Pan Weidong / Ren Hai, Key Laboratory of natural product chemistry, Chinese Academy of Sciences, Guizhou Province

The oxidation of alcohols to alkoxy radicals has always been a challenging topic in the field of organic synthesis How to develop cheap and easily available catalysts to oxidize alcohol to form alkoxy radicals and realize the functionalization reaction initiated by alkoxy radicals has very important theoretical significance and practical value Recently, pan Weidong / Ren Hai research group, Key Laboratory of natural product chemistry, Chinese Academy of Sciences, Guizhou Province (Key Laboratory of natural product chemistry, Guizhou Medical University) has made new discoveries and breakthroughs in this field (organic letters, 2019, DOI: 10.1021/acs.org lett 9b02394) Brief introduction of Pan Weidong / Ren Hai research group pan Weidong / Ren Hai research group has 7 fixed staff members, including 3 with doctor's degree; 1 post doctoral student, 2 doctoral students and 11 graduate students He is mainly engaged in the research of pharmaceutical chemistry and synthesis methodology based on natural product orientation Pan Weidong, a researcher, graduated from the 6th University of Paris in France in October 2005 with a Ph.D in molecular chemistry From 2005 to 2007, he worked as a postdoctoral researcher in bioorganic chemistry at Namur University in Belgium At present, he is a researcher in the Key Laboratory of natural product chemistry, Chinese Academy of Sciences, Guizhou Province (the Key Laboratory of natural product chemistry, Guizhou Medical University), deputy director and discipline leader of the State Key Laboratory of medicinal plant efficacy and utilization jointly established by the Ministry of Guizhou Province He is mainly engaged in the research of natural pharmaceutical chemistry, with the main research directions as follows: 1) the discovery, total synthesis and derivative synthesis of natural pharmaceutical active lead compounds; 2) the research of pesticide from plant (monomer or compound preparation) He has successively been selected into the "light of the west" talent plan of Chinese Academy of Sciences, the "one hundred" level candidates of the "ten hundred thousand" talent training plan of Guizhou Province, the outstanding young scientific and technological talents of Guizhou Province, the 12th Youth Science and technology award of Guizhou Province, the special allowance of Guizhou government and the administrator of Guizhou Province, etc He has successively presided over more than 20 scientific research projects such as the major science and technology special project of "major new drug creation" of the Ministry of science and technology and the National Fund (5 projects) More than 80 papers have been published on relevant research results, including more than 40 SCI papers published by the first or corresponding author; 8 domestic and foreign patents have been applied, including 2 PCT international patents (1 patent authorized by the United States); 1 first prize of Guizhou science and technology progress Prof Ren Hai graduated from Tongji University in 2012 with a bachelor's degree in engineering In 2017, he received his doctorate from Shanghai Institute of organic chemistry, Chinese Academy of Sciences, and studied with Academician Tang Yong, a famous organic chemist Since May 2018, he has worked in the Key Laboratory of natural product chemistry, Chinese Academy of Sciences, Guizhou Province (the Key Laboratory of natural product chemistry, Guizhou Medical University) for scientific research The "light of the West - Young Scholars" of Chinese Academy of Sciences mainly focuses on the research of metal catalyzed organic synthesis methodology and application Frontier research achievements: Research on the formation and functionalization of oxazoline / copper catalyzed alkoxy radicals Since the 1990s, the research on copper catalyzed aerobic oxidation of alcohols to corresponding carbonyl compounds has made rapid development and a series of encouraging results However, the oxidation of alcohol to oxygen radicals catalyzed by copper has not been reported As a kind of chemical raw material, chromol has been widely used in synthetic chemistry The common reaction is mainly dependent on the strong nucleophilic of indole aromatic ring in chromol module, but the direct use of the tandem reaction initiated by alcohol hydroxyl of chromol to construct indole heterocyclic compounds is rare Recently, the research group selected chromol as the reaction substrate, and successfully realized the formation of alkoxy radicals using oxazoline / Cu (II) catalyst without adding oxidants such as tempo; then, alkoxy radicals generated C3 free radical furan indoline intermediate through intramolecular addition ring Under the solvation effect, the intermediate can generate different products through free radical dimerization and alkoxylation respectively, and finally realize the one-step synthesis of novel 3a, 3A '- difuran indoline and 3-alkoxy substituted furan indoline compounds (Fig 1) Figure 1: the formation of alkoxy radicals catalyzed by copper and the functionalization reaction (source: Organic letters) Under the optimized conditions, the research team studied the universality of the reaction substrate Under the condition of THF as solvent, our group found that the chromoalcohol substrate with electron rich substituents on benzene ring had better effect and could achieve medium to excellent yield It is worth mentioning that this is the first time to realize the synthesis of 3a, 3A '- difuran indoline, a kind of chiral center compound with continuous high steric hindrance, which has very high efficiency and atomic economy (Fig 2) When alcohol is selected as the solvent, the reaction has a wider range of substrate universality Using this method, a series of 3-alkoxy substituted furan indoline derivatives can be synthesized efficiently and economically (Fig 3) Figure 2: substrate universality of free radical dimerization (source: organicletters) Figure 3: substrate universality of alkoxylation (source: organicletters) the research team has carried out a systematic and in-depth study on the mechanism of this reaction (Figure 4) First, they added 1 equivalent of tempo to the reaction system, and found that there was the formation of aldehyde, the product of aerobic oxidation, which proved that Cu (II) - or intermediate could be formed under the condition of the catalyst Through the classical free radical clock experiment, they proved the formation of alkoxy radicals under this catalytic condition When chromol was cross tested with n-methylindole substrate with small steric hindrance, the product of dimerization could also obtain considerable yield, which indirectly proved that the reaction went through the process of C (SP 3) - C (SP 3) radical dimerization The research group has also done a lot of research on catalysts, including the preparation and catalytic activity of catalyst complexes, the measurement of redox potential of catalysts, etc., which provides strong evidence for the alkoxy radical pathway of the reaction The possible reaction pathway proposed finally is shown in Figure 4D: first, Cu (II) species and alcohol form intermediate a through ligand exchange reaction, and then they form alkoxy radical intermediate B through single electron transfer The intermediate undergoes the addition of intramolecular alkoxy radicals to form intermediate C, and intermediate C undergoes the dimerization of carbon radicals to form target product 2A Meanwhile, intermediate C can be further oxidized to form 3-carbocation intermediate, which is captured by alkoxy group to form product 3 At present, the application of this strategy and more in-depth mechanism research are in progress Figure 4: reaction mechanism and possible reaction path (source: organicletters) Summary: Pan Weidong / Ren Hai project first reported the process of copper catalyzed alcohol hydroxyl oxidation to alkoxy radicals, and realized the functional reaction initiated by alkoxy radicals In this strategy, novel 3a, 3A '- difuranoindoline and 3-alkoxy substituted furoindoline compounds were constructed efficiently and economically This work was published on organic letters under the title of "oxazoline - / copper catalyzed alkoxyl radical generation: solved switched to access 3a, 3A '- bisfuroindoline and 3-alkoxyl furoindoline" (DOI: 10.1021 / ACS Org lett 9b02394) Ren Hai is the first and co-author of this article, and pan Weidong is the co-author The above research was supported by the science and technology foundation of Guizhou Province, the National Key Laboratory for the efficacy and utilization of medicinal plants jointly established by the Ministry of science and technology of Guizhou Province, and the "light of the West youth scholar" project of the Chinese Academy of Sciences 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.