Zhang Yuan group, Lanzhou University: visible light induced functionalization of glycine derivative CSP3 − h for the preparation of polysubstituted 1,3-oxazolidine

Introduction polysubstituted 1,3-oxazolidines are common structural units in active natural products and drug molecules, and are important synthesis intermediates Therefore, the development of mild and efficient synthesis methods of polysubstituted 1,3-oxazolidines has attracted the attention of many chemists Recently, Zhang Yuan, the State Key Laboratory of functional organic molecular chemistry, Lanzhou University, reported a new method for the preparation of polysubstituted 1,3-oxazolidines by the visible light-induced functionalization of glycine derivative C SP3 − H The results were published in organic letters (DOI: 10.1021/acs.orglett.0c00234) Introduction to associate professor Zhang Yuan, associate professor of Lanzhou University, master's supervisor In 2003, he graduated from the school of chemistry and chemical engineering of Lanzhou University In 2008, he received his Ph.D degree from the State Key Laboratory of functional organic molecular chemistry, Lanzhou University Since July 2008, he has worked in the State Key Laboratory of functional organic molecular chemistry, Lanzhou University At present, the main research interests are visible light induced synthesis methodology, synthesis of functional porous organic polymers (POPs) and application of heterogeneous catalysis So far, more than 30 academic papers have been published and two national invention patents have been authorized Leading scientific achievements: the visible light-induced functionalization of glycine derivative CSP3 − h for the preparation of polysubstituted 1,3-oxazolidine C SP3 − h oxidation functionalization is considered to be the most direct and efficient synthesis method for the construction of C − C bond Compared with the traditional coupling reaction of constructing C − C bond, this new reaction avoids the tedious process of pre functionalization and de functionalization, greatly reduces the reaction steps, and has good atomic economy In recent years, the efficient synthesis of α - amino acids and heterocyclic compounds by functionalization of glycine derivative C SP3 − h has attracted extensive attention of researchers (Fig 1) However, such reactions usually require a dose of oxidants and transition metal catalysts, and some reactions need to be carried out at higher temperatures (Fig 1a) Therefore, considering the environment and practical application, the development of more "green" catalytic system and milder reaction conditions is still an urgent problem to be solved In the past decade, visible light induced redox catalysis has attracted great interest and has been widely used in organic synthesis In particular, visible light catalysis has recently been successfully used in the functionalization of glycine derivative C SP3 − H However, these reactions usually require the use of ruthenium, iridium and other precious metal photosensitizers (Fig 1b), which may limit the scale and practicability of these reaction systems In view of this, Zhang Yuan's group recently developed a visible light induced cycloaddition reaction of glycine derivatives with aryl epoxides in the form of [3 + 2], which can efficiently prepare a series of polysubstituted 1,3-oxazolidines at room temperature and air atmosphere (Fig 1c) In this reaction, a complex of electron donor acceptor (EDA) was formed between glycine derivative and benzyl iodine, and then charge transfer was induced by visible light It is worth mentioning that, unlike the previous reactions, this reaction does not need photocatalyst, metal catalyst and other oxidizing reagents, which provides a new activation mode for the functionalization of glycine derivatives with C SP3 − H Figure 1 The functional reaction of glycine derivative C SP3 − H (source: Organic letters) the author first optimized the reaction conditions with glycine ethyl ester and styrene oxide as raw materials Under the optimal conditions (HI (30 mol%), DCE / CH3CN (20 / 1), 5W blue LED) obtained the target product in 67% yield (8.5: 1dr) Control experiments show that visible light and air are indispensable in the reaction Then the author first investigated the substrate application of glycine derivatives (Fig 2) All kinds of aryl substituted glycine esters 1 can react with styrene oxide 2A The position and electronic effect of substituents on the aromatic ring have little effect on the reaction efficiency and stereoselectivity, and all kinds of esters have no obvious effect on the reaction Besides glycine ester, other glycine derivatives such as glycine amide, glycine derived dipeptide and α - aminoketone can also participate in this reaction Figure 2 Substrate application range of glycine derivatives (source: Organic letters) the author also investigated the substrate application range of ethylene oxide derivatives (Figure 3) All kinds of aryl substituted ethylene oxide derivatives can react smoothly However, when alkylated ethylene oxide is used as the substrate, the reaction can not take place Fig 3 Application scope of epoxide substrate (source: Organic letters) The author designed a series of experiments to study the mechanism of this reaction (Fig 4) When the free radical inhibitor tempo was added to the reaction system, the reaction was completely inhibited, and the adducts of tempo and alkyl radicals could be detected by high-resolution mass spectrometry, which indicated that the reaction might go through a free radical process Under the standard reaction conditions, benzyl iodide compound 7 can also react with glycine ester 1a The red shift phenomenon after mixing 1a and 7 can be observed by UV-Vis absorption spectrum Therefore, the author speculates that 1a and 7 can form EDA complex In addition, under the standard reaction conditions, imine 9 can also react with epoxy 2a, which shows that imine 9 is also an important intermediate in the reaction process Figure 4 Mechanism experiment (source: Organic letters) Based on the above experimental results, the author speculated the possible reaction mechanism (Figure 5) Firstly, styrene oxide 2a was rapidly converted into benzyl iodide 7 under the action of Hi, and glycine ester 1a (donor) and 7 (acceptor) formed EDA complex a Then, a undergoes electron transfer induced by visible light, forming free radical ion pair B B can be further dissociated into free radicals C and D Then, the free radical D is oxidized to benzyl iodide 7 by O 2, at the same time, O 2 is converted to O 2 − • (which can be detected by EPR), and the imine 9 is obtained by extracting electrons and protons from the free radical C Finally, the intermediate e is formed by the reaction of benzyl iodide 7 and imine 9, and then 1,3-oxazolidine 3a is formed by intramolecular nucleophilic substitution Figure 5 Possible reaction mechanism (source: Organic letters) related research was published in organic letters (DOI: 10.1021 / ACS Orglett 0c00234) The first author is Yang Xiaorong, Ph.D student of Lanzhou University, and the corresponding author is Zhang Yuan, associate professor of Lanzhou University The research work is supported by NSFC and NSFC of Gansu Province Today, Yang Xiaorong pays more and more attention to the characters and scientific research in the economic life, China has ushered in the "node of the outbreak of science and technology" 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.