- Facile diversification of simple benzo[b]thiophenes via thienobenzyne intermediates
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Thienobenzynes, which are thiophene-fused novel benzyne species, are efficiently generated via an iodine-magnesium exchange reaction of ortho-iodoaryl triflate-type precursors using a silylmethyl Grignard reagent as the activator. The method allows for facile preparation of a diverse range of multisubstituted benzothiophenes from readily available simple benzothiophenes.
- Morita, Takamoto,Yoshida, Suguru,Kondo, Masakazu,Matsushita, Takeshi,Hosoya, Takamitsu
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- Highly enantioselective construction of CF3-bearing all-carbon quaternary stereocenters: Hiral spiro-fused bisoxazoline ligands with 1,1′-binaphthyl sidearm for asymmetric Michael-type Friedel-Crafts reaction
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A novel class of chiral spiro-fused bisoxazoline ligands possessing a deep chiral pocket was prepared. The developed ligands have been employed in the nickel-catalyzed highly enantioselective Michael-type Friedel-Crafts reaction, affording the products bearing a trifluoromethylated all-carbon quaternary stereocenter with moderate to excellent yields (up to 99%) and good to excellent enantioselectivies (up to > 99.9% ee). Moreover, a proposed model of chiral pocket revealed that the attack of indole from the Re-face of β-CF3-β-disubstituted nitroalkene was favorable.
- Bao, Robert Li-Yuan,Fu, Kang,Shi, Lei
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- Oxidation of fluoroalkyl alcohols using sodium hypochlorite pentahydrate [1]
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Fluoroalkyl alcohols are effectivity oxidized to the corresponding fluoroalkyl carbonyl compounds by reaction with sodium hypochlorite pentahydrate in acetonitrile in the presence of acid and nitroxyl radical catalysts. Although the reaction proceeded slower under a nitroxyl radical catalyst- free condition, the desired carbonyl compounds were obtained in high yields. For the reaction with fluoroalkyl allylic alcohols, the corresponding α,β-epoxyketone hydrates were obtained in high yields.
- Kirihara, Masayuki,Suzuki, Katsuya,Nakakura, Kana,Saito, Katsuya,Nakamura, Riho,Tujimoto, Kazuki,Sakamoto, Yugo,Kikkawa, You,Shimazu, Hideo,Kimura, Yoshikazu
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- CARBENE MASS TAGGING
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The disclosure relates to a diazirine precursor mass tag compound represented by structural formula (I). Also disclosed is a method for detecting analytes in a sample, comprising derivatizing the analytes with the compound of formula (I), and detecting th
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Page/Page column 22
(2020/12/07)
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- Palladium-catalyzed fluoroacylation of (Hetero)arylboronic acid with fluorothioacetates at ambient temperature
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A palladium-catalyzed fluoroacylation of (hetero)aryl boronic acid with the fluorothioacetates is described at ambient temperature. A variety of aryl, and heteroaryl boronic acids are compatible in the reaction, affording the corresponding fluoroalkyl ketones in moderate to good yields. Further late-stage di-, and trifluoroacylation of drug molecule clofibrate and estrone demonstrated the synthetic practicability of this protocol.2009 Elsevier Ltd. All rights reserved.
- Ban, Shu-Rong,Cao, Ya-Fang,Dai, Hui-Xiong,Wang, Xing,Xu, Hui,Yi, Xing
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supporting information
(2020/03/23)
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- Selective Acylation of Aryl- A nd Heteroarylmagnesium Reagents with Esters in Continuous Flow
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A selective acylation of readily accessible organomagnesium reagents with commercially available esters proceeds at convenient temperatures and short residence times in continuous flow. Flow conditions allow us to prevent premature collapse of the hemiacetal intermediates despite noncryogenic conditions, thus furnishing ketones in good yields. Throughout, the coordinating ability of the ester and/or Grignard was crucial for the reaction outcome. This was leveraged by the obtention of several bisaryl ketones using 2-hydroxy ester derivatives as substrates.
- Heinz, Benjamin,Djukanovic, Dimitrije,Ganiek, Maximilian A.,Martin, Benjamin,Schenkel, Berthold,Knochel, Paul
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supporting information
p. 493 - 496
(2020/01/31)
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- Fluoroform: an Efficient Precursor for the Trifluoromethylation of Aromatic Esters by Sodium Diisopropylamide with Trialkylamines
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The trifluoromethanide anion is the postulated key intermediate in nucleophilic trifluoromethylation reactions. It is believed to be incompatible with Na+ cation due to the strong Na–F bond. However, herein we demonstrate that it could be prepared for the first time. Trialkylamines can be used as cation chelating agents to stabilize the isolated –CF3 ion to realize trifluoromethylation reaction. With this strategy, trifluoromethyl aromatic ketones could be effectively synthesized from fluoroform and aromatic esters with diisopropyl aminosodium (NaDA) and trialkylamines.
- Han, Zhaomeng,Chen, Sihan,Tu, Yongjun,Lian, Xiongdong,Li, Gongyong
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supporting information
p. 4658 - 4661
(2019/08/07)
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- Enantioselective Synthesis of Trifluoromethyl α,β-Unsaturated δ-Lactones via Vinylogous Aldol-Lactonization Cascade
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The novel vinylogous aldol-lactonization cascade of alkylidene oxindole with trifluoromethyl ketones is presented. The reaction, catalyzed by a bifunctional tertiary amine, provides an efficient application of the vinylogous reactivity of alkylidene oxindoles for the preparation of enantioenriched trifluoromethylated α,β-unsaturated δ-lactones.
- Crotti, Simone,Di Iorio, Nicola,Mazzanti, Andrea,Righi, Paolo,Bencivenni, Giorgio
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p. 12440 - 12448
(2018/10/09)
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- Oxidation of α-trifluoromethyl and non-fluorinated alcohols: Via the merger of oxoammonium cations and photoredox catalysis
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We present an alcohol oxidation strategy to access α-trifluoromethyl ketones (TFMKs) merging catalytic oxoammonium cation oxidation with visible-light photoredox catalysis. This work uses 4-acetamido-(2,2,6,6-tetramethyl-piperidin-1-yl)oxyl as an organic oxidant capable of generating TFMKs in good yields. The methodology serves as an improvement over previous reports of an analogous oxidation strategy requiring superstoichiometric quantities of oxidant. Both primary and secondary non-fluorinated alcohols can also be oxidised in good yields.
- Pistritto, Vincent A.,Paolillo, Joshua M.,Bisset, Kathryn A.,Leadbeater, Nicholas E.
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p. 4715 - 4719
(2018/07/06)
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- Palladium-Catalyzed Trimethylenemethane Cycloaddition of Olefins Activated by the δ-Electron-Withdrawing Trifluoromethyl Group
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α-Trifluoromethyl-styrenes, trifluoromethyl-enynes, and dienes undergo palladium-catalyzed trimethylenemethane cycloadditions under mild reaction conditions. The trifluoromethyl group serves as a unique δ-electron-withdrawing group for the activation of the olefin toward the cycloaddition. This method allows for the formation of exomethylene cyclopentanes bearing a quaternary center substituted by the trifluoromethyl group, compounds of interest for the pharmaceutical, agrochemical, and materials industries. In the diene series, the cycloaddition operates in a [3 + 4] and/or [3 + 2] manner to give rise to seven- and/or five-membered rings. This transformation greatly improves the scope of the TMM cycloaddition technology and provides invaluable insights into the reaction mechanism.
- Trost, Barry M.,Debien, Laurent
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p. 11606 - 11609
(2015/09/28)
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- A coupling of benzamides and donor/acceptor diazo compounds to form γ-lactams via Rh(III)-catalyzed C-H activation
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The coupling of O-pivaloyl benzhydroxamic acids with donor/acceptor diazo compounds provides isoindolones in high yield. The reaction tolerates a broad range of benzhydroxamic acids and diazo compounds, including substituted 2,2,2-trifluorodiazoethanes. Mechanistic experiments suggested that C-H activation is turnover-limiting and irreversible and that insertion of the diazo compound favors electron-deficient substrates.
- Hyster, Todd K.,Ruhl, Kyle E.,Rovis, Tomislav
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supporting information
p. 5364 - 5367
(2013/05/22)
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- Highly efficient synthesis of aryl and heteroaryl trifluoromethyl ketones via o-iodobenzoic acid (IBX)
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A two-step process for the synthesis of aryl and heteroaryl trifluoromethyl ketones from the corresponding aldehydes is described. Trifluoromethyl alcohols were prepared from aryl and heteroaryl aldehydes in excellent yields using catalytic amount of K2CO3. The trifluoromethyl alcohols were then oxidized conveniently and efficiently by o-iodoxybenzoic acid (IBX) under mild conditions to get the desired functionalized aryl and heteroaryl trifluoromethyl ketones.
- Cheng, Huicheng,Pei, Yu,Leng, Faqiang,Li, Jingya,Liang, Apeng,Zou, Dapeng,Wu, Yangjie,Wu, Yusheng
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p. 4483 - 4486
(2013/07/26)
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- FLUORINATED PHOSPHONIUM IONIC SALTS LINKED TO CARBENE-PRECURSORS
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Fluorinated phosphonium salts are linked to a diazirine moiety. A carbene precursor was photochemically generated from the diazirine to covalently attach the salt to substrates e.g., cotton and paper. Surface-coated substrates were found to have anti-wett
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Page/Page column 26; 30
(2013/08/15)
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- Oxidation of α-trifluoromethyl alcohols using a recyclable oxoammonium salt
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A simple, mild method for the oxidation of α-trifluoromethyl alcohols to trifluoromethyl ketones (TFMKs) using the oxoammonium salt 4-acetylamino-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate (1) is described. Under basic conditions, oxidation proceeds rapidly and affords good to excellent yields of TFMKs, without concomitant formation of the hydrate. The byproduct of the oxidation, 4-acetylamino-2,2,6,6-tetramethyl-1- piperidinyloxy (1c), is easily recovered and can be conveniently reoxidized to regenerate the oxoammonium salt.
- Kelly, Christopher B.,Mercadante, Michael A.,Hamlin, Trevor A.,Fletcher, Madison H.,Leadbeater, Nicholas E.
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p. 8131 - 8141
(2013/01/15)
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- A new entry for the oxidation of fluoroalkyl-substituted methanol derivatives: Scope and limitation of the organoiodine(V) reagent-catalyzed oxidation
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Oxidation of various fluoroalkyl-substituted methanol derivatives under the influence of a catalytic amount of sodium 2-iodobenzenesulfonate and Oxone in CH3CN or CH3NO2 was investigated in detail. The efficiency of the newly developed oxidation was also evaluated by comparison to other oxidations, such as Dess-Martin, PDC, and Swern oxidation.
- Tanaka, Yusuke,Ishihara, Takashi,Konno, Tsutomu
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experimental part
p. 99 - 104
(2012/05/07)
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- Diazirine-modified gold nanoparticle: Template for efficient photoinduced interfacial carbene insertion reactions
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Photolysis of a 3-aryl-3-(trifluoromethyl)diazirine-modified monolayer-protected gold nanoparticles (2-C12MPNs), with a core size of 1.8 ± 0.3 nm, in the presence of model carbene trapping reagents leads to efficient, essentially quantitative, modification of the interface via carbene insertion reactions. The utility of carbene insertion reactions as a general approach for the modification of Au-MPNs to provide a breadth of new structures available was demonstrated using acetic acid, methanol, benzyl alcohol, phenol, benzylamine, methyl acrylate, and styrene (10a-g, respectively) as electrophilic carbene trapping agents to form the corresponding modified 3a-g-C12MPNs. The 1.8 ± 0.3 nm gold nanoparticles bearing a diazirine group (2-C12MPNs) were synthesized using the ligand exchange reaction with the requisite 3-aryl-3-(trifluoromethyl) diazirinealkylthiol. The 2-C12MPNs and the resulting products of the reaction on the MPN (3a-g-C12MPN) were fully characterized by IR, 1H NMR, and 19F NMR spectroscopy and, when applicable, transmission electron microscopy (TEM). Verification for the 3a-g-C 12MPNs was accomplished by comparison of the spectral data to those of obtained for the photoreactions of 3-(3-methoxyphenyl)-3-(trifluoromethyl)- 3H-diazirine as a model with 10a-g.
- Ismaili, Hossein,Lee, Soo,Workentin, Mark S.
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scheme or table
p. 14958 - 14964
(2011/10/31)
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- Design and synthesis of a tag-free chemical probe for photoaffinity labeling
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The novel aromatic diazirine-containing benzoic acid 22 was prepared via the diazirine 11 as the key intermediate. After formylation of the aryl ring and cleavage of the methyl ether function of aldehyde 12, the phenolic hydroxy group was converted into the ether 21 terminating in an alkyne function. Oxidation of the aldehyde to the carboxylic acid provided the chemical probe 22 designed for tag-free photoaffinity labeling. In a proof-of-concept study it could be shown that irradiation of the simple ester 23 indeed yields the methanol insertion product 24. A subsequent click reaction with benzyl azide 20 led to the triazole 25. A more complicated example was realized with the esterification of bafilomycin A1 (27) with acid 22. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.
- Mayer, Timo,Maier, Martin E.
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p. 4711 - 4720
(2008/03/13)
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- Surface modification of nylon 6,6 using a carbene insertion approach
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The diazirine functionalised fluorenone, 3-[3-(trifluoromethyl)diazirin-3- yl]phenyl-9-oxo-9H-fluorene-2-carboxylate was synthesised to act as a model compound capable of modifying a wide variety of polymeric substrates. Photochemical activation of the diazirine moiety of the fluorenone derivative was utilised to afford highly reactive carbenes capable of insertion into or addition to a wide variety of functionalities. In this paper the photoinduced attachment of a fluorenone derivative to nylon 6,6 has been studied using UV-visible spectroscopic analysis. Incorporation of the fluorenone chromophore onto the backbone of nylon at different loading levels and after different coating cycles has been investigated and is detailed in this paper. the Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2006.
- Blencowe, Anton,Cosstick, Kevin,Hayes, Wayne
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- Aryldiazirine-modified pyroglutamates: Photoaffinity labels for glutamate
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The synthesis of an aryldiazirine-modified pyroglutamate is reported for potential application as a photoaffinity label at glutamate receptors. Detailed 13C NMR and 19F NMR spectroscopic characterisation data for these trifluoromethy
- Bentz, Emilie L.,Gibson, Hannah,Hudson, Clare,Moloney, Mark G.,Seldon, Debbie A.,Wearmouth, Edwina S.
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p. 247 - 250
(2007/10/03)
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- Palladium-catalyzed regio- and stereoselective formate reduction of fluorine-containing allylic mesylates. A new entry for the construction of a tertiary carbon attached with a fluoroalkyl group
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The regioselective palladium-catalyzed formate reduction of γ-fluoroalkylated allylic esters is described. Reduction of the allylic esters under the influence of palladium with a monodentate phosphine ligand proceeded preferentially at the γ position, the corresponding reduction products with a fluoroalkyl group at the tertiary carbon being afforded in high yields. When the chiral allylic ester was employed, complete chirality transfer was observed, leading to the optically active materials in high yields.
- Konno, Tsutomu,Takehana, Tsuyoshi,Mishima, Makoto,Ishihara, Takashi
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p. 3545 - 3550
(2007/10/03)
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- Design, synthesis and evaluation of novel hydroxyamides as orally available anticonvulsants
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Themisone, also known as Atrolactamide, was found, in the 1950s, to be a very potent anticonvulsant. It was hypothesized that the -CF3 substitution would maintain the anticonvulsant activity. Anticonvulsant testing of our novel compounds by the
- Schenck, Hilary A.,Lenkowski, Paul W.,Choudhury-Mukherjee, Indrani,Ko, Seong-Hoon,Stables, James P.,Patel, Manoj K.,Brown, Milton L.
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p. 979 - 993
(2007/10/03)
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- Synthesis of trifluoromethyl ketones by palladium-catalyzed cross-coupling reaction of phenyl trifluoroacetate with organoboron compounds
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Cross-coupling reaction of aryl trifluoroacetates with organoboron compounds catalyzed by palladium complexes gives trifluoromethyl ketones in moderate to excellent yields under mild conditions. The catalytic process has been designed on the basis of fundamental studies dealing with oxidative addition of phenyl trifluoroacetate to a Pd(0) complex to give a (phenoxo)(trifluoroacetyl)palladium(II) complex and its subsequent reaction with phenylboronic acid to liberate phenyl trifluoromethyl ketone. The catalytic cycle is proposed to be composed of (a) oxidative addition of the ester to give acyl(aryloxo)palladium intermediate, (b) the subsequent transmetallation with arylboron compounds, and (c) reductive elimination. Palladium(0) complexes, as well as catalysts prepared in situ from palladium acetate and 3 molar amounts of tributylphosphine or phosphite at room temperature, serve as convenient and effective catalysts. The process is applicable to a wide range of phenyl- and naphthylboronic acids to give various aryl trifluoromethyl ketones under mild conditions. Aryl perfluoroalkyl ketone derivatives can be similarly prepared in high yields from various phenyl perfluoroalkanecarboxylates and arylboronic acids.
- Kakino,Shimizu,Yamamoto
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p. 371 - 376
(2007/10/03)
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- Acyclic amides as estrogen receptor ligands: Synthesis, binding, activity and receptor interaction
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We have prepared a series of bisphenolic amides that mimic bibenzyl and homobibenzyl motifs commonly found as substructures in ligands for the estrogen receptor (ER). Representative members were prepared from three classes: N-phenyl benzamides, N-phenyl acetamides, and N-benzyl benzamides; in some cases the corresponding thiocarboxamides and sulfonamides were also prepared. Of these three classes, the N-phenyl benzamides had the highest affinity for ER, the N-phenyl acetamides had lower, and the N-benzyl benzamides were prone to fragmentation via a quinone methide intermediate. In the N-phenyl benzamide series, the highest affinity analogues had bulky N-substituents; a CF3 group, in particular, conferred high affinity. The thiocarboxamides bound better than the corresponding carboxamides and these bound better than the corresponding sulfonamides. Binding affinity comparisons suggest that the p-hydroxy group on the benzoate ring, which contributes most to the binding, is playing the role of the phenolic hydroxyl of estradiol. Computational studies and NMR and X-ray crystallographic analysis indicate that the two anilide systems studied have a strong preference for the s-cis or exo amide conformation, which places the two aromatic rings in a syn orientation. We used this structural template, together with the X-ray structure of the ER ligand binding domain, to elaborate an additional hydrogen bonding site on a benzamide system that elevated receptor binding further. When assayed on the individual ER subtypes, ERα and ERβ, these compounds show modest binding affinity preference for ERα. In a reporter gene transfection assay of transcriptional activity, the amides generally have full to nearly full agonist character on ERα, but have moderate to full antagonist character on ERβ. One high affinity carboxamide is 500-fold more potent as an agonist on ERα than on ERβ. This work illustrates that ER ligands having simple amide core structures can be readily prepared, but that high affinity binding requires an appropriate distribution of bulk, polarity, and functionality. The strong conformational preference of the core anilide function in all of these ligands defines a rather rigid geometry for further structural and functional expansion of these series. Copyright (C) 2000 Elsevier Science Ltd.
- Stauffer, Shaun R.,Sun, Jun,Katzenellenbogen, Benita S.,Katzenellenbogen, John A.
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p. 1293 - 1316
(2007/10/03)
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- Process for preparing trifluoromethyl ketones
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A process is described for preparing trifluoromethyl ketones of the formula I STR1 where R has the given meanings, wherein an alcohol of the formula II STR2 is reacted with a compound of the formula IV where n has the given meaning.
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- A Novel Family of Aromatic Diazirines for Photoaffinity Labeling
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A series of simple methods for modifying diazirines bearing an aromatic ring has been accomplished.This first versatile approach involving direct substitution on the aromatic ring of diazirines has been achieved by means of the aromatic thallation of (alkoxyphenyl)diazirines.Introduction of the thallium moiety was successfully followed by nitration, iodination, or palladium-catalyzed carbonylation to give a family of substituted aryldiazirines useful for photolabeling.For instance, diazirines labeled with a nitro group can be detected by spectrophotometric methods, and those labeled with an iodo group can be useful in tracer experiments.The (methoxyphenyl)diazirines were also found to be stable under certain demethylation conditions, thus providing a potential source of diazirines with modifiable phenol hydroxyl groups.By means of this approach, a spacer arm to link diazirines with ligands was readily introduced.Radioactive diazirines labeled with carbon-14 or tritium were also prepared using this method.All the new diazirines were derived from a pair of simple (methoxyphenyl)diazirines.The ease of derivatization of the (alkoxyphenyl)diazirines described here may offer a practical approach to simplify the time-consuming methods currently used for diazirine synthesis.
- Hatanaka, Yasumaru,Hashimoto, Makoto,Kurihara, Hiroko,Nakayama, Hitoshi,Kanaoka, Yuichi
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p. 383 - 387
(2007/10/02)
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- Influence of Alkyl-Chain Fluorination on the Action of Mammary Tumor Inhibiting 2,3-Bis(hydroxyphenyl)butanes and 2,3-Bis(hydroxyphenyl)but-2-enes
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trans-1,2-Bis(trifluoromethyl)-1,2-bis(4- and 3-hydroxyphenyl)ethenes 2 and 4 were prepared by reductive coupling (TiCl4/Zn/pyridine) of the methoxy-substituted α,α,α-trifluoroacetophenones, separation of the resulting cis- and trans-stilbene derivatives,
- Hartmann, Rolf W.,Heindl, Alexander,Schneider, Martin R.,Schoenenberger, Helmut
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p. 322 - 328
(2007/10/02)
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- Charge-Transfer Quenching of Triplet α-Trifluoroacetophenones
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The effects of ring substituents and of aromatic quenchers on the photoreduction by toluene of α,α,α-trifluoroacetophenone (AF3) have been measured.A plot of log kCT vs. ionization potential of the donor indicates that ΔGCT equals 22percent ΔG for the full electron transfer.A corresponding plot of log kCT vs. the triplet state reduction potential of ring-substituted AF3's, if analyzed as linear, would indicate that there is no intrinsic difference in reactivity between n,?* and ?,?* triplets but would also indicate that ΔGCT equals 42percent ΔG.The discrepancy between the 22 and 42percent is suggested to involve differing reactivities of n,?* and ?,?* triplets.If n,?* triplets are substantially more reactive, the plot vs. triplet reduction potential is expected to curve upward as the equilibrium population of n,?* triplet increases with substitution.
- Wagner, Peter J.,Lam, Henry M. H.
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p. 4167 - 4172
(2007/10/02)
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