Li Yun, associate professor of Lanzhou University: using silver nitrate and naphthalenesulfonic acid to catalyze the construction of spiro-2-oxabicyclo [2.2.2] octane skeleton with high stereoselectivity

Introduction recently, Li Yun group of Lanzhou University reported that under the catalysis of silver nitrate and naphthalenesulfonic acid, a spiro-2-oxabicyclo [2.2.2] octane skeleton with four chiral centers was constructed by the series reaction of oxo Diels alder and 1,2-alkyl migration with high stereoselectivity (Figure 1) The reaction conditions of this method are very mild, the functional group is well tolerated, and the atom utilization rate reaches 100% It is suitable for most of the electron absorbing and electron donating amphiphiles, and provides a new idea for the synthesis of a large class of natural products with oxaoctane bridge ring skeleton (Fig 2) The results were published online in org Lett (DOI: 10.1021/acs.orglett.9b00251) Fig 1 Construction of spiro-2-oxabicyclo [2.2.2] octane skeleton (source: org Lett.) Fig 2 Introduction of Li Yun, associate professor, 2004 He graduated from pharmaceutical engineering of Sichuan University in, and was sent to Shanghai Institute of organic chemistry of Chinese Academy of Sciences to study for doctor's degree in the same year He was engaged in the synthesis of artemisinin and its analogues, a natural antimalarial product From 2009 to 2012, he conducted postdoctoral research at Novartis institutes for biomedical research (NIBR), engaged in asymmetric metal catalytic reaction research and preliminary research and development of new epigenetic drugs In 2012, he was employed by the school of chemistry and chemical engineering of Lanzhou University to carry out teaching and research in the State Key Laboratory of functional organic molecular chemistry The main research fields include the total synthesis of natural products and the study of transition metal catalytic reaction methodology At present, he has published more than 20 research papers on the international important academic journals, angelw.chem Int ed., org Lett., chem Commun., chem EUR J Frontier scientific research achievements: it is well known that under the catalysis of transition metal, o-alkynylbenzaldehyde 4 is very easy to isomerize, resulting in intermediate 6, and then [3 +2] or [4+2] cycloaddition reaction between 6 and olefin, to construct the framework of spiro -2- oxybicyclo [2.2.2] octane with high stereoselectivity by using silver nitrate and naphthalene sulfonic acid In this paper, the author envisions that when there is a tension tertiary alcohol at the end of alkynyl group, alkynaldehyde will first undergo Yamamoto type [4 + 2] cycloaddition reaction to form the intermediate 7 of onium ion, and then semipinacol rearrangement reaction will take place in this intermediate, and then the product of heterospiro ring will be obtained in a step with high efficiency (Fig 3) Fig 3 At the beginning of the study on the design of reaction process (source: org Lett.), the author selected a large number of reaction conditions with substrate 4A and styrene as model substrate (Table 1) At the beginning of the experiment, the author found that when only PD (OAC) 2 was added, the reaction would not happen at all, but after adding 1-naphthalenesulfonic acid (1-nsa), a single isomer 10A could be separated Based on the hydrogen, carbon and single crystal data of 10 years, the author confirmed that the reaction was carried out as previously predicted, and then screened Pt, Ni, Ag and other metal catalysts It was found that the optimal yield of 74% could be obtained under the synergistic catalysis of AgNO3 and 1-nsa Then, the solvent and Bronsted acid were screened It was found that the best reaction conditions were 25 ℃, CH2Cl2 as solvent, AgNO3 and 1-nsa as catalyst Table 1 Catalyst screening (source: org Lett.) after determining the best reaction conditions, the author began to expand the alkynaldehyde substrate, and found that when the alkynaldehyde linked benzene ring is connected with electron absorption group (4g-4k), the reaction rate will be faster and the yield will be higher Moreover, when the alkynyl terminal is connected to the heterocyclic ring (4m - 4O), the reaction can also proceed normally Because of the tension of the five membered ring, the reaction effect is not as good as that of the four membered ring (Fig 4) Fig 4 Alkynaldehyde expansion (source: org Lett.) Fig 5 After alkynaldehyde expansion (source: org Lett.) is completed, the author has expanded the amphiphilic body (Fig 5) The results show that the reaction effect is better when the olefins have electron rich groups In order to prove the reliability and practicability of the reaction, the product 10A was synthesized on the scale of gram (Fig 6) Fig 6 Gram scale preparation (source: org Lett.) at the end of the paper, the author conducted derivatization of product 10a, including Baeyer Villiger reaction, Wittig reaction, asymmetric reduction of carbonyl, epoxidation, etc., and achieved good yield and stereoselectivity (Fig 7) Figure 7 Derivation of product (source: org Lett.) conclusion: Li Yun group of Lanzhou University realized Yamamoto type cycloaddition tandem semipinacol for the first time under green mild conditions by CO catalysis of silver and Bronsted acid A new method for the construction of oxaoctane bridge ring skeleton with high atom utilization was developed by rearrangement reaction, and the practical value of this method was great This paper was completed by Zhang Qingyu, Ph.D., Wang Jianping and Wei Yansheng 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.