- 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
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supporting information
p. 2923 - 2928
(2021/09/07)
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- Deoxyfluorination of (Hetero)aryl Aldehydes Using Tetramethylammonium Fluoride and Perfluorobutanesulfonyl Fluoride or Trifluoromethanesulfonic Anhydride
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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.
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p. 398 - 401
(2019/09/06)
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- Controlling the cleavage of carbon-carbon bonds to generate α,α-difluorobenzyl carbanions for the construction of difluoromethylbenzenes
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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.
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p. 11665 - 11675
(2019/10/02)
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- Difluoromethyl-substituted compound (by machine translation)
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[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)
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Paragraph 0060; 0061
(2019/10/17)
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- OXALAMIDES AS MODULATORS OF INDOLEAMINE 2,3-DIOXYGENASE
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The present invention relates to novel compounds which act as modulators of indoleamine 2,3-dioxygenase (IDOl) and to the use of said compounds in the prophylaxis and/or treatment of diseases or conditions mediated by indoleamine 2,3-dioxygenase. The inve
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Page/Page column 59
(2019/07/19)
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- Visible-Light-Driven Oxidative Mono- and Dibromination of Benzylic sp 3 C-H Bonds with Potassium Bromide/Oxone at Room Temperature
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Benzylic sp 3 C-H bonds have been successfully brominated with potassium bromide by using Oxone as an oxidant in water/dichloromethane under visible light at room temperature. Toluene, ethylbenzene and other alkylbenzenes bearing an electron-withdrawing group, such as Br, Cl, COMe, CO 2 Et, CO 2 H, CN or NO 2, provide the corresponding benzylic monobromides in good to excellent yields in this reaction. Dibromides can also be produced in the presence of excess potassium bromide in a prolonged reaction time. Control of the illuminance of visible light (~500 lux) is crucial to achieving both high yield and high selectivity in these brominations. Mono- and difluorides can be conveniently prepared through nucleophilic substitutions of the benzylic bromides with potassium fluoride.
- Zhao, Mengdi,Li, Meiqi,Lu, Wenjun
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p. 4933 - 4939
(2018/12/14)
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- Palladium-Catalyzed Decarbonylative Difluoromethylation of Acid Chlorides at Room Temperature
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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
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supporting information
p. 16871 - 16876
(2018/11/23)
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- Nickel-Catalyzed Aromatic Cross-Coupling Difluoromethylation of Grignard Reagents with Difluoroiodomethane
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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
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supporting information
p. 5340 - 5343
(2018/09/12)
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- Synthesis of Aryldihalomethanes by Denitrogenative Dihalogenation of Benzaldehyde Hydrazones
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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.
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p. 2222 - 2228
(2017/07/07)
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- Synthesis, reactivity, and catalytic applications of isolable (NHC)Cu(CHF2) complexes
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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.
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supporting information
p. 1220 - 1223
(2017/05/29)
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- Visible-light-initiated difluoromethylation of arene diazonium tetrafluoroborates
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A mild and efficient method for the radical addition of α-aryl-β,β-difluoroenol silyl with arene diazonium tetrafluoroborates at room temperature has been disclosed, which involves an innate radical long chain cycle, so only a small amount (0.05 mol%) of photocatalyst and a short light exposure time are required as radical initiators. A proposed mechanism for the transformation is also illustrated based on the results of control experiments and quantum calculations. A variety of α-aryl-α,α-difluoroketones were formed in moderate to high yields, and can be easily further transformed into various difluoromethylarenes under basic conditions.
- Wu, Ye-Bin,Lu, Guo-Ping,Zhou, Bao-Jing,Bu, Mei-Jie,Wan, Li,Cai, Chun
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supporting information
p. 5965 - 5968
(2016/05/24)
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- DIFLUOROMETHYL ZINC COMPOUND
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PROBLEM TO BE SOLVED: To provide a production method of difluoromethyl group-containing aromatic compounds which are useful as synthetic intermediates. SOLUTION: A difluoromethyl zinc-TALED complex compound is derived from a bis(trifluoromethyl)zinc-DMPU complex compound (DMPU represents N,N'-dimethylpropylene urea) and represented by formula (1). A production method of a difluoromethyl group-containing aromatic compound has a step to conduct a difluoromethylation reaction by using the difluoromethyl zinc-TALED complex compound. CHF2-Zn.TALED(1)(TALED is a tetraalkylethylenediamine). SELECTED DRAWING: None COPYRIGHT: (C)2017,JPOandINPIT
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Paragraph 0040
(2017/04/03)
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- Palladium-Catalyzed Negishi Cross-Coupling Reaction of Aryl Halides with (Difluoromethyl)zinc Reagent
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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
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supporting information
p. 3690 - 3693
(2016/08/16)
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- Copper-Catalyzed Difluoromethylation of Aryl Iodides with (Difluoromethyl)zinc Reagent
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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
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supporting information
p. 3686 - 3689
(2016/08/16)
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- Denitrogenative hydrofluorination of aromatic aldehyde hydrazones using (difluoroiodo)toluene
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An operationally simple conversion of aromatic aldehyde hydrazones to monofluoromethylated arenes is reported. The hypervalent iodine reagent TolIF2 serves as an oxidant, converting the hydrazone to the corresponding diazo compounds. The by-product of the oxidation process, HF, is consumed in situ by a denitrogenative hydrofluorination reaction of the diazo group.
- Kulkarni, Kaivalya G.,Miokovic, Boris,Sauder, Matthew,Murphy, Graham K.
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p. 9907 - 9911
(2016/10/31)
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- Method of manufacturing arom. defluoromethyl compd.
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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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- Sandmeyer difluoromethylation of (hetero-)arenediazonium salts
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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.
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supporting information
p. 5984 - 5987
(2015/01/08)
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- A new method for aromatic difluoromethylation: Copper-catalyzed cross-coupling and decarboxylation sequence from aryl iodides
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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
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p. 5560 - 5563
(2011/12/05)
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- Fluorination reactions in microreactors
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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.
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scheme or table
p. 3022 - 3024
(2009/02/04)
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- Selective electrolytic fluorinations in 70% HF/30% pyridine
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The selective fluorination of compounds containing benzylic hydrogen atoms was accomplished by electrolysis in a mixture of 70% HF and 30% pyridine (Olah's reagent) using a square wave alternating current (1.76-2.75 V, 0.02-0.05 Hz) and Pt electrodes. This method can be used in the laboratory to prepare conveniently gram-size quantities of monofluorinated products. An ion radical mechanism has been proposed.
- Lee, Sarah M.,Roseman, Jamie M.,Zartman, C. Blair,Morrison, Eamonn P.,Harrison, Sean J.,Stankiewicz, Corrie A.,Middleton
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- Conversion of the Carbonyl Group to CF2 Using IF
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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)
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- Syntheses of New Aromatic Compounds with Fluorinated Side Chains and their Chemical Reactivity
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The syntheses of a wide range of aromatic compounds of the type p-Y-C6H4CF2X(4-13) are described, and the chemical behavior of these compounds as a function of substituent Y is investigated .Analogously the pyridine derivatives 15, 17, and 18 were synthesized and characterized.From a correlation of the 19F-NMR data of these compounds with the Hammett constant of Y, participation of C-F ?-back-donation is seen as the cause for an observed shift of the 19F signals to lower field.
- Haas, Alois,Spitzer, Martin,Lieb, Max
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p. 1329 - 1340
(2007/10/02)
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- gem-Difluoro Compounds: A Convenient Preparation from Ketones and Aldehydes by Halogen Fluoride Treatment of 1,3-Dithiolanes
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gem-Difluoro compounds can be prepared from ketones and aldehydes by formation of the corresponding 1,3-dithiolanes, followed by reaction with 1,3-dibromo-5,5-dimethylhydantoin and pyridinium poly(hydrogenfluoride) (HF-pyridine) in methylene chloride.The
- Sondej, Susan C.,Katzenellenbogen, John A.
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p. 3508 - 3513
(2007/10/02)
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- Fluorination process
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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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