- Tetrasubstituted 1,3-Enynes by Gold-Catalyzed Direct C(sp2)-H Alkynylation of Acceptor-Substituted Enamines
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A gold-catalyzed synthesis of tetrasubstituted 1,3-enynes from hypervalent iodine(III) reagents and activated alkenes is reported. This reaction involves an in situ formed alkynyl Au(III) species and a subsequent direct C(sp2)-H functionalization of alkenes, offering 26 enynes in 62-92% yield with excellent functional group tolerance.
- Han, Chunyu,Tian, Xianhai,Zhang, Huili,Rominger, Frank,Hashmi, A. Stephen K.
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supporting information
p. 4764 - 4768
(2021/06/30)
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- Green synthesis method of nicotinic acid ester compounds based on non-metallic conditions
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The invention discloses a green synthesis method based on nicotinic acid ester compounds under non-metallic conditions, and belongs to the technical field of organic synthesis. The method comprises the following steps of (III) replacing cyclopropanol and (II) substituted enamine ester as a raw material, taking tetramethyl piperidine nitrogen oxide as an oxidizing agent, 110 - 130 °C, stirring and reacting in an organic solvent to synthesize a (I) nicotinate compound. The invention provides a green synthesis method based on nicotinic acid ester compounds under non-metallic conditions, wherein cyclopropanols and enamine esters are taken as raw materials, and a polysubstituted nicotinate is synthesized through a strategy of oxidative dehydrogenation of ketene cyclization.
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Paragraph 0058; 0061
(2021/09/29)
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- Multi-component synthesis of 3-substituted indoles and their cyclisation to α-carbolines: Via I2-promoted intramolecular C2 oxidative amination/aromatisation at room temperature
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Condensation of indoles, aldehydes and pyrazol-5-amine in the presence of ceric ammonium nitrate gives 3-substituted indoles. These then cyclise to α-carbolines at room temperature through I2-promoted intramolecular C2 amination and aromatisation in open air. A plausible mechanism is proposed based on some controlled experiments.
- Deka, Bhaskar,Baruah, Pranjal K.,Deb, Mohit L.
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supporting information
p. 7806 - 7810
(2018/11/21)
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- Synthesis of trifluoromethylated 2H-azirines through Togni reagent-mediated trifluoromethylation followed by PhIO-mediated azirination
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The reaction of enamine compounds with the Togni reagent in the presence of CuI afforded β-trifluoromethylated enamine intermediates, which were converted directly to biologically interesting trifluoromethylated 2H-azirines by an iodosobenzene (PhIO)-mediated intramolecular azirination in a one-pot process.
- Sun, Jiyun,Zhen, Xiaohua,Ge, Huaibin,Zhang, Guangtao,An, Xuechan,Du, Yunfei
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supporting information
p. 1452 - 1458
(2018/07/05)
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- Tandem Thorpe Reaction/Palladium Catalyzed Asymmetric Allylic Alkylation: Access to Chiral β-enaminonitriles with Excellent Enantioselectivity
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A new type of nucleophile, a 3-imino nitrile carbanion generated in situ by Thorpe reaction of acetonitrile with a base, was developed successfully and applied in a Pd-catalyzed asymmetric allylic alkylation with mono-substituted allyl reagents under Pd/S
- Bai, Da-Chang,Liu, Xiu-Yan,Li, Hao,Ding, Chang-Hua,Hou, Xue-Long
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p. 212 - 215
(2017/02/05)
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- In situ click chemistry generation of cyclooxygenase-2 inhibitors
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Cyclooxygenase-2 isozyme is a promising anti-inflammatory drug target, and overexpression of this enzyme is also associated with several cancers and neurodegenerative diseases. The amino-acid sequence and structural similarity between inducible cyclooxygenase-2 and housekeeping cyclooxygenase-1 isoforms present a significant challenge to design selective cyclooxygenase-2 inhibitors. Herein, we describe the use of the cyclooxygenase-2 active site as a reaction vessel for the in situ generation of its own highly specific inhibitors. Multi-component competitive-binding studies confirmed that the cyclooxygenase-2 isozyme can judiciously select most appropriate chemical building blocks from a pool of chemicals to build its own highly potent inhibitor. Herein, with the use of kinetic target-guided synthesis, also termed as in situ click chemistry, we describe the discovery of two highly potent and selective cyclooxygenase-2 isozyme inhibitors. The in vivo anti-inflammatory activity of these two novel small molecules is significantly higher than that of widely used selective cyclooxygenase-2 inhibitors.
- Bhardwaj, Atul,Kaur, Jatinder,Wuest, Melinda,Wuest, Frank
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- Acid-promoted rapid solvent-free access to substituted 1,4-dihydropyridines from β-ketothioamides
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β-Ketothioamides (KTAs) have been used as building blocks with aldehydes and β-enaminonitriles for synthesis of 1,4-dihydropyridines in the presence of AcOH under solvent-free conditions within 5 min. This new strategy exhibits remarkable features such as high chemoselectivity, mild reaction conditions, easily available substrates, and good yields.
- Li, Ming,Sun, Ke-Na,Wen, Li-Rong
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p. 21535 - 21539
(2016/03/08)
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- Enantioselective biocatalytic hydrolysis of β-aminonitriles to β-amino-amides using Rhodococcus rhodochrous ATCC BAA-870
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A range of β-aminonitriles (3-amino-3-phenylpropanenitrile and derivatives) were synthesised by reaction of various benzonitriles with acetonitrile and subsequent reduction of the resulting acrylonitrile products. These compounds were hydrolysed to the co
- Chhiba, Varsha,Bode, Moira L.,Mathiba, Kgama,Kwezi, Wendy,Brady, Dean
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experimental part
p. 68 - 74
(2012/04/10)
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- Rhodium-catalyzed asymmetric hydrogenation of β-acetylamino acrylonitriles
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The rhodium-catalyzed asymmetric hydrogenation of β-acetylamino acrylonitriles was investigated by using monophosphine and bisphosphine ligands. It was found that an Rh-QuinoxP complex exhibited high enantioselectivities for β-aryl substituted β-acetylamino acrylonitriles and the Rh-JosiPhos CyPF-t-Bu complex was proven to be effective for the hydrogenation of tetrasubstituted olefins from cyclic β-acetylamino acrylonitriles.
- Ma, Miaofeng,Hou, Guohua,Wang, Junru,Zhang, Xumu
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experimental part
p. 506 - 511
(2011/06/17)
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- Design and synthesis of substituted N-(1,3-diphenyl-1H-pyrazol-5-yl) benzamides as positive allosteric modulators of the metabotropic glutamate receptor subtype 5
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Based on SAR in the alkyne class of mGlu5 receptor negative allosteric modulators and a set of amide-based positive allosteric modulators, optimized substitution of the aryl bring was used to create substituted N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamides.
- Zou, Mu-Fa,Cao, Jianjing,Rodriguez, Alice L.,Jeffrey Conn,Newman, Amy Hauck
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scheme or table
p. 2650 - 2654
(2011/06/20)
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- Highly efficient RhI-catalyzed asymmetric hydrogenation of β-amino acrylonitriles
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(Figure Presented) It takes two to TangPhos: β-Amino acrylonitriles can be readily prepared from acetonitriles. Both of the E/Z isomers undergo hydrogenation with excellent enantioselectivity by using the Rh-TangPhos (TangPhos = l, 1'-ditert-butyl-(2, 2')-diphospholane) catalyst system. The products, chiral β-amino nitriles, are valuable chiral building blocks for many drugs.
- Ma, Miaofeng,Hou, Guohua,Sun, Tian,Zhang, Xiaowei,Li, Wei,Wang, Junru,Zhang, Xumu
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supporting information; experimental part
p. 5301 - 5304
(2010/09/08)
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- Cyanophenylation of aromatic nitriles by terephthalonitrile dianion: Is the charge-transfer complex a key intermediate?
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The interaction of terephthalonitrile (1) dianion (12-) with benzonitrile (2) or m-tolunitrile (3) provides 4,4′-dicyanobiphenyl (4) or 4,4′-dicyano-2-methylbiphenyl (5), respectively. This result shows that dianion 12- serves as a reagent for p-cyanophenylation of aromatic nitriles. Based on experimental data, such as the chemical trapping of the 4,4′-dicyanobiphenyl precursor 4-cyano-1-(p-cyanophenyl)cyclohexa-2,5-dienyl anion (7) and the failure to obtain biphenyl 4 through the interaction of independently generated radical anions (RAs) 1- and 2-, as well as on the results of quantum-chemical calculations, a mechanism is suggested that includes a charge-transfer complex (CTC) between 12- and the aromatic nitrile as the key intermediate. The formation of this CTC is followed either by an intracomplex electron transfer (ET) and recombination of terephthalonitrile and aromatic nitrile RAs within an unequilibrated RA pair, or by synchronous ET and bonding of the ipso-carbon atom of terephthalonitrile with the p-carbon atom of the aromatic nitrile. The synthetic significance of p-cyanophenylation of arenecarbonitriles by dianion 12- is illustrated by the high yield of biphenyl product 4 (approx. 90%) as well as by the possibility of a one-pot synthesis of 4-butyl-4′-cyanobiphenyl and 4-butyl-4′-cyano-2-methylbiphenyl by successive treatment of dianion 12- with nitrile 2 or 3 and butyl bromide. Wiley-VCH Verlag GmbH & Co, KGaA, 69451 Weinheim, Germany, 2005.
- Panteleeva, Elena V.,Shchegoleva, Lyudmila N.,Vysotsky, Viktor P.,Pokrovsky, Leonid M.,Shteingarts, Vitalij D.
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p. 2558 - 2565
(2007/10/03)
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- A new expedient route to 2,6-diaryl-3-cyano-4- (trifluoromethyl)pyridines
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1-Aryl-4,4,4-trifluoro-1,3-butanediones 1 react with β-amino-β- arylacrylonitrile 2, readily available from acetonitrile with aryl nitriles in the presence of potassium t-butoxide, to afford the corresponding 2,6- diaryl-3-cyano-4-(trifluoromethyl)pyridin
- Yamaguchi,Katsuyama,Funabiki,Matsui,Shibata
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p. 805 - 810
(2007/10/03)
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- Thienoisothiazoles. III. The Synthesis and Reactions of 3-Phenyl-5-alkylthioisothiazole-4-carbonitriles and 3-Phenylthienoisothiazoles
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Oxidation of the alkyl 3-amino-4-cyano-3-phenylpropenedithioates (1), obtained by alkylation of the condensation product of 3-amino-3-phenylpropenenitrile and carbon disulfide, produced 3-phenyl-5-alkylthioisothiazole-4-carbonitrile (2a-d).The ease of nucleophilic displacement of the S-alkyl group in the isothiazole (2a) was utilized to synthesize the isothiazoles (2f-j). 3-Phenylthioisothiazole (3e) was prepared by deamination, hydrolysis and decarboxylation of the intermediate ethyl 4-amino-3-phenylthienoisothiazole-5-carboxylate (3a), which was obtained was obtained by ring-closure of ethyl 2-(4-cyano-3-phenylisothiazol-5-ylthio)acetate (2d). 3-Phenylthienoisothiazole was unreactive towards weaker electrophiles, but undergoes bromination and nitration in the α-position of the thiophen ring.The position of substituents in 5-bromo- (3w) and 5-nitro-3-phenylthienoisothiaole (4a) was verified by alternative synthesis. the attempted deamination of 4-amino-5-bromo-3-phenylthienoisothiazole (3o) and 4-amino-5-nitro-3-phenyltheienoisothiazole (3r) yielded 3-phenyl-5-nitrothienoisothiazol-4-ol (3s) only, but the isomeric 4-bromo-3-phenylthienoisothiazole (3v) was obtained bt decarboxylation of 4-bromo-3-phenylthienoisothiazole-5-carboxylic acid (3u).An alternative synthesis of the 5-nitro derivative was achieved by decarboxylation of 5-nitro-3-phenylthienoisothiazole-4-carboxylic acid (3z).Mild reduction of 3-phenylthienoisothiazole derivatives, (3a,b) and (4c), with hydrogen sulfide or hypophosphorous acid afforded the substituted 3-(α-aminobenzylidene)-2,3-dihydrothiophen-2-thiones (5a-c), and the 3-benzoyl-2-alkylthiothiophen derivatives (6a,b), were obtained by a one-step synthesis, which avoided the isolation of the air-sensitive intemediates.
- Krebs, Hans-Dieter
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p. 1291 - 1306
(2007/10/02)
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- A GENERAL SYNTHESIS OF 3-AMINO-2-ALKENENITRILES BY THE CROSS-THORPE REACTION
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Highly selective cross-Thorpe reaction is achieved between an α-lithioalkanenitriles and a protected cyanohydrin to give 4-alkoxy-4-amino-2-alkenenitrile, which, in turn, is converted by deprotection and acetylation followed by hydrogenolysis to 3-amino-2
- Kobayashi, Kazuhiro,Hiyama, Tamejiro
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p. 3509 - 3512
(2007/10/02)
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- Potential antiarthritic agents. II. Benzoylacetonitriles and β-aminocinnamonitriles
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Benzoylacetonitrile and β-aminocinnamonitrile are shown to possess potent intiinflammatory activity in the rat adjuvant arthritis model. In a series of phenyl-substituted analogues, only o-, m-, and p-fluorobenzoylacetonitrile and m- and p-fluoro-β-aminocinnamonitrile retained activity. Additionally, β-amino-2- and β-amino-3-thiopheneacrylonitrile and β-oxo-2- and β-oxo-3-thiophenepropionitrile exhibited similar activity. These agents are not believed to be acting via prostaglandin synthetase inhibition. The metabolic profile of benzoylacetonitrile is also described.
- Ridge,Hanifin,Harten,Johnson,Menschik,Nicolau,Sloboda,Watts
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p. 1385 - 1389
(2007/10/09)
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