Huang Huawen, Ji Xiaozhao and their collaborators, Xiangtan University: new progress in visible light mediated decarbonylation of fatty aldehydes in Minisci type alkylation at room temperature and air

In recent years, visible light induced photocatalytic oxidation-reduction has become one of the hot spots in the field of organic synthesis From the point of view of green chemistry, using green and cheap oxygen as oxidant in the mild visible light catalytic redox system is of great significance to the research and development of oxidation reaction On the other hand, aza arene is the basic framework of many functional molecules, such as dyes, pesticides, pharmaceuticals, materials, etc Recently, Huang Huawen, Ji Xiaozhan and their collaborators from the green synthesis and catalysis team of Xiangtan University reported the visible light mediated aldehyde decarbonylation Minisci reaction in room temperature air, which realized the alkylation of azaarenes under mild conditions Relevant research results were recently published on Green Chemistry (DOI: 10.1039 / c9gc03008e) Brief introduction to the green synthesis and catalysis team of Xiangtan University Professor Deng Guojun was the team leader when the green synthesis and catalysis team of Xiangtan University was established in 2009 At present, the team includes 2 professors, 4 associate professors, 1 lecturer, 2 postdoctoral students, 8 doctoral students and more than 50 master students The research group is mainly engaged in the research of organic synthesis methodology based on the generation of C-C bond and c-heterobond, and has undertaken more than 20 projects at the provincial and ministerial level, including 10 national science and technology funds A lot of research achievements have been made in nitro hydrogen reduction, cyclohexanone dehydrogenation aromatization, sulfite selective conversion, oxime ester conversion, indole direct functionalization, heterocycle formation involving inorganic sulfur and green oxidation involving molecular oxygen More than 100 SCI papers have been published, 11 of which have been selected into ESI High cited paper At present, 7 doctoral students and more than 40 master's degree students have been trained, among which 3 papers have won excellent doctoral and master's degree papers in Hunan Province Profile of Associate Professor Huang Huawen, Associate Professor Huang Huawen, graduated from Northwest University in June 2009 with a Bachelor of engineering degree He graduated from South China University of technology in 2014 and obtained a doctor's degree in engineering In July of the same year, he entered the school of chemistry of Xiangtan University and then joined the "green synthesis and catalysis" team led by Deng Guojun In 2016, he was supported by China Scholarship Fund to go to University of Gottingen for further study as a postdoctoral fellow, and his cooperative tutor was Professor Lutz Ackermann In 2019, he was selected into the support plan of "Hunan young talents" of Hunan Province He is now an associate professor and master supervisor of the school of chemistry, Xiangtan University Since taking part in the work, research has been carried out on the theme of "development and application of new strategies for environmentally friendly organic synthesis chemistry", and a series of original achievements have been achieved At present, more than 40 SCI papers (30 if > 5.0) have been published by the first author or corresponding author Related research papers have been cited more than 2700 times (he cited more than 2500 times), and three papers have been selected as ESI high cited papers 15 patents have been applied for (4 authorized) As a specially invited reviewer of international authoritative journals such as ACS catalyst., org Lett., adv synth Catalyst Ji Xiaoxian, associate professor, graduated from Henan University of technology in June 2009 with a Bachelor of Science degree He graduated from South China University of technology in 2014 and obtained a doctor's degree in engineering In July of the same year, he entered the school of chemistry of Xiangtan University and then joined the "green synthesis and catalysis" team led by Deng Guojun He is now an associate professor and master supervisor of the school of chemistry, Xiangtan University Since taking part in the work, the subject of "combination of mild visible light catalysis and oxygen oxidation" has been studied, and a series of original results have been achieved At present, he has published more than 10 SCI papers as the first author or corresponding author Cutting edge scientific research achievements: visible light mediated decarbonylation of aliphatic aldehydes in room temperature air is a new development of Minisci reaction, i.e free radical addition of nitrogen-containing heterocycles, which provides an important path for the construction of functional azaarenes In recent years, Minisci reaction has been widely studied, including the development of some mild photocatalytic redox systems, but in many cases, it is necessary to use stoichiometric strong oxidants or raise the temperature to produce the required free radicals For example, when aldehydes are used as free radical precursors, excessive strong oxidants such as phenyliodoacetate, potassium persulfate, peroxide, etc are usually needed (Fig 1a) In 2015, Yang Luo et al Of Xiangtan University reported the decarbonylation and alkylation reaction using Di tert butyl peroxide at high temperature (Fig 1b) In 2018, Lei Aiwen group of Wuhan University reported the visible light catalyzed acylation of azaarenes (Fig 1c) initiated by tert butyl hydrogen peroxide Recently, Ji Xiaozhan and Huang Huawen of Xiangtan University reported the visible light mediated Minisci type alkylation of aldehydes in room temperature air (Fig 1D) This method can be compatible with a series of azaarenes with specific functional groups to prepare products of secondary alkylation and tertiary alkylation of azaarenes The mechanism study shows that, unlike the reported mechanism of photocatalysis of aldehyde to form carbonyl radical anion, this reaction can form active species with strong oxidation ability through photoexcitation, and then lead to the formation of acyl radical This new reaction mode can be used to design decarbonylation coupling reaction with oxygen as green oxidant under mild conditions Relevant research results were recently published on Green Chemistry (DOI: 10.1039 / c9gc03008e) (source: Green Chemistry) firstly, 4-methylquinoline (1a) and 2-ethylhexanal (2a) were selected as the model reactants of oxidative decarbonylation and alkylation under visible light catalysis (Table 1) When 0.5 mol% [IrdF (CF 3) PPy 2 (dtbbpy)]PF 6 is used as photocatalyst, 1.1 chemical equivalent CF 3 SO 3 H is used as acid, 0.5 chemical equivalent LiBr is used as additive, acetone / water is used as solvent, and 35 W led blue light is used as light source in the air atmosphere, the decarbonylation alkylation product 3A (entry1) is obtained with 40% NMR yield The results of acid screening showed that CH 3So 3h, (PH) 2PO 2h, TsOH · H 2O had a certain promoting effect on the formation of 3A (entries 2-4), and TsOH · H 2O had the best reaction effect The results showed that 1,2-dichloroethane (DCE) was superior to other solvents, and 3a (entry 6) was obtained with 67% NMR yield The author further explored a series of halide additives and found that only bromine can be used in the decarbonylation alkylation reaction (entries 9-14), while iodide and chloride can completely inhibit the reaction Among other bromides, NaBr has the same reactivity as LiBr (entry9) However, in comparison, the reaction system with NaBr is cleaner than that with LiBr or other reaction systems without NaBr, i.e fewer by-products are reduced It is speculated that NaBr may enhance the oxidation ability of the catalytic system At last, the author screened the photocatalyst and found that 4czipn, a simple and easy to get non-metallic carbazole photosensitizer, had the best reaction effect (70% NMR yield, entry 18) Other compounds, such as Eosin Y, Bengal rose red and Ru (bpy) 3pf6, showed lower catalytic activity When the amount of catalyst 4czipn was increased to 1 mol%, the reaction yield (85% NMR, entry 19) was significantly increased The control experiment shows that visible light and air atmosphere are essential for the decarbonylation reaction (entry 20) (source: Green Chemistry) the author investigated the universality of aldehyde substrate (Fig 2) When α - branched aliphatic aldehydes are used, the decarbonylation coupling alkylation can be carried out smoothly, and the target product (yield 75-93%, 3a-3e) can be obtained in high yield The reactivity of cyclic aldehydes such as cyclohexylformaldehyde and cyclopentaldehyde decreased slightly (yield 31-69%, 3F - 3H) The pyrrole group with BOC protection can be successfully connected to quinoline skeleton by this reaction (yield 52%, 3H) Two kinds of perfume molecules, cyclaldehyde and Lilial, showed good activity in the decarbonylation coupling reaction, the yields were 62% and 80% (3I and 3j), respectively In this system, 2-tert-butyl-4-methylquinoline (yield 90%, 3K) was obtained by TERT alkylation of neopentaldehyde When the reaction scale was expanded to 8 mmol, the corresponding products (3C and 3k, 76% and 82% respectively) could still be produced Due to the high carbon bond dissociation energy of primary alkylaldehydes and aromatic aldehydes, and the poor stability of corresponding free radicals, the two kinds of substrates can not undergo decarbonylation coupling reaction in this photo oxidation-reduction system (source: Green Chemistry) next, the author investigated the n-heteroarene substrate range (Fig 3-4) The product of C2 alkylation (54%, 4a) was obtained in medium yield from unsubstituted quinoline The reaction of 4-ethyl and 4-chloroquinoline was very effective, and the corresponding products (4b, 4C) were obtained in high yield The brominated quinolines at C3, C5, C6 and C7 can all react effectively with medium to excellent yields (42-84%, 4d-4f, 4I) Using other quinoline substrates containing donor methoxy (4h) or acceptor ester (4J), nitro (4K), trifluoromethyl (4m) and cyano (4P), the yield range is between 30% and 93% The alkylation products 4q and 4R were obtained in excellent yields In addition, two biologically active molecules, quinofen and hydroquinine, can also react successfully (73% and 71%, 4S and 4T) In addition to quinoline, other nitrogen-containing heterocyclic frameworks, such as pyridine, isoquinoline, phenanthroline, etc., can obtain the corresponding products (5a-5c) in medium yield in this reaction system The yield of heterocycles containing multiple nitrogen atoms such as 1,10-phenanthroline (5d), 2,3-diazoline (5e), quinoxaline (5F), imidazo [1,2-a] pyridine (5g) is low, while benzothiazole can get the target product (47%, 5H) in medium yield (source: Green Chemistry) in order to verify the reaction mechanism, the author made a series of control experiments (Fig 5) The author first found that free radical scavengers such as tempo, BHT and 1,1 '- stilbene (DPE) could inhibit the formation of model reaction products (Fig 5a), indicating that free radical pathway might be involved in the reaction process Secondly, the author confirmed the o-acylhydroxyamines formed by the capture of acyl radicals in the system by tempo by NMR and HRMS In addition, the fluorescence quenching experiments of the reactant and O 2 on the photocatalyst showed that the protonated 4-methylquinoline and 2-ethylhexanal (2a) had no obvious quenching effect, while O 2 had a strong quenching effect on the excited 4czipn (KSV > 300) These results indicate that the oxidation of oxygen to the catalyst may be the initial step of the reaction On this basis, the possible reaction mechanism (Fig