Li guigen, Nanjing University: copper and cobalt co catalyzed cross dehydrogenation coupling reaction of benzoxazoles

As an important structural unit, lead bis azaaryl compounds are widely found in drugs, functional materials, ligands and natural products The cross dehydrogenation coupling reaction (CDC) can avoid pre functionalization, and the by-product is only hydrogen or water, which is an ideal strategy to construct C-C bond In recent years, the formation of 1,3-nitro-heterocyclic-1,3-nitro-heterocyclic compounds by the strategy of cross dehydrogenation coupling has attracted extensive attention and made some progress At present, the existing problems are high loading of heavy metal salts and narrow range of substrates Recently, Professor Li guigen, research group of Institute of chemistry and biomedical science, School of chemistry and chemical engineering, Nanjing University, used CO (NO 3) 2.6h 2O / Cu (OAC) 2.h 2O for the first time In the catalytic system, oxygen in the air is used as oxidant, and with the aid of sodium acetate, valuable asymmetric bis heteroaryl compounds have been constructed, including the selective construction of bis benzoxazoles, which has not been reported in previous CDC reactions The cross dehydrogenation and coupling of (benzo) azole can be realized by using the catalytic amount of cobalt and copper, which provides a new method for the synthesis of biarylhydrocyclic compounds with potential activity and application value In addition, this reaction avoids the use of equivalent heavy metal salt in the previous reaction, and conforms to the principles of economy and environmental protection The results were published in green chem (DOI: 10.1039 / c9gc02464f) Fig 1 cross dehydrogenation and coupling reaction of (benzo) triazole catalyzed by cobalt and copper (source: Green chem.) brief introduction of Professor Li guigen's research group main research directions and recent achievements of Professor Li guigen's research group: (1) development of new chiral ligands We found and defined the chirality of polyhedral 3D and the symmetry of polyhedral pseudo C 2 The latest achievement "multilayer 3D chirality and its synthetic assembly" was published on research (research, 2019, 6717104) (2) Development of new chiral gap reagent and gap chemical technology Green chemical synthesis without column chromatography or recrystallization is realized through gap Chemistry (J org Chem 2016, 81, 2488; J org Chem 2016, 81, 7654; J org Chem 2018, 83, 644) (3) Hydrocarbon bond functionalization and cross dehydrogenation coupling reaction (nature commin 2015, 6, 6462; J am Chem SOC., 2016, 138, 12775; chem – EUR J., 2016, 22, 12286; J org Chem., 2016, 81, 11743; org Lett., 2016, 181258; org Lett., 2017, 19, 4676; org Lett., 2017, 19, 5589; green chem 2019 , DOI: 10.1039/c9gc02464f ）。 Welcome to join the research group of Professor Li guigen, School of chemistry and chemical engineering, Nanjing University Prof Li guigen was born in September 1962 Bachelor of Jiangsu Normal University (1984), master of Nankai University (1987), assistant professor of Chemistry Department of Nanjing University from 1987 to 1990 He received his Ph.D from the University of Arizona in 1995 From 1995 to 1997, he played a key role in the research of 2001 Nobel Prize in chemistry by Professor K Barry Sharpless In 1997, he successively served as assistant professor / Associate Professor / Professor / Professor / professor with the highest honor of Texas Institute of Technology (Paul Whitfield horn Professor) and adjunct professor of Nanjing University National Fund for Distinguished Young Scholars (Overseas), 2011 China national special expert, Jiangsu Province "entrepreneurship and innovation plan", Nanjing City "321 plan" winner 2015-2018 was selected as "China's highly cited scholars" for four consecutive years Presided over key and general projects of NSFC At present, he is the evaluation expert of National Natural Science Award, Chen Jiageng science award of Chinese Academy of Sciences, Organization Department of the Central Committee, State Administration of foreign experts, Natural Science Foundation Committee, excellent achievement award of scientific research of institutions of higher learning of the Ministry of education, national fund for Distinguished Young scholars and other awards, consultant expert of strategic research project research group of the Ministry of education, member of International Advisory Committee of Shanghai Jiaotong University（ 2015-2016), member of innovation team of Shanghai Institute of organic chemistry, Chinese Academy of Sciences (2004-2011), distinguished expert of life chemistry collaborative innovation center of Nanjing University, member of Academic Committee and International Committee of School of chemical engineering, executive director of Institute of chemistry and biomedical science of Nanjing University, chairman of Southwest Branch of American Chemical Society, etc More than 330 papers were published, h-index = 53, of which 5 papers were top 1% highly cited papers The main contributions are as follows: (1) the 3D chirality of polyhedron, the chirality of organic sandwich and the symmetry of pseudo C 2 of polyhedron were found and defined (2) A new type of chiral gap reagent and the application of gap chemistry were established to realize the green chemical synthesis without column chromatography or recrystallization (3) Metal catalyzed amination of alkenes and alkynes was realized (4) The first polypeptide liquid phase synthesizer in the world (www.gappetides Com) was established (5) A new chemical concept of gasyn (Group assisted synthesis) was proposed The design of functional groups was used to improve the efficiency of organic synthesis (6) It can be used in the synthesis of β - halogenated Morita Baylis Hillman (MBH) and non Lewis base induced MBH (7) Domino cyclization and site-specific hydrocarbon bond functionalization Lu Hongjian, associate professor, distinguished professor of Jiangsu Province, doctoral supervisor, team leader of "functional organic small molecule synthesis" of Nanjing University He graduated from China University of science and technology in 2001 In 2006, he graduated from Shanghai Institute of organic chemistry with the tutor of Professor Li Chaozhong From 2007 to 2012, he was engaged in postdoctoral research at the University of South Florida, with the tutor of Professor Peter X Zhang In July 2012, he was an associate professor of the school of chemistry and chemical engineering of Nanjing University So far, 12 articles have been published in the top journals of primary chemistry, such as angelw Chem Int ed., J am Chem SOC., etc., and a series of outstanding research results have been achieved With an area of about 200 square meters, it now directs a research team composed of four doctoral students, five postgraduate students, one assistant researcher and several undergraduate students Presided over two general projects of NSFC (2015-2018; 2019-2022), and participated in a key project of NSFC (2014-2018) as a sub project leader As the chief scientist, he established a scientific research team and presided over the scientific and technological innovation team of "blue and green project" in Jiangsu Province (2014-2017) In 2012, he was hired as "Jiangsu special professor", and in 2015, he was assessed as excellent, and obtained the qualification of "Jiangsu special professor" Frontier research achievements: copper and cobalt co catalyzed cross dehydrogenation coupling reaction of oxygen oxidation (benzo) oxazole compounds is an important structural unit of commercial drugs, functional materials, ligands and natural products The cross dehydrogenation coupling (CDC) reaction is the most ideal strategy for the formation of C-C bond, which can remove the hydrogen atoms from two molecules or two carbon atoms on one molecule and produce coupling without the need for advanced functionalization and greatly shorten the reaction steps However, it is particularly challenging to synthesize heterocyclic compounds by using CDC reaction method The main reasons include: (1) the nitrogenous heterocyclic compounds with weak acidity are easy to be oxidized, and the coupling reaction conditions are often strong; (2) the nitrogenous heterocyclic compounds with weak acidity are prone to self coupling reaction Therefore, the team needs to control the reactivity and selectivity of the two metallization processes in the catalytic cycle, to suppress the unwanted self coupling reaction, so as to improve the yield of cross coupling reaction Fig 2 in recent years, 1,3-nitrogen-containing heterocycle-1 has been formed through the CDC reaction strategy, in which heavy metal salt is used as oxidant and air is used as oxidant, Remarkable progress has been made in 3-nitrogenous heterocyclic compounds (Fig 2) In 2011, the ofial research group first reported the CDC reaction of benzoxazoles with oxazole or thiazole using palladium as catalyst and equivalent silver salt as oxidant; in 2012, you research group reported the cross dehydrogenation coupling of more similar Oxazoles with Oxazoles under palladium catalysis and copper salt as oxidant; in 2012, Wang In the same year, Zhang group realized the reaction of benzothiazole and thiazole by using the amount of copper catalyst under the action of equivalent silver carbonate However, there are still many problems to be overcome First of all, the equivalent heavy metal is used as oxidant in the reaction, which has great environmental pollution and high reaction cost Secondly, this type of cross coupling reaction has never been reported for the selective construction of benzoxazoles - benzoxazoles Therefore, it is of great significance for the economy and environmental protection of practical production to find a green oxidant to realize a wider range of benzoxazole CDC reactions It has been reported that transition metal catalyzed coupling reactions can be realized by using air or oxygen as oxidant, but these reactions are mainly used to construct self coupling products, which are not suitable for selectively constructing cross coupling products Recently, researchers have found that Co metal catalysis has a unique application in CDC reaction It can not only control the reactivity and selectivity of the metallization process related to the catalytic cycle, but also inhibit the formation of self coupling products, so as to improve the yield of CDC reaction In 2006, Li group reported for the first time the CDC reaction of 1,3-dicarbonyl compounds with allyl compounds under co catalysis of cobalt and copper In 2015, Lei research group reported the CDC reaction using zinc and indium as co catalyst, triethylamine as base, aldehyde and terminal alkyne In 2018, Zhang research group reported the CDC reaction of compounds containing guiding groups co catalyzed by cobalt and manganese with oxygen as oxidant Inspired by these reports and the previous studies on coupling reactions, Professor Li guigen's research group reported the co catalyzed (benzo) azole type CDC reactions with air as oxidant The results of substrate screening showed that benzothiazole 1A could cross dehydrogenate with benzoxazole 1B in 76% yield with Cu (OAC) 2 · H 2O and CO (NO 3) 2 · 6h 2O as catalysts and 1.0 equivalent sodium acetate as assistance Fig 3 CDC reaction of benzothiazole and benzoxazole with different substituents (source: Green chem.) under the optimal conditions, the author screened the substrate range of benzothiazole and benzoxazole (Fig 3), and found that benzothiazole can react with electron donor benzoxazole (3b, 3C, 3D and 3G) ）It can also react with electron absorbing benzoxazole (3E and 3f) in good yield Benzoxazole can also