- HETEROCYCLIC COMPOUNDS AS ANTI-VIRAL AGENTS
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The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof: which inhibit Respiratory Syncytial Virus (RSV) or HMPV. The present invention further relates to pharmaceutical compositions comp
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Page/Page column 47
(2021/07/31)
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- Ni-Catalyzed Defluorination for the Synthesis of gem-Difluoro-1,3-dienes and Their [4 + 2] Cycloaddition Reaction
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A nickel-catalyzed defluorination of α-trifluoromethylated allyl/propargyl carbonates using bis(pinacolato)diboron (B2pin2) as a reactant is described. The reaction proceeds under relatively mild reaction conditions, providing conjug
- Zhou, Minqi,Zhang, Jian,Zhang, Xing-Guo,Zhang, Xingang
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supporting information
p. 671 - 674
(2019/01/21)
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- Enantioselective Palladium-Catalyzed [3+2] Cycloaddition of Trimethylenemethane and Fluorinated Ketones
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A nitrile-substituted trimethylenemethane (TMM) donor undergoes palladium-catalyzed [3+2] cycloadditions with fluorinated ketones to generate tetrasubstituted trifluoromethylated centers in high enantioselectivity under mild conditions. The generation of the palladium–TMM complex was achieved by a self-deprotonation strategy, which shows remarkable improvements in regiocontrol, efficiency, and atom economy of asymmetric [3+2] cycloadditions. Moreover, the versatility of the nitrile group provides direct access to a variety of synthetically useful intermediates, including amides, aldehydes, and esters. The developed reaction conditions allow for the synthesis of a wide variety of aromatic, heteroaromatic, and aliphatic fluorinated dihydrofurans in excellent regio- and enantioselectivities.
- Trost, Barry M.,Mata, Guillaume
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supporting information
p. 12333 - 12337
(2018/09/10)
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- NHC-Copper(I) Halide-Catalyzed Direct Alkynylation of Trifluoromethyl Ketones on Water
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An efficient and easily scalable NHC-copper(I) halide-catalyzed addition of terminal alkynes to 1,1,1-trifluoromethyl ketones, carried out on water for the first time, is reported. A series of addition reactions were performed with as little as 0.1-2.0?mo
- Czerwiński, Pawe?,Molga, Edyta,Cavallo, Luigi,Poater, Albert,Michalak, Micha?
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supporting information
p. 8089 - 8094
(2016/06/13)
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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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- Development of (Trifluoromethyl)zinc Reagent as Trifluoromethyl Anion and Difluorocarbene Sources
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The trifluoromethylation of carbonyl compounds is accomplished by the stable (trifluoromethyl)zinc reagent generated and then isolated from CF3I and ZnEt2, which can be utilized as a trifluoromethyl anion source (CF3-). The reaction proceeds smoothly with diamine as a ligand and ammonium salt as an initiator, providing the corresponding trifluoromethylated alcohol products. Moreover, the (trifluoromethyl)zinc reagent can also be employed as a difluorocarbene source (:CF2) not only for gem-difluoroolefination of carbonyl compounds with phosphine but also for gem-difluorocyclization of alkenes or alkynes via the thermal decomposition, respectively.
- Aikawa, Kohsuke,Toya, Wataru,Nakamura, Yuzo,Mikami, Koichi
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supporting information
p. 4996 - 4999
(2015/11/03)
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- An efficient route to 3-trifluoromethylpyrazole via cyclization/1,5-H shift and its applications in the synthesis of bioactive compounds
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A methodology for regioselective synthesis of 3-trifluoromethylpyrazole from the reaction of trifluoromethyl alkenone and tosylhydrazone has been developed. The reaction was proposed to proceed through a tandem cyclization and 1,5-H shift reaction, which can be applied to the synthesis of bioactive compounds like Celecoxib, Mavacoxib, and SC-560.
- Wang, Yongdong,Han, Jing,Chen, Jie,Cao, Weiguo
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p. 8256 - 8262
(2015/10/05)
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- Polyfluoroalkylation of carbonyl compounds by polyfluoroalkyl anions generated from polyfluorocarboxamides
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Polyfluoroalkyl anions, generated by reduction of (polyfluoroalkanoyl)piperidines with Et3BHK, were used for the polyfluoroalkylation of carbonyl compounds. Trifluoromethylation of aromatic aldehydes proceeded in good yields, and that of aliphatic aldehydes afforded a moderate yield. In contrast, the yield was low when the reaction involved benzophenone. Pentafluoroethylation and octafluorobutylation of aldehydes were also carried out by using the corresponding (polyfluoroalkanoyl)piperidines, which were prepared from commercially available polyfluorocompounds. The (polyfluoroalkanoyl)piperidines were also prepared through polyfluorination, and were used in the polyfluoroalkylation of aldehydes.
- Wakita, Natshumi,Hara, Shoji
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p. 1201 - 1212
(2016/11/07)
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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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- 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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- Synthesis of γ-fluoroalkylated allylic amines derivatives via palladium-catalyzed Overman rearrangement
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A Pd-catalyzed Overman rearrangement of α-fluoroalkylated allylic trichloroacetimidates has been developed. This reaction allows for an efficient synthesis of γ-fluoroalkylated allylic amine derivatives with excellent regio- and stereo-selectivities under
- Jiang, Xin-Yi,Chu, Lingling,Wang, Ruo-Wen,Qing, Feng-Ling
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p. 6853 - 6857,5
(2012/12/12)
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- Synthesis of γ-fluoroalkylated allylic amines derivatives via palladium-catalyzed Overman rearrangement
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A Pd-catalyzed Overman rearrangement of α-fluoroalkylated allylic trichloroacetimidates has been developed. This reaction allows for an efficient synthesis of γ-fluoroalkylated allylic amine derivatives with excellent regio- and stereo-selectivities under
- Jiang, Xin-Yi,Chu, Lingling,Wang, Ruo-Wen,Qing, Feng-Ling
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p. 6853 - 6857
(2013/01/15)
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- Regiospecific and diastereoselective aldol reaction of chiral N-sulfinyl metalloenamines with α,β-unsaturated trifluoromethyl ketones: Asymmetric synthesis of tertiary trifluoromethyl allylic carbinols
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Regiospecific and diastereoselective aldol type reaction of chiral N-sulfinyl metalloenamines with α,β-unsaturated trifluoromethyl ketones was reported, which affords the corresponding tertiary trifluoromethyl allylic carbinols in high yields with good di
- Liu, Zhen-Jiang,Zhang, Fan,Liu, Jin-Tao
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scheme or table
p. 102 - 107
(2012/03/11)
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- Nonenzymatic kinetic resolution of racemic 2,2,2-trifluoro-1-aryl ethanol via enantioselective acylation
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Kinetic resolution of a series of 2,2,2-trifluoro-1-aryl ethanol with (R)-benzotetramisole as the catalyst has been investigated. The result showed that when the aryl group in the substrate was a phenyl (or a phenyl substituted by an electron-donating group) or a naphthyl (an extended phenyl) group, the system could give an s value higher than 20. Preparative KR examples demonstrated the applicability of this method in the preparation of some of enantiomerically pure 2,2,2-trifluoro-1-aryl ethanol or 2,2,2-trifluoro-1-aryl-ethyl iso-butyrate.
- Xu, Qing,Zhou, Hui,Geng, Xiaohong,Chen, Peiran
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supporting information; experimental part
p. 2232 - 2238
(2009/07/11)
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- N-heterocyclic carbene catalyzed trifluoromethylation of carbonyl compounds
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(Chemical Equation Presented) A novel N-heterocyclic carbene (NHC) catalyzed trifluoromethylation reaction of carbonyl compounds was discovered. Both enolizable and nonenolizable aldehydes and α-keto esters undergo facile trifluoromethylation with TMSCF3 at room temperature in the presence of only 0.5-1 mol % of the commercially available NHC (1), providing CF3-substituted alcohols in good yields. Selective trifluoromethylation of aldehydes over ketones can be achieved under NHC catalysis. These conditions are mild and simple and tolerate a variety of functional groups.
- Song, Jinhua J.,Tan, Zhulin,Reeves, Jonathan T.,Gallou, Fabrice,Yee, Nathan K.,Senanayake, Chris H.
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p. 2193 - 2196
(2007/10/03)
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- Trifluoromethanesulfinamide from ephedrine: A more efficient trifluoromethylating reagent
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Nucleophilic trifluoromethylation of non-enolizable and enolizable carbonyl compounds was achieved with the trifluoromethanesulfinamide derived from O-silylated ephedrine. In contrast to the trifluoroacetamide analog, previously described, this reagent is able to trifluoromethylate more acidic enolizable compounds.
- Roussel, Solveig,Billard, Thierry,Langlois, Bernard R.,Saint-Jalmes, Laurent
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p. 2119 - 2122
(2007/10/03)
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- The polar effect on the regiochemistry of nucleophilic substitution of trifluoromethylated π-allylpalladium complex
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Allylic nucleophilic substitution of trifluoromethyl-group substituted cinnamyl carbonate with diethyl malonate anion in the presence of palladium complex catalyst gave regio- and stereoselectively the SN2′ product. The regiochemistry caused by
- Okano, Takashi,Matsubara, Hiroyoshi,Kusukawa, Takahiro,Fujita, Makoto
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- Microreactors for the synthesis of fluorinated materials
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The utility of microreactor for the synthesis of α-fluoro-α, β-unsaturated esters, trifluoromethylation and Michael addition reaction, is described.
- Miyake, Noriaki,Kitazume, Tomoya
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p. 243 - 246
(2007/10/03)
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- Enantioselective reduction of α,β-unsaturated ketones bearing the trifluoromethyl group
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α,β-Unsaturated ketones bearing the trifluoromethyl group were enantioselectively reduced by a variety of reagents to the corresponding secondary allylic alcohols with e.e. in the range 87-99%. The influence of the trifluoromethyl group on the enantioselectivity is discussed.
- Nenajdenko, Valentine G.,Smolko, Konstantin I.,Balenkova, Elizabeth S.
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p. 1259 - 1266
(2007/10/03)
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- Kinetic resolution of acyclic secondary allylic silyl ethers catalyzed by chiral ketones
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Kinetic resolution of acyclic secondary allylic silyl ethers by chiral dioxiranes generated in situ from chiral ketones (R)-1 and (R)-2 and Oxone was investigated. An efficient and catalytic method has been developed for kinetic resolution of those substrates with a CCl3, tert-butyl, or CF3 group at the α-position. In particular, high selectivities (S up to 100) were observed for kinetic resolutions of racemic α-trichloromethyl allylic silyl ethers 7 and 9-15 catalyzed by ketones (R)-2. Both the recovered substrates and the resulting epoxides were obtained in high enantiomeric excess. On the basis of steric and electrostatic interactions between the chiral dioxiranes and the racemic substrates, a model was proposed to rationalize the enantioselectivities and diastereoselectivities in the chiral ketone-catalyzed kinetic resolution process.
- Yang,Jiao,Yip,Lai,Wong
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p. 4619 - 4624
(2007/10/03)
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- A facile stereocontrolled synthesis of anti-alpha-(trifluoromethyl)-beta-amino alcohols.
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A short stereocontrolled preparation of anti-alpha-(trifluoromethyl)-beta-amino alcohols is described, involving an initial CF(3) transfer to cinnamaldehyde and a one-step, three-component condensation of 3,3,3-trifluorolactic aldehyde, an alkenyl (aryl)
- Prakash,Mandal,Schweizer,Petasis,Olah
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p. 3173 - 3176
(2007/10/03)
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- Enzymes in organic synthesis, 15. - Short enzymatic synthesis of L- fucose analogs
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A short enzymatic route for the synthesis of L-fucose analogs modified at the nonpolar terminus is reported. In particular, fucose derivatives bearing extended linear (1b) and branched (1e) saturated, or various unsaturated (1c, 1d) aliphatic chains have been prepared, in order to increase hydrophobic contacts. The rather general approach involves a sequential application of the recombinant enzymes L-fuculose 1-phosphate aldolase (FucA) and L-fucose ketol isomerase (FucI) from E. coli. Enantiomerically pure L-fucose analogs have been prepared in up to 30% overall yield starting from the appropriate hydroxyaldehyde precursors and dihydroxyacetone phosphate as readily available components. Unsaturated 2- hydroxyaldehydes have been efficiently prepared by alk(en/yn)yl Grignard addition to cinnamaldehyde followed by controlled ozonolysis of the styrene fragment.
- Fessner, Wolf-Dieter,Go?e, Claudius,Jaeschke, Georg,Eyrisch, Oliver
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p. 125 - 132
(2007/10/03)
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- A chiral triaminosulfonium salt: Design and application to catalytic asymmetric synthesis
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The first chiral triaminosulfonium salt, tris((S,S)-3,4-diphenylpyrrolidino)sulfonium difluorotriphenylstannate, catalyzes trifluoromethylation of benzaldehyde with (trifluoromethyl)trimethylsilane to give the corresponding optically active alcohol with 52% ee.
- Kuroki, Yoshichika,Iseki, Katsuhiko
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p. 8231 - 8234
(2007/10/03)
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- A unique chelating effect of Sc(OTf)3 to organofluorine compounds
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The scandium trifluoromethanesulfonate-catalyzed cleavage of acetate bearing two or three fluorine atoms at a position β to an acetoxy group proceeds exceptionally rapidly. The high efficiency of the hydrolysis is caused by a chelating effect of scandium with the fluorine atoms and an acetate moiety.
- Kajiro, Hiroshi,Mori, Atsunori,Nishihara, Yasushi,Hiyama, Tamejiro
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p. 459 - 460
(2007/10/03)
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- One-pot stereoselective synthesis of perfluoroalkylated (E)-allylic alcohols mediated by Ti(OPri)4 and Ph3P
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Synthesis of perfluoroalkylated (E)-allylic alcohols by the 'one-pot' reaction of equimolar amounts of aldehyde, 3-bromo-1,1,1-trifluoroacetone (or α-bromoalkyl perfluoroalkyl ketone), triphenylphosphine and titanium(IV) isopropoxide is described. The red
- Shen, Yanchang,Zhang, Yuming,Zhou, Yuefen
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p. 1759 - 1763
(2007/10/03)
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- Cesium fluoride catalyzed trifluoromethylation of esters, aldehydes, and ketones with (trifluoromethyl)trimethylsilane
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The low reactivity of carboxylic esters toward (trifluoromethyl)trimethylsilane (TMS-CF3) was investigated. A universal cesium fluoride catalyzed procedure for nucleophilic trifluoromethylation was developed. At room temperature (25 °C, with catalytic amounts of cesium fluoride, carboxylic esters were found to react to give the silyl ether intermediates, which afforded the trifluoromethyl ketones after hydrolysis. Sulfonic, sulfinic, and selenic esters also show good reactivity, giving novel trifluoromethylated compounds. The trifluoromethylation method was also applied to aldehydes and ketones, which were transformed to trifluoromethyl silyl ether intermediates and afforded trifluoromethylated alcohols in excellent yields after acid hydrolysis. Ethylene glycol dimethyl ether was used as solvent for solid or high boiling substrates, and benzonitrile was used for the low boiling substrates.
- Singh, Rajendra P.,Cao, Ganfeng,Kirchmeier, Robert L.,Shreeve, Jean'ne M.
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p. 2873 - 2876
(2007/10/03)
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- 19F nuclear magnetic resonance spectroscopy for the quantitative detection and classification of carbonyl groups in lignins
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A novel method that permits the quantitative detection and classification of various carbonyl groups in lignins has been developed. The proposed method was optimized with the quantitative trifluoromethylation of a series of carbonyl-containing lignin-like model compounds. This effort was followed by 19F NMR spectral analyses of the resulting fluorine derivatives allowing for a thorough understanding of their structure/19F chemical shift relationships. The various carbonyl groups present in lignins were also investigated by trifluoromethylating them in the presence of catalytic amounts of tetramethylammonium fluoride (TMAF), followed by hydrolysis with TMAF in tetrahydrofuran. By using a variety of selective reactions, it became possible to assign a number of prominent 19F NMR signals to a variety of carbonyl groups present in lignins. These studies demonstrated that the proposed method can be applied to the quantitative determination of carbonyl groups that are present in soluble native and technical lignins.
- Ahvazi, Behzad C.,Crestini, Claudia,Argyropoulos, Dimitris S.
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p. 190 - 201
(2007/10/03)
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- Novel reductive olefination mediated by Ti(O-i-Pr)4 and Ph3P. One-pot synthesis of trifluoromethylated trans-allylic alcohols
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A novel reductive olefination mediated by Ti(O-i-Pr)4 and Ph3P and its application to the 'one-pot' synthesis of perfluoroalkylated frans-allylic alcohols are described.
- Shen, Yanchang,Zhang, Yuming,Zhou, Yuefen
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p. 2195 - 2196
(2007/10/03)
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- Synthesis of allylic trifluoromethyl alcohols from 1-trifluoromethyl-epoxy ethers
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α-Thiophenyl ketones are easily available by the regioselective ring-opening of 1-trifluoromethyl-epoxy ethers with phenyl sodium thiolate. Their in situ reduction with NaBH4, followed by oxidation with NaIO4 and thermal decompositio
- Begue, Jean-Pierre,Bonnet-Delpon, Daniele,Kornilov, Andrei,Fischer-Durand, Nathalie
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- Trifluoromethylation and pentafluoroethylation of terpenoid carbonyl compounds used in perfumery
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The reaction of trifluoromethylsilane with a variety of terpenoid carbonyl compounds and other carbonyl compounds used in perfumery gave the corresponding trifluoromethylated derivatives.Pentafluoroethylated compounds were similarly obtained from the reac
- Watanabe, Shoji,Fujita, Tsutomu,Sakamoto, Masami,Mino, Yasuhiro,Kitazume, Tomoya
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- The interaction of 4-ethoxy-1,1,1-trifluoro-3-buten-2-one with C-nucleophiles - organo-magnesium and -zinc compounds
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4-Ethoxy-1,1,1-trifluoro-3-buten-2-one (1) reacts with phenylmagnesium bromide to give ethoxy group substitution products while the reaction of 1 with organozinc compounds gives products arising from 1,2-addition to the carbonyl group.Enone 1 reacts with electron-rich aromatic systems such as indole and N,N-dimethylaniline in the presence of a Lewis acid catalyst to give a β-arylvinyltrifluoromethylketone.
- Gorbunova, M. G.,Gerus, I. I.,Kukhar, V. P.
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- REDUCTION OF AMINO DERIVATIVES OF FLUORINE-CONTAINING Β-DIKETONES BY SODIUM BOROHYDRIDE
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The reduction of β-aminovinyl ketones containing a fluoroalkyl substituent at the carbonyl carbon atom leads in the general case to a mixture of the corresponding β-hydroxy ketone, substituted allyl alcohol, and 1,3-diol.The experimental conditions and st
- Ratner, V. G.,Pashkevich, K. I.
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p. 1046 - 1049
(2007/10/02)
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- Reactions of Trifluoromethyl Bromide and Related Halides: Part 9. Comparison between Additions to Carbonyl Compounds, Enamines, and Sulphur Dioxide in the Presence of Zinc
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A Barbier procedure, under moderate pressure, was used for the trifluoromethylation of various carbonyl compounds, starting from trifluoromethyl bromide and zinc in pyridine.Trifluoromethyl methanols were obtained from aldehydes and trifluoromethyl ketones from activated esters.Ethyl benzoate, or acetone, induced the formation of the solvated trifluoromethylzinc derivatives which did not react with carbonyl cpompounds.Consequently, the Barbier condensation in that case was considered to involve nascent organometallics reacting near the zinc surface.The reaction with sulphur dioxide, leading to trifluoromethanesulphinate, showed striking differences from that of carbonyl compounds.It was shown that the main pathway occcured in solution.This condensation was interpreted by the initial formation of sulphur dioxide radical anion, which reacts with trifluoromethyl bromide by a single-electron-transfer process.Attempts to condense iminium salts failed when a hydrogen atom was lacking in the α position.When the iminium ion can be transformed in situ to an enamine, a reaction occured, leading to α-trifluoromethyl ketones.This condensation was interpreted by a chain mechanism involving trifluoromethyl radicals.
- Tordeux, Marc,Francese, Catherine,Wakselman, Claude
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p. 1951 - 1957
(2007/10/02)
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- SYNTHETIC APPROACH TO STEREOISOMERS OF ALLYLIC ALCOHOLS POSSESING A TRIFLUOROMETHYL GROUP
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A number of stereoisomers of optically pure allylic alcohols with a trifluoromethyl group were prepared, utilizing the enantiotopic specifity of assymetric hydrolysis of their acetates by hydrolyses.Their absolute configurat
- Kitazume, Tomoya,Lin, Jeng Tain,Yamazaki, Takashi,Takeda, Mitsunori
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p. 177 - 188
(2007/10/02)
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- Synthesis of Trifluoromethyl-substituted Methanols: a Barbier Procedure under Pressure
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Synthesis of trifluoromethyl methanols can be achieved by stirring a mixture of carbonyl compound, zinc powder, and pyridine under a slight pressure of trifluoromethyl bromide.
- Francese, Catherine,Tordeux, Marc,Wakselman, Claude
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p. 642 - 643
(2007/10/02)
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- PALLADIUM AND NICKEL-CATALYZED PERFLUOROALKYLATION OF ALDEHYDES USING ZINC AND PERFLUOROALKYL HALIDES
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A room temperature method for the conversion of perfluoroalkyl iodides to α-perfluoroalkyl carbinols under Pd or Ni catalysis is reported.The use of trifluoromethyl bromide provides an economical procedure for trifluoromethyl substituted carbinols.
- O'Reilly, Neil J.,Maruta, Masamichi,Ishikawa, Nobuo
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p. 517 - 520
(2007/10/02)
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