Research group of Professor Wang Qingmin of Nankai University: ortho-c (SP3) - H monofluorination of heteroatom alkanes under the cooperation of photo oxidation reduction catalyst and hydrogen atom transfer catalyst

Introduction: monofluoroalkenes are widely used in material science and pharmaceutical chemistry, for example, to improve the efficacy, lipid solubility and anti enzyme degradation On this basis, new methods of synthesizing fluoroolefins have been developed rapidly In recent years, a series of mild and efficient methods of C (SP 2) - H bond monofluorination have been reported However, the monofluorination of C (SP 3) - H bond is still a great challenge The development of visible light catalytic oxidation strategy provides the possibility for its realization Recently, the research group of Professor Wang Qingmin of Nankai University has made a breakthrough in this field Under the condition of photocatalysis, the hydrogen atom is grabbed by quinine to produce heteroatom ortho free radical, and the hydrofluoroenyl radical is obtained by photocatalysis reduction of epidifluoroethylene, and the product of heteroatom ortho monofluorination is obtained by cross coupling of two free radicals The relevant research results are published in org Lett（ DOI: 10.1021/acs.orglett.9b01491 ）。 Professor Wang Qingmin's brief introduction the research work of the research group at present includes: separation, identification, total synthesis and structural transformation of natural pesticides; molecular design, synthesis, biological activity and structure-activity relationship of new and efficient green chemical pesticides; total synthesis of natural products and efficient construction of heterocyclic molecular framework; construction of heterocyclic molecules by free radical reaction under photocatalysis Brief introduction to Professor Wang Qingmin, professor and doctoral supervisor Born in March 1970, graduated from the Department of modern physics, Lanzhou University with a bachelor's degree in radiochemistry in 1994, and obtained master's degree in organic chemistry and doctor's degree in agricultural pharmacy from Nankai University in 1997 and 2000 respectively In June 2000, he received a doctorate degree and stayed in school He was promoted to associate professor in December 2000, professor in December 2004 and doctoral supervisor in 2005 In 2004, it was selected into the "new century excellent talents support plan" of the Ministry of education, and in 2017, it was selected into the leading talents of Shandong Taishan industry (high-efficiency ecological agriculture innovation) Mainly engaged in the research and development of natural pesticide, green chemical pesticide and drug Since the work was carried out independently, I have worked in the international authoritative journal J agric Food chem., pest manag SCI., J Med Chem., angelw Chem Int ed., chem SCI., Arts & Rheumatism, org Lett., chem Commin., adv synth Catalyst, Chem EUR J et al Published more than 200 papers included in SCI; applied for more than 80 invention patents in China, the United States and Europe as the first inventor, authorized more than 40 invention patents in China, the United States and Europe; published 3 works (Chapter) A new clean production method of biomimetic pesticide pyrethroid series products, major pesticide varieties and high-end fine chemicals has been invented, which has been successfully applied to industrial production and has produced huge economic benefits A number of super efficient fungicides for plant virus disease control, green insecticides and acaricides as well as national class I new drugs have been created, which are in different stages of industrial development It has undertaken more than 30 scientific research projects, such as the national special fund for outstanding doctoral dissertation authors, the National Natural Science Foundation, the national science and technology support plan, 973 project, the national key R & D plan, the key project of the Ministry of education, the key project of Tianjin applied basic and cutting-edge technology research plan, and the special scientific research fund for the doctoral discipline point of colleges and universities In 2002, he won the national excellent doctoral dissertation, 2003 "youth Chemistry Award" of China Chemical Society, 2005 "invention patent award" of Tianjin, 2007 "Life Chemistry Research Award of Wuxi apptec", 2010 "10th Tianjin Youth Science and Technology Award", 2010 "achievement transformation award of seeking truth" of 13th China Association for science and technology, 2015 "The ninth Dabei agricultural science and Technology Award", the fifth "dedicated" award of Nankai University, the first prize of teaching gold, and the fourth "excellent doctoral dissertation instructor of Nankai University" 21 doctoral students and 41 master's students were trained They respectively won the National Excellent Doctoral Dissertation nomination award, Tianjin excellent doctoral dissertation, Nankai University Excellent Doctoral Dissertation, Nankai University excellent master's dissertation and national scholarship Frontier research achievements: the research team of Professor Wang Qingmin of Nankai University of heteroatom alkane ortho-c (SP 3) - H monofluoroalkylation under the cooperation of photo oxidation reduction catalyst and hydrogen atom transfer catalyst has done a series of pioneering work in photocatalysis of heteroatom ortho radical reaction (org Lett 2016, 18, 4686; Chem EUR J 2017, 23, 10871; org Lett 2018 , 20 , 5661 ; Chem Eur J 2018 , 24 , 9269 ; Chem Eur J 2018 , 24 , 11283; Adv Synth Catal 2018 , 360 , 287; Chem EUR J doi: 10.1002/chem.201901349), relevant invitation review published in Chem EUR J (DOI: 10.1002/chem.201804873), and recently realized heteroatom ortho monofluorination org Lett (DOI: 10.1021 / ACS Orglett 9b01491) Under the condition of photocatalysis, Hashmi team realized the direct functionalization of the n-adjacent C-H bond of the tertiary amine, but it is still a challenge for some active molecules such as secondary amines containing protective groups, oxygen-containing and sulfur-containing compounds, which is due to their high oxidation potential, photocatalyst can not directly oxidize these compounds Inspired by macmillam's research group, the author has successfully realized the monofluorination of heteroatom neighborhood by cooperating with visible light redox catalysis and hydrogen atom transfer catalysis (Figure 1) The reaction conditions are mild, with good functional group compatibility and substrate application scope, and for a variety of drugs and natural products, functional modification can be carried out later Fig 1 photocatalysis of heteroatom o-trifluorenylation (source: org Lett.) the author optimized the reaction conditions with (diphenyl) - 1,1-difluoroethylene and N-Boc pyrrolidine as raw materials (Table 1) When IR [DF (CF 3) PPy] 2 (dtbbpy) pf 6 was used as photocatalyst, quinine ring as hat catalyst, potassium phosphate as base, acetonitrile: water = 10:1 as solvent, the target product was obtained with 75% separation yield Table 1 Optimization of reaction conditions (source: org Lett.) after obtaining the optimal conditions, the author first inspected the application scope of difluoroethylene (Figure 2) When there are electron withdrawing substituents or electron supplying substituents in the aromatic ring, good yields can be obtained In addition, when an aryl group on difluoroethylene is replaced by a methyl or hydrogen atom (3jb-3nb), a better yield can still be obtained The selectivity of E / Z is lower when the asymmetric difluorodiene is used as the substrate (3eb-3nb) This result proves that the reaction may be realized by free radical coupling Figure 2 Application scope of difluoroethylene (source: org Lett.) later, the author investigated the substrate scope of nitroalkanes (Figure 3) For the 4-7-membered nitrogen-containing ring system, chain like secondary amines and different protective groups, the reaction can occur well, and the reaction can occur selectively on the first carbon The author thinks that the reaction takes place preferentially at the first carbon due to the higher activity of the first carbon radical reaction Fig 3 investigation of the range of azaalkane substrates (source: org Lett.) further, the author investigated the range of other heteroatom alkane substrates (Fig 4) For alkanes containing oxygen and sulfur, the reaction has a good yield In the case of THF as solvent, the yield of the reaction can be 95% to get the product of tetrahydrofuran cyclization At the same time, the author found that the reaction still had some activity for xylene, trimethylene and other inert reactants Fig 4 investigation of other heteroatom alkane substrate range (source: org Lett.) in order to investigate the practicability of the reaction, the author prepared the reaction in g-order, and modified the two natural products and drugs in the later stage of functionalization, and obtained good yield (Fig 5) Fig 5 functional study of natural products and drugs in the later stage (source: org Lett.) in order to understand the mechanism of this reaction, the author conducted in-depth study (Fig 6) When tempo and 1,2-stilbene were added to the reaction system, the reaction was completely inhibited When 1o was used as the reaction substrate, the ring closing product was obtained in 83% yield The fluorescence quenching experiment shows that the initial step of the reaction is the photocatalytic oxidation of quinine ring The switch experiments show that the reaction can only be carried out under light Fig 6 mechanism study (source: org Lett.) finally, the author proposed the possible mechanism of the reaction (Fig 7) Under the condition of illumination, the photocatalyst is excited The trivalent photocatalyst in the excited state oxidizes quinine to n-positive radical e, and at the same time, the photocatalyst in the bivalent state is obtained The n-boc-pyrrolidine is extracted by n-positive radical e to obtain n-neighboring radical species G The reduction of (diphenyl) - 1,1-difluoroethylene by divalent photocatalyst and the departure of fluoride anion lead to the monofluoroalkenyl radical h, and the cross coupling of the two radicals g and H leads to the final product Figure 7 Possible mechanism (source: org Lett.) this achievement was recently published in org Lett (DOI: 10.1021 / ACS Orglett 9b01491) The first author of this paper is Tian Hao, a doctoral student from the Institute of elements, Nankai University, and the corresponding author is Professor Wang Qingmin, Nankai University The above research work was supported by national key R & D plan (2018yfd02010) and National Natural Science Foundation (21732002, 21672117) A review of previous reports: Professor Wang Qingmin's research group of Nankai University: visible Minisci C-H alkylation of non activated haloalkanes; Professor Wang Qingmin's research group of Nankai University: Silver Copper Co catalyzed intramolecular cyclization / desulfonamide / dehydrogenation for high efficiency synthesis of substituted carbazole Today, science and technology elements are increasingly valued 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, chembeangoapp, chembeango official microblog, CBG wechat subscription number and other platforms jointly launch the column of "people and scientific research", approach the domestic representative research group, pay attention to their research, listen to their stories, record their demeanor, and explore their scientific research spirit.