- Nickel-Catalyzed C–H Trifluoromethylation of Electron-Rich Heteroarenes
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The first example of a nickel-catalyzed C–H trifluoromethylation of electron-rich heteroarenes, including imidazopyridines, indoles and thiophenes, has been developed with the commercially available and relatively inexpensive industrial raw material iodotrifluoromethane (CF3I) as the trifluoromethylating reagent. The synthetic potential of this method is demonstrated by its successful application to the direct trifluoromethylation of the biologically active molecules melatonin and zolmitriptan. (Figure presented.).
- Wu, Yun,Zhang, Hao-Ran,Jin, Ruo-Xing,Lan, Quan,Wang, Xi-Sheng
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Read Online
- Reductant-Induced Free Radical Fluoroalkylation of Nitrogen Heterocycles and Innate Aromatic Amino Acid Residues in Peptides and Proteins
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A series of fluoroalkylated cyclic λ3-iodanes and their hydrochloride salts was prepared and used in a combination with sodium ascorbate in buffer or aqueous methanol mixtures for radical fluoroalkylation of a range of substituted indoles, pyrroles, tryptophan or its derivatives, and Trp residues in peptides. As demonstrated on several peptides, the aromatic amino acid residues of Trp, Tyr, Phe, and His are targeted with high selectivity to Trp. The functionalization method is biocompatible, mild, rapid, and transition-metal-free. The proteins myoglobin, ubiquitin, and human carbonic anhydrase I were also successfully functionalized.
- Rahimidashaghoul, Kheironnesae,Klimánková, Iveta,Hubálek, Martin,Korecky, Michal,Chvojka, Matú?,Pokorny, Daniel,Matou?ek, Václav,Fojtík, Luká?,Kavan, Daniel,Kuka?ka, Zdeněk,Novák, Petr,Beier, Petr
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Read Online
- Control of site selectivity in trifluoromethylation of alkenes bearing a pendant indolyl group: Synthesis of CF3-containing tetrahydrocarbazoles
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We present a tetrahydrocarbozole-forming carbo-trifluoromethylation of indoles bearing an alkenyl group at the C3 position. The reaction proceeded selectively with the combination of TsOH·H2O as a catalyst and CH2Cl2 as a solvent. The site-selectivity could be altered by changing the reaction solvent; the use of THF instead of CH2Cl2 increased the formation of aromatic trifluoromethylation products.
- Murakami, Ryo,Sekine, Daisuke,Aoki, Yuma,Kawamura, Shintaro,Sodeoka, Mikiko
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- Trifluoromethylation of heterocycles via visible light photoredox catalysis
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A method has been developed for the visible light-induced trifluoromethylation of heterocyclic compounds. A variety of electron-rich heterocycles were transformed into trifluoromethylated products by using CF 3I as the trifluoromethyl radical source and Ru(bpy) 3Cl2 as the photocatalyst under mild reaction conditions. This operationally simple and eco-friendly process can introduce trifluoromethyl groups without prefunctionalization.
- Iqbal, Naeem,Choi, Sungkyu,Ko, Euna,Cho, Eun Jin
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Read Online
- Exploring the Structure and Performance of Cd–Chalcogenide Photocatalysts in Selective Trifluoromethylation
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The field of heterogeneous photoredox catalysis has grown substantially and impacted organic synthesis because of the affordability and reusability of catalysts. This study reports radical trifluoromethylation with Cd–chalcogenide semiconductors. Cd semiconductors, particularly CdSe, are readily available, commercial, visible-light-responsive, heterogeneous photocatalysts. The potential of readily available Cd semiconductors, particularly CdSe, is confirmed by their increased photocatalytic activity toward trifluoromethylation with various substrates, such as (hetero)arenes and vinylic amides/acids, via addition, cyclization, and decarboxylation under visible light. The economic significance of this strategy is also highlighted through the scalable synthesis of biologically active molecules followed by catalyst reuse. Moreover, these catalysts are relatively inexpensive compared with transition metal-based homogeneous photocatalysts, presently used in organic synthesis.
- Muralirajan, Krishnamoorthy,Kancherla, Rajesh,Bau, Jeremy A.,Taksande, Mayur Rahul,Qureshi, Muhammad,Takanabe, Kazuhiro,Rueping, Magnus
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p. 14772 - 14780
(2021/12/09)
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- Rational Design and Development of Low-Price, Scalable, Shelf-Stable and Broadly Applicable Electrophilic Sulfonium Ylide-Based Trifluoromethylating Reagents
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The development of two highly reactive electrophilic trifluoromethylating reagents (trifluoromethyl)(4-nitrophenyl)bis(carbomethoxy)methylide (1g) and (trifluoromethyl)(3-chlorophenyl)bis(carbomethoxy)methylide (1j) through structure-activity study was described. Under mild conditions, reagent 1g reacted with β-ketoesters and silyl enol ethers to give α-trifluoromethylated-β-ketoesters or α-trifluoromethylated ketones in high yields. In addition, reagent 1g could serve as a trifluoromethyl radical for a variety of trifluoromethylative transformations under visible light irradiation, including radical trifluoromethylation of electron-rich indoles and pyrroles and sodium aryl sulfinates as well as trifluoromethylative difunctionalization with styrene derivatives. On the other hand, as a complimentary, under reductive coupling conditions, reagent 1j reacted with a variety of (hetero)aryl iodides for the formation of trifluoromethylated (hetero)arenes.
- Ge, Hangming,Ling, Yijing,Liu, Yafei,Lu, Long,Shen, Qilong
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p. 1667 - 1682
(2021/05/28)
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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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- Solid-State Radical C?H Trifluoromethylation Reactions Using Ball Milling and Piezoelectric Materials
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The application of piezoelectricity for the generation of trifluoromethyl (CF3) radicals is reported together with the development of a method for the mechanochemical C?H trifluoromethylation of aromatic compounds. As compared to conventional solution-based approaches, this mechanoredox C?H trifluoromethylation enables cleaner and more sustainable access to a wide range of trifluoromethylated N-heterocycles and peptides, which are important structural motifs in modern drug discovery. This study thus represents an important milestone for future applications of mechanoredox systems to medicinal and pharmaceutical science.
- Ito, Hajime,Kubota, Koji,Lee, Joo Won,Pang, Yadong
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supporting information
p. 22570 - 22576
(2020/10/21)
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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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- CATALYST-FREE AND REDOX-NEUTRAL INNATE TRIFLUOROMETHYLATION AND ALKYLATION OF (HETERO)AROMATICS ENABLED BY LIGHT
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The present disclosure relates to reagents and method for performing trifluoromethylation, difluoromethylation or alkylation of aromatic or heteroaromatic rings in a redox-neutral manner without any catalyst which are enabled by light. In addition, there are methods for synthesizing the starting reagents used in the trifluoromethylation, difluoromethylation or alkylation reactions.
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Page/Page column 16-18
(2019/04/26)
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- Metal-free oxidative trifluoromethylation of indoles with CF3SO2Na on the C2 position
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An efficient method of synthesizing 2-trifluoromethylindoles from indoles with easy-to-handle, cheap and low-toxic CF3SO2Na under metal-free conditions is described, which selectively introduces trifluoromethyl to indoles on the C2 position. The desired product can be obtained in 0.7 g yield. A radical intermediate may be involved in this transformation.
- Xie, Jiao-Jiao,Wang, Zhi-Qing,Jiang, Guo-Fang
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p. 35098 - 35101
(2019/11/14)
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- 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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- Visible-Light-Induced Trifluoromethylation of Unactivated Alkenes with Tri(9-anthryl)borane as an Organophotocatalyst
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Tri(9-anthryl)borane was successfully applied as an organophotocatalyst for the visible-light-induced trifluoromethylation of unactivated alkenes with CF3I. The mild reaction conditions tolerated a variety of functional groups, and the reaction could be extended to perfluoroalkylations with C3F7I and C4F9I. Mechanistic studies revealed that the photoredox catalysis involves an oxidative quenching pathway.
- Moon, Jisu,Moon, Yu Kyung,Park, Do Dam,Choi, Sukyung,You, Youngmin,Cho, Eun Jin
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p. 12925 - 12932
(2019/09/30)
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- Simple Photo-Induced Trifluoromethylation of Aromatic Rings
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The trifluoromethylation of various aromatic compounds with Umemoto reagent II (2,8-difluoro-5-(trifluoromethyl)-5 H -dibenzo[ b, d ]thiophen-5-ium triflate) proceeded in moderate to good yields under simple photo-irradiation conditions without any cataly
- Egami, Hiromichi,Ito, Yuta,Ide, Takafumi,Masuda, Shuya,Hamashima, Yoshitaka
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p. 2948 - 2953
(2018/07/03)
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- A novel method for preparing S-(perfluoroalkyl)-dibenzothiophenium trifluoromethanesulfonate
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A method for preparing S-(perfluoroalkyl)-dibenzothiophenium trifluoromethanesulfonate shown as a general formula (I) by a one-pot process with significant effects is disclosed by the invention. The method includes reacting a biphenyl compound, perfluoroalkyl sulfonate, trifluoroacetic anhydride and trifluoromethanesulfonic acid. The biphenyl compound can be recovered and utilized so that the method is an environmentally friendly preparing method.
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Paragraph 0100; 0104
(2018/04/01)
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- COMPOSITIONS AND METHODS OF PROMOTING ORGANIC PHOTOCATALYSIS
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The invention provides novel compounds and methods that are useful in promoting reactions that proceed through an oxidative quenching pathway. In certain embodiments, the reactions comprise atom transfer radical polymerization.
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Paragraph 0066; 0068; 0217-0218
(2018/09/12)
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- Circumventing Intrinsic Metal Reactivity: Radical Generation with Redox-Active Ligands
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Nickel complexes have gained sustained attention as efficient catalysts in cross-coupling reactions and co-catalysts in dual systems due to their ability to react with radical species. Central to this reactivity is nickel's propensity to shuttle through several accessible redox states from Ni0 to NiIV. Here, we report the catalytic generation of trifluoromethyl radicals from a nickel complex bearing redox-active iminosemiquinone ligands. This unprecedented reactivity is enabled through ligand-based oxidation performing electron transfer to an electrophilic CF3+ source while the nickel oxidation state is preserved. Additionally, extension of this reactivity to a copper complex bearing a single redox equivalent is reported, thus providing a unified reactivity scheme. These results open new pathways in radical chemistry with redox-active ligands.
- Jacquet, Jérémy,Cheaib, Khaled,Ren, Yufeng,Vezin, Hervé,Orio, Maylis,Blanchard, Sébastien,Fensterbank, Louis,Desage-El Murr, Marine
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supporting information
p. 15030 - 15034
(2017/10/12)
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- Visible-Light-Induced Trifluoromethylation of Highly Functionalized Arenes and Heteroarenes in Continuous Flow
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We report a continuous-flow protocol for the trifluoromethylation of arenes, heteroarenes, and benzofused heterocycles. This photoredox methodology relies on the use of solid sodium trifluoromethanesulfinate (CF 3 SO 2 Na) as the trifluoromethylating agent and the iridium complex [Ir{dF(CF 3)ppy} 2 ](dtbpy)]PF 6 as the photoredox catalyst. A diverse set of highly functionalized heterocycles proved compatible with the methodology, and moderate to good yields were obtained within 30 minutes of residence time.
- Abdiaj, Irini,Bottecchia, Cecilia,Alcazar, Jesus,No?l, Timothy
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p. 4978 - 4985
(2017/10/06)
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- Catalyst-Free and Redox-Neutral Innate Trifluoromethylation and Alkylation of Aromatics Enabled by Light
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The Minisci alkylation is useful to functionalize aromatics via alkyl radical addition. Current approaches to prepare alkyl radicals follow either oxidative or reductive pathways from various functional groups. Developing new strategy beyond these traditional methods remains elusive yet highly significant. In this article, we present a redox-neutral and catalyst-free protocol to engender alkyl radicals in the context of trifluoromethylation and general alkylation of arenes. This protocol, via the Norrish type I concept to produce alkyl radicals, accommodates various functional groups and delivers the product in good yields. This method identified a series of compounds as the trifluoromethylation and alkylation reagents assisted by light. It is expected that these compounds can find potential applications in other radical-involved reactions.
- Liu, Peng,Liu, Wenbo,Li, Chao-Jun
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supporting information
p. 14315 - 14321
(2017/10/17)
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- Powerful, Thermally Stable, One-Pot-Preparable, and Recyclable Electrophilic Trifluoromethylating Agents: 2,8-Difluoro- and 2,3,7,8-Tetrafluoro-S-(trifluoromethyl)dibenzothiophenium Salts
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Although many electrophilic trifluoromethylating agents have been reported to date, practically useful reagents have yet to be developed. S-(Trifluoromethyl)dibenzothiophenium salts, known as Umemoto's reagents, have two significant drawbacks that have ha
- Umemoto, Teruo,Zhang, Bin,Zhu, Tianhao,Zhou, Xiaocong,Zhang, Peng,Hu, Song,Li, Yuanqiang
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p. 7708 - 7719
(2017/08/14)
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- Sunlight decatungstate photoinduced trifluoromethylations of (hetero)aromatics and electron-poor olefins
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Tetrabutylammonium decatungstate has been exploited to photoinduce the trifluoromethylation of (hetero)aromatics and electron-poor olefins. The process made use of the cheap Langlois' reagent (CF3SO2Na) and occurred under sunlight irradiation in an acetonitrile/water mixture. The trifluoromethylation of (hetero)aromatics required the use of potassium persulfate as an additive and the mono- or bis-trifluoromethylated adducts were obtained, depending on the actual reaction conditions and the chosen substrate.
- Corsico, Sara,Fagnoni, Maurizio,Ravelli, Davide
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p. 1375 - 1380
(2017/09/23)
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- Halogen-Bond-Promoted Photoactivation of Perfluoroalkyl Iodides: A Photochemical Protocol for Perfluoroalkylation Reactions
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A new protocol for photochemical perfluoroalkylation reactions using perfluoroalkyl iodide, amine additive, and THF solvent is reported. This protocol does not require a photoredox catalyst and proceeds at ambient temperature with irradiation from a compact fluorescent lamp, low-intensity UV lamp, or sunlight. This protocol can be applied to the synthesis of perfluoroalkyl-substituted phenanthridines as well as effect the iodo-perfluoroalkylation of alkenes/alkynes and the C-H perfluoroalkylation of electron-rich arenes and heteroarenes. This C-H perfluoroalkylation reaction offers a unique method for site-selective labeling of oligopeptides at the tryptophan residue.
- Wang, Yaxin,Wang, Junhua,Li, Guo-Xing,He, Gang,Chen, Gong
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supporting information
p. 1442 - 1445
(2017/03/23)
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- Strongly Reducing, Visible-Light Organic Photoredox Catalysts as Sustainable Alternatives to Precious Metals
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Photoredox catalysis is a versatile approach for the construction of challenging covalent bonds under mild reaction conditions, commonly using photoredox catalysts (PCs) derived from precious metals. As such, there is need to develop organic analogues as sustainable replacements. Although several organic PCs have been introduced, there remains a lack of strongly reducing, visible-light organic PCs. Herein, we establish the critical photophysical and electrochemical characteristics of both a dihydrophenazine and a phenoxazine system that enables their success as strongly reducing, visible-light PCs for trifluoromethylation reactions and dual photoredox/nickel-catalyzed C?N and C?S cross-coupling reactions, both of which have been historically exclusive to precious metal PCs.
- Du, Ya,Pearson, Ryan M.,Lim, Chern-Hooi,Sartor, Steven M.,Ryan, Matthew D.,Yang, Haishen,Damrauer, Niels H.,Miyake, Garret M.
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supporting information
p. 10962 - 10968
(2017/08/22)
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- Copper-Catalyzed C-H Difluoroalkylations and Perfluoroalkylations of Alkenes and (Hetero)arenes
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A general and facile synthetic method for C(sp2)-H difluoroalkylations and perfluoroalkylations of alkenes and (hetero)arenes with commercially available fluoroalkyl halides has been developed with a copper-amine catalyst system. This method is characterized by high yields, mild reaction conditions, low-cost catalyst, broad substrate scope, and excellent functional group compatibility, therefore providing a convenient synthetic strategy toward various difluoroalkyl- and perfluoroalkyl-substituted alkenes and (hetero)arenes.
- Wang, Xiaoyang,Zhao, Shuang,Liu, Jing,Zhu, Dingsheng,Guo, Minjie,Tang, Xiangyang,Wang, Guangwei
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supporting information
p. 4187 - 4190
(2017/08/23)
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- Continuous Flow Homolytic Aromatic Substitution with Electrophilic Radicals: A Fast and Scalable Protocol for Trifluoromethylation
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We report an operationally simple and rapid continuous flow radical C?C bond formation under Minisci-type reaction conditions. The transformations are performed at or below room temperature employing hydrogen peroxide (H2O2) and dimethylsulfoxide (DMSO) as reagents in the presence of an FeIIcatalyst. For electron-rich aromatic and heteroaromatic substrates, C?C bond formation proceeds satisfactorily with electrophilic radicals including.CF3,.C4F9,.CH2CN, and.CH2CO2Et. In contrast, electron-poor substrates exhibit minimal reactivity. Importantly, trifluoromethylations and nonafluororobutylations using CF3I and C4F9I as reagents proceed exceedingly fast with high conversion for selected substrates in residence times of a few seconds. The attractive features of the present process are the low cost of the reagents and the extraordinarily high reaction rates. The direct application of the protocol to dihydroergotamine, a complex ergot alkaloid, yielded the corresponding trifluoromethyl ergoline derivative within 12 seconds in a continuous flow microreactor on a 0.6 kg scale. The trifluoromethyl derivative of dihydroergotamine is a promising therapeutic agent for the treatment of migraines.
- Monteiro, Júlia L.,Carneiro, Paula F.,Elsner, Petteri,Roberge, Dominique M.,Wuts, Peter G. M.,Kurjan, Katherine C.,Gutmann, Bernhard,Kappe, C. Oliver
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supporting information
p. 176 - 186
(2017/01/09)
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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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- HALOGENATED S-(PERFLUOROALKYL) DIBENZOTHIOPHENIUM SALT AND ITS PRODUCTION METHODS
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Halogenated S-(perfluoroalkyl) dibenzothiophenium salt represented by the following general formula (I). This compound is a new, reactive, and industrially useful reagent for perfluoroalkylating organic compounds. The reagent can be prepared by a one-pot process or a two-step reaction process from a halogenated biphenyl and easily isolated by a filtration method. In addition, the halogenated biphenyl can be recovered by desulfurization from a halogenated dibenzothiophene obtained as a side-product by the usage of the reagent.
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Page/Page column 28-29
(2016/07/27)
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- Simple and Clean Photoinduced Aromatic Trifluoromethylation Reaction
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We describe a simple, metal-and oxidant-free photochemical strategy for the direct trifluoromethylation of unactivated arenes and heteroarenes under either ultraviolet or visible light irradiation. We demonstrated that photoexcited aliphatic ketones, such as acetone and diacetyl, can be used as promising low-cost radical initiators to generate CF3 radicals from sodium triflinate efficiently. The broad utility of this strategy and its benefit to medicinal chemistry are demonstrated by the direct trifluoromethylation of unprotected bidentate chelating ligand, xanthine alkaloids, nucleosides, and related antiviral drug molecules.
- Li, Lu,Mu, Xiaoyue,Liu, Wenbo,Wang, Yichen,Mi, Zetian,Li, Chao-Jun
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supporting information
p. 5809 - 5812
(2016/06/09)
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- Mechanisms and applications of cyclometalated Pt(II) complexes in photoredox catalytic trifluoromethylation
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The incorporation of a trifluoromethyl group into an existing scaffold can provide an effective strategy for designing new drugs and agrochemicals. Among the numerous approaches to trifluoromethylation, radical trifluoromethylation mediated by visible light-driven photoredox catalysis has gathered significant interest as it offers unique opportunities for circumventing the drawbacks encountered in conventional methods. A limited understanding of the mechanism and molecular parameters that control the catalytic actions has hampered the full utilization of photoredox catalysis reactions. To address this challenge, we evaluated and investigated the photoredox catalytic trifluoromethylation reaction using a series of cyclometalated Pt(ii) complexes with systematically varied ligand structures. The Pt(ii) complexes were capable of catalyzing the trifluoromethylation of non-prefunctionalized alkenes and heteroarenes in the presence of CF3I under visible light irradiation. The high excited-state redox potentials of the complexes permitted oxidative quenching during the cycle, whereas reductive quenching was forbidden. Spectroscopic measurements, including time-resolved photoluminescence and laser flash photolysis, were performed to identify the catalytic intermediates and directly monitor their conversions. The mechanistic studies provide compelling evidence that the catalytic cycle selects the oxidative quenching pathway. We also found that electron transfer during each step of the cycle strictly adhered to the Marcus normal region behaviors. The results are fully supported by additional experiments, including photoinduced ESR spectroscopy, spectroelectrochemical measurements, and quantum chemical calculations based on time-dependent density functional theory. Finally, quantum yields exceeding 100% strongly suggest that radical propagation significantly contributes to the catalytic trifluoromethylation reaction. These findings establish molecular strategies for designing trifluoromethyl sources and catalysts in an effort to enhance catalysis performance.
- Choi, Won Joon,Choi, Sungkyu,Ohkubo, Kei,Fukuzumi, Shunichi,Cho, Eun Jin,You, Youngmin
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p. 1454 - 1464
(2015/02/19)
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- Metal-free photocatalytic radical trifluoromethylation utilizing methylene blue and visible light irradiation
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The use of organofluorine compounds, especially those with an incorporated trifluoromethyl moiety, has increased dramatically in both the pharmaceutical and agrochemical industry. It has therefore become imperative to develop a mild and efficient synthetic technique for the inclusion of trifluoromethyl groups. Herein, we report the first use of methylene blue as a photosensitizer for the catalytic radical trifluoro- and hydrotrifluoromethylation of electron-rich heterocycles as well as terminal alkenes and alkynes under visible light irradiation. These reactions proceed with moderate to good yields at low catalyst concentrations; short irradiation times; and most importantly, without the need for potentially toxic transition-metal catalysts. In this work, considerable emphasis was also placed on understanding the kinetics of the mechanistically key steps through the use of laser flash photolysis techniques to more efficiently optimize the reaction conditions.
- Pitre, Spencer P.,McTiernan, Christopher D.,Ismaili, Hossein,Scaiano, Juan C.
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p. 2530 - 2535
(2014/08/18)
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- Rapid trifluoromethylation and perfluoroalkylation of five-membered heterocycles by photoredox catalysis in continuous flow
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Trifluoromethylated and perfluoroalkylated heterocycles are important building blocks for the synthesis of numerous pharmaceutical products, agrochemicals and are widely applied in material sciences. To date, trifluoromethylated and perfluoroalkylated hetero-aromatic systems can be prepared utilizing visible light photoredox catalysis methodologies in batch. While several limitations are associated with these batch protocols, the application of microflow technology could greatly enhance and intensify these reactions. A simple and straightforward photocatalytic trifluoromethylation and perfluoroalkylation method has been developed in continuous microflow, using commercially available photocatalysts and microflow components. A selection of five-membered hetero-aromatics were successfully trifluoromethylated (12 examples) and perfluoroalkylated (5 examples) within several minutes (8-20 min). Photo workflow: A simple and straightforward photocatalytic method for perfluoroalkylation in continuous flow is developed. A photo-microreactor, constructed from commercially available components, enables accelerated photocatalysis employing [Ru(bpy)3Cl2] as photocatalyst under irradiation by blue LED light. A series of electron-rich hetero-aromatics is successfully trifluoromethylated within 8-16 min. Also, a selection of hetero-aromatics is perfluoroalkylated within 10-20 min.
- Straathof, Natan J. W.,Gemoets, Hannes P. L.,Wang, Xiao,Schouten, Jaap C.,Hessel, Volker,Noel, Timothy
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p. 1612 - 1617
(2014/07/08)
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- Rapid trifluoromethylation of indole derivatives
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Rapid trifluoromethylation of indole derivatives was achieved using trimethylsilyltriflate as the catalyst. Good to high yields were observed within only 5 min at room temperature. This reaction system is able to provide not only the mono-trifluoromethyla
- Miyazaki, Ayako,Shimizu, Ryo,Egami, Hiromichi,Sodeoka, Mikiko
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p. 979 - 983
(2013/08/23)
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- Direct C2-trifluoromethylation of indole derivatives catalyzed by copper acetate
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Direct C2-selective trifluoromethylation of indole derivatives was achieved with Togni's hypervalent iodine reagent and CuOAc as a catalyst in MeOH under mild conditions, affording the desired C2-trifluoromethylated indoles in good yield (up to 90%).
- Shimizu, Ryo,Egami, Hiromichi,Nagi, Tatsuya,Chae, Jungha,Hamashima, Yoshitaka,Sodeoka, Mikiko
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experimental part
p. 5947 - 5949
(2010/11/21)
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- Electrophilic trifluoromethylation of arenes and N-heteroarenes using hypervalent iodine reagents
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The reaction of hypervalent iodine trifluoromethylating reagents with a variety of arenes and N-heteroarenes gives access to the corresponding trifluoromethylated compounds. In comparative studies, 1-trifluoromethyl-1,3- dihydro-3,3-dimethyl-1,2-benziodoxole (2) proved to be the superior to 1-trifluoromethyl-1,2-benziodoxol-3-(1H)-one (1) for the direct aromatic trifluoromethylation. Depending on the individual substrates, additives such as zinc bis(trifluoromethylsulfonyl)imide or tris(trimethylsilyl)silyl chloride proved helpful in promoting the reactions. In the case of nitrogen heterocycles a pronounced tendency for the incorporation of the trifluoromethyl group at the position adjacent to nitrogen was observed.
- Wiehn, Matthias S.,Vinogradova, Ekaterina V.,Togni, Antonio
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experimental part
p. 951 - 957
(2010/10/02)
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