- Rapid and column-free syntheses of acyl fluorides and peptides usingex situgenerated thionyl fluoride
-
Thionyl fluoride (SOF2) was first isolated in 1896, but there have been less than 10 subsequent reports of its use as a reagent for organic synthesis. This is partly due to a lack of facile, lab-scale methods for its generation. Herein we report a novel protocol for theex situgeneration of SOF2and subsequent demonstration of its ability to access both aliphatic and aromatic acyl fluorides in 55-98% isolated yields under mild conditions and short reaction times. We further demonstrate its aptitude in amino acid couplings, with a one-pot, column-free strategy that affords the corresponding dipeptides in 65-97% isolated yields with minimal to no epimerization. The broad scope allows for a wide range of protecting groups and both natural and unnatural amino acids. Finally, we demonstrated that this new method can be used in sequential liquid phase peptide synthesis (LPPS) to afford tri-, tetra-, penta-, and decapeptides in 14-88% yields without the need for column chromatography. We also demonstrated that this new method is amenable to solid phase peptide synthesis (SPPS), affording di- and pentapeptides in 80-98% yields.
- Lee, Cayo,Sammis, Glenn M.,Thomson, Brodie J.
-
p. 188 - 194
(2021/12/31)
-
- Gram-Scale Preparation of Acyl Fluorides and Their Reactions with Hindered Nucleophiles
-
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?
-
-
- Metal-free approach for hindered amide-bond formation with hypervalent iodine(iii) reagents: application to hindered peptide synthesis
-
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
-
p. 848 - 855
(2021/02/09)
-
- Cooperative NHC/Photoredox Catalyzed Ring-Opening of Aryl Cyclopropanes to 1-Aroyloxylated-3-Acylated Alkanes
-
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
-
supporting information
p. 25252 - 25257
(2021/10/29)
-
- Fluorination method
-
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.
- -
-
Paragraph 0081-0125
(2021/01/12)
-
- 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 0111-0112; 0114-0115; 0126
(2021/05/29)
-
- Deoxyfluorination of Carboxylic, Sulfonic, Phosphinic Acids and Phosphine Oxides by Perfluoroalkyl Ether Carboxylic Acids Featuring CF2O Units
-
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
-
supporting information
p. 1225 - 1232
(2021/05/04)
-
- Deoxyfluorination of Carboxylic Acids with KF and Highly Electron-Deficient Fluoroarenes
-
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
-
p. 6066 - 6074
(2021/05/29)
-
- Deoxyfluorination of Carboxylic Acids with CpFluor: Access to Acyl Fluorides and Amides
-
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
-
supporting information
p. 1764 - 1768
(2021/03/03)
-
- Carboxylic Acid Deoxyfluorination and One-Pot Amide Bond Formation Using Pentafluoropyridine (PFP)
-
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.
-
supporting information
p. 5793 - 5798
(2021/08/01)
-
- Acyl fluorides from carboxylic acids, aldehydes, or alcohols under oxidative fluorination
-
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
-
supporting information
p. 847 - 852
(2021/02/06)
-
- Acyl fluorides as direct precursors to fluoride ketyl radicals: Reductive deuteration using SmI2and D2O
-
A highly chemoselective reductive deuteration of acyl fluorides to provide α,α-dideuterio alcohols with exquisite levels of deuterium incorporation was developed using SmI2 and D2O as the deuterium source. This method introduces acyl fluorides as attracti
- Li, Hengzhao,Peng, Mengqi,Lai, Zemin,Ning, Lei,Chen, Xingyue,Zhang, Xiaoxu,Wang, Pengjie,Szostak, Roman,Szostak, Michal,An, Jie
-
supporting information
p. 5195 - 5198
(2021/05/31)
-
- Synthesis of Acyl Fluorides via DAST-Mediated Fluorinative C-C Bond Cleavage of Activated Ketones
-
A new protocol for preparation of acyl fluorides was developed by recognizing activated ketones as starting materials. The method provides a different scope compared with previously reported methods that employ carboxylic acids as substrates. A working hypothesis of pull-and-push-driven fluorinative C-C bond cleavage was successfully demonstrated by the simple addition of diethylaminosulfur trifluoride (DAST) derivatives to α-oximinoketones. The designed reaction system led to a highly efficient and chemoselective reaction. The wide availability of the ketones allowed for a range of synthetically useful aryloyl and aliphatic acyl fluorides including those containing chiral skeletons. The method is mild, fast, scalable, and potentially one-pot operative.
- Kim, Danhee,Lim, Hee Nam
-
p. 7465 - 7469
(2020/10/09)
-
- Cooperative NHC and Photoredox Catalysis for the Synthesis of β-Trifluoromethylated Alkyl Aryl Ketones
-
Despite the great potential of radical chemistry in organic synthesis, N-heterocyclic carbene (NHC)-catalyzed reactions involving radical intermediates are not well explored. This communication reports the three-component coupling of aroyl fluorides, styrenes and the Langlois reagent (CF3SO2Na) to give various β-trifluoromethylated alkyl aryl ketones with good functional group tolerance in moderate to high yields by cooperative photoredox/NHC catalysis. The alkene acyltrifluoromethylation proceeds via radical/radical cross coupling of ketyl radicals with benzylic C-radicals. The ketyl radicals are generated via SET reduction of in situ formed acylazolium ions whereas the benzylic radicals derive from trifluoromethyl radical addition onto styrenes.
- D?ben, Nadine,Meng, Qing-Yuan,Studer, Armido
-
supporting information
p. 19956 - 19960
(2020/09/04)
-
- Synthesis of Arylstannanes via Palladium-Catalyzed Decarbonylative Coupling of Aroyl Fluorides
-
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
-
supporting information
p. 776 - 781
(2019/11/14)
-
- Methoxylation of Acyl Fluorides with Tris(2,4,6-trimethoxyphenyl)phosphine via C-OMe Bond Cleavage under Metal-Free Conditions
-
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
-
p. 7526 - 7533
(2020/06/27)
-
- Synthesis of Acyl Fluorides from Carboxylic Acids Using NaF-Assisted Deoxofluorination with XtalFluor-E
-
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
-
p. 10253 - 10260
(2020/08/12)
-
- Tertiary-Amine-Initiated Synthesis of Acyl Fluorides from Carboxylic Acids and CF3SO2OCF3
-
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
-
supporting information
p. 16261 - 16265
(2020/12/01)
-
- Halide-Accelerated Acyl Fluoride Formation Using Sulfuryl Fluoride
-
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.
-
supporting information
p. 6682 - 6686
(2020/09/02)
-
- Rapid synthesis of acyl fluorides from carboxylic acids with Cu(O2CCF2SO2F)2
-
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
-
supporting information
(2020/11/20)
-
- N-Hydroxybenzimidazole as a structurally modifiable platform forN-oxyl radicals for direct C-H functionalization reactions
-
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
-
p. 5772 - 5778
(2020/06/22)
-
- Efficient cleavage of tertiary amide bonds: Via radical-polar crossover using a copper(ii) bromide/Selectfluor hybrid system
-
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
-
p. 12323 - 12328
(2020/12/08)
-
- Benzoyl Fluorides as Fluorination Reagents: Reconstruction of Acyl Fluorides via Reversible Acyl C-F Bond Cleavage/Formation in Palladium Catalysis
-
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
-
p. 856 - 861
(2020/03/05)
-
- Nickel-catalyzed decarbonylative stannylation of acyl fluorides under ligand-free conditions
-
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
-
-
- Synthesis of 2-Substituted Propenes by Bidentate Phosphine-Assisted Methylenation of Acyl Fluorides and Acyl Chlorides with AlMe3
-
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
-
supporting information
p. 3640 - 3643
(2019/05/17)
-
- Direct Access to Acyl Fluorides from Carboxylic Acids Using a Phosphine/Fluoride Deoxyfluorination Reagent System
-
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
-
-
- Nickel-catalysed decarbonylative borylation of aroyl fluorides
-
The first Ni(cod)2/PPh3 catalyst system has been established for decarbonylative borylation of aroyl fluorides with bis(pinacolato)diboron. A wide range of functional groups in the substrates were well tolerated. The ease of access of the starting aroyl fluorides indicates that these results might become an alternative to the existing decarbonylation events.
- Wang, Zhenhua,Wang, Xiu,Nishihara, Yasushi
-
supporting information
p. 13969 - 13972
(2019/01/03)
-
- 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
-
supporting information
p. 9985 - 9988
(2018/09/11)
-
- Multiple Approaches to the in Situ Generation of Anhydrous Tetraalkylammonium Fluoride Salts for SNAr Fluorination Reactions
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This article focuses on the development of practical approaches to the in situ generation of anhydrous fluoride salts for applications in nucleophilic aromatic substitution (SNAr) reactions. We report herein that a variety of combinations of inexpensive nucleophiles (e.g., tetraalkylammonium cyanide and phenoxide salts) and fluorine-containing electrophiles (e.g., acid fluoride, fluoroformate, benzenesulfonyl fluoride, and aryl fluorosulfonate derivatives) are effective for this transformation. Ultimately, we demonstrate that the combination of tetramethylammonium 2,6-dimethylphenoxide and sulfuryl fluoride (SO2F2) serves as a particularly practical route to anhydrous tetramethylammonium fluoride. This procedure is applied to the SNAr fluorination of a range of electron-deficient aryl and heteroaryl chlorides as well as nitroarenes.
- Cismesia, Megan A.,Ryan, Sarah J.,Bland, Douglas C.,Sanford, Melanie S.
-
p. 5020 - 5026
(2017/05/24)
-
- Sulfur–Fluoride Exchange (SuFEx)-Mediated Synthesis of Sterically Hindered and Electron-Deficient Secondary and Tertiary Amides via Acyl Fluoride Intermediates
-
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.
-
supporting information
p. 9990 - 9995
(2017/08/01)
-
- Acyl azolium fluorides for room temperature nucleophilic aromatic fluorination of chloro- and nitroarenes
-
The reaction of acid fluorides with N-heterocyclic carbenes (NHCs) produces anhydrous acyl azolium fluorides. With appropriate selection of acid fluoride and NHC, these salts can be used for the room temperature SNAr fluorination of a variety of aryl chlorides and nitroarenes.
- Ryan, Sarah J.,Schimler, Sydonie D.,Bland, Douglas C.,Sanford, Melanie S.
-
supporting information
p. 1866 - 1869
(2015/04/27)
-
- Palladium-catalyzed fluorocarbonylation using N-formylsaccharin as CO source: General access to carboxylic acid derivatives
-
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
-
supporting information
p. 5370 - 5373
(2013/11/06)
-
- Equilibrium shift in the rhodium-catalyzed acyl transfer reactions
-
Rhodium/phosphine complexes catalyze equilibrium acyl transfer reactions between acid fluorides, aryl esters, acylphosphine sulfides, and thioesters. The use of appropriate co-substrates to accept heteroatom groups shifted the equilibrium to desired products. Acylphosphine sulfides and aryl esters were converted to acid fluorides using benzoylpentafluorobenzene as the fluoride donor, and the fluorination reaction of thioesters employed (4-tolylthio) pentafluorobenzene. Acid fluorides were converted into acylphosphine sulfides and thioesters using diphosphine disulfides and disulfides/triphenylphosphine, respectively. Aryl esters were obtained from acid fluorides and phenols in the presence of triphenylsilane. Aryl esters, acylphosphine sulfides, and thioesters were also interconverted in the presence of rhodium complexes. These rhodium-catalyzed acyl transfer reactions proceeded under neutral conditions without using acid or base. The involvement of acyl rhodium intermediates in these reactions was suggested by the carbothiolation reaction of thioesters and alkynes.
- Arisawa, Mieko,Igarashi, Yui,Kobayashi, Haruki,Yamada, Toru,Bando, Kentaro,Ichikawa, Takuya,Yamaguchi, Masahiko
-
supporting information; experimental part
p. 7846 - 7859
(2011/10/12)
-
- Rhodium-catalyzed interconversion between acid fluorides and thioesters controlled using heteroatom acceptors
-
A rhodium complex catalyzed the equilibrium acyl transfer reaction between acid fluorides and thioesters. In the presence of fluoride or thiolate acceptors, the reaction could be shifted to either product. RhH(PPh 3)4-dppe catalyzed the reaction of acid fluorides and diorgano disulfides in the presence of triphenylphosphine giving thioesters, which was accompanied by triphenylphosphine difluoride. The same complex catalyzed the reaction of aryl thioesters and hexafluorobenzene giving acid fluorides, which was accompanied by 1,4-di(arylthio)-2,3,5,6- tetrafluorobenzenes.
- Arisawa, Mieko,Yamada, Toru,Yamaguchi, Masahiko
-
supporting information; experimental part
p. 6090 - 6092
(2011/01/04)
-
- A convenient, one-pot procedure for the preparation of acyl and sulfonyl fluorides using Cl3CCN, Ph3P, and TBAF(t -BuOH) 4
-
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
-
experimental part
p. 3049 - 3052
(2011/02/25)
-
- Fluorination reactions in microreactors
-
The DAST-mediated conversion of a range of alcohols to the corresponding fluorides in a microstructured device is described. This safe, practical fluorination method will facilitate reactions currently challenging on large scale. The Royal Society of Chem
- Gustafsson, Tomas,Gilmour, Ryan,Seeberger, Peter H.
-
scheme or table
p. 3022 - 3024
(2009/02/04)
-
- [Bis(2-methoxyethyl)amino]sulfur Trifluoride, the Deoxo-Fluor Reagent: Application toward One-Flask Transformations of Carboxylic Acids to Amides
-
The use of the Deoxo-Fluor reagent is a versatile method for acyl fluoride generation and subsequent one-flask amide coupling. It provides mild conditions and facile purification of the desired products in good to excellent yields. We have explored the utility of this reagent for the one-flask conversion of acids to amides and Weinreb amides and as a peptide-coupling reagent.
- White, Jonathan M.,Tunoori, Ashok Rao,Turunen, Brandon J.,Georg, Gunda I.
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p. 2573 - 2576
(2007/10/03)
-
- Preparation of acyl fluorides with hydrogen fluoride-pyridine and 1,3-dicyclohexylcarbodiimide
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This work presents an efficient procedure for preparing acyl fluorides by simply reacting carboxylic acid with hydrogen fluoride-pyridine and 1,3-dicyclohexylcarbodiimide (DCC) in dichloromethane. The acyl fluorides were converted in situ to the corresponding benzyl carboxylic esters by adding benzyl alcohol and triethylamine to the reaction mixture.
- Chen, Chinpiao,Chien, Chin-Tzu,Su, Chu-Hsiang
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- 1-acyl-4-benzylpyridinium tetrafluoroborates: Stability, structural properties, and utilization for the synthesis of acyl fluorides
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1-Acyl-4-benzylpyridinium salts 4 containing nonnucleophilic anions X- such as CF3SO3-, FSO3-, and BF4- can be generated quantitatively and in situ from 1-acyl-4-alkylidene-1,4-dihydropyridines 1a-f and the corresponding acid, HX. The BF4- salts reveal an interesting and unexpected thermal instability which allows the convenient synthesis of carboxylic acid fluorides 5b-f. This procedure offers advantages over known methods: All operations can be performed in a standard glass apparatus and do not require high pressures. The formation of RCOF 5 is assisted by the pyridine moiety of 4, which splits off and functions as a Lewis base to intercept the BF3 acid. The structural and electronic relationships as well as dominating differences between the very reactive cations of 4 and their almost 'inert' uncharged precursors, the dihydropyridines 1, are discussed both on the fundament of experimental evidence (X-ray structures of 1f and the extremely reactive and very labile 4f) and theoretical investigations (ab initio and DFT MO calculations).
- Wagner, Ruediger,Wiedel, Bernd,Guenther, Wolfgang,Goerls, Helmar,Anders, Ernst
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p. 2383 - 2390
(2007/10/03)
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- Rearrangement and radical mediated decarboxylation of trimethylsilyl benzoates using xenon difluoride
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Treatment of trimethylsilyl benzoates 1 with xenon difluoride in CH2Cl2 or C6F6 results in a novel ester rearrangement and formation of aryl fluoroformates 2: rearrangement is not observed in MeCN solution in wh
- Nongkunsarn, Pakawan,Ramsden, Christopher A.
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p. 121 - 122
(2007/10/03)
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- Die Reacktionen von Bis(perfluoralkyl)cadmium-Komplexen mit Arylcarbonsaeurechloriden: Synthese von Aryl(perfluoralkyl)ketonen, (Perfluoralkyl-dihydropyridin)arylcarbonsaeureamiden, α,α-Bis(trifluormethyl)benzylalkoholen und Benzoesaeure-α,α-bis(trifluormethyl)benzylestern
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Perfluoroalkylcadmium complexes react with aroyl halides in the presence of strong bases such as pyridine to give the corresponding ketones ArCORf (which can be isolated in 5-51percent yield) and (perfluoroalkyldihydropyridine)aroylamides.The pure substances are obtained by chromatography.Aroyl fluorides and α,α-bis(trifluoromethyl)benzyl alcohols and benzoic acid-α,α-bis(trifluoromethyl)benzyl esters can be isolated as by-products.The dependency of the products formed on the kind of bases used as well as the reaction mechanisms are described.All products were identified by their 19F, 1H, 13C NMR, mass and IR spectra, and by elemental analysis.
- Naumann, Dieter,Finke, Martina,Lange, Horst,Dukat, Wolfgang,Tyrra, Wieland
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p. 215 - 237
(2007/10/02)
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- Reactions of Aldehydes with Cesium Fluoroxysulfate
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Various aromatic and aliphatic aldehydes reacted at 35-40 deg C in CH3CN with CsSo4F giving acid fluorides in a good yield.In some cases formation of fluorohydrocarbons was also observed.Hammett correlation analysis of the transformation of various substituted benzaldehydes (p-OCH3, p-CH3, p-F, p-CF3, m-NO2) gave the reaction constant ρ+ = -0.38.Solvent polarity strongly influenced the conversion of aldehydes into acid fluorides, being in acetonitrile almost quantitative and completely halted in CH2Cl2, n-hexane, or tetrahydrofuran.The presence of nitrobenzene, often used as a radical scavenger, considerably reduced the acid fluoride formation.Based on experimental observations was concluded that the main intermediates involved in the conversion of aldehydes into acid fluorides with CsSO4F must be of a radical nature.
- Stavber, Stojan,Planinsek, Zdenka,Zupan, Marko
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p. 5334 - 5337
(2007/10/02)
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- Catalytic Acid Fluoride Synthesis via Carbonylation of Organic Bromides in the Presence Potassium Fluoride
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Various aryl bromides were carbonylated under an atmospheric pressure of carbon monoxide in DMF in the presence of potassium fluoride to give aroyl fluorides in excellent yields.The carbonylation was promoted by the addition of phase transfer catalysts, but the contamination with water reduced the selectivity.
- Okano, Tamon,Harada, Nobuyuki,Kiji, Jitsuo
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p. 1741 - 1743
(2007/10/02)
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- MILD CONVERSION OF PRIMARY ALCOHOLS AND ALDEHYDES TO ACID FLUORIDES WITH CAESIUM FLUOROXYSULPHATE
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Caesium fluoroxysulphate in acetonitrile medium at 35 deg C converts primary alcohols and alkyl, as well as aryl aldehydes, to acid fluorides in high yield.
- Stavber, Stojan,Planinsek, Zdenka,Zupan, Marko
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p. 6095 - 6096
(2007/10/02)
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- Efficient acid fluoride synthesis via carbonylation of organic halides
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Palladium, platinum, cobalt, and rhodium triphenylphosphine complexes were found to catalyze the formation of acid fluorides via carbonylation of organic halides with fluoride salts.For palladium complex-catalyzed reactions, the use of cesium fluoride in polar solvents such as acetone and acetonitrile exhibited superior performance.The reaction took place even under an atmospheric pressure of carbon monoxide.The success of the acid fluoride synthesis is discussed in terms of the facility of oxidative addition of the starting material and the product.
- Sakakura, Toshiyasu,Chaisupakitsin, Malinee,Hayashi, Teruyuki,Tanaka, Masato
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p. 205 - 212
(2007/10/02)
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- The Relationship between 19F Substituent Chemical Shifts and Electron Densities: meta- and para-Substituted Benzoyl Fluorides
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The 19F substituent chemical shifts (SCS) of meta- and para-benzoyl fluorides are found to correlate well with substituent parameters using the dual substituent parameter (DSP) equation, indicating that they reflect electronic perturbations induced by the substituent.The direction of the SCS values is such that donating substituents cause upfield shifts whilst acceptors cause downfield shifts.STO-3G calculations indicate that substituents induce only very small changes in ?-electron density about the fluorine atom, but that these changes correlate reasonably well with the observed SCS values.For the para series, the slope of the relationship between Δq?F and 19F SCS is 5000 ppm/electron, indicating the great sensitivity of the fluorine atom to small changes in electron density.
- Brownlee, Robert T. C.,Craik, David J.
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p. 186 - 191
(2007/10/02)
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