- Energetics of 6-methoxyquinoline and 6-methoxyquinoline N-oxide: The dissociation enthalpy of the (N-O) bond
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The standard (p° = 0.1MPa) molar enthalpies of formation, at T = 298.15K, were determined using static-bomb calorimetry for crystalline 6-methoxyquinoline N-oxide (6MeOQUINO), as -(85.6 ± 3.7) kJ·mol-1 and liquid 6-methoxyquinoline (6MeOQUI), -(25.8 ± 2.2)kJ·mol-1. The standard molar enthalpies of sublimation/vaporization, at T = 298.15K, were measured by microcalorimetry and from the enthalpies of formation of the gaseous compounds, the dissociation enthalpy Dm0 of the (N+-O-) dative covalent bond was derived, as (269.2 ± 5.0)kJ·mol-1.
- Da Silva, Maria D.M.C. Ribeiro,Santos, Luis M.N.B.F.,Silva, Ana L.R.,Fernandes, Oscar,Acree Jr.
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Read Online
- Electrochemical-Oxidation-Promoted Direct N-ortho-Selective Difluoromethylation of Heterocyclic N-Oxides
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An efficient and green electrochemical N-ortho-selective difluoromethylation method of various quinoline and isoquinoline N-oxides has been developed. In this method, sodium difluoromethanesulfinate (HCF2SO2Na) was used as the source of the difluoromethyl moiety, and various N-ortho-selective difluoromethylation quinoline and isoquinoline N-oxides were obtained in good to excellent yields under a constant current. In addition, the reaction was easy to scale up and maintained a good yield. Preliminary mechanism studies suggested that the reaction undergoes a free-radical addition and hydrogen elimination pathway.
- Zhang, Dong,Cai, Jinlin,Du, Jinze,Wang, Qingdong,Yang, Jinming,Geng, Rongqing,Fang, Zheng,Guo, Kai
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supporting information
p. 1434 - 1438
(2022/03/01)
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- Quinoline Ligands Improve the Classic Direct C?H Functionalisation/Intramolecular Cyclisation of Diaryl Ethers to Dibenzofurans
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The C?H functionalisation approach to the synthesis of dibenzofurans is hampered by a number of problems. Herein we describe the evolution of a cheap, bench stable quinoline ligand, which obviates most of the current limitations and allows for a high yielding synthesis of a range of valuable dibenzofurans. Dibenzofurans are important motifs in natural products and compounds with wide biological activity.
- Mackey, Katrina,Jones, David J.,Pardo, Leticia M.,McGlacken, Gerard P.
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supporting information
p. 495 - 498
(2021/01/12)
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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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- Deoxygenative C2-heteroarylation of quinoline N-oxides: Facile access to α-Triazolylquinolines
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A metal-and additive-free, highly efficient, step-economical deoxygenative C2-heteroarylation of quinolines and isoquinolines was achieved from readily available N-oxides and N-sulfonyl-1,2,3-Triazoles. A variety of α-Triazolylquinoline derivatives were synthesized with good regioselectivity and in excellent yields under mild reaction conditions. Further, a gram-scale and one-pot synthesis illustrated the efficacy and simplicity of the developed protocol. The current transformation was also found to be compatible for the late-stage modification of natural products.
- Sontakke, Geetanjali S.,Shukla, Rahul K.,Volla, Chandra M. R.
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supporting information
p. 485 - 493
(2021/03/22)
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- Metal-free C8-H functionalization of quinolineN-oxides with ynamides
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The metal-free C8-H functionalization of quinolineN-oxides with ynamides is unveiled for the first time by the intramolecular Friedel-Crafts-type reaction of quinolyl enolonium intermediates generated from Br?nsted acid-catalyzed addition of quinolineN-ox
- Hu, Weican,Zhang, Feiyang,Chen, Chen,Qi, Tianhang,Shen, Yanlong,Qian, Guoying,Rong, Zhouting
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supporting information
p. 6995 - 6998
(2021/07/21)
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- Copper/manganese oxide catalyzed regioselective amination of quinoline N-oxides: An example of synergistic cooperative catalysis
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An atom economical and efficient protocol for C-2 amination of quinoline N-oxides using our synthesized recyclable heterogeneous Cu–MnO catalyst has been reported here. Direct C[sbnd]H aminations of heterocyclic N-oxides with secondary amine were carried out under base, and ligand-free conditions in good to excellent yields. The major advantage is that air is used as a sole oxidant and our catalyst is recycled several times.
- Sahoo, Tapan,Thakur, Dinesh,Panda, Asit Baran,Ghosh, Subhash Chandra
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supporting information
(2021/09/29)
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- Deoxygenative Amination of Azine-N-oxides with Acyl Azides via [3 + 2] Cycloaddition
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A transition-metal-free deoxygenative C-H amination reaction of azine-N-oxides with acyl azides is described. The initial formation of an isocyanate from the starting acyl azide via a Curtius rearrangement can trigger a [3 + 2] dipolar cycloaddition of polar N-oxide fragments to generate the aminated azine derivative. The applicability of this method is highlighted by the late-stage and sequential amination reactions of complex bioactive compounds, including quinidine and fasudil. Moreover, the direct transformation of aminated azines into various bioactive N-heterocycles illustrates the significance of this newly developed protocol.
- Ghosh, Prithwish,Han, Sang Hoon,Han, Sangil,Kim, Dongeun,Kim, In Su,Kim, Saegun,Kwon, Na Yeon,Mishra, Neeraj Kumar
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p. 2476 - 2485
(2020/03/13)
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- Developing Inhibitors of the p47phox-p22phox Protein-Protein Interaction by Fragment-Based Drug Discovery
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Nicotinamide adenine dinucleotide phosphate oxidase isoform 2 is an enzyme complex, which generates reactive oxygen species and contributes to oxidative stress. The p47phox-p22phox interaction is critical for the activation of the catalytical NOX2 domain, and p47phox is a potential target for therapeutic intervention. By screening 2500 fragments using fluorescence polarization and a thermal shift assay and validation by surface plasmon resonance, we found eight hits toward the tandem SH3 domain of p47phox (p47phoxSH3A-B) with KD values of 400-600 μM. Structural studies revealed that fragments 1 and 2 bound two separate binding sites in the elongated conformation of p47phoxSH3A-B and these competed with p22phox for binding to p47phoxSH3A-B. Chemical optimization led to a dimeric compound with the ability to potently inhibit the p47phoxSH3A-B-p22phox interaction (Ki of 20 μM). Thereby, we reveal a new way of targeting p47phox and present the first report of drug-like molecules with the ability to bind p47phox and inhibit its interaction with p22phox.
- Solbak, Sara Marie ?ie,Zang, Jie,Narayanan, Dilip,H?j, Lars Jakobsen,Bucciarelli, Saskia,Softley, Charlotte,Meier, Sebastian,Langkilde, Annette Eva,Gotfredsen, Charlotte Held,Sattler, Michael,Bach, Anders
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p. 1156 - 1177
(2020/03/10)
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- Co(III)-Catalyzed C-H Amidation of Nitrogen-Containing Heterocycles with Dioxazolones under Mild Conditions
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A cobalt(III)-catalyzed C-8 selective C-H amidation of quinoline N-oxide using dioxazolone as an amidating reagent under mild conditions is disclosed. The reaction proceeds efficiently with excellent functional group compatibility. The utility of the current method is demonstrated by gram scale synthesis of C-8 amide quinoline N-oxide and by converting this amidated product into functionalized quinolines. Furthermore, the developed catalytic method is also applicable for C-7 amidation of N-pyrimidylindolines and ortho-amidation of benzamides.
- Dhiman, Ankit Kumar,Thakur, Ankita,Kumar, Inder,Kumar, Rakesh,Sharma, Upendra
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p. 9244 - 9254
(2020/08/14)
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- Cobalt-Catalyzed C8-Dienylation of Quinoline-N-Oxides
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An efficient Cp*CoIII-catalyzed C8-dienylation of quinoline-N-oxides was achieved by employing allenes bearing leaving groups at the α-position as the dienylating agents. The reaction proceeds by CoIII-catalyzed C?H activation of qui
- Khan, Salman,Nair, Akshay M.,Shukla, Rahul K.,Volla, Chandra M. R.
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supporting information
p. 17042 - 17048
(2020/08/05)
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- Visible-Light-Mediated C-H Alkylation of Pyridine Derivatives
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We report herein a visible-light-mediated C-H alkylation of pyridine derivatives that proceeds by simple combination of a large variety of N-alkoxypyridinium ions with alkanes in the presence of 2 mol % of fac-Ir(ppy)3 under blue illumination. The mild reaction conditions together with the high group functional tolerance make of this process a useful synthetic platform for the construction of structurally strained heterocycles. Detailed mechanistic investigations, including density functional theory calculations and quantum yield measurement, allowed us to understand factors controlling the reactivity and the selectivity of the reaction.
- Rammal, Fatima,Gao, Di,Boujnah, Sondes,Gaumont, Annie-Claude,Hussein, Aqeel A.,Lakhdar, Sami
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supporting information
p. 7671 - 7675
(2020/10/09)
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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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- Catalytic Selective Metal-Free Cross-Coupling of Heteroaromatic N-Oxides with Organosilanes
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A metal-free, regioselective C-H functionalization of heteroaromatic N-oxides has been developed. The method enables the synthesis of various benzylated and alkynylated N-heterocycles in a transition-metal-free manner employing organosilanes as coupling partners. The unanticipated reactivity has been exploited for the synthesis of a number of symmetrical disubstituted acetylenes from ethynyltrimethylsilane via carbon-silicon bond metathesis.
- Puthanveedu, Mahesh,Polychronidou, Vasiliki,Antonchick, Andrey P.
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supporting information
p. 3407 - 3411
(2019/05/10)
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- Copper-Catalyzed Deoxygenative C2-Sulfonylation of Quinoline N -Oxides with DABSO and Phenyldiazonium Tetrafluoroborates for the Synthesis of 2-Sulfonylquinolines via a Radical Reaction
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An efficient and practical method for the synthesis of 2-sulfonylquinolines through copper-catalyzed deoxygenative C2-sulfonylation of quinoline N -oxides with 1,4-diazabicyclo[2.2.2]octane bis(sulfur dioxide) (DABSO) and phenyldiazonium tetrafluoroborates is demonstrated. Products with various substituents were obtained in moderate to high yields.
- Deng, Qi,Dong, Dao-Qing,Li, Guang-Hui,Wang, Zu-Li,Yan, Shi-Qiang
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p. 3313 - 3319
(2019/08/28)
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- Cu-Catalyzed carbamoylation: Versus amination of quinoline N -oxide with formamides
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An efficient, direct carbamoylation and amination of quinoline N-oxides with formamides to access 2-carbamoyl and 2-amino quinolines has been developed through copper-catalyzed C-C and C-N bond formations via cross-dehydrogenative coupling reactions. The reaction proceeds smoothly over a broad range of substrates with excellent functional group tolerance under mild conditions. Mechanistic studies suggest that the reaction is initiated by formamide radical or decarbonylative aminyl radical formation in the presence of TBHP, according to the different substituent on the N atom of formamide.
- Zhang, Yan,Zhang, Shiwei,Xu, Guangxing,Li, Min,Tang, Chunlei,Fan, Weizheng
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supporting information
p. 309 - 314
(2019/01/10)
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- Hypervalent Iodine(III)-Mediated Regioselective Cyanation of Quinoline N-Oxides with Trimethylsilyl Cyanide
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A regioselective cyanation of quinoline N-oxides with trimethylsilyl cyanide was developed by using (Diacetoxyiodo) benzene (PIDA) as mediated hypervalent iodine(III) reagent under metal-free and base-free reaction conditions to obtain 2-cyanoquinolines. The efficient PIDA reagent could play the role of an activator of the substrates and an accelerator of N?O bond cleavage. The reaction system featured a wide range of substrate suitability and high yields. The procedure was enlarged gram-scale to synthesize the tuberculosis (TB) inhibitor. Finally, according to some experimental results, a plausible mechanism for the cyanation reaction is proposed. (Figure presented.).
- Xu, Feng,Li, Yuqin,Huang, Xin,Fang, Xinjie,Li, Zhuofei,Jiang, Hongshuo,Qiao, Jingyi,Chu, Wenyi,Sun, Zhizhong
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supporting information
p. 520 - 525
(2018/12/13)
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- RhIII-Catalyzed Straightforward Synthesis of Benzophenanthroline and Benzophenanthrolinone Derivatives using Anthranils
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An efficient pot-economic and step-economic RhIII-catalyzed site-selective direct amination/annulation strategy was developed for the synthesis of benzophenanthroline derivatives using quinoline N-oxides and anthranils. The method was further extended to the synthesis of nitrogen-containing extended π-conjugated benzophenanthrolinone derivatives. Late-stage functionalizations of cinchonidine and cinchophen derivatives and synthesis of a bioactive quinolino-indole were achieved.
- Biswas, Aniruddha,Sarkar, Souradip,Samanta, Rajarshi
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p. 3000 - 3004
(2019/02/13)
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- Rh/O2-Catalyzed C8 Olefination of Quinoline N-Oxides with Activated and Unactivated Olefins
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The rhodium/O2 system-catalyzed distal C(sp2)-H olefination of quinoline N-oxides is developed. Molecular oxygen has been explored as an economic and clean oxidant, an alternative to inorganic oxidants. A wide substrate scope with respect to quinoline N-oxides and olefins (activated acrylates and styrenes; unactivated aliphatic olefins) demonstrates the robustness of the developed catalytic method. Interestingly, 2-substituted quinoline N-oxides also afforded good yields of the corresponding C8-olefinated products. Kinetic isotope studies and deuterium-labeling experiments have been performed to understand the preliminary mechanistic pathway. The applicability of the developed method is demonstrated by utilizing natural product-derived substrates and by converting the C8-olefinated quinoline N-oxides into various other useful molecules.
- Sharma, Ritika,Kumar, Rakesh,Sharma, Upendra
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p. 2786 - 2797
(2019/02/26)
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- Catalyst-Free Synthesis of 2-Anilinoquinolines and 3-Hydroxyquinolines via Three-Component Reaction of Quinoline N-Oxides, Aryldiazonium Salts, and Acetonitrile
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A rapid microwave-assisted, catalyst-free, three-component synthesis of various 2-anilinoquinolines from quinoline N-oxides and aryldiazonium salts in acetonitrile under microwave irradiation is reported. This reaction utilizes acetonitrile as a single nitrogen source and involves the formation of two new C-N bonds via the formal [3 + 2] cycloaddition reaction. In the case of 2-substituted quinolines, 3-hydroxyquinoline was observed as the main product via a 1,3 shift of the oxygen atom from N-oxide to the C3 position of quinolines.
- Dhiman, Ankit Kumar,Chandra, Devesh,Kumar, Rakesh,Sharma, Upendra
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p. 6962 - 6969
(2019/06/14)
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- Highly Enantioselective Catalytic Addition of Grignard Reagents to N-Heterocyclic Acceptors
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General methods to prepare chiral N-heterocyclic molecular scaffolds are greatly sought after because of their significance in medicinal chemistry. Described here is the first general catalytic methodology to access a wide variety of chiral 2- and 4-substituted tetrahydro-quinolones, dihydro-4-pyridones, and piperidones with excellent yields and enantioselectivities, utilizing a single catalyst system.
- Guo, Yafei,Harutyunyan, Syuzanna R.
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supporting information
p. 12950 - 12954
(2019/08/07)
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- Synergy of anodic oxidation and cathodic reduction leads to electrochemical deoxygenative C2 arylation of quinoline: N-oxides
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The first example of electrochemical deoxygenative C2 arylation of quinoline N-oxides using sulfonyl hydrazines was demonstrated in this work. By employing both anodic oxidation and cathodic reduction, a variety of 2-arylquinolines were synthesized under metal catalyst-, exogenous-oxidant-, and exogenous-reductant-free conditions.
- Yuan, Yong,Jiang, Minbao,Wang, Tao,Xiong, Yunkui,Li, Jun,Guo, Huijiao,Lei, Aiwen
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supporting information
p. 11091 - 11094
(2019/09/20)
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- Regioselective Cyanation of Six-Membered N-Heteroaromatic Compounds Under Metal-, Activator-, Base- and Solvent-Free Conditions
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A regioselective cyanation of heteroaromatic N-oxides with trimethylsilyl cyanide has been developed to obtain 2-substituted N-heteroaromatic nitrile without the requirement of any external activator-, metal-, base-, and solvent. The present protocol is a straightforward, one-pot heteroaromatic C?H cyanation process, and proceeds smoothly in conventional heating but also under microwave irradiation with shorter reaction times. This approach now allows access to a broad class of quinoline N-oxides and other heteroarene N-oxides with high to good yields and can also be scaled up to obtain gram quantities. Further application of this process was observed and utilized in late-stage cyanation of the anti-malarial drug quinine as well as transformation of the 2-cyanoazines to a series of biologically important molecules. Based on the experimental observations, a plausible mechanism has also been proposed highlighting the dual role of trimethylsilyl cyanide as a nitrile source and as an activating agent. (Figure presented.).
- Sarmah, Bikash Kumar,Konwar, Monuranjan,Bhattacharyya, Dipanjan,Adhikari, Priyanka,Das, Animesh
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supporting information
p. 5616 - 5625
(2019/11/22)
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- Exogenous-oxidant-and catalyst-free electrochemical deoxygenative C2 sulfonylation of quinoline: N-oxides
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An exogenous-oxidant-and catalyst-free electrochemical deoxygenative C2 sulfonylation reaction has been achieved. By employing quinoline N-oxides as the starting materials, the electrochemical C-H sulfonylation of electron-deficient quinolines was indirectly achieved at room temperature and a variety of sulfonylated quinoline derivatives were synthesized in modest to high yield with excellent regioselectivity. Notably, this protocol is the first example for synthesizing sulfonylated electron-deficient heteroarenes/arenes through electrochemistry.
- Jiang, Minbao,Yuan, Yong,Wang, Tao,Xiong, Yunkui,Li, Jun,Guo, Huijiao,Lei, Aiwen
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supporting information
p. 13852 - 13855
(2019/11/21)
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- Method for synthesizing quinoline oxynitride from quinoline compound by ultrasonic-assisted oxidation
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The invention discloses a method for synthesizing quinoline oxynitride from a quinoline compound by ultrasonic-assisted oxidation. The quinoline compound and hydrogen peroxide are subjected to nitrogen oxidation reaction under the ultrasonic-assisted condition and perfluorosulfonic acid resin (Nafion-H) catalytic action to obtain quinoline oxynitride. The method has the advantages that the raw materials are easy to obtain, reaction conditions are simple and mild, greenness and energy conservation are achieved, and reaction selectivity and yield are high; energy is saved and the compatibility of substrate functional groups is excellent; in particular, the perfluorosulfonic acid resin can be recycled as an acid catalyst, so that not only is the reaction cost reduce, but also the reaction yield is increased, also the pollution problem in traditional oxidation reaction is avoided and a relatively high application value is achieved.
- -
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Paragraph 0061; 0062; 0063
(2018/06/21)
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- Transition-Metal-Free Regioselective Alkylation of Quinoline N-Oxides via Oxidative Alkyl Migration and C?C Bond Cleavage of tert-/sec-Alcohols
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An unprecedented C2-alkylation of quinoline N-oxide derivatives via C?C bond activation of tert- and sec-alkyl alcohol is described using hypervalent iodine (III) reagent PhI(OAc)2 (PIDA). This regioselective alkylation using mild hypervalent iodine reagents is more practical, operationally simple and transition metal free. The reaction proceeds efficiently with a broad range of substrates including quinoline, isoquinoline, and pyridine N-oxides using a variety of tert-/sec- alcohols. From experimental outcome, we also propose a rationalized mechanism, mediated by PIDA. (Figure presented.).
- Sen, Chiranjit,Ghosh, Subhash C.
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supporting information
p. 905 - 910
(2018/01/11)
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- Dehydrogenative etherification homocoupling of heterocyclic N-oxides
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A novel approach was developed for the dehydrogenative etherification homocoupling of heterocyclic N-oxides in the presence of silver oxide and PyBroP. Various substrates were well tolerated and the desired products were obtained in moderate to good yields. Generally, this reaction features excellent functional group compatibility, broad substrate scope and good regioselectivity.
- Zhang, Dong,Qiao, Kai,Yuan, Xin,Zheng, Mingwei,Fang, Zheng,Wan, Li,Guo, Kai
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supporting information
p. 1752 - 1756
(2018/04/10)
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- Structure-based design and profiling of novel 17β-HSD14 inhibitors
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The human enzyme 17β-hydroxysteroid dehydrogenase 14 (17β-HSD14) oxidizes the hydroxyl group at position 17 of estradiol and 5-androstenediol using NAD+ as cofactor. However, the physiological role of the enzyme remains unclear. We recently des
- Braun, Florian,Bertoletti, Nicole,M?ller, Gabriele,Adamski, Jerzy,Frotscher, Martin,Guragossian, Nathalie,Madeira Gírio, Patrícia Alexandra,Le Borgne, Marc,Ettouati, Laurent,Falson, Pierre,Müller, Sebastian,Vollmer, Günther,Heine, Andreas,Klebe, Gerhard,Marchais-Oberwinkler, Sandrine
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supporting information
p. 61 - 76
(2018/06/01)
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- Visible Light-Mediated Decarboxylative Alkylation of Pharmaceutically Relevant Heterocycles
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A net redox-neutral method for the decarboxylative alkylation of heteroarenes using photoredox catalysis is reported. Additionally, this method features the use of simple, commercially available carboxylic acid derivatives as alkylating agents, enabling the facile alkylation of a variety of biologically relevant heterocyclic scaffolds under mild conditions.
- Sun, Alexandra C.,McClain, Edward J.,Beatty, Joel W.,Stephenson, Corey R. J.
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supporting information
p. 3487 - 3490
(2018/06/26)
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- RhIII-Catalyzed Direct C8-Arylation of Quinoline N-Oxides using Diazonaphthalen-2(1H)-ones: A Practical Approach towards 8-aza BINOL
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An efficient RhIII-catalyzed redox-neutral method for the direct C8-arylation of quinoline N-oxides using diazonaphthalen-2(1H)-one as coupling partner has been demonstrated. The developed method is simple, scalable and straightforward with a w
- Ghosh, Bidhan,Biswas, Aniruddha,Chakraborty, Soumen,Samanta, Rajarshi
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supporting information
p. 2388 - 2392
(2018/05/30)
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- Hydroheteroarylation of Unactivated Alkenes Using N-Methoxyheteroarenium Salts
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We report the first reductive coupling of unactivated alkenes with N-methoxy pyridazinium, imidazolium, quinolinium, and isoquinolinium salts under hydrogen atom transfer (HAT) conditions, and an expanded scope for the coupling of alkenes with N-methoxy pyridinium salts. N-Methoxy pyridazinium, imidazolium, quinolinium, and isoquinolinium salts are accessible in 1-2 steps from the commercial arenes or arene N-oxides (25-99%). N-Methoxy imidazolium salts are accessible in three steps from commercial amines (50-85%). In total 36 discrete methoxyheteroarenium salts bearing electron-donating, electron-withdrawing, alkyl, aryl, halogen, and haloalkyl substituents were prepared (several in multigram quantities) and coupled with 38 different alkenes. The transformations proceed under neutral conditions at ambient temperature, provide monoalkylation products exclusively, and form a single alkene addition regioisomer. Preparatively useful and complementary site selectivities in the addition of secondary and tertiary radicals to pyidinium salts are documented: harder secondary radicals favor C-2 addition (2->10:1), while softer tertiary radicals favor bond formation to C-4 (4.7->29:1). A diene possessing a 1,2-disubstituted and 2,2-disubstituted alkene undergoes hydropyridylation at the latter exclusively (61%) suggesting useful site selectivities can be obtained in polyene substrates. The methoxypyridinium salts can also be employed in dehydrogenative arylation, borono-Minisci, and tandem arylation processes. Mechanistic studies support the involvement of a radical process.
- Ma, Xiaoshen,Dang, Hester,Rose, John A.,Rablen, Paul,Herzon, Seth B.
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supporting information
p. 5998 - 6007
(2017/05/04)
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- Intermolecular Amidation of Quinoline N-Oxides with Arylsulfonamides under Metal-Free Conditions
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An efficient method for the synthesis of N-(quinolin-2-yl)sulfonamides is described. The intermolecular amidation of quinoline N-oxides with sulfonamides proceeded smoothly in the presence of PhI(OAc)2 and PPh3 to afford N-(quinolin-
- Yu, Xiaoqiang,Yang, Sana,Zhang, Yue,Guo, Mingju,Yamamoto, Yoshinori,Bao, Ming
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supporting information
p. 6088 - 6091
(2017/11/27)
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- 2,2′-Homocoupled Azine N,N′-Dioxides or Azine N-Oxides: CDC- or SNAr-Controlled Chemoselectivity
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An unprecedented Cu(OAc)2- and LiOtBu-mediated homocoupling of azine N-oxides to yield 2,2′-azine N,N′-dioxides is reported. This is the first instance in which copper has been used to catalyze the homodimerization reaction, especially of 2-phenylpyridine N-oxides. In the absence of catalytic copper, the reaction follows an alternative pathway, and instead of dioxides it yields 2,2′-azine N-monoxides. This latter protocol works efficiently with a range of N-heterocyclic oxides of pyridine, 2-phenylpyridine, quinoline and N-aryl-1,2,3-triazole. It is scalable, offers high regioselectivity and gives the products in moderate to high yields. The observed chemoselectivity between the copper-assisted and copper-free protocols is routed through oxidative cross-dehydrogenative coupling (CDC) and nucleophilic aromatic substitution of hydrogen (SNAr) pathways, respectively.
- Jha, Abadh Kishor,Jain, Nidhi
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p. 4765 - 4772
(2017/09/07)
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- Iodine/TBHP-Promoted One-Pot Deoxygenation and Direct 2-Sulfonylation of Quinoline N-Oxides with Sodium Sulfinates: Facile and Regioselective Synthesis of 2-Sulfonylquinolines
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A highly efficient iodine/TBHP-mediated one-pot deoxygenative and regioselective 2-sulfonylation of quinoline N-oxides with sodium sulfinate salts has been developed. This metal-, base-, and phosphorus-free protocol employs readily accessible and easy-to-handle reagents and can be conveniently carried out at room temperature under mild conditions, providing an alternative access to a series of 2-sulfonylquinolines and other related heteroaryl sulfone products in moderate-to-excellent yields within a short reaction time.
- Sumunnee, Ladawan,Buathongjan, Chonchanok,Pimpasri, Chaleena,Yotphan, Sirilata
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supporting information
p. 1025 - 1032
(2017/02/15)
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- Metal-free phosphonation of heteroarene N-oxides with trialkyl phosphite at room temperature
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A new protocol is described for the conversion of heteroarene N-oxides to heteroarylphosphonates through in situ activation with bromotrichloromethane. The N-oxides of isoquinoline, quinoline, quinoxaline and 1,10-phenanthroline were fast transformed into the corresponding heteroarylphosphonates in up to 92% yield under mild conditions in the absence of solvent and metal catalysts. The good functional group tolerance, low cost, feasibility of scale up, and wide availability of reagents make this method a prominent complement to the Hirao coupling.
- Chen, Ming-Tao,You, Xia,Bai, Li-Gang,Luo, Qun-Li
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supporting information
p. 3165 - 3169
(2017/04/21)
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- Copper-Catalyzed Direct, Regioselective Arylamination of N-Oxides: Studies to Access Conjugated π-Systems
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An efficient copper(I)-catalyzed direct regioselective arylamination of various heterocyclic N-oxides was achieved successfully under redox-neutral conditions using anthranils as arylaminating reagents. The developed protocol is simple, straightforward, and economic with a broad range substrate scope. The dual functional groups in the final molecules were utilized to construct structurally and functionally diverse nitrogen-containing organic π-conjugated systems.
- Biswas, Aniruddha,Karmakar, Ujjwal,Nandi, Shiny,Samanta, Rajarshi
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p. 8933 - 8942
(2017/09/11)
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- Rhodium-Catalyzed Remote C-8 Alkylation of Quinolines with Activated and Unactivated Olefins: Mechanistic Study and Total Synthesis of EP4 Agonist
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Reported herein is a rhodium(III)-catalyzed regioselective distal C(sp2)-H bond alkylation of quinoline N-oxides using olefins as alkyl source and N-oxide as the traceless directing group. The reaction exhibits broad substrate scope with excellent selectivity for C-8 position and good yields of alkylated products. The usefulness of the developed catalytic protocol is established by synthesis of EP4 agonist. In mechanistic study, C-8 olefinated quinoline was identified as the reaction intermediate, which gets reduced to desired C-8 alkylated product in the presence of a rhodium(I) species (produced from rhodium(III) during reaction) and formic acid. Formic acid is produced from dimethylformamide in the presence of silver tetrafluoroborate. (Figure presented.).
- Sharma, Ritika,Kumar, Inder,Kumar, Rakesh,Sharma, Upendra
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supporting information
p. 3022 - 3028
(2017/09/08)
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- Highly Enantioselective Direct Synthesis of Endocyclic Vicinal Diamines through Chiral Ru(diamine)-Catalyzed Hydrogenation of 2,2′-Bisquinoline Derivatives
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An asymmetric hydrogenation of 2,2′-bisquinoline and bisquinoxaline derivatives, catalyzed by chiral cationic ruthenium diamine complexes, was developed. A broad range of chiral endocyclic vicinal diamines were obtained in high yields with excellent diastereo- and enantioselectivity (up to 93:7 dl/meso and >99 % ee). These chiral diamines could be easily transformed into a new class of chiral N-heterocyclic carbenes (NHCs), which are important but difficult to access.
- Ma, Wenpeng,Zhang, Jianwei,Xu, Cong,Chen, Fei,He, Yan-Mei,Fan, Qing-Hua
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p. 12891 - 12894
(2016/10/04)
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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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- Catalyst and solvent-free alkylation of quinoline N-oxides with olefins: A direct access to quinoline-substituted α-hydroxy carboxylic derivatives
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A catalyst/solvent-free, one-pot and operationally simple method for the synthesis of quinoline-substituted α-hydroxy carboxylic derivatives by the hydroxyheteroarylation of olefins with quinoline N-oxides is reported. The reaction features a high atom-economy, mild and reagent/solvent-free conditions, broad substrate scope and good selectivity with high yields. A preliminary mechanistic study to shed light into the reaction pathway was also carried out.
- Kumar, Rakesh,Kumar, Inder,Sharma, Ritika,Sharma, Upendra
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supporting information
p. 2613 - 2617
(2016/03/05)
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- Regioselective Chlorination of Quinoline N-Oxides and Isoquinoline N-Oxides Using PPh3/Cl3CCN
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A novel method for the regioselective C2-chlorination of heterocyclic N-oxides has been developed. PPh3/Cl3CCN were used as chlorinating reagents and the desired N-heterocyclic chlorides were obtained smoothly in satisfactory yields. The reactions proceeded in a highly efficient and selective manner across a broad range of substrates demonstrating excellent functional group tolerance. In addition, this chlorination reaction can be used for the modification of N-heterocyclic scaffolds of appealing ligands and pharmaceuticals.
- Qiao, Kai,Wan, Li,Sun, Xiaoning,Zhang, Kai,Zhu, Ning,Li, Xin,Guo, Kai
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p. 1606 - 1611
(2016/04/05)
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- Cu-Catalyzed Deoxygenative C2-Sulfonylation Reaction of Quinoline N-Oxides with Sodium Sulfinate
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An unexpected Cu-catalyzed deoxygenative C2-sulfonylation reaction of quinoline N-oxides in the presence of radical initiator K2S2O8 was developed that used sodium sulfinate as a sulfonyl coupling partner. The mechanism studies indicate that the reaction proceeds via Minisci-like radical coupling step to give sulfonylated quinoline with good chemical yields.
- Du, Bingnan,Qian, Ping,Wang, Yang,Mei, Haibo,Han, Jianlin,Pan, Yi
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supporting information
p. 4144 - 4147
(2016/08/30)
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- Benzylation of heterocyclic N-oxides via direct oxidative cross-dehydrogenative coupling with toluene derivatives
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A novel cross-dehydrogenative coupling (CDC) of heterocyclic N-oxides with toluene derivatives has been discussed, allowing for the facile synthesis of a broad range of structurally diverse C1-benzyl quinoline N-oxides, isoquinoline N-oxides and pyridine N-oxides, including two methylated quinoline N-oxides in particular. This protocol not only extends the application of toluenes in synthetic organic chemistry, but also offers an alternative method to prepare benzylated heterocyclic N-oxides without any metal involved, which is important in medicinal chemistry.
- Wan,Qiao,Sun,Di,Fang,Li,Guo
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supporting information
p. 10227 - 10232
(2016/12/07)
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- A general synthesis of bis(o-azaheteroaryl)methane derivatives from N-oxides of azines and azoles
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A general method of preparation of derivatives of bis(o-azaheteroaryl)methanes from aromatic N-oxides is reported, the key step of which is a 1,3-dipolar cycloaddition between N-oxides of azines or azoles and in situ generated terminal difluoroalkenes containing an o-azaheteroaryl substituent at the double bond. Selected products were applied for the preparation of two novel unsymmetrical analogues of BODIPY fluorescent dyes, containing both an imidazole and a quinoline or isoquinoline unit.
- Szpunar, Magdalena,Loska, Rafa?
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supporting information
p. 2133 - 2137
(2015/03/31)
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- Copper-catalyzed oxygen atom transfer of N-oxides leading to a facile deoxygenation procedure applicable to both heterocyclic and amine N-oxides
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Deoxygenation of various types of N-oxides including both heterocyclic and alkyl(aryl)amine derivatives has successfully been developed by the copper-catalyzed oxygen atom transfer using diazo compounds as the oxygen acceptor. The reaction proceeds smoothly over a broad range of substrates with excellent functional group tolerance under mild conditions. This journal is
- Jeong, Jisu,Lee, Donggun,Chang, Sukbok
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supporting information
p. 7035 - 7038
(2015/04/22)
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- Synthesis of 8-Aminoquinolines by Using Carbamate Reagents: Facile Installation and Deprotection of Practical Amidating Groups
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Described herein is the development of practical routes to 8-aminoquinolines by using readily installable and easily deprotectable amidating reagents. Two scalable procedures were optimized under RhIII-catalyzed conditions: i) the use of pre-generated chlorocarbamates and ii) a two-step one-pot process that directly employs carbamates. Both approaches are highly convenient for the gram-scale synthesis of 8-aminoquinolines under mild conditions. Facile deprotection of the synthetically versatile amidating groups was achieved under the Pd-catalyzed transfer hydrogenation conditions with simultaneous deoxygenation of quinoline N-oxides, thus yielding 8-aminoquinolines in excellent overall efficiency.
- Gwon, Donghyeon,Hwang, Heejun,Kim, Hye Kyung,Marder, Seth R.,Chang, Sukbok
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supporting information
p. 17200 - 17204
(2016/01/25)
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- Copper-catalyzed direct amination of quinoline N-oxides via C-H bond activation under mild conditions
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A highly efficient and concise one-pot strategy for the direct amination of quinoline N-oxides via copper-catalyzed dehydrogenative C-N coupling has been developed. The desired products were obtained in good to excellent yields for 22 examples starting from the parent aliphatic amines. This methodology provides a practical pathway to 2-aminoquinolines and features a simple system, high efficiency, environmental friendliness, low reaction temperature, and ligand, additives, base, and external oxidant free conditions.
- Zhu, Chongwei,Yi, Meiling,Wei, Donghui,Chen, Xuan,Wu, Yangjie,Cui, Xiuling
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supporting information
p. 1840 - 1843
(2014/05/06)
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- Direct 2-acetoxylation of quinoline N-oxides via copper catalyzed C-H bond activation
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An efficient and direct 2-acetoxylation of quinoline N-oxides via copper(i) catalyzed C-H bond activation has been developed. This transformation was achieved using TBHP as an oxidant in the cross-dehydrogenative coupling (CDC) reaction of quinoline N-oxides with aldehydes, and provided a practical pathway to 2-acyloxyl quinolines.
- Chen, Xuan,Zhu, Chongwei,Cui, Xiuling,Wu, Yangjie
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supporting information
p. 6900 - 6902
(2013/07/26)
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- Synthesis of alkyl aryl(heteroaryl)acetates from N-oxides, 1,1-difluorostyrenes, and alcohols
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Derivatives of aryl(heteroaryl)acetic acids or aryl(heteroaryl)methanes are formed from imidazole or thiazole N-oxide, 1,1-difluorostyrene, and an alcohol, amine, or water in a three-component reaction, which probably occurs via 1,3-dipolar cycloaddition.
- Loska, Rafal,Szachowicz, Katarzyna,Szydlik, Dorota
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supporting information
p. 5706 - 5709
(2013/12/04)
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- NOVEL SUBSTITUTED QUINOLINE COMPOUNDS AS S-NITROSOGLUTATHIONE REDUCTASE INHIBITORS
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The present invention is directed to novel quinoline compounds useful as S-nitrosoglutathione reductase (GSNOR) inhibitors, pharmaceutical compositions comprising such compounds, and methods of making and using the same.
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Page/Page column 74
(2012/04/23)
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- NOVEL SUBSTITUTED BICYCLIC AROMATIC COMPOUNDS AS S-NITROSOGLUTATHIONE REDUCTASE INHIBITORS
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The present invention is directed to novel substituted bicyclic aromatic compounds useful as S-nitrosoglutathione reductase (GSNOR) inhibitors, pharmaceutical compositions comprising such compounds, and methods of making and using the same.
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Page/Page column 90-91
(2012/06/30)
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