- FAR INFRARED SPECTRA AND BARRIERS TO INTERNAL ROTATION OF BENZALDEHYDE, BENZOYL FLUORIDE, BENZOYL CHLORIDE AND ACETOPHENONE
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The far infrared (250-40 cm-1) spectra of gaseous benzaldehyde, benzoyl fluoride, benzoyl chloride and acetophenone have been recorded.The fundamental CHO torsion for benzaldehyde has been observed at 110.85 cm-1 with three excited states at 109.51, 106.52 and 104.17 cm-1 along with several "hot bands" arising from the frequency bending modes.The corresponding fundamental for benzoyl fluoride has been observed at 63.36 cm-1 with one well defined excited state at 61.91 cm-1.Similarly, bands observed at 44.6 and 49.5 cm-1 in the spectra of benzoyl chloride and acetophenone, respectively, have been assigned to the fundamental CXO torsions of these molecules.These data have allowed for the determination of the twofold barrier which governs the internal rotation of the CXO moiety and have been found to be 1611 cm-1 (4.61 kcal mol-1), 1739 cm-1 (4.97 kcal mol-1), 1162 cm-1 (3.32 kcal mol-1) and 1103 cm-1 (3.15 kcal mol-1) for the aldehyde, fluoride, chloride and ketone, respectively.These results are compared to previously obtained values for two of the molecules and to some corresponding barriers for several related molecules.
- Durig, J. R.,Bist, H. D.,Furic, K.,Qiu, J.,Little, T. S.
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Read Online
- Proton Sponge Hydrofluoride as a Soluble Fluoride Ion Source
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Proton Sponge (PS) hydrofluoride has been prepared and is totally soluble in acetonitrile; this system was used to generate carbanions from hexafluoropropene and to form carbon-fluorine bonds by reaction with 2,4,6-trichloropyrimidine and by reaction with benzoyl chloride (Proton Sponge hydrochloride is insoluble in acetonitrile).
- Chambers, Richard D.,Holmes, Thomas F.,Korn, Stewart R.,Standford, Graham
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Read Online
- Acyl fluorides from carboxylic acids, aldehydes, or alcohols under oxidative fluorination
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We describe a novel reagent system to obtain acyl fluorides directly from three different functional group precursors: carboxylic acids, aldehydes, or alcohols. The transformation is achieved via a combination of trichloroisocyanuric acid and cesium fluoride, which facilitates the synthesis of various acyl fluorides in high yield (up to 99%). It can be applied to the late-stage functionalization of natural products and drug molecules that contain a carboxylic acid, an aldehyde, or an alcohol group.
- Liang, Yumeng,Zhao, Zhengyu,Taya, Akihito,Shibata, Norio
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supporting information
p. 847 - 852
(2021/02/06)
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- Gram-Scale Preparation of Acyl Fluorides and Their Reactions with Hindered Nucleophiles
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A series of acyl fluorides was synthesized at 100 mmol scale using phase-transfer-catalyzed halogen exchange between acyl chlorides and aqueous bifluoride solution. The convenient procedure consists of vigorous stirring of the biphasic mixture at room temperature, followed by extraction and distillation. Isolated acyl fluorides (usually 7-20 g) display excellent purity and can be transformed into sterically hindered amides and esters when treated with lithium amide bases and alkoxides under mild conditions.
- Barbasiewicz, Micha?,Tryniszewski, Micha?
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supporting information
(2021/11/30)
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- Metal-free approach for hindered amide-bond formation with hypervalent iodine(iii) reagents: application to hindered peptide synthesis
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A new bio-inspired approach is reported for amide and peptide synthesis using α-amino esters that possess a potential activating group (PAG) at the ester residue. To activate the ester functionality under mild metal-free conditions, we exploited the facile dearomatization of phenols with hypervalent iodine(iii) reagents. Using a pyridine-hydrogen fluoride complex, highly reactive acyl fluoride intermediates can be successfully generated, thereby allowing for the smooth formation of sterically hindered amides and peptides from bulky amines and α-amino esters, respectively.
- Lee, Hyo-Jun,Huang, Xiao,Sakaki, Shigeyoshi,Maruoka, Keiji
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p. 848 - 855
(2021/02/09)
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- Cooperative NHC/Photoredox Catalyzed Ring-Opening of Aryl Cyclopropanes to 1-Aroyloxylated-3-Acylated Alkanes
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Cyclopropanes are an important class of building blocks in organic synthesis. Herein, a ring-opening/arylcarboxylation/acylation cascade reaction for the 1,3-difunctionalization of aryl cyclopropanes enabled by cooperative NHC and organophotoredox catalysis is reported. The cascade works on monosubstituted cyclopropanes that are in contrast to the heavily investigated donor–acceptor cyclopropanes more challenging to be difunctionalized. The key step is a radical/radical cross coupling of a benzylic radical generated in the photoredox catalysis cycle with a ketyl radical from the NHC catalysis cycle. The transformation features metal-free reaction conditions and tolerates a diverse range of functionalities.
- Daniliuc, Constantin G.,Studer, Armido,Zuo, Zhijun
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supporting information
p. 25252 - 25257
(2021/10/29)
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- Radical-Mediated Activation of Esters with a Copper/Selectfluor System: Synthesis of Bulky Amides and Peptides
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Herein, we describe a new approach for the activation of esters via a radical-mediated process enabled by a copper/Selectfluor system. A variety of para-methoxybenzyl esters derived from bulky carboxylic acids and amino acids can be easily converted into the corresponding acyl fluorides, directly used in the one-pot synthesis of amides and peptides. As a proof of concept, this method was applied to the iterative formation of sterically hindered amide bonds.
- Matsumoto, Akira,Wang, Zhe,Maruoka, Keiji
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p. 5401 - 5411
(2021/04/12)
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- Fluorination method
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In order to overcome the problems of high cost and low stability of the existing fluorination reagents for preparing acyl fluoride, sulfonyl fluoride and phosphoryl fluoride compounds, the invention provides a fluorination method, which comprises the following operation steps of: adding a fluorination reagent into a substrate, wherein the fluorination reagent comprises cations M and anions, the anions are selected from one or more of perfluoropolyether chain carboxylic acid anions as shown in the specification: CF3(OCF2)nCO2, wherein n is selected from 1-10; the substrate comprises a carboxylic acid compound, a sulfonic acid compound, a phosphoric acid compound and a phosphine oxide compound; and carrying out fluorination reaction to obtain acyl fluoride, sulfonyl fluoride and phosphoryl fluoride products. According to the fluorination method provided by the invention, the perfluoropolyether chain carboxylate is used as a fluorination reagent, so that the dehydroxylation fluorination reaction of the carboxylic acid compound, the sulfonic acid compound and the phosphoric acid compound and the fluorination reaction of the phosphine oxide compound are realized, the product yield isrelatively high, and the fluorination method has relatively good universality for different substrates.
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Paragraph 0081-0125
(2021/01/12)
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- Deoxyfluorination of Carboxylic, Sulfonic, Phosphinic Acids and Phosphine Oxides by Perfluoroalkyl Ether Carboxylic Acids Featuring CF2O Units
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The deoxyfluorination of carboxylic, sulfonic, phosphinic acids and phosphine oxides is a fundamentally important approach to access acyl fluorides, sulfonyl fluorides and phosphoric fluorides, thus the development of inexpensive, stable, easy-to-handle, versatile, and efficient deoxyfluorination reagents is highly desired. Herein, we report the use of potassium salts of perfluoroalkyl ether carboxylic acids (PFECA) featuring CF2O units as deoxyfluorination reagents, which are generated mainly as by-products in the manufacture of hexafluoropropene oxide (HFPO). The synthesis of acyl fluorides, sulfonyl fluorides and phosphoric fluorides can be realized via carbonic difluoride (COF2) generated in situ from thermal degradation of the PFECA salt.
- Zhao, Shiyu,Guo, Yong,Su, Zhaoben,Wu, Chengying,Chen, Wei,Chen, Qing-Yun
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supporting information
p. 1225 - 1232
(2021/05/04)
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- Deoxyfluorination of Carboxylic Acids with CpFluor: Access to Acyl Fluorides and Amides
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3,3-Difluoro-1,2-diphenylcyclopropene (CpFluor), a bench-stable fluorination reagent, has been developed in the deoxyfluorination of carboxylic acids to afford various acyl fluorides. This all-carbon-based fluorination reagent enabled the efficient transformation of (hetero)aryl, alkyl, alkenyl, and alkynyl carboxylic acids to the corresponding acyl fluorides under the neutral conditions. This deoxyfluorination method was featured by the synthesis of acyl fluorides with in-situ formed CpFluor, as well as the one-pot amidation reaction of carboxylic acids via in-situ formed acyl fluorides.
- Wang, Xiu,Wang, Fei,Huang, Fengfeng,Ni, Chuanfa,Hu, Jinbo
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supporting information
p. 1764 - 1768
(2021/03/03)
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- Direct amidation of acid fluorides using germanium amides
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Amide functional groups are an essential linkage that are found in peptides, proteins, and pharmaceuticals and new methods are constantly being sought for their formation. Here, a new method for their preparation is presented where germanium amides Ph3GeNR2convert acid fluorides directly to amides. These germanium amides serve to abstract the fluorine atom of the acid fluoride and transfer their amide group -NR2to the carbonyl carbon, and so function as amidation reagents.
- Hayatifar, Ardalan,Elifritz, Emily A.,Bloom, Molly B.,Pixley, Kaitlyn M.,Fennell, Christopher J.,Weinert, Charles S.
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supporting information
p. 4490 - 4493
(2021/04/12)
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- Deoxyfluorination of Carboxylic Acids with KF and Highly Electron-Deficient Fluoroarenes
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A deoxyfluorination reaction of carboxylic acids using potassium fluoride (KF) and highly electron-deficient fluoroarenes is reported here, giving acyl fluorides in moderate to excellent yield (57-92% based on NMR integration and 34-95% for isolated examples).
- Mao, Siyu,Kramer, Jordan H.,Sun, Haoran
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p. 6066 - 6074
(2021/05/29)
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- Carboxylic Acid Deoxyfluorination and One-Pot Amide Bond Formation Using Pentafluoropyridine (PFP)
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This work describes the application of pentafluoropyridine (PFP), a cheap commercially available reagent, in the deoxyfluorination of carboxylic acids to acyl fluorides. The acyl fluorides can be formed from a range of acids under mild conditions. We also demonstrate that PFP can be utilized in a one-pot amide bond formation via in situ generation of acyl fluorides. This one-pot deoxyfluorination amide bond-forming reaction gives ready access to amides in yields of ≤94%.
- Brittain, William D. G.,Cobb, Steven L.
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supporting information
p. 5793 - 5798
(2021/08/01)
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- N-Hydroxybenzimidazole as a structurally modifiable platform forN-oxyl radicals for direct C-H functionalization reactions
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Methods for direct functionalization of C-H bonds mediated byN-oxyl radicals constitute a powerful tool in modern organic synthesis. While severalN-oxyl radicals have been developed to date, the lack of structural diversity for these species has hampered further progress in this field. Here we designed a novel class ofN-oxyl radicals based onN-hydroxybenzimidazole, and applied them to the direct C-H functionalization reactions. The flexibly modifiable features of these structures enabled facile tuning of their catalytic performance. Moreover, with these organoradicals, we have developed a metal-free approach for the synthesis of acyl fluoridesviadirect C-H fluorination of aldehydes under mild conditions.
- Hatanaka, Miho,Jiang, Julong,Maruoka, Keiji,Matsumoto, Akira,Sakamoto, Ryu,Sakurai, Shunya,Tsuzuki, Saori,Yoshii, Tomomi
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p. 5772 - 5778
(2020/06/22)
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- Synthesis of Arylstannanes via Palladium-Catalyzed Decarbonylative Coupling of Aroyl Fluorides
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Aryl stannanes are valuable precursors in organic transformations, but their synthetic methods are limited. Here we present a Pd-catalyzed decarbonylative stannylation of acid fluorides in the absence of exogenous base. Various aryl stannanes were efficiently prepared from bench-stable transition metal catalyst and ligand with broad functional group compatibility and substrate scope including natural products and pharmaceuticals. This protocol was also successfully used to a late-stage diversification of an existing uricosuric drug probenecid. (Figure presented.).
- Kayumov, Muzaffar,Zhao, Jian-Nan,Mirzaakhmedov, Sharafitdin,Wang, Dong-Yu,Zhang, Ao
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supporting information
p. 776 - 781
(2019/11/14)
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- Methoxylation of Acyl Fluorides with Tris(2,4,6-trimethoxyphenyl)phosphine via C-OMe Bond Cleavage under Metal-Free Conditions
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Acyl fluorides are subjected to methoxylation with tris(2,4,6-trimethoxyphenyl)phosphine (TMPP) to afford the corresponding methyl esters in good to excellent yields. This transformation is featured by C(sp2)-OMe bond cleavage under metal-free conditions. Unprecedented utilization of TMPP as a methoxylating agent realized the installation of an OMe group into the desired products.
- Ishida, Takumi,Nishihara, Yasushi,Wang, Xiu,Wang, Zhenhua
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p. 7526 - 7533
(2020/06/27)
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- C-F Bond Activation of a Perfluorinated Ligand Leading to Nucleophilic Fluorination of an Organic Electrophile
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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.
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supporting information
p. 2116 - 2124
(2020/07/23)
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- Efficient cleavage of tertiary amide bonds: Via radical-polar crossover using a copper(ii) bromide/Selectfluor hybrid system
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A novel approach for the efficient cleavage of the amide bonds in tertiary amides is reported. Based on the selective radical abstraction of a benzylic hydrogen atom by a CuBr2/Selectfluor hybrid system followed by a selective cleavage of an N-C bond, an acyl fluoride intermediate is formed. This intermediate may then be derivatized in a one-pot fashion. The reaction proceeds under mild conditions and exhibits a broad substrate scope with respect to the tertiary amide moiety as well as to nitrogen, oxygen, and carbon nucleophiles for the subsequent derivatization. Mechanistic studies suggest that the present reaction proceeds via a radical-polar crossover process that involves benzylic carbon radicals generated by the selective radical abstraction of a benzylic hydrogen atom by the CuBr2/Selectfluor hybrid system. Furthermore, a synthetic application of this method for the selective cleavage of peptides is described. This journal is
- Maruoka, Keiji,Matsumoto, Akira,Wang, Zhe
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p. 12323 - 12328
(2020/12/08)
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- Synthesis of Acyl Fluorides from Carboxylic Acids Using NaF-Assisted Deoxofluorination with XtalFluor-E
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The synthesis of acyl fluorides using the deoxofluorination reaction of carboxylic acids using XtalFluor-E is described. This transformation, assisted by a catalytic amount of NaF, occurs at room temperature in EtOAc, where XtalFluor-E behaves as the activating agent and the fluoride source. A wide range of acyl fluorides were obtained in moderate to excellent yields (36-99%) after a simple filtration on a pad of silica gel. We also demonstrated that sequential deoxofluorination/amidation was possible.
- Gonay, Marie,Batisse, Chloé,Paquin, Jean-Fran?ois
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p. 10253 - 10260
(2020/08/12)
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- Tertiary-Amine-Initiated Synthesis of Acyl Fluorides from Carboxylic Acids and CF3SO2OCF3
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A convenient method for deoxyfluorination of aromatic and aliphatic carboxylic acids with CF3SO2OCF3 in the presence of a suitable base at room temperature has been developed. The reaction allows a straightforward access to a variety of acyl fluorides and proves that CF3SO2OCF3 is an effective deoxyfluorination reagent for carboxylic acids. The method features simplicity, expeditiousness, high efficiency, ease of handling, good functional group tolerance, a wide range of substrates, excellent yields of products, compatibility of many amine initiators, use of environmentally friendly reagents, and effortless removal of byproducts. This reaction represents the first utilization of trifluoromethyl trifluoromethanesulfonate as a fluorination reagent.
- Song, Hai-Xia,Tian, Ze-Yu,Xiao, Ji-Chang,Zhang, Cheng-Pan
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supporting information
p. 16261 - 16265
(2020/12/01)
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- Halide-Accelerated Acyl Fluoride Formation Using Sulfuryl Fluoride
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Herein, we report a new one-pot sequential method for SO2F2-mediated nucleophilic acyl substitution reactions starting from carboxylic acids. A mechanistic study revealed that SO2F2-mediated acid activation proceeds via the anhydride, which is then converted to the corresponding acyl fluoride. Tetrabutylammonium chloride or bromide accelerate the formation of acyl fluoride. Optimized halide-accelerated conditions were used to synthesize acyl fluorides in 30-80percent yields, and esters, amides, and thioesters in 72-96percent yields without reoptimization for each nucleophile.
- Foth, Paul J.,Malig, Thomas C.,Yu, Hao,Bolduc, Trevor G.,Hein, Jason E.,Sammis, Glenn M.
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supporting information
p. 6682 - 6686
(2020/09/02)
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- Rapid synthesis of acyl fluorides from carboxylic acids with Cu(O2CCF2SO2F)2
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Acyl fluorides have moderate electrophilicity and a very good balance between stability and reactivity. Utilization of acyl fluorides as versatile building blocks in transition-metal catalysis attracts fast-growing and great attention recently. Development of rapid and operationally simple synthetic methods for acyl fluorides has always been desirable. We report herein a rapid, simple and efficient acyl fluoride synthesis from carboxylic acids with Cu(O2CCF2SO2F)2 as a deoxofluorination reagent. Notably, Cu(O2CCF2SO2F)2 was readily prepared in large scale from inexpensive starting material, and previously used as a good trifluoromethylating reagent.
- Le, Bingjun,Wu, Hao,Hu, Xiaojun,Zhou, Xiumiao,Guo, Yong,Chen, Qing-Yun,Liu, Chao
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supporting information
(2020/11/20)
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- Benzoyl Fluorides as Fluorination Reagents: Reconstruction of Acyl Fluorides via Reversible Acyl C-F Bond Cleavage/Formation in Palladium Catalysis
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This report describes the formation of value-added acyl fluorides by means of palladium-catalyzed acyl-exchange reactions between acyl fluorides and acid anhydrides. This method allows using a simple and commercially available acyl fluoride, benzoyl fluoride, as the fluoride source for the easy and efficient preparation of a variety of more complex acyl fluorides. The results of this study suggest that this reaction proceeds via a reversible acyl C-F bond cleavage/formation at the palladium center.
- Ogiwara, Yohei,Hosaka, Shintaro,Sakai, Norio
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p. 856 - 861
(2020/03/05)
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- Organocatalyzed Fluoride Metathesis
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A new organocatalyzed fluoride metathesis reaction between fluoroarenes and carbonyl derivatives is reported. The reaction exchanges fluoride (F-) and alternate nucleophiles (OAc-, OCO2R-, SR-, Cl-, CN-, NCS-). The approach provides a conceptually novel route to manipulate the fluorine content of organic molecules. When the fluorination and defluorination steps are combined into a single catalytic cycle, a byproduct free and 100% atom-efficient reaction can be achieved.
- Mulryan, Daniel,White, Andrew J. P.,Crimmin, Mark R.
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supporting information
p. 9351 - 9355
(2020/11/30)
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- Carbonyl-Directed Aliphatic Fluorination: A Special Type of Hydrogen Atom Transfer Beats out Norrish II
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Recently, our group reported that enone and ketone functional groups, upon photoexcitation, can direct site-selective sp3 C-H fluorination in terpenoid derivatives. How this transformation actually occurred remained mysterious, as a significant number of mechanistic possibilities came to mind. Herein, we report a comprehensive study describing the reaction mechanism through kinetic studies, isotope-labeling experiments, 19F NMR, electrochemical studies, synthetic probes, and computational experiments. To our surprise, the mechanism suggests intermolecular hydrogen atom transfer (HAT) chemistry is at play, rather than classical Norrish hydrogen atom abstraction as initially conceived. What is more, we discovered a unique role for photopromoters such as benzil and related compounds that necessitates their chemical transformation through fluorination in order to be effective. Our findings provide documentation of an unusual form of directed HAT and are of crucial importance for defining the necessary parameters for the development of future methods.
- Ghorbani, Fereshte,Harry, Stefan Andrew,Capilato, Joseph N.,Pitts, Cody Ross,Joram, Jacob,Peters, Garvin N.,Tovar, John D.,Smajlagic, Ivor,Siegler, Maxime A.,Dudding, Travis,Lectka, Thomas
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p. 14710 - 14724
(2020/10/13)
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- Oxidatively Induced Aryl-CF3 Coupling at Diphosphine Nickel Complexes
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This communication describes the synthesis of a series of diphosphine NiII(Ph)(CF3) complexes and studies of their reactivity toward oxidatively induced Ph-CF3 bond-forming reductive elimination. Treatment of these complexes with the one-electron outer-sphere oxidant ferrocenium hexafluorophosphate (FcPF6) affords benzotrifluoride, but the yield varies dramatically as a function of diphosphine ligand. Diphosphines with bite angles of less than 92° afforded 3. In contrast, those with bite angles between 95 and 102° formed PhCF3 in yields ranging from 62 to 77%.
- Bour, James R.,Roy, Pronay,Canty, Allan J.,Kampf, Jeff W.,Sanford, Melanie S.
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supporting information
p. 3 - 7
(2020/01/03)
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- Unusual Electronic Effects of Ancillary Ligands on the Perfluoroalkylation of Aryl Iodides and Bromides Mediated by Copper(I) Pentafluoroethyl Complexes of Substituted Bipyridines
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Several perfluoroalkylcopper compounds have been reported previously that serve as reagents or catalysts for the perfluoroalkylation of aryl halides. However, the relationships between the reactivity of such complexes and the electronic properties of the ancillary ligands are unknown, and such relationships are not well-known in general for copper complexes that mediate or catalyze cross coupling. We report the synthesis and characterization of a series of pentafluoroethylcopper(I) complexes ligated by bipyridine ligands possessing varied electronic properties. In contrast to the limited existing data on the reactivity of L2Cu(I)-X complexes bearing amine and pyridine-type ligands in Ullmann-type aminations with aryl halides, the reactions of aryl halides with pentafluoroethylcopper(I) complexes bearing systematically varied bipyridine ligands were faster for complexes bearing less electron-donating bipyridines than for complexes bearing more electron-donating bipyridines. Analysis of the rates of reaction and the relative populations of the neutral complexes [(R2bpy)CuC2F5] and ionic complexes [(R2bpy)2Cu][Cu(C2F5)2] formed by these reagents in solution suggests that this effect of electronics on the reaction rate results from an unusual trend of faster oxidative addition of aryl halides to [(R2bpy)CuC2F5] complexes containing less electron-donating R2bpy ligands than to those containing more electron-donating R2bpy ligands.
- Kalkman, Eric D.,Mormino, Michael G.,Hartwig, John F.
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supporting information
p. 19458 - 19465
(2019/12/25)
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- Nickel-catalyzed decarbonylative stannylation of acyl fluorides under ligand-free conditions
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Nickel-catalyzed decarbonylative stannylation of acyl fluorides under ligand-free conditions was disclosed. A variety of aromatic acyl fluorides are capable of reacting with silylstannanes in the presence of cesium fluoride. A one-pot decarbonylative stannylation/Migita-Kosugi-Stille reaction of benzoyl fluoride, giving rise to the direct formation of the corresponding cross-coupled products, further demonstrated the synthetic utility of the present method. This newly developed methodology with a good functional-group compatibility via C-F bond cleavage and C-Sn bond formation under nickel catalysis opens a new area for the functionalization of acyl fluorides in terms of carbon-heteroatom bond formation.
- Wang, Xiu,Wang, Zhenhua,Liu, Li,Asanuma, Yuya,Nishihara, Yasushi
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- Synthesis of 2-Substituted Propenes by Bidentate Phosphine-Assisted Methylenation of Acyl Fluorides and Acyl Chlorides with AlMe3
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Bidentate phosphine-assisted methylenation of acyl fluorides and acyl chlorides with substituted with aryl, alkenyl, and alkyl groups trimethylaluminum afforded an array of 2-substituted propene derivatives. The addition of a catalytic amount of DPPM increased an efficiency of the reactions. Trimethylaluminum as the methylenation reagent not only eliminates the presynthesis of methylene transfer reagent, but provides an efficient method for the synthesis of a series of 2-substituted propenes.
- Wang, Xiu,Wang, Zhenhua,Asanuma, Yuya,Nishihara, Yasushi
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supporting information
p. 3640 - 3643
(2019/05/17)
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- Selective C?N Bond Cleavage of N-Acylisatins: Towards High Performance Acylation/Arylation/Transamination Reagents
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New multipurpose arylation/acylation/transamination reagents, N-acylisatins, have been developed by selective ‘inside-outside’ C?N bond cleavage under different catalytic conditions. As activated amides, N-acylisatins undergo Rh-catalyzed C?H arylation and Pd-catalyzed acylation by cleavage outside the C?N bond, and the desired biaryls and diaryl ketones were obtained in good to excellent yields. Generally, the combination of N-acylisatins with amines leads to a ring-opening reaction and formation of transamination products in a predictable manner through inside C?N bond cleavage. Interestingly, treatment of N-acylisatins with amines lead to unexpected outer-ring transamination products when CsF is added, which shows that CsF can favor the outside C?N bond cleavage path. Notably, this work presents a new strategy for multiple chemical transformations of a single amide to achieve various products by selective C?N bond cleavage. (Figure presented.).
- Xiong, Li,Deng, Rong,Liu, Tingting,Luo, Zhongfeng,Wang, Zijia,Zhu, Xiao-Feng,Wang, Hui,Zeng, Zhuo
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p. 5383 - 5391
(2019/11/03)
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- Cesium Fluoride and Copper-Catalyzed One-Pot Synthesis of Benzoxazoles via a Site-Selective Amide C?N Bond Cleavage
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We report herein a two-step one-pot strategy for the synthesis of benzoxazoles from amides by using cesium fluoride/copper as catalysts. This approach involves the in situ generation of acyl fluorides from the corresponding amides, and the acyl fluorides undergo transamidation and cyclization to give benzoxazoles in good yields. In this work, the amide C?N bonds are activated by CsF to form the acyl fluoride intermediates, which further react with o-bromoanilines to efficiently yield benzoxazoles. Notably, this methodology demonstrates a broad substrate scope, as primary/secondary benzamides are well tolerated, and this process might facilitate the development of one-pot transformations of amides. (Figure presented.).
- Luo, Zhongfeng,Wu, Hongxiang,Li, Yue,Chen, Yuwen,Nie, Jingyi,Lu, Siqi,Zhu, Yulin,Zeng, Zhuo
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p. 4117 - 4125
(2019/08/01)
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- Direct Access to Acyl Fluorides from Carboxylic Acids Using a Phosphine/Fluoride Deoxyfluorination Reagent System
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A fast and simple method for deoxyfluorination of carboxylic acids is presented. The protocol employs commodity chemicals (PPh3, NBS, fluoride), affording products in excellent yields under mild conditions. Acyloxyphosphonium ion, the key reaction intermediate, was identified by NMR spectroscopic methods. Br?nsted acidic conditions are essential for efficient C-F bond formation. The protocol displays scalability, high functional group tolerance, chemoselectivity, and easy purification of products. Deoxyfluorination of active pharmaceutical ingredients was established.
- Munoz, Socrates B.,Dang, Huong,Ispizua-Rodriguez, Xanath,Mathew, Thomas,Prakash, G.K. Surya
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- Catalytic C?H/C?F Coupling of Azoles and Acyl Fluorides
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A method for the palladium/copper-catalyzed direct acylation of azoles with acyl fluorides is described. This study reports the first examples of acyl fluorides being used as acylation reagents in transition-metal-catalyzed aromatic C?H bond functionalization reactions. Depending on the reaction temperature, decarbonylative coupling may also occur. Mechanistic studies suggest that the cleavage of the aromatic C?H bond, promoted by a copper-phosphine species, is not the rate-limiting step of this acylation.
- Ogiwara, Yohei,Iino, Yurika,Sakai, Norio
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p. 6513 - 6516
(2019/04/27)
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- Synthesis of acyl fluorides via photocatalytic fluorination of aldehydic C-H bonds
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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
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supporting information
p. 9985 - 9988
(2018/09/11)
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- The selective electrochemical fluorination of S-alkyl benzothioate and its derivatives
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We herein report that the regioselective anodic fluorination of S-alkyl benzothioate and its derivatives in various aprotic solvents using Et3N·nHF (n = 3-5) and Et4NF·nHF (n = 3-5) as supporting electrolyte and a fluorine source successfully provided the corresponding α-fluorinated products in moderate yields. Dichloromethane containing Et4NF·4HF was found to be the most suitable combination as electrolytic solvent and supporting salt as well as fluorine source for the anodic fluorination. The electrochemical fluorination of cyclic benzothioates such as benzothiophenone was also achieved.
- Kuribayashi, Shunsuke,Kurioka, Tomoyuki,Inagi, Shinsuke,Lu, Ho-Jung,Uang, Biing-Jiun,Fuchigami, Toshio
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p. 389 - 396
(2018/02/19)
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- Photochemical activation of SF6 by N-heterocyclic carbenes to provide a deoxyfluorinating reagent
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The activation of the greenhouse gas SF6 using electron-rich N-heterocyclic carbenes gave 2,2-difluoroimidazolines or 2,2-difluoroimidazolidines as well as 2-thio derivatives of the carbene precursors. The N-heterocyclic carbenes can also convert SF4 to give similar products. The difluoroimidazolidine derivatives were applied in deoxyfluorination reactions. Furthermore, the activation of SF6 and the fluorination can be coupled in a one-pot process to convert 1-octanol into 1-fluorooctane.
- Tomar, Pooja,Braun, Thomas,Kemnitz, Erhard
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supporting information
p. 9753 - 9756
(2018/09/10)
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- Trifluoromethyl Benzoate: A Versatile Trifluoromethoxylation Reagent
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Trifluoromethyl benzoate (TFBz) is developed as a new shelf-stable trifluoromethoxylation reagent, which can be easily prepared from inexpensive starting materials using KF as the only fluorine source. The synthetic potency of TFBz is demonstrated by trifluoromethoxylation-halogenation of arynes, nucleophilic substitution of alkyl (pseudo)halides, cross-coupling with aryl stannanes, and asymmetric difunctionalization of alkenes. The unprecedented trifluoromethoxylation-halogenation of arynes proceeds smoothly at room temperature with the aid of a crown ether-complexed potassium cation, which significantly stabilizes the trifluoromethoxide anion derived from TFBz.
- Zhou, Min,Ni, Chuanfa,Zeng, Yuwen,Hu, Jinbo
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supporting information
p. 6801 - 6805
(2018/05/31)
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- High-throughput evaluation of in situ-generated cobalt(III) catalysts for acyl fluoride synthesis
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Using a high-throughput experimental procedure, a series of cobalt(iii) complexes of the general formula CpRCo(I)(X)(L) were prepared and screened for their activity towards the catalytic nucleophilic fluorination of benzoyl chloride. A highly active catalyst was identified, and successfully employed in a mild and effective protocol for the synthesis of a group of acyl fluoride compounds.
- Lee, Graham M.,Clément, Roxanne,Baker, R. Tom
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p. 4996 - 5003
(2017/11/09)
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- Sulfur–Fluoride Exchange (SuFEx)-Mediated Synthesis of Sterically Hindered and Electron-Deficient Secondary and Tertiary Amides via Acyl Fluoride Intermediates
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Amide bond formation is one of the most executed reactions in chemistry and biology. This is largely due to the ubiquity of the amide functional group in biological molecules, natural products and pharmaceutically important drugs. We report here the development of “SuFExAmide”: a new sulfur–fluoride exchange (SuFEx) click chemistry based protocol for the efficient amidation of carboxylic acids via acyl fluoride intermediates. We have developed benzene-1,3-disulfonyl fluoride as a cost effective, powerful and versatile coupling agent, which delivers challenging secondary and tertiary amides in excellent yields from sterically hindered and electron-deficient amines. The straightforward method offers significant benefits over existing protocols in terms of substrate scope, efficiency and ease of operation and is demonstrated by the synthesis of 44 amides, including GNF6702, an antiprotozoal drug candidate. In the majority of cases, the amide products are obtained in high yield without the need for excess reagents or chromatographic purification.
- Smedley, Christopher J.,Barrow, Andrew S.,Spiteri, Christian,Giel, Marie-Claire,Sharma, Pallavi,Moses, John E.
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supporting information
p. 9990 - 9995
(2017/08/01)
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- Rearrangement in a Tripodal Nitroxide Ligand to Modulate the Reactivity of a Ti-F Bond
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The tripodal nitroxide ligand [(2-tBuNO)C6H4CH2)3N]3- (TriNOx3-) binds the Ti(IV) cation and prevents inner-sphere coordination of chloride in the complex [Ti(TriNOx)]Cl (1). The ligand undergoes an η2-NO to κ1-O rearrangement to enable a fluoride ion to bind in the related complex Ti(TriNOx)F (2). Computational and reactivity studies demonstrated that the ligand rearrangement contributed to the enthalpy change in the transfer of a fluoride anion.
- Boreen, Michael A.,Bogart, Justin A.,Carroll, Patrick J.,Schelter, Eric J.
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p. 9588 - 9593
(2015/10/12)
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- A convenient photocatalytic fluorination of unactivated C-H bonds
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Fluorination reactions are essential to modern medicinal chemistry, thus providing a means to block site-selective metabolic degradation of drugs and access radiotracers for positron emission tomography imaging. Despite current sophistication in fluorination reagents and processes, the fluorination of unactivated C-H bonds remains a significant challenge. Reported herein is a convenient and economic process for direct fluorination of unactivated C-H bonds that exploits the hydrogen abstracting ability of a decatungstate photocatalyst in combination with the mild fluorine atom transfer reagent N-fluorobenzenesulfonimide. This operationally straightforward reaction provides direct access to a wide range of fluorinated organic molecules, including structurally complex natural products, acyl fluorides, and fluorinated amino acid derivatives. The direct fluorination of unactivated C(sp3)-H bonds is catalyzed by the inexpensive photocatalyst tetrabutylammonium decatungstate (TBADT). This convenient reaction provides direct access to a wide range of fluorinated organic molecules, including structurally complex natural products, acyl fluorides, and fluorinated amino acids.
- Halperin, Shira D.,Fan, Hope,Chang, Stanley,Martin, Rainer E.,Britton, Robert
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supporting information
p. 4690 - 4693
(2014/05/20)
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- (Re)Investigation of the reactivity of uranium hexafluoride toward several organic functions at room temperature
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The annual worldwide production of UF6 is very large and this compound is not used. Consequently, it could be interesting to find some applications as organic reagent. UF6 could be considered as an oxidizer of various functions. However, it seems also present some possibilities as a fluorinating reagent in mild conditions.
- Roy, Olivier,Marquet, Bernard,Alric, Jean-Paul,Jourdan, Alex,Morel, Bertrand,Langlois, Bernard R.,Billard, Thierry
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- Palladium-catalyzed fluorocarbonylation using N-formylsaccharin as CO source: General access to carboxylic acid derivatives
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N-Formylsaccharin, an easily accessible crystalline compound, has been employed as an efficient CO source in Pd-catalyzed fluorocarbonylation of aryl halides to afford the corresponding acyl fluorides in high yields. The reactions use a near-stoichiometric amount of the CO source (1.2 equiv) and tolerate diverse functional groups. The acyl fluorides obtained could be readily transformed into various carboxylic acid derivatives such as carboxylic acid, esters, thioesters, and amides in a one-pot procedure.
- Ueda, Tsuyoshi,Konishi, Hideyuki,Manabe, Kei
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supporting information
p. 5370 - 5373
(2013/11/06)
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- Palladium-catalyzed carbonylative coupling reactions of aryl iodides with hexamethyldisilane (HMDS) to benzoyl silanes
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A novel procedure for the palladium-catalyzed carbonylative synthesis of acyl silanes has been developed. Starting from aryl iodides and hexamethyldisilane (HMDS) various benzoyl silanes are produced in moderate to good yields.
- Wu, Xiao-Feng,Neumann, Helfried,Beller, Matthias
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experimental part
p. 582 - 584
(2012/02/02)
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- Arylsulfur chlorotetrafluorides as useful fluorinating agents: Deoxo- and dethioxo-fluorinations
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Usage of arylsulfur chlorotetrafluorides 1 as versatile deoxo- and dethioxo-fluorinating agents is described. There have been developed two convenient methods for the in situ preparation of reactive arylsulfur trifluorides 2 from 1. The one is reduction of 1 with a reducer such as pyridine to 2, and the other is disproportionation of 1 with a diaryl disulfide to 2 with evolution of chlorine gas. The latter method is a convenient way to get neat 2 from 1. The in situ prepared 2 fluorinates many kinds of substrates such as alcohols, aldehydes, ketones, diketones, and carboxylic acids to give the corresponding CF, CF2, CF2CF2, and CF 3 compounds in high yields. 2 also fluorinates various sulfur compounds including CS groups to give CF2, OCF2, CF 3, and OCF3 compounds in high yields. Reactions of 2 with diols or bis(trimethylsilyl) derivatives of diols or amino alcohols provided the corresponding deoxofluoro-arylsulfinylation products in high yields. In addition, it has been found that chlorotetrafluorides 1 directly and effectively react with the sulfur compounds to give the corresponding fluoro compounds in high yields. Since they are the intermediates for the production of industrially useful arylsulfur pentafluorides, arylsulfur chlorotetrafluorides 1, in particular, phenylsulfur chlorotetrafluoride (1a) are expected to find use as inexpensive and versatile deoxo- and dethioxo-fluorinating agents for the preparation of many organofluoro compounds.
- Umemoto, Teruo,Singh, Rajendra P.
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experimental part
p. 17 - 27
(2012/09/07)
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- Nucleophilic fluorination reactions starting from aqueous fluoride ion solutions
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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.
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supporting information; experimental part
p. 1444 - 1446
(2011/05/08)
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- A convenient, one-pot procedure for the preparation of acyl and sulfonyl fluorides using Cl3CCN, Ph3P, and TBAF(t -BuOH) 4
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Various carboxylic acids were converted into acyl fluorides in excellent yields by treatment with trichloroacetonitrile, triphenylphosphine, and TBAF(t-BuOH)4 at room temperature. The reaction was applicable to the preparation of acid-sensitive amino acid fluorides without deprotection or rearrangement
- Kim, Joong-Gon,Jang, Doo Ok
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experimental part
p. 3049 - 3052
(2011/02/25)
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- Aminodifluorosulfinium salts: Selective fluorination reagents with enhanced thermal stability and ease of handling
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Diethylaminodifluorosulfinium tetrafluoroborate (XtalFluor-E) and morpholinodifluorosulfinium tetrafluoroborate (XtalFluor-M) are crystalline fluorinating agents that are more easily handled and significantly more stable than Deoxo-Fluor, DAST, and their analogues. These reagents can be prepared in a safer and more cost-efficient manner by avoiding the laborious and hazardous distillation of dialkylaminosulfur trifluorides. Unlike DAST, Deoxo-Fluor, and Fluolead, XtalFluor reagents do not generate highly corrosive free-HF and therefore can be used in standard borosilicate vessels. When used in conjunction with promoters such as Et3N3HF, Et3N2HF, or DBU, XtalFluor reagents effectively convert alcohols to alkyl fluorides and carbonyls to gem-difluorides. These reagents are typically more selective than DAST and Deoxo-Fluor and exhibit superior performance by providing significantly less elimination side products.
- Lheureux, Alexandre,Beaulieu, Francis,Bennett, Christopher,Bill, David R.,Clayton, Simon,Laflamme, Franois,Mirmehrabi, Mahmoud,Tadayon, Sam,Tovell, David,Couturier, Michel
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supporting information; experimental part
p. 3401 - 3411
(2010/07/07)
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- DISUBSTITUTED-AMINODIFLUOROSULFINIUM SALTS, PROCESS FOR PREPARING SAME AND METHOD OF USE AS DEOXOFLUORINATION REAGENTS
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The invention relates to disubstituted-aminodifluorosulfinium salts represented by the formula (I). Processes for preparing same and methods of use as deoxofluorinating reagent is also provided.
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Page/Page column 51
(2010/12/31)
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- Facile formation of N-acyl-oxazolidinone derivatives using acid fluorides
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A mild method is presented for the formation of N-acylated oxazolidinones that employs acid fluorides and mild bases, such as iPr 2NEt and NEt3. Optimized reaction conditions for two types of substrates have been developed utilizing either the oxazolidinone itself or the corresponding in situ generated O-silyloxazolidinones resulting in the formation of the desired N-acylated products in high yields of up to 98%.
- Schindler, Corinna S.,Forster, Patrik M.,Carreira, Erick M.
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supporting information; experimental part
p. 4102 - 4105
(2010/11/19)
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- A deeper insight into direct trifluoromethoxylation with trifluoromethyl triflate
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Commercially available fluorides (silver fluoride and n-tetrabutylammonium triphenyldifluorosilicate), combined with TFMT, allow a simple generation, in situ, of silver and n-tetrabutylammonium trifluoromethoxides which were able to react with electrophilic substrates. Silver trifluoromethoxide, which is usually more efficient than n-tetrabutylammonium trifluoromethoxide, converts, under mild conditions, primary aliphatic bromides and iodides, as well as primary and secondary benzylic or allylic bromides to the corresponding trifluoromethoxylated compounds. Several trifluoromethyl ethers, which could be valuable building-blocks, were prepared in such a way.
- Marrec, Olivier,Billard, Thierry,Vors, Jean-Pierre,Pazenok, Sergii,Langlois, Bernard R.
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experimental part
p. 200 - 207
(2010/04/30)
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