Liu Yankai group, Ocean University of China: asymmetric organic catalytic synthesis of spiro bridge or cage heterocyclic compounds

The heterocyclic skeleton containing spiro bridged or cage like multi ring system can be used as an important intermediate for the synthesis of compounds with pharmacological and physiological activities Therefore, the asymmetric synthesis of such skeletons has attracted the attention of chemists Recently, Liu Yankai group of Ocean University of China has developed an efficient multi-component catalytic system, which can synthesize a series of spiro bridge or cage heterocyclic compounds with high stereoselectivity The results were recently published in the organizational letters (DOI: 10.1021/acs.orglett.9b02375) Liu Yankai, associate professor, received his Ph.D from Sichuan University in July, 2010, under the guidance of Professor Chen Yingchun (outstanding youth) Main research interests: asymmetric synthesis catalyzed by small chiral organic molecules and synthesis of chiral drugs In 2009, as an exchange student, a 4-month chiral asymmetric catalysis study was carried out in Prof a berkesel research group, University of Cologne, Germany In 2011, he won Marie Curie fellowship, the most famous scholarship in the European Union, and conducted postdoctoral research under the guidance of Prof P melchiorre, Institute of Chemical Research of Catalonia (iciq) in Spain Leading scientific research achievements: asymmetric organic catalytic synthesis of spiro bridge or cage heterocyclic compounds The research team found that o-hydroxycinnamaldehyde, due to its structural characteristics, is very suitable for the construction of complex multi ring system with bridge ring structure after being activated by imine salt Therefore, the author thought that through its reaction with multi carbonyl substrate, it may be possible to realize chiral spiro- Construction of bridge ring and cage like multi ring skeleton However, due to the existence of multiple reaction sites in the substrate, how to control the regioselectivity and stereoselectivity of the reaction is an urgent problem to be solved In order to overcome this difficulty, the author proposed a new catalytic model: o-hydroxycinnamaldehyde was activated to obtain imine positive ion in the presence of secondary amine catalyst and carboxylic acid, and formed ion pair with carboxylic acid negative ion; bifunctional thiourea tertiary amine catalyst activated bicarbonate substrate and o-hydroxycinnamaldehyde in the form of imine salt by hydrogen bond The final five component catalyst substrate complex can produce spiro bridge or cage heterocyclic compounds with high regioselectivity and stereoselectivity When aromatic dicarbonyl substrate 2 is applied, the product 5 containing spiro bridged framework can be obtained successfully Through the establishment of model reaction and the selection of conditions, the author obtains the optimal reaction conditions, and further studies the applicability of the substrate (Figure 1) Fig 1 substrate scope investigation I (source: Organic letters) the author further found that when aliphatic dicarbonyl substrate was applied, the reaction would go through different processes to obtain complex cage heterocyclic product 7 The author also inspected the applicability of the substrate (Fig 2) Fig 2 substrate range investigation II (source: Organic letters) Then, the author carried out a series of structural transformations on substrates 5A and 7a respectively (Fig 3) Firstly, substrate 5A can be oxidized to product 8 under the action of DMP, fluorinated product 9 can be obtained under the action of DAST, and compounds 10 and 11 can be obtained under the action of BF3 · Et2O and bnsh and et3sih respectively In addition, substrate 7a can react with Swern to produce product 12 Compound 13 can be obtained under the action of BF 3 · et 2O and et 3sih Reaction with acetic anhydride in alkaline condition can introduce acetyl group to hydroxyl to produce product 14 Figure 3 product derivatization (source: Organic letters) summary, the author has developed a new catalytic system, which can construct a complex structure of screw bridge ring and cage skeleton with high region and high stereoselectivity In addition, by controlling the type of substrate, the reaction can go through different processes to get different skeleton products The developed reaction substrate has a wide range of applications and high stereoselectivity The first unit to complete this paper is the school of medicine of Ocean University of China Liu Yankai, associate professor of the school of medicine of Ocean University of China, and Wang Cong, Professor of nuclear magnetic office, are the co correspondents of this article The first author of this paper is Wang Chen, a postgraduate of School of medicine, Ocean University of China, supported by NSFC Shandong joint fund 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 website, chembeangoapp, chembeango official micro blog, CBG information wechat subscription number and other platforms jointly launch the column of "people and scientific research", approach the representative research groups in China, pay attention to their research, listen to their stories, record their demeanor, and explore their scientific research spirit.