- Photorelease of Pyridines Using a Metal-Free Photoremovable Protecting Group
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The photorelease of bioactive molecules has emerged as a valuable tool in biochemistry. Nevertheless, many important bioactive molecules, such as pyridine derivatives, cannot benefit from currently available organic photoremovable protecting groups (PPGs). We found that the inefficient photorelease of pyridines is attributed to intramolecular photoinduced electron transfer (PET) from PPGs to pyridinium ions. To alleviate PET, we rationally designed a strategy to drive the excited state of PPG from S1 to T1 with a heavy atom, and synthesized a new PPG by substitution of the H atom at the 3-position of 7-dietheylamino-coumarin-4-methyl (DEACM) with Br or I. This resulted in an improved photolytic efficiency of the pyridinium ion by hundreds-fold in aqueous solution. The PPG can be applied to various pyridine derivatives. The successful photorelease of a microtubule inhibitor, indibulin, in living cells was demonstrated for the potential application of this strategy in biochemical research.
- Dong, Zaizai,Fang, Xiaohong,Kou, Xiaolong,Tan, Weihong,Tang, Xiao-Jun,Wu, Yayun,Zhang, Zhen,Zhao, Rong,Zhou, Wei
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supporting information
p. 18386 - 18389
(2020/08/24)
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- Selective fluorination of pyridine and its derivatives in the presence of high-oxidation-state transition metals
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The oxidative fluorination of pyridine and 4-ethylpyridine under chemical and electro-chemical conditions in the presence of transition metal (high-oxidation-state nickel, cobalt, and silver) salts was studied. The chemical fluorination affords 2-fluoropyridine in all cases, while the electrochemical fluorination results in 2-fluoroor 3-fluoropyridine depending on the catalyst used.
- Gryaznova,Khrizanforova,Kholin,Khrizanforov,Budnikova, Yu. H.
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p. 1798 - 1804
(2017/03/22)
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- Mild fluorination of chloropyridines with in situ generated anhydrous tetrabutylammonium fluoride
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This paper describes the fluorination of nitrogen heterocycles using anhydrous NBu4F. Quinoline derivatives as well as a number of 3- and 5-substituted pyridines undergo high-yielding fluorination at room temperature using this reagent. These results with anhydrous NBu4F compare favorably to traditional halex fluorinations using alkali metal fluorides, which generally require temperatures of ≥100 °C.
- Allen, Laura J.,Muhuhi, Joseck M.,Bland, Douglas C.,Merzel, Rachel,Sanford, Melanie S.
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p. 5827 - 5833
(2014/07/08)
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- An improved catalyst system for the Pd-catalyzed fluorination of (hetero)aryl triflates
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The stable Pd(0) species [(1,5-cyclooctadiene)(L·Pd)2] (L = AdBrettPhos) has been prepared and successfully evaluated as a precatalyst for the fluorination of aryl triflates derived from biologically active and heteroaryl phenols, challenging substrates for our previously reported catalyst system. Additionally, this precatalyst activates at room temperature under neutral conditions, generates 1,5-cyclooctadiene as the only byproduct, and leads to overall cleaner reaction profiles.
- Lee, Hong Geun,Milner, Phillip J.,Buchwald, Stephen L.
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p. 5602 - 5605
(2013/11/19)
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- Catalytic hydrodefluorination of fluoroaromatics with silanes as hydrogen source at a binuclear rhodium complex: Characterization of key intermediates
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Stoichiometric and catalytic hydrodefluorination reactions of fluorinated aromatic substrates on using [Rh(μ-H)(dippp)]2 (1) (dippp = 1,3-bis(diisopropylphosphino)propane) as catalyst and HSiEt3 as a hydrogen source are reported. Treatment of the hydrido complex 1 with the fluoroarenes gave the fluorido complex [Rh(μ-F)(dippp)]2 (2) and organic hydrodefluorination products. An unusual ortho-selectivity was observed in the reaction of 2,3,5,6-tetrafluoropyridine and pentafluorobenzene giving the 1,2-hydrodefluorinated products. The binuclear structure of complex 2 in the solid state was confirmed by X-ray diffraction. The fluorido complex 2 reacted with HSiEt3 and HSiiPr3 by elimination of the corresponding fluorosilanes to afford the η2-silane hydrido complexes [Rh(H)(η2-HSiEt3)(dippp)] (3) and [Rh(H)(η2-HSiiPr3)(dippp)] (4), respectively. The structures of the complexes 3 and 4 were derived from NMR data and DFT calculations. Catalytic reactions of pentafluoropyridine, 2,3,5,6-tetrafluoro- pyridine or 2,3,5,6-tetra-fluoropyridine, hexa- and pentafluorobenzene with HSiEt3 in the presence of 5 mol% of 1 afforded hydrodefluorination products with up to 19 turnovers after 48 h at 50 C. In contrast to the stoichiometric reactions, the catalytic transformations resulted predominantly in hydrodefluorinations at the para-position of the nitrogen atom in the heterocycles giving evidence for two different C-F activation pathways. Compound 3 can be considered to be an intermediate in the catalytic hydrodefluorinations of the fluoroarenes.
- Zámostná, Lada,Ahrens, Mike,Braun, Thomas
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p. 132 - 142
(2013/10/01)
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- FLUORINATION OF ORGANIC COMPOUNDS
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Methods for fluorinating organic compounds are described herein.
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Page/Page column 24
(2012/11/06)
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- Deoxyfluorination of phenols
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An operationally simple ipso fluorination of phenols with a new deoxyfluorination reagent is presented.
- Tang, Pingping,Wang, Weike,Ritter, Tobias
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supporting information; experimental part
p. 11482 - 11484
(2011/10/02)
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- Efficient synthesis of aryl fluorides
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Chemical Equation Presented Creating C-F bonds: A novel electrophilic fluorination of aryl and heteroaryl Crignard reagents has been discovered and was used for the efficient synthesis of various aryl fluoride derivatives (see picture; THF = tetrahydrofuran).
- Anbarasan, Pazhamalai,Neumann, Helfried,Beller, Matthias
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experimental part
p. 2219 - 2222
(2010/06/17)
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- Silver-catalyzed protodecarboxylation of heteroaromatic carboxylic acids
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[Chemical Equation Presented] A simple and highly efficient protodecarboxylation procedure for a variety of heteroaromatic carboxylic acids catalyzed by Ag2CO3 and AcOH in DMSO is described. This methodology can also perform the selective monoprotodecarboxylation of several aromatic dicarboxylic acids.
- Lu, Pengfel,Sanchez, Carolina,Cornella, Josep,Larrosa, Igor
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supporting information; experimental part
p. 5710 - 5713
(2010/02/28)
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- Fluorination of boronic acids mediated by silver(I) Triflate
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A regiospecific Ag-mediated fluorination reaction of aryl- and alkenylboronic acids and esters Is reported. The fluorination reaction uses commercially available reagents, does not require the addition of exogenous ligands, and can be performed on a multigram scale. This report discloses the first practical reaction sequence from arylboronic acid to aryl fluorides.
- Furuya, Takeru,Ritter, Toblas
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supporting information; experimental part
p. 2860 - 2863
(2009/12/05)
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- Removal of fluorine from and introduction of fluorine into polyhalopyridines: An exercise in nucleophilic hetarenic substitution
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Starting from six industrially available fluorinated pyridines, an expedient access to all three tetrafluoropyridines (2-4), all six trifluoropyridines (5-10), and the five non-commercial difluoropyridines (11-14 and 16) was developed. The methods employed for the selective removal of fluorine from polyfluoropyridines were the reduction by metals or complex hydrides and the site-selective replacement by hydrazine followed by dehydrogenation-dediazotation or dehydrochlorination-dediazotation. To introduce an extra fluorine atom, a suitable precursor was metalated and chlorinated before being subjected to a chlorine/ fluorine displacement process.
- Bobbio, Carla,Rausis, Thierry,Schlosser, Manfred
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p. 1903 - 1910
(2007/10/03)
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- Polyhalogenated heterocyclic compounds. Part 42. Fluorinated nitrogen heterocycles with unusual substitution patterns
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Reductive replacement of fluorine in 3,5-dichloro-2,4,6-trifluoropyridine 2a and pentafluoropyridine 2 using DIBAL and LAH leads to useful syntheses of fluoro and chlorofluoro pyridine derivatives. Replacement of fluorine by bromine using a mixture of HBr and AlBr3 is extremely efficient, giving excellent routes to 2,4,6-tribromo-3,5-difluoropyridine 3. Bromofluoro-pyrimidine and -quinoxaline derivatives have also been efficiently synthesised from perfluorinated precursors. Catalytic hydrogenation of bromofluoro heterocycles gives high yields of the corresponding fluorinated heterocycles. Reactions of nucleophiles with 3 gives surprising results. Soft nucleophiles, e.g. PhSNa displace bromine whereas hard nucleophiles, e.g. MeONa, displace fluorine. British Crown Copyright 1998, Defence Evaluation and Research Agency. Published by the Royal Society of Chemistry with the permission of the controller of Her Britannic Majesty's Stationery Office.
- Chambers, Richard D.,Hall, Christopher W.,Hutchinson, John,Millar, Ross W.
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p. 1705 - 1713
(2007/10/03)
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- Facile preparation of aromatic fluorides by deaminative fluorination of aminoarenes using hydrogen fluoride combined with bases
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One-pot deaminative fluorination of aminoarenes including heteroaromatics, namely, diazotization of aminoarenes followed by in situ fluoro-dediazoniation of the corresponding diazonium ions, was successfully accomplished to produce fluoroarenes in high yields by using hydrogen fluoride combined with base solutions. The diazotization stage has been found to play the most important part in yielding fluoroarenes effectively. It was greatly influenced by the composition of the HF solution and enhanced by employing appropriate amounts of bases such as pyridine under carefully controlled conditions. The fluoro-dediazoniation stage was effectively accelerated photochemically to afford fluoroarenes having polar substituents such as hydroxyl, nitro and so on in high yields.
- Yoneda,Fukuhara
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- Kinetics, Mechanisms, and Catalysts of Oxygen Atom Transfer Reactions of S-Oxide and Pyridine N-Oxide Substrates with Molybdenum(IV,VI) Complexes: Relevance to Molybdoenzymes
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The kinetics and mechanism of the oxygen atom transfer reactions MoO2(L-NS2) + (RF)3P -> MoO(L-NS2)(DMF) + (RF)3PO (1) and MoO(L-NS2)(DMF + XO -> MoO2(L-NS2) + X, with X = (RF)2SO (2) and 3-fluoropyridine N-oxide (3), heve been investigated in DMF solutions (L-NS2 = 2,6-bis(2,2-diphenyl-2-mercaptoethyl)pyridine(2-), RF = p-C6H4F).The following rate constants (297.5 K) and activation parameters were obtained: reaction 1, k2 = 9.7 (4) X 10-3 M-1 s-1, ΔH(excit.) = 11.7 (6) kcal/mol, ΔS(excit.) = -28.4 (1.6) eu; reaction 2, k1 = 14.0 (7) X 10-4 s-1, ΔH(excit.) = 22.1 (1.3) kcal/mol, ΔS(excit.) = 2.6 (1.6) eu; reaction 3, k1 = 16.0 (8) X 10-4 s-1, ΔH(excit.) = 23.4 (1.4) kcal/mol, ΔS(excit.) = 7.2 (2.0) eu. reactions 2 and 3 exhibit saturation kinetics, under which the rate-determining step is intramolecular atom transfer.Mechanisms and transition states are proposed.The activation parameters are the first measured for oxo transfer from substrate; the small activation entropies suggest a transition state structurally similar to the complex MoO(L-NS2)(XO) formed in a labile equilibrium prior to oxo transfer to Mo.Coupling of reaction 1 with reaction 2 or 3 affords the catalytic reaction 4, (RF)3P + XO -> (RF)3PO + X; no reaction occurs in the absence of the Mo catalyst.The kinetics of catalysis were examined by monitoring the concentrations of reactants and products by 19F NMR spectroscopy.After 15 h, each system showed ca. 100 turnovers.Reaction 4 with XO = (RF)2SO has a catalytic rate constant of 7 X 10-3 M-1 s-1, close to the value for reaction 1.This and other considerations show that the catalytic rate is limited by the rate of oxo transfer from the Mo(VI) complex MoO2(L-NS2). An attempt to establish the catalytic mechanism led to detection of inhibition; the inhibitory species could not be identified.These results provide the most detailed information on the kinetics and mechanisms of Mo-mediated oxygen atom transfer and demonstrate the efficacy of 19F NMR for detecting and monitoring catalysis and determining catalytic velocities and rate constants.The relation of these results to the enzymatic reduction of N-oxides ans S-oxides is briefly discussed.
- Caradonna, John P.,Reddy, P. Rabindra,Holm, R. H.
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p. 2139 - 2144
(2007/10/02)
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- A Facile Preparation of Fluoropyridines from Aminopyridines via Diazotation and Fluorodediazoniation in HF or HF-Pyridine Solutions
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Fluoropyridines were prepared in high yields by dizotation of aminopyridines in HF or HF-pyridine solutions, followed by dediazoniation in situ at 20-60 deg C.
- Fukuhara, Tsuyoshi,Yoneda, Norihiko,Suzuki, Akira
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p. 435 - 438
(2007/10/02)
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- HOMOTRANSMETALLATION DES HALOGENO-3 PYRIDINES BROMEES EN -2 OU -4 PAR LE N-BUTYLLITHIUM. PROPOSITION D'UN NOUVEAU MECANISME DE TELESUBSTITUTION DU BROME.
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These are new examples of the homotransmetallation reaction.Instead of the ordinary bromo-metal exchange it is possible to obtain selectively from the 2-bromo 3-fluoro or 2-bromo 3-chloro pyridines the 2-bromo 3-halogeno 4-lithio pyridines, which is very interesting for synthetic utility.From the 4-bromo 3-halogeno pyridines, we can see an isomerization with an halogen dance mechanism and we obtain the 5-bromo 3-halogeno 4-lithio pyridines.In the case of the 2-bromo 3-fluoro pyridine we explain a telesubstitution of bromine from 2 to 4 by a transitory homotransmetallation reaction during the Li-Br exchange.
- Mallet, M.,Queguiner, G.
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p. 2253 - 2262
(2007/10/02)
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- IONIC HYDROGEN BOND. 4. INTRAMOLECULAR AND MULTIPLE BONDS. PROTONATION AND COMPLEXES OF AMIDES AND AMINO ACID DERIVATIVES.
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The paper examines the proton affinities and ionic hydrogen bonding of some amides and of the N-acetylated amino acid derivative CH//3CONHCH(CH//3)COOCH//3. The thermochemistry of these species can serve as a model for the energetics of protonated intermediates in acid hydrolysis of amides and the energetics of protonated amide groups in proteins.
- Meot-Ner (Mautner)
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p. 278 - 283
(2007/10/02)
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