- THE EFFECT OF CHARCOAL ON THE TRIFLUOROMETHYLATION OF ARYL CHLORIDES USING BURTON'S REAGENT
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The reactivity of the trifluoromethylating system copper-dibromodifluoromethane-N,N-dimethylacetamide towards aryl chlorides can be enhanced by the addition of charcoal.
- Clark, James H.,McClinton, Martin A.,Jones, Craig W.,Landon, Philip,Bishop, D.,Blade, R. J.
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- 4-Position-Selective C-H Perfluoroalkylation and Perfluoroarylation of Six-Membered Heteroaromatic Compounds
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The first 4-position-selective C-H perfluoroalkylation and perfluoroarylation of six-membered heteroaromatic compounds were achieved using nucleophilic perfluoroalkylation and perfluoroarylation reagents. The regioselectivity was controlled by electrophilically activating the heteroaromatic rings, while sterically hindering the 2-position, with a sterically bulky borane Lewis acid. The reaction proceeded in good yield, even in gram scale, and by a sequential reaction without isolating the intermediates. This reaction could be applied to late-stage trifluoromethylation of a bioactive compound.
- Nagase, Masahiro,Kuninobu, Yoichiro,Kanai, Motomu
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- Trifluoromethylation of (hetero)aryl iodides and bromides with copper(i) chlorodifluoroacetate complexes
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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)
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- Copper-mediated perfluoroalkylation of heteroaryl bromides with (phen)CuRF
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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.
- Mormino, Michael G.,Fier, Patrick S.,Hartwig, John F.
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supporting information
p. 1744 - 1747
(2014/04/17)
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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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- The Direct Trifluoromethylation of Aryl Chlorides using Burton's Reagent
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The copper-dibromodifluoromethane-N,N-dimethylacetamide reaction system trifluoromethylates electronically activated aryl chlorides possessing ortho groups capable of interacting with the metal.
- Clark, James H.,McClinton, Martin A.,Blade, Robert J.
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p. 638 - 639
(2007/10/02)
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