Chen Jiuxi's team from Wenzhou University: palladium catalyzed series reaction of 2 - (cyanomethoxy) chalcone with arylboric acid: selective synthesis of benzofurano [2,3-c] pyridine derivatives

Introduction: Chen Jiuxi's team, School of chemistry and materials engineering, Wenzhou University, is dedicated to the study of the series reaction of organoboron reagents and nitriles catalyzed by transition metals Recently, the research group has made new progress in this field: palladium catalyzed series reaction of 2 - (cyanomethoxy) chalcone with arylboric acid was developed to selectively synthesize benzofurano [2,3-c] pyridine derivatives (DOI: 10.1021/acs.orglett 9b04185) Profile of Professor Chen Jiuxi: Chen Jiuxi, Oujiang distinguished professor, researcher, master supervisor of Wenzhou University, top young talents of Zhejiang "ten thousand talents plan", director of local cooperation department and director of Continuing Education Department of Wenzhou University In 2004, he graduated from the Department of chemistry of Wenzhou Normal University (now the school of chemistry and materials engineering of Wenzhou University), obtained the master's degree of Wenzhou University in 2007, obtained the doctor's degree of Zhejiang University of technology in 2014, and has worked in Wenzhou University since September 2007 In recent years, a series of research achievements have been made in the series reaction of organoboron reagents and nitriles catalyzed by transition metals He has presided over the projects of National Natural Science Foundation, Zhejiang Natural Science Foundation and Zhejiang public welfare technology application research plan, etc.; he has published more than 90 SCI papers in the journals of org Lett., green chem., chem Commun., org Chem Front., J org Chem., adv synth Catalyst., etc., authorized more than 30 invention patents, and won the third prize (ranking first) of Zhejiang science and technology award“ Excellent projects (ranking first) of Zhejiang Natural Science Foundation during the 11th five year plan Brief introduction of frontier scientific research achievements: palladium catalyzed series reaction of 2 - (cyanomethoxy) chalcone and arylboric acid: selective synthesis of benzofurano [2,3-c] pyridine derivatives in the field of organic and material chemistry It is an important research hotspot to generate high value-added target products through selective dominoes with easy to obtain substrates as starting materials Based on the strategy of conjugation of arylboric acid with α, β - unsaturated aldehydes and ketones catalyzed by transition metals, the preparation of β - aryl substituted carbonyl molecules has attracted wide attention (J org Chem 2005, 70, 9651 − 9653; J org Chem 2017, 82, 8023 − 8030; ORG Lett 2010, 12, 2536 − 2539; org Lett 2007, 9, 343 − 346; angel Chem Int ed 2003 , 42 , 2768-2770 ； J Org Chem 1995 , 6 0
, 883-888 ； Adv Synth Catal   2007 , 349 , 1759–1764 ） 。 Inspired by the previous palladium catalyzed series reaction of nitriles and arylboric acid (org Lett 2019, 21, 7697 – 7701; org Lett 2018, 20, 3083 − 3087; org Lett 2017, 19, 218), the author proposes to use the easily available α containing compounds, A series reaction of 2 - (cyanomethoxy) chalcone with aromatic boric acid was carried out Different seven membered heterocyclic compounds were selectively constructed by intermediate a or B However, the synthesis of benzofurano [2,3-c] pyridine derivatives, which are difficult to be prepared by traditional methods, was unexpectedly realized Figure 1 Selective construction of benzofurano [2, 3-c] pyridine (source: Org Lett.) firstly, the author screened a series of conditions such as catalyst, ligand, solvent and reaction time Finally, palladium acetate was selected as catalyst, new cuprous reagent as ligand, three FLUOROACETIC acid as additive, and tetrahydrofuran as solvent Under these conditions, the universality of the reaction was investigated The results show that all kinds of substituted 2 - (cyanomethoxy) chalcone and arylboronic acid can obtain the corresponding products in medium to good yields Figure 2 Application scope of reaction substrate (source: org Lett.) in addition, the structure of 4D product was further determined by X-ray crystal diffraction, as shown in the figure below Fig 3 Structure of product 4D (source: org Lett.) in order to verify the applicability of benzofuran [2,3-c] pyridine derivatives, the author selected 9 different products to study their photophysical properties As shown in FIG 4A and Fig 4b, these products show strong blue fluorescence in both liquid and solid state The fluorescence wavelength of liquid is 484 to 492 nm, and that of solid is 405 to 440 nm Compared with the solution state, the wavelength of the solid material shifts red, and the fluorescence intensity decreases These effects may be attributed to the weak intermolecular interaction between the molecules in the aggregation state At the same time, the author also studied the luminescent properties of compound 3a in different THF / H 2O mixtures (Fig 4C) By measuring the fluorescence emission of 3A compounds in toluene, dichloromethane (DCM), ethyl acetate (EA) and DMSO, the effect of solvent polarity on 3A was studied (Fig 4D) Finally, we use a set of Gauss 09 program to calculate the density functional theory and study the optical properties of these compounds at the molecular level Using B3LYP / 6-31 + G * method, we calculated the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) energy levels of the derivatives (Fig 4e) Figure 4 Photophysical properties (source: org Lett.) after exploring the universality of the substrate and the application of the product, the author studied the reaction mechanism First, the reaction was attempted without the addition of phenylboronic acid, and 3 - (2-oxo-2-phenylethyl) benzofuran-2-methylnitrile (6a) was not obtained (Fig 5a) In addition, intermolecular competition experiments were carried out under standard conditions (Fig 5b) Chalcone (7a) and 2-phenoxyacetonitrile (7b) reacted with phenylboronic acid to produce 82% and 91% of 1,3,3-triphenyl-1-propanone (8a) and 1-phenyl-2-phenoxy-1-ethanone (8B), respectively At the same time, it was found that 7b was more likely to transform when it was used The results show that in palladium catalyzed addition reaction, arylboric acid preferentially reacts with cyano group Fig 5 Control experiment (source: org Lett.) based on the above experimental results, the author proposed a possible mechanism for the synthesis of benzofuran [2,3-c] pyridine (Fig 6) First, palladium catalyst and aromatic boric acid are converted to metal, and then cyano group is coordinated with PD to form intermediate a Subsequently, imino palladium intermediate B was obtained by carbopalladization of cyano group In the presence of TFA, B protonated to produce imine intermediate C (or imine tautomerism to form enamine intermediate d), and released palladium catalyst Intermediate e is obtained by intramolecular Michael addition of intermediate C or D, and then cyclized to intermediate F Finally, the intermediate f is oxidized to form a stable π - conjugated benzofuran [2,3-c] pyridine framework Figure 6 Possible mechanism (source: org Lett.) Summary: Chen Jiuxi's research group successfully realized the PD (II) catalyzed series reaction of 2 - (cyanomethoxy) chalcone and arylboric acid, which provided a new strategy for the synthesis of a series of valuable benzofuran [2,3-c] pyridines which are difficult to be prepared by traditional routes By using thiophene-3-yl boric acid as coupling reagent, the chemical method can also be used to synthesize 1 - (thiophene-3-phenyl) benzofuran [2,3-c] pyridine Moreover, benzofuran [2,3-c] pyridine has important practical significance in expanding the types and applications of fluorescent materials The research results were published in org Lett (DOI: 10.1021/acs.orglett 9b04185) The first author of this paper is Xiong Wen, a 2018 graduate student from Wenzhou University, whose research has been assisted by other graduate students and teachers of the research team The part of optical physical properties was completed by Lei Yunxiang, Ph.D student of Beijing University of technology, and the corresponding author was Professor Chen Jiuxi The research work was supported by NSFC (21572162) and Zhejiang Natural Science Foundation (ly16b020012, lq18b020006) Today, people and scientific research are getting more and more attention in 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.