Li Yang research group of Chongqing University: trifunctionalization of aromatic ring through the nucleophilic reaction of aromatic alkyne and Diels alder series connection

As one of the most active organic intermediates, lead arylyne can realize the ortho bifunctionalization of aromatic ring Since the beginning of this century, with the wide application of its mild formation and the development of new reaction types, the chemistry of arylacetylene has made rapid development In recent years, Professor Li Yang's research group of Chongqing University has been devoted to the preparation and application of polysubstituted aromatic hydrocarbons from arylalkynes, and has made a series of achievements The research group has realized the multi-functional transformation of various aromatic Alkynes by using the independently developed 1,2-phenylenediyne reagent (dominoene) and other methods (j.am Chem SOC., 2015, 137, 5670; j.am Chem SOC 2016, 138, 10814; j.am Chem SOC., 2017, 139, 623; j.am Chem SOC., 2018, 140, 3555; J Am Chem Soc 2018 , 140 , 13214; Org Lett .,  2016 ,  18 , 3130; Org Lett .,  2016 ,  18 , 3726; Org Lett .,  2018 ,  20 , 1919; Chem Soc Rev .,  2017 ,  46 , 1707 ）。 Recently, Professor Li Yang's research group has made the latest progress in this field The research results are published in angelw Chem Int ed (DOI: 10.1002 / anie 201911730) Prof Li Yang's research group focuses on two fields: synthetic organic chemistry and bioinorganic chemistry In the field of synthetic organic chemistry, the goal of the research group is to construct complex molecular skeleton quickly through novel and green chemical conversion means, so as to provide a new way for the synthesis of bioactive and drug active molecules One of the main research directions is to prepare a wide range of polysubstituted aryl compounds through the intermediate preparation of aryl alkyne activity; in Bioinorganic Chemistry Xiang, the research group is committed to creating a new multi tooth ligand framework with pre-organization characteristics, which can be used in the biomimetic coordination of polynuclear metals, and hopes to further obtain the application of the catalytic chemical conversion of polynuclear metals Prof Li Yang, Li Yang, received his bachelor's degree (inorganic hydrothermal synthesis) from Jilin University in 2000; his doctor's degree (total synthesis of natural products) from the University of Georgia in July 2006; his postdoctoral research (organic methodology) at the University of Toronto in Canada in September 2006; his postdoctoral research (organic methodology) in May 2009, may 2012 MIT is engaged in postdoctoral research (bioinorganic chemistry); since July 2012, professor and doctoral supervisor of School of chemistry and chemical engineering, Chongqing University "Thieme Chemistry Journals Award" (2016) and "Asian core program letureship awards" (2018, Singapore and Thailand) Frontier scientific research achievements: in recent years, through the nucleophilic reaction of Domino and Diels alder series connection to realize the trifunctionalization of aromatic ring, the research group has realized the amphiphilic transformation of thiobenzoamide and sulfonamide by using 1,2-phenylenediyne (Figure 1a, strategy I), and obtained the multi functionalized products of benzene ring Then, we further use domino to combine nucleophilic and olefinic reactions, and realize orderly series connection of different reaction types, so as to obtain a variety of products with benzo-n-heterocyclic skeleton structure (Fig 1b, Strategy II) Recently, based on the previous research work, the research group took the styrene structure as the reaction end of the series reaction of 2,3-alkyne II, and obtained the benzo fused ring structure with [6, N, 6,6] skeleton structure by using the nucleophilic of 1,2-phenylenediyne and Diels alder ring addition series (Fig 1b) Figure 1 Research background and project design (source: angelw Chem Int ed.) In this study, the project team further explored the leaving and reactivity of the second leaving group in the precursor of 1,2-phenylenediyne The study found that there were 2, The condition a of 6-difluorobenzenesulfonic acid radical leaving group has more advantages than the other precursors (Fig 2) To some extent, it makes up for the TPTB reagent containing two high active OTF groups (the first generation of dominoenzene alkyne precursor, bailingwei reagent 2096316) and ttpm containing a relatively inert OTS group The absence of departure between reagents (the second generation of the precursor of domino benzyne and the reagent 9110775) Fig 2 Comparison of the activity of different precursors of dominoene (source: Angel W chem Int ed.) then the research team expanded the range of substrates and found that the reaction has a variety of substrate application range (Fig 3) The highly condensed [6, N, 6,6] - tetracyclic and [6,5,6,6,6] - pentacyclic structures can be obtained by the nucleophilic DA series reaction of 1,2-phenylenediyne with sulfonamide substrates with styrene structure Among them, the [6,5,6,6,6] - pentacyclic architecture (6R ~ 6V) has a specific enantioselectivity Figure 3 Substrate range (source: angelw Chem Int ed.) it is worth mentioning that 6W of nitrogen heterocyclic product can be converted into ergot base framework (Figure 4) Compound 6W was synthesized by two steps of pyridine N-methylation and NaBH 4 reduction in one pot Then compound 11 removed TS group and oxidative dehydrogenation to obtain ergot base framework 12 The synthesis route is simple and efficient Fig 4 Synthesis of ergot base skeleton (source: angel Chem Int ed.): Professor Li Yang's research group has realized the series connection of nucleophilic and Diels alder reactions by using the precursor of domino benzyne In one step, three chemical bonds of C-N, C-C and C-C have been constructed, and the three functional structures of aromatic ring with benzo polycyclic system have been obtained At the same time, the departures of different departing groups and the enantioselectivity of the series reaction were studied This reaction provides a convenient and efficient method for the synthesis of benzo - polycyclic framework, which has potential application value The above research work was supported by the general program of NSFC (21772017) 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