- Cross-Coupling through Ag(I)/Ag(III) Redox Manifold
-
In ample variety of transformations, the presence of silver as an additive or co-catalyst is believed to be innocuous for the efficiency of the operating metal catalyst. Even though Ag additives are required often as coupling partners, oxidants or halide scavengers, its role as a catalytically competent species is widely neglected in cross-coupling reactions. Most likely, this is due to the erroneously assumed incapacity of Ag to undergo 2e? redox steps. Definite proof is herein provided for the required elementary steps to accomplish the oxidative trifluoromethylation of arenes through AgI/AgIII redox catalysis (i. e. CEL coupling), namely: i) easy AgI/AgIII 2e? oxidation mediated by air; ii) bpy/phen ligation to AgIII; iii) boron-to-AgIII aryl transfer; and iv) ulterior reductive elimination of benzotrifluorides from an [aryl-AgIII-CF3] fragment. More precisely, an ultimate entry and full characterization of organosilver(III) compounds [K]+[AgIII(CF3)4]? (K-1), [(bpy)AgIII(CF3)3] (2) and [(phen)AgIII(CF3)3] (3), is described. The utility of 3 in cross-coupling has been showcased unambiguously, and a large variety of arylboron compounds was trifluoromethylated via [AgIII(aryl)(CF3)3]? intermediates. This work breaks with old stereotypes and misconceptions regarding the inability of Ag to undergo cross-coupling by itself.
- Demonti, Luca,Mézailles, Nicolas,Nebra, Noel,Saffon-Merceron, Nathalie
-
supporting information
p. 15396 - 15405
(2021/10/12)
-
- Mechanistic Insight into Copper-Mediated Trifluoromethylation of Aryl Halides: The Role of CuI
-
The synthesis, characterization, and reactivity of key intermediates [Cu(CF3)(X)]-Q+ (X = CF3 or I, Q = PPh4) in copper-mediated trifluoromethylation of aryl halides were studied. Qualitative and quantitative studies showed [Cu(CF3)2]-Q+ and [Cu(CF3)(I)]-Q+ were not highly reactive. Instead, a much more reactive species, ligandless [CuCF3] or DMF-ligated species [(DMF)CuCF3], was generated in the presence of excess CuI. On the basis of these results, a general mechanistic map for CuI-promoted trifluoromethylation of aryl halides was proposed. Furthermore, on the basis of this mechanistic understanding, a HOAc-promoted protocol for trifluoromethylation of aryl halides with [Ph4P]+[Cu(CF3)2]- was developed.
- Liu, He,Wu, Jian,Jin, Yuxuan,Leng, Xuebing,Shen, Qilong
-
p. 14367 - 14378
(2021/09/13)
-
- Solvated Nickel Complexes as Stoichiometric and Catalytic Perfluoroalkylation Agents**
-
The acetonitrile-solvated [(MeCN)Ni(C2F5)3]? was prepared in order to compare and contrast its reactivity with the known [(MeCN)Ni(CF3)3]? towards organic electrophiles. Both [(MeCN)Ni(CF3)3]? and [(MeCN)Ni(C2F5)3]? successfully react with aryl iodonium and diazonium salts as well as alkynyl iodonium salts to give fluoroalkylated organic products. Electrochemical analysis of [(MeCN)NiII(C2F5)3]? suggests that, upon electro-oxidation to [(MeCN)nNiIII(C2F5)3], reductive homolysis of a perfluoroethyl radical occurs, with the concomitant formation of [(MeCN)2NiII(C2F5)2]. Catalytic C?H trifluoromethylations of electron-rich arenes were successfully achieved using either [(MeCN)Ni(CF3)3]? or the related [Ni(CF3)4]2?. Stoichiometric reactions of the solvated nickel complexes reveal that “ligandless” nickel is exceptionally capable of serving as reservoir of CF3 groups under catalytically relevant conditions.
- Shreiber, Scott T.,Vicic, David A.
-
supporting information
p. 18162 - 18167
(2021/07/14)
-
- A highly stable all-in-one photocatalyst for aryl etherification: The NiIIembedded covalent organic framework
-
The efficient conversion of aryl bromides to the corresponding aryl alkyl ethers by dual nickel/photocatalysis has seen great progress, but difficulties of recycling the photosensitizer or nickel complexes cause problems of sustainability. Here, we report the design of a novel, highly stable vinyl bridge 2D covalent organic framework (COF) containing Ni, which combines the role of photosensitizer and reactive site. The as-prepared sp2c-COFdpy-Ni acts as an efficient heterogeneous photocatalyst for C-O cross coupling. The sp2c-COFdpy-Ni can be completely recovered and used repeatedly without loss of activity, overcoming the limitations of the prior methods. Preliminary studies reveal that strong interlayer electron transfer may facilitate the generation of the proposed intermediate sp2c-COFdpy-NiI in a bimolecular and self-sustained manner. This all-in-one heterogeneous photocatalyst exhibits good compatibility of substrates and tolerance of functional groups. The successful attempt to expand the 2D COFs with this new catalyst into photocatalytic organic transformation opens an avenue for photoredox/transition metal mediated coupling reactions.
- Chen, Hao,Dong, Wenbo,Hu, Jianxiang,Rao, Li,Wang, Pei,Wang, Shengyao,Xiang, Yonggang,Yang, Yi
-
p. 5797 - 5805
(2021/08/23)
-
- NOVEL METHOD FOR PRODUCING PERFLUOROALKYLATING AGENTS USING MONOHYDROPERFLUOROALKANE AS STARTING MATERIAL, AND METHOD FOR PRODUCING AROMATIC PERFLUOROALKYL COMPOUND USING THE SAME
-
PROBLEM TO BE SOLVED: To provide a simple method for producing trifluoromethyltriol borate potassium from trifluoromethane. SOLUTION: There is provided a method for producing a compound represented by the formula [7], comprising: reacting a monohydroperfluoroalkane with a base and trialkyl borate in an organic solvent; and then reacting the reaction solution with triol. [In the formula, RF is an alkyl group such as a linear chain of C1-2, and a perfluoroalkyl group in which all H on C is substituted with F; R6 is H or a C1-2 linear alkyl group, or the like; M may be a metal or the like belonging to Group I, Group II, Group III, Group IV, Group V, Group VI, Group VII, Group VIII, Group IX, Group X, Group XI, Group XII, and Group XIII in the periodic table of elements, and they may be a single substance or a mixture of a plurality of substances and y corresponds to the oxidation number of the substance represented by M.] SELECTED DRAWING: None COPYRIGHT: (C)2021,JPOandINPIT
- -
-
Paragraph 0138-0139; 0141-0143
(2021/04/09)
-
- NOVEL METHOD FOR PRODUCING PERFLUOROALKYLATING AGENTS USING MONOHYDROPERFLUOROALKANE AS STARTING MATERIAL, AND METHOD FOR PRODUCING AROMATIC PERFLUOROALKYL COMPOUND USING THE SAME
-
PROBLEM TO BE SOLVED: To provide a method for producing an aromatic perfluoroalkyl compound using silylated trifluoromethyl carbinol. SOLUTION: There is provided a method for producing an aromatic perfluoroalkyl compound represented by the general formula [10], in which a compound represented by the formula [9] and a compound represented by the formula [1] are reacted in an organic solvent in the presence of a copper catalyst, a nitrogen ligand and a metal fluoride. R7-X...[9], RF-R7...[10] [In the formula, R7 is an aryl group or the like which may have a substituent; X is F, Cl, Br or I; RF is an alkyl group such as a linear chain of C1-2, and a perfluoroalkyl group in which all H on C is substituted with F; R1 and R2 are each independently H or a C1-2 linear alkyl group, or the like; R1 and R2 may be integrated to form a ring; and R3, R4 and R5 are each independently H or a C1-2 linear alkyl group, or the like.] SELECTED DRAWING: None COPYRIGHT: (C)2021,JPOandINPIT
- -
-
Paragraph 0138-0139; 0141-0143
(2021/04/09)
-
- NOVEL METHOD FOR PRODUCING PERFLUOROALKYLATING AGENTS USING MONOHYDROPERFLUOROALKANE AS STARTING MATERIAL, AND METHOD FOR PRODUCING AROMATIC PERFLUOROALKYL COMPOUNDS USING THE SAME
-
To provide a simple method for producing silylated trifluoromethylcarbinol from trifluoromethane.SOLUTION: There is provided a method for producing a compound represented by the formula [1], in which the compound is obtained by reacting a monohydroperfluoroalkane, a carbonyl compound, and NaH in an organic solvent and then reacting the reaction solution with a silylating agent. [In the formula, RF is an alkyl group such as a linear chain of C1 to 2, and a perfluoroalkyl group in which all H on C is substituted with F; R1 and R2 are independently alkyl groups such as a linear chain of H or C1 to 2, or the like respectively; R1 and R2 may be integrated to form a ring; and R3, R4 and R5 are independently H or C1 to 2 linear alkyl groups, or the like respectively.]SELECTED DRAWING: None
- -
-
Paragraph 0138-0143
(2021/04/02)
-
- Solar-driven tandem photoredox nickel-catalysed cross-coupling using modified carbon nitride
-
Nickel-catalysed aryl amination and etherification are driven with sunlight using a surface-modified carbon nitride to extend the absorption of the photocatalyst into a wide range of the visible region. In contrast to traditional homogeneous photochemical methodologies, the lower cost and higher recyclability of the metal-free photocatalyst, along with the use of readily available sunlight, provides an efficient and sustainable approach to promote nickel-catalysed cross-couplings. This journal is
- Qin, Yangzhong,Martindale, Benjamin C. M.,Sun, Rui,Rieth, Adam J.,Nocera, Daniel G.
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p. 7456 - 7461
(2020/08/03)
-
- Cathodic C-H Trifluoromethylation of Arenes and Heteroarenes Enabled by an in Situ-Generated Triflyltriethylammonium Complex
-
While several trifluoromethylation reactions involving the electrochemical generation of CF3 radicals via anodic oxidation have been reported, the alternative cathodic, reductive radical generation has remained elusive. Herein, the first cathodic trifluoromethylation of arenes and heteroarenes is reported. The method is based on the electrochemical reduction of an unstable triflyltriethylammonium complex generated in situ from inexpensive triflyl chloride and triethylamine, which produces CF3 radicals that are trapped by the arenes on the cathode surface.
- Cantillo, David,Jud, Wolfgang,Kappe, C. Oliver,Maljuric, Snjezana
-
supporting information
(2019/10/08)
-
- Electrochemically Driven, Ni-Catalyzed Aryl Amination: Scope, Mechanism, and Applications
-
C-N cross-coupling is one of the most valuable and widespread transformations in organic synthesis. Largely dominated by Pd- and Cu-based catalytic systems, it has proven to be a staple transformation for those in both academia and industry. The current study presents the development and mechanistic understanding of an electrochemically driven, Ni-catalyzed method for achieving this reaction of high strategic importance. Through a series of electrochemical, computational, kinetic, and empirical experiments, the key mechanistic features of this reaction have been unraveled, leading to a second generation set of conditions that is applicable to a broad range of aryl halides and amine nucleophiles including complex examples on oligopeptides, medicinally relevant heterocycles, natural products, and sugars. Full disclosure of the current limitations and procedures for both batch and flow scale-ups (100 g) are also described.
- Kawamata, Yu,Vantourout, Julien C.,Hickey, David P.,Bai, Peng,Chen, Longrui,Hou, Qinglong,Qiao, Wenhua,Barman, Koushik,Edwards, Martin A.,Garrido-Castro, Alberto F.,Degruyter, Justine N.,Nakamura, Hugh,Knouse, Kyle,Qin, Chuanguang,Clay, Khalyd J.,Bao, Denghui,Li, Chao,Starr, Jeremy T.,Garcia-Irizarry, Carmen,Sach, Neal,White, Henry S.,Neurock, Matthew,Minteer, Shelley D.,Baran, Phil S.
-
supporting information
p. 6392 - 6402
(2019/04/17)
-
- Mechanism of Photoredox-Initiated C-C and C-N Bond Formation by Arylation of IPrAu(I)-CF3 and IPrAu(I)-Succinimide
-
Herein, we report on the photoredox-initiated gold-mediated C(sp2)-CF3 and C(sp2)-N coupling reactions. By adopting gold as a platform for probing metallaphotoredox catalysis, we demonstrate that cationic gold(III) complexes are the key intermediates of the C-C and C-N coupling reactions. The high-valent gold(III) intermediates are accessed by virtue of photoredox catalysis through a radical chain process. In addition, the bond-forming step of the coupling reactions is the reductive elimination from cationic gold(III) intermediates, which is supported by isolation and crystallographic characterization of key Au(III) intermediates.
- Kim, Suhong,Toste, F. Dean
-
p. 4308 - 4315
(2019/01/25)
-
- Ligand-free trifluoromethylation of iodoarenes by use of 2-Aryl-2-trifluoromethylbenzimidazoline as new trifluoromethylating reagent
-
N-Methyl 2-aryl-2-trifluoromethylbenzimidazolines were synthesized and utilized in the trifluoromethylation reaction of iodoarenes in the presence of copper(I) salt and base. Iodoarenes bearing electron-donating and electron-withdrawing groups were tolerant to this reaction in the absence of a ligand and gave trifluorotoluene derivatives in good to high yields.
- Miyagawa, Masamichi,Ishikawa, Taisuke,Shinkai, Kota,Akiyama, Takahiko
-
supporting information
p. 29 - 31
(2019/01/04)
-
- Isolation of OH-bridged Ag(i)/Cu(iii) and ion-pair Cu(i)/Cu(iii) trifluoromethyl complexes with monophosphines
-
Cu(iii)-CF3 complexes are important intermediates of both synthetic and mechanistic interest. This study describes the isolation, and spectroscopic and X-ray crystallographic characterization of CuIII-CF3 complexes 2-4 with typical monophosphine ligands PPh3 and Buchwald-type biarylmonophosphines. Distinct from the ion-pair [P2Cu(i)]+[Cu(iii)(CF3)4]? structures of 2 and 4 (P: PPh3 or SPhos), complex 3 exhibits a novel OH-bridged Ag(i)-Cu(iii) dinuclear structure with XPhos-coordinated linear Ag(i) and square planar Cu(iii) components. This is the first heterobimetallic Cu(iii)-CF3 complex confirmed by both solution-phase NMR spectroscopy and solid state X-ray crystal structure analysis. Complex 3 is found to have the LUMO orbital of major σ*(Cu-CF3) nature and electrophilic CF3 ligands. Accordingly, complex 3 is able to trifluoromethylate 2 equivalents of aryl boronic acids in up to quantitative yields, regardless of the inert or oxidative conditions. In contrast, the ion-pair complexes 2 and 4 show low reactivity. This study enriches the coordination and reactivity chemistry of Cu(iii)-CF3 compounds and shows the feasibility of modulation of structures and reactivity by ligand design, which may inspire future efforts on Cu(iii)-CF3 chemistry.
- Xiao, Chang,Zhang, Song-Lin
-
supporting information
p. 848 - 853
(2019/01/21)
-
- Reductive Elimination to Form C(sp3)-N Bonds from Palladium(II) Primary Alkyl Complexes
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Reductive eliminations to form alkyl-nitrogen bonds are rare, and examples of this reaction from isolated complexes containing simple, unstabilized primary alkyl groups have not been observed. We report the synthesis of stable neopentylpalladium(II) anilido and methyleneamido complexes that undergo reductive elimination to form the C(sp3)-N bonds in N-neopentyl anilines and N-neopentyl imines, respectively. The synthesis and isolation of these complexes were enabled by weak chelation of palladium by P,O ancillary ligands. DFT calculations suggest that neopentylpalladium(II) complexes undergo reductive elimination by a concerted mechanism resembling a migration of the alkyl ligand to the nitrogen either following initial dissociation of the oxygen donor or in concert with lengthening of the Pd-O bond, depending on the identities of the reacting and ancillary ligands.
- Peacock, D. Matthew,Jiang, Quan,Cundari, Thomas R.,Hartwig, John F.
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supporting information
p. 3243 - 3247
(2018/10/05)
-
- A radical approach to the copper oxidative addition problem: Trifluoromethylation of bromoarenes
-
Transition metal–catalyzed arene functionalization has been widely used for molecular synthesis over the past century. In this arena, copper catalysis has long been considered a privileged platform due to the propensity of high-valent copper to undergo reductive elimination with a wide variety of coupling fragments. However, the sluggish nature of oxidative addition has limited copper’s capacity to broadly facilitate haloarene coupling protocols. Here, we demonstrate that this copper oxidative addition problem can be overcome with an aryl radical–capture mechanism, wherein the aryl radical is generated through a silyl radical halogen abstraction. This strategy was applied to a general trifluoromethylation of aryl bromides through dual copper-photoredox catalysis. Mechanistic studies support the formation of an open-shell aryl species.
- Le, Chip,Chen, Tiffany Q.,Liang, Tao,Zhang, Patricia,MacMillan, David W. C.
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p. 1010 - 1014
(2018/06/12)
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- Diverse copper(iii) trifluoromethyl complexes with mono-, bi- and tridentate ligands and their versatile reactivity
-
Cu(iii) trifluoromethyl complexes are proposed as essential intermediates for many copper-promoted trifluoromethylation reactions, but remain elusive and scarcely explored. We report herein the isolation and spectroscopic and X-ray crystallographic charac
- Zhang, Song-Lin,Xiao, Chang,Wan, Hai-Xing
-
supporting information
p. 4779 - 4784
(2018/04/11)
-
- NEW MANUFACTURING METHOD OF PERFLUORO ALKYLATING AGENT WHICH USED MONOHYDROPERFLUOROALKANE AS STARTING MATERIAL, AND METHOD FOR MANUFACTURING AROMATIC PERFLUORO ALKYL COMPOUND USING THE SAME
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PROBLEM TO BE SOLVED: To provide a method for manufacturing silanized trifluoromethyl carbinol, potassium trifluoromethyl triol borate and an aromatic trifluoromethyl compound from trifluoromethane. SOLUTION: There are provided a method for manufacturing silanized trifluoromethyl carbinol in which trifluoromethyl carbinol obtained by reacting trifluoromethane with a carbonyl compound in the presence of a base is reacted with silanizing agent; or a method for manufacturing potassium trifluoromethyl triol borate in which potassium trifluoromethyl trimethoxy borate obtained by reacting trifluoromethane with trimethoxy borane in the presence of a base is reacted with a triol; and a method for manufacturing an aromatic trifluoromethyl compound obtained by making an aromatic iodide act on silanized trifluoromethyl carbinol or potassium trifluoromethyl triol borate in the presence of catalytic amount of copper (I) iodide and 9,10-phenanthroline. SELECTED DRAWING: None COPYRIGHT: (C)2019,JPOandINPIT
- -
-
Paragraph 0139; 0141
(2018/12/14)
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- Copper-Promoted Conversion of Aromatic Amines into Trifluoromethylated Arenes: One-Pot Sandmeyer Trifluoromethylation
-
A simple copper-promoted one-pot Sandmeyer trifluoromethylation of aromatic amines with Langlois’ reagent has been demonstrated. The reaction is performed in mild reaction conditions under an air atmosphere with good substrate scope and functional group compatibility. It provides an alternative and straightforward synthetic approach to access a variety of trifluoromethylated arenes.
- Hong, Jianquan,Wang, Guifu,Huo, Lianguang,Zheng, Changge
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supporting information
p. 1761 - 1767
(2017/09/06)
-
- Method for synthesizing trifluoromethyl aromatic compounds
-
The invention aims to provide a method for converting arylamine into trifluoromethyl aromatic compounds under simple conditions. The trifluoromethyl aromatic compounds can be widely applied to the fields of pesticides, medicines, organic materials and the like. The method is characterized by comprising steps of (1), synthesizing Toni reagents alpha from sodium periodate, 2-iodobenzoic acid, acetic anhydride, cesium fluoride and Ruppert reagents; (2), dissolving the arylamine and hydrochloric acid in 1, 2-dichloroethane, stirring the arylamine, the hydrochloric acid and the 1, 2-dichloroethane for 5-10 min to obtain mixtures, adding tert-butyl nitrite into the mixtures under low-temperature conditions, carrying out stirring reaction for 30-60 min to obtain reaction products, adding tetrafluoroboric acid tetra-acetonitrile copper, the Toni reagents alpha and sodium bicarbonate into the reaction products and carrying micro-heat reaction for 10-20 hours; sequentially filtering, washing and drying reaction liquid after reaction is completely carried out and carrying out column chromatography separation and purification on the reaction liquid to obtain target products. The method has the advantage that the trifluoromethyl aromatic compounds can be widely applied to the fields of pesticides, medicines, organic materials and the like.
- -
-
Paragraph 0021; 0022
(2017/08/29)
-
- Stoichiometric and Catalytic Aryl-Perfluoroalkyl Coupling at Tri-tert-butylphosphine Palladium(II) Complexes
-
This Communication describes studies of Ph-RF (RF = CF3 or CF2CF3) coupling at Pd complexes of general structure (PtBu3)PdII(Ph)(RF). The CF3 analogue participates in fast Ph-CF3 coupling (II complex. Furthermore, they show that this undesired pathway can be circumvented by changing from a CF3 to a CF2CF3 ligand. Ultimately, the insights gained from stoichiometric studies enabled the identification of Pd(PtBu3)2 as a catalyst for the Pd-catalyzed cross-coupling of aryl bromides with TMSCF2CF3 to afford pentafluoroethylated arenes.
- Ferguson, Devin M.,Bour, James R.,Canty, Allan J.,Kampf, Jeff W.,Sanford, Melanie S.
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supporting information
p. 11662 - 11665
(2017/09/07)
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- Phosphovanadomolybdic acid catalyzed direct C-H trifluoromethylation of (hetero)arenes using NaSO2CF3 as the CF3 source and O2 as the terminal oxidant
-
A direct C-H trifluoromethylation of (hetero)arenes using NaSO2CF3 (Langlois' reagent) as the CF3 source and O2 as the terminal oxidant has been developed. In the presence of catalytic amounts of phosphovanadomolybdic acids, such as H6PV3Mo9O40, various kinds of substituted benzenes and heteroaromatic compounds could be converted into the corresponding trifluoromethylated products.
- Li, Chifeng,Suzuki, Kosuke,Yamaguchi, Kazuya,Mizuno, Noritaka
-
supporting information
p. 1417 - 1420
(2017/02/23)
-
- NOVEL TRIFLUOROMETHYLATION AGENT, AND METHOD FOR PRODUCING TRIFLUOROMETHYL GROUP-CONTAINING COMPOUND USING THE SAME
-
PROBLEM TO BE SOLVED: To provide a trifluoromethylation agent useful as medical and agrochemical intermediates and electronic material intermediates, and a method for producing a trifluoromethyl group-containing compound using the same. SOLUTION: The present invention provides a method for producing a trifluoromethyl group-containing compound by making trifluoromethyl group-containing borate salt represented by formula (1) react with aromatic iodide, in the presence of a copper salt catalyst and a ligand (R1 is methyl, ethyl or C3-10 straight, branched, or cyclic alkyl). SELECTED DRAWING: None COPYRIGHT: (C)2017,JPOandINPIT
- -
-
Paragraph 0052-0054
(2017/07/25)
-
- Ligand-dependent formation of ion-pair CuI/CuIII trifluoromethyl complexes containing bisphosphines
-
We report novel ion-pair bisphosphine CuI/CuIII trifluoromethyl complexes [(P2)2CuI]+[CuIII(CF3)4]- (P2 = DPPE, BINAP or Xantphos) fea
- Zhang, Song-Lin,Bie, Wen-Feng
-
supporting information
p. 17588 - 17592
(2016/11/18)
-
- Trifluoromethylation of (hetero)aryl iodides and bromides with copper(i) chlorodifluoroacetate complexes
-
A new copper-mediated trifluoromethylation reaction using copper(i) chlorodifluoroacetate complexes as reagents is reported. The complex [L2Cu][O2CCF2Cl] (L = bpy, dmbpy, phen) reacted with (hetero)aryl iodides and bromides in the presence of CsF in DMF at 75 °C to afford the trifluoromethylarenes in good to excellent yields. High compatibility with various chemical functions or (hetero)cycles was also observed in the reaction. A reaction mechanism involving a difluorocarbene intermediate, along with a subsequent formation of a -CF3 anion was proposed.
- Lin, Xiaoxi,Li, Zhengyu,Han, Xiaoyan,Weng, Zhiqiang
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p. 75465 - 75469
(2016/08/24)
-
- Isolation and characterization of copper(III) trifluoromethyl complexes and reactivity studies of aerobic trifluoromethylation of arylboronic acids
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The isolation, characterization and reactivity of transition metal trifluoromethyl complexes are fundamental and challenging topics in trifluoromethylation chemistry. We report herein the synthesis and isolation of two new complexes [(phen)CuI(PPh3)2]+[CuIII(CF3)4]- (2) and (phen)CuIII(CF3)3 (3) as well as a known complex (bpy)CuIII(CF3)3 (4) at room temperature. 2 and 3 have been fully characterized using 1H, 19F, 31P NMR, elemental analyses and X-ray crystallography. Reactivity studies indicate that 2 is unreactive toward arylboronic acids. In contrast, 3 and 4 can react with various aryl and heteroaryl boronic acids to deliver trifluoromethylated arenes in good to quantitative yields under mild conditions. The presence of a fluoride additive in DMF under aerobic conditions is crucial to these reactions. This study provides fundamental information about the structure and reactivity of elusive Cu(iii) trifluoromethyl complexes that have been proposed as relevant reactive intermediates in many trifluoromethylation reactions.
- Zhang, Song-Lin,Bie, Wen-Feng
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p. 70902 - 70906
(2016/08/05)
-
- DBU-Promoted Trifluoromethylation of Aryl Iodides with Difluoromethyltriphenylphosphonium Bromide
-
DBU-promoted trifluoromethylation of aryl iodides with difluoromethyltriphenylphosphonium bromide (DFPB) in the presence of copper source is described. In this transformation, DBU not only acts as base to deprotonate the difluoromethyl group in DFPB to generate difluoromethylene phosphonium ylide Ph3P+CF2-, but also converts the difluorocarbene generated from ylide Ph3P+CF2- into trifluoromethyl anion, finally resulting in the trifluoromethylation of aryl iodides. The reactions proceeded smoothly to afford expected products in moderate to good yields.
- Wei, Yun,Yu, Liuying,Lin, Jinhong,Zheng, Xing,Xiao, Jichang
-
p. 481 - 484
(2016/06/01)
-
- Trifluoromethylation of haloarenes with a new trifluoro-methylating reagent Cu(O2CCF2SO2F)2
-
A new trifluoromethylating reagent Cu(O2CCF2SO2F)2, which easily decomposes to generate active CuCF3 species in DMF at room temperature, has been conveniently prepared from inexpensive starting materials on a large scale. This new reagent can be applied to efficiently trifluoromethylate a variety of haloarenes under mild conditions, providing good-to-excellent yields of the desired products.
- Zhao, Gang,Wu, Hao,Xiao, Zhiwei,Chen, Qing-Yun,Liu, Chao
-
p. 50250 - 50254
(2016/06/15)
-
- Copper-mediated trifluoromethylation of diaryliodonium salts with difluoromethyltriflate
-
The reaction of diaryliodonium salts with difluoromethyltriflate in the presence of TBAT and CuTC gave the corresponding trifluoromethylated arenes in moderate yields. Compared to other difluorocarbene-derived trifluoromethylation reactions, the current one proceeded at mild reaction conditions (room temperature) within short reaction time (5 min).
- Yang, Jing-Yun,Xu, Xiu-Hua,Qing, Feng-Ling
-
-
- Palladium-Catalyzed Trifluoromethylation of (Hetero)Arenes with CF3Br
-
The CF3 group is an omnipresent motif found in many pharmaceuticals, agrochemicals, catalysts, materials, and industrial chemicals. Despite well-established trifluoromethylation methodologies, the straightforward and selective introduction of such groups into (hetero)arenes using available and less expensive sources is still a major challenge. In this regard, the selective synthesis of various trifluoromethyl-substituted (hetero)arenes by palladium-catalyzed C-H functionalization is herein reported. This novel methodology proceeds under comparably mild reaction conditions with good regio- and chemoselectivity. As examples, trifluoromethylations of biologically important molecules, such as melatonin, theophylline, caffeine, and pentoxifylline, are showcased.
- Natte, Kishore,Jagadeesh, Rajenahally V.,He, Lin,Rabeah, Jabor,Chen, Jianbin,Taeschler, Christoph,Ellinger, Stefan,Zaragoza, Florencio,Neumann, Helfried,Brückner, Angelika,Beller, Matthias
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supporting information
p. 2782 - 2786
(2016/02/27)
-
- METHOD FOR PREPARATION OF FLUORO, CHLORO AND FLUOROCHLORO ALKYLATED COMPOUNDS BY HOMOGENEOUS CATALYSIS
-
The invention discloses a method for preparation of fluoro, chloro and fluorochloro alkylated compounds by homogeneous Pd catalyzed fluoro, chloro and fluorochloro alkylation with fluoro, chloro and fluorochloroalkyl halides in the presence of di(1-adamantyl)-n-butylphosphine and in the presence of 2,2,6,6-tetramethylpiperidine 1-oxyl.
- -
-
Page/Page column 15; 16; 17
(2016/06/01)
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- Copper-catalysed synthesis of trifluoromethyl(hetero)arenes from di(hetero)aryl-λ3-iodanes
-
An efficient synthesis of trifluoromethylated (hetero)arenes has been achieved through the regioselective copper-catalyzed trifluoromethylation of di(hetero)aryl-λ3-iodanes, employing readily available trifluoromethyltrimethylsilane. The reaction works well for both symmetrical and unsymmetrical di(hetero)aryl-λ3-iodanes with good regioselectivity and also tolerates diverse functional groups such as bromo, iodo, cyano, nitro, ester, ketone and enolizable ketone.
- Pandey, Vinay Kumar,Anbarasan, Pazhamalai
-
p. 18525 - 18529
(2016/02/27)
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- Decarboxylative Trifluoromethylating Reagent [Cu(O2CCF3)(phen)] and Difluorocarbene Precursor [Cu(phen)2][O2CCF2Cl]
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This article describes the new economic decarboxylative trifluoromethylating reagent [Cu(phen)(O2CCF3)] (1; phen=1,10-phenanthroline) and the efficient difluorocarbene precursor [Cu(phen)2][O2CCF2Cl] (2). Treatment of copper tert-butoxide with phen and subsequent addition of trifluoroacetic acid or chlorodifluoroacetic acid afforded air-stable complexes 1 and 2, respectively, which were characterized by X-ray crystallography. The copper(I) ion in 1 is coordinated by a bidentate phen ligand, a monodentate trifluoroacetate group, and a molecule of CH3CN in a distorted tetrahedral coordination geometry. The molecular structure of 2 adopts an ionic form that consists of a [Cu(phen)2]+ cation and a chlorodifluoroacetate anion. Complex 1 reacted with a variety of aryl and heteroaryl halides to form trifluoromethyl (hetero)arenes in good yields. The corresponding Hammett plot exhibited a linear relationship and a reaction parameter (ρ)=+0.56±0.02, which indicated that the trifluoromethylation reaction proceeded via a nucleophilic reactive species. Complex 2 reacts with phenols to produce aryl difluoromethyl ethers in modest-to-excellent yields. Mechanistic investigations revealed that the difluoromethylation reaction proceeds by initial copper-mediated formation of difluorocarbene and subsequent concerted addition of difluorocarbene to the phenol to form a three-center transition state.
- Lin, Xiaoxi,Hou, Chuanqi,Li, Haohong,Weng, Zhiqiang
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supporting information
p. 2075 - 2084
(2016/02/12)
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- TCDA: Practical Synthesis and Application in the Trifluoromethylation of Arenes and Heteroarenes
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A practical synthesis of the reagent trimethylsilyl chlorodifluoroacetate (TCDA) is reported on 50 g scale. The trifluoromethylation with TCDA was optimized, and the reaction shows very broad scope with respect to electron-deficient, -neutral, -rich aryl/heteroaryl iodides, as well as excellent functional group tolerability, such as ester, amide, aldehyde, hydroxyl, and carboxylic acid. The reagent was also applied to the late-stage trifluoromethylation of three medicinally relevant compounds. Additionally, the building block trifluoromethylpyridine and one drug related molecule Boc-Fluoxetin were synthesized in 10 g scale by this method, demonstrating its practical applications in process chemistry.
- Wang, Jian,Zhang, Xiaomin,Wan, Zehong,Ren, Feng
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p. 836 - 839
(2016/05/19)
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- Cyclic-Protected Hexafluoroacetone as an Air-Stable Liquid Reagent for Trifluoromethylations
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An air-stable liquid trifluoromethylating reagent is readily synthesized from gaseous hexafluoroacetone and 2-methylproline on a gram scale. The reaction of the trifluoromethylating reagent with tert-butoxy cuprate K[Cu(OtBu)2] leads to the CuCF3in high yield. This species is directly formed from the tetrahedral cuprate intermediate through intramolecular migration of the trifluoromethyl group to copper. The CuCF3reagent prepared in situ by our method can be used for the trifluoromethylation of aryl iodides, arylboronic acids, and terminal alkynes in good to excellent yields, even on a gram scale. Furthermore, the CuC2F5reagent can be prepared in the same way, and this can be used in the pentafluoroethylation of arylboronic acids or aryl bromides in good to excellent yields.
- Negishi, Kazuyuki,Aikawa, Kohsuke,Mikami, Koichi
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p. 4099 - 4104
(2016/08/24)
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- BIS(TRIFLUOROMETHYL)ZINC DMPU COMPLEX, MANUFACTURING METHOD THEREOF AND MANUFACTURING METHOD OF TRIFLUOROMETHYL GROUP-CONTAINING COMPOUND USING THE SAME
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PROBLEM TO BE SOLVED: To provide a bis(trifluoromethyl)zinc DMPU complex stable under room temperature and useful as a reaction reagent, a manufacturing method thereof and a manufacturing method of a trifluoromethyl group-containing compound using the same. SOLUTION: A method of obtaining a trifluoromethyl group-containing compound by reacting with a substituted aromatic iodide under a copper (I) catalyst after obtaining a bis(fluoromethyl)zinc DMPU complex represented by the formula (1) (CF3)2Zn (DMPU)2 (1), where DMPU represents N,N'-dimethyl propylene urea, by reacting dialkyl zinc, trifluoromethyl halide and N,N'-dimethyl propylene urea in an organic solvent, then filtration or solvent leaving removal of precipitate. COPYRIGHT: (C)2015,JPOandINPIT
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Paragraph 0030-0032
(2018/11/22)
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- Oxidation of Ni(II) to Ni(IV) with Aryl Electrophiles Enables Ni-Mediated Aryl-CF3 Coupling
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This communication describes the synthesis and reactivity of NiIV(aryl)(CF3)2 complexes supported by trispyrazolylborate and 4,4′-di-tert-butylbipyridine ligands. We demonstrate that isolable NiIV complexes can be accessed under mild conditions via the oxidation of NiII precursors with S-(trifluoromethyl)dibenzothiophenium triflate as well as with diaryliodonium and aryl diazonium reagents. The NiIV intermediates undergo high yielding aryl-CF3 bond-forming reductive elimination. These studies support the potential viability of NiIV intermediates in nickel-catalyzed coupling reactions involving diaryliodonium and aryldiazonium electrophiles.
- Bour, James R.,Camasso, Nicole M.,Sanford, Melanie S.
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supporting information
p. 8034 - 8037
(2015/07/08)
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- New Reagent for Highly Efficient Synthesis of Trifluoromethyl-Substituted Arenes and Heteroarenes
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A new reagent trimethylsilyl chlorodifluoroacetate (TCDA) is reported for the introduction of a -CF3 group to arenes and heteroarenes. Compared with current known reagents, TCDA shows very broad scope with respect to electron-deficient, -neutral, and -rich aryl/heteroaryl iodides as well as excellent functional group tolerance, including ester, amide, aldehyde, hydroxyl, and carboxylic acid. (Chemical Equation Presented).
- Zhang, Xiaomin,Wang, Jian,Wan, Zehong
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supporting information
p. 2086 - 2089
(2015/05/13)
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- Catalytic trifluoromethylation of aryl- and vinylboronic acids by 2-cyclopropyl-1-(trifluoromethyl)benzo[ b ]thiophenium triflate
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Catalytic trifluoromethylation of aryl- and vinylboronic acids by 2-cyclopropyl-1-(trifluoromethyl)benzo[b]thiophenium triflate is described. In the presence of a catalytic amount of CuOAc and 2,4,6-collidine in ethyl acetate, the reaction proceeded in good to high yields for various substrates under mild reaction conditions at room temperature.
- Arimori, Sadayuki,Shibata, Norio
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supporting information
p. 1632 - 1635
(2015/04/14)
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- 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU)-promoted decomposition of difluorocarbene and the subsequent trifluoromethylation
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Difluorocarbene derived from various carbene precursors could be effectively decomposed by 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). This decomposition process was successfully applied in the subsequent trifluoromethylation of a variety of (hetero)aryl iodides without the addition of an external fluoride ion. Mechanistic investigation revealed the detailed difluorocarbene conversion process in which the decomposed difluorocarbene is finally transformed into a fluoride ion and carbon monoxide.
- Zheng, Jian,Lin, Jin-Hong,Deng, Xiao-Yun,Xiao, Ji-Chang
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supporting information
p. 532 - 535
(2015/03/04)
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- Stable but reactive perfluoroalkylzinc reagents: Application in ligand-free copper-catalyzed perfluoroalkylation of aryl iodides
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The aromatic perfluoroalkylation catalyzed by a copper(I) salt with bis(perfluoroalkyl)zinc reagents Zn(RF)2(DMPU)2, which were prepared and then isolated as a stable white powder from perfluoroalkyl iodide and diethylzinc, was accomplished to provide the perfluoroalkylated products in good-to-excellent yields. The advantages of this reliable and practical catalytic reaction are 1) airstable and easy-to-handle bis(perfluoroalkyl)zinc reagents can be utilized, 2) the reagent is reactive and hence the operation without activators and ligands is simple, and 3) not only trifluoromethylation but also perfluoroalkylation can be attained.
- Aikawa, Kohsuke,Nakamura, Yuzo,Yokota, Yuki,Toya, Wataru,Mikami, Koichi
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supporting information
p. 96 - 100
(2015/02/05)
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- Copper-mediated trifluoromethylation using phenyl trifluoromethyl sulfoxide
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A new method for the generation of trifluoromethylcopper ( CuCF3 ) species from readily available phenyl trifluoromethyl sulfoxide has been developed. The CuCF3 reagent can be applied in efficient trifluoromethylations of aryl iodides and activated aryl bromides in the absence of additional ligands. Furthermore, the CuCF3 species can also undergo oxidative cross-coupling with terminal alkynes and arylboronic acids.
- Li, Xinjin,Zhao, Jingwei,Zhang, Liang,Hu, Mingyou,Wang, Limin,Hu, Jinbo
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supporting information
p. 298 - 301
(2015/03/04)
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- A universal procedure for the [18F]trifluoromethylation of aryl iodides and aryl boronic acids with highly improved specific activity
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Herein we describe a valuable method for the introduction of the [18F]CF3 group into arenes with highly improved specific activity by the reaction of [18F]trifluoromethane with aryl iodides or aryl boronic acids. This [su
- Vanderborn, Dion,Sewing, Claudia,Herscheid,Windhorst, Albert D.,Orru, Romano V. A.,Vugts, Danielle J.
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supporting information
p. 11046 - 11050
(2015/03/30)
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- Trifluoromethylation of arenediazonium salts with fluoroform-derived CuCF3 in aqueous media
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A new protocol has been developed for trifluoromethylation of arenediazonium salts with moisture-sensitive CuCF3 (from fluoroform) in aqueous media. The reaction is governed by a radical mechanism, tolerates a broad variety of functional groups, and is applicable to the synthesis of complex, polyfunctionalized molecules. This journal is the Partner Organisations 2014.
- Lishchynskyi, Anton,Berthon, Guillaume,Grushin, Vladimir V.
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supporting information
p. 10237 - 10240
(2014/08/18)
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- One-pot sandmeyer trifluoromethylation and trifluoromethylthiolation
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Practical one-pot procedures were developed for both Sandmeyer-type trifluoromethylations and trifluoromethylthiolations. Starting from broadly available (hetero)aromatic amines, various benzotrifluorides were synthesized in high yields via in situ diazotization and copper-mediated trifluoromethylation using the inexpensive Ruppert-Prakash trifluoromethylating reagent. In the presence of sodium thiocyanate as a sulfur source, aryl trifluoromethyl thioethers are exclusively formed.
- Bayarmagnai, Bilguun,Matheis, Christian,Risto, Eugen,Goossen, Lukas J.
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supporting information
p. 2343 - 2348
(2014/07/21)
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- Copper-mediated trifluoromethylation of aryl-, heteroaryl-, and vinyltrifluoroborates with Langlois' reagent
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An effortless and realistic procedure for the copper-mediated trifluoromethylation of aryl-, heteroaryl- and vinyltrifluoroborates with CF3 radicals generated from NaSO2CF3 and tert-butyl hydroperoxide (TBHP) is presented. The developed method produces trifluoromethyl arenes and -alkenes in good to excellent yields and a wide range of electronically and structurally diverse substrates are tolerated.
- Dubbaka, Srinivas Reddy,Salla, Manohar,Bolisetti, Raghu,Nizalapur, Shashidhar
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p. 6496 - 6499
(2014/02/14)
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- Mechanism of trifluoromethylation of aryl halides with CuCF3and the ortho effect
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A combined experimental (radical clock, kinetic, Hammett) and computational (DFT, MM) study of the trifluoromethylation reaction of aryl halides with CuCF3 reveals a nonradical mechanism involving Ar-X oxidative addition to the Cu(I) center as the rate determining step. The reaction is second order, first order in each reactant with ΔG? ≈ 24 kcal/mol for PhI (computed ΔG? = 21.9 kcal/ mol). An abrupt change in the gradient on the Hammett plot of log(kR/ kH) versus σp for 11 p-RC6H4I substrates produces two correlations (ρ = +0.69 and +1.83), which is temptingly suggestive of two different reaction pathways. Only one mechanism is operational, however, as advocated by a single linear correlation with σp- (ρ = +0.91), analysis of the experimental ρ values, close similarity of the transition states varying in R and displaying clear signs of -M interactions, and excellent reproduction of the plot by DFT. The long-known yet previously uncomprehended ortho effect has been quantified, for the first time, using the reaction of CuCF3 with a series of o-RC6H4Br: R(kR/kH) = H (1) 2Me (850) 2 (4300) 2H (150 000). With minor contributions from electronic factors, the ortho effect is largely determined by (i) the stabilizing coordination of the o-substituent to Cu in the transition state with the Cu?O distance varying directly with the barrier and (ii) the steric bulk of the o-substituent that raises the ground state free energy of the haloarene (Go ortho - Go H or Go ortho - Go para) by inflicting molecular strain and consequently weakening the Ar-X bond.
- Konovalov, Andrey I.,Lishchynskyi, Anton,Grushin, Vladimir V.
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supporting information
p. 13410 - 13425
(2015/03/30)
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- Efficient copper-catalyzed trifluoromethylation of aromatic and heteroaromatic iodides: The beneficial anchoring effect of borates
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Efficient copper-catalyzed trifluoromethylation of aromatic iodides was achieved with TMSCF3 in the presence of trimethylborate. The Lewis acid was used to anchor the in situ generated trifluoromethyl anion and suppress its rapid decomposition. Broad applicability of the new trifluoromethylating reaction was demonstrated in the functionalization of different aromatic and heteroaromatic iodides.
- Gonda, Zsombor,Kovacs, Szabolcs,Weber, Csaba,Gati, Tamas,Meszaros, Attila,Kotschy, Andras,Novak, Zoltan
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supporting information
p. 4268 - 4271
(2014/09/30)
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- Cu-catalyzed trifluoromethylation of aryl iodides with trifluoromethylzinc reagent prepared in situ from trifluoromethyl iodide
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The trifluoromethylation of aryl iodides catalyzed by copper(I) salt with trifluoromethylzinc reagent prepared in situ from trifluoromethyl iodide and Zn dust was accomplished. The catalytic reactions proceeded under mild reaction conditions, providing th
- Nakamura, Yuzo,Fujiu, Motohiro,Murase, Tatsuya,Itoh, Yoshimitsu,Serizawa, Hiroki,Aikawa, Kohsuke,Mikami, Koichi
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p. 2404 - 2409
(2014/01/06)
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- Trifluoromethylation of aryl and heteroaryl halides with fluoroform-derived CuCF3: Scope, limitations, and mechanistic features
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Fluoroform-derived CuCF3 recently discovered in our group exhibits remarkably high reactivity toward aryl and heteroaryl halides, performing best in the absence of extra ligands. A broad variety of iodoarenes undergo smooth trifluoromethylation with the ligandless CuCF3 at 23-50 C to give the corresponding benzotrifluorides in nearly quantitative yield. A number of much less reactive aromatic bromides also have been trifluoromethylated, including pyridine, pyrimidine, pyrazine, and thiazole derivatives as well as aryl bromides bearing electron-withdrawing groups and/or ortho substituents. Only the most electrophilic chloroarenes can be trifluoromethylated, e.g., 2-chloronicotinic acid. Exceptionally high chemoselectivity of the reactions (no side-formation of arenes, biaryls, and C2F5 derivatives) has allowed for the isolation of a large number of trifluoromethylated products in high yield on a gram scale (up to 20 mmol). The CuCF3 reagent is destabilized by CuX coproduced in the reaction, the magnitude of the effect paralleling the Lewis acidity of CuX: CuCl > CuBr > CuI. While SNAr and SRN1 mechanisms are not operational, there is a well-pronounced ortho effect, i.e., the enhanced reactivity of ortho-substituted aryl halides 2-RC6H4X toward CuCF3. Intriguingly, this ortho-effect is observed for R = NO2, COOH, CHO, COOEt, COCH3, OCH3, and even CH3, but not for R = CN. The fluoroform-derived CuCF3 reagent and its reactions with haloarenes provide an unmatched combination of reactivity, selectivity, and low cost.
- Lishchynskyi, Anton,Novikov, Maxim A.,Martin, Eddy,Escudero-Adan, Eduardo C.,Novak, Petr,Grushin, Vladimir V.
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p. 11126 - 11146
(2013/12/04)
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- Direct synthesis of a trifluoromethyl copper reagent from trifluoromethyl ketones: Application to trifluoromethylation
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Being economic with fluorine: The direct synthesis of CuCF3 from a cuprate reagent and trifluoromethyl ketones, as one of the most economical and efficient trifluoromethyl sources, was accomplished. The advantages of this method are all of reagents employed are low-cost, operation is simple, and the yield of CuCF3 is virtually quantitative (see scheme). Furthermore, three types of trifluoromethylations smoothly proceeded to provide the corresponding products in high yields. Copyright
- Serizawa, Hiroki,Aikawa, Kohsuke,Mikami, Koichi
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supporting information
p. 17692 - 17697
(2014/01/17)
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