116470-67-8Relevant articles and documents
New Reagent for Highly Efficient Synthesis of Trifluoromethyl-Substituted Arenes and Heteroarenes
Zhang, Xiaomin,Wang, Jian,Wan, Zehong
, p. 2086 - 2089 (2015)
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).
A radical approach to the copper oxidative addition problem: Trifluoromethylation of bromoarenes
Le, Chip,Chen, Tiffany Q.,Liang, Tao,Zhang, Patricia,MacMillan, David W. C.
, p. 1010 - 1014 (2018/06/12)
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.
Trifluoromethylation of (hetero)aryl iodides and bromides with copper(i) chlorodifluoroacetate complexes
Lin, Xiaoxi,Li, Zhengyu,Han, Xiaoyan,Weng, Zhiqiang
, p. 75465 - 75469 (2016/08/24)
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.
Decarboxylative Trifluoromethylating Reagent [Cu(O2CCF3)(phen)] and Difluorocarbene Precursor [Cu(phen)2][O2CCF2Cl]
Lin, Xiaoxi,Hou, Chuanqi,Li, Haohong,Weng, Zhiqiang
supporting information, p. 2075 - 2084 (2016/02/12)
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.
Electron-deficient heteroarenium salts: An organocatalytic tool for activation of hydrogen peroxide in oxidations
?turala, Ji?í,Bohá?ová, Soňa,Chudoba, Josef,Metelková, Radka,Cibulka, Radek
, p. 2676 - 2699 (2015/03/18)
A series of monosubstituted pyrimidinium and pyrazinium triflates and 3,5-disubstituted pyridinium triflates were prepared and tested as simple catalysts of oxidations with hydrogen peroxide, using sulfoxidation as a model reaction. Their catalytic efficiency strongly depends on the type of substituent and is remarkable for derivatives with an electron-withdrawing group, showing reactivity comparable to that of flavinium salts which are the prominent organocatalysts for oxygenations. Because of their high stability and good accessibility, 4-(trifluoromethyl)pyrimidinium and 3,5-dinitropyridinium triflates are the catalysts of choice and were shown to catalyze oxidation of aliphatic and aromatic sulfides to sulfoxides, giving quantitative conversions, high preparative yields and excellent chemoselectivity. The high efficiency of electron-poor heteroarenium salts is rationalized by their ability to readily form adducts with nucleophiles, as documented by low pKR+ values (pKR+ red > -0.5 V). Hydrogen peroxide adducts formed in situ during catalytic oxidation act as substrate oxidizing agents. The Gibbs free energies of oxygen transfer from these heterocyclic hydroperoxides to thioanisole, obtained by calculations at the B3LYP/6-311++g(d,p) level, showed that they are much stronger oxidizing agents than alkyl hydroperoxides and in some cases are almost comparable to derivatives of flavin hydroperoxide acting as oxidizing agents in monooxygenases.
Copper-mediated perfluoroalkylation of heteroaryl bromides with (phen)CuRF
Mormino, Michael G.,Fier, Patrick S.,Hartwig, John F.
, p. 1744 - 1747 (2014/04/17)
The attachment of perfluoroalkyl groups onto organic compounds has been a major synthetic goal over the past several decades. Previously, our group reported phenanthroline-ligated perfluoroalkyl copper reagents, (phen)CuR F, which react with aryl iodides and aryl boronates to form the corresponding benzotrifluorides. Herein the perfluoroalkylation of a series of heteroaryl bromides with (phen)CuCF3 and (phen)CuCF 2CF3 is reported. The mild reaction conditions allow the process to tolerate many common functional groups. Perfluoroethylation with (phen)CuCF2CF3 occurs in somewhat higher yields than trifluoromethylation with (phen)CuCF3, creating a method to generate fluoroalkyl heteroarenes that are less accessible from trifluoroacetic acid derivatives.
Trifluoromethylation of aryl and heteroaryl halides with fluoroform-derived CuCF3: Scope, limitations, and mechanistic features
Lishchynskyi, Anton,Novikov, Maxim A.,Martin, Eddy,Escudero-Adan, Eduardo C.,Novak, Petr,Grushin, Vladimir V.
, p. 11126 - 11146 (2013/12/04)
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.
Me3SiCF3/AgF/Cu - A new reagents combination for selective trifluoromethylation of various organic halides by trifluoromethylcopper, CuCF3
Kremlev, Mikhail M.,Mushta, Aleksej I.,Tyrra, Wieland,Yagupolskii, Yurii L.,Naumann, Dieter,M?ller, Angela
experimental part, p. 67 - 71 (2012/03/10)
An alternative copper halide-free route to obtain highly reactive trifluoromethylcopper species has been developed via the reaction of silver fluoride and trimethyl(trifluoromethyl)silane followed by a redox transmetallation with elemental copper. The composition of the reactive intermediate was investigated by means of UV/Vis/NIR, ESR, 19F NMR spectroscopy and ESI mass spectrometry. "Trifluoromethylcopper" prepared by the oxidative transmetallation route exhibits excellent reactivity and selectivity in substitutions of iodine or bromine bond to aromatic or heterocyclic compounds for trifluoromethyl groups without any additional catalyst.
THE TRIFLUOROMETHYLATION OF CHLOROAROMATICS USING THE COPPER-CF2Br2-DIALKYLAMIDE REACTION SYSTEM
Clark, James H.,Denness, James E.,McClinton, Martin A.,Wynd, Andrew J.
, p. 411 - 426 (2007/10/02)
The in situ generation of CuCF3 from the reaction of copper, dibromodifluoromethane and either N,N-dimethylformamide or N,N-dimethylacetamide (Burton's reagent) has been used for the direct substitution of chlorine by CF3 in a number of aromatic substrates.Particular attention has been paid to the effects of ring substituents on the efficiency of reaction.
The Direct Trifluoromethylation of Aryl Chlorides using Burton's Reagent
Clark, James H.,McClinton, Martin A.,Blade, Robert J.
, p. 638 - 639 (2007/10/02)
The copper-dibromodifluoromethane-N,N-dimethylacetamide reaction system trifluoromethylates electronically activated aryl chlorides possessing ortho groups capable of interacting with the metal.
