- Facile Synthesis of γ-Ketonitriles in Water via C(sp2)–H Activation of Aromatic Aldehydes over Cu?g-C3N4 under Visible-Light
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A facile C(sp2)–H activation of aldehyde under visible-light conditions using Cu?g-C3N4 as photocatalyst and water as solvent is reported. The envisaged method involves photocatalytic intermolecular Stetter reaction using
- Bhardiya, Smita R.,Rai, Ankita,Rai, Vijai K.,Sheshma, Harendra,Singh, Manorama,Verma, Fooleswar
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p. 5841 - 5846
(2020/09/21)
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- Photochemical generation of acyl and carbamoyl radicals using a nucleophilic organic catalyst: Applications and mechanism thereof
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We detail a strategy that uses a commercially available nucleophilic organic catalyst to generate acyl and carbamoyl radicals upon activation of the corresponding chlorides and anhydrides via a nucleophilic acyl substitution path. The resulting nucleophilic radicals are then intercepted by a variety of electron-poor olefins in a Giese-type addition process. The chemistry requires low-energy photons (blue LEDs) to activate acyl and carbamoyl radical precursors, which, due to their high reduction potential, are not readily prone to redox-based activation mechanisms. To elucidate the key mechanistic aspects of this catalytic photochemical radical generation strategy, we used a combination of transient absorption spectroscopy investigations, electrochemical studies, quantum yield measurements, and the characterization of key intermediates. We identified a variety of off-the-cycle intermediates that engage in a light-regulated equilibrium with reactive radicals. These regulated equilibriums cooperate to control the overall concentrations of the radicals, contributing to the efficiency of the overall catalytic process and facilitating the turnover of the catalyst. This journal is
- Balletti, Matteo,De Pedro Beato, Eduardo,Mazzarella, Daniele,Melchiorre, Paolo
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p. 6312 - 6324
(2020/08/24)
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- A Photochemical Organocatalytic Strategy for the α-Alkylation of Ketones by using Radicals
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Reported herein is a visible-light-mediated radical approach to the α-alkylation of ketones. This method exploits the ability of a nucleophilic organocatalyst to generate radicals upon SN2-based activation of alkyl halides and blue light irradiation. The resulting open-shell intermediates are then intercepted by weakly nucleophilic silyl enol ethers, which would be unable to directly attack the alkyl halides through a traditional two-electron path. The mild reaction conditions allowed functionalization of the α position of ketones with functional groups that are not compatible with classical anionic strategies. In addition, the redox-neutral nature of this process makes it compatible with a cinchona-based primary amine catalyst, which was used to develop a rare example of enantioselective organocatalytic radical α-alkylation of ketones.
- Goti, Giulio,Melchiorre, Paolo,O?eka, Maksim,Schweitzer-Chaput, Bertrand,Spinnato, Davide
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supporting information
p. 9485 - 9490
(2020/04/09)
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- Syntheses of Pyrroles, Pyridines, and Ketonitriles via Catalytic Carbopalladation of Dinitriles
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The first example of the Pd-catalyzed addition of organoboron reagents to dinitriles, as an efficient means of preparing 2,5-diarylpyrroles and 2,6-diarylpyridines, has been discussed here. Furthermore, the highly selective carbopalladation of dinitriles with organoboron reagents to give long-chain ketonitriles has been developed as well. Based on the broad scope of substrates, excellent functional group tolerance, and use of commercially available substrates, the Pd-catalyzed addition reaction of arylboronic acid and dinitriles is expected to be significant in future synthetic procedures.
- Qi, Linjun,Li, Renhao,Yao, Xinrong,Zhen, Qianqian,Ye, Pengqing,Shao, Yinlin,Chen, Jiuxi
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p. 1097 - 1108
(2020/01/22)
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- A Novel Ketonitrile Synthesis by Palladium-Catalyzed Carbonylative Coupling Reactions of Amides with Arylboronic Acids
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A novel, efficient, and simple procedure to synthesize diverse ketonitriles by palladium-catalyzed Suzuki coupling of amides through N–C cleavage has been developed. This procedure features mild conditions, a broad substrate scope, and easily prepared substrates, providing a simple and efficient access to a variety of ketonitriles.
- Mai, Wen-Peng,Liu, Yang,Sui, Hong-Dai,Xiao, Yong-Mei,Mao, Pu,Lu, Kui
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supporting information
p. 7814 - 7819
(2019/12/24)
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- Ag2CO3-mediated direct functionalization of alkyl nitriles: Facile synthesis of γ-ketonitriles through nitrile alkylation of enol acetates
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Direct C(sp3)-H functionalization of alkyl nitriles is a low toxic and facile route to nitrile-containing compounds. In this research, the Ag2CO3-mediated nitrile methylenation of enol acetates is developed to prepare γ-ketonitriles through the direct C(sp3)-H oxidative functionalization of acetonitrile. A radical pathway is proposed, and acetonitrile serves both as solvent and CN-containing radical source.
- Cheng, Pi,Wang, Wei,Wang, Lin,Zeng, Jianguo,Reiser, Oliver,Liang, Yun
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p. 1408 - 1412
(2019/05/06)
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- Copper-Catalyzed Decarboxylative Oxyalkylation of Alkynyl Carboxylic Acids: Synthesis of ?-Diketones and ?-Ketonitriles
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A novel copper-catalyzed decarboxylative oxyalkylation of alkynyl carboxylic acids with ketones and alkylnitriles via direct C(sp3)-H bond functionalization to construct new C-C bonds and C-O double bonds was developed. This transformation is featured by wide functional group compatibility and the use of readily available reagents, thus affording a general approach to ?-diketones and ?-ketonitriles. A possible mechanism is proposed.
- Li, Yi,Shang, Jia-Qi,Wang, Xiang-Xiang,Xia, Wen-Jin,Yang, Tao,Xin, Yangchun,Li, Ya-Min
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supporting information
p. 2227 - 2230
(2019/03/26)
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- Light-Driven Vitamin B12-Catalysed Generation of Acyl Radicals from 2-S-Pyridyl Thioesters
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Acyl radicals are invaluable intermediates in organic synthesis, however their generation remains challenging. Herein, we present an unprecedented light-driven, cobalt-catalysed method for the generation of acyl radicals from readily available 2-S-pyridyl thioesters. The synthetic potential of this methodology was demonstrated in the Giese-type acylation of activated olefins in the presence of heptamethyl cobyrrinate. This vitamin B12 derivative proved to be the most efficient catalyst in the studied process. The developed method features broad substrate scope (38 examples), good functional group tolerance, and mild reaction conditions. Moreover, it is easily scalable (illustrated on a 20-fold scale-up procedure), enabling its preparative use. Mechanistic studies revealed that the reaction proceeds via a radical pathway with the key steps involving the formation of an acyl-vitamin B12 complex and subsequent photolysis of the Co?C bond. (Figure presented.).
- Ociepa, Micha?,Baka, Oskar,Narodowiec, Jakub,Gryko, Dorota
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supporting information
p. 3560 - 3565
(2017/10/24)
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- Copper(i)-catalyzed ring-opening cyanation of cyclopropanols
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A copper(i)-catalyzed ring-opening cyanation of cyclopropanols was developed. The reaction provides an alternative method to achieve β-cyano ketones efficiently. This reaction exhibits good functional group compatibility under mild conditions and can be scaled up to the gram scale. Preliminary mechanistic studies suggest that the reaction might go through a free radical process.
- Feng, Yi-Si,Shu, Yong-Jin,Cao, Ping,Xu, Tao,Xu, Hua-Jian
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supporting information
p. 3590 - 3593
(2017/07/07)
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- Chemoselective Access to γ-Ketoesters with Stereogenic Quaternary α-Center or γ-Keto Nitriles by Aerobic Reaction of α-Cyanoesters and Styrenes
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Chemoselective access to either γ-ketoesters with a quaternary all-carbon α-stereogenic center or γ-keto nitriles is described by copper-catalyzed aerobic reaction of styrenes with α-cyanoesters. Formal oxo-enolation or oxo-cyanomethylation of styrenes is achieved via a sequence of addition of enolate (or cyanomethyl) radical to olefin and oxidation of the resulting radical adduct. This method starts from abundant and cheap feedstock under aerobic conditions, without any prefunctionalization or the production of stoichiometric metal salts waste, making it very attractive for practical use.
- Zhang, Song-Lin,Wang, Xian-Jin,Yu, Ze-Long
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supporting information
p. 3139 - 3142
(2017/06/23)
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- Preparation γ - par phenyle and γ - ketoester method (by machine translation)
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The invention relates to a process for preparing γ - par phenyle and γ - ketoester method, characterized in that comprises the following experimental procedure: catalyst/ligand/additive under the catalytic action of, in the environment of oxygen, with the α - cyano ester substituted styrene mixed solution for 60 - 100 °C oil bath pot reaction 12 - 20 h; cooling after reaction to the room temperature, by extraction, washing, drying and chromatography, to obtain the product γ - par phenyle and γ - ketoester. The invention of each reaction raw material, catalyst, ligand, additive and solvent are industrial commodities, simple and easy to obtain, the price is cheap, and performance is quite stable, does not need special storage conditions, the operation is convenient. The invention has advantages of low cost, high yield, the process is simple, and less pollution and the like. (by machine translation)
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Paragraph 0089-0093
(2018/04/01)
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- Unactivated C(sp3)-H Bond Functionalization of Alkyl Nitriles with Vinylarenes and Mechanistic Studies
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The first example of a metal-free unactivated C(sp3)-H bond functionalization of alkyl nitriles with terminal vinylarenes to provide γ-ketonitrile derivatives is described. This protocol features simple operations, a broad substrate scope, and atom and step economy. In addition, Cu-catalyzed C(sp3)-H bond functionalization of azodiisobutyronitrile (AIBN) and analogues with terminal vinylarenes to generate γ-ketonitriles was also studied. A preliminary free-radical pathway was confirmed by capturing an alkyl radical, and a conjugate system was found that can stabilize radical intermediates and be in favor of this transformation. Density functional theory (DFT) calculations also provide important evidence of the free-radical pathway.
- Lan, Xing-Wang,Wang, Nai-Xing,Bai, Cui-Bing,Lan, Cui-Lan,Zhang, Tong,Chen, Shi-Lu,Xing, Yalan
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supporting information
p. 5986 - 5989
(2016/12/09)
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- Synthetic strategy toward γ-KETO NITRILES and their Biocatalytic conversion to asymmetric γ-lactones
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Asymmetric γ-hydroxy nitriles are valuable intermediates because hydrolysis of the nitriles can result in an intramolecular cyclization to chiral γ-lactones, which have a variety of biological uses. Starting with an assortment of different aldehydes (alkyl and aryl) a 4-step synthesis of γ-keto nitriles was developed. These prochiral substrates were then screened against a library of ketoreductases for their ability to stereoselectively reduce the carbonyl. Enzymes from the short chain dehydrogenase family showed activity and these enzymatic reactions were scaled up to produce a diverse set of chiral γ-lactones.
- Franz, Sarah E.,Watkins, Richard R.,Wright, Laura A.,Weaver, Blair A.,Hartage, Ramon C.,Ghiviriga, Ion,Gumina, Giuseppe,Feske, Brent D.
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p. 2171 - 2178
(2013/08/23)
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- Carbon-carbon bond cleavage of α-substituted benzoins by retro-benzoin condensation; A new method of synthesizing ketones
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When α-benzylbenzoin (3a, α-benzyl-α-hydroxybenzyl phenyl ketone) was treated with potassium cyanide (1) in N,N-dimethylformamide at 80°C for 1h, the carbon-carbon bond was cleaved, resulting in the formation of deoxybenzoin (4a, benzyl phenyl ketone) and benzaldehyde (2a). This carbon- carbon bond cleavage proceeds through a retro-benzoin condensation mechanism. This method of synthesizing ketones was applied to several α-substituted benzoins (3), and the corresponding ketones (4) were formed in good yields. Further, we found that the cyanide ion-donating ability of tetrabutylammonium cyanide (6, Bu4NCN) is more effective than that of potassium cyanide (1, KCN). As expected from the chemical analogy between cyanide ion and azolium ylide, several azolium salts (7) can also be employed in the retro-benzoin condensation as catalysts. The benzoin derivatives 3 were synthesized in the following three ways; reaction of alkyl halide (9) with benzoin (5), Michael addition of benzoin (5) with acceptors (10), and Grignard reaction of benzils (8). Alkylation of the benzoins without isolation, followed by carbon-carbon bond cleavage, readily afforded the corresponding ketones (4).
- Miyashita, Akira,Suzuki, Yumiko,Okumura, Yoko,Iwamoto, Ken-Ichi,Higashino, Takeo
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- Synthesis of ketones by retro-benzoin condensation catalyzed by potassium cyanide
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The treatment of 2-benzyl-1,2-diphenyl-2-hydroxyethanone (3a, benzylbenzoin) with potassium cyanide in DMF gave deoxybenzoin (4a). The formation of deoxybenzoin (4a) proceeds through retro-benzoin condensation by catalytic action of cyanide ion. Similarly, retro-benzoin condensation applied to several substituted benzoins 3 resulted in the formation of the corresponding ketones 4 in excellent yields.
- Miyashita,Suzuki,Okumura,Higashino
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p. 252 - 254
(2007/10/03)
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- Acyl Radicals: Intermolecular and Intramolecular Alkene Addition Reactions
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A full study of the use of phenyl selenoesters as precursors to acyl radicals and their subsequent participation in intermolecular and intramolecular alkene addition reactions is detailed.Primary alkyl-, vinyl-, and arylsubstituted acyl radicals generated by Bu3SnH treatment of the corresponding phenyl selenoesters participate cleanly in intermolecular addition reactions with alkenes bearing electron-withdrawing or radical-stabilizing substituents at rates that exceed those of the potentially competitive decarbonylation or reduction.Similarly, their intramolecular addition to activated or unactivated alkenes proceeds without significant competitive reduction or decarbonylation and at rates generally >/= 1 x 106 s-1 with some occuring at rates >/= 3 x 107 s-1.Consistent with their behavior in intermolecular addition reactions, the 5-exo-trig cyclizations of secondary and tertiary alkyl-substituted acyl radicals to an unactivated olefin acceptor may be accompanied by varying degrees of decarbonylation, even under low-temperature free-radical conditions.Studies are presented which suggest that the intramolecular additions of acyl radicals to alkenes under the conditions detailed herein may be regarded as irreversible, kinetically controlled processes which exhibit regioselectivity that is predictable based on well-established empirical rules set forth for the analogous free-radical cyclization reactions of alkyl radicals.
- Boger, Dale L.,Mathvink, Robert J.
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p. 1429 - 1443
(2007/10/02)
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- (Phenylmethoxy)phenyl Derivatives of Ω-Oxo- and Ω-Tetrazolylalkanoic Acids and Related Tetrazoles. Synthesis and Evaluation as Leukotriene D4 Receptor Antagonists
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Two series of (phenylmethoxy)phenyl compounds derived from the structure of LY163443 were synthesized and evaluated as leukotriene D4 receptor antagonists.In the Ω--Ω-oxoalkanoic acid series, 5-phenyl>-3,3-dimethyl-5-oxopentanoic acid (8) was the most potent antagonist of LTD4-induced contractions of guinea pig ileum (pKB of 7.60) and LTD4 pressor response in pithed rats (ED50 of 1.4 mg/kg iv).Replacing the carboxylic acid function with 5-tetrazole gave slightly more potent compounds.Inthe Ω-alkyl>tetrazolyl>alkanoic acid series, replacing the carboxylic acid with 5-tetrazole gave compounds that were equally effective in the guinea pig ileum but more potent in vivo against the LTD4 pressor response in rat.The pKB value in the guinea pig ileum for 1--2H-tetrazol-5-yl>methyl>phenoxy>methyl>phenyl>ethanone (25) was 7.87 and the ED50 for antagonism of the LTD4 pressor response was 4.0 mg/kg iv.The sodium salts of 8 (9) and 25(26) given by the iv route of administration antagonized LTD4-induced cardiovascular alterations in anesthetized rat and LTD4-induced bronchoconstriction in guinea pig in a dose-dependent manner.Oral activity was also demonstrated against the LTD4-induced bronchoconstriction in guinea pig.
- Dillard, Robert D.,Hahn, Richard A.,McCullough, Doris,Carr, F. Patrick,Rinkema, Lynn E.,et al.
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p. 2768 - 2778
(2007/10/02)
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- Acylcobalt Salophen Reagents. Precursors to Acyl Radical Intermediates for Use in Carbon-to-Carbon Bond-forming Reactions to Alkenes
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Acylcobalt salophen reagents (6) are conveniently synthesised from carboxylic acid chlorides following treatment with the sodium derivative (5) produced from reduction of cobalt(II) salophen with sodium amalgam in tetrahydrofuran at room temperature.The acylcobalt salophens (6) undergo homolytic cleavage in the presence of light from a conventional 300 W sunlamp to give acyl radicals (24) which then undergo additions to activated carbon-to-carbon double bonds, leading to enones, viz. (26) , or saturated ketones, viz. (34) .Intramolecular cyclisations of the acylcobalt salophens (42a) and (42b) lead to the ylidenecyclopentanones (43) and (45), respectively.
- Coveney, Donal J.,Patel, Vinod F.,Pattenden, Gerald,Thompson, David M.
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p. 2721 - 2729
(2007/10/02)
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- Phenyl Selenoesters as Effective Precursors of Acyl Radicals for Use in Intermolecular Alkene Addition Reactions
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The scope of the use of phenyl selenoesters as effective precursors to acyl radicals for use in intermolecular olefin addition reactions is detailed.
- Boger, Dale L.,Mathvink, Robert J.
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p. 1777 - 1779
(2007/10/02)
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- Process for preparing ketones
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Ketones are prepared by reacting an aromatic or heterocyclic aldehyde in the presence of a cyanide ion with an unsaturated compound having the formula (I): STR1 wherein R1, R2 and R3 are the same or different and are selected from the group of hydrogen, optionally substituted aliphatic, cycloaliphatic, araliphatic, aromatic, heterocyclic and carboxylic acid ester and R4 is nitrile (CN), --CO--R5 or --CO--OR5 wherein R5 is selected from the group of optionally substituted aliphatic, cycloaliphatic, araliphatic, aromatic and heterocyclic and R1 and R2 and/or R1 and R3 and/or R2 and R5 or R3 and R5 together with the carbon atoms to which they are attached as substituents may also form a carbocyclic or heterocyclic ring. Ketones prepared according to the process of the invention have the formula: STR2 wherein R1 ' and R3 ' are identical or different and are selected from the group of hydrogen, lower alkyl having up to 3 C-atoms and optionally substituted phenyl; and R6 ' is optionally substituted phenyl or a pyridyl.
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