Formation of aryl ethers

A polymer-bound guanidine base 31 has been used for the formation of aryl ethers from suitable phenols and alkyl halides. In addition to serving as a base to affect deprotonation, reagent 31 also acts as a sequestering agent for excess starting phenol (reaction 11).26... 

The coordination of Cr(CO)3 does not activate aryl chloride sufficiently for Williamson diaryl ether formation to occur. Smooth formation of aryl ether 222 proceeds by reacting the easily prepared arene-Ru complex 220 of the highly functionalized aryl chloride with phenol 219. Decomplexation of 221 by irradiation gives 222, and the product is used for the synthesis of the BCF rings of ristocetin A [57],... 

Multiple arylations of polybromobenzenes have been conducted to generate electron-rich arylamines. Tribromotriphenylamine and 1,3,5-tribromobenzene all react cleanly with A-aryl piperazines using either P(o-tolyl)3 or BINAP-ligated catalysts to form hexamine products [107]. Reactions of other polyhalogenated arenes have also been reported [108]. Competition between aryl bromides and iodides or aryl bromides and chlorides has been investigated for the formation of aryl ethers [109], and presumably similar selectivity is observed for the amination. In this case bro-mo, chloroarenes reacted preferentially at the aryl bromide position. This selectivity results from the faster oxidative addition of aryl bromides and is a common selectivity observed in cross-coupling. Sowa showed complete selectivity for amination of the aryl chloro, bromo, or iodo over aryl-fluoro linkages [110]. This chemistry produces fluoroanilines, whereas the uncatalyzed chemistry typically leads to substitution for fluoride. 

As with polystyrene sulfonic resins, Nafion-based acid catalysts are highly efficient for hydration and dehydration processes and, in general, for condensation reactions that occur with the formation of water or similar secondary products. Formation of ethers has been studied for various alcohols [109-111]. Dehydration of 1,4- and 1,5-diols at 135 °C affords the corresponding cyclic ethers such as 20 in excellent yields (Scheme 10.7), while 1,3-diols experience different transformations depending on their structure [112]. The dehydration of 1,2-diols mainly proceeds via the pinacol rearrangement. Further condensation of the initially formed carbonyl compound and unreacted diol affords 1,3-dioxolanes [113]. The catalyst could be efficiently reused following a reactivation protocol. Formation of aryl ethers is also possible, and the synthesis of dibenzofurans 21 (X = O) from 2,2 -dihydroxybiphenyls has been reported (Scheme 10.7) [114]. The related reaction... 

As an example, a new palladium based method has been developed for the alkylation of tyrosine residues [34], In this reaction, allylic carbonates, esters, and carbamates are activated by palladium(O) complexes in aqueous solution, resulting in the formation of electrophilic zr -allyl complexes (such as 16), Fig. 10.3-8(a). These species react at pH 8-10 with the phenolate anions of tyrosine residues, resulting in the formation of aryl ether 17 and regeneration of the Pd(0) catalyst. The reaction requires no organic cosolvent, is catalytic in palladium, and requires P(m-QjH4S03 )3 as a water-soluble phosphine ligand. In contrast to alkyl or allylic halides, the inert character of the allyloxycarbonyl compounds used in this reaction ensures that nonspecific... 

When an alcohol is used as the reducing agent, the yield of deaminated aromatic compound is often very unsatisfactory owing to extensive formation of aryl ethers. Use of lower alcohols favors ether formation, whereas use of higher alcohols favors formation of the hydrocarbons for example, benzenediazonium chloride gives only anisole when methanol is used, a little benzene and much phenetole when ethanol is used, but much benzene and very little benzyl phenyl ether when benzyl alcohol is used. 

The formation of aryl ethers of (hydroxyalkyl)-phosphonic or -phosphinic derivatives from the corresponding haloalkyl phosphorus(V) acid derivative and a metal phenate may present unfortunate difficulties depending on the particular halogen, but these have been overcome by the use of sulphonate substrates, in particular the 0-4-chlorobenzenesulphonyl esters of the phosphonic or phosphinic derivative, in reactions with sodium phenates. A study of the alcoholysis reactions of the O-p-tosylates of the cis and trans isomers of diethyl (2-hydroxycyclo-hexyl)phosphonate, has shown that with a 60° dihedral angle between the two functions, the rate of reaction is sensitive to solvent nucleophilicity, and the evidence supports a bimolecular displacement. When the dihedral angle is 180°, the lack of dependence of rate on solvent and other features, support the involvement of carbocationic intermediates, with their stabilization by the phosphono group . ... 

TABLE 1. Effective Catalyst Systems for the Formation of Aryl Ethers from Aryl Halides... 

Subsequent work reported some improvements on this chanistry when nickel catalysts were used, particularly for the formation of silyl aryl ethers. However, another tQ)proach was the use of phosphines that are weaker donors than standard triarylphosphine ligands. Use of a palladium catalyst containing a DPPF analog bearing p-CFj groups on each phaiyl ring led to improved yields as part of the first examples of Pd-catalyzed formation of diaryl ethers from aryl haUdes (Eq. A)P Nonetheless, neither of these changes in catalyst composition led to the formation of aryl ethers from unactivated aryl hahdes in a synthetically valuable fashion. 

No studies on the mechanism of the complete catalytic cycle for formation of aryl ethers from aryl halides have been conducted, but the elementary reactions in the cycle are likely to be similar to those in the catalytic cycle for formation of aryl amines. Oxidative addition, formation of an alkoxo complex, and reductive elimination of ether are likely to occur. It is the slow reductive elimination of ether that allows for amide complexes to form and undergo reductive elimination in the presence of t-BuO" instead of undergoing reductive elimination of ether. 

Other metal salts and complexes also catalyze the formation of C-N, C-O, and C-S bonds from organic electrophiles. Thus, a mixture of [Ni(COD)2] and a bidentate phosphine catalyzes the formation of aryl ethers from aryl halides and alkoxides [410]. In some cases, the reactions occur under milder conditions and with higher yields than when catalyzed by Pd complexes. 

Copper-catalyzed Aryl Ether Formation. Traditional methods for formation of aryl ethers involve stoichiometric Ullmann couplings. A new system was developed exploiting catalytic CuCl and NMI as a ligand. The title compound was chosen due to its similarities to histidine, a common amino acid for binding metals. This methodology was applied to the synthesis of the insecticide diafenthiuron that produced the desired aryl ether in greater than 98% yield compared to 39% reported in current patents (eq 32). ... 

The primary mechanism for formation of aryl ether linkages involves nucleophilic aromatic substitution of an activated leaving group by phenolate. Polar aprotic solvents, e.g., dimethylsulfoxide (DMSO), N-methylpyrrolidone (NMP) and dimethylacetamide (DMAC) are required to effect the reaction. The use of dimethylproylene urea has been reported as an alternative solvent... 

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