- Manganese-Catalyzed Dehydrogenative Alkylation or α-Olefination of Alkyl-Substituted N-Heteroarenes with Alcohols
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Catalysis with earth-abundant transition metals is an option to help save our rare noble-metal resources and is especially interesting when novel reactivity or selectivity patterns are observed. We report here on a novel reaction, namely the dehydrogenative alkylation or α-olefination of alkyl-substituted N-heteroarenes with alcohols. Manganese complexes developed in our laboratory catalyze the reaction with high efficiency whereas iron and cobalt complexes stabilized by the same ligands are essentially inactive. Hydrogen is liberated during the reaction, and bromine and iodine functional groups as well as olefins are tolerated. A variety of alkyl-substituted N-heteroarenes can be functionalized, and benzylic and aliphatic alcohols undergo the reaction.
- Zhang, Guoying,Irrgang, Torsten,Dietel, Thomas,Kallmeier, Fabian,Kempe, Rhett
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- Deaminative Olefination of Methyl N-Heteroarenes by an Amine Oxidase Inspired Catalyst
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We explored the bioinspired o-quinone cofactor catalyzed aerobic primary amine dehydrogenation for a cascade olefination reaction with nine different methyl N-heteroarenes, including pyrimidines, pyrazines, pyridines, quinolines, quinoxolines, benzimidazoles, benzoxazoles, benzthiazoles, and triazines. An o-quinone catalyst phd (1,10-phenanthroline-5,6-dione) combined with a Br?nsted acid catalyzed the reaction. N-Heteroaryl stilbenoids were synthesized in high yields and (E)-selectivities under mild conditions using oxygen (1 atm) as the sole oxidant without needing transition-metal salt, ligand, stoichiometric base, or oxidant.
- Thorve, Pradip Ramdas,Maji, Biplab
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supporting information
p. 542 - 547
(2021/01/26)
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- Waste-minimized synthesis of C2 functionalized quinolines exploiting iron-catalysed C-H activation
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Herein we present an efficient and regioselective iron-catalyzed methodology for the external oxidant-free functionalization of quinoline-N-oxides. The protocol, based on the use of inexpensive and easily accessible FeSO4, showed broad applicability to a wide range of substrates. An additional green feature of this synthetic methodology is H2O being the only by-product. Experimental and computational investigations provide support to a mechanism based on a facile C-H activation event. The green efficiency of the process has also been carefully assessed using: (i) metrics related to the synthetic process (AE, Yield, 1/SF, MRP and RME); (ii) safety/hazard metrics (SHZI and SHI); and (iii) metrics related to the metal used as the catalyst (Abundance, OEL and ADP). In addition to the many advantages of this protocol related to the green iron catalyst used and the safety/hazard features of the process, an E-factor value of ca. 0.92 (84 to >99% reduction compared to known protocols) evidently confirms the sustainable efficiency of the procedure presented. Practical utility has also been demonstrated by performing the reaction efficiently on a multi-gram scale. This journal is
- Ferlin, Francesco,Zangarelli, Agnese,Lilli, Simone,Santoro, Stefano,Vaccaro, Luigi
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supporting information
p. 490 - 495
(2021/01/28)
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- MnO2 mediated sequential oxidation/olefination of alkyl-substituted heteroarenes with alcohols
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A practical and efficient ligand-free MnO2 mediated sequential oxidation and olefination has been developed for the facile synthesis of a broad range of unsaturated N-heteroazaarenes from simple alkyl-substituted heteroarenes and alcohols. The procedure tolerates a series of functional groups, such as methoxyl, chloro, bromo, iodo, vinyl, phenolic and hetero groups, providing the olefination products in moderate to good yields.The protocol could be conducted at mild conditions and used environmentally friendly air as the clear oxidant.
- Zhang, Chunyan,Li, Zehua,Fang, Yanchen,Jiang, Shaohua,Wang, Maorong,Zhang, Guoying
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supporting information
(2020/02/15)
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- Preparation method of trans-disubstituted olefin
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The invention relates to the technical field of organic chemical synthesis, and in particular, relates to a preparation method of trans-disubstituted olefin. According to the preparation method, primary alcohol and methyl azacycle are taken as raw materials, transition metal salt, nitric oxide and alkali are taken as catalysts, an organic solution is taken as a reaction medium, and reaction is carried out in an oxygen atmosphere. According to the preparation method, a reaction by-product is only water, the environment is not polluted, the required transition metal catalyst is cheap and easy toobtain, the reaction does not need high temperature, and the reaction cost and the requirements on reaction conditions can be reduced.
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Paragraph 0142-0149
(2020/02/27)
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- A heterogeneous and recoverable palladium catalyst to access the regioselective C-H alkenylation of quinoline: N -oxides
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Herein, we disclose the first C-2-selective C-H alkenylation of quinoline N-oxides catalyzed using a heterogeneous palladium catalyst. The protocol does not require the use of an external oxidant and it is applicable to an ample substrate scope always showing excellent site selectivity. This process is made accessible by the use of a specific 1,2,3-triazolium-tagged heterogeneous polymeric catalytic system. The catalyst can be efficiently recovered and reused with no decrease of its catalytic performance and hot filtration and mercury poisoning tests suggest that its mechanism of action is operatively heterogeneous. In addition, mechanistic studies revealed that C-H activation reaction pathways are operative, setting the stage for the direct synthesis of 2-functionalized quinolines using N-oxide functionality as both a directing group and an oxidant.
- Chen, Shaomin,Ferlin, Francesco,Gu, Yanlong,Piermatti, Oriana,Sciosci, Daniele,Vaccaro, Luigi,Valentini, Federica
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supporting information
p. 6560 - 6566
(2020/11/09)
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- Iron-Catalyzed Coupling of Methyl N-Heteroarenes with Primary Alcohols: Direct Access to E-Selective Olefins
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An efficient Fe-catalyzed system is reported for direct α-olefination of methyl-substituted N-heteroarenes with primary alcohols. The catalytic dehydrogenative coupling enables a series of functionalized E-olefinated N-heteroaromatics with excellent selectivity (>99%). Initial mechanistic studies including deuterium-labeling experiments provide evidence for the participation of the benzylic C-H/D bond of alcohols.
- Das, Jagadish,Vellakkaran, Mari,Sk, Motahar,Banerjee, Debasis
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supporting information
p. 7514 - 7518
(2019/10/02)
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- Nickel-catalysed direct α-olefination of alkyl substituted N-heteroarenes with alcohols
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Catalytic α-olefination of alkylheteroarenes with primary alcohols via dehydrogenative coupling is presented. A simple nickel catalyst system stabilised by readily available nitrogen ligands enables a series of interesting E-configured vinylarenes (confirmed by X-ray crystal-structure analysis) to be synthesised in good to excellent yields with olefin/alkane selectivity of >20:1. Hydrogen and water are generated as byproducts and quantitative determination of H2 was performed.
- Das, Jagadish,Vellakkaran, Mari,Banerjee, Debasis
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supporting information
p. 7530 - 7533
(2019/07/04)
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- Microwave-assisted, rapid synthesis of 2-vinylquinolines and evaluation of their antimalarial activity
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A rapid and efficient synthesis of 2-vinylquinolines via trifluoromethanesulfonamide-mediated olefination of 2-methylquinoline and aldehyde under microwave irradiation is reported. Biological evaluation of these scaffolds demonstrates that 2-vinylquinolines 3x-3z possess excellent antimalarial activities against chloroquine-resistant Dd2 strain of Plasmodium falciparum (IC50 100 nM).
- Huang, Guang,Solano, Claribel Murillo,Su, Yuxin,Ezzat, Nameer,Matsui, Shino,Huang, Liuyu,Chakrabarti, Debopam,Yuan, Yu
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supporting information
p. 1736 - 1740
(2019/06/05)
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- Direct Alkenylation of 2-Methylquinolines with Aldehydes through Synergistic Catalysis of 1,3-Dimethylbarbituric Acid and HOAc
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An efficient and practical direct alkenylation of 2-methylquinolines with aldehydes has been achieved through a novel synergistic organocatalysis. The HOAc- activated 2-methylquiolines undergo a Michael addition to 1,3-dimethylbarbituric acid-activated aldehydes, followed by a retro-Michael addition to release 1,3-dimethylbarbituric acid and the target products. The transformation produced various 2-alkenylquinolines with good to excellent yields and featured mild reaction conditions, atom- and step-economy, good functional group tolerance, and operational simplicity. (Figure presented.).
- Liang, En,Wang, Junqi,Wu, Yinrong,Huang, Liangbin,Yao, Xingang,Tang, Xiaodong
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supporting information
p. 3619 - 3623
(2019/07/10)
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- Green synthesis method of alkenyl azaarene compounds
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The invention discloses a green synthesis method of alkenyl azaarene compounds. The process of the method is as follows: 2-methyl quinoline derivatives and aldehyde compounds are used as reaction rawmaterials, acids and active methylene compounds are used
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Paragraph 0032-0034; 0044
(2019/10/01)
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- A trans-substituted olefin preparation method (by machine translation)
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This invention relates to a trans-substituted olefin preparation method, which belongs to the technical field of organic chemical synthesis. The method adopts the simple alcohol and methyl nitrogen-containing heterocyclic as the starting material, by transition metal-catalyzed alkene base reaction, to obtain trans-substituted olefin compound. The reaction raw material, catalyst and additives is cheap, simple synthesis technology, greatly reduces the cost of synthesizing; mild reaction conditions, high yield, easy industrialization; the reaction of raw materials and catalyst cleaning toxic, small pollution to the environment. The trans-substituted olefin compound and its derivatives as an important fine chemicals, in the medical, agricultural chemicals, perfume and photoelectric and other industries have wide application. (by machine translation)
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Paragraph 0106; 0107; 0109; 0110
(2018/07/30)
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- Manganese-Catalyzed Direct Olefination of Methyl-Substituted Heteroarenes with Primary Alcohols
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Herein, we present the first catalytic direct olefination of methyl-substituted heteroarenes with primary alcohols through an acceptorless dehydrogenative coupling. The reaction is catalyzed by a complex of the earth-abundant transition metal manganese that is stabilized by a bench-stable NNN pincer ligand derived from 2-hydrazinylpyridine. The reaction is environmentally benign, producing only hydrogen and water as byproducts. A large number of E-disubstituted olefins were selectively obtained with high efficiency.
- Barman, Milan K.,Waiba, Satyadeep,Maji, Biplab
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supporting information
p. 9126 - 9130
(2018/07/25)
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- Design, synthesis, and in vitro evaluation of quinolinyl analogues for α-synuclein aggregation
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Here we report the synthesis and in vitro evaluation of 25 new quinolinyl analogues for α-synuclein aggregates. Three lead compounds were subsequently labeled with carbon-11 or fluorine-18 to directly assess their potency in a direct radioactive competitive binding assay ng both α-synuclein fibrils and tissue homogenates from Alzheimer's disease (AD) cases. The modest binding affinities of these three radioligands toward α-synuclein were comparable with results from the Thioflavin T fluorescence assay. However, all three ligand also showed modest binding affinity to the AD homogenates and lack selectivity for α-synuclein. The structure–activity relationship data from these 25 analogues will provide useful information for design and synthesis of new compounds for imaging α-synuclein aggregation.
- Yue, Xuyi,Dhavale, Dhruva D.,Li, Junfeng,Luo, Zonghua,Liu, Jialu,Yang, Hao,Mach, Robert H.,Kotzbauer, Paul T.,Tu, Zhude
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p. 1011 - 1019
(2018/03/01)
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- Iodine-Catalyzed Direct C-H Alkenylation of Azaheterocycle N-Oxides with Alkenes
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An efficient and regioselective alkenylation of azaheterocycle N-oxides with alkenes catalyzed by iodine under metal- and external oxidant-free reaction conditions has been developed. A variety of (E)-2-styrylazaheterocycles have been produced in moderate
- Zhang, Zhenhao,Pi, Chao,Tong, Heng,Cui, Xiuling,Wu, Yangjie
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supporting information
p. 440 - 443
(2017/02/10)
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- Lanthanum Pentafluorobenzoate-Catalyzed Aerobic Oxidative Olefination of Benzylamines with 2-Methylquinoline through Deamination and C-H Bond Functionalization
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An efficient direct aerobic oxidative olefination of the methyl groups of 2-methylquinolines with benzylamines in the presence of a rare-earth-metal Lewis acid catalyst to give 2-styrylquinolines was successfully developed. Preliminary mechanistic studies revealed that the oxidative olefination reaction proceeds through a Lewis acid-catalyzed 2-methylquinoline-aldehyde condensation and an amine-aldehyde condensation.
- Mao, Dan,Zhu, Xiaoyan,Hong, Gang,Wu, Shengying,Wang, Limin
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supporting information
p. 2481 - 2484
(2016/10/21)
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- C2-Alkenylation of N-heteroaromatic compounds: Via Br?nsted acid catalysis
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Substituted heteroaromatic compounds, especially those based on pyridine, hold a privileged position within drug discovery and medicinal chemistry. However, functionalisation of the C2 position of 6-membered heteroarenes is challenging because of (a) the difficulties of installing a halogen at this site and (b) the instability of C2 heteroaryl-metal reagents. Here we show that C2-alkenylated heteroaromatics can be accessed by simple Br?nsted acid catalysed union of diverse heteroarene N-oxides with alkenes. The approach is notable because (a) it is operationally simple, (b) the Br?nsted acid catalyst is cheap, non-toxic and sustainable, (c) the N-oxide activator disappears during the reaction, and (d) water is the sole stoichiometric byproduct of the process. The new protocol offers orthogonal functional group tolerance to metal-catalysed methods and can be integrated easily into synthetic sequences to provide polyfunctionalised targets. In broader terms, this study demonstrates how classical organic reactivity can still be used to provide solutions to contemporary synthetic challenges that might otherwise be approached using transition metal catalysis.
- Crisenza, Giacomo E. M.,Dauncey, Elizabeth M.,Bower, John F.
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supporting information
p. 5820 - 5825
(2016/07/06)
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- Direct alkenylation of alkylazaarenes with aldehydes through C(sp3)-H functionalization under catalytic InCl3 activation
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Under the influence of InCl3 as a Lewis acid catalyst, a methodology on the C(sp3)-H functionalization of alkylazaarenes has been demonstrated through the activation of benzylic C-H bonds towards their addition reaction with the appropriate electrophiles. This methodology was chiefly applied in the direct alkenylation of primary and secondary benzylic C-H bonds of alkylazaarenes with aldehydes. A variety of alkenyl products were afforded in generally good yields including the starting alkenyl intermediate used in the synthesis of montelukast and other related molecules.
- Jamal, Zaini,Teo, Yong-Chua,Lim, Gina Shiyun
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p. 2132 - 2138
(2016/04/19)
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- Metal-free oxidative olefination of primary amines with benzylic C-H bonds through direct deamination and C-H bond activation
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An oxidative olefination reaction between aliphatic primary amines and benzylic sp3 C-H bonds has been achieved using N-bromosuccinimide as catalyst and tert-butyl hydroperoxide as oxidant. The olefination proceeds under mild metal-free conditions through direct deamination and benzylic C-H bond activation, and provides easy access to biologically active 2-styrylquinolines with (E)-configuration. This journal is the Partner Organisations 2014.
- Gong, Liang,Xing, Li-Juan,Xu, Tong,Zhu, Xue-Ping,Zhou, Wen,Kang, Ning,Wang, Bin
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supporting information
p. 6557 - 6560
(2014/08/18)
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- Cobalt-catalyzed direct alkenylation of 2-methylquinolines with aldehydes via C(sp3)-H functionalization in water
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The direct C(sp3)-H alkenylation of 2-methylquinolines with aldehydes as a simple methodology to afford 2-alkenylated quinolines is reported. In the presence of catalytic CoCl2 in water, the economically and ecologically sound transformation is proposed to proceed via the direct benzylic addition to the aldehyde followed by an elimination step to provide 2-alkenylated quinolines in good to excellent yield of up to 95%. Georg Thieme Verlag Stuttgart New York.
- Jamal, Zaini,Teo, Yong-Chua
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supporting information
p. 2049 - 2053
(2014/11/08)
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- Iron-catalyzed C(sp3)-H functionalization of methyl azaarenes: A green approach to azaarene-substituted α- Or β-hydroxy carboxylic derivatives and 2-alkenylazaarenes
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Bioactive azaarene-substituted lactic acids, β-hydroxy esters, 3-hydroxy-2H-indol-2-ones, and 2-alkenylazaarenes were prepared in moderate-to-excellent yields via C(sp3)-H functionalization of methyl azaarenes with carbonyl compounds in the presence of iron(ii) acetate as an inexpensive, nontoxic, efficient catalyst. The application of this atom-, step-economic, and environmentally friendly method was demonstrated by a gram-scale synthesis of 3-[(E)-2-(7-chloroquinolin-2-yl)vinyl]benzaldehyde, a key intermediate of leukotriene receptor antagonist (Montelukast).
- Pi, Danwei,Jiang, Kun,Zhou, Haifeng,Sui, Yuebo,Uozumi, Yasuhiro,Zou, Kun
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p. 57875 - 57884
(2015/01/08)
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- A fluorescent styrylquinoline with combined therapeutic and diagnostic activities against Alzheimer's and prion diseases
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(E)-6-Methyl-4′-amino-2-styrylquinoline (3) is a small molecule with the proper features to potentially diagnose, deliver therapy and monitor response to therapy in protein misfolding diseases. These features include compound fluorescent emission in the NIR region and its ability to interact with both Aβ and prion fibrils, staining them with high selectivity. Styrylquinoline 3 also inhibits Aβ self-aggregation in vitro and prion replication in the submicromolar range in a cellular context. Furthermore, it is not toxic and is able to cross the blood brain barrier in vitro (PAMPA test).
- Staderini, Matteo,Auli?, Suzana,Bartolini, Manuela,Tran, Hoang Ngoc Ai,González-Ruiz, Víctor,Pérez, Daniel I.,Cabezas, Nieves,Martínez, Ana,Martín, M. Antonia,Andrisano, Vincenza,Legname, Giuseppe,Menéndez, J. Carlos,Bolognesi, Maria Laura
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supporting information
p. 225 - 229
(2013/03/29)
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- Oxidative olefination of secondary amines with carbon nucleophiles
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An unprecedented olefination reaction of secondary amines with carbon nucleophiles has been developed through C-N/C-H functionalization under metal-free oxidative conditions. In the presence of a stoichiometric amount of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), a range of secondary N-alkylanilines smoothly underwent oxidative olefination with 2-alkylazaarenes, acetophenone, and malononitrile to give structurally diverse polysubstituted alkenes in moderate to excellent yields with excellent (E) selectivity. Preliminary mechanistic studies revealed that the oxidative olefination reaction proceeds through amine oxidation followed by imine olefination. A range of secondary N-alkylanilines smoothly underwent DDQ-promoted oxidative olefination with 2-alkylazaarenes, acetophenone, and malononitrile to give structurally diverse alkenes in moderate to excellent yields with excellent (E) selectivity. Mechanistically, the reaction proceeds through amine oxidation followed by imine olefination (DDQ = 2,3-dichloro-5,6-dicyano-1,4-benzoquinone). Copyright
- Zhang, Yong-Gang,Xu, Jing-Kun,Li, Xi-Ming,Tian, Shi-Kai
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supporting information
p. 3648 - 3652
(2013/07/19)
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- A catalyst-free benzylic C-H bond olefination of azaarenes for direct mannich-like reactions
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A highly efficient synthesis of trans-alkenylazaarene under catalyst-free conditions was developed via the addition of methylazaarenes to N-sulfonyl aldimines and a subsequent C-N elimination in situ. A one-pot procedure for this addition-elimination was also developed. The reaction could tolerate a broad substrate scope and give the corresponding alkenylazaarenes in high yields.
- Yan, Yizhe,Xu, Kun,Fang, Yang,Wang, Zhiyong
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p. 6849 - 6855
(2011/10/04)
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- Iron-catalyzed direct alkenylation of 2-substituted azaarenes with N -sulfonyl aldimines via C-H bond activation
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A novel iron-catalyzed alkenylation of 2-substituted azaarenes through sp3 C-H bond activation has been developed. A favorable E2-elimination is proposed as a key step to cleavage of C-H and C-N bonds for the construction of a C=C bond in high stereoselectivity. This transformation represents an efficient way to synthesize 2-alkenylated azaarenes from simple starting materials.
- Qian, Bo,Xie, Pan,Xie, Yinjun,Huang, Hanmin
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supporting information; experimental part
p. 2580 - 2583
(2011/06/25)
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