- From Stoichiometric Reagents to Catalytic Partners: Selenonium Salts as Alkylating Agents for Nucleophilic Displacement Reactions in Water
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The ability of chalcogenium salts to transfer an electrophilic moiety to a given nucleophile is well known. However, up to date, these reagents have been used in stoichiometric quantities, producing a substantial amount of waste as byproducts of the reaction. In this report, we disclose further investigation of selenonium salts as S-adenosyl-L-methionine (SAM) surrogates for the alkylation of nucleophiles in aqueous solutions. Most importantly, we were able to convert the stoichiometric process to a catalytic system employing as little as 10 mol % of selenides to accelerate the reaction between benzyl bromide and other alkylating agents with sodium cyanide in water. Probe experiments including 77Se NMR and HRMS of the reaction mixture have unequivocally shown the presence of the selenonium salt in the reaction mixture. (Figure presented.).
- Martins, Nayara Silva,ángel, Alix Y. Bastidas,Anghinoni, Jo?o M.,Lenard?o, Eder J.,Barcellos, Thiago,Alberto, Eduardo E.
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supporting information
p. 87 - 93
(2021/11/03)
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- Direct C(sp3)-H Cyanation Enabled by a Highly Active Decatungstate Photocatalyst
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A highly efficient, direct C(sp3)-H cyanation was developed under mild photocatalytic conditions. The method enabled the direct cyanation of various C(sp3)-H substrates with excellent functional group tolerance. Notably, complex natural products and bioactive compounds were efficiently cyanated.
- Kim, Kunsoon,Lee, Seulchan,Hong, Soon Hyeok
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supporting information
p. 5501 - 5505
(2021/07/26)
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- Assembly of α-(Hetero)aryl Nitriles via Copper-Catalyzed Coupling Reactions with (Hetero)aryl Chlorides and Bromides
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α-(Hetero)aryl nitriles are important structural motifs for pharmaceutical design. The known methods for direct synthesis of these compounds via coupling with (hetero)aryl halides suffer from narrow reaction scope. Herein, we report that the combination of copper salts and oxalic diamides enables the coupling of a variety of (hetero)aryl halides (Cl, Br) and ethyl cyanoacetate under mild conditions, affording α-(hetero)arylacetonitriles via one-pot decarboxylation. Additionally, the CuBr/oxalic diamide catalyzed coupling of (hetero)aryl bromides with α-alkyl-substituted ethyl cyanoacetates proceeds smoothly at 60 °C, leading to the formation of α-alkyl (hetero)arylacetonitriles after decarboxylation. The method features a general substrate scope and is compatible with various functionalities and heteroaryls.
- Chen, Ying,Xu, Lanting,Jiang, Yongwen,Ma, Dawei
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supporting information
p. 7082 - 7086
(2021/02/26)
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- CO2-Enabled Cyanohydrin Synthesis and Facile Iterative Homologation Reactions**
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Thermodynamic and kinetic control of a chemical process is the key to access desired products and states. Changes are made when a desired product is not accessible; one may manipulate the reaction with additional reagents, catalysts and/or protecting groups. Here we report the use of carbon dioxide to accelerate cyanohydrin synthesis under neutral conditions with an insoluble cyanide source (KCN) without generating toxic HCN. Under inert atmosphere, the reaction is essentially not operative due to the unfavored equilibrium. The utility of CO2-mediated selective cyanohydrin synthesis was further showcased by broadening Kiliani–Fischer synthesis under neutral conditions. This protocol offers an easy access to a variety of polyols, cyanohydrins, linear alkylnitriles, by simply starting from alkyl- and arylaldehydes, KCN and an atmospheric pressure of CO2.
- Juhl, Martin,Petersen, Allan R.,Lee, Ji-Woong
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p. 228 - 232
(2020/11/30)
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- Reductive cyanation of organic chlorides using CO2 and NH3 via Triphos–Ni(I) species
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Cyano-containing compounds constitute important pharmaceuticals, agrochemicals and organic materials. Traditional cyanation methods often rely on the use of toxic metal cyanides which have serious disposal, storage and transportation issues. Therefore, there is an increasing need to develop general and efficient catalytic methods for cyanide-free production of nitriles. Here we report the reductive cyanation of organic chlorides using CO2/NH3 as the electrophilic CN source. The use of tridentate phosphine ligand Triphos allows for the nickel-catalyzed cyanation of a broad array of aryl and aliphatic chlorides to produce the desired nitrile products in good yields, and with excellent functional group tolerance. Cheap and bench-stable urea was also shown as suitable CN source, suggesting promising application potential. Mechanistic studies imply that Triphos-Ni(I) species are responsible for the reductive C-C coupling approach involving isocyanate intermediates. This method expands the application potential of reductive cyanation in the synthesis of functionalized nitrile compounds under cyanide-free conditions, which is valuable for safe synthesis of (isotope-labeled) drugs.
- Dong, Yanan,Li, Yuehui,Yang, Peiju,Zhao, Shizhen
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- Copper-Catalyzed Cyanation of N-Tosylhydrazones with Thiocyanate Salt as the "cN" Source
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A novel protocol for the synthesis of α-aryl nitriles has been successfully achieved via a copper-catalyzed cyanation of N-tosylhydrazones employing thiocyanate as the source of cyanide. The features of this method include a convenient operation, readily available substrates, low-toxicity thiocyanate salts, and a broad substrate scope.
- Huang, Yubing,Yu, Yue,Zhu, Zhongzhi,Zhu, Chuanle,Cen, Jinghe,Li, Xianwei,Wu, Wanqing,Jiang, Huanfeng
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p. 7621 - 7627
(2017/07/26)
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- I2-Mediated oxidative bicyclization of 4-pentenamines to prolinol carbamates with CO2 incorporating oxyamination of the C=C bond
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A metal-free oxyamination reaction of alkenes with ambient CO2 is reported. In the presence of I2 and DBU, CO2 is applied in situ as a protecting group to regulate the nucleophilicity of the amino group and facilitate the bicyclization of 4-pentenamines with high chemoselectivity. Moreover, this reaction provided a feasible approach to prepare prolinol carbamates with good tolerance of functional groups and high efficiency under mild conditions.
- Wang, Sheng,Zhang, Xiaowei,Cao, Chengyao,Chen, Chao,Xi, Chanjuan
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supporting information
p. 4515 - 4519
(2017/10/13)
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- Ametoctradin is a Potent Qo Site Inhibitor of the Mitochondrial Respiration Complex III
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Ametoctradin is a new Oomycete-specific fungicide under development by BASF. It is a potent inhibitor of the bc1 complex in mitochondrial respiration. However, its detailed action mechanism remains unknown. In the present work, the binding mode of ametoctradin was first uncovered by integrating molecular docking, MD simulations, and MM/PBSA calculations, which showed that ametoctradin should be a Qo site inhibitor of bc1 complex. Subsequently, a series of new 1,2,4-triazolo[1,5-a]pyrimidine derivatives were designed and synthesized to further understand the substituent effects on the 5- and 6-position of 1,2,4-triazolo[1,5-a]pyrimidine. The calculated binding free energies (ΔGcal) of newly synthesized analogues as Qo site inhibitors correlated very well (R2 = 0.96) with their experimental binding free energies (ΔGexp). Two compounds (4a and 4c) with higher inhibitory activity against porcine SQR than ametoctradin were successfully identified. The structural and mechanistic insights obtained from the present study will provide a valuable clue for future designing of a new promising bc1 inhibitor.
- Zhu, Xiaolei,Zhang, Mengmeng,Liu, Jingjing,Ge, Jingming,Yang, Guangfu
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p. 3377 - 3386
(2015/04/14)
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- The Concise Synthesis of Unsymmetric Triarylacetonitriles via Pd-Catalyzed Sequential Arylation: A New Synthetic Approach to Tri- and Tetraarylmethanes
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The selective synthesis of multiarylated acetonitriles via sequential palladium-catalyzed arylations of chloroacetonitrile is reported. The three aryl groups are installed via a Pd-catalyzed Suzuki-Miyaura cross coupling reaction followed by back-to-back C-H arylations to afford triarylacetonitriles in three steps with no over-arylation at any step. The triarylacetonitrile products can be converted into highly functionalized species including tetraarylmethanes. This new strategy provides rapid access to a variety of unsymmetrical tri- and tetraarylmethane derivatives from simple, readily available starting materials. (Chemical Presented)
- Nambo, Masakazu,Yar, Muhammad,Smith, Joel D.,Crudden, Cathleen M.
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supporting information
p. 50 - 53
(2015/07/28)
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- Two-step cyanomethylation protocol: Convenient access to functionalized aryl- and heteroarylacetonitriles
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A two-step protocol has been developed for the introduction of cyanomethylene groups to metalated aromatics through the intermediacy of substituted isoxazoles. A palladium-mediated cross-coupling reaction was used to introduce the isoxazole unit, followed by release of the cyanomethylene function under thermal or microwave-assisted conditions. The intermediate isoxazoles were shown to be amenable to further functionalization prior to deprotection of the sensitive cyanomethylene motif, allowing access to a wide range of aryl- and heteroaryl-substituted acetonitrile building blocks.
- Lindsay-Scott, Peter J.,Clarke, Aimee,Richardson, Jeffery
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p. 476 - 479
(2015/03/05)
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- Copper-catalyzed cyanation of benzyl chlorides with non-toxic K 4[Fe(CN)6]
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Copper-based catalysts were firstly introduced into the cyanation of benzyl chlorides with non-toxic K4[Fe(CN)6]. The presented method avoids the use of extremely poisonous alkali cyanides and precious palladium catalysts. No other reagent apart from CuI, K4[Fe(CN) 6] and toluene was used in the cyanation, showing that the presented protocol is simple and practical. A series of benzyl chlorides were smoothly cyanated in up to 85% yield under the optimal conditions.
- Ren, Yunlai,Dong, Chuanhua,Zhao, Shuang,Sun, Yanpei,Wang, Jianji,Ma, Junying,Hou, Chaodong
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supporting information; experimental part
p. 2825 - 2827
(2012/07/17)
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- Pd-catalyzed cyanation of benzyl chlorides with nontoxic K 4[Fe(CN)6]
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Non-toxic K4[Fe(CN)6] was demonstrated to be effective as a green cyanating agent for the cyanation of alkyl halides using PPh3/Pd(OAc)2 as a catalyst system. The presented method allowed a series of benzyl chlorides to be smoothly cyanated in up to 88% yield. In order to avoid or suppress the deactivation of the catalyst, the reaction was required to be performed in a stringent inert ambiance.
- Ren, Yunlai,Yan, Mengjie,Zhao, Shuang,Sun, Yanpei,Wang, Jianji,Yin, Weiping,Liu, Zhifei
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scheme or table
p. 5107 - 5109
(2011/10/05)
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- Synthesis of α-Aryl nitriles through palladium-catalyzed decarboxylative coupling of cyanoacetate salts with aryl halides and triflates
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Worth its salt: The palladium-catalyzed decarboxylative coupling of the cyanoacetate salt as well as its mono- and disubstituted derivatives with aryl chlorides, bromides, and triflates is described (see scheme). This reaction is potentially useful for the preparation of a diverse array of α-aryl nitriles and has good functional group tolerance. S-Phos=2-(2,6- dimethoxybiphenyl)dicyclohexylphosphine), Xant-Phos=4,5-bis(diphenylphosphino)- 9,9-dimethylxanthene. Copyright
- Shang, Rui,Ji, Dong-Sheng,Chu, Ling,Fu, Yao,Liu, Lei
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supporting information; experimental part
p. 4470 - 4474
(2011/06/24)
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- Palladium-catalyzed cyanomethylation of aryl halides through domino Suzuki coupling-isoxazole fragmentation
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A one-pot protocol for the cyanomethylation of aryl halides through a palladium-catalyzed reaction with isoxazole-4-boronic acid pinacol ester was developed. Mechanistically, the reaction proceeds through (1) Suzuki coupling, (2) base-induced fragmentation, and (3) deformylation as shown by characterization of all postulated intermediates. Under optimized conditions (PdCl2dppf, KF, DMSO/H2O, 130 °C) a broad spectrum of aryl bromides could be converted into arylacetonitriles with up to 88% yield.
- Velcicky, Juraj,Soicke, Arne,Steiner, Roland,Schmalz, Hans-Guenther
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supporting information; experimental part
p. 6948 - 6951
(2011/06/19)
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- ANTHELMINTIC BENZO[D]ISOXAZOLYL BENZAMIDE DERIVATIVES
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The present invention is concerned with novel anthelmintic N-benzo[d]isoxazol-6-yl-benzamide derivatives and the pharmaceutically acceptable acid addition salts thereof, compositions comprising said novel Compounds, processes for preparing said Compounds and compositions, and the use thereof as a medicine, in particular in treatment, control and prevention of endo- and ectoparasite infections in warm-blooded animals.
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Page/Page column 12
(2009/01/24)
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- Mild palladium-catalyzed selective monoarylation of nitriles
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Two new palladium-catalyzed procedures for the arylation of nitriles under less basic conditions than previously reported have been developed. The selective monoarylation of acetonitrile and primary nitriles has been achieved using α-silyl nitriles in the presence of ZnF2. This procedure is compatible with a variety of functional groups, including cyano, keto, nitro, and ester groups, on the aryl bromide. The arylation of secondary nitriles occurred in high yield by conducting reactions with zinc cyanoalkyl reagents. These reaction conditions tolerated base-sensitive functional groups, such as ketones and esters. The combination of these two methods, one with a-silyl nitriles and one with zinc cyanoalkyl reagents, provides a catalytic route to a variety of benzylic nitriles, which have not only biological significance but utility as synthetic intermediates. The utility of these new coupling reactions has been demonstrated by a synthesis of verapamil, a clinically used drug for the treatment of heart disease, by a three-step route from commercial materials that allows convenient variation of the aryl group.
- Wu, Lingyun,Hartwig, John F.
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p. 15824 - 15832
(2007/10/03)
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- 3-benzyl-1,2,4-triazolo[4,3-α] pyrazines
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3-benzyl-1,2,4-triazolo [4,3-α] pyrazines are prepared. They are useful as anticonvulsants.
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- ELECTRFLUORATION EN POSITION BENZYLIQUE DANS LE SULFOLANE
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The use of sulfolane as a solvent instead of acetonitrile in the electrofluorination of benzylic derivatives 1, (R=H, Cl) gives greater yields of benzylic fluorides 2, since the formation of acetamide byproducts 4 is prevented.However, the parallel fluorination of the aromatic nucleus is not avoided under these conditions.
- Laurent, Eliane,Marquet, Bernard,Tardivel, Robert
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p. 115 - 126
(2007/10/02)
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- 2-aryl-ethyl ether derivatives and insecticidal and acaricidal agents containing said derivatives
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The present invention relates to 2-arylethyl ether or thioether derivatives represented by the following general formula [I]: STR1 wherein Ar stands for an aryl group, R1 stands for straight or branched chain alkyl group of 1 to 6 carbons, R2 stands for a hydrogen atom, or a methyl or ethyl group, R3 stands for a halogen atom, or a methyl or methoxyl group, R4 stands for a hydrogen or halogen atom, or a lower alkyl or lower alkoxy group, and n is an integer of 1 or 2 with the proviso that when n is 2, the groups R4 may be the same or different, and Y stands for an oxygen or sulfur atom, and also to processes for the preparation of these ethers or thioethers and a use of these ethers or thioethers. These compounds of the present invention have excellent insecticidal and acaricidal activities while the toxicity of these compounds are very low.
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- Photochemical Aromatic Cyanomethylation: Aromatic Substitution by Way of Radical Cations
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Photolysis at 254 nm of chloroacetonitrile in the presence of aromatic hydrocarbons led to ring cyanomethylation.In addition radical coupling products were found, especially with toluene where 3-phenylpropionitrile, succinonitrile, and bibenzyl accompanied the tolylacetonitriles.These same byproducts were obtained from toluene and chloroacetonitrile upon thermolysis with peroxide initiators, but no nuclear cyanomethylation was observed.The mechanism for aromatic cyanomethylation involves initial excitation of the aromatic hydrocarbons, followed by an electron transfer (probably by way of an exiplex) to chloroacetonitrile, which was found to quench aromatic fluorescence at high rates.Direct spectral evidence for the resulting radical cation with p-dimethoxybenzen was obtained by using flash laser spectroscopy.Loss of a chloride ion from the resulting radical anion produces a cyanomethyl radical in close proximity to an aromatic radical cation.Coupling leads to the aromatic substitution products whereas radicals escaping from the cage account for the observed byproducts.
- Kurz, M. E.,Lapin, S. C.,Miriam, K.,Hagen, T. J.,Qian, X. Q.
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p. 2728 - 2733
(2007/10/02)
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- Synthesis and Absolute Configuration of (-)-Rothrockene, a Non-Head-To-Tail Monoterpene
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The total synthesis of (-)-rothrockene, trans-1-(1-methylethenyl)-2-(2-methyl-1-propenyl)cyclopropane, and its enantiomer is described.Utilization of (-)-(R)-N,S-dimethyl-S-phenylsulfoximine in the synthesis allowed for resolution of a precursor, regio- and diastereoface selectivity in a Simmons-Smith cyclopropanation, determination of absolute configuration based on X-ray crystallography, and introduction of a side-chain double bond.The absolute configuration of the natural substance is shown to be 1R,2S.
- Barbachyn, Michael R.,Johnson, Carl R.,Glick, Milton D.
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p. 2746 - 2748
(2007/10/02)
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- 2-Arylpropyl ether or thioether derivatives and insecticidal and acaricidal agents containing said derivatives
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The present invention relates to 2-arylpropyl ether or thioether derivatives represented by the following general formula [I]: STR1 wherein Ar stands for an aryl group, R stands for a methyl or ethyl group, Y stands for an oxygen or sulfur atom, and B stands for a group represented by the following formula [II]: STR2 or the following general formula [III]: STR3 wherein Z stands for an oxygen or sulfur atom or a carbonyl or methylene group, R1 stands for a hydrogen or halogen atom or a lower alkyl group or a lower alkoxy group, and n is an integer of from 1 to 5 with the proviso that when n is 2 or more, the groups R1 may be the same or different, and also to processes for the preparation or these ethers of thioethers and a use of these ethers or thioethers. These compounds of the present invention have excellent insecticidal and acaricidal activities while the toxicity of these compounds are very low.
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- Photochemical Aromatic Cyanomethylation
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Cyanomethylation is accomplished by the photolysis of chloroacetonitrile in the presence of aromatics by way of electron transfer followed by radical coupling.
- Lapin, Stephen,Kurz, Michael E.
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p. 817 - 818
(2007/10/02)
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