- PROCESSES FOR FLUORINATION
-
The present technology relates to fluorination reactions. Specifically, processes useful for making the fungicide compound, DFT are disclosed. More broadly, also disclosed herein are processes useful for deoxyfluorination at the α-aromatic position of a given compound.
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-
Paragraph 0179; 0184-0187; 0196
(2021/04/10)
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- Decarbonylative Fluoroalkylation at Palladium(II): From Fundamental Organometallic Studies to Catalysis
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This Article describes the development of a decarbonylative Pd-catalyzed aryl-fluoroalkyl bond-forming reaction that couples fluoroalkylcarboxylic acid-derived electrophiles [RFC(O)X] with aryl organometallics (Ar-M′). This reaction was optimized by interrogating the individual steps of the catalytic cycle (oxidative addition, carbonyl de-insertion, transmetalation, and reductive elimination) to identify a compatible pair of coupling partners and an appropriate Pd catalyst. These stoichiometric organometallic studies revealed several critical elements for reaction design. First, uncatalyzed background reactions between RFC(O)X and Ar-M′ can be avoided by using M′ = boronate ester. Second, carbonyl de-insertion and Ar-RF reductive elimination are the two slowest steps of the catalytic cycle when RF = CF3. Both steps are dramatically accelerated upon changing to RF = CHF2. Computational studies reveal that a favorable F2C-H - -X interaction contributes to accelerating carbonyl de-insertion in this system. Finally, transmetalation is slow with X = difluoroacetate but fast with X = F. Ultimately, these studies enabled the development of an (SPhos)Pd-catalyzed decarbonylative difluoromethylation of aryl neopentylglycol boronate esters with difluoroacetyl fluoride.
- Lalloo, Naish,Malapit, Christian A.,Taimoory, S. Maryamdokht,Brigham, Conor E.,Sanford, Melanie S.
-
supporting information
p. 18617 - 18625
(2021/11/16)
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- Electrochemical-Promoted Nickel-Catalyzed Oxidative Fluoroalkylation of Aryl Iodides
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This work describes a general strategy for metal-catalyzed cross-coupling of fluoroalkyl radicals with aryl halides under electrochemical conditions. The contradiction between anodic oxidation of fluoroalkyl sulfinates and cathodic reduction of low-valent nickel catalysts can be well addressed by paired electrolysis, allowing for direct introduction of fluorinated functionalities into aromatic systems.
- Zou, Zhenlei,Li, Heyin,Huang, Mengjun,Zhang, Weigang,Zhi, Sanjun,Wang, Yi,Pan, Yi
-
supporting information
p. 8252 - 8256
(2021/11/01)
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- Synthesis of L-Au(I)-CF2H Complexes and Their Application as Transmetalation Shuttles to the Difluoromethylation of Aryl Iodides
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We describe herein two alternative protocols to efficiently prepare difluoromethylgold(I) complexes bearing ancillary ligands with different electronic and steric properties. LAu-OX (X = H andt-Bu) species, formed in the presence of base, have been identified as intermediate complexes involved in these transformations. The application of these compounds as “CF2H transmetalation shuttles” from gold to palladium has been demonstrated in a Pd-catalyzed difluoromethylation reaction of aryl iodides, in which the Au-to-Pd transfer of “CF2H” is feasible under stoichiometric conditions. These findings will pave the way for catalytic manifolds in gold chemistry.
- García-Domínguez, Patricia
-
supporting information
p. 2923 - 2928
(2021/09/07)
-
- Base-Catalyzed H/D Exchange Reaction of Difluoromethylarenes
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The budding deuteriodifluoromethyl group (CF2D) is a potentially significant functional group in medicinal chemistry. Herein, we investigated t-BuOK-catalyzed H/D exchange reaction of difluoromethylarenes in DMSO-d6 solution. The method provides excellent
- Huang, Linwei,Liu, Wei,Zhao, Liang-Liang,Zhang, Zengyu,Yan, Xiaoyu
-
p. 3981 - 3988
(2021/03/09)
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- 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.
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-
Paragraph 0148-0150; 0152
(2021/05/29)
-
- Visible-light photoredox-catalyzed selective carboxylation of C(sp3)?F bonds with CO2
-
It is highly attractive and challenging to utilize carbon dioxide (CO2), because of its inertness, as a nontoxic and sustainable C1 source in the synthesis of valuable compounds. Here, we report a novel selective carboxylation of C(sp3)?F bonds with CO2 via visible-light photoredox catalysis. A variety of mono-, di-, and trifluoroalkylarenes as well as α,α-difluorocarboxylic esters and amides undergo such reactions to give important aryl acetic acids and α-fluorocarboxylic acids, including several drugs and analogs, under mild conditions. Notably, mechanistic studies and DFT calculations demonstrate the dual role of CO2 as an electron carrier and electrophile during this transformation. The fluorinated substrates would undergo single-electron reduction by electron-rich CO2 radical anions, which are generated in situ from CO2 via sequential hydride-transfer reduction and hydrogen-atom-transfer processes. We anticipate our finding to be a starting point for more challenging CO2 utilization with inert substrates, including lignin and other biomass.
- Bo, Zhi-Yu,Chen, Lin,Gao, Tian-Yu,Jing, Ke,Lan, Yu,Liu, Shi-Han,Luo, Shu-Ping,Yan, Si-Shun,Yu, Bo,Yu, Da-Gang
-
supporting information
p. 3099 - 3113
(2021/11/16)
-
- PROCESSES FOR FLUORINATION
-
The present technology relates to fluorination reactions. Specifically, processes useful for making the fungicide compound, DFT are disclosed. More broadly, also disclosed herein are processes useful for deoxyfluorination at the α-aromatic position of a given compound.
- -
-
Paragraph 0188
(2020/03/05)
-
- Organophotoredox Hydrodefluorination of Trifluoromethylarenes with Translational Applicability to Drug Discovery
-
Molecular editing such as insertion, deletion, and single atom exchange in highly functionalized compounds is an aspirational goal for all chemists. Here, we disclose a photoredox protocol for the replacement of a single fluorine atom with hydrogen in electron-deficient trifluoromethylarenes including complex drug molecules. A robustness screening experiment shows that this reductive defluorination tolerates a range of functional groups and heterocycles commonly found in bioactive molecules. Preliminary studies allude to a catalytic cycle whereby the excited state of the organophotocatalyst is reductively quenched by the hydrogen atom donor, and returned in its original oxidation state by the trifluoromethylarene.
- Sap, Jeroen B.I.,Straathof, Natan J.W.,Knauber, Thomas,Meyer, Claudio F.,Meyer, Claudio F.,Médebielle, Maurice,Buglioni, Laura,Genicot, Christophe,Trabanco, Andrés A.,No?l, Timothy,Am Ende, Christopher W.,Gouverneur, Véronique
-
supporting information
p. 9181 - 9187
(2020/07/10)
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- Deoxyfluorination of (Hetero)aryl Aldehydes Using Tetramethylammonium Fluoride and Perfluorobutanesulfonyl Fluoride or Trifluoromethanesulfonic Anhydride
-
This Communication describes the conversion of (hetero)aryl aldehydes into the corresponding (hetero)aryl difluoromethyl products using anhydrous NMe4F in combination with perfluorobutanesulfonyl fluoride or trifluoromethanesulfonic anhydride.
- Ferguson, Devin M.,Melvin, Patrick R.,Sanford, Melanie S.
-
p. 398 - 401
(2019/09/06)
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- A carboxamide is the cyanogen source of aromatic nitrile to the preparation method of the (by machine translation)
-
The invention discloses a method for preparing aromatic nitrile, is under the action of the nickel catalyst, in order to carboxamide is the cyanogen source, and with various substituents haloarene coupled reactions, preparing aromatic nitrile. The reaction temperature is 100 - 160 °C, the reaction time is 6 - 24 hours. It overcomes the traditional aromatic nitrile of the synthesis method operation of complex steps, requires the use of a toxic, more expensive, functionalization of the cyanogen source as the reaction raw material and the like. Compared with the traditional method, this method is simple to use cheap, green non-toxic of the formamide is cyano sources; without the need of external dehydrating agent, formamide in the nickel catalyst of the catalytic dehydration at the same time, with a nickel catalyst in coordination with the halogenated aromatic hydrocyanation, more economic, high-efficiency, environmental protection; at the same time the method exhibits good substrate universality, to air, moisture, light are not sensitive, high yield, product separation and purification is simple, with wide application. (by machine translation)
- -
-
Paragraph 0015; 0016; 0017; 0018-0024; 0116; 0117-0120
(2019/05/08)
-
- Difluoromethyl-substituted compound (by machine translation)
-
[Problem] to provide a, simple and inexpensive manufacturing method is difluoromethyl substituted compounds using a reagent. [Solution] a method for producing a compound using a catalyst [...] difluoromethyl-substituted,(I) the catalyst, a nickel compound and nitrogen in the bidentate ligand, raw Ar a-Z " in the formula, the Ar, substituted or unsubstituted aryl group or a substituted or unsubstituted 5 - 10 membered heteroaryl group C6 a-14, Z is, (OR) B2 Or a group represented by a is represented MgX. " Compound represented, difluoromethyl-substituted compounds, Ar e CF2 A method for producing a compound represented by H, or(II) catalyst, a palladium compound and a diphosphine ligand, raw material is Q-a B (OR1 )2 " In the formula, Q is, substituted or unsubstituted aryl C6 a-10, 5 - 10 membered heteroaryl or substituted or unsubstituted, or Ar1 A group represented by - CH=CH - shown. R1 Is, a hydrogen atom or an alkyl group C1 a-6. " Compounds, a compound represented by Q-a Zn-to-Q or, difluoromethyl-substituted compounds, Q-to-CF2 A method for producing a compound represented by H. [Drawing] no (by machine translation)
- -
-
Paragraph 0060; 0061
(2019/10/17)
-
- Controlling the cleavage of carbon-carbon bonds to generate α,α-difluorobenzyl carbanions for the construction of difluoromethylbenzenes
-
Controlling the cleavage of carbon-carbon bonds during a chemical reaction is a substantial challenge; however, synthetic methods that accomplish this objective produce valuable and often unexplored reactivity. We have designed a mild process to generate α,α-difluorobenzyl carbanions in the presence of potassium carbonate by exploiting the cleavage of C-C bonds during the release of trifluoroacetate. The initiating reagent is potassium carbonate, which represents an improvement over existing protocols that require a strong base. Fragmentation studies across substituted arenes and heteroarenes were conducted along with computational analyses to elucidate reactivity trends. Furthermore, the mildly generated α,α-difluorobenzyl carbanions from electron-deficient aromatics and heteroaromatic rings can react with aldehydes to create derivatives of difluoromethylbenzenes, which are valuable synthetic targets.
- Khatri, Hari R.,Han, Changho,Luong, Erica,Pan, Xiaoliang,Adam, Amna T.,Alshammari, Maali D.,Shao, Yihan,Colby, David A.
-
p. 11665 - 11675
(2019/10/02)
-
- Ligand-Less Iron-Catalyzed Aromatic Cross-Coupling Difluoromethylation of Grignard Reagents with Difluoroiodomethane
-
Iron-catalyzed cross-coupling difluoromethylations of the Grignard reagents with difluoroiodomethane provide various aromatic difluoromethyl products in good yields, not employing sterically demanding ligands. Difluoromethylations proceed within 30 min at -20 °C with 2.0 equiv of the Grignard reagents and FeCl3 or Fe(acac)3 (2.5 mol %). Mechanistic investigations clarify difluoromethyl radical intervention; Fe(0) ate is initially generated. Single-electron transfer from Fe(0) ate to difluoroiodomethane takes place. Recombination with aryl groups gives Ar-CF2Hs. The catalyst can be regenerated by the Grignard reagents.
- Motohashi, Hirotaka,Kato, Miki,Mikami, Koichi
-
p. 6483 - 6490
(2019/05/16)
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- Palladium-Catalyzed Difluoromethylation of Aryl Chlorides and Bromides with TMSCF2H
-
A palladium-catalyzed cross-coupling of aryl chlorides/bromides with TMSCF2H is described. Two different catalysts, Pd(dba)2/BrettPhos and Pd(PtBu3)2, are demonstrated and provide a variety of difluoromethylated arenes in good yields.
- Ferguson, Devin M.,Malapit, Christian A.,Bour, James R.,Sanford, Melanie S.
-
p. 3735 - 3740
(2019/04/11)
-
- Room Temperature Deoxyfluorination of Benzaldehydes and α-Ketoesters with Sulfuryl Fluoride and Tetramethylammonium Fluoride
-
A method for the room temperature deoxyfluorination of benzaldehydes and α-ketoesters using sulfuryl fluoride and Me4NF is described. A large scope of aryl and heteroaryl substrates is demonstrated, and this method compares favorably to other common deoxyfluorination methods for many substrates.
- Melvin, Patrick R.,Ferguson, Devin M.,Schimler, Sydonie D.,Bland, Douglas C.,Sanford, Melanie S.
-
supporting information
p. 1350 - 1353
(2019/03/08)
-
- Substituted amide phenol compound and its preparation method, pharmaceutical composition and use thereof
-
The invention discloses substituted-amide phenolic compounds, their preparation method, a pharmaceutical composition and an application thereof. The compounds have a structure as shown in the general formula I, wherein Z, L and Q are as defined in the spe
- -
-
Paragraph 0328-0332
(2019/07/04)
-
- Method for preparing alpha-aryl/heteroaryl/alkenyl-alpha,alpha-difluoromethyl compounds
-
The invention discloses a method for preparing alpha-aryl/heteroaryl/alkenyl-alpha,alpha-difluoromethyl compounds. The preparation method for the alpha-aryl/heteroaryl/alkenyl-alpha,alpha-difluoromethyl compounds as shown in a formula C which is described
- -
-
Paragraph 0141; 0142; 0143; 0150; 0151; 0152; 0204; 0205
(2018/09/08)
-
- Palladium-Catalyzed Decarbonylative Difluoromethylation of Acid Chlorides at Room Temperature
-
Methods for the direct synthesis of difluoromethylated arenes are sparse, despite the importance of the difluoromethyl group in medical, agro-, and materials chemistry. A palladium-catalyzed decarbonylative cross-coupling reaction of acid chlorides with a difluoromethyl zinc reagent is achieved to access difluoromethylated compounds. The transformation proceeds at room temperature and shows broad functional group tolerance, thus providing a general and efficient method for decarbonylative difluoromethylation of a wide range of aromatic carboxylic acids.
- Pan, Fei,Boursalian, Gregory B.,Ritter, Tobias
-
supporting information
p. 16871 - 16876
(2018/11/23)
-
- Metallaphotoredox Difluoromethylation of Aryl Bromides
-
Herein, we report a convenient and broadly applicable strategy for the difluoromethylation of aryl bromides by metallaphotoredox catalysis. Bromodifluoromethane, a simple and commercially available alkyl halide, is harnessed as an effective source of difluoromethyl radical by silyl-radical-mediated halogen abstraction. The merger of this fluoroalkyl electrophile activation pathway with a dual nickel/photoredox catalytic platform enables the difluoromethylation of a diverse array of aryl and heteroaryl bromides under mild conditions. The utility of this procedure is showcased in the late-stage functionalization of several drug analogues.
- Bacauanu, Vlad,Cardinal, Sébastien,Yamauchi, Motoshi,Kondo, Masaru,Fernández, David F.,Remy, Richard,MacMillan, David W. C.
-
supporting information
p. 12543 - 12548
(2018/09/18)
-
- Nickel-Catalyzed Aromatic Cross-Coupling Difluoromethylation of Grignard Reagents with Difluoroiodomethane
-
The nickel-catalyzed cross-coupling difluoromethylation of the Grignard reagents with difluoroiodomethane is shown to provide the corresponding aromatic difluoromethyl products in excellent to moderate yields. The difluoromethylation proceeds smoothly within 1 h at room temperature with 1.5 equiv of the Grignard reagents in the presence of Ni(cod)2/TMEDA (2.5-0.5 mol %). Mechanistic studies clarify that the oxidative addition of the Ni(0) catalyst to difluoroiodomethane provides the TMEDA-Ni(II)(CF2H)I complex. This intermediate is transformed to TMEDA-Ni(II)(CF2H)Ph via transmetalation with PhMgBr. The reductive elimination takes place to give the aromatic cross-coupling difluoromethylation product along with regeneration of the TMEDA-Ni(0) catalyst. Electron paramagnetic resonance (EPR) and radical clock analyses of the nickel-catalyzed reaction provide no EPR active Ni(I) and Ni(III) species at around g = 2 and only a trace amount of the cyclization product.
- Motohashi, Hirotaka,Mikami, Koichi
-
supporting information
p. 5340 - 5343
(2018/09/12)
-
- Nickel-Catalyzed Difluoromethylation of Arylboronic Acids with Bromodifluoromethane
-
Although bromodifluoromethane (BrCF2H) is a simple and readily available fluorine source, direct formation of difluoromethylated arenes with BrCF2H has not been reported. Herein, we describe an efficient method to access difluoromethylated arenes through a nickel-catalyzed difluoromethylation of arylboronic acids with BrCF2H. The reaction exhibits high efficiency, good functional group tolerance and broad substrate scope, thus providing an efficient route for applications in drug discovery and development. Preliminary mechanistic studies reveal that a difluoromethyl radical is involved in the reaction.
- Fu, Xia-Ping,Xiao, Yu-Lan,Zhang, Xingang
-
supporting information
p. 143 - 146
(2018/01/05)
-
- Iron-Catalyzed Difluoromethylation of Arylzincs with Difluoromethyl 2-Pyridyl Sulfone
-
We report the first iron-catalyzed difluoromethylation of arylzincs with difluoromethyl 2-pyridyl sulfone via selective C-S bond cleavage. This method employs the readily available, bench-stable fluoroalkyl sulfone reagent and inexpensive iron catalyst, allowing facile access to structurally diverse difluoromethylated arenes at low temperatures. The experiment employing a radical clock indicates the involvement of radical species in this iron-catalyzed difluoromethylation process.
- Miao, Wenjun,Zhao, Yanchuan,Ni, Chuanfa,Gao, Bing,Zhang, Wei,Hu, Jinbo
-
supporting information
p. 880 - 883
(2018/02/07)
-
- Synthesis of Aryldihalomethanes by Denitrogenative Dihalogenation of Benzaldehyde Hydrazones
-
We report a denitrogenative dihalogenation reaction of phenyldiazomethanes in which the hypervalent iodine reagents PhICl2 and TolIF2 act as surrogates for elemental chlorine and fluorine. Halogen transfer from iodane to aryldiazomethane is described, as is a tandem oxidative dihalogenation reaction between iodane and hydrazone. This is the first use of non-α-stabilized diazo compounds in this reaction, which provided an efficient synthesis of aryldifluoromethane (ArCHF2) and aryldichloromethane (ArCHCl2) derivatives. (Figure presented.).
- Zhao, Zhensheng,Kulkarni, Kaivalya G.,Murphy, Graham K.
-
supporting information
p. 2222 - 2228
(2017/07/07)
-
- Chlorodifluoromethane-triggered formation of difluoromethylated arenes catalysed by palladium
-
Difluoromethylated aromatic compounds are of increasing importance in pharmaceuticals, agrochemicals and materials. Chlorodifluoromethane (ClCF2H), an inexpensive, abundant and widely used industrial raw material, represents the ideal and most straightforward difluoromethylating reagent, but introduction of the difluoromethyl group (CF2H) from ClCF2H into aromatics has not been reported. Here, we describe a direct palladium-catalysed difluoromethylation method for coupling ClCF2H with arylboronic acids and esters to generate difluoromethylated arenes with high efficiency. The reaction exhibits a remarkably broad substrate scope, including heteroarylboronic acids, and was used for difluoromethylation of a range of pharmaceuticals and biologically active compounds. Preliminary mechanistic studies revealed that a palladium difluorocarbene intermediate is involved in the reaction. Although numerous metal-difluorocarbene complexes have been prepared, the catalytic synthesis of difluoromethylated or difluoromethylenated compounds involving metal-difluorocarbene complexes has not received much attention. This new reaction therefore also opens the door to understand metal- difluorocarbene complex catalysed reactions.
- Feng, Zhang,Min, Qiao-Qiao,Fu, Xia-Ping,An, Lun,Zhang, Xingang
-
p. 918 - 923
(2017/09/01)
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- Synthesis, reactivity, and catalytic applications of isolable (NHC)Cu(CHF2) complexes
-
Difluoromethyl copper complexes have been proposed as key intermediates in a variety of Cu-catalyzed difluoromethylation reactions. However, studies of these putative intermediates have been impeded by the low stability of these [Cu(CHF2)] species. This report describes the synthesis of isolable N-heterocyclic carbene ligated copper(I) difluoromethyl complexes. The stoichiometric reactions of these complexes with aryl electrophiles (i.e., diaryliodonium salts, aryl iodides, and aryl bromides) are described. In addition, Nheterocyclic carbene copper(I) species are demonstrated to serve as catalysts for the cross-coupling of aryl iodides with (difluoromethyl)trimethylsilane to afford difluoromethyl arene products.
- Bour, James R.,Kariofillis, Stavros K.,Sanford, Melanie S.
-
supporting information
p. 1220 - 1223
(2017/05/29)
-
- Synthesis of trifluoromethyl moieties by late-stage copper (I) mediated nucleophilic fluorination
-
The nucleophilic fluorination of bromodifluoromethyl derivatives mediated by the complex (PPh3)3CuF is described. Under the reaction conditions, different trifluoroacetates, trifluoroketones, trifluoroarenes and trifluoroacetamides were obtained in good yields.
- Bermejo Góme, Antonio,González, Miguel A. Cortés,Lübcke, Marvin,Johansson, Magnus J.,Schou, Magnus,Szabó, Kálmán J.
-
-
- Palladium-Catalyzed Negishi Cross-Coupling Reaction of Aryl Halides with (Difluoromethyl)zinc Reagent
-
The palladium-catalyzed Negishi cross-coupling reaction of aryl iodides and bromides with (difluoromethyl)zinc reagent bearing a diamine such as TMEDA is achieved to provide the difluoromethylated aromatic compounds in good to excellent yields. The advantages of (difluoromethyl)zinc reagent are that (1) the derivatives, which possess different stability and reactivity, can be readily prepared via ligand screening and (2) transmetalation of a difluoromethyl group from the zinc reagent to palladium catalyst efficiently proceeds without an activator.
- Aikawa, Kohsuke,Serizawa, Hiroki,Ishii, Koki,Mikami, Koichi
-
supporting information
p. 3690 - 3693
(2016/08/16)
-
- Copper-Catalyzed Difluoromethylation of Aryl Iodides with (Difluoromethyl)zinc Reagent
-
The combination of difluoroiodomethane and zinc dust or diethylzinc can readily lead to (difluoromethyl)zinc reagents. Therefore, the first copper-catalyzed difluoromethylation of aryl iodides with the zinc reagents is accomplished to afford the difluorom
- Serizawa, Hiroki,Ishii, Koki,Aikawa, Kohsuke,Mikami, Koichi
-
supporting information
p. 3686 - 3689
(2016/08/16)
-
- Direct Difluoromethylation of Aryl Halides via Base Metal Catalysis at Room Temperature
-
A stable and isolable difluoromethyl zinc reagent has been prepared through the reaction of ICF2H with diethyl zinc and DMPU. This new zinc reagent is a free-flowing solid and can be used in combination with a nickel catalyst to difluoromethylate aryl iodides, bromides, and triflates at room temperature. Such mild conditions for the catalytic difluoromethylation of these substrates are unprecedented.
- Xu, Long,Vicic, David A.
-
supporting information
p. 2536 - 2539
(2016/03/12)
-
- Method of manufacturing arom. defluoromethyl compd.
-
PROBLEM TO BE SOLVED: To provide a method for easily producing an aromatic compound having a difluoromethyl group in high yield while using a reagent having low toxicity. SOLUTION: The method for producing the aromatic difluoromethyl compound includes reacting an aromatic difluoroacetic acid in the presence of a metal halide (especially potassium fluoride). COPYRIGHT: (C)2011,JPOandINPIT
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-
Paragraph 0036; 0048; 0049
(2018/11/22)
-
- Sandmeyer difluoromethylation of (hetero-)arenediazonium salts
-
A Sandmeyer-type difluoromethylation process has been developed that allows the straightforward conversion of (hetero-)arenediazonium salts into the corresponding difluoromethyl (hetero-)arenes under mild conditions. The actual difluoromethylating reagent, a difluoromethyl-copper complex, is formed in situ from copper thiocyanate and TMS-CF2H. The diazonium salts are either preformed or generated in situ from broadly available aromatic amines.
- Matheis, Christian,Jouvin, Kvin,Goossen, Lukas J.
-
supporting information
p. 5984 - 5987
(2015/01/08)
-
- A new method for aromatic difluoromethylation: Copper-catalyzed cross-coupling and decarboxylation sequence from aryl iodides
-
A new methodology for aromatic difluoromethylation is described. Aryl iodides reacted with α-silyldifluoroacetates upon treatment with copper catalyst in DMSO or DME to give the corresponding aryldifluoroacetates in moderate to good yields. The subsequent hydrolysis of aryldifluoroacetates and KF-promoted decarboxylation afforded a variety of difluoromethyl aromatics.
- Fujikawa, Kenichi,Fujioka, Yasutaka,Kobayashi, Akira,Amii, Hideki
-
p. 5560 - 5563
(2011/12/05)
-
- BICYCLIC COMPOUNDS USEFUL AS CATHEPSIN S INBHIBITORS
-
Compounds of formula (I), wherein R1, R2, R3, Ra and E are are defined within, and pharmaceutically acceptable salts, solvates, hydrates and N-oxides thereof having utility in the treatment of disorders mediated by cathepsin S.
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-
Page/Page column 41-42
(2010/11/29)
-
- CATHEPSIN S INHIBITORS
-
Compounds of the formula (I) where R1 is C1-C4 straight or branched alkyl, optionally substituted with up to three substituents selected from halo and hydroxy; R2 is halo, hydroxy, methyloxy, or C1-C2 alkyl, which alkyl is optionally substituted with up to three halogens or an hydroxy or a methyloxy; D is - C3-C7 alkylene-, thereby defining a cycloalkyl ring; E is -C(=O)-, -S(=O)m-, -NRdS(=O)m-, -NRaC(=O)-, -OC(=O)-, R3 is an optionally substituted carbocyclic or heterocyclic ring R10 is H, ORc, SRc or together with the gem H is =O or (ORc)2; Ra is independently selected from H, C1-C4 alkyl; have utility in the inhibition of cathepsin S and are thus useful pharmaceuticals against disorders such as autoimmune disorders and chronic pain.
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-
Page/Page column 96-97
(2010/11/08)
-
- Dynamics of bond breaking in ion radicals. Mechanisms and reactivity in the reductive cleavage of carbon-fluorine bonds of fluoromethylarenes
-
The reductive cleavage mechanism and reactivity of the carbon-fluorine bonds in fluoromethylarenes are investigated, in liquid ammonia and in DMF, by means of cyclic voltammetry and/or redox catalysis as a function of the number of fluorine atoms and of the structure of the aryl moiety. The reduction of the trifluoro compounds, eventually leading to complete defluorination, involves the di- and monofluoro derivatives as intermediates. Carbenes do not transpire along the reaction pathway. Application of the intramolecular dissociative electron transfer model allows the quantitative rationalization, in terms of driving force and intrinsic barrier, of the variation of the cleavage reactivity of the primary anion radical with the number of fluorine atoms and of the structure of the aryl moiety as well as with the solvating properties of the medium. When, related to the structural factors thus uncovered, the primary anion radical generates the di- and monofluoro intermediates far from the electrode surface, their reduction occurs homogeneously giving rise to an apparently direct six-electron process according to an internal redox catalysis mechanism. Conversely, with rapid cleavages, the reduction of the di- and monofluoro intermediates takes place at the electrode surface and the stepwise expulsion of the fluorides ions transpire in the cyclic voltammetric patterns.
- Andrieux, Claude P.,Combellas, Catherine,Kanoufi, Fredéric,Savéant, Jean-Michel,Thiébault, André
-
p. 9527 - 9540
(2007/10/03)
-
- Conversion of the Carbonyl Group to CF2 Using IF
-
A novel method for the transformation of CO -> CF2 is described.The easily made hydrazone derivatives of the carbonyl moiety are reacted under mild conditions with IF prepared directly from the corresponding elements.Various hydrazones have been examined and compared with each other.Unsubstituted ones are usually the most suitable although they are not always easy to purify and store.N-Methyl- and N,N-dimethylhydrazones also give quite satisfactory results.The more easily made dinitrophenyl hydrazones (DNPs), semicarbazones, and tosylhydrazones also react, but the yields of the desired CF2 compounds are usually lower.Oximes could also be successfully reacted.The two main byproducts of the reaction are the parent carbonyl compounds, which can be recycled, and the α-iododifluoro derivatives.The latter upon treatment with LiAlH4 or Bu3SnH were reduced to the desired product, thus increasing the overall yields.
- Rozen, Shlomo,Zamir, Dov
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p. 4695 - 4700
(2007/10/02)
-
- Fluorination process
-
Aromatic compounds containing an α-fluoroalkyl or α,α-difluoroalkyl side chain are prepared by reacting selected aromatic compounds with a mixture of HF and a metal oxide which is PbO2 or NiO2 at -30° to +80° C. Exemplary is the conv
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