- C?F Bond Activation by Silylium Cation/Phosphine Frustrated Lewis Pairs: Mono-Hydrodefluorination of PhCF3, PhCF2H and Ph2CF2
-
Single defluorination of aryl polyfluoromethyl functionalities is achieved by both intra- and intermolecular silylium cation/phosphine Lewis pairs. Phosphine-captured aryl fluoromethyl cations are then treated with Br?nsted base to complete the first mono
- Mallov, Ian,Ruddy, Adam J.,Zhu, Hui,Grimme, Stefan,Stephan, Douglas W.
-
-
Read Online
- A class of phase-transfer catalyst with interionic strain: Insight into the bonding of disubstituted N-vs carbene-stabilized NI-centered cations
-
The straightforward synthesis of a class of nitrogen-based phase-transfer catalysts (PTCs) having markedly dissociated anions due to interionic donor-donor "ion pair strain" and use for catalyzing benzylation and benzylic fluorination is reported. Provided also is insight into the bonding of disubstituted N- vs so-called divalent carbene-stablized NI-centered cations and the unprecedented finding of a cyclopropenium based C-H···πaryl interaction.
- Mirabdolbaghi, Roya,Dudding, Travis,Stamatatos, Theocharis
-
-
Read Online
- Catalytic Formation of C(sp3)-F Bonds via Heterogeneous Photocatalysis
-
Due to their chemical, physical, and biological properties, fluorinated compounds are widely employed throughout society. Yet, despite their critical importance, current methods of introducing fluorine into compounds suffer from severe drawbacks. For example, several methods are noncatalytic and employ stoichiometric equivalents of heavy metals. Existing catalytic methods, on the other hand, exhibit poor activity, generality, selectivity and/or have not been achieved by heterogeneous catalysis, despite the many advantages such an approach would provide. Here, we demonstrate how selective C(sp3)-F bond synthesis can be achieved via heterogeneous photocatalysis. Employing TiO2 as photocatalyst and Selectfluor as mild fluorine donor, effective decarboxylative fluorination of a variety of carboxylic acids can be achieved in very short reaction times. In addition to displaying the highest turnover frequencies of any reported fluorination catalyst to date (up to 1050 h-1), TiO2 also demonstrates excellent levels of durability, and the system is catalytic in the number of photons required; i.e., a photon efficiency greater than 1 is observed. These factors, coupled with the generality and mild nature of the reaction system, represent a breakthrough toward the sustainable synthesis of fluorinated compounds.
- Tarantino, Giulia,Hammond, Ceri
-
-
Read Online
- Fluorine as a hydrogen-bond acceptor: Experimental evidence and computational calculations
-
Hydrogen-bonding interactions play an important role in many chemical and biological systems. Fluorine acting as a hydrogen-bond acceptor in intermolecular and intramolecular interactions has been the subject of many controversial discussions and there are different opinions about it. Recently, we have proposed a correlation between the propensity of fluorine to be involved in hydrogen bonds and its 19F NMR chemical shift. We now provide additional experimental and computational evidence for this correlation. The strength of hydrogen-bond complexes involving the fluorine moieties CH 2F, CHF2, and CF3 was measured and characterized in simple systems by using established and novel NMR methods and compared to the known hydrogen-bond complex formed between acetophenone and p-fluorophenol. Implications of these results for 19F NMR screening are analyzed in detail. Computed values of the molecular electrostatic potential at the different fluorine atoms and the analysis of the electron density topology at bond critical points correlate well with the NMR results.
- Dalvit, Claudio,Invernizzi, Christian,Vulpetti, Anna
-
-
Read Online
- New fluoride ion reagent from pentafluoropyridine
-
A new nucleophilic fluorinating agent, derived from reaction of dimethylaminopyridine (DMAP) with pentafluoropyridine, has been synthesised and assessed in various carbon-fluorine bond forming processes.
- Murray, Christopher B.,Sandford, Graham,Korn, Stewart R.,Yufit, Dmitrii S.,Howard, Judith A.K.
-
-
Read Online
- Polymer-Supported Potassium Fluoride - A Versatile Fluorination Reagent
-
The nucleophilic reactivity of potassium fluoride was found to be appreciably enhanced via the despersion of KF onto an inert polymeric support.This crosslinked polystyrene was conveniently synthesized with high surface area and porosity.
- Liu, Hanfan,Wang, Ping,Sun, Pengnian
-
-
Read Online
- Acceleration of the Fluorination of Benzyl Halide by the Combination of Lead Fluoride and Sodium Salt
-
A new composite reagent, a combination of lead fluoride (PbF2) and a small amount of sodium salt (NaX, X=F, Br etc.) was found to be useful for facilitating heterogeneous fluorination of substituted benzyl halides in acetonitrile.
- Ichihara, Junko,Hanafusa, Terukiyo,Takai, Yoshio,Ito, Yoshiaki
-
-
Read Online
- Nucleophilic fluorination reactions starting from aqueous fluoride ion solutions
-
The sulfonium borane 2+ reacts with fluoride anions in MeOH/H2O mixtures to afford the zwitterionic fluoroborate 2-F as an easily isolable nonhygroscopic solid. In dry acetonitrile, 2-F reacts with PhS- to afford the anionic fluoroborate 1-F-. The latter is very labile and acts as a nucleophilic fluorination reagent toward a variety of substrates including alkylhalides and electron-deficient aromatic compounds. This approach may become broadly applicable to nucleophilic fluorination procedures that involve wet fluoride sources.
- Zhao, Haiyan,Gabbai, Francois P.
-
-
Read Online
- Tetraphenylphosphonium Hydrogendifluoride: a New Source of Fluoride Ion
-
Tetraphenylphosphonium hydrogendifluoride, a soluble and thermally stable reagent, acts as a source of fluoride ion in a variety of organic reactions.
- Brown, Stephen J.,Clark, James H.
-
-
Read Online
- Anhydrous tetrabutylammonium fluoride
-
Tetrabutylammonium fluoride (TBAF) is prepared at low temperature by nucleophilic aromatic substitution of hexafluorobenzene with tetrabutylammonium cyanide. Adventitious water is scavenged during this synthesis by the generated hexacyanobenzene, which readily adds water under basic conditions. Contrary to expectations, TBAF is stable to Hofmann elimination in polar aprotic solvents under anhydrous conditions. Added hydroxylic solvents are shown to catalyze the decomposition of TBAF and to catalyze proton exchange with DMSO. The synthetic utility of this salt is described briefly. Copyright
- Sun, Haoran,DiMagno, Stephen G.
-
-
Read Online
- Ionic liquids as recyclable solvents for diethylaminosulfur trifluoride (DAST) mediated fluorination of alcohols and carbonyl compounds
-
The first simple and efficient method for the synthesis of mono and gem-difluorinated molecules using [C8mim][PF6] ionic liquid as a recyclable solvent medium with diethylaminosulfur trifluoride (DAST) as the fluorinating reagent, is reported.
- Das, Saibal,Chandrasekhar, Srivari,Yadav, Jhillu Singh,Grée, René
-
-
Read Online
- SUBSTRATE DEPENDENT SOLVENT EFFECTS IN NUCLEOPHILIC FLUORINE TRANSFER REACTIONS
-
The rate of fluorination of organic substrates by potassium fluoride in aprotic solvents is subject to substrate dependent solvent effects.
- Clark, J. H.,MacQuarrie, D.
-
-
Read Online
- A new type of phase-transfer catalysis via continuous transfer of fluoride anions to the organic phase in the form of potassium difluorotriphenylstannate
-
Fluorination of alkyl halides and sulfonates is efficiently executed in a liquid-solid phase-transfer catalysis system with Ph3SnF as phase-transfer catalyst acting via continuous formation of lipophilic Ph 3SnF2 anions entering the organic phase in the form of the potassium salt.
- Ma?kosza, Mieczys?aw,Bujok, Robert
-
-
Read Online
- THE SYNTHESIS OF ORGANOFLUORINE COMPOUNDS USING POTASSIUM FLUORIDE-TETRAPHENYLPHOSPHONIUM BROMIDE SYSTEMS.
-
The reactivity of potassium fluoride in nucleophilic fluorine transfer reactions can appreciably enhanced by the presence of tetraphenyl phosphonium bromide.Rate accelerations are especially large in non dipolar aprotic solvents.
- Clark, James H.,Macquarrie, Duncan J.
-
-
Read Online
- Reaction evolution of a solvate fluoride ionic liquid induced fluorination process probed by Raman spectroscopy
-
Currently, about 30% of new approved drugs contained fluorine atoms and most of them are made through fluorination reactions using various kinds of fluorinating reagents. In the current work, we report a facile and more accessible way to probe the fluorination evolution at different stages using a newly developed fluorinating reagent (1-ethyl-3-methylimmidazolium fluoride-ethylene glycol, [C2C1im]F-EG). Benzyl bromide was converted to benzyl fluoride using this fluorinating reagent under mild conditions. A more accessible Raman method, compared to NMR, was used to probe the reaction process due to the products having their own characteristic Raman vibrational frequencies because of the formation of different C-X bonds. Thus the yield of the product at different time scales could be then quantified based on their relative intensities, providing a fresh insight into the fluorination process. This method could be applied in other reactions to reflect the important fluorination process, which methodologically reports a facile way to probe reaction processes.
- Chen, Zhengfei,Deng, Meng,Gao, Zhanghua,Jiang, Zhijiang,Li, Lichun,Tang, Haodong
-
-
Read Online
- 1,1,3,3,3-Pentafluoropropene secondary amine adducts new selective fluorinating agents
-
Addition of secondary amine SA (dimethylamine DMA, diethylamine DEA, pyrrolidine Pyr, piperidine Pip, morpholine Mor) to pentafluoropropene PFP gives rise to generation of mixtures of two products (1-dialkylamine-1,3,3,3-tetrafluoropropene and N,N-dialkyl-1,1,3,3,3-pentafluoropropylamine) in different ratios. Those reaction mixtures, however, were found to be efficient fluorinating agents replacing hydroxyl groups in alcohols into fluorine. In general, they react with alcohols yielding corresponding fluorides, equimolar amounts of appropriate 3,3,3-trifluoropropionamide and hydrogen fluoride. Aliphatic primary alcohols including octanol and benzylic alcohol yield only alkyl fluorides. The secondary and tertiary alcohols, beside the desired fluorides, give usually considerably amount of alkenes.
- Koroniak, Henryk,Walkowiak, Justyna,Grys, Krzysztof,Rajchel, Andrzej,Alty, Adam,Du Boisson, Rick
-
-
Read Online
- METHOD AND REAGENT FOR DEOXYFLUORINATION
-
A safe, simple, and selective method and reagent for deoxyfluorination is disclosed. With the method and reagent disclosed herein, organic compounds such as carboxylic acids, carboxylates, carboxylic acid anhydrides, aldehydes, and alcohols can be fluorinated by using the most common nucleophilic fluorinating reagents and electron deficient fluoroarenes as mediators under mild conditions, giving corresponding fluoroorganic compounds in excellent yield with a wide range of functional group compatibility and easy product purification. For example, directly utilizing KF for deoxyfluorination of carboxylic acids provides the most economical and the safest pathway to access acyl fluorides, key intermediates for syntheses of peptide, amide, ester, and dry fluoride salts.
- -
-
Paragraph 0148-0150; 0152; 0160
(2021/05/29)
-
- PROCESSES FOR FLUORINATION
-
The present technology relates to fluorination reactions. Specifically, processes useful for making the fungicide compound, DFT are disclosed. More broadly, also disclosed herein are processes useful for deoxyfluorination at the α-aromatic position of a given compound.
- -
-
Paragraph 0179; 0184; 0214-0215
(2021/04/10)
-
- Copper-Catalyzed Functionalization of Benzylic C-H Bonds with N-Fluorobenzenesulfonimide: Switch from C-N to C-F Bond Formation Promoted by a Redox Buffer and Br?nsted Base
-
A copper catalyst in combination with N-fluorobenzenesulfonimide (NFSI) has been reported to functionalize benzylic C-H bonds to the corresponding benzylic sulfonimides via C-N coupling. Here, we reported a closely related Cu-catalyzed method with NFSI that instead leads to C-F coupling. This switch in selectivity arises from changes to the reaction conditions (Cu/ligand ratio, temperature, addition of base) and further benefits from inclusion of MeB(OH)2 in the reaction. MeB(OH)2 is shown to serve as a "redox buffer"in the reaction, responsible for rescuing inactive Cu(II) for continued promotion of fluorination reactivity.
- Buss, Joshua A.,Golden, Dung L.,Stahl, Shannon S.,Vasilopoulos, Aristidis
-
supporting information
p. 5749 - 5752
(2020/10/02)
-
- C(sp3)-H Fluorination with a Copper(II)/(III) Redox Couple
-
Despite the growing interest in the synthesis of fluorinated organic compounds, few reactions are able to incorporate fluoride ions directly into alkyl C-H bonds. Here, we report the C(sp3)-H fluorination reactivity of a formally copper(III) fluoride complex. The C-H fluorination intermediate, LCuF, along with its chloride and bromide analogues, LCuCl and LCuBr, were prepared directly from halide sources with a chemical oxidant and fully characterized with single-crystal X-ray diffraction, X-ray absorption spectroscopy, UV-vis spectroscopy, and 1H nuclear magnetic resonance spectroscopy. Quantum chemical calculations reveal significant halide radical character for all complexes, suggesting their ability to initiate and terminate a C(sp3)-H halogenation sequence by sequential hydrogen atom abstraction (HAA) and radical capture. The capability of HAA by the formally copper(III) halide complexes was explored with 9,10-dihydroanthracene, revealing that LCuF exhibits rates 2 orders of magnitude higher than LCuCl and LCuBr. In contrast, all three complexes efficiently capture carbon radicals to afford C(sp3)-halogen bonds. Mechanistic investigation of radical capture with a triphenylmethyl radical revealed that LCuF proceeds through a concerted mechanism, while LCuCl and LCuBr follow a stepwise electron transfer-halide transfer pathway. The capability of LCuF to perform both hydrogen atom abstraction and radical capture was leveraged to enable fluorination of allylic and benzylic C-H bonds and α-C-H bonds of ethers at room temperature.
- Bower, Jamey K.,Cypcar, Andrew D.,Henriquez, Brenda,Stieber, S. Chantal E.,Zhang, Shiyu
-
supporting information
p. 8514 - 8521
(2020/05/28)
-
- C-F Bond Activation of a Perfluorinated Ligand Leading to Nucleophilic Fluorination of an Organic Electrophile
-
We report a fluorine transfer reaction in which fluorine from a perfluorinated ligand undergoes C-F bond activation and transfers to an electrophile, resulting in the formation of a new fluorinated product and dimerization of the monodefluorinated complex. Treatment of [(η5,κ2C-C5Me4CH2C6F5CH2NC3H2NMe)-RhCl] with the organic electrophile, toluoyl chloride, resulted in the formation of a rhodium(III) metallocycle via C-F bond activation assisted defluorinative coupling. Fission of the C-F bond liberated nucleophilic fluoride, which converted acyl chloride to acyl fluoride. The overall reaction was monitored using a multivariate analysis approach in real time.
- Hanson-Heine, Magnus W. D.,Licence, Peter,Marr, Andrew C.,Morgan, Patrick J.,Saunders, Graham C.,Thomas, Hayden P.
-
supporting information
p. 2116 - 2124
(2020/07/23)
-
- A rings-in-pores net: Crown ether-based covalent organic frameworks for phase-transfer catalysis
-
We herein present a new family of crown ether-based covalent organic frameworks (CE-COFs) for the first time. The CE-COFs show excellent phase-transfer catalytic performance in various nucleophilic substitution reactions.
- Guo, Wen-Di,Hu, Bingwen,Jiang, Wei-Ling,Lou, Xiaobing,Ma, De-Li,Qi, Qiao-Yan,Shen, Ji-Chuang,Shen, Ming,Yang, Hai-Bo,Zhao, Xin
-
supporting information
p. 595 - 598
(2020/01/29)
-
- Copper-Catalyzed C-H Fluorination/Functionalization Sequence Enabling Benzylic C-H Cross Coupling with Diverse Nucleophiles
-
Site-selective transformation of benzylic C-H bonds into diverse functional groups is achieved via Cu-catalyzed C-H fluorination with N-fluorobenzenesulfonimide (NFSI), followed by substitution of the resulting fluoride with various nucleophiles. The benzyl fluorides generated in these reactions are reactive electrophiles in the presence of hydrogen-bond donors or Lewis acids, allowing them to be used without isolation in C-O, C-N, and C-C coupling reactions.
- Buss, Joshua A.,Golden, Dung L.,Stahl, Shannon S.,Vasilopoulos, Aristidis
-
supporting information
(2020/08/24)
-
- PROCESSES FOR FLUORINATION
-
The present technology relates to fluorination reactions. Specifically, processes useful for making the fungicide compound, DFT are disclosed. More broadly, also disclosed herein are processes useful for deoxyfluorination at the α-aromatic position of a given compound.
- -
-
Paragraph 0188
(2020/03/05)
-
- Nickel-catalyzed monofluoromethylation of (hetero)aryl bromides via reductive cross-coupling
-
A mild and efficient nickel-catalyzed direct monofluoromethylation of (hetero)aryl bromides by reductive cross-coupling has been developed. This method exhibits good efficiency, wide functional-group compatibility, and suitability for aryl and heteroaryl bromides with abundant industrial raw material BrCH2F. This strategy provides an efficient way to synthesize monofluoromethylated molecules for drug discovery.
- Yin, Han,Sheng, Jie,Zhang, Kai-Fan,Zhang, Zi-Qi,Bian, Kang-Jie,Wang, Xi-Sheng
-
supporting information
p. 7635 - 7638
(2019/07/09)
-
- 9-Borabicyclo[3.3.l]nonane-induced Friedel-Crafts benzylation of arenes with benzyl fluorides
-
Friedel-Crafts benzylation of arenes with benzyl fluorides using 9-borabicyclo[3.3.l]nonane (9-BBN) as a mediator has been developed. This provides a simple and cheap route to the activation of C-F bonds to synthesize 1,1-diarylmethanes in good to excellent yields (up to 98%) under mild conditions. Functional group tolerance and the mechanism are considered.
- Guo, Jing,Bamford, Karlee L.,Stephan, Douglas W.
-
supporting information
p. 5258 - 5261
(2019/06/07)
-
- Expanding the repertoire of cyclopropenium ion phase transfer catalysis: Benzylic fluorination
-
The application of cyclopropenium ion as a phase transfer catalyst for benzylic fluorination in high yields is reported. Integral to the mechanisms of these fluorination reactions was the role of in situ derived cyclopropenium fluoride complexes, the existence of which was supported by 1H, 19F NMR and UV–Vis spectroscopy. Density functional theory calculations were applied to gain insight into the mechanism of these reactions.
- Dempsey, Katie,Mir, Roya,Smajlagic, Ivor,Dudding, Travis
-
p. 3507 - 3511
(2018/05/25)
-
- Synthesis of acyl fluorides via photocatalytic fluorination of aldehydic C-H bonds
-
Acyl fluorides are versatile acylating agents owing to their unique stability. Their synthesis, however, can present challenges and is typically accomplished through deoxyfluorination of carboxylic acids. Here, we demonstrate that acyl fluorides can be prepared directly from aldehydes via a C(sp2)-H fluorination reaction involving the inexpensive photocatalyst sodium decatungstate and electrophilic fluorinating agent N-fluorobenzenesulfonimide. This convenient fluorination strategy enables direct conversion of aliphatic and aromatic aldehydes into acylating agents.
- Meanwell, Michael,Lehmann, Johannes,Eichenberger, Marc,Martin, Rainer E.,Britton, Robert
-
p. 9985 - 9988
(2018/09/11)
-
- Exploring the Reducing Ability of Organic Dye (Acr+-Mes) for Fluorination and Oxidation of Benzylic C(sp3)-H Bonds under Visible Light Irradiation
-
The excellent oxidizing capability of acridinium-based organic dye (Acr+-Mes) is fully studied in photoredox catalysis. However, its reducing ability is always considered weak for organic transformation. The reducing ability of Acr+-Mes is developed by Selectfluor to achieve effective fluorination and oxidation of benzylic C(sp3)-H bonds under visible light irradiation, which is not available for the direct use of oxidizing ability of excited Acr+-Mes. Mechanistic insights provided strong evidence for the oxidative quenching of Acr+-Mes.
- Xiang, Ming,Xin, Zhi-Kun,Chen, Bin,Tung, Chen-Ho,Wu, Li-Zhu
-
supporting information
p. 3009 - 3012
(2017/06/07)
-
- Radical C-H Fluorination Using Unprotected Amino Acids as Radical Precursors
-
We report a unique example of utilizing unprotected amino acids for benzylic C-H fluorination via a radical process. α-Aminoalkyl radicals are readily generated via oxidative decarboxylation of unprotected amino acids using a simple silver(I) catalyst and Selectfluor, which serves as both a mild oxidant and source of electrophilic fluorine. Mechanistic investigation shows that coordination of the unprotected amino acid plays a crucial role in lowering the oxidation potential of Ag(I), enabling oxidation under mild conditions. Mono- or difluorination is possible by controlling the stoichiometry of amino acid and fluorine source.
- Hua, Alyssa M.,Mai, Duy N.,Martinez, Ramon,Baxter, Ryan D.
-
supporting information
p. 2949 - 2952
(2017/06/07)
-
- Synthesis, Characterization, and Reactivity of Thermally Stable Anhydrous Quaternary Ammonium Fluorides
-
The synthesis and properties of a new class of anhydrous quaternary ammonium fluorides, based on the rigid skeleton azabicyclo[2.2.2]octane, is described. Compounds 2a-d were easily prepared by passing the corresponding ammonium iodides over fluoride-based resin followed by drying their hydrated form at 100 or 140 °C under reduced pressure. The stability (experimental and theoretical study), solubility, reactivity, and characterization by solution and solid-state MAS NMR are discussed.
- Elias, Shlomi,Karton-Lifshin, Naama,Yehezkel, Lea,Ashkenazi, Nissan,Columbus, Ishay,Zafrani, Yossi
-
supporting information
p. 3039 - 3042
(2017/06/23)
-
- Hypervalent Iodine(III)-Mediated Oxidative Fluorination of Alkylsilanes by Fluoride Ions
-
The first example of a hypervalent iodine(III)-mediated oxidative fluorination of alkylsilanes by fluoride ions without the use of transition metals is demonstrated. This reaction is operationally simple, scalable, and proceeds under mild reaction conditions. Mechanistic studies suggest the involvement of a single-electron transfer resulting from the interaction of an organopentafluorosilicate and aryliodonium difluoride, which were generated in situ from the corresponding alkylsilane and iodosobenzene, respectively, in the presence of fluoride ions.
- Xu, Peng,Wang, Feng,Fan, Guilan,Xu, Xiufang,Tang, Pingping
-
supporting information
p. 1101 - 1104
(2017/01/18)
-
- METAL OXIDE CATALYZED RADIOFLUORINATION
-
Inter alia, the first titania-catalyzed [18F]-radiofluorination in highly aqueous medium is provided. In embodiments, the method utilizes titanium dioxide, 1 : 1 acetonitrile- thexyl alcohol solvent mixture and tetrabutylammonium bicarbonate as a base. Radiolabeling may be directly performed with aqueous [18F]fluoride without the need for drying/azeotroping step, which reduces radiosynthesis time while keeping high fluoride conversion. The general applicability of the synthetic strategy to the synthesis of the wide range of PET probes from tosylated precursors is demonstrated.
- -
-
Paragraph 0111; 0113
(2016/02/28)
-
- Palladium-Catalyzed Monofluoromethylation of Arylboronic Esters with Fluoromethyl Iodide
-
The first palladium-catalyzed direct monofluoromethylation of arylboronic esters to produce monofluoromethyl arenes is reported. The reaction is typically carried out at room temperature within 4 h and has a good functional group tolerance. The monofluoromethylating agent, CH2FI, was readily prepared via a halogen-exchange process.
- Hu, Jingyu,Gao, Bing,Li, Lingchun,Ni, Chuanfa,Hu, Jinbo
-
p. 3086 - 3089
(2015/06/30)
-
- Solvent free nucleophilic introduction of fluorine with [bmim][F]
-
1-n-Butyl-3-methylimidazolium fluoride ([bmim][F]) proved very efficient fluorinated reagent for nucleophilic substitution over sulfonate esters and alkyl halides. Preparation of the ionic liquid as well as its use as the reagent has been performed to be the more eco-friendly as possible. No organic solvent is needed for the fluoride introduction, reaction times are reduced by using microwave as the heating source, and the ionic liquids carefully recycled. Furthermore, no special care has to be taken as the presence of water in [bmim][F] was not deleterious to the transformation yield.
- Bouvet, Sébastien,Pégot, Bruce,Marrot, Jérome,Magnier, Emmanuel
-
p. 826 - 829
(2014/02/14)
-
- Photocatalyzed benzylic fluorination: Shedding "light" on the involvement of electron transfer
-
The photocatalyzed oxidation of benzylic compounds by 1,2,4,5-tetracyanobenzene (TCB) in the presence of Selectfluor provides a synthetically efficient route to electron deficient, less substituted, and otherwise inaccessible benzylic fluorides. The virtue of this system is multifold: it is metal-free and mild, and the reagents are inexpensive. Mechanistically, the data suggest the intimate formation of intermediate radical cations in the key radical forming step, as opposed to a concerted hydrogen atom transfer process.
- Bloom, Steven,McCann, Michael,Lectka, Thomas
-
supporting information
p. 6338 - 6341
(2015/01/16)
-
- Simulating microwave chemistry in a resistance-heated autoclave made of semiconducting silicon carbide ceramic
-
"Microwave chemistry" without microwaves: A resistance-heated SiC autoclave can effectively mimic the sealed-vessel capabilities, rapid heating and cooling profiles, and excellent process-control features that are inherent to modern microwave reactors. Applied to synthetic chemistry, the ready-to-assemble small device provides identical results as can be obtained in a (costly) microwave system (see figure). Copyright
- Obermayer, David,Damm, Markus,Kappe, C. Oliver
-
supporting information
p. 15827 - 15830
(2014/04/03)
-
- Electrochemical fluorination using halogen mediators in ionic liquid hydrogen fluoride salt
-
In order to utilize ammomium halides (Et4NX, X=Cl, Br, I) as halogenmediator for electrocatalytic fluorination, cyclic voltammetry measurements of the halides were investigated. The catalytic current of the halides in the presence of a dithioacatal compound was observed and the macro-scale electrolysis of dithioacetals using the halogen mediator was also carried out in ionic liquid hydrogen fluoride (HF) salt to give the corresponding fluorinated products in excellent yields. The recycle use of the halogen mediator in the electrochemical fluorination was successfully demonstrated. More inexpensive halides such as potassium bromide and potassium iodide could be soluble in HF salt and worked well as halogen mediator for the electrocatalytic fluorination.
- Takahashi, Kohta,Inagi, Shinsuke,Fuchigami, Toshio
-
p. G3046-G3052
(2013/07/05)
-
- Direct fluorination of cyclic carbonates and closo-K2[B 12H12] in a slug-flow ministructured reactor
-
A novel minireactor for direct fluorination of organic and inorganic substances was tested. The reactor consists of nickel-coated copper blocks with mechanically machined 1 mm channels and is equipped with an active cooling system. The direct fluorination of ethylene carbonate and propylene carbonate is described. For the fluorinated propylene carbonate, the NMR data of various fluorinated isomers were determined. The Gibbs reaction energies for the direct fluorination of ethylene and propylene carbonate were calculated at the reliable G3 level of theory. The excellent decomposition stability of the cyclic carbonates against high fluorine and HF concentrations also qualifies them as good solvents for direct fluorination processes, especially for ionic substrates. In this respect, the direct fluorination of the inorganic salt closo-K2[B12H12] in cyclic carbonates is presented.
- Hill, Mathias,Baron, Patrick,Cobry, Keith,Goll, Sascha K.,Lang, Philipp,Knapp, Carsten,Scherer, Harald,Woias, Peter,Zhang, Pengcheng,Krossing, Ingo
-
p. 292 - 301
(2013/08/23)
-
- Visible light-promoted metal-free C-H activation: Diarylketone-catalyzed selective benzylic mono- and difluorination
-
We report herein an operationally simple method for the direct conversion of benzylic C-H groups to C-F. We show that visible light can activate diarylketones to abstract a benzylic hydrogen atom selectively. Adding a fluorine radical donor yields the benzylic fluoride and regenerates the catalyst. The selective formation of mono- and difluorination products can be achieved by catalyst control. 9-Fluorenone catalyzes benzylic C-H monofluorination, while xanthone catalyzes benzylic C-H difluorination. The scope and efficiency of this new C-H fluorination method are significantly better than those of the existing methods. This is also the first report of selective C-H gem-difluorination.
- Xia, Ji-Bao,Zhu, Chen,Chen, Chuo
-
supporting information
p. 17494 - 17500
(2014/01/06)
-
- Photo-fluorodecarboxylation of 2-aryloxy and 2-aryl carboxylic acids
-
Coming to light: The title reaction simply requires an aqueous alkaline solution of Selectfluor and light. The method is inexpensive and effective for a wide range of neutral and electron-poor 2-aryloxy and 2-aryl acetic acids to provide fluoromethyl ethers (see scheme) and benzyl fluorides, respectively. The mechanism most likely proceeds through an initial aryl excitation with a subsequent single-electron transfer. Copyright
- Leung, Joe C. T.,Chatalova-Sazepin, Claire,West, Julian G.,Rueda-Becerril, Montserrat,Paquin, Jean-Fran?ois,Sammis, Glenn M.
-
supporting information
p. 10804 - 10807
(2013/01/15)
-
- Mechanistic studies on direct arylation of pyridine N -oxide: Evidence for cooperative catalysis between two distinct palladium centers
-
Direct arylations of pyridine N-oxide (PyO), a convenient method to prepare 2-arylpyridines, catalyzed by Pd(OAc)2 and PtBu3 have been proposed to occur by the generation of a PtBu3-ligated arylpalladium acetate complex, (PtBu3)Pd(Ar)(OAc) (1), and the reaction of this complex with PyO. We provide strong evidence that 1 does not react directly with PyO. Instead, our data imply that the cyclometalated complex [Pd(OAc)(tBu2PCMe2CH2)]2, which is generated from the decomposition of 1, reacts with PyO and serves as a catalyst for the reaction of PyO with 1. The reaction of PyO with 1 occurs with an induction period, and the reaction of 1 with excess PyO in the presence of [Pd(OAc)(tBu2PCMe2CH2)]2 is zeroth-order in 1. Moreover, the rates of reactions of PyO with bromobenzene catalyzed by [Pd(OAc)(tBu2PCMe2CH2)] 2 and [Pd(PtBu3)2] depend on the concentration of [Pd(OAc)(tBu2PCMe2CH2)]2 but not on the concentration of [Pd(PtBu3)2]. Finally, the reaction of 1 with a model heteroarylpalladium complex containing a cyclometalated phosphine, [(PEt3)Pd(2-benzothienyl)(tBu 2PCMe2CH2)], rapidly formed the arylated heterocycle. Together, these data imply that the rate-determining C-H bond cleavage occurs between PyO and the cyclometalated [Pd(OAc)(tBu 2PCMe2CH2)]2 rather than between PyO and 1. In this case, the resulting heteroarylpalladium complex transfers the heteroaryl group to 1, and C-C bond-formation occurs from (PtBu 3)Pd(Ar)(2-pyridyl oxide). This mechanism proposed for the direct arylation of PyO constitutes an example of C-H bond functionalization in which C-H activation occurs at one metal center and the activated moiety undergoes functionalization after transfer to a second metal center.
- Tan, Yichen,Barrios-Landeros, Fabiola,Hartwig, John F.
-
supporting information; experimental part
p. 3683 - 3686
(2012/04/23)
-
- Selective elemental fluorination in ionic liquids
-
Selective elemental fluorination in ionic liquids (ILs) will be presented as a new methodology. The tested reagents are organic disulphides and organic iodides. In addition, the stabilities of the ionic liquids [EMIM][(C 2F5)3PF3], [BMPL][(C 2F5)3PF3], [BMPL][OTf] and [BMPL][B(CN)4] against diluted fluorine (5 vol% in nitrogen) are investigated.
- Hirschberg,Ignat'ev,Wenda,Willner
-
experimental part
p. 50 - 53
(2012/05/07)
-
- Oxidation of primary aliphatic and aromatic aldehydes with difluoro(aryl)-λ3-bromane
-
Oxidation of primary aliphatic aldehydes with p- trifluoromethylphenyl(difluoro)-λ3-bromane in dichloromethane at 0 °C afforded acid fluorides selectively in good yields, while that of aromatic aldehydes in chloroform at room temperature produced aryl difluoromethyl ethers. A larger migratory aptitude of aryl groups compared to primary alkyl groups during a 1,2-shift from carbon to an electron-deficient oxygen atom in bromane(III) Criegee-type intermediates will result in these differences in the reaction courses.
- Ochiai, Masahito,Yoshimura, Akira,Hoque, Md. Mahbubul,Okubo, Takuji,Saito, Motomichi,Miyamoto, Kazunori
-
supporting information; experimental part
p. 5568 - 5571
(2011/12/03)
-
- Steric crowding makes challenging Csp3 - F reductive eliminations feasible
-
A high-yielding fluorination of (triphos)Pt-R+ has been achieved using an array of F+ sources, with XeF2 yielding R-F in minutes. The C-F coupling proved to be a stereoretentive process that proceeds via a concerted reductive elimination from a putative dicationic Pt(IV) center. The larger the steric congestion of the (triphos)Pt-Csp3+ complexes, the more efficient the fluorination, seemingly a result of sterically accelerated C-F reductive elimination along with simultaneous deceleration of its competing processes (β-H elimination).
- Zhao, Shu-Bin,Becker, Jennifer J.,Gagne, Michel R.
-
scheme or table
p. 3926 - 3929
(2011/10/03)
-
- Recyclable polymer-supported iodobenzene-mediated electrocatalytic fluorination in ionic liquid
-
The electrochemical fluorination of organosulfur compounds in triethylamine/hydrofluoric acid (Et3N-5HF) with polystyrene-supported iodobenzene (PSIB) and tetraethylammonium chloride (Et4NCl) was performed successfully in an undivided cell under constant current conditions to afford the corresponding fluorinated compounds in moderate to good yields. Recycle use of the PSIB could be achieved due to its easy separation. Notably, the mediatory activity of the iodobenzene derivative was not appreciably changed even after 10 recycle uses.
- Sawamura, Takahiro,Kuribayashi, Shunsuke,Inagi, Shinsuke,Fuchigami, Toshio
-
experimental part
p. 2757 - 2760
(2010/12/25)
-
- METHODS FOR SILVER-PROMOTED FLUORINATION OF ORGANIC MOLECULES
-
The methods of the disclosure may be used for the fluorination of organic compounds, and in particular aryl organic compounds other than just benzyl halogens. It is within the scope of the present disclosure, for organic compounds comprising an electrophi
- -
-
Page/Page column 5-6
(2010/06/22)
-
- Use of perfluoro groups in nucleophilic 18F-fluorination
-
Substrates with leaving groups that contained perfluoro moieties were investigated in labelling chemistry in order to exploit their properties to improve reactivity and purification. [18F](Fluoromethyl)benzene was used as the model target compound. Precursors containing perfluoroalkyl and perfluoroaryl sulfonate moieties were subjected to nucleophilic 18F-fluorination, and the impact of perfluoro groups on the substitution reaction and product purification was investigated. [ 18F]Fluoride interacted with perfluoroalkyl chains, precluding nucleophilic substitution. When perfluoroaryl groups were used, the substitution proceeded, and the separation of product was explored. The radiolabelled product was obtained in 32% analytical yield and the radiochemical purity was increased to approximately 77% using fluorous solid phase extraction purification. Copyright
- Blom, Elisabeth,Karimi, Farhad,Langstroem, Bengt
-
experimental part
p. 24 - 30
(2010/04/24)
-
- A new and direct trifluoromethoxylation of aliphatic substrates with 2,4-dinitro(trifluoromethoxy)benzene
-
The reaction of tetrabutylammonium triphenyldifluorosilicate with 2,4-dinitro(trifluoromethoxy)benzene, in acetonitrile and under microwave irradiation, generates a trifluoromethoxide anion which is able to substitute activated bromides (benzyl bromide, cinnamyl bromide), as well as, to some extent, alkyl iodides. Aliphatic trifluoromethyl ethers are thus formed. This is the first example of the nucleophilic displacement of the trifluoromethoxy group from an activated aromatic ring.
- Marrec, Olivier,Billard, Thierry,Vors, Jean-Pierre,Pazenok, Sergii,Langlois, Bernard R.
-
body text
p. 2831 - 2837
(2010/12/25)
-
- Discovery of 4-tert-butyl-2,6-dimethylphenylsulfur trifluoride as a deoxofluorinating agent with high thermal stability as well as unusual resistance to aqueous hydrolysis, and its diverse fluorination capabilities including deoxofluoro-arylsulfinylation with high stereoselectivity
-
Versatile, safe, shelf-stable, and easy-to-handle fluorinating agents are strongly desired in both academic and industrial arenas, since fluorinated compounds have attracted considerable interest in many areas, such as drug discovery, due to the unique effects of fluorine atoms when incorporated into molecules. This article describes the synthesis, properties, and reactivity of many substituted and thermally stable phenylsulfur trifluorides, in particular, 4-tert-butyl-2,6-dimethylphenylsulfur trifluoride (Fluolead, 1k), as a crystalline solid having surprisingly high stability on contact with water and superior utility as a deoxofluorinating agent compared to current reagents, such as DAST and its analogues. The roles of substiuents on 1k in thermal and hydrolytic stability, fluorination reactivity, and the high-yield fluorination mechanism it undergoes have been clarified. In addition to fluorinations of alcohols, aldehydes, and enolizable ketones, 1k smoothly converts non-enolizable carbonyls to CF2 groups, and carboxylic groups to CF3 groups, in high yields. 1k also converts C(=S) and CH3SC(=S)O groups to CF2 and CF3O groups, respectively, in high yields. In addition, 1k effects highly stereoselective deoxofluoro-arylsulfinylation of diols and amino alcohols to give fluoroalkyl arylsulfinates and arylsulfinamides, with complete inversion of configuration at fluorine and the simultaneous, selective formation of one conformational isomer at the sulfoxide sulfur atom. Considering the unique and diverse properties, relative safety, and ease of handling of 1k in addition to its convenient synthesis, it is expected to find considerable use as a novel fluorinating agent in both academic and industrial arenas.
- Umemoto, Teruo,Singh, Rajendra P.,Xu, Yong,Saito, Norimichi
-
supporting information; experimental part
p. 18199 - 18205
(2011/03/18)
-
- POTASSIUM FLUORIDE DISPERSION SOLUTION, AND PROCESS FOR PRODUCTION OF FLUORINATED ORGANIC COMPOUND USING THE SAME
-
A potassium fluoride dispersion essentially consisting of potassium fluoride and an aprotic organic solvent having a boiling point higher than that of methanol, which is obtainable by mixing a mixture containing potassium fluoride and 5 to 50 parts by weight of methanol per 1 part by weight of potassium fluoride with the aprotic organic solvent followed by concentrating the obtained mixture, and a process for producing a fluorine-containing organic compound comprising contacting an organic compound having at least one group capable of being substituted nucleophilically with a fluorine atom with the potassium fluoride dispersion.
- -
-
Page/Page column 8-9
(2009/04/25)
-
- Palladium(0)-mediated rapid methylation and fluoromethylation on carbon frameworks by reacting methyl and fluoromethyl iodide with aryl and alkenyl boronic acid esters: Useful for the synthesis of [11C]CH 3-C-and [18F]FCH2-C-containing PET tracers (PET = positron emission tomography)
-
The rapid methylation and fluoromethylation on aryl and alkenyl carbon frameworks by reacting methyl and fluoromethyl iodide with aryl and alkenyl boronates have been studied with the focus on the realization of the synthesis of [11C]CH3- and [18F]FCH2-labeled positron emission tomography (PET) tracers. The coupling of methyl iodide and pinacol phenylboronate (40 equiv) is accomplished in > 91% yield within 5 min at 60 °C under the conditions of [Pd2(dba)3]/P(o- CH3C6H4)3/K2CO 3 (0.5:2:2; dba = di-benzylideneacetone) in DMF. The reaction shows a high generality and is applicable to various types of aryl and alkenyl boronates, giving the corresponding methylated derivatives in high yields (80-99). This reaction is also useful for the rapid incorporation of the fluoromethyl group. Thus, this boron protocol provides a firm chemical basis for the synthesis of 11C- and 18F-incorporated PET tracers and can be used as a complementary method for [11C]methylation together with our previous and ongoing processes using organotributylstannanes.
- Doi, Hisashi,Ban, Ikuya,Nonoyama, Akihito,Sumi, Kengo,Kuang, Chunxiang,Hosoya, Takamitsu,Tsukada, Hideo,Suzuki, Masaaki
-
experimental part
p. 4165 - 4171
(2009/12/01)
-
- C-ARYL GLYCOSIDE COMPOUNDS FOR THE TREATMENT OF DIABETES AND OBESITY
-
This invention relates to a compound of generic formula (I): (I) as well as a pharmaceutically acceptable salt thereof, a tautomer, optical isomer or a mixture of optical isomers in any proportion, in particular a mixture of enantiomers, and particularly a racemate mixture, in particular for use thereof as a drug, notably in the treatment of diabetes.
- -
-
Page/Page column 78
(2009/10/30)
-
- METHOD OF RAPID METHYLATION, KIT FOR PREPARING PET TRACER AND METHOD OF PRODUCING PET TRACER
-
It is intended to provide a method of rapid methylation of an aromatic compound or an alkenyl compound, which is capable of obtaining an aromatic compound or an alkenyl compound labeled with a methyl group or a fluoromethyl group under a mild condition rapidly in high yield using an organic boron compound whose toxicity is not so high as a substrate; a kit for preparing a PET tracer to be used in the same, and a method of producing a PET tracer using the same. In an aprotic polar solvent, methyl iodide or X-CH2F (wherein X is a functional group which can be easily released as an anion), an organic boron compound in which an aromatic ring or an alkenyl group is attached to boron are subjected to cross-coupling in the presence of a palladium(0) complex, a phosphine ligand, and a base.
- -
-
Page/Page column 11-12
(2009/07/10)
-
- Nucleophilic fluoroalkylation of α,β-enones, arynes, and activated alkynes with fluorinated sulfones: Probing the hard/soft nature of fluorinated carbanions
-
(Chemical Equation Presented) We have successfully accomplished the nucleophilic fluoroalkylation of α,β-enones, arynes, and activated alkynes with fluorinated sulfones. It was found that for acylic α,β-enones, although the reaction medium and the structure of the enones can all influence the regioselectivity of the nucleophilic alkylation reactions, the hard/soft nature of the carbanions played a major role. By using the 1,4- and 1,2-addition product ratio as a probe to determine the hard/soft nature of the above-mentioned four halogenated carbanions, the order of the softness of these carbanions can be given as follows: [(PhSO2) 2CF-] (20) ≈ PhSO2CCl2 - (32) > PhSO2CHF- (31) > PhSO 2CF2- (30). In the case of fluoroalkylation of aryne (35 as the precursor) and α,β-acetylenic ketones 46 with fluorobis(phenylsulfonyl)methane (21), fluorobis(phenylsulfonyl)methylated arenes 36 and β-fluorobis(phenylsulfonyl)methylated α,β-enones 47 were obtained as the corresponding products in good yields. During the reaction between 2-fluoro-2-(phenylsulfonyl)acetophenone (34) and arynes or activated alkynes 46, an intramolecular tandem reaction process leads to the formation of acyl-fluoroalkylated arenes 43 or α-acyl-β- fluoroalkylated α,β-enones 48. It turned out that the softness of a fluorine-bearing carbanion (such as 20 or 33 derived from 21 or 34) plays a crucial role for the success of the nucleophilic fluoroalkylation reactions with arynes and some activated alkynes (α,β-acetylenic ketones).
- Ni, Chuanfa,Zhang, Laijun,Hu, Jinbo
-
p. 5699 - 5713
(2008/12/21)
-
- SUBSTITUTED PHENYLSULFUR TRIFLUORIDE AND OTHER LIKE FLUORINATING AGENTS
-
Novel substituted phenylsulfur trifluorides that act as fluorinating agents are disclosed. Also disclosed are methods for their preparation and methods for their use in introducing one or more fluorine atoms into target substrate compounds.
- -
-
Page/Page column 21; 22
(2008/06/13)
-
- Substituted phenylsulfur trifluoride and other like fluorinating agents
-
Novel substituted phenylsulfur trifluorides that act as fluorinating agents are disclosed. Also disclosed are methods for their preparation and methods for their use in introducing one or more fluorine atoms into target substrate compounds.
- -
-
Page/Page column 20-21
(2008/06/13)
-
- Anhydrous flouride salts and reagents and methods for their production
-
Anhydrous organic fluoride salts and reagents prepared by a method comprising the nucleophilic substitution of a fluorinated aromatic or fluorinated unsaturated organic compound with a salt having the formula: [QnM]x+Ax?in an inert polar, aprotic solvent; wherein M is an atom capable of supporting a formal positive charge, the n groups Q are independently varied organic moieties, n is an integer such that the [QnM] carries at least one formal positive charge, x is an integer defining the number of formal positive charge(s), +, carried by the [QnM], A? is an anionic nucleophile capable of substituting for F in the fluorinated compound and F represents fluorine or a radioisotope thereof.
- -
-
Page/Page column 5
(2008/06/13)
-