- A Unified and Desymmetric Approach to Chiral Tertiary Alkyl Halides
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Enantioenriched tertiary alkyl halides are prevalent in bioactive molecules and can serve as versatile synthetic intermediates to construct complex structures. While conventional access to these motifs often hinges on stereoselective carbon-halogen or carbon-carbon bond formation reactions, desymmetric approaches using halogenated and prochiral tetrasubstituted carbons are largely elusive in comparison. Here, we report that a suite of dinuclear zinc catalysts with a prolinol- or pipecolinol-derived tetradentate ligand can reductively desymmetrize a large collection of easily available halomalonic esters to α-halo-β-hydroxyesters. These polyfunctionalized tertiary alkyl fluorides, chlorides, and bromides proved to be useful intermediates toward fluorinated drug analogs and polyhalogenated monoterpenes. The facile intramolecular epoxidation of the chiral chloride and bromide products has also enabled expeditious access to natural products containing tertiary alcohol motifs.
- Huang, Zhongxing,Low, Kam-Hung,Zhang, Suihan,Zheng, Yin,Zi, Weiwei
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supporting information
p. 1951 - 1961
(2022/02/09)
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- HETEROARYL COMPOUNDS AS IRAK INHIBITORS AND USES THEREOF
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The present invention relates to compounds of Formula (I) and pharmaceutically acceptable compositions thereof, useful as IRAK inhibitors.
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Paragraph 00180
(2017/05/02)
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- New promising lithium malonatoborate salts for high voltage lithium ion batteries
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Three new lithium salts, lithium difluoro-2-methyl-2-fluoromalonatoborate (LiDFMFMB), lithium difluoro-2-ethyl-2-fluoromalonatoborate (LiDFEFMB), and lithium difluoro-2-propyl-2-fluoromalonatoborate (LiDFPFMB), have been synthesized and evaluated for application in lithium ion batteries. These new salts are soluble in a mixture of ethylene carbonate (EC) and ethyl methyl carbonate (EMC) (1:2 by wt) and 1.0 M salt solutions can be easily prepared. The ionic conductivities of these new salts are close to those of LiBF4 and LiPF6. Cyclic voltammograms reveal that these new salt based electrolytes can passivate both natural graphite and high voltage spinel LiNi0.5Mn1.5O4 (LNMO) to form effective solid electrolyte interphases (SEIs). In addition, these new salt-based electrolytes exhibit good cycling stability with high coulombic efficiencies in both LiNi0.5Mn1.5O4 and graphite based half-cells and full cells.
- Sun, Xiao-Guang,Wan, Shun,Guang, Hong Yu,Fang, Youxing,Reeves, Kimberly Shawn,Chi, Miaofang,Dai, Sheng
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p. 1233 - 1241
(2017/02/05)
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- HETEROARYL COMPOUNDS AS IRAK INHIBITORS AND USES THEREOF
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The present invention relates to compounds of Formula (I) and pharmaceutically acceptable compositions thereof, useful as IRAK inhibitors.
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Paragraph 00160
(2017/04/11)
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- METHOD FOR PRODUCING FLUOROMALONIC ESTER DERIVATIVE
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PROBLEM TO BE SOLVED: To provide a method for producing a fluoromalonic ester derivative, useful as a raw material of electronic materials and as a synthetic intermediate of an agrochemical, which does not use or waste an expensive fluorinating agent and also has a short process. SOLUTION: A fluoromalonic ester derivative represented by a formula (2) is produced by reacting a malonic ester derivative with the 2-position modified with R3 with N-fluoro-bis(methanesulfonyl)imide in the presence of a Lewis acid. (R1 and R2 are each independently a methyl group, an ethyl group, a C3-4 linear, branched or cyclic alkyl group, a phenyl group, or a benzyl group; and R3 is H, a methyl group or an ethyl group.) SELECTED DRAWING: None COPYRIGHT: (C)2016,JPO&INPIT
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Paragraph 0031-0033
(2017/02/24)
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- Methyl NFSI: Atom-economical alternative to NFSI shows higher fluorination reactivity under Lewis acid-catalysis and non-catalysis
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Me-NFSI was first reported in 1994. Despite its atom-economical structure and similarity to a well-explored fluorinating reagent, NFSI, Me-NFSI has not appeared in the literature in over 20 years. We disclose that Me-NFSI is more effective for the fluorination of active methines under Lewis acid-catalysis and non-catalysis than NFSI.
- Fukushi, Kazunobu,Suzuki, Satoru,Kamo, Tomohiro,Tokunaga, Etsuko,Sumii, Yuji,Kagawa, Takumi,Kawada, Kosuke,Shibata, Norio
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supporting information
p. 1864 - 1868
(2016/04/19)
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- Are carboxylic esters really refractory to DAST? On the fluorination of α-hydroxyesters with DAST
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Diethyl 2-alkyl-2-hydroxymalonates react with DAST almost exclusively at the ester carbonyl giving a mixture of ethyl 2-(ethoxydifluoromethyl)-2-hydroxyalkanoates, 1,1-bis(ethoxydifluoromethyl)alkan-1-ols when administered at room temperature in dichloromethane. The reaction was exploited in the synthesis of nucleus- and side-chain polyfluorinated indoles. The fluorination of substituted diethyl 2-[(1-tert-butoxycarbonylindol-3-yl)methyl]-2-hydroxymalonates with DAST gave a mixture of ethyl 2-(ethoxydifluoromethyl)-2-hydroxy-3-(1-tert-butoxycarbonylindol-3-yl)propionate, diastereomeric 1′-tert-butoxycarbonyl-2′-hydroxy-2,2-diethoxycarbonylspiro(cyclopropane-1,3′-indoline) and only traces of 1,1-bis(ethoxydifluoromethyl)-2-(1-tert-butoxycarbonylindol-3-yl)ethanol. The composition of these mixtures changes depending on the reaction conditions. Regioselectively substituted ethyl 2-hydroxy-2-[(1-tert-butoxycarbonylindol-3-yl)methyl]-3,3,3-trifluoropropionate reacts with DAST at 0 °C in dichloromethane giving satisfactory yields of the corresponding 1-ethoxy-2-[(1-tert-butoxycarbonylindol-3-yl)methyl]-1,1,3,3,3-pentafluoropropan-2-ols as the exclusive reaction products. In the same reaction conditions, ethyl 3-(1-tert-butoxycarbonylindol-3-yl)-2-hydroxypropionate mainly provides 1′-tert-butoxycarbonyl-2′-hydroxy-2,2-diethoxycarbonylspiro(cyclopropane-1,3′-indoline) together with the “normal” fluorination product ethyl 3-(1-tert-butoxycarbonylindol-3-yl)-2-fluoropropionate. A plausible mechanism of this process is proposed in the following.
- Lepri, Susan,Buonerba, Federica,Maccaroni, Paola,Goracci, Laura,Ruzziconi, Renzo
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supporting information
p. 82 - 91
(2015/04/27)
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- METHOD OF PRODUCING MONOFLUOROMALONIC ACID DERIVATIVE
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PROBLEM TO BE SOLVED: To provide a method of producing a monofluoromalonic acid ester derivative that has a high yield, facilitates separation of a product, and allows industrial production. SOLUTION: A malonic acid ester derivative (1) is reacted with a hydrogen fluoride source in the presence of an iodosylbenzene derivative or an iodobenzene derivative and an oxidizing agent, to produce a monofluoromalonic acid derivative (4). COPYRIGHT: (C)2015,JPOandINPIT
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Paragraph 0046-0049
(2017/02/24)
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- A stable fluorinated and alkylated lithium malonatoborate salt for lithium ion battery application
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A new fluorinated and alkylated lithium malonatoborate salt, lithium bis(2-methyl-2-fluoromalonato)borate (LiBMFMB), has been synthesized for lithium ion battery application. A 0.8 M LiBMFMB solution is obtained in a mixture of ethylene carbonate (EC) and ethyl methyl carbonate (EMC) (1:2 by wt). The new LiBMFMB based electrolyte exhibits good cycling stability and rate capability in LiNi0.5Mn1.5O4 and graphite based half-cells.
- Wan, Shun,Jiang, Xueguang,Guo, Bingkun,Dai, Sheng,Goodenough, John B.,Sun, Xiao-Guang
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supporting information
p. 9817 - 9820
(2015/06/16)
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- A Convenient Synthesis of 2-Fluoro- and 2-Chloromalonic Esters Mediated by Hypervalent Iodine
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Direct fluorination of malonic esters with a reagent system of iodosylbenzene and Et3N·5HF gave the corresponding 2-fluoromalonic esters in good to high yields. Direct chlorination using iodosylbenzene and hydrochloric acid also provided the 2-chloromalonates in high yields.
- Kitamura, Tsugio,Muta, Kensuke,Oyamada, Juzo
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p. 3241 - 3245
(2015/10/19)
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- Induction of B- to Z-DNA transition by copper and zinc complexes with C(15) substituted macrocyclic pentaaza ligands
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The new macrocyclic ligand 15-fluoro-15-methyl-l,4,7,10,13- pentaazacyclohexadecan-14,16-dione (2) was synthesised and its crystal structure determined together with the ones of the known analogues of 2, 15-fluoro-1,4,7,10,13-pentaazacyclohexadecan-14,16-dione (1) and 15,15-difluoro-1,4,7,10,13-pentaazacyclohexadecan-14,16-dione (3). The binding behaviour of all three ligands to copper and zinc was studied in the solid state. They can bind to the metal centre by either triple coordination (N3) with all secondary amines or after double deprotonation of the two amides with all five nitrogen atoms (N5). The N5 coordination mode is favoured by the presence of one or two fluorine substituents at the C(15) position and by a high pH in the case of aqueous solutions. Circular dichroism titrations of poly d(GC) with the metal complexes showed that only 4 and 5, that is the copper complexes of 1 and 2, induced a complete B- to Z-DNA transition. The degree of cooperativity of the transition was found to be 3.4 and 7.3 for 4 and 5 respectively. As a possible hypothesis to explain this difference, the additional methyl group in 5 compared with 4 may be involved in a hydrophobic interaction with the DNA. Ligand 2, the copper complex 6 of the bis fluoro substituted ligand 3, and the zinc complex 7 of ligand 1 did not induce any change in the direction of Z-DNA. In the case of 6, the CD spectrum of the DNA actually showed no change at all, indicating that the complex was even not interacting with the B form of DNA. Therefore it is assumed that the bis fluoro substitution is causing the complex to be in the neutral N5 coordination mode at the experimental conditions of pH 7. The electrostatic contribution together with the shielding effect of the ligand might explain the absence of any interaction with the DNA. The Royal Society of Chemistry 2005.
- Spingler, Bernhard,Da Pieve, Chiara
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p. 1637 - 1643
(2007/10/03)
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- Process for the preparation of esters
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A process for the preparation of an ester, especially fluorinated esters R1 O.OC--CHR2 --CO.OR3, R1 and R3 are each independently selected from alkyl, cycloalkyl and aryl. R2 is selected from hydrogen, alkyl, cycloalkyl. The method includes the steps of covering a corresponding compound of formula 2: R1 O.OC--CHR2 --CO.OR3 in the presence of a base, of salt of a compound of formula 2, into corresponding compound of formula 1 by the reaction of elemental fluorine.
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- Elemental fluorine. Part 3 [1]. The preparation of dialkyl fluoromalonates by direct fluorination
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Dialkyl fluoromalonates have been prepared by treating the sodium derivatives of the parent dialkyl malonates with elemental fluorine.
- Chambers,Hutchinson,Thomson
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p. 165 - 166
(2007/10/03)
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- Site-Selective Fluorination of Organic Compounds Using 1-Alkyl-4-fluoro-1,4-diazabicyclooctane Salts (Selectfluor Reagents)
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The new "N-F"-type electrophilic reagent family of 1-alkyl-4-fluoro-1,4-diazabicyclooctane salts (derived from elemental fluorine (F2) and 1-alkyl-1,4-diazabicyclooctane salts) has been found to be very effective for the fluorination of a wide variety of organic substrates.These include steroidal enol acetates and silyl enol ethers, phenyl-substituted olefins, sulfides bearing α-H atoms, certain carbanions, and mildly activated aromatic compounds.The products were obtained with good yields and regioselectivity under very mild reaction conditions.
- Lal, G. Sankar
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p. 2791 - 2796
(2007/10/02)
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- Nucleophilic substitution versus electron transfer: 2. SN2 at fluorine and electron transfer are competing and different pathways in electrophilic fluorinations
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A comparison between the observed rate constants of electrophilic fluorinations and the calculated rates for electron transfer gives for the first time kinetic proof that nucleophilic attack at fluorine has to occur in order to explain the high reaction rates. The low yields of fluorinated products under conditions where ET becomes important are an indication that SN2 and ET are competing and different pathways.
- Differding,Wehrli
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p. 3819 - 3822
(2007/10/02)
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- Power and structure-variable fluorinating agents. The N-fluoropyridinium salt system
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The usefulness of the N-fluoropyridinium salt system as a source of fluorinating agents was examined by using substituted or unsubstituted N-fluoropyridinium triflates 1-11, N-fluoropyridinium salts possessing other counteranions 1a-d and 3a, and the counteranion-bound salts, N-fluoropyridinium-2-sulfonates 12 and 13. Electrophilic fluorinating power was found to vary remarkably according to the electronic nature of the ring substituents. This power increased as the electron density of positive nitrogen sites decreased, and this was correlated to the pKa values of the corresponding pyridines. By virtue of this variation, it was possible to fluorinate a wide range of nucleophilic substrates differing in reactivity. It is thus possible to fluorinate aromatics, carbanions, active methylene compounds, enol alkyl or silyl ethers, vinyl acetates, ketene silyl acetals, and olefins through the proper use of salts pentachloro 6 through 2,4,6-trimethyl 2, their power decreasing in this order. All the reactions could be explained on the basis of a one-electron-transfer mechanism. N-Fluoropyridinium salts showed high chemoselectivity in fluorination, the extent depending on the reactive moiety. In consideration of these Findings, selective 9α-fluorination of steroids was carried out by reacting 1 with tris(trimethylsilyl ether) 73 of a triketo steroid. Regio- or stereoselectivity in fluorination was determined by a N-fluoropyridinium salt structure. Steric bulkiness of the N-F surroundings hindered the ortho fluorination of phenols and aniline derivatives, while the capacity for hydrogen bonding on the part of the counteranions prompted this process, and the counteranion-bound salts 12 and 13 underwent this fluorination exclusively or almost so. Both bulky N-fluoropyridinium triflates 2 and 7 preferentially attacked the 6-position of the conjugated vinyl ester of a steroid from the unhindered β-direction to give a thermally unstable 6β-fluoro isomer. On the basis of these results, N-fluoropyridinium salts may be concluded to constitute a system that can serve as a source of the most ideal fluorinating agents for conducting desired selective fluorination through fluorinating capacity or structural alteration.
- Umemoto, Teruo,Fukami, Shinji,Tomizawa, Ginjiro,Harasawa, Kikuko,Kawada, Kosuke,Tomita, Kyoichi
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p. 8563 - 8575
(2007/10/02)
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- Carbanion Fluorination with Xenon Difluoride in the Presence of Sulfur (II) Derivatives
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An electrophilic fluorination reagent capable of fluorinating carbanions in moderate yield is obtained from the reaction of xenon difluoride with Sulfur II derivatives such as dimethyl sulfide.
- Patrick, Timothy B.,Nadji, Sourena
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p. 415 - 420
(2007/10/02)
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- N-FLUOROPYRIDINIUM TRIFLATE AND ITS DERIVATES: USEFUL FLUORINATING AGENTS
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N-Fluoropyridinium triflate and its derivates, stable and nonhygroscopic crystals, were found to be widely applicable reagents for mild and selective fluorination of a variety of organic compounds.
- Umemoto, Teruo,Kawada, Kosuke,Tomita, Kyoichi
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p. 4465 - 4468
(2007/10/02)
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- Fluorination of carbanions with N-fluoro-N-alkylsulfonamides
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Process for fluorinating an organic carbanion, which process comprises contacting and reacting, in a dry inert atmosphere, the compound of the formula selected from STR1 wherein STR2 is the carbanion, M is a counter ion, and X is a halide and a selected N-flouro-N-alkylsulfonamide.
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- 1-Fluoro-2-pyridone: A Useful Fluorinating Reagent
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1-Fluoro-2-pyridone (mp 50-53 degC) has been prepared by reaction of 5percent fluorine in nitrogen and 2-(trimethylsiloxy)pyridine in FCCl3 at -78 degC.After sublimation, the pyridone is used as a selective fluorinating agent in the preparation of some fl
- Purrington, Suzanne T.,Jones, Walda Ann
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p. 761 - 762
(2007/10/02)
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