- Organic semiconductor photocatalyst can bifunctionalize arenes and heteroarenes
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Photoexcited electron-hole pairs on a semiconductor surface can engage in redox reactions with two different substrates. Similar to conventional electrosynthesis, the primary redox intermediates afford only separate oxidized and reduced products or, more rarely, combine to one addition product. Here, we report that a stable organic semiconductor material, mesoporous graphitic carbon nitride (mpg-CN), can act as a visible-light photoredox catalyst to orchestrate oxidative and reductive interfacial electron transfers to two different substrates in a two- or three-component system for direct twofold carbon–hydrogen functionalization of arenes and heteroarenes. The mpg-CN catalyst tolerates reactive radicals and strong nucleophiles, is straightforwardly recoverable by simple centrifugation of reaction mixtures, and is reusable for at least four catalytic transformations with conserved activity.
- Ghosh, Indrajit,Khamrai, Jagadish,Savateev, Aleksandr,Shlapakov, Nikita,Antonietti, Markus,K?nig, Burkhard
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p. 360 - 366
(2019/08/15)
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- Palladium-Catalyzed Late-Stage Direct Arene Cyanation
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Methods for direct benzonitrile synthesis are sparse, despite the versatility of cyano groups in organic synthesis and the importance of benzonitriles for the dye, agrochemical, and pharmaceutical industries. We report the first general late-stage aryl C–H cyanation with broad substrate scope and functional-group tolerance. The reaction is enabled by a dual-ligand combination of quinoxaline and an amino acid-derived ligand. The method is applicable to direct cyanation of several marketed small-molecule drugs, common pharmacophores, and organic dyes. Benzonitriles are some of the most versatile building blocks for organic synthesis, in particular in the pharmaceutical industry, but general methods to make them by direct C–H functionalization are unknown. In this issue of Chem, Ritter and coworkers describe a late-stage aryl C–H cyanation with broad substrate scope and functional-group tolerance, enabled by a palladium-dual-ligand catalyst system. The reaction may serve for the late-stage modification of drug candidates. Aryl nitriles constitute an important class of organic compounds that are widely found in natural products, pharmaceuticals, agricultural chemicals, dyes, and materials. Moreover, nitriles are versatile building blocks to access numerous other important molecular structure groups. However, no general method for direct aromatic C–H cyanation is known. All approaches to date require either an appropriate directing group or reactive electron-rich substrates, such as indoles, which limit their synthetic applications. Here we describe an undirected, palladium-catalyzed late-stage aryl C–H cyanation reaction for the synthesis of complex aryl nitriles that would otherwise be more challenging to produce. The wide substrate scope and good functional-group tolerance of this reaction provide direct and quick access to structural diversity for pharmaceutical and agrochemical development.
- Zhao, Da,Xu, Peng,Ritter, Tobias
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supporting information
p. 97 - 107
(2019/01/21)
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- Electrochemical C-H cyanation of electron-rich (Hetero)arenes
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A straightforward method for the electrochemical C-H cyanation of arenes and heteroarenes that proceeds at room temperature in MeOH, with NaCN as the reagent in a simple, open, undivided electrochemical cell is reported. The platinum electrodes are passivated by ad-sorbed cyanide, which allows conversion of an exceptionally broad range of electron-rich substrates all the way down to dialkyl arenes. The cyanide electrolyte can be replenished with HCN, opening opportunities for salt-free industrial C-H cyanation.
- Hayrapetyan, Davit,Rit, Raja K.,Kratz, Markus,Tschulik, Kristina,Goo?en, Lukas J.
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supporting information
p. 11288 - 11291
(2018/10/20)
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- Development of Decarboxylative Cyanation Reactions for C-13/C-14 Carboxylic Acid Labeling Using an Electrophilic Cyanating Reagent
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Degradation-reconstruction approaches for isotope labeling synthesis have been known for their remarkable efficiency, but applications are scarce due to some fundamental limitations of the chemistries developed to date. The decarboxylative cyanation reaction, as a degradation-reconstruction approach, is especially useful in rapid carboxylic acid carbon isotope labeling, however development toward its application as a widespread technique has stalled at the early stages due to numerous limitations which include somewhat narrow applicability. Employing the electrophilic cyanating reagent N-cyano-N-phenyl-p-toluenesulfonamide (NCTS) as the cyano source, efficient decarboxylative cyanation chemistry has been developed for aryl and alkyl carboxylic acids respectively with two rationally designed reaction pathways. The reactions provided good yields of nitrile products from carboxylic acids, with complete retention of isotopic purity from the [13CN]-NCTS used. The reaction conditions are relatively mild requiring no oxidant and no excess toxic heavy metal and the reagent [13/14CN]-NCTS is a stable, easy-to-handle crystalline solid that can be prepared quickly and effectively from the readily available [13/14C]-KCN. The following work describes this novel and efficient method for alkyl and aryl carboxylic acid isotopic labeling using a single reagent.
- Song, Fengbin,Salter, Rhys,Chen, Lu
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p. 3530 - 3537
(2017/04/11)
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- Direct C-H Cyanation of Arenes via Organic Photoredox Catalysis
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Methods for the direct C-H functionalization of aromatic compounds are in demand for a variety of applications, including the synthesis of agrochemicals, pharmaceuticals, and materials. Herein, we disclose the construction of aromatic nitriles via direct C-H functionalization using an acridinium photoredox catalyst and trimethylsilyl cyanide under an aerobic atmosphere. The reaction proceeds at room temperature under mild conditions and has proven to be compatible with a variety of electron-donating and -withdrawing groups, halogens, and nitrogen- and oxygen-containing heterocycles, as well as aromatic-containing pharmaceutical agents.
- McManus, Joshua B.,Nicewicz, David A.
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supporting information
p. 2880 - 2883
(2017/03/11)
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- Straightforward conversion of arene carboxylic acids into aryl nitriles by palladium-catalyzed decarboxylative cyanation reaction
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A one-pot procedure to convert aromatic carboxylic acids into aromatic nitriles is described. The methodology is based on a palladium(II)-catalyzed decarboxylative cyanation reaction using cyanohydrins as soluble cyanide sources. The described reaction worked on a panel of substrates and is additionally of particular interest for the straightforward preparation of 13C- or 14C-labeled compounds.
- Ouchaou, Kahina,Georgin, Dominique,Taran, Frédéric
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experimental part
p. 2083 - 2086
(2010/10/03)
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- Regioselective photocycloaddition of pyridine derivatives to electron-rich alkenes
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Irradiation of a benzene solution of 3-cyano-2,6-dimethoxypyridine in the presence of ethyl vinyl ether (EVE) gave 1:1 photoadducts, 3-cyano -5-ethoxy-2,8-dimethoxy-4,5-dihydroazocine, in good yields, whose structure was established by X-ray single-crystal analysis. The photoadduct was produced via cycloaddition between the C3-C4 position of the pyridine derivatives and an alkene chromophore. On the other hand, 3-cyano -2,6-dimethoxy-4-methylpyridine cycloadds to EVE at the C2-C3 position of the pyridine ring upon irradiation. The difference is explained on the basis of the steric effect.
- Sakamoto, Masami,Sano, Takeru,Fujita, Shohei,Ando, Masaru,Yamaguchi, Kentaro,Mino, Takashi,Fujita, Tsutomu
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p. 1447 - 1450
(2007/10/03)
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- Methyl orthocarboxylates as methylating agents of heterocycles
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Methylation reactions occurring between trimethyl orthocarboxylates or N,N-dimethylcarboxamide dimethyl acetals and various hydroxylated heterocycles, involving a lactam-lactim tautomeric equilibrium, were investigated as an alternative to classic methyla
- Janin, Yves L.,Huel, Christiane,Flad, Genevieve,Thirot, Sylvie
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p. 1763 - 1769
(2007/10/03)
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- Reactions of Malononitrile with Acetylenic Esters and Ketones
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The addition of malononitrile to acetylenic esters and acetylenic ketones catalysed by sodium alkoxides leads to the formation of 3- and 5-cyano-2-pyridones, 2-cyano- and 2,6-dicyano-aniline derivatives, and other products.
- Kandeel, Kamal A.,Vernon, John M.,Dransfield, Trevor A.,Fouli, Fouli A.,Youssef, Ahmed S. A.
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p. 2101 - 2117
(2007/10/02)
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- Transformations of trichloromethyl groups during reactions of 3-trichloromethylpyridines with methoxide
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When methoxide ion attacks an unsubstituted 2- or 6-position of a 3-trichloromethylpyridine, a hydrogen shift leads to a methoxy-substituted 3-dichloromethylpyridine. Further reaction of the dichloromethyl group with methoxide gives the corresponding acetal. This type of reaction has been applied to several chlorinated 3-trichloromethylpyridines and to 3- trichloromethylpyridine itself; a convenient synthesis of the latter is described.
- Dainter, Ronald S.,Jackson, Tracey,Omar, Abdirahman H. H.,Suschitzky, Hans,Wakefield, Basil J.,Hughes, Nigel,Nelson, Anthony J.,Varvounis, George
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p. 283 - 287
(2007/10/02)
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