Research group of Professor Yan Hong of Nanjing University: the coupling reaction of nested carborane and nitrogen heterocyclic boron

Because of its unique physical and chemical properties, lead carborane has been widely used in coordination chemistry, material chemistry, pharmaceutical chemistry, supramolecular chemistry and other fields The first problem to be solved is how to modify carborane purposefully Since the 1960s, the functionalization strategy of carbon end of carborane has been widely studied In recent years, boron hydrogen bond selective functionalization method based on guiding strategy has been widely used The method of boron hydrogen bond selective functionalization on nested carborane still needs to be explored Therefore, it is a challenging task to develop an efficient and mild nested carborane functionalization method Recently, the research group of Professor Yan Hong of Nanjing University has made new progress in this field (angel Chem Int ed., DOI: 10.1002/anie.201904940) Brief introduction of Professor Yanhong's research group Professor Yanhong's research group has long been committed to the development of functional methods of carborane and the study of its properties At present, many progress has been made in the fields of selective functionalization of boron hydrogen bonds, the synthesis of light-emitting molecules containing carborane framework and so on The research group has published more than 160 papers in internationally renowned academic journals, including J am Chem SOC., angel Chem Int ed., chem SCI., scientceadvances, etc At present, the research group has 1 associate professor, 7 doctoral students, 3 master students and 3 undergraduate students Professor Jian jieyanhong, Professor of School of chemistry and chemical engineering, Nanjing University In 1993, he received a doctor's degree from Nanjing University, and then he was engaged in postdoctoral research in Switzerland, Germany and America's Notre Dame In 2005, he was a chemist of American nano VA Inc and was employed as a professor and doctoral supervisor by Nanjing University in September of the same year In 2008, he was awarded as the outstanding academic backbone leader of young and middle-aged people in the "blue and blue project" of Jiangsu Province In 2009, he was awarded the national fund for Distinguished Young Scholars In 2011, he was appointed as Tang Zhongying's special professor in Nanjing National Laboratory of micro structure (Preparatory) In 2012, he was selected into the award program of high-level discipline leader (special Professor) of Nanjing University In 2012, he won the second prize of natural science of the Ministry of education, 2015 He was elected as a foreign academician of the Russian Academy of natural sciences Frontier research achievements: the coupling reaction of nested carborane and nitrogen heterocyclic boron nitrogen oxidation without metal participation is widely used in catalysis, coordination chemistry and pharmaceutical chemistry due to its good water solubility and cyclopentadiene like coordination property The nested carborane derivatives can be prepared not only indirectly by the closed carborane debonding reaction, but also directly by electrophilic substitution reaction, oxidative substitution reaction and electrophilic induced nucleophilic substitution reaction However, these methods have some disadvantages, such as poor substrate applicability, easy to produce by-products and low atomic economy Based on the literature research and the research background of the research group, the author replaced the metal oxidant in the oxidation substitution reaction with the organic oxidant DDQ (2,3-dichloro-5,6-cyano-p-benzoquinone), and successfully obtained the nested carborane derivatives substituted by nitrogen heterocycles at the boron end Fig 1 The coupling reaction of nested carborane with nitrogen heterocyclic compounds The author first optimized the reaction conditions by using C-terminal diphenyl substituted nested carborane tetramethylammonium salt and 4-phenylpyridine as raw materials Under the optimal conditions, a single boron nitrogen coupling target product was obtained with 94% separation yield In order to investigate the substrate application scope of this method, the author first investigated a series of pyridine and quinoline substrates containing different substituents (Fig 2a, b) The results show that the steric effect of the substituent of nitrogen atom can obviously affect the reaction efficiency, but the electronic effect of substituent has no obvious effect on the reaction, and the final product can be obtained with excellent yield The compatibility of the reaction with halogen, olefin, amino group, ester group and other sensitive groups showed that the reaction had good functional compatibility Other nitrogen-containing heterocyclic compounds, such as imidazole, thiazole and oxazole, were also investigated It was found that these substrates can also react smoothly (Fig 2C) In addition, the author also found that for the nested carborane substrates with different substituents, the nitrogen atom tends to attack the boron atom with smaller ortho resistance (Fig 2D) The experimental results show that this method has excellent applicability to different nitrogen heterocyclic substrates Fig 2 Study on the application scope of intermolecular substrates Further research shows that this synthesis method can also be used for the synthesis of carborane conglomerates (Fig 3) Under the optimum reaction conditions, the intramolecular boron nitrogen coupling products can be obtained with the highest yield of 97% in one hour The results of substrate expansion show that the reaction is also affected by the steric hindrance effect of N-substituents The author has tried the gram reaction and obtained good yield This indicates that this one-step and efficient method has more synthesis and application value Figure 3 Study on the application scope of intramolecular substrate The author tried to use this method to modify two drug molecules (clotrimazole and miconazole) containing imidazole ring, and finally obtained two new molecules containing nested carborane with more than 70% separation yield When exploring the luminescent properties of boron nitrogen coupling products, the authors found that compounds 2n and 3I have AIE (aggregation induced emission) and solvation properties, respectively, in which the quantum efficiency of compound 3I in THF solvent reaches 80% (Fig 4) Figure 4 Study on the post modification and luminescent properties of the drug molecules by nested carborane Firstly, the mechanism of the reaction was verified by deuterium generation experiment The experimental results show that the reaction process may include two processes: Bridge hydrogen leaving and boron end hydrogen migration on nested carborane (Figure 5a) Based on the DFT calculation of the reaction with Liang Yong of Nanjing University, the reaction mechanism is inferred as follows: firstly, the nested carborane reacts with one molecule DDQ to form the intermediate I with one electron, and then the intermediate I takes the remaining electrons and Bridge hydrogen by another molecule DDQ to form the electric neutral intermediate II Then, the nucleophilic attack of pyridine nitrogen atom on the boron atom with small potential resistance, accompanied by the migration of hydrogen atom on boron to the neighboring boron atom, and finally the hydrogen atom moves to the other two boron atoms to form a new bridge hydrogen (Fig 5b) Figure 5 Deuterium generation experiment and reaction mechanism In conclusion, the author realized the efficient coupling reaction of nested carborane and nitrogen heterocyclic compounds by DDQ The method realizes the functionalization of inert boron hydrogen bond of carborane under mild conditions by using organic oxidant, avoids the side reactions caused by the use of metal oxidant and the use of transition metal catalyst, which meets the requirements of green chemistry The experimental work was completed by Yang Zhongming, a doctoral student, Liu Wei, a research group of Liang Yong, Nanjing University, and the spectral experiment by Zhao Weijia, a graduate student The research work was supported by the National Natural Science Foundation of China (2182010204215100421803030), the national youth program, Jiangsu Natural Science Foundation (bk20170631) and the high performance computing center (HPCC) of Nanjing 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 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 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