Li Junlong research group of Chengdu University: palladium catalyzed selective [3 + 2] cyclization of 5-alkenylthiazolone to construct multi-season carbon parallel framework

Li Junlong, research group of Sichuan Institute of antibiotic industry, Chengdu University, has been devoted to the study of catalytic synthesis for a long time Recently, the research group has made new progress in this field: through palladium catalyzed [3 + 2] cyclization of 5-alkenylthiazolone and alkenyl carbonate, with excellent chemical selectivity and non enantioselectivity, we have constructed a parallel ring skeleton with multiple heteroatom quaternary carbon centers Relevant results are published online in org Lett (org Lett., 2019, 21, 7478-7483) The first author is Dr Liu Yue from Sichuan Institute of antibiotic industry, Chengdu University Li Junlong, born in 1986, is a distinguished researcher of Sichuan Institute of antibiotic industry, Chengdu University In 2013, he graduated from Sichuan University and studied under Professor Chen Yingchun, engaged in the research of asymmetric organic small molecule catalysis Subsequently, with the support of Humboldt scholarship, he went to the Institute of organic chemistry of the University of Minster in Germany for postdoctoral research and studied with the famous chemist, Professor Frank glorius, to continue his research work in the direction of asymmetric catalysis In May 2015, he joined Sichuan Antibiotic Industry Research Institute of Chengdu University to independently carry out scientific research work, mainly engaged in catalytic synthesis and Research on new synthesis routes of chiral drugs Since our independent work, we have continued to study all kinds of asymmetric catalytic cyclization reactions At the same time, we focus on the development of some new catalytic strategies At present, as the first author or corresponding author, he has published a number of relevant research results in the international mainstream academic journals of chemistry such as angelw Chem Int ed., ACS catalyst., green chem., org Lett., chem Commun., adv synth Catalyst Some of the research results are further introduced by synfacts, synfacts and other columns Leading scientific research achievements: palladium catalyzed selective [3 + 2] cyclization of 5-alkenylthiazolinone to construct multi-season carbon parallel framework Compounds containing heteroatom quaternary carbon centers are widely used in natural products, pesticides and drugs due to their unique biological activities Researchers have been committed to the synthesis of such framework However, there are few reports about the catalytic synthesis of quaternary carbon centers which are replaced by three different types of heteroatoms In the previous work, the research group reported an example of efficient construction of complex 6,8-dobco drug skeleton (ACS catalyst 2019, 9, 8256) by one-step chemical reaction with vinyl carbonate (VECs) as substrate, catalyzed by metal / organic relay Inspired by this work, the authors constructed a novel framework containing multiple quaternary carbon centers by palladium catalyzed [3 + 2] cyclization of VECs and 5-alkenylthiazolidone (Fig 1) Interestingly, the highly electrophilic unsaturated amides in the structure of 5-alkenylthiazolidone usually undergo cyclization in a variety of catalytic systems, while in this palladium catalytic system, they do not affect the normal progress of the target reaction Fig 1 palladium catalyzed [3 + 2] cyclization of 5-alkenylthiazolone (source: org Lett.) under optimized conditions, the universality of the reaction substrate was studied Firstly, the 5-alkenylthiazolidone-1 with different electronic effect groups, aromatic thick ring and aromatic heterocycle was used as the substrate for the reaction, and thiazolo [2,3-b] oxazolidone-3 was obtained with excellent chemical and non enantioselectivity Subsequently, the author further studied the substrate compatibility of vecs2, and the results showed that the reaction also showed good universality for the substituents on vecs2 (Fig 2) Fig 2 study on the application scope of substrate-1 (source: org Lett.) it is worth mentioning that the substrate of six membered cyclic compound VECs 4 can also be well compatible with the reaction, and the corresponding product 5 can be obtained through the [4 + 2] cyclization reaction (Fig 3) The author has obtained a series of six membered bicycles with multiple quaternary carbon centers Fig 3 substrate application Study-2 (source: org Lett.) due to the unique n, O of thiazolo [2,3-b] oxazolidone product 3, The author further explored the potential of S-SUBSTITUTED quaternary carbon centers, and found that Fisher carbene, which was produced in situ by 3-diazo-indole, can selectively insert between C-S bonds in the paracyclic structure under the condition of rhodium catalysis, and form complex spiro-cyano-indole 7 with spiro quaternary carbon centers The study of substrate universality shows that the reaction has good expansion value and application potential (Figure 4) Fig 4 study on the application scope of the substrate-3 (source: org Lett.) in addition, the author further carried out derivative transformation for spirooxyindole 7b to explore the possibility of introducing more heteroatom quaternary carbon centers into the molecular structure The experimental results show that when m-CPBA is added into toluene solution at 50 ° C, 7b can undergo stereoselective oxidation of exoolefins and sulfur atoms at the same time, resulting in compound 8a, whose structure and relative configuration are confirmed by X-ray single crystal diffraction When m-CPBA was used, dichloromethane was used as the solvent, and the reaction temperature was reduced to 0 ° C, 7b only selectively oxidized sulfur atoms, and 8b was obtained In addition, at 0 ° C, using dichloromethane as the solvent, treating 8b with vinyl magnesium bromide and tmscl will further trigger conjugation 1, 4-addition, tmscl mediated Pummerer reaction and rearrangement cyclization were carried out in series A new indole heterocyclic compound 9 with quaternary carbon center on the seven membered ring was obtained Its product structure and stereostructure were confirmed by X-ray single crystal diffraction Fig 5 further derivative transformation of compound 7b (source: org Lett.) the research results are published in org Lett (org Lett., 2019, 21, 7478-7483) This scientific research achievement has been greatly supported by the National Natural Science Foundation of China, the "thousand talents plan" of Sichuan Province, the outstanding youth fund of Sichuan Province, the "Chengdu floating plan" of Chengdu talents, and the research start-up project of Chengdu University 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 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