- Trifluoromethylation of Electron-Rich Alkenyl Iodides with Fluoroform-Derived ligandless CuCF3
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We herein present a flexible approach for the incorporation of CF3 units into a predefined site of electron-rich alkenes that exploits the regiocontrolled introduction of an iodine handle and subsequent trifluoromethylation of the C(sp2)-I bond using fluoroform-derived ligandless CuCF3. The broad substrate scope and functional group tolerance together with the scalability and purity of the resulting products enabled the controlled, late-stage synthesis of single regioisomers of complex CF3-scaffolds, such as sugars, nucleosides (antivirals), and heterocycles (indoles and chromones), with potential for academic and industrial applications.
- Mestre, Jordi,Lishchynskyi, Anton,Castillón, Sergio,Boutureira, Omar
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- Photoinduced Trifluoromethylation of Arenes and Heteroarenes Catalyzed by High-Valent Nickel Complexes
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We describe a series of air-stable NiIII complexes supported by a simple, robust naphthyridine-based ligand. Access to the high-valent oxidation state is enabled by the CF3 ligands on the nickel, while the naphthyridine exhibits either a monodentate or bidentate coordination mode that depends on the oxidation state and sterics, and enables facile aerobic oxidation of NiII to NiIII. These NiIII complexes act as efficient catalysts for photoinduced C(sp2)?H bond trifluoromethylation reactions of (hetero)arenes using versatile synthetic protocols. This blue LED light-mediated catalytic protocol proceeds via a radical pathway and demonstrates potential in the late-stage functionalization of drug analogs.
- Deolka, Shubham,Govindarajan, Ramadoss,Khaskin, Eugene,Fayzullin, Robert R.,Roy, Michael C.,Khusnutdinova, Julia R.
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supporting information
p. 24620 - 24629
(2021/10/08)
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- Nickel(IV)-Catalyzed C-H Trifluoromethylation of (Hetero)arenes
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This Article describes the development of a stable NiIV complex that mediates C(sp2)-H trifluoromethylation reactions. This reactivity is first demonstrated stoichiometrically and then successfully translated to a NiIV-catalyzed C-H trifluoromethylation of electron-rich arene and heteroarene substrates. Both experimental and computational mechanistic studies support a radical chain pathway involving NiIV, NiIII, and NiII intermediates.
- Meucci, Elizabeth A.,Nguyen, Shay N.,Camasso, Nicole M.,Chong, Eugene,Ariafard, Alireza,Canty, Allan J.,Sanford, Melanie S.
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supporting information
p. 12872 - 12879
(2019/08/26)
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- A methodology for the photocatalyzed radical trifluoromethylation of indoles: A combined experimental and computational study
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A methodology for the direct introduction of the trifluoromethyl group on to indole scaffolds is presented. The procedure involves the use of sodium trifluoromethylsulfinate (Langlois reagent) as the source of the trifluoromethyl radical, and is performed photochemically with 2-tert-butylanthraquinone as a photocatalyst. The reaction has also been probed computationally. Reaction kinetics and molecular orbital analyses from our quantum chemical computations successfully predict and rationalize the formation of the experimentally observed product and, in the case of 1-methylbenzimidazole, even reproduce the same qualitative trends in regioisomer preference.
- Miller, Shelli A.,van Beek, Bas,Hamlin, Trevor A.,Bickelhaupt, F. Matthias,Leadbeater, Nicholas E.
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supporting information
p. 94 - 100
(2018/08/28)
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- For the production of sulfur [...] hydrocarbon or heteroaromatic hydrocarbon compound and its preparation method (by machine translation)
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The invention discloses a trifluoro-methylthio arene or azacalixarene compound and a preparation method thereof. The preparation method of the trifluoro-methylthio arene or azacalixarene compound comprises the following steps: in an organic solvent, carrying out substitution reaction on a compound shown in a formula I and nitrogen-trifluoro-methylthio saccharin shown in a formula II in presence of a catalyst, so that a compound shown in a formula III is obtained. The preparation method of the trifluoro-methylthio arene or azacalixarene compound has the advantages that reaction materials can be easily controlled to be in single substitution, toxicity is low, and environmental protection is realized; meanwhile, application range of substrate is wide, equipment requirement is low, and operation is simple. The general formula (I), the general formula (II) and the formula (III) are described in the specification.
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Paragraph 0052; 0053; 0054
(2018/09/02)
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- Redox-ligand sustains controlled generation of CF3 radicals by well-defined copper complex
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A well-defined copper complex bearing iminosemiquinone ligands performs single electron reduction of an electrophilic CF3+ source into CF3 radicals. This redox behavior is enabled by the ligand which shuttles through two different redox states (iminosemiquinone and iminobenzoquinone) while the copper center is preserved as a Cu(ii). This system was used in the trifluoromethylation of silyl enol ethers, heteroaromatics and in the hydrotrifluoromethylation of alkynes. This is the first example of cooperative redox catalysis for the controlled generation of CF3 radicals.
- Jacquet, Jérémy,Blanchard, Sébastien,Derat, Etienne,Desage-El Murr, Marine,Fensterbank, Louis
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p. 2030 - 2036
(2016/03/05)
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- A method for synthesizing three fluoromethylation aromatic hydrocarbon
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The invention provides a synthetic method for a trifluoromethyl methylation arene. The trifluoromethyl methylation arene is prepared by reacting a halogenated arene, copper powder, elemental iodine and trifluoroacetic anhydride in an organic solvent under an inert atmosphere protection state. The method has the advantages of being simple and efficient, cheap in raw materials, low in synthetic cost, high in universality and repeatability, and the like, and can be popularized and applied to the fields of the synthesis of trifluoromethyl methylation aromatic derivatives.
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Paragraph 0059; 0060; 0061
(2017/02/09)
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- Iron-catalyzed trifluoromethylation of enamide
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Herein the first example of the iron(II)-catalyzed trifluoromethylation of enamide using mild and simple reaction conditions is reported. The method is cost-effective and uses the easy-to-handle Togni's reagent as the electrophilic CF3 source. This transformation is totally regioselective at the C3 position of enamides and exhibits broad substrate scope, good functional group tolerance and thus demonstrates its useful application in a late-stage fluorination strategy.
- Rey-Rodriguez, Romain,Retailleau, Pascal,Bonnet, Pascal,Gillaizeau, Isabelle
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supporting information
p. 3572 - 3575
(2015/03/04)
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- New Reagent for Highly Efficient Synthesis of Trifluoromethyl-Substituted Arenes and Heteroarenes
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A new reagent trimethylsilyl chlorodifluoroacetate (TCDA) is reported for the introduction of a -CF3 group to arenes and heteroarenes. Compared with current known reagents, TCDA shows very broad scope with respect to electron-deficient, -neutral, and -rich aryl/heteroaryl iodides as well as excellent functional group tolerance, including ester, amide, aldehyde, hydroxyl, and carboxylic acid. (Chemical Equation Presented).
- Zhang, Xiaomin,Wang, Jian,Wan, Zehong
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supporting information
p. 2086 - 2089
(2015/05/13)
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- Copper-mediated trifluoromethylation of heteroaromatic compounds by trifluoromethyl sulfonium salts
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Copper is king! A convenient method for the synthesis of trifluoromethylated heteroaromatic compounds under mild conditions has been developed based on the observation that 1 can be reduced by certain metals (see scheme). Substrate 1 is assumed to be reduced by copper via a single-electron transfer mechanism, and CuCF3 is the most probable intermediate in this reaction. DMF=N,N-dimethylformamide, Tf=triflate.
- Zhang, Cheng-Pan,Wang, Zong-Ling,Chen, Qing-Yun,Zhang, Chun-Tao,Gu, Yu-Cheng,Xiao, Ji-Chang
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supporting information; experimental part
p. 1896 - 1900
(2011/04/16)
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- Trifluoromethylation of various aromatic compounds by CF3I in the presence of Fe(II) compound, H2O2 and dimethylsulfoxide
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Trifluoromethylation of aromatic and hetero-aromatic compounds by CF3I in the presence of Fe(II) compound, H2O2 and dimethylsulfoxide was investigated. Various trifluoromethylated benzene derivatives, six-membered nitrogen-containing aromatic compounds and five-membered hetero-aromatic compounds were obtained under mild conditions. General orientation of electrophilic substitution of aromatic compounds was observed similarly as reported in other radical trifluoromethylation previously.
- Kino, Tatsuhito,Nagase, Yu,Ohtsuka, Yuhki,Yamamoto, Kyoko,Uraguchi, Daisuke,Tokuhisa, Kenji,Yamakawa, Tetsu
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body text
p. 98 - 105
(2010/03/03)
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- Photoinduced Electron-transfer Reaction of Difluorodiiodomethane with Azaaromatic Compounds and Enamines
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Irradiation of difluorodiiodomethane 1 with pyrroles, indole and imidazoles in dimethylformamide gives the corresponding trifluoromethylated products, whereas irradiation with enamines results in 2-trifluoromethyl ketones.A photoinduced electron-transfer mechanism is proposed.
- Chen, Qing-Yun,Li, Zhan-Ting
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p. 645 - 648
(2007/10/02)
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- Perfluoroalkylations of Nitrogen-containing Heteroaromatic Compounds with Bis(perfluoroalkanoyl) Peroxides
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Perfluoroalkylations of nitrogen-containing heteroaromatic compounds with bis(perfluoroalkanoyl) peroxides were studied.Bis(trifluoroacetyl) peroxide, bis(heptafluorobutyryl) peroxide, and bis(pentadecafluoro-octanoyl) peroxide were found to be useful and effective reagents for perfluoromethylations, perfluoropropylations or perfluoroheptylations of pyrrole and its derivatives, while these peroxide could not be applied for the perfluoroalkylations of pyridine or imidazole.For the perfluoroalkylations with the peroxides, electron transfer from the substrate to the peroxide, which affords a perfluoroalkyl radical of the substrate in a solvent cage, is proposed.In pyrrols, since the delocalization of the N lone pair to ?-systems lowers the nucleophilicity of the N lone pair and increases the electron density at the ?-orbital, the electron transfer readily occurred and perfluoroallkylated pyrroles were obtained in good yield and regioselectively.However, nucleophilic attack of the lone pair to the O-O bond of the peroxide was superior to the electron transfer in pyridine or imidazole of which the N lone pairs are very nucleophilic.
- Yoshida, Masato,Yoshida, Tatsuro,Kobayashi, Michio,Kamigata, Nobumasa
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p. 909 - 914
(2007/10/02)
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