- Ion-Molecule Reactions in Gaseous CF4/CO Mixtures. Formation and Reactivity of CF3CO(1+) Ions
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The reactivity of CF3CO(1+) ions, formed via two different routes, has been studied in the gas phase by the joint use of mass spectrometric and radiolytic techniques, spanning a pressure range from 10-8 Torr to ca. 1 atm.The 23 kcal mol-1 exothermic addition of CF3(1+) to CO provides a route to CF3CO(1+) requiring third-body stabilization of the adduct ion.In the 10-8 Torr pressure regime of Fourier transform ion cyclotron resonance (FT-ICR) spectrometry, CF3CO(1+) ions from electron ionization (EI) induced fragmentation of trifluoroacetic anhydride yield NuCF3(1+) products from oxygen-centered nucleophiles (Nu) and XC6H4CO(1+) ions from aromatics (C6H5X).At ca. 1 atm trifluoroacetylated products are efficiently formed even with strongly deactivated aromatics, showing distinct intra- and intermolecular selectivity features pertaining to the reactant CF3CO(1+) ions.The reactivity pattern is interpreted according to a kinetic interplay of collisional and chemical events depending on the activation of C6H5X toward electrophilic attack.
- Cacace, Fulvio,Crestoni, Maria Elisa,Fornarini, Simonetta
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- UNUSUALLY LARGE KINETIC DEUTERIUM ISOTOPE EFFECTS ON OXIDATION REACTIONS. 1. THE MECHANISM OF HYDROXIDE-CATALYSED PERMANGANATE OXIDATION OF PhCD(CF3)OH AND PhCD(CH3)OH IN WATER
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The oxidation of 1-phenyl-2,2,-trifluoroethanol (ROH) with potassium permanganate in 0.2 M aqueous sodium hydroxide solution at 25 deg C provides 2,2,2-trifluoroacetophenone as the sole product.The reaction rate constant, which was measured under pseudo-first order conditions by following the decrease in substrate concentration as a function of time, was found to be substantially smaller than previously reported.The primary kinetic deuterium isotope effect was measured as k2H/k2D= 14.7 +/- 1.0.A hydrogen-transfer mechanism involving significant tunnelling is proposed.The oxidation of 1-phenylethanol under similar reaction conditions yields acetophenone as the initial product.The kinetic deuterium isotope effect was found to be k2H/k2D = 5.2 +/- 0.8.
- Thibblin, Alf
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- CARBON-14 KINETIC ISOTOPE EFFECTS AND MECHANISM IN THE SOLVOLYSIS OF 1,1,1-TRIFLUORO-2-PHENYL-2-PROPYL-3-14C p-TOLUENESULFONATE
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In the solvolysis of 1,1,1-trifluoro-2-phenyl-2-propyl-3-14C p-toluenesulfonate there is only a small βC isotope effect, k/βk = 1.008+/-0.002.The result is as expected for a branching SN1/E1 reaction (mostly SN1).This is the first example of such a measurement.
- Guo, Zili,Fry, Arthur
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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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- Decarbonylative Fluoroalkylation at Palladium(II): From Fundamental Organometallic Studies to Catalysis
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This Article describes the development of a decarbonylative Pd-catalyzed aryl-fluoroalkyl bond-forming reaction that couples fluoroalkylcarboxylic acid-derived electrophiles [RFC(O)X] with aryl organometallics (Ar-M′). This reaction was optimized by interrogating the individual steps of the catalytic cycle (oxidative addition, carbonyl de-insertion, transmetalation, and reductive elimination) to identify a compatible pair of coupling partners and an appropriate Pd catalyst. These stoichiometric organometallic studies revealed several critical elements for reaction design. First, uncatalyzed background reactions between RFC(O)X and Ar-M′ can be avoided by using M′ = boronate ester. Second, carbonyl de-insertion and Ar-RF reductive elimination are the two slowest steps of the catalytic cycle when RF = CF3. Both steps are dramatically accelerated upon changing to RF = CHF2. Computational studies reveal that a favorable F2C-H - -X interaction contributes to accelerating carbonyl de-insertion in this system. Finally, transmetalation is slow with X = difluoroacetate but fast with X = F. Ultimately, these studies enabled the development of an (SPhos)Pd-catalyzed decarbonylative difluoromethylation of aryl neopentylglycol boronate esters with difluoroacetyl fluoride.
- Lalloo, Naish,Malapit, Christian A.,Taimoory, S. Maryamdokht,Brigham, Conor E.,Sanford, Melanie S.
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supporting information
p. 18617 - 18625
(2021/11/16)
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- Novel Friedel-Crafts reaction method and catalyst thereof
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The present invention relates to a novel method for preparing or synthesizing an acylated or alkylated aryl compound, such as acylated or alkylated benzene, through a reaction called Friedel-Crafts, and a novel catalyst for the method. The present invention particularly relates to a novel environment-friendly method for synthesizing the Friedel-Crafts reaction of the acylated or alkylated compound.
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Paragraph 0196-0199
(2020/02/29)
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- REACTIVE EXTRACTION OF WATER
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Described herein are methods and compounds for extracting water from an aqueous solution. For example, some embodiments include method for extracting water from an aqueous solution, comprising contacting the aqueous solution with a compound comprising one or more carbonyl moieties having an equilibrium constant for a hydration of the carbonyl moiety of at least about 0.5; separating a composition comprising the hydrated compound from the aqueous solution; and reacting the hydrated compound to obtain water.
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Paragraph 0073-0076
(2020/04/09)
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- Decarboxylative and Deaminative Alkylation of Difluoroenoxysilanes via Photoredox Catalysis: A General Method for Site-Selective Synthesis of Difluoroalkylated Alkanes
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A general method for site-selective difluoroalkylation of alkyl carboxylic redox esters with difluoroenoxysilanes through photoredox-catalyzed decarboxylative reaction has been developed. The reaction can also be extended to aliphatic amine derived pyridinium salts. This method has the advantages of high efficiency, mild reaction conditions, and broad substrate scope, including primary, secondary, and sterically hindered tertiaryl alkyl substrates, providing a general and practical route for applications in organic synthesis and pharmaceutical studies.
- Song, Heng,Cheng, Ran,Min, Qiao-Qiao,Zhang, Xingang
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supporting information
p. 7747 - 7751
(2020/10/09)
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- Catalytic AgF-Initiated Intramolecular 1,3-Sulfonyl Migration of gem-Difluorovinyl Sulfonates to α,α-Difluoro-β-ketosulfones
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A 1,3-sulfonyl migration of difluorovinyl sulfonates initiated by a catalytic amount of silver fluoride is presented. α,α-Difluoro-β-ketosulfones were successfully prepared in excellent yields. This method features high chemoselectivity, good functional group tolerance, high atom economy, and mild, environmentally benign reaction conditions. Furthermore, mechanistic experiments indicate that this migration proceeds in an intermolecular pathway and the corresponding sulfinates are possible intermediates.
- Chen, Lei,Li, Xiong,Li, Yue,Lian, Zhong,Sun, Haotian,Xiong, Baojian,Xu, Jie
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supporting information
p. 9263 - 9268
(2020/11/30)
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- Decarboxylative Amination: Diazirines as Single and Double Electrophilic Nitrogen Transfer Reagents
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The ubiquity of nitrogen-containing small molecules in medicine necessitates the continued search for improved methods for C-N bond formation. Electrophilic amination often requires a disparate toolkit of reagents whose selection depends on the specific structure and functionality of the substrate to be aminated. Further, many of these reagents are challenging to handle, engage in undesired side reactions, and function only within a narrow scope. Here we report the use of diazirines as practical reagents for the decarboxylative amination of simple and complex redox-active esters. The diaziridines thus produced are readily diversifiable to amines, hydrazines, and nitrogen-containing heterocycles in one step. The reaction has also been applied in fluorous phase synthesis with a perfluorinated diazirine.
- Chandrachud, Preeti P.,Wojtas, Lukasz,Lopchuk, Justin M.
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supporting information
p. 21743 - 21750
(2021/01/11)
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- PROCESSES AND COMPOUNDS FOR THE DECARBOXYLATIVE AMINATION OF REDOX-ACTIVE ESTERS WITH DIAZIRINES
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The invention described herein relates generally to processes for the synthesis of amine-containing organic compounds. More specifically, described herein relates to processes for the decarboxylative amination of redox-active esters with diazirines and the products formed thereof. Compounds for use in the above processes are also described.
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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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- Catalytic Enantioselective Direct Aldol Addition of Aryl Ketones to α-Fluorinated Ketones
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The catalytic enantioselective synthesis of α-fluorinated chiral tertiary alcohols from (hetero)aryl methyl ketones is described. The use of a bifunctional iminophosphorane (BIMP) superbase was found to facilitate direct aldol addition by providing the strong Br?nsted basicity required for rapid aryl enolate formation. The new synthetic protocol is easy to perform and tolerates a broad range of functionalities and heterocycles with high enantioselectivity (up to >99:1 e.r.). Multi-gram scalability has been demonstrated along with catalyst recovery and recycling. 1H NMR studies identified a 1400-fold rate enhancement under BIMP catalysis, compared to the prior state-of-the-art catalytic system. The utility of the aldol products has been highlighted with the synthesis of various enantioenriched building blocks and heterocycles, including 1,3-aminoalcohol, 1,3-diol, oxetane, and isoxazoline derivatives.
- Barber, David M.,Dixon, Darren J.,Thomson, Connor J.
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supporting information
p. 5359 - 5364
(2020/02/28)
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- Catalytic Oxidation of Alcohols Using a 2,2,6,6-Tetramethylpiperidine-N-hydroxyammonium Cation
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The oxidation of alcohols to aldehydes, ketones, and carboxylic acids is reported using 2,2,6,6-tetramethylpiperidine-4-acetamido-hydroxyammonium tetrafluoroborate as a catalyst in conjunction with sodium hypochlorite pentahydrate as a terminal oxidant. The reaction is generally complete within 30–120 min using an acetonitrile/water mix as the solvent, and no additives are required. Product yields are good to excellent and of particular note is that the methodology can be used to access aryl α-trifluoromethyl ketones.
- Miller, Shelli A.,Bisset, Kathryn A.,Leadbeater, Nicholas E.,Eddy, Nicholas A.
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supporting information
p. 1413 - 1417
(2019/01/04)
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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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- Visible light-promoted umpolung coupling of aryl tri-/difluoroethanones with 2-alkenylpyridines
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Tertiary alcohols bearing a trifluoromethyl group are of considerable medicinal interest. Using an umpolung strategy, we herein report the first intermolecular reductive cross-coupling of aryl tri-/difluoroethanones with 2-alkenylpyridines with the aid of a Br?nsted acid catalyst upon visible-light irradiation. This metal-free reaction is operationally simple and performed at ambient temperature, allowing access to desired tertiary alcohols with tri-/difluoromethyl groups in moderate to excellent yields. The commercially available and easily handled Hantzsch ester effectively serves as an electron donor, as well as a hydrogen atom source.
- Xu, Xiao,Min, Qing-Qiang,Li, Na,Liu, Feng
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supporting information
p. 11017 - 11020
(2018/10/08)
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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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- New entry for fluorinated carbocycles: Unprecedented 3,6-disubstituted 1,1,2,2-tetrafluorocyclohexane derivatives
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The synthetic protocols for symmetrical/unsymmetrical 3,6-disubstituted 1,1,2,2-tetrafluorocyclohexane molecules were successfully established for the first time. Some of thus obtained tetrafluorinated cyclohexanes underwent recrystallization to afford trans-configured products preferentially. One of the unsymmetrical trans-disubstituted tetrafluorocyclohexanes, trans-1-ethyl-2,2,3,3-tetrafluoro-4-[4-(trans-4-n-propylcyclohex-1-yl)phenyl]cyclohexane, was found to possess a low birefringence Δn (0.073) and a large negative dielectric anisotropy Δε (–9.4) in a binary mixture system, which were very prominent as characteristics of LC molecules in VA-mode driving LC displays.
- Yamada, Shigeyuki,Hashishita, Shohei,Konishi, Hideaki,Nishi, Yuji,Kubota, Toshio,Asai, Tomoyuki,Ishihara, Takashi,Konno, Tsutomu
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- A asymmetric synthesis fluorine methyl chiral season carbon compound containing three method
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The invention belongs to the technical field of an organic synthesis method, and particularly relates to a method for asymmetrically synthesizing a chiral quaternary carbon compound containing trifluoromethyl. The method comprises the following step: reacting trifluoromethyl nitroolefin with a 2-acetylaza aromatic compound to asymmetrically synthesize (R)-3- trifluoromethyl-3-nitryl methyl-1-(aza aromatic ring-2-yl)-butyl-1-acetone under the catalysis of bisoxazoline chiral ligand and a nickel catalyst in an organic solvent by adopting asymmetrically catalytic Michael addition reaction. The method is high in reaction yield and high in optical purity. The method disclosed by the invention can be used for a preparation tool for providing a trifluoromethyl quaternary carbon chiral compound.
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Paragraph 0030; 0031; 0032
(2017/08/25)
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- A β-Carbon elimination strategy for convenient: In situ access to cyclopentadienyl metal complexes
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The electronic and steric properties of tailored cyclopentadienyl (Cp) ligands are powerful handles to modulate the catalytic properties of their metal complexes. This requires the individual preparation, purification and storage of each ligand/metal combination. Alternative, ideally in situ, complexation protocols would be of high utility. We disclose a new approach to access Cp metal complexes. Common metal precursors rapidly react with cyclopentadienyl carbinols via β-carbon eliminations to directly give the Cp-metal complexes. An advantage of this is the direct and flexible use of storable pre-ligands. No auxiliary base is required and the Cp complexes can be prepared in situ in the reaction vessel for subsequent catalytic transformations.
- Smits,Audic,Wodrich,Corminboeuf,Cramer
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p. 7174 - 7179
(2017/10/05)
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- Stoichiometric and Catalytic Aryl-Perfluoroalkyl Coupling at Tri-tert-butylphosphine Palladium(II) Complexes
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This Communication describes studies of Ph-RF (RF = CF3 or CF2CF3) coupling at Pd complexes of general structure (PtBu3)PdII(Ph)(RF). The CF3 analogue participates in fast Ph-CF3 coupling (II complex. Furthermore, they show that this undesired pathway can be circumvented by changing from a CF3 to a CF2CF3 ligand. Ultimately, the insights gained from stoichiometric studies enabled the identification of Pd(PtBu3)2 as a catalyst for the Pd-catalyzed cross-coupling of aryl bromides with TMSCF2CF3 to afford pentafluoroethylated arenes.
- Ferguson, Devin M.,Bour, James R.,Canty, Allan J.,Kampf, Jeff W.,Sanford, Melanie S.
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supporting information
p. 11662 - 11665
(2017/09/07)
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- Synthesis of trifluoromethyl moieties by late-stage copper (I) mediated nucleophilic fluorination
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The nucleophilic fluorination of bromodifluoromethyl derivatives mediated by the complex (PPh3)3CuF is described. Under the reaction conditions, different trifluoroacetates, trifluoroketones, trifluoroarenes and trifluoroacetamides were obtained in good yields.
- Bermejo Góme, Antonio,González, Miguel A. Cortés,Lübcke, Marvin,Johansson, Magnus J.,Schou, Magnus,Szabó, Kálmán J.
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- Dendrimer-like core cross-linked micelle stabilized ultra-small gold nanoclusters as a robust catalyst for aerobic oxidation of α-hydroxy ketones in water
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As one of the most general and promising stabilizers, dendrimers have been widely used to prepare ultra-small gold nanoclusters. However, the complex synthesis of dendrimers hinders the further application of protected nanoclusters. Here we report a facile strategy to prepare an alternative material via core cross-linking of self-assembled micelles. The resulting dendrimer-like core cross-linked micelles (DCCMs) retain the main characteristics of dendrimers and avoid complex chemical synthesis. As expected, the DCCMs could easily encapsulate gold nanoparticles within their cores. The ultra-small clusters of Au5 were prepared without the participation of external reductants. Importantly, the DCCM stabilized noble gold clusters furnish excellent catalytic activity and perfect reusability for aerobic oxidation of α-hydroxy ketones in water. Only in open air the oxidation could be repeated up to 48 times with negligible turn-over frequency change. The total turnover number (TON) of the reaction reached unexpectedly >48 000, the highest TON for metal catalysed oxidation of hydroxy ketones so far. The further mechanism study hints that the carboxylic group of substrates might be involved in the catalytic process. The simple catalyst preparation, the environmentally benign reaction conditions, and the excellent catalytic performance and durability make the novel DCCM protected gold nanocluster a green catalyst.
- Yu, Yangyang,Lin, Chenlu,Li, Bing,Zhao, Pengxiang,Zhang, Shiyong
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supporting information
p. 3647 - 3655
(2016/07/06)
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- Copper-Mediated Trifluoroacetylation of Arenediazonium Salts with Ethyl Trifluoropyruvate
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A copper-mediated trifluoroacetylation of various arenediazonium salts with ethyl trifluoropyruvate is reported. The reaction proceeded smoothly under mild conditions at room temperature giving trifluoromethyl aryl ketones in moderate to good yields. A variety of functional groups, including methoxy, hydroxy, ester, ketone, trifluoromethyl, and halide groups, were well tolerated. A possible reaction mechanism involving an aryl radical intermediate was proposed and supported by experimental evidence. This reaction provides a new route to trifluoromethyl aryl ketones, notable synthetic targets, from the corresponding anilines.
- Wu, Wei,Tian, Qinli,Chen, Taotao,Weng, Zhiqiang
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supporting information
p. 16455 - 16458
(2016/11/11)
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- Palladium-catalyzed carbonylative coupling of aryl iodides with an organocopper reagent: A straightforward procedure for the synthesis of aryl trifluoromethyl ketones
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A palladium-catalyzed carbonylative coupling of aryl iodides with a (trifluoromethyl)copper reagent has been developed. A wide range of substrates have been transformed into their corresponding trifluoromethyl ketones in good to excellent yields under mild conditions with high efficiency and excellent functional-group compatibility. Preliminary mechanistic investigations suggest that the transmetallation of an acylpalladium intermediate with the (trifluoromethyl)copper reagent seems to be involved in the catalytic cycle. Notably, this report represents one of the few studies on carbonylative coupling with organocopper reagents.
- Zhu, Fengxiang,Yang, Guangfu,Zhou, Shaolin,Wu, Xiao-Feng
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p. 57070 - 57074
(2016/07/07)
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- Aldehyde and Ketone Synthesis by P450-Catalyzed Oxidative Deamination of Alkyl Azides
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Heme-containing proteins have recently attracted increasing attention for their ability to promote synthetically valuable transformations not found in nature. Following the recent discovery that engineered variants of myoglobin can catalyze the direct conversion of organic azides into aldehydes, we investigated the azide oxidative deamination reactivity of a variety of hemoproteins featuring different heme coordination environments. Our studies show that although several heme-containing enzymes possess basal activity in this reaction, an engineered variant of the bacterial cytochrome P450 CYP102A1 constitutes a particularly efficient biocatalyst for promoting this transformation, and it exhibits a broad substrate scope along with high catalytic activity (up to 11 300 turnovers), excellent chemoselectivity, and enhanced reactivity toward secondary alkyl azides to yield ketones. Mechanistic studies and Michaelis–Menten analyses provided insight into the mechanism of the reaction and the impact of active-site mutations on the catalytic properties of the P450. Altogether, these studies demonstrate that engineered P450 variants represent promising biocatalysts for the synthesis of aryl aldehydes and ketones through the oxidative deamination of alkyl azides under mild reaction conditions.
- Giovani, Simone,Alwaseem, Hanan,Fasan, Rudi
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p. 2609 - 2613
(2016/08/30)
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- Efficient conversion of primary azides to aldehydes catalyzed by active site variants of myoglobin
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The oxidation of primary azides to aldehydes constitutes a convenient but underdeveloped transformation for which no efficient methods are available. Here, we demonstrate that engineered variants of the hemoprotein myoglobin can catalyze this transformation with high efficiency (up to 8500 turnovers) and selectivity across a range of structurally diverse aryl-substituted primary azides. Mutagenesis of the 'distal' histidine residue was particularly effective in enhancing the azide oxidation reactivity of myoglobin, enabling these reactions to proceed in good to excellent yields (37-89%) and to be carried out at a synthetically useful scale. Kinetic isotope effect, isotope labeling, and substrate binding experiments support a mechanism involving heme-catalyzed decomposition of the organic azide followed by alpha hydrogen deprotonation to generate an aldimine which, upon hydrolysis, releases the aldehyde product. This work provides the first example of a biocatalytic azide-to-aldehyde conversion and expands the range of non-native chemical transformations accessible through hemoprotein-mediated catalysis.
- Giovani, Simone,Singh, Ritesh,Fasan, Rudi
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p. 234 - 239
(2015/12/30)
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- Convenient stereoselective synthesis of β-perfluoroalkyl α,β-unsaturated esters via H?rner-Wadsworth-Emmons reactions
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Condensation of H?rner-Wadsworth-Emmons reagents 3 and ketones 2 with a perfluoroalkyl (Rf) moiety prepared in situ was proved to be significantly efficient and powerful methods for the construction of a wide variety of α,β-unsaturated esters with Rf and R1 groups both at the β-position due to convenient avoidance of usually tedious as well as troublesome isolation steps of these ketones 2.
- Yamazaki, Takashi,Mano, Noriko,Hikage, Reo,Kaneko, Tsutomu,Kawasaki-Takasuka, Tomoko,Yamada, Shigeyuki
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p. 8059 - 8066
(2015/12/30)
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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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- One-pot multistep synthesis of trisubstituted alkenes from N -tosylhydrazones and alcohols
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A one-pot procedure for the synthesis of trisubstituted alkenes from N-tosylhydrazones and alcohols is reported. This procedure combines the aerobic oxidation reaction and Wittig reaction in one pot, which avoids using of environmentally toxic oxidants and isolation of the intermediates. The simple procedure makes it very attractive for the synthesis of trisubstituted alkenes when alcohols are used as starting materials. A variety of trisubstituted alkenes as well as trifluoromethyl-substituted alkenes were obtained in moderate to good yields (up to 84%) with good E-selectivity (up to 99%). Georg Thieme Verlag Stuttgart.New York.
- Sha, Qiang,Wei, Yunyang
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supporting information
p. 2353 - 2361
(2014/11/08)
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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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- 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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- Catalytic asymmetric hydrogenation of α-CF3- or β-CF3-Substituted acrylic acids using Rhodium(I) complexes with a combination of chiral and achiral ligands
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Only the mixture works! Acrylic acid derivatives with CF3 substituents in α or β position were efficiently hydrogenated in the presence of a RhI complex with a chiral secondary phosphine oxide (SPO; see scheme) and an achiral Ph3P as ligands. The corresponding propanoic acid derivatives were obtained with generally high conversion (>99 %) and high enantioselectivity (92->99 %). Copyright
- Dong, Kaiwu,Li, Yang,Wang, Zheng,Ding, Kuiling
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supporting information
p. 14191 - 14195
(2014/01/06)
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- Organocatalysis approach to trifluoromethylation with fluoroform
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The organic base methodology exploits an access to generate the "trifluoromethyl anion" for carbonyl, ester, acid halide, epoxide, deuterium donor, and carbon dioxide substrates to afford the trifluoromethylation products with good overall efficiency even in organocatalysis conditions. The NMR analysis of the mixture of fluoroform and P4-base shows no change thereof. However, on addition of electrophiles, the trifluoromethylation products were obtained efficiently.
- Zhang, Yuan,Fujiu, Motohiro,Serizawa, Hiroki,Mikami, Koichi
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supporting information
p. 367 - 371
(2014/01/06)
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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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- 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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- Taming of fluoroform: Direct nucleophilic trifluoromethylation of Si, B, S, and C centers
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Fluoroform (CF3H), a large-volume by-product of the manufacture of Teflon, refrigerants, polyvinylidene fluoride (PVDF), fire-extinguishing agents, and foams, is a potent and stable greenhouse gas that has found little practical use despite the growing importance of trifluoromethyl (CF3) functionality in more structurally elaborate pharmaceuticals, agrochemicals, and materials. Direct nucleophilic trifluoromethylation using CF3H has been a challenge. Here, we report on a direct trifluoromethylation protocol using close to stoichiometric amounts of CF3H in common organic solvents such as tetrahydrofuran (THF), diethyl ether, and toluene. The methodology is widely applicable to a variety of silicon, boron, and sulfur-based electrophiles, as well as carbon-based electrophiles.
- Surya Prakash,Jog, Parag V.,Batamack, Patrice T. D.,Olah, George A.
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p. 1324 - 1327
(2013/02/22)
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- Purification and characterization of an NADH-dependent alcohol dehydrogenase from Candida maris for the synthesis of optically active 1-(pyridyl)ethanol derivatives
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A novel (R)-specific alcohol dehydrogenase (AFPDH) produced by Candida maris IFO10003 was purified to homogeneity by ammonium sulfate fractionation, DEAE-Toyopearl, and Phenyl-Toyopearl, and characterized. The relative molecular mass of the native enzyme was found to be 59,900 by gel filtration, and that of the subunit was estimated to be 28,900 on SDS-polyacrylamide gel electrophoresis. These results suggest that the enzyme is a homodimer. It required NADH as a cofactor and reduced various kinds of carbonyl compounds, including ketones and aldehydes. AFPDH reduced acetylpyridine derivatives, β-keto esters, and some ketone compounds with high enantioselectivity. This is the first report of an NADH-dependent, highly enantioselective (R)-specific alcohol dehydrogenase isolated from a yeast. AFPDH is a very useful enzyme for the preparation of various kinds of chiral alcohols.
- Kawano, Shigeru,Yano, Miho,Hasegawa, Junzo,Yasohara, Yoshihiko
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experimental part
p. 1055 - 1060
(2012/02/03)
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- Fluoro-substituted ketones from nitriles using acidic and basic reaction conditions
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Fluoro-substituted aliphatic nitriles are shown to undergo the Houben-Hoesch reactions with arenes in CF3SO3H to give fluoro-substituted ketones in good yields. The fluorine substituents appear to enhance the reactivities of the nitriles (and the nitrilium ion intermediates) compared to similar aliphatic nitriles. Fluoro-substituted ketones are also shown to be accessible through the reactions of organometallic reagents and fluoro-substituted nitriles.
- Raja, Erum K.,Klumpp, Douglas A.
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supporting information; experimental part
p. 5170 - 5172
(2011/10/13)
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- Unusual reactions of Grignard reagents toward fluoroalkylated esters
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Fluorine-containing esters were demonstrated to be convenient substrates for construction of the corresponding ketones by low temperature reaction with Grignard reagents followed by warming up to 0 °C, while heating the mixture up to 80 °C readily promoted the reduction of the ketones obtained by the generated magnesium alkoxides whose mechanism was speculated as Meerwein-Ponndorf-Verley type reduction by computational technique.
- Yamazaki, Takashi,Terajima, Tsukasa,Kawasaki-Taskasuka, Tomoko
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p. 2419 - 2424
(2008/09/18)
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- Remarkable substituent effects on the oxidizing ability of tetraarylbismuthonium tetrafluoroborates in alcohol oxidation
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Substituent effects on the oxidizing ability of tetraarylbismuthonium tetrafluoroborates in alcohol oxidation are reported. Intermolecular and intramolecular competition experiments on geraniol oxidation by the combined use of tetraarylbismuthonium tetrafluoroborates and N,N,N′,N′- tetramethylguanidine (TMG) have revealed that the oxidizing ability of the bismuthonium salt increases by the introduction of methyl groups at the ortho position and an electron-withdrawing group at the para position of the aryl ligands. The intermolecular and intramolecular H/D kinetic isotope effects observed for the competitive oxidation of p-bromobenzyl alcohols have shown that the present oxidation reaction consists of fast pre-equilibrium leading to alkoxytetraarylbismuth(V) intermediates (first step) and α-hydrogen abstraction by the aryl ligand attached to the bismuth (second step). The experimental results demonstrate that the electron-deficient aryl ligands enhance the electrophilicity at the bismuth center to put forward the first step and that the bulky ligands destabilize the alkoxybismuth(V) intermediates to accelerate the second step. The newly explored mesityl- and 2,6- xylyltriarylbismuthonium salts have proven to convert primary and secondary alcohols to the corresponding carbonyl compounds with high efficiency under mild conditions. A remarkable steric effect of these oxidants has also been exhibited in the chemoselective oxidation between primary and secondary benzylic alcohols.
- Matano, Yoshihiro,Suzuki, Takeshi,Iwata, Takaharu,Shinokura, Tomonori,Imahori, Hiroshi
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experimental part
p. 1621 - 1628
(2009/05/06)
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- Process research on the preparation of 1-(3-trimethylsilylphenyl)-2,2,2- trifluoroethanone by a friedel-crafts acylation reaction
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Zifrosilone (1-(3-trimethylsilylphenyl)-2,2,2-trifluoroethanone) (3) is a Cholinesterase inhibitor that has been studied for the treatment of Alzheimer's disease. Process research has been carried out on a route to convert phenyltrimethylsilane to 3 by Friedel-Crafts acylation using trifluoroacetic anhydride. Kinetics and products analyses suggest that the optimal conditions for this reaction are noncatalytic amounts of aluminum chloride, dichloromethane solvent and as low a temperature as can be practically used in a scaled-up process. Significant separation challenges to isolate 3 from the isomer byproduct 1-(4-trimethykilylphenyl)-2,2,2-trifluoroethanone) (4) remain. These challenges were investigated using vapor-liquid equilibrium studies.
- Wolf, Richard A.
-
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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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- Photochemical generation of highly destabilized vinyl cations: The effects of α- and β-trifluoromethyl versus α- and β-methyl substituents
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(Chemical Equation Presented). The photochemical reactions in methanol of the vinylic halides 1-4, halostyrenes with a methyl or a trifluoromethyl substituent at the α- or β-position, have been investigated quantitatively. Next to E/Z isomerization, the reactions are formation of vinyl radicals, leading to reductive dehalogenation products, and formation of vinyl cations, leading to elimination, nucleophilic substitution, and rearrangement products. The vinyl cations are parts of tight ion pairs with halide as the counterion. The elimination products are the result of β-proton loss from the primarily generated α-CH3 and α-CF3 vinyl cations, or from the α-CH3 vinyl cation formed from the β-CH3 vinyl cation via a 1,2-phenyl shift. The β-CF 3 vinyl cation reacts with methanol yielding nucleophilic substitution products, no migration of the phenyl ring producing the α-CF3 vinyl cation occurs. The α-CF3 vinyl cation, which is the most destabilized vinyl cation generated thus far, gives a 1,2-fluorine shift in competition with proton loss. The experimentally derived order of stabilization of the vinyl cations photogenerated in this study, α-CF3 3 3 3, is corroborated by quantum chemical calculations, provided the effect of solvent is taken into account.
- Van Alem, Kaj,Belder, Geerte,Lodder, Gerrit,Zuilhof, Han
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p. 179 - 190
(2007/10/03)
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- Method for expedient synthesis of [18F]-labeled α-trifluoromethyl ketones
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The present invention is directed to a convenient method of synthesizing radiolabeled α-trifluoromethyl ketones by a fluorination reaction. The present invention also relates to imaging agents and markers for identifying cell proliferation, or viral infection. The markers and imaging agents including the radiolabeled α-trifluoromethyl ketones that are prepared by the present method.
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Page/Page column 7
(2008/06/13)
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- Site directed synthesis of mono and disubstituted SF5- polyfluoroalkyl benzenes
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A novel method for the preparation of o-, m-, p-SF5CF 2CFYC6H4X (Y = Br, F and X = m-Br, p-Br, Cl, CH3, CF3, NO2, o-NO2, F, CF 3, CH(CH3)2) derivatives was devised by a two-step reaction: SF5Br-addition to o-, m-, p-CF2= CFC6H4X followed by reaction of AgBF4 with the o-, m-, p-SF5CF2CFBrC6H4X adducts. Additional studies have been carried out with several derivatives and includes the preparation of SF5CF2C(O)C6H5, p-CF3CFBrC6H4NO2, SF 5CF2CF2C6H3(NO 2)2, SF5CF2CF2C 6H3(NH2)2, and an SF 5CF2CF2-containing polyimide and dye. The complete characterization (IR, NMR, and MS) of these compounds is given.
- Winter,Dodean,Smith,Anilkumar,Burton,Gard
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p. 1202 - 1214
(2007/10/03)
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- Carbocation-forming reactions in ionic liquids
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A number of trifluoroacetates, mesylates, and triflates have been studied in ionic liquids. Several lines of evidence indicate that all of these substrates react via ionization to give carbocationic intermediates. For example, cumyl trifluoroacetates give mainly the elimination products, but the Hammett ρ+ value of -3.74 is consistent with a carbocationic process. The analogous exo-2-phenyl-endo-3-deutero-endo-bicyclo-[2.2.1]hept-2-yl trifluoroacetate gives an elimination where loss of the exo-hydrogen occurs from a cationic intermediate. 1-Adamantyl mesylate and 2-adamantyl triflate react to give simple substitution products derived from capture of 1- and 2-adamantyl carbocations by the residual water in the ionic liquid. The triflate derivative of pivaloin, trans-2-phenylcyclopropylcarbinyl mesylate, 2,2-dimethoxycyclobutyl triflate, the mesylate derivative of diethyl (phenylhydroxymethyl)-thiophosphonate, and Z-1-phenyl-5-trimethylsilyl-3-penten- 1-yl trifluoroacetate all give products derived carbocation rearrangements (kΔ processes), anti-7-Norbornenyl mesylate gives products with complete retention of configuration, indicative of involvement of the delocalized 7-norbornenyl cation. 1,6-Methano[10]annulen-11-yl triflate reacts in [BMIM][NTf2] to give 1,6-methano[10]annulen-11-ol, along with naphthalene, an oxidized product derived from loss of trifluoromethanesulfinate ion. Analogous loss of CF3SO2- can be seen in reaction of PhCH(CF3)OTf. Ionic liquids are therefore viable solvents for formation of carbocationic intermediates via kc and k Δ processes.
- Creary, Xavier,Willis, Elizabeth D.,Gagnon, Madeleine
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p. 18114 - 18120
(2007/10/03)
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- Trifluoromethylation of carbonyl compounds with sodium trifluoroacetate
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In the presence of copper(I) iodide as catalyst, a variety of carbonyl compounds, such as aldehydes, ketones and acid anhydrous, could be trifluoromethylated with sodium trifluoroacetate to give the corresponding alcohols in moderate to high yields, and a possible mechanism was proposed to explain the roles of catalyst and solvent in the reaction system.
- Chang, Ying,Cai, Chun
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p. 937 - 940
(2007/10/03)
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- Remarkable substituent effects on the oxidizing ability of triarylbismuth dichlorides in alcohol oxidation
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Substituent effects on the oxidizing ability of triarylbismuth dichlorides were examined by intermolecular and intramolecular competition experiments on geraniol oxidation in the presence of DBU. It was found that the oxidizing ability of the dichlorides increases with increasing electron-withdrawing ability of the para substituents, and by introduction of a methyl group at the ortho position of the aryl ligands attached to the bismuth. The intermolecular and intramolecular H/D kinetic isotope effects observed for the competitive oxidation of p-bromobenzyl alcohols indicate that the rate-determining step involves C-H bond cleavage. Several primary and secondary alcohols were oxidized efficiently under mild conditions by the combined use of newly developed organobismuth(V) oxidants and DBU.
- Matano, Yoshihiro,Hisanaga, Teppei,Yamada, Hisatsugu,Kusakabe, Shingo,Nomura, Hazumi,Imahori, Hiroshi
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p. 8676 - 8680
(2007/10/03)
-
- Alkoxide- and hydroxide-induced nucleophilic trifluoromethylation using trifluoromethyl sulfone or sulfoxide
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(Matrix presented) The first alkoxide- and hydroxide-induced nucleophilic trifluoromethylation of carbonyl compounds, disulfides, and other electrophiles, using phenyl trifluoromethyl sulfone 1a (sulfoxide 1b) is reported. The trifluoromethyl sulfone 1a or sulfoxide 1b acts as a CF3 - synthon. Both sulfone 1a and sulfoxide 1b are commercially available and can also be conveniently prepared from trifluoromethane. The new methodology provides a convenient route for efficient trifluoromethylation.
- Prakash, G. K. Surya,Hu, Jinbo,Olah, George A.
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p. 3253 - 3256
(2007/10/03)
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- A general method of halogenation for synthesis of α-halodifluoromethyl ketones and [18F]-labeled trifluoromethyl ketones
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A convenient general method of halogenations suitable for synthesis of α-halodifluoromethyl ketones is reported. Reaction of 2,2-difluoro-1-aryl-1-trimethylsiloxyethenes (difluoro silyl enol ethers) (2a-e) with halogens at low temperature (-30 to -78 °C) produced a high yield of α-halodifluoromethyl ketones (1a-j). This one-step simple method can be highly useful for synthesis of [18F]-labeled α-trifluoromethyl ketones.
- Prakash, G.K. Surya,Hu, Jinbo,Alauddin, Mian M.,Conti, Peter S.,Olah, George A.
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p. 239 - 243
(2007/10/03)
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- Catalytic aerobic oxidative decarboxylation of α-trifluoromethyl-α-hydroxy acids to trifluoromethyl ketones
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The oxidative decarboxylation of α-trifluoromethyl-α-hydroxy acids to trifluoromethyl ketones is carried out under mild catalytic aerobic conditions using a cobalt(III) complex in the presence of pivalaldehyde.
- Blay, Gonzalo,Fernández, Isabel,Marco-Aleixandre, Alicia,Monje, Belén,Pedro, José R,Ruiz, Rafael
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p. 8565 - 8571
(2007/10/03)
-
- Facile oxidation of alcohols to carbonyl compounds using a tris(2-methylphenyl)-bismuth dichloride-DBU binary system
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High efficiency and chemoselectivity as well as the facile isolation of the carbonyl products by simple workup procedures characterize a new method of alcohol oxidation. A variety of primary and secondary alcohols are oxidized to aldehydes and ketones by the combined use of tris(2-methylphenyl)bismuth dichloride and 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU) under mild conditions [Eq. (1)].
- Matano, Yoshihiro,Nomura, Hazumi
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p. 3028 - 3031
(2007/10/03)
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