- Synthesis of Fluorinated Alkyl Aryl Ethers by Palladium-Catalyzed C-O Cross-Coupling
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Herein, we report a highly effective protocol for the cross-coupling of (hetero)aryl bromides with fluorinated alcohols using the commercially available precatalyst tBuBrettPhos Pd G3 and Cs2CO3 in toluene. This Pd-catalyzed coupling features a short reaction time, excellent functional group tolerance, and compatibility with electron-rich and-poor (hetero)arenes. The method provides access to 18F-labeled trifluoroethyl ethers by cross-coupling with [18F]trifluoroethanol.
- Szpera, Robert,Isenegger, Patrick G.,Ghosez, Maxime,Straathof, Natan J. W.,Cookson, Rosa,Blakemore, David C.,Richardson, Paul,Gouverneur, Véronique
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supporting information
p. 6573 - 6577
(2020/09/02)
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- Oxalic Diamides and tert-Butoxide: Two Types of Ligands Enabling Practical Access to Alkyl Aryl Ethers via Cu-Catalyzed Coupling Reaction
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A robust and practical protocol for preparing alkyl aryl ethers has been developed, which relies on using two types of ligands to promote Cu-catalyzed alkoxylation of (hetero)aryl halides. The reaction scope is very general for a variety of coupling partners, particularly for challenging secondary alcohols and (hetero)aryl chlorides. In case of coupling with aryl chlorides and bromides, two oxalic diamides serve as the powerful ligands. The tert-butoxide is first demonstrated as a ligand for Cu-catalyzed coupling reaction, leading to alkoxylation of aryl iodides complete at room temperature. Additionally, a number of carbohydrate derivatives are applicable for this coupling reaction, affording the corresponding carbohydrate-aryl ethers in 29-98% yields.
- Chen, Zhixiang,Jiang, Yongwen,Zhang, Li,Guo, Yinlong,Ma, Dawei
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supporting information
p. 3541 - 3549
(2019/02/26)
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- Well-defined copper(I) fluoroalkoxide complexes for trifluoroethoxylation of aryl and heteroaryl bromides
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Copper(I) fluoroalkoxide complexes bearing dinitrogen ligands were synthesized and the structure and reactivity of the complexes toward trifluoroethoxylation, pentafluoropropoxylation, and tetrafluoropropoxylation of aryl and heteroaryl bromides were investigated. Efficiency drive: A series of copper(I) fluoroalkoxide complexes bearing N,N ligands have been prepared and structurally characterized. These well-defined complexes serve as efficient reagents for the fluoroalkoxylation of aryl and heteroaryl bromides to produce a wide range of trifluoroethyl, pentafluoropropyl, and tetrafluoropropyl (hetero)aryl ethers in good to excellent yields.
- Huang, Ronglu,Huang, Yangjie,Lin, Xiaoxi,Rong, Mingguang,Weng, Zhiqiang
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supporting information
p. 5736 - 5739
(2015/05/19)
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- Transition-Metal-Mediated Synthesis of Trifluoroethyl Aryl Ethers
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A series of well-defined copper(I) fluoroalkoxide complexes, [(phen)2Cu][OCH2RF], have been shown to undergo trifluoroethoxylation, pentafluoropropoxylation, and tetrafluoropropoxylation with aryl and heteroaryl bromides to generate the corresponding trifluoroethyl, pentafluoropropyl, and tetrafluoropropyl (hetero)aryl ethers in good to excellent yields. The reaction tolerates a variety of functional groups and demonstrates efficient scalability and practicality.
- Huang, Yangjie,Huang, Ronglu,Weng, Zhiqiang
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p. 2327 - 2331
(2015/10/19)
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- Facile synthesis of trifluoroethyl aryl ethers through copper-catalyzed coupling of CF3CH2OH with aryl- and heteroaryl boronic acids
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An efficient copper-catalyzed Chan-Lam reaction of trifluoroethanol with a variety of aryl- and heteroaryl boronic acids has been developed. This research provides a practical method to synthesize trifluoroethyl aryl ethers in moderate to good yields under mild conditions.
- Wang, Ruixin,Wang, Liang,Zhang, Kena,Li, Jingya,Zou, Dapeng,Wu, Yangjie,Wu, Yusheng
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supporting information
p. 4815 - 4818
(2015/07/20)
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- Metal-free arylations via photochemical activation of the Ar-OSO 2R bond in aryl nonaflates
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The photolysis of electron-rich aryl nonaflates (ArONfs) in protic media was investigated and heterolysis of the Ar-OS bond (from 3ArONf) took place. The reaction generated a triplet phenyl cation that added to π-bond nucleophiles. This metal-free arylation method was made further useful by adopting in situ preparation of ArONf from the corresponding phenol.
- Raviola, Carlotta,Canevari, Veronica,Protti, Stefano,Albini, Angelo,Fagnoni, Maurizio
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supporting information
p. 2704 - 2708
(2013/10/08)
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- Iodonium Cyclophanes for SECURE Arene Functionalization
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This disclosure relates to compounds, reagents, and methods useful in the synthesis of aryl fluorides, for example, in the preparation of 18F labeled radiotracers. For example, this disclosure provides universal “locked” aryl substituents that result in StereoElectronic Control of Unidirectional Reductive Elimination (SECURE) from diaryliodonium salts. The reagents and methods provided herein may be used to access a broad range of compounds, including aromatic compounds, heteroaromatic compounds, amino acids, nucleotides, and synthetic compounds.
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Page/Page column 27
(2011/08/08)
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- Unprecedented directing group ability of cyclophanes in arene fluorinations with diaryliodonium salts
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For the first time it is shown that exceptionally electron-rich arene rings can be fluorinated exclusively during the reductive elimination reactions of diaryliodonium fluorides. The 5-methoxy[2.2]paracyclophan-4-yl directing group simultaneously reduces unproductive aryne chemistry and eliminates ligand exchange reactions by a combination of steric and electronic effects. Use of the cyclophane directing group permits an unprecedented degree of control in fluorination reactions of diaryliodonium salts.
- Graskemper, Joseph W.,Wang, Bijia,Qin, Linlin,Neumann, Kiel D.,Dimagno, Stephen G.
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scheme or table
p. 3158 - 3161
(2011/08/06)
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- Fluoride-promoted ligand exchange in diaryliodonium salts
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Diaryliodonium salts are shown to undergo rapid, fluoride-promoted aryl exchange reactions at room temperature in acetonitrile. Aryl exchange is shown to be exquisitely sensitive to the concentration of fluoride ion in solution; fast exchange is observed as the fluoride concentration approaches a stoichiometric amount at 50 mM substrate concentration. The reaction is slowed, but not halted if benzene is the solvent, indicating that free fluoride ion or a four-coordinate anionic I(III) species may be responsible for the exchange. The fluoride-promoted aryl exchange reaction is general and allows direct measurement of the relative stabilities of diaryliodonium salts featuring different aryl substituents. The aryl exchange reaction may be of practical use for the preparation of hitherto inaccessible diaryliodonium salts, thus it also has implications for labeling radiotracers for molecular imaging with 18F-fluoride (t1/2 = 109.7 min).
- Wang, Bijia,Cerny, Ronald L.,Uppaluri, Shriharsha,Kempinger, Jayson J.,Dimagno, Stephen G.
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body text
p. 1113 - 1121
(2011/02/25)
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- Regiospecific reductive elimination from diaryliodonium salts
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(Figure Presented) Out-of-plane steric bulk furnished by a cyclophane substituent on iodine(III) strongly destabilizes the transition state in the reductive elimination from diaryliodonium salts and leads to regiochemical control (dubbed SECURE), as is demonstrated by computational and experimental studies. This approach should be general for high-valent maingroup and transition metal ions. X=N3, OAc, PhO, CF3CH2O, SCN, PhS.
- Wang, Bijia,Graskemper, Joseph W.,Qin, Linlin,DiMagno, Stephen G.
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supporting information; experimental part
p. 4079 - 4083
(2010/08/07)
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- Facile access to fluorinated aryl and vinyl ethers through copper-catalysed reaction of fluoro alcohols
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Fluorinated alcohols react with aryl and vinyl halides by copper-catalysed cross-coupling reactions to afford the corresponding ethers. With trifluoroethanol (TFE) the reaction proceeds with both iodides and bromides and a wide range of aromatic substituents are tolerated. When higher fluorinated homologues such as C7P15CH2OH were used, the corresponding products were obtained in good yields, thus of-fering an interesting entry to fluorous tagging.
- Vukga, Daniela,Legros, Juelien,Crousse, Benoit,Bonnet-Delpon, Daniele
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experimental part
p. 3513 - 3518
(2009/12/01)
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- Revealing phenylium, phenonium, yinylenephenonium, and benzenium ions in solution
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The 4-methoxyphenylium ion has been generated in the triplet state ( 3An+) by photolysis of 4-chloroanisole in polar media and detected by flash photolysis (λmax = 400nm). This is the first detection of a phenylium ion in solution by flash photolysis and the assignment is supported by time-dependent density functional theory (TD-DFT) calculations. In neat solvents, the cation was reduced to anisole, a process initiated by electron transfer from the starting compound (3An+ + AnCl→An?+AnCf?+, with the radical cation detected at 470 nm, then An?→ AnH). Addition of π nucleophiles to the 3An+ cation offers a novel access to a number of other cationic intermediates under mild, nonacidic conditions. Two intermediates are successively formed with alkenes, a diradical cation and the phenonium ion, which are detected at 440 and 320 nm, respectively, by flash photolysis and are in accordance with calculations. Allylanisoles or β-alkoxyalkylanisoles are the end products, with a small amount of α-alkoxyalkylanisoles that arises from a Wagner-Meerwein rearrangement to form benzyl cations. Further intermediates that have been predicted and detected are the phenylvinylium ion, possibly in equilibrium with the vinylenephenonium ion, with 1-hexyne (λmax = 340 nm) and the benzenium ion with benzene (λmax = 380nm). The final products were anisylhexyne and methoxybiphenyl (an analogous product and intermediate were detected with thiophene).
- Manet, Ilse,Monti, Sandra,Grabner, Gottfried,Protti, Stefano,Dondi, Daniele,Dichiarante, Valentina,Fagnoni, Maurizio,Albini, Angelo
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p. 1029 - 1039
(2008/12/20)
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- The β effect of silicon in phenyl cations
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Irradiation of chloroanisoles, phenols, and N,N-dimethylanilines bearing a trimethylsilyl (TMS) group in the ortho position with respect to the chlorine atom caused photoheterolysis of the Ar-Cl bond and formation of the corresponding ortho-trimethylsilylphenyl cations in the triplet state. The β effect of silicon on these intermediates has been studied by comparing the resulting chemistry in alcoholic solvents with that of the silicon-free analogues and by computational analysis (at the UB3LYP/6-311+G(2d,p) level in MeOH). TMS groups little affect the photophysics and the photocleavage of the starting phenyl chlorides, while stabilizing the phenyl cations, both in the triplet (ca. 4 kcal/mol per group) and, dramatically, in the singlet state (9 kcal/mol). As a result, although triplet phenyl cations are the first formed species, intersystem crossing to the more stable singlets is favored with chloroanisoles and phenols. Indeed, with these compounds, solvent addition to give aryl ethers (from the singlet) competed efficiently with reduction or arylation (from the triplet). In the case of the silylated 4-chloro-N,N- dimethylaniline, the triplet cation remained in the ground state and trapping by π nucleophiles remained efficient, though slowed by the steric bulk of the TMS group. In alcohols, the silyl group was eliminated via a photoinduced protiodesilylation during the irradiation. Thus, the silyl group could be considered as a directing, photoremovable group that allowed shifting to the singlet phenyl cation chemistry and was smoothly eliminated in the same one-pot procedure.
- Dichiarante, Valentina,Salvaneschi, Andrea,Protti, Stefano,Dondi, Daniele,Fagnoni, Maurizio,Albini, Angelo
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p. 15919 - 15926
(2008/09/20)
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- Solvolysis of methoxy-substituted diaryliodonium tetrafluoroborates: Attempted generation of a stabilized aryl cation
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Solvolyses of monomethoxy- and dimethoxyphenyl(phenyl)iodonium (ArI +Ph) tetrafluoroborates were carried out in methanol and 2,2,2-trifluoroethanol (TFE) at 130°C. The solvolysis products include alkoxide substitution products (ArOR and PhOR) as well as iodoarenes (PhI and ArI). The ratios of ArOR/PhOR range from 8/2 to 4/6. The results are argued against formation of aryl cation. Copyright
- Fujita, Morifumi,Mishima, Eri,Okuyama, Tadashi
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p. 241 - 244
(2008/03/13)
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- A meta effect in organic photochemistry? The case of SN1 reactions in methoxyphenyl derivatives
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The photochemistry of isomeric methoxyphenyl chlorides and phosphates has been examined in different solvents (and in the presence of benzene) and found to involve the triplet state. With the chlorides, C-Cl bond homolysis occurs in cyclohexane and is superseded by heterolysis in polar media, while the phosphate group is detached (heterolytically) only in polar solvents. Under such conditions, the isomeric triplet methoxyphenyl cations are the first formed intermediates from both precursors, but intersystem crossing (isc) to the singlets can take place. Solvent addition (forming the acetanilide in MeCN, the ethers in alcohols, overall a SN1 solvolysis) is a diagnostic reaction for the singlet cation, as reduction and trapping by benzene are for the corresponding triplet. Solvolysis is most important with the meta isomer, for which the singlet is calculated (UB3LYP/6-31g(d)) to be the ground state of the cation (ΔE = 4 kcal/mol) and isc is efficient (kisc ca. 1 × 108 s-1), and occurs to some extent with the para isomer (isoenergetic spin states, fee ca. 1.7 × 106 s -1). The triplet is the ground state with the ortho isomer, and in that case isc does not compete, although trapping by benzene is slow because of the hindering of C1 by the substituent. The position of the substituent thus determines the energetic order of the cation spin states, in particular through the selective stabilization of the singlet by the m-methoxy group, a novel case of "meta effect".
- Dichiarante, Valentina,Dondi, Daniele,Protti, Stefano,Fagnoni, Maurizio,Albini, Angelo
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p. 5605 - 5611
(2008/02/04)
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- Aryl Cations from Aromatic Halides. Photogeneration and Reactivity of 4-Hydroxy(methoxy)phenyl Cation
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The photochemistry of 4-chlorophenol (1) and 4-chloroanisole (2) has been examined in a range of solvents and found to lead mainly to reductive dehalogenation, through a homolytic path in cyclohexane and a heterolytic path in alcohols. Heterolysis of 1 and 2 in methanol and 2,2,2-trifluoroethanol offers a convenient access to triplet 4-hydroxy- and 4-methoxyphenyl cations. These add to π nucleophiles, viz., 2,3-dimethyl-2-butene, cyclohexene, and benzene, giving the arylated products in medium to good yields. Wagner-Meerwein hydride and alkyl migration are evidence for the cationic mechanism of the addition to alkenes. Arylation (with no rearrangement) was obtained to some extent also in nonprotic polar solvents such as MeCN and ethyl acetate, reasonably via an exciplex and with efficiency proportional to the nucleophilicity of the trap (2,3-dimethyl-2-butene > cyclohexene ? benzene).
- Protti, Stefano,Fagnoni, Maurizio,Mella, Mariella,Albini, Angelo
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p. 3465 - 3473
(2007/10/03)
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- A product analytical study of the thermal and photolytic decomposition of some arenediazonium salts in solution
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Products of thermal and photochemical reactions of eleven arenediazonium tetrafluoroborates in various solvents have been analyzed. All compounds in most solvents undergo unimolecular heterolysis to give singlet aryl cations which are captured by solvent. This mechanism is dominant for arenediazonium ions without electron-withdrawing substituents in all solvents, and the only reaction observed in water. Additionally, appreciable yields of fluoroarenes are obtained by fluoride abstraction by the aryl cation from fluorinated solvents and from tetrafluoroborate in fluorinated solvents. Yields from photochemical processes are very similar to those from thermal reactions indicating that the main reactions proceed through common or very similar intermediates. Aryl cations formed from ion-paired diazonium ions may react with the counterion, but fragmentation of dissociated diazonium ions leads only to solvent-derived product. Some arenediazonium ions in some solvents undergo an alternative radical reaction leading principally to hydrodediazoniation. It is proposed that this reaction involves initial rate-limiting electron transfer from ethanol to the arenediazonium ion followed rapidly by homolysis of the resultant aryldiazenyl radical. Within the same solvent cage, the aryl radical then either abstracts an α-hydrogen from the ethanol radical cation generated in the first step to give the reduction product and protonated acetaldehyde, or combines with it at the oxygen to give a protonated aryl ethyl ether.
- Canning, Peter S. J.,Maskill, Howard,McCrudden, Katharine,Sexton, Brian
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p. 789 - 800
(2007/10/03)
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