epoxy imine C, which was ring opened under the catalysis of iron (III) to produce ketene D The intermediate e was obtained by intramolecular nucleophilic addition of enamine to enamine D, and pyridine compound 2 was obtained by elimination, and iron (III) catalyst and water were released The intermediate B can also be isomerized into intermediate F, then hydrolyzed to form isoxazoline 3, and the by-product ketone h is released Figure 5 possible reaction mechanism (source: greenchem 2018, DOI: 10.1039/c8gc00630j) The research results are published on greenchemistry Chen Chunhua, a master's student, is the first author of the paper, and Professor Mo Dongliang and Professor Su Guifa are co correspondents The research was supported by the National Natural Science Foundation of China, Guangxi Natural Science Foundation, National Key Laboratory of medicinal resource chemistry and drug molecular engineering, and Guangxi University's "hundred talents plan" fund for introducing overseas high-level talents 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, chembeango app, 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.