- Access to substituted trifluoromethyl ketones using the versatile synthetic intermediate (E)-1,1-dimethyl-2-(1,1,1-trifluoropropan-2-ylidene)hydrazine
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The N,N-dimethylhydrazone of 1,1,1-trifluoroacetone, (E)-1,1-dimethyl-2-(1,1,1-trifluoropropan-2-ylidene)hydrazine, has been shown to undergo a diverse set of reactions following deprotonation with n-butyl-lithium; including alkylation, addition to ketones and aldehydes, as well as palladium-catalyzed cross-couplings with aryl bromides. Mild hydrolysis of the N,N-dimethylhydrazone products from these transformations affords the corresponding trifluoromethyl ketones in good to excellent yields.
- Judd, Ted C.,Brown, Derek B.
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supporting information
p. 4455 - 4458
(2017/10/30)
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- Catalytic highly enantioselective transfer hydrogenation of β-trifluoromethyl nitroalkenes. An easy and general entry to optically active β-trifluoromethyl amines
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In the presence of a thiourea catalyst, β-CF3 nitroalkenes react with Hantzsch esters in a highly enantioselective fashion, giving a broad range of β-CF3 amine precursors with a tertiary stereocentre at the β-position. This reaction
- Martinelli, Emilie,Vicini, Anna Chiara,Mancinelli, Michele,Mazzanti, Andrea,Zani, Paolo,Bernardi, Luca,Fochi, Mariafrancesca
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supporting information
p. 658 - 660
(2015/01/09)
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- Copper-Catalyzed Trifluoromethylation of Aliphatic N-Arylhydrazones: A Concise Synthetic Entry to 2-Trifluoromethylindoles from Simple Aldehydes
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The copper-catalyzed C(sp2)-H trifluoromethylation of N,N-disubstituted hydrazones using the Togni reagent is demonstrated to proceed efficiently for aliphatic aldehyde-derived substrates. The success of the reactions relied on the choice of the N,N-diphenylamino group as the terminal hydrazone amino group where N,N-dialkylamino groups were preferred for (hetero)aromatic aldehyde-derived substrates. In addition, the trifluoromethylated N-arylhydrazones are shown to be ideal substrates for Fischer indole synthesis allowing a straightforward, three-step access to 2-trifluoromethylindole derivatives from simple aldehydes.
- Prieto, Alexis,Landart, Mélissa,Baudoin, Olivier,Monteiro, Nuno,Bouyssi, Didier
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supporting information
p. 2939 - 2943
(2015/09/28)
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- Economical and practical strategies for synthesis of α-trifluoromethylated amines
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A powerful approach to synthesize α-trifluoromethylated amines has been developed. The method is operationally simple, broad in substrate scope and amenable to scale-up using trifluoroacetic anhydride. Meanwhile, the strategy not only provided a versatile approach to synthesize α-trifluoromethylated amines but also provides a new method for exploring the new reactivity of trifluoroacetic anhydride.
- Jiang,Cheng,Yuan
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p. 2406 - 2408
(2016/05/19)
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- Highly efficient synthesis of chiral α-CF3 amines via Rh-catalyzed asymmetric hydrogenation
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Highly enantioselective catalytic asymmetric hydrogenation of α-CF3-enamides has been achieved by employing rhodium-DuanPhos as the catalyst, which provides a readily accessible method for the synthesis of chiral trifluoromethylated amines. The reaction has a broad substrate scope; both aryl- and alkyl-substituted α-CF3-enamides worked smoothly and afford the corresponding chiral amines in high yields and excellent enantioselectivities (up to 99% ee).
- Jiang, Jun,Lu, Wenxin,Lv, Hui,Zhang, Xumu
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supporting information
p. 1154 - 1156
(2015/03/14)
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- Stereoselective transformations of α-trifluoromethylated ketoximes to optically active amines by enzyme-nanometal cocatalysis: Synthesis of (s)-inhibitor of phenylethanolamine n-methyltransferase
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One-pot cascade synthesis of optically active α-trifluoromethylated amines directly from ketoximes was accomplished with the use of Candida antarctica lipase B and catalysts prepared by atomic layer deposition (ALD). Compared to the commercial palladium catalyst, the ALD-prepared catalysts showed much higher activity and afforded various α-trifluoromethylated amides in good yields and with high enantioselectivity. One of the enantiopure amides was further hydrolyzed into the corresponding amine, which was treated as a crucial starting material for total synthesis of (S)-inhibitor of phenylethanolamine N-methyltransferase without loss of chiral information.
- Cheng, Guilin,Wu, Qi,Shang, Zeyu,Liang, Xinhua,Lin, Xianfu
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p. 2129 - 2133
(2014/08/05)
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- Highly selective trifluoroacetic ester/ketone metathesis: An efficient approach to trifluoromethyl ketones and esters
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A highly selective and atom efficient 'trifluoroacetic ester/ketone metathesis' has been sincerely witnessed. Enolizable alkyl (at least two non-hydrogen atoms) aryl ketones were found to react readily with ethyl trifluoroacetate under the promotion of NaH to afford trifluoroacetic ester/ketone exchange products, trifluoromethyl ketones (TFMKs), and aromatic acid esters, which were quite different from the general Claisen condensation products, 1,3-diketones. The outcome of the reaction between ketone and ethyl trifluoroacetate is strongly related to the structures of substrates, the steric congestion caused by alkyl group is in favor of the C-C bond cleavage. DFT investigation further disclosed that the metathesis reaction was a kinetically favored pathway. Using only a slight excess of cheap trifluoromethylation reagent, simple operation and mild conditions make it a practical method for preparation of TFMKs on large scale, as well as a new choice of converting aryl alkyl ketones to aromatic acid esters.
- Zhou, Yuhan,Yang, Dongmei,Luo, Gen,Zhao, Yilong,Luo, Yi,Xue, Na,Qu, Jingping
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p. 4668 - 4674
(2014/06/23)
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- Chemoenzymatic dynamic kinetic resolution of α-trifluoromethylated amines: Influence of substitutions on the reversed stereoselectivity
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Enzymatic resolution of α-trifluoromethylated amines via kinetic resolution (KR), dynamic kinetic resolution (DKR) employing CALB-Pd/Al 2O3, and a one-pot sequential process of KR/DKR/KR was investigated comparatively for the first time. Although CALB-catalyzed KR of α-trifluoromethylated amines with substituents of methyl (1a), isopropyl (1c), phenyl (1d) and benzyl group (1e) can provide good stereoselectivity factors E from 31 to >200 respectively, DKR and sequential process of KR/DKR/KR possess better practical application potential because of the higher conversion (62%-84%) and the similar enantiomeric excesses (90%-99%). The enantiopreference and inversion for the α-trifluoromethylated amines displayed by CALB were observed and explained by docking modes. Namely, for 1,1,1-trifluoro-2-propylamine (1a), the product amide with R-configuration was obtained, and the enantiopreference was converted to S for the amines (1b-1e) with substituents larger than methyl group. The catalysts recycle, and scale-up experiments were demonstrated successfully. All these results indicated the high efficiency and green feature of this enzymatic process, and its application significance.
- Cheng, Guilin,Xia, Bo,Wu, Qi,Lin, Xianfu
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p. 9820 - 9828
(2013/09/02)
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- Synthesis and application of benzyl-TMS derivatives as bench stable benzyl anion equivalents
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The regioselective benzylic metalation of toluenes using BuLi/KO tBu/TMP(H) (LiNK metalation conditions) and subsequent transmetalation to Si by reaction with TMSCl provides a general one-pot procedure for the synthesis of substituted benzyltrimethylsilanes. ArCH 2Si(Me)3 derivatives are bench stable reagents yet can serve as benzyl anion equivalents under mild reaction conditions. Following activation with fluoride they can successfully participate in a wide range of additions to both non-enolizable and enolizable carbonyls. In addition, their use in the synthesis of isochromanones and trifluoromethylated amines is illustrated. The broad synthetic scope and mild practical conditions of use for ArCH2Si(Me)3 reagents demonstrate their general potential as benzyl anion equivalents.
- Das, Manas,O'Shea, Donal F.
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p. 6448 - 6460
(2013/07/26)
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- Synthesis of trifluoromethyl ketones via tandem Claisen condensation and retro-Claisen C-C bond-cleavage reaction
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A highly efficient, operationally simple approach to trifluoromethyl ketones has been developed that builds on the use of a tandem process involving Claisen condensation and retro-Claisen C-C bond cleavage reaction. Enolizable alkyl phenyl ketones were found to react readily with ethyl trifuoroacetate under the promotion of NaH to afford trifluoroacetic ester/ketone exchange products, trifluoromethyl ketones, which were quite different from the general Claisen condensation products, β-diketones. This procedure uses readily available starting materials and can be extended to the preparation of perfluoroalkyl ketones in excellent yield.
- Yang, Dongmei,Zhou, Yuhan,Xue, Na,Qu, Jingping
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p. 4171 - 4176
(2013/06/05)
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- Exalted resonance demands in the substituent effects on the acetolyses of 2-arylethyl trifluoromethanesulfonates destabilized by cn and cf3 groups
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Substituent effects on the acetolysis rates of 2-aryl-l-cyano-l- (trifluoromethyl)ethyl trifluoromethanesulfonates (α-OTf) and 2-aryl-2-cyano-2-(trifluoromethyl)ethyl trifluoromethanesulfonates (ss-OTf) were investigated by using LArSR equation. The obtained p and r+ values were p = -3.28, r+ = 0.98 and p = -3.48,r+ = 0.93 for the acetolysis of α-OTf and ss-OΥi, respectively. The obtained p values are comparable to those for typical aryl-assisted solvolyses, but the r+ values are much larger. The large r+ values suggest that the ester bond cleavages in the deactivated aryl-assisted solvolyses are assisted by the strong participation of the ss-aryl group.
- Usui, Satoshi,Tsuboya, Shoko,Umezawa, Yukthiro,Hazama, Ken,Okamura, Mutsuo
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experimental part
p. 254 - 260
(2009/05/30)
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- Activation of pig liver esterase in organic media with organic polymers. Application to the enantioselective acylation of racemic functionalized secondary alcohols
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Pig liver esterase (PLE) shows practically no activity in acylation of alcohols with vinylic esters in organic solvents. However, addition of methoxypoly(ethylene glycol) (MPEG), bovine serum albumin (BSA), TentaGelAmino resin (TGA), or aminomethyl polystyrene (AMPS) confers activity to PLE in acylation of alcohols with vinyl propionate in organic solvents of low water content. Polymer-activated PLE showed high enantioselectivities (E > 100) in the acylation of racemic 1-alkoxy-, 1-ethylsulfanyl-, and 1-fluoro-3-aryl-2-propanols as well as racemic 1-phenoxy-2-propanol and racemic 1-methoxy-2-phenoxy-2-propanol. The synthetic utility of polymer-activated PLE has been demonstrated by the gram-scale resolution of 1-methoxy-3-phenyl-2-propanol, 1-ethylsulfanyl-3-phenyl-2-propanol, 1-methoxy-3-p-methoxyphenyl-2-propanol, 1- fluoro-3-phenyl-2-propanol, and 1-methoxy-3-phenoxy-2-propanol. In PLE-catalyzed acylation of alcohols with vinyl propionate, acetaldehyde and propionic acids, both being detrimental to the enzyme, are formed as byproducts. In addition, the water content of the system, which is critical for the activity of pig liver esterase, is lowered because of a competing enzymatic hydrolysis of the acyl donor. The polymers TGA, BSA, and AMPS not only scavenge the aldehyde and the acid through imine formation and neutralization, respectively, but replenish at least in part also the water consumed in the competing hydrolysis of the acyl donor. A recovery of PLE together with the polymer was achieved without major loss of activity through their immobilization on a water-saturated polyaramide membrane, which occurs spontaneously in organic solvents.
- Gais,Jungen,Jadhav
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p. 3384 - 3396
(2007/10/03)
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- New catalytic oxidation of trifluoromethyl carbinols by a ruthenium(II) complex
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The first catalytic oxidation of trifluoromethyl carbinols has been accomplished by a novel ruthenium(II) complex using sodium periodate as an oxidant. Trifluoromethyl ketones were obtained under mild conditions and in excellent yields. (C) 2000 Elsevier Science Ltd.
- Kesavan, Venkitasamy,Bonnet-Delpon, Danièle,Bégué, Jean-Pierre,Srikanth, Abirami,Chandrasekaran, Srinivasan
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p. 3327 - 3330
(2007/10/03)
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- Microbicidal agents based on thiophene-2-carboxylic acid derivatives
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PCT No. PCT/EP97/06368 Sec. 371 Date May 26, 1999 Sec. 102(e) Date May 26, 1999 PCT Filed Nov. 14, 1997 PCT Pub. No. WO98/23605 PCT Pub. Date Jun. 4, 1998Novel microbicidal compositions based on thiophene-2-carboxylic acid derivatives, some of which are k
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- Synthesis and evaluation of 3-trifluoromethyl-7-substituted-1,2,3,4- tetrahydroisoquinolines as selective inhibitors of phenylethanolamine N- methyltransferase versus the α2-adrenoceptor
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A series of 3-trifluoromethyl-1,2,3,4-tetrahydroisoquinolines was synthesized and evaluated as inhibitors of phenylethanolamine N- methyltransferase (PNMT) and as inhibitors of the binding of clonidine at the α2-adrenoceptor. These compounds we
- Grunewald, Gary L.,Caldwell, Timothy M.,Li, Qifang,Criscione, Kevin R.
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p. 3315 - 3323
(2007/10/03)
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- Mise en evidence d'une reactivite specifique des trifluoromethylcetones vis-a-vis du bromure d'allylmagnesium
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We wish to report on an unusual reactivity of allylmagnesium bromide.This Grignard reagent acts as a reducing agent towards trifluoromethylated ketones.A single electron transfer is suggested to explain the reductive process.By using an excess of allylmagnesium bromide, an exclusive addition reaction is obtained.The stereochemistry of both addition and reduction reactions is discussed. - Keywords: Trifluoromethyl ketones; Trifluoromethyl alcohols; Allylmagnesium bromide; Single electron transfer; Stereochemistry; NMR spectroscopy; IR spectroscopy; Mass spectrometry
- Felix, Caroline,Laurent, Andre,Mison, Pierre
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- Synthesis of CF3-Substituted Quinolines from β-Chloro-β-trifluoromethyl-vinylaldehydes. I.
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3-(Trifluoromethyl)-acroleines 2 have been synthesized through VILSMEIER's reaction from α-Trifluoromethylketones 1.The reaction of 2 with anilines and naphthylamines gives in good yields 2-trifluoromethylquinolines 4 and benzoquinolines 5.
- Greif, Dieter,Riedel, Dirk,Feindt, Andreas,Pulst, Manfred
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- A New and Efficient Synthesis of Trifluoromethyl Ketones from Carboxylic Acids. Part I.
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Trifluoromethyl ketones can be prepared in good yield from primary carboxylic acid chlorides by reaction with pyridine and trifluoroacetic anhydride followed by aqueous work up.
- Boivin, Jean,El Kaim, Laurent,Zard, Samir Z.
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p. 2573 - 2584
(2007/10/02)
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- Process for the preparation of insecticidal, nematicidal and acaricidal 4-substituted-5-(trifluoromethyl)pyrrole-3-carbonitrile compounds
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There is provided a process for the preparation of 4-substituted-5-(trifluoromethyl)pyrrole-3-carbonitrile compounds which are useful as insecticidal, nematicidal and acaricidal agents.
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- An expedient access to trifluoromethyl ketones from carboxylic acids
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Trifluoromethyl ketones are prepared in good yield from carboxylic acid chlorides by reaction with pyridine and trifluoroacetic anhydride.
- Boivin, Jean,El Kaim, Laurent,Zard, Samir Z.
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p. 1285 - 1288
(2007/10/02)
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- Oxidation of Fluoroalkyl-Substituted Carbinols by the Dess-Martin Reagent
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The efficient oxidation of mono-, di-, tri-, and perfluoroalkyl-substituted carbinols has been accommplished by the Dess-Martin periodinane oxidant.A variety of functional groups are compatible with the oxidation procedure.Monitoring the oxidation by 19F NMR indicated that a discreet periodinane intermediate is formed during the course of the reaction.Nonnucleophilic or sterically encumbered α-thiofluoro carbinols were readily oxidized; however, a nucleophilic α-thio-substituted trifluoromethyl carbinol was not.A tert-butyl alcohol modified periodinane oxidant was ultimately employed to achieve oxidation in this example.
- Linderman, Russell J.,Graves, David M.
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p. 661 - 668
(2007/10/02)
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Secondary aziridiness, substituted by a trifluoromethyl group were prepared by reacting Grignard reagents with oximes or a N,N,N-trimethylhydrazonium salt bearing a trifluoromethyl substituent. Contrary to the results obtained with hydrogenated substrates, ethyl magnesium bromide acted exclusively as a reducing agent. The structure of aziridine 5a was determined from X-ray crystallographic data.
- Quinze,Laurent,Mison,Faure
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p. 211 - 232
(2007/10/02)
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- NOUVELLE SYNTHESE DE TRIFLUOROMETHYLCETONES ET D' α-BROMO TRIFLUOROMETHYLCETONES
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We report a new method for the preparation of trifluoromethylketones, as an alternative to the use of organometallics.The condensation of phosphonium ylides with trimethylsilyl trifluoroacetate provides silyloxy enol ethers whose hydrolysis leads to trifluoromethylketones.Bromation of the same silyloxy enol ether is also a convenient preparation of α-bromo trifluoromethylketone.
- Begue, J. P.,Mesureur, D.
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p. 271 - 282
(2007/10/02)
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- AN EFFICIENT PROCEDURE FOR THE OXIDATION OF FLUORINATED CARBINOLS
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The oxidation of di and trifluorocarbinols has been accomplished in high yields using the Dess-Martin periodane oxidant.
- Linderman, Russell J.,Graves, David M.
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p. 4259 - 4262
(2007/10/02)
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- Reactions de Wittig et d'Horner-Emmons en serie trifluoromethylee: synthese de nouveaux F-alkyl esters isomeres α,β et β,γ insatures
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New F-alkyl α,β and β,γ-unsaturated esters were obtained by Wittig and Horner-Emmons reactions using n-butyl and benzyl trifluoromethyl ketones.A mechanism for formation is discussed.
- Trabelsi, Hedi,Bertaina, Brigitte,Cambon, Aime
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p. 426 - 431
(2007/10/02)
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