- Visible-Light-Promoted Metal-Free Synthesis of (Hetero)Aromatic Nitriles from C(sp3)?H Bonds**
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The metal-free activation of C(sp3)?H bonds to value-added products is of paramount importance in organic synthesis. We report the use of the commercially available organic dye 2,4,6-triphenylpyrylium tetrafluoroborate (TPP) for the conversion of methylarenes to the corresponding aryl nitriles via a photocatalytic process. Applying this methodology, a variety of cyanobenzenes have been synthesized in good to excellent yield under metal- and cyanide-free conditions. We demonstrate the scope of the method with over 50 examples including late-stage functionalization of drug molecules (celecoxib) and complex structures such as l-menthol, amino acids, and cholesterol derivatives. Furthermore, the presented synthetic protocol is applicable for gram-scale reactions. In addition to methylarenes, selected examples for the cyanation of aldehydes, alcohols and oximes are demonstrated as well. Detailed mechanistic investigations have been carried out using time-resolved luminescence quenching studies, control experiments, and NMR spectroscopy as well as kinetic studies, all supporting the proposed catalytic cycle.
- Murugesan, Kathiravan,Donabauer, Karsten,K?nig, Burkhard
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supporting information
p. 2439 - 2445
(2020/12/07)
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- Acyl Cyanides as Bifunctional Reagent: Application in Copper-Catalyzed Cyanoamidation and Cyanoesterification Reaction
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Cu-catalyzed domino decyanation and cyanation reaction of acyl cyanides with amines or alcohols have been developed. The cyano sources were generated in situ via C-CN cleavage yielding the corresponding cyano substituted amides or esters in moderate to excellent yields. This approach features a cheap copper catalyst, domino decyanation and cyanation reaction, readily available starting materials, broad substrate scope, operational simplicity, and the potential for further transformation of the cyano group.
- Chen, Zhengwang,Wen, Xiaowei,Zheng, Weiping,He, Ruolan,Chen, Dou,Cao, Dingsheng,Long, Lipeng,Ye, Min
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p. 5691 - 5701
(2020/04/10)
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- Ligand-Promoted Non-Directed C?H Cyanation of Arenes
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This article reports the first example of a 2-pyridone accelerated non-directed C?H cyanation with an arene as the limiting reagent. This protocol is compatible with a broad scope of arenes, including advanced intermediates, drug molecules, and natural products. A kinetic isotope experiment (kH/kD=4.40) indicates that the C?H bond cleavage is the rate-limiting step. Also, the reaction is readily scalable, further showcasing the synthetic utility of this method.
- Liu, Luo-Yan,Yeung, Kap-Sun,Yu, Jin-Quan
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supporting information
p. 2199 - 2202
(2019/01/24)
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- Continuous-Flow Pd-Catalyzed Carbonylation of Aryl Chlorides with Carbon Monoxide at Elevated Temperature and Pressure
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The development of a continuous-flow protocol for a palladium-catalyzed methoxycarbonylation of (hetero)aryl chlorides using carbon monoxide gas and methanol is described. (Hetero)aryl chlorides are the least expensive of the aryl halides, but are underutilized in carbonylation reactions due to their very poor reactivity. The described protocol exploits intensified conditions at elevated temperature and pressure, which are readily accessed within a continuous-flow environment, to provide moderate to excellent product yields (11 examples) in a short 16 min residence time. The continuous-flow protocol enables the safe and potentially scalable carbonylation of aryl chlorides using CO gas.
- Mata, Alejandro,Hone, Christopher A.,Gutmann, Bernhard,Moens, Luc,Kappe, C. Oliver
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p. 997 - 1001
(2019/01/24)
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- Methyl esters of 2-(N-hydroxycarbamimidoyl)benzoyl-substituted α-amino acids as promising building blocks in peptidomimetic synthesis: a comparative study
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Abstract: An efficient and simple synthetic protocol for the synthesis of a number methyl esters of 2-(N-hydroxycarbamimidoyl)benzoyl-substituted (S)-α-amino acids via subsequent coupling and hydroxyamination of 2-cyanobenzamide derivatives has been developed. Comparative analysis of three pseudopeptide series based on 2-cyano- and 2-amidoxime-substituted benzoic acid and its pyridine and pyrazine counterparts has been provided and it has revealed a practical advantage of the benzoic acid derivatives due to their greater availability. The impact of the nitrogen atom in the aromatic ring on the trans/cis-amide equilibrium in the proline derivatives is discussed. Graphical abstract: [Figure not available: see fulltext.]
- Tkachuk, Volodymyr A.,Hordiyenko, Olga V.,Omelchenko, Irina V.,Medviediev, Volodomir V.,Arrault, Axelle
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p. 2293 - 2309
(2018/11/02)
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- Metal-free radical aromatic carbonylations mediated by weak bases
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We report a new method of metal-free alkoxycarbonylation. This reaction involves the generation of aryl radicals from arenediazonium salts by a very weak base (HCO2Na) under mild conditions. Subsequent radical trapping with carbon monoxide and alcohols gives alkyl benzoates. The conditions (metal-free, 1 equiv. base, MeCN, r.t., 3 h) tolerate various functional groups (I, Br, Cl, CF3, SF5, NO2, ester). Mechanistic studies indicate the operation of a radical aromatic substitution mechanism.
- Koziakov, Denis,Jacobi Von Wangelin, Axel
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supporting information
p. 6715 - 6719
(2017/08/22)
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- A highly efficient, ligand-free and recyclable SBA-15 supported Cu 2O catalyzed cyanation of aryl iodides with potassium hexacyanoferrate(ii)
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SBA-15 supported Cu2O nanoparticles (Cu2O/SBA-15) have been fabricated and characterized. The as-prepared Cu2O/SBA-15 is a highly effective catalyst for cyanation of aryl iodides using non-toxic K4[Fe(CN)6] as a cyanide source in dimethylformamide (DMF). The approach achieves a high selectivity and an excellent yield without using any ligands and base additives. Moreover, the Cu2O/SBA-15 catalyst shows wide functional group tolerance and reusability with a slight loss of activity. the Partner Organisations 2014.
- Yin, Wenzhu,Liu, Rui,He, Guangke,Lv, Wangjie,Zhu, Hongjun
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p. 37773 - 37778
(2014/11/07)
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- Skeletal rearrangement of cyano-substituted iminoisobenzofurans into alkyl 2-cyanobenzoates catalyzed by B(C6F5)3
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An efficient method for the direct conversion of cyano-substituted iminoisobenzofurans into their corresponding alkyl 2-cyanobenzoates has been developed. This transformation proceeds via cleavage of C-C, C-O, and C-N bonds in starting iminoisobenzofurans. DFT study revealed that intermediate α-iminonitriles are produced in situ via C-C bond formation between 2-iminium benzoates and a cyanide ion. Generation of isocyanide as the byproduct in a more thermodynamic manner in DFT calculations also supports the experimental results.
- Li, Jing,Okuda, Yasuhiro,Zhao, Jiaji,Mori, Seiji,Nishihara, Yasushi
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supporting information
p. 5220 - 5223
(2014/12/11)
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- Synthesis and evaluation of novel azoles as potent antifungal agents
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Using a rational approach to the design of antifungal agents, a series of azole agents with 1,3,4-oxadiazole side chains were designed and synthesized. The results of preliminary in vitro antifungal tests with eight human pathogenic compounds showed that all of the title compounds exhibited excellent activities against all of the tested fungi except Aspergillus fumigatus. Compounds 11e and 11f were found to be the most effective, with a minimum inhibitory concentration of 0.0039 μg/mL, followed by voriconazole, which has a MIC of 0.0625 μg/mL. The 1,3,4-oxadiazole side chain is not the major contributor but plays a role in eliciting the observed antifungal activity.
- Li, Liangjing,Ding, Hao,Wang, Baogang,Yu, Shichong,Zou, Yan,Chai, Xiaoyun,Wu, Qiuye
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supporting information
p. 192 - 194
(2014/01/17)
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- Copper-catalyzed cyanation of aryl iodide with the combined cyanide source of urea and DMSO
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A simple copper-catalyzed cyanation of aryl iodide with the combination of urea and dimethyl sulfoxide as a cyanide source is achieved, providing nitriles in moderate to good yields. This new approach represents an exceedingly practical and safe method for the synthesis of aryl nitriles.
- Zheng, Kui,Liu, Bin,Chen, Shuyou,Chen, Fan
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supporting information
p. 5250 - 5252
(2013/09/02)
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- Palladium-catalyzed cyanation of aryl halides with CuSCN
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A palladium-catalyzed cyanation of aryl halides and borons has been developed by employing cuprous thiocyanate as a safe cyanide source. This protocol avoids the use of a highly toxic cyanide source, providing aromatic nitriles in moderate to good yields with good functional tolerance.
- Zhang, Guo-Ying,Yu, Jin-Tao,Hu, Mao-Lin,Cheng, Jiang
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p. 2710 - 2714
(2013/05/08)
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- A non-metal catalysed oxidation of primary azides to nitriles at ambient temperature
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A novel non-metal catalyzed oxidation of organic azides to nitriles under solvent-free conditions is presented employing catalytic amounts of KI, and DABCO in aq. TBHP at room temperature. This non-metal catalyzed oxidation of azides provides good selectivity as double and triple bonds were not oxidized under the present reaction conditions. The Royal Society of Chemistry 2012.
- Lamani, Manjunath,Devadig, Pradeep,Prabhu, Kandikere Ramaiah
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p. 2753 - 2759
(2012/11/07)
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- A concise and cascade synthesis of batracylin and substituted isoindolo-[1,2- b ]quinazolin-12(10 H)-ones
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A concise, highly convergent, and practical synthesis of the clinical-phase anticancer agent batracylin in a two-stage process in excellent yield is described. The B and C rings of this tetracyclic heterocycle are constructed by cascade cyclization of 5-nitro-2-aminobenzyl alcohol with 2-cyanomethyl benzoate in trifluoroacetic acid in good yield in a single-pot reaction. A plausible mechanism for the cascade reaction is also proposed. As part of these studies, a range of batracylin derivatives with different substituents on the C and D rings are synthesized. Georg Thieme Verlag Stuttgart.
- Shankar,Wagh, Manoj Balu,Madhubabu,Vembu,Kumar, U. K. Syam
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supporting information; experimental part
p. 844 - 848
(2011/06/21)
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- Copper-mediated cyanation of aryl halide with the combined cyanide source
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A simple copper-mediated cyanation of aryl halide with the combination of ammonium bicarbonate and N,N-dimethylformamide as a cyanide source is achieved, providing nitriles in moderate to good yields. This new approach represents an exceedingly practical and safe method for the synthesis of aryl nitriles.
- Zhang, Guoying,Ren, Xinyi,Chen, Jianbin,Hu, Maolin,Cheng, Jiang
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supporting information; experimental part
p. 5004 - 5007
(2011/11/12)
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- An efficient oxidation of primary azides catalyzed by copper iodide: A convenient method for the synthesis of nitriles
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A wide range of primary azides have been efficiently oxidized by a catalytic amount of CuI and TBHP into their corresponding nitriles in aqueous solution. A variety of oxidizable functional groups were well tolerated under the reaction conditions, and oxidation of secondary azides furnished their corresponding ketones (see scheme; TBHP=tert-butyl hydroperoxide).
- Lamani, Manjunath,Prabhu, Kandikere Ramaiah
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supporting information; experimental part
p. 6622 - 6625
(2010/11/04)
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- Shape-dependent catalytic activity of copper oxide-supported Pd(0) nanoparticles for Suzuki and cyanation reactions
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Palladium nanoparticles supported on different shapes of nanocrystalline CuO are prepared by the treatment of Cu(NO3)2 and Pd(OAc)2 in polyethylene glycol (PEG-6000). The shapes of the CuO/Pd composite are dependent on the amount of PEG used. Suzuki coupling was catalyzed efficiently by the oval-shaped material, whereas the rod shape facilitates the cyanation reaction. The CuO/Pd catalyst is recovered and reused for subsequent Suzuki reactions; however, cyanation poisons the catalyst for further use. Both these reactions are very clean and high yielding.
- Chattopadhyay, Kalicharan,Dey, Raju,Ranu, Brindaban C.
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supporting information; experimental part
p. 3164 - 3167
(2009/08/09)
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- Synthesis and evaluation of novel aromatic substrates and competitive inhibitors of GABA aminotransferase
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The design, synthesis, and evaluation of novel γ-aminobutyric acid aminotransferase (GABA-AT) inhibitors and inactivators can lead to the discovery of new GABA-related therapeutics. To this end, a series of aromatic amino acid compounds was synthesized to aid in the design of new inhibitors and inactivators of GABA-AT. All compounds were tested as competitive inhibitors of GABA-AT. The amino acids with benzylic amines were also tested as substrates for GABA-AT. It was found that these compounds were all poor competitive inhibitors of GABA-AT, but some were substrates of the enzyme, suggesting their utility as scaffolds for potential GABA-AT mechanism-based inactivators. Computer modeling was used to rationalize the substrate activity of the various compounds.
- Clift, Michael D.,Silverman, Richard B.
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p. 3122 - 3125
(2008/12/22)
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- Application of polymer-supported triphenylphosphine and microwave irradiation to the palladium-catalyzed cyanation of aryl triflates
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A variety of aryl nitriles were prepared in excellent yield from the palladium(II) acetate-catalyzed cross-coupling of aryl triflates and zinc cyanide under microwave irradiation conditions. To facilitate purification, polymer-supported triphenylphosphine was used as the palladium ligand. Comparison to the corresponding thermal conditions revealed much shorter reaction times with comparable yields. Copyright Taylor & Francis Group, LLC.
- Srivastava, Rajiv R.,Zych, Andrew J.,Jenkins, David M.,Wang, Hong-Jun,Chen, Zhen-Jia,Fairfax, David J.
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p. 431 - 438
(2007/10/03)
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- Chemoselective nucleophilic arylation and single-step oxidative esterification of aldehydes using siloxanes and a palladium-phosphinous acid as a reaction switch
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Aldehydes and siloxanes form methyl esters in a single step through mild oxidative esterification in the presence of a palladium catalyst or, alternatively, afford secondary alcohols via TBAF-promoted arylation in the absence of a catalyst at increased temperatures under otherwise identical reaction conditions. Copyright
- Lerebours, Rachel,Wolf, Christian
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p. 13052 - 13053
(2008/02/08)
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- A facile direct conversion of aldehydes to esters and amides using acetone cyanohydrin
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Aromatic aldehydes with electron-withdrawing groups undergo rapid reactions with a variety of alcohols and secondary amines to afford the corresponding esters and amides, respectively, in high yields, when treated with NaCN or acetone cyanohydrin and base under ambient reaction conditions. In case of α,β-unsaturated aldehydes, simultaneous reduction of the CC bond along with esterification occurred to produce the saturated esters in high yields.
- Raj, I. Victor Paul,Sudalai
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p. 8303 - 8306
(2007/10/03)
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- Carboxylation and esterification of functionalized arylcopper reagents
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Functionalized arylcopper reagents have been produced in good yields at 25 °C from activated copper and the corresponding functionalized aryl iodides without the need of traditional organolithium or Grignard precursors. These organocopper compounds will undergo carboxylation with CO2 to form the corresponding copper benzoates. In turn, these salts can be acidified to produce the functionalized aryl acids or treated with appropriate alkyl halides in the presence of a dipolar aprotic solvent to generate the corresponding aryl esters. This methodology permits the formation of functionalized organic acids and esters that could not be generated by the carboxylation of organomagnesium compounds.
- Ebert, Greg W.,Juda, Wayne L.,Kosakowski, Robert H.,Ma, Bing,Dong, Liming,Cummings, Keith E.,Phelps, Mwita V. B.,Mostafa, Adel E.,Luo, Jianyuan
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p. 4314 - 4317
(2007/10/03)
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- Preparation of highly potent and selective non-peptide antagonists of the arginine vasopressin V1A receptor by introduction of a 2-ethyl-1H-1-imidazolyl group
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To find a new series of arginine vasopressin (AVP) V1A receptor antagonists, the influence of the 2-phenyl group of 2-phenyl-4′-[(2,3,4,5- tetrahydro-1H-1-benzazepin-1-yl)carbonyl]benzanilide (7) was investigated. Replacement of the 2-phenyl group by a 2-ethyl-1H-imidazol-1-yl group was effective in yielding a V1A-selective compound. Moreover, this imidazolyl group was introduced in the same position in YM-35471 (6), and further studies of these compounds were performed. Consequently, we found that the (Z)-4′-({4,4-difluoro-5-[(N-cyclo-propylcarbamoyl) methylene]-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl}carbonyl)-2-(2-ethyl-1H-1- imidazol-1-yl)benzanilide (9f) exhibited highly potent affinity and selectivity, and was the most potent antagonist for the V1A receptor among our compounds. The synthesis and pharmacological evaluation of these compounds are described in this paper
- Shimada, Yoshiaki,Akane, Hiroaki,Taniguchi, Nobuaki,Matsuhisa, Akira,Kawano, Noriyuki,Kikuchi, Kazumi,Yatsu, Takeyuki,Tahara, Atsuo,Tomura, Yuichi,Kusayama, Toshiyuki,Wada, Koh-Ichi,Tsukada, Junko,Tsunoda, Takashi,Tanaka, Akihiro
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p. 764 - 769
(2007/10/03)
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- Progress in the palladium-catalyzed cyanation of aryl chlorides
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The development of new palladium catalysts for the cyanation of various aryl and heteroaryl chlorides is described. The combination of amine co-catalysts with chelating phosphine ligands, for example, 1,4-bis(diphenylphosphino)butane (dppb) or 1,5-bis(diphenylphosphino)pentane (dpppe), allows an efficient cyanation of chloroarenes with simple potassium cyanide. General palladium-catalyzed cyanation of nonactivated and deactivated chloroarenes is possible for the first time. Studies of the oxidative addition of aryl halides to palladium triphenylphosphine complexes in the presence and absence of amines suggest that the co-catalyst is capable of preventing catalyst deactivation caused by the presence of excess cyanide ions in solution.
- Sundermeier, Mark,Zapf, Alexander,Mutyala, Sateesh,Baumann, Wolfgang,Sans, Juergen,Weiss, Stefan,Beller, Matthias
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p. 1828 - 1836
(2007/10/03)
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- Palladium-catalyzed cyanation reactions of aryl chlorides
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We have discovered an efficient cyanation of aryl chlorides which employs Pd2(dba)3, dppf and Zn as the catalyst and Zn(CN)2 as the cyanide source. Both electron-deficient and electron-rich aryl chlorides are effectively cyanated under these conditions. This discovery represents the first successful palladium-catalyzed cyanation of both electron-deficient and electron-rich aryl chlorides. (C) 2000 DuPont Pharmaceuticals Company.
- Jin, Fuqiang,Confalone, Pat N.
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p. 3271 - 3273
(2007/10/03)
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- Palladium-catalyzed cyanation of aryl and heteroaryl iodides with copper(i) cyanide
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The palladium-catalyzed cyanation of aryl and heteroaryl iodides or bromides using copper(i) cyanide as a cyano group source afforded the corresponding aryl and heteroaryl cyanides in good yields.
- Sakamoto, Takao,Ohsawa, Kazutoshi
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p. 2323 - 2326
(2007/10/03)
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- Aprotic diazotization in the presence of cuprous cyanide
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In a procedure of extreme simplicity and rapidity a mixture of an aromatic primary amine, copper (I) cyanide and an alkyl nitrite in dimethyl sulphoxide yielded fair to moderate yields of the corresponding nitriles. Side processes observed were reduction (NH2&[H), nitration (NH2←NO2) and hydroxylation (NH2&[OH). In the case of polyhaloanilines halogen dance products could be detected.
- Giumanini, Angelo G.,Verardo, Giancarlo,Geatti, Paola,Strazzolini, Paolo
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p. 7137 - 7148
(2007/10/03)
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- Aryl Mesylates in Metal Catalyzed Homo- and Cross-Coupling Reactions. 4. Scope and Limitations of Aryl Mesylates in Nickel Catalyzed Cross-Coupling Reactions
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This paper describes the synthetic utility of aryl mesylates derived from phenols in various transition metal-catalyzed cross-coupling reactions.The Ni(0)-catalyzed cross-couplings of aryl mesylates with organometallic carbanion synthons (organotin, -magnesium, and -zinc compounds) are described.It is demonstrated that Stille-type coupling reaction based on organotin compounds results in low yields due to the sluggish transmetalation step of the reaction cycle.Good to high yields of cross-coupled products are obtained by using more reactive organomagnesium and -zinc compounds as coupling partners.The Ni(0)-catalyzed cyanation of aryl mesylates is also described.Various aryl mesylates are converted to aryl nitriles in high yields by reaction with KCN in the presence of Ni(0) catalyst in DMF.In addition, the Ni(0)-catalyzed aromatic nucleophilic substitution reaction of aryl mesylates with the heteroatom-nucleophile, benzenethiolate anion, is also presented.
- Percec, Virgil,Bae, Jin-Young,Hill, Dale H.
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p. 6895 - 6903
(2007/10/03)
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- Nucleophilic Displacement Catalyzed by Transition Metal. IX. *CHCl3-DPPF Catalyzed Cyanation of Aryl Halides and Aryl Triflates
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A catalyst system comprising *CHCl3 and DPPF was proved to be efficient for the cyanation of aryl iodides and aryl triflates with KCN.The reactivities of aryl substrates decreased in the order ArI > ArOTf > ArBr.
- Takagi, Kentaro,Sasaki, Ken,Sakakibara, Yasumasa
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p. 1118 - 1121
(2007/10/02)
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- THALLIUM IN ORGANOC SYNTHESIS. 63. A CONVENIENT SYNTHESIS OF AROMATIC NITRILES
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Aromatic nitriles are readily formed by heating arylthallium bis(trifluoracetates) with CuCN in acetonitrile.
- Taylor, Edward C.,Katz, Alan H.,McKillop, Alexander
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p. 5473 - 5476
(2007/10/02)
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- NMR STUDIES ON IMIDINES. III. (1)H AND (13)C NUCLEAR MAGNETIC RESONANCE STUDY ON THE TAUTOMERISM AND GEOMETRICAL ISOMERISM OF 3-IMINOISOINDOLINONE AND SOME ALKYLATED DERIVATIVES. OBSERVATION OF E AND Z ISOMERS ABOUT A FREE IMINO GROUPING
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3-Iminoisoindolinone (1) and some N-alkyl derivatives (8, 9, 10, 11, 12, 16 and 17) have been fully examined by (1)H and (13)C NMR spectroscopy. 3-(Methylimino)isoindolinone (12) cannot be obtained by reaction of 1 with methylamine, because it rearranges to 3-imino-2-methylisoindolinone (11), which reacts further to 2-methyl-3-(methylimino)isoindolinone (10).Both compounds have been shown to adopt the E configuration predominantly (88 percent for 11 at -55 deg C (CDCl3); 100 percent for 10). 3-(Methylimino)isoindolinone (12) favours the Z configuration (96 percent). Analogous results are found for the butyl derivatives (16, 17). 3-Imino isoindolinone (1) is present as the imino tautomer for 70 percent in DMSO-d6 solution as established by comparison of (13)C NMR chemical shift values of 1 with those of model compounds, 3-imino-2-methyl isoindolinone (11) and 3-(dimethylamino)isoindolinone (8).The tautomeric equilibrium is more extreme towards the imino form for the N-methyl and N-butyl derivatives 12 and 16. 2,3,4,5-tetrahydroisoindolinopyrimidin-6-one served as the imino model compound together with 10. (1)H and(13)C NMR data are given for several phthalic acid derivatives.
- Spiessens, Luc I.,Anteunis, Marc J. O.
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p. 965 - 994
(2007/10/02)
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- Oxadiazole benzoic acid derivatives as herbicides
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New 2-(1,3,4-oxadiazole-2-yl) benzoic acids and salts and esters thereof, as well as certain 2-(2-oxazolyl) benzoic acids, salts and esters, having the formula: SPC1 Where X is nitrogen or C-R" (R" being hydrogen or methyl), R is phenyl or various substituents, and R' and the Y's are hydrogen or various substituents, are effective preemergence or postemergence herbicides, on various crops. The chemicals act selectively and are useful against purple nutsedge and in cranberry. Oxadiazoles of the invention may be made by reacting a benzhydrazide with phthalic anhydride to form a hydrazide which is cyclized by removal of the elements of water, using as a catalyst fuming sulfuric acid or dimethylformamide-sulfur trioxide complex.
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