C(aryl)-O bond formation from aryl methanesulfonates via consecutive deprotection and S(N)Ar reactions with aryl halides in an ionic liquid

An efficient K3PO4-mediated synthesis of unsymmetrical diaryl ethers using the ionic liquid [Bmim]BF4 (1-butyl-3-methylimidazolium tetrafluoroborate) as solvent has been developed. The procedure involves consecutive deprotection of aryl methane-sulfonates and a nucleophilic aromatic substitution (S(N)Ar) with activated aryl halides.     

A practical synthesis of aryl tetrafluoroethyl ethers via the improved reaction of phenols with 1,2-dibromotetrafluoroethane

An efficient and practical synthesis of various aryl tetrafluoroethyl ethers by the reaction of phenols with 1,2-dibromotetrafluoroethane and the subsequent reduction with zinc dust was described. The nucleophilic substitution of 1,2-dibromotetrafluoroethane with phenols initiated by bromophilic attack was improved by using Cs₂CO₃ as a base and DMSO as a solvent.     

Influence of hydrogen bonding in the activation of nucleophiles: PhSH-(catalytic) KF in N-methyl-2-pyrrolidone as an efficient protocol for selective cleavage of alkyl/aryl esters and aryl alkyl ethers under nonhydrolytic and neutral conditions

The nucleophilicity of arenethiols can be augmented via hydrogen bonding with "naked" halide anion. The activity of the halide anions follow the order F(-) > Cl(-) approximately Br(-) approximately I(-) and is dependent on the countercation (Bu(4)N approximately Cs approximately K > Na > Li). The solvent plays an important role in nucleophilic activation as well as regeneration of the effective nucleophile (e.g. ArS(-)) and those with high dielectric constant, high molecular polarizability, high donor number (DN), and low acceptor number (AN) are the most effective. Selective deprotection of alkyl/aryl esters and aryl alkyl ethers can be achieved under nonhydrolytic and neutral conditions by the treatment with thiophenol in 1-methyl-2-pyrrolidone (NMP) in the presence of a catalytic amount of KF. Aryl esters are selectively deprotected in the presence of alkyl esters and alkyl methyl ethers during intramolecular competitions.     

Catalytic SNAr Hexafluoroisopropoxylation of Aryl Chlorides and Bromides

Fluoroalkyl aryl ethers are valuable structural motifs in pharmaceuticals because compounds with these motifs are more metabolically stable and more lipophilic than their nonfluorinated analogues. However, hexafluoroisopropyl aryl ethers have not been extensively studied, presumably because of the lack of efficient synthetic methods. Herein, we describe a rhodium-catalyzed nucleophilic aromatic substitution of aryl chlorides or bromides, which act as the limiting reagents, with weakly nucleophilic hexafluoro-2-propanol under mild reaction conditions. This method provides diverse hexafluoroisopropyl aryl ethers. We demonstrated the generality of this method by carrying out reactions of a large array of unactivated aryl halides, and we found that the success of the reactions relied on arene activation by means of η⁶-coordination.     

Investigations on 2,3'-Biquinolyls. 12. Alkylation and Arylation of 2,3'-Biquinolyl Dianion with Organometallic Compounds. New Type of Reaction for Dianions of Aromatic Compounds

2,3'-Biquinolyl dianion reacts with organolithium and organomagnesium compounds with the formation, after treatment of the reaction mixture with water, of 2'-alkyl(aryl)-1',2'-dihydro-2,3'-biquinolyls, and, after treatment of the reaction mixture with alkyl halides, of 1'-alkyl-2'-alkyl(aryl)-1',2'-dihydro-2,3'-biquinolyls. The reaction includes attack of the nucleophilic reagent with an electron transfer to a molecule of solvent.     

Reductive cleavage versus hydrogenation of allyl aryl ethers and allylic esters using sodium borohydride/catalytic ruthenium(III) in various aqueous solvent mixtures

The reduction of allyl aryl ethers using sodium borohydride in the presence of a catalytic amount of ruthenium(III) chloride in various aqueous solvent mixtures at 0 °C was examined. In aqueous tetrahydrofuran, hydrogenation was the favored pathway (85-100% yield of the corresponding aryl propyl ether); whereas in aqueous N-methylformamide, reductive cleavage predominated (4:1 mixture of phenolic product/aryl propyl ether). In order to gain some insight into the mechanism for this process, 3-octyn-1-ol and trans-2-decen-1-yl acetate were subjected to similar reductive conditions; and both substrates afforded products inconsistent with a single-electron-transfer mechanism.     

Heck reactions of 2-substituted enol ethers with aryl bromides catalysed by a tetraphosphine/palladium complex

cis,cis,cis-1,2,3,4-Tetrakis(diphenylphosphinomethyl)cyclopentane/[PdCl(C₃H₅)]₂ efficiently catalyses the Heck reaction of β-substituted enol ethers with aryl bromides. Employing β-methoxystyrene, 3-ethoxyacrylonitrile or methyl 3-methoxyacrylate, the regioselective α-arylation of these enol ethers was observed in all cases, and mixtures of Z and E isomers were generally obtained, which in many cases yielded a single ketone product after acid treatment. The stereoselectivity of this reaction depends on steric and electronic factors, and better stereoselectivities in favour of Z isomers were observed with electron-rich or sterically congested aryl bromides. Better yields were obtained for this reaction with electron-rich or sterically congested aryl bromides than with electron-poor aryl bromides. This observation suggests that with these β-substituted enol ethers the rate-limiting step of the catalytic cycle is not the oxidative addition of the aryl bromide to the palladium complex.     

P(i-BuNCH2CH2)3N: an efficient promoter for the nucleophilic aromatic substitution reaction of aryl fluorides with aryl TBDMS (or TMS) ethers

[reaction: see text]. The nucleophilic aromatic substitution reaction between electron-deficient aryl fluorides and aryl TBDMS (or TMS) ethers has been shown to be efficiently promoted by proazaphosphatranes such as P(i-BuNCH(2)CH(2))(3)N (3). Excellent yields of diaryl ether products were obtained under unusually mild conditions.     

Alkaline aqueous solution promoted debromination of 1,2 dibromo-fluorocarbons – A convenient method for electron deficient perfluorovinyl ethers

A facile and efficient base-mediated protocol for debromination of vic-dibromides in perfluoroalkyl(aryl) compounds in aqueous medium has been demonstrated. With mild reaction conditions, the developed strategy has a good substrate scope and electron-deficient olefin products were obtained in good yields. A mechanistic explanation of the debromination is offered with three key experimental observations: (1) the reactions are accelerated by the more electron-rich nucleophiles, (2) the reactions are promoted by the more electron poor vic-dibromides in perfluoroalkyl compounds, and (3) the nucleophilic side reaction is preventable. It is evident that the electronic factors strongly dictate vic-dibromides elimination to the perfluorovinyl ethers, which are the precursors for various perfluorinated polymers. The different reaction conditions were tested in implicit solvent (water) conditions, which helped to confirm the E2-like mechanism.     

碱性介质中邻硝基芳香醚的醚键稳定性研究

设计合成了一系列的邻硝基芳香醚,对碱性介质中芳醚键的稳定性进行了研究。选用对硝基甲苯为内标,用高效液相色谱仪对邻硝基芳香醚的醚键断裂程度进行了分析,并用内标法计算出它们的转化率。结果表明,由于-NO2的存在,邻硝基芳香醚在碱性溶液中易发生亲核取代反应,使醚键断裂,从而使这类化合物出现不稳定性。发现邻硝基苯氧丙酸亲核取代的异常情况,推测可能是分子内邻基参与的亲核取代反应。     

Intramolecular Aryl Migration of Diaryliodonium Salts: Access to ortho‐Iodo Diaryl Ethers

By using vicinal trifluoromethanesulfonate‐substituted diaryliodonium salts, a novel approach was developed for the synthesis of ortho‐iodo diaryl ethers by intramolecular aryl migration. The reaction conditions are mild with a broad substrate scope. Mechanistic insight suggests a sulfonyl‐directed nucleophilic aromatic substitution pathway. Additionally, the product ortho‐iodo diaryl ethers serve as versatile synthons as demonstrated with several coupling reactions. Furthermore, a useful thyroxine analogue of the 3‐iodo‐l ‐thyronine (3‐T₁) derivative was synthesized by this aryl migration procedure.     

Facile construction of the benzofuran and chromene ring systems via PdII-catalyzed oxidative cyclization

[reaction: see text]. We herein report the development of one-pot procedures for the conversion of allyl aryl ethers to 2-methylbenzofurans (via sequential Claisen rearrangement and oxidative cyclization) and for the conversion of aryl homoallyl ethers to chromenes (via direct oxidative cyclization). It is likely that both reactions proceed via a common Pd-catalyzed pathway involving olefin activation, nucleophilic attack, and beta-hydride elimination.     

Formation of chiral aryl ethers from enantiopure amine or alcohol substrates

Three methods for the preparation of chiral aryl ethers are demonstrated. N,N-Disulfonylimide derivatives are used in the stereoselective formation of aryl ethers from chiral amines. Nucleophilic attack of aryloxide anions on the cyclic N,N-disulfonylimide derivative of (S)-1-phenylethylamine afforded the (R)-1-phenylethyl phenyl and 2-naphthyl ethers with 83–87 and 70–79% inversion of configuration, respectively. The results are compared with results from alternative methods for the preparation of homochiral aryl ethers from chiral alcohols with complete retention and inversion of configuration, respectively.     

P(MeNCH2CH2)3N: an efficient catalyst for the desilylation of tert-butyldimethylsilyl ethers

tert-Butyldimethylsilyl (TBDMS) ethers of primary, secondary, and tertiary alcohols and phenolic TBDMS ethers are desilylated to their corresponding alcohols and phenols, respectively, in DMSO, at 80 degrees C, in 68-94% yield in the presence of 0.2-0.4 equiv of P(MeNCH2CH2)3N. Using P(i-PrNCH2-CH2)3N as the catalyst, 85-97% yields of desilylated alcohols were obtained from TBDMS ethers of 1-octanol, 2-phenoxyethanol, and racemic alpha-phenyl ethanol. These are the first examples of desilylations of silyl ethers catalyzed by nonionic bases. Both catalysts were much less effective for the desilylation of tert-butyldiphenylsilyl (TBDPS) ethers (22-45% yield) under the same conditions as used for TBDMS ethers. Possible pathways involving nucleophilic attack of the anion of the solvent molecule (generated by the catalyst) at the Si-O bond of silyl ether or a prior activation of the silyl ether by the catalyst via a P-Si interaction followed by nucleophilic attack of the solvent anion are proposed on the basis of 1H and 31P NMR experimental data.     

An efficient fluoride-mediated O-arylation of sterically hindered halophenols with silylaryl triflates under mild reaction conditions

The reaction between 2,6-dihalophenols and 2-(trimethylsilyl)aryl triflates in the presence of CsF using acetonitrile as solvent at room temperature led to the formation of functionalized diaryl ethers in very good yields.     

Demand-based thiolate anion generation under virtually neutral conditions: influence of steric and electronic factors on chemo- and regioselective cleavage of aryl alkyl ethers

Thiolate anions have been generated in a "demand-based" fashion under virtually neutral conditions for chemoselective deprotection of aryl alkyl ethers. Solvents play the critical role in making the reaction effective and should have high values of epsilon (>30), molecular polarizabilities (>10), and DN (>27) and low values of AN (<14). However, it is the combined effect of all of these physical properties that make a particular solvent effective. The reaction rates of cleavage of various aryl alkyl ethers are dependent on the steric crowding around the O-alkyl carbon and follow the order propargyl approximately allyl approximately benzyl > methyl > ethyl. Electron-withdrawing substituents increase the rate of ether cleavage reaction. The influence of the steric and electronic factors have been successfully exploited for selective deprotection of aryl alkyl ethers during inter- and intramolecular competitions.     

Synthesis of primary aromatic amides by aminocarbonylation of aryl halides using formamide as an ammonia synthon

Primary aromatic amides were prepared by a palladium-catalyzed aminocarbonylation reaction of aryl halides in high yields (70-90%) using formamide as the amine source. The reactions require a palladium catalyst in combination with a nucleophilic Lewis base such as imidazole or 4-(dimethylamino)pyridine (DMAP). Aryl, heteroaryl, and vinyl bromides and chlorides were converted to the primary amides under mild conditions (5 bar, 120 degrees C) using 1 mol % of a palladium-phosphine complex. Best results were obtained in dioxane using triphenylphosphine as the ligand and DMAP as the base. For activated aryl bromides, a phosphine-to-palladium ratio of 2:1 was sufficient, but less reactive aryl bromides or aryl chlorides required ligand-to-palladium ratios up to 8:1 in order to stabilize the catalyst and achieve full conversion. The influence of catalyst, base, solvent, pressure, and temperature was studied in detail. The mechanism of the reaction could be clarified by isolating and identifying the reaction intermediates. In addition, methylamides and dimethylamides were prepared by the same method using N-methylformamide and N,N-dimethylformamide as the amine source.     

New strategy for the synthesis of N-aryl pyrroles: Cu-catalyzed C-N cross-coupling reaction of trans-4-hydroxy-l-proline with aryl halides

trans-4-Hydroxy-l-proline is used for the first time as an effective nucleophilic coupling partner with aryl halides mediated by copper iodide with Cs₂CO₃ as the base and DMSO as the solvent. Utilizing this protocol cross-coupling of trans-4-hydroxy-l-proline with a wide variety of substituted aryl halides to produce N-aryl pyrroles in moderate to good yields.     

Ring-closure reactions through intramolecular substitution of thiophenoxide by oxygen and nitrogen nucleophiles: simple stereospecific synthesis of 4,5-dihydroisoxazoles and 4,5-dihydropyrazoles

A new and simple method for the stereospecific synthesis of 3,5-disubstituted-4,5-dihydro-isoxazoles (chiral isoxazolines) from readily available oximes of chiral Michael adducts of thiophenol to chalcones is reported. An analogous reaction with the N-arylhydrazones of the Michael adduct gave nonracemic 1-(aryl)-3,5-diphenyl-4,5-dihydro-1H-pyrazoles (chiral pyrazolines), but these products are configurationally unstable. The key step of the synthesis is the ring-closure reaction, which occurs by a stereospecific intramoleculer nucleophilic substitution of thiophenoxide.     

Ring-opening polymerization of macrocyclic aryl ether ketone oligomers containing the 1,2-dibenzoylbenzene moiety

Facile ring-opening polymerization of cyclic aryl ether oligomers containing the 1,2-dibenzoylbenzene moiety to form high molecular weight linear polymers in the presence of a nucleophilic initiator is described. The polymerization can be initiated in the melt in the presence of a nucleophilic initiator such as potassium carbonate, cesium fluoride, and alkali phenoxides. Various alkali phenoxides were investigated as potential nucleophilic initiators. The polymerization reaction rate in the melt increases in the order of K⁺ > Na⁺ > Cs⁺, and in the order of ⁻OPhPhO⁻ > PhO⁻ > PhOPhO⁻ > PhPhO⁻. However, the polymerization in an aprotic dipolar solvent is faster in the presence of cesium phenoxide than in the presence of potassium phenoxide. Polymerization of the cyclic oligomers in solution demonstrates that the ring-opening polymerization proceeds via a chain-growth mechanism and involves a transetherification reaction between linear and cyclic aryl ether oligomers. The ring-chain equilibrium is much more favorable towards linear polymers. Since little or no ring strain exists in the cyclic system, the transetherification reactions are indiscriminate with regards to cyclic or linear chains and the interchain equilibration is also a facile process during polymerization. This intermolecular transetherification has been demonstrated by using low molecular weight aryl ethers to control the molecular weight of the polymer formed via ring-opening polymerization. © 1996 John Wiley & Sons, Inc.