O-Arylation of phenols

The copper acetate-mediated inter- and intramolecular O-arylation of phenols with phenylboronic acid was the key step in the preparation of natural or macrocyclic biphenyl ethers. The intramolecular macrocyclization was mild and tolerant of chemical functionality (Equation (238)). The protocol has been used for the synthesis of (—)-teje-... 

A more prevalent reaction is the arylation of various organic substituents for which an extensive and eomplex chemistry has been established. Thus C- and O-arylations of phenols and enols are known as well as some S- and N-arylations. Some of these reactions can be facilitated by addition of a catalytie amount of a copper salt. 

Larock and coworkers have also reported the transition metal-free O-arylation of phenols and carboxyUc acids by arynes [11b, 13]. Phenols bearing either electron-donating or electron-withdrawing substituents react smoothly, leading to the corresponding diaryl ethers in excellent yields (Equation 12.9). 

By using the fluoride-induced generation of arynes from o-(silyl)aryl triflates, Larock and Liu have developed the aryne-mediated A-arylation of amines, sulfonamides, and carbamates as well as the O-arylation of phenols and carboxylic acids. Remarkably, a wide variety of functional... 

In 2011, Swapnaefaf. [124] reported the application of alumina-supported CuO-catalyzed (13 wt% Cu) O-arylation of phenols and alcohols with aryl (including heteroaryl halides) bromides and iodides under ligand-free conditions. The yields were generally moderate to good. The catalyst could be used up to three cycles without losing activity. 

The preference for O acylation of phenols arises because these reactions are kmetically controlled O acylation is faster than C acylation The C acyl isomers are more stable how ever and it is known that aluminum chloride is a very effective catalyst for the conversion of aryl esters to aryl ketones This isomerization is called the Fries rearrangement... 

Acceptor-substituted haloarenes have been successfully used to O-arylate phenols by aromatic nucleophilic substitution (Table 7.14). The most common arylating agents are 2-fluoro-l-nitroarenes, 2-halopyridines, 2-halopyrimidines, and 2-halotriazines. When sufficiently reactive haloarenes are used, the reaction proceeds smoothly with either the arylating agent or the phenol linked to the support. The thallium(III) nitrate catalyzed arylation of phenols with aryl iodides has been used for macrocycli-zations on solid phase [184], Burgess and co-workers have developed a solid-phase synthesis of 3-turri mimetics based on ring-closure by aromatic nucleophilic substitution (Entry 4, Table 7.14 see also Table 10.5). Phenols, alkylamines, and thiols have been successfully used as nucleophiles for this type of macrocyclization [185],... 

O-Glycosidation of phenols.3 O-Aryl glycosides can be obtained in high yield by reaction of glycosyl fluorides with phenols in the presence of 4-A MS and this activator system. This hafnium complex is superior to Cp2ZrCl2, which is more useful for glycosidation of alcohols. 

O-Arylation of alcohols or phenols cannot be performed by copper diacetate-catalyzed reactions using aryllead triacetates as the source of the aryl ligand. However, Dodonov et at. reported that tetraphenyllead reacts with primary and secondary alcohols in the presence of copper diacetate to afford the derived O-phenyl ethers in moderate yields ranging from 1.25 to 1.8 mol. of ether per mole of the lead reagent (Equation (100)). Phenol and tert-butyl alcohol afforded lower yields of the ethers (0.72-0.95 mole per mole of the lead reagent).117... 

In the presence or absence of a copper catalyst, O-arylation of alcohols and phenols by Ph3Bi(OAc)2 proceeds to give the corresponding aryl ethers.196-198 The monophenylation of m-l,2-cyclopentanediol with Ph3Bi(OAc)2 in the presence of a Cu(n) complex bearing a chiral triamine or diamine ligand affords an a-hydroxy phenyl ether with moderate enantiomeric excesses up to 38% (Equation (127)).199 The copper-catalyzed O-arylation has been success-fully applied to the synthesis of immunosuppressive macrolides. 

Attempted O-arylation of 5-hydroxypyrazole 360 resulted in aryl migration from the initially formed ether 361 to give 4-arylpyrazole-l/7-5-ol derivatives 362 (Scheme 36) <1996BKC113>. l-Acyl-5-hydroxy-lf/-pyrazoles are useful acylating agents for alcohols, phenols, amines, and hydrazines <1998AC0455>. 

The first example of O-arylation of a phenolic compound was reported by Razuvaev et al who showed that the decomposition of pentaphenylbismuth (4) in the presence of phenol (8) led to diphenyl ether (9).31 An intermediate phenoxytetraphenylbismuth (66) was suggested to decompose by two different pathways, the first one affording diphenyl ether (9) in 46% and the second one leading to phenol in 48% yield and to benzyne, eventually leading to tarry products. 

In general, the rate of the reaction of arylation of phenols by aryllead triacetate increases with the electron density of the phenolic substrate. Thus, when pyridine is used as a base, no reaction is generally observed with electron-poor phenols, such as 2,6-dichlorophenol or 2,6-dichloro-4-nitrophenol. However, the reaction of the sodium salt of perfluorophenol (50) with phenyllead triacetate under more forcing conditions led to the product of ort o-arylation, the 6-aryl-2,4-cyclohexadienone (51) together with minor amounts of the product of para-arylation (52) and the unsymmetrical diaryl ether (53). 

The O-arylation of appropriate phenols using symmetrical iodonium salts has been employed in the synthesis of hydroxylated and methoxylated polybrominated diphenyl ethers, some of which are related to natural products [872,873]. For example, several polybrominated diphenyl ethers 680 have been prepared by the reaction of iodonium salt 678 with phenols 679 in iV,iV-dimethylacetamide (DMAC) solution in the presence of base (Scheme 3.272) [872]. 

The most common preparative method to prepare the aryl allyl ether is the Williamson s ether synthesis [la,b]. Typically, aryl allyl ethers can be obtained from phenol derivatives and allylic halide under basic conditions (KjCOj) in refluxing acetone. This method is convenient for the preparation of simple allyl aryl ethers. However, some side reactions such as a competitive C-allylation (Sn2 type reaction) often accompany the formation of undesired byproducts. Mitsunobu reaction of phenol derivatives with allylic alcohols instead of allylic halides can be used under mild conditions [13]. In particular, when the allyl halide is unstable, this procedure is effective instead of the Williamson s ether synthesis. This method is also useful for the preparation of chiral allyl aryl ether from chiral allylic alcohol with inversion at the chiral center. Palladium catalyzed O-allylation of phenols is also applicable, but sometimes a lack of site-selectivity with unsymmetrical allylic carbonate [14] may be a problematic issue. 

Chan DMT, Monaco KL, Wang R-P, Winters MP (1998) New N- and O-arylations with phenylboronic acids and cu nic acetate. Tetrahedron Lett 39(19) 2933—2936 24. Evans DA, Katz JL, West TR (1998) Synthesis of diaryl ethers through the eopper-piomoted arylation of phenols with arylboronie aeids. An expedient synthesis of thyroxine. 

As a metal-mediated approach, intramolecular Ullman-type reaction of 2-(2-haloaryl)phenols with copper salts has been used for dibenzofuran synthesis [35]. However, harsh reaction conditions are generally required. On the other hand, Liu et al. developed the copper-mediated intramolecular O-arylation of 2-(2-haloaryl)phenols under milder and neutral conditions [36]. The reaction of 2-(2-chloroaryl)phenols 65 with electron-withdrawing substituent(s) gave the corresponding dibenzofurans 66 in high yields (Scheme 23.25). They also demonstrated the... 

O-Methylation of phenolic compotmds can be efficiently carried out by tetra-methylammonium chloride in diglyme or poly ethyleneglycol (PEG) at temperatures of 150-160 °C and in the presence of either NaOH or K COj. The benzylation and methylation of phenols occiu, where the benzylation product was always predominating. With allyl-substituted phenols as substrates and using NaOH as a base, it was feasible to achieve both the alkylation and the double-bond isomerization of the allyl group to obtain (E/Z)-propenyl-substituted methyl and benzyl aryl ethers in a single preparative step (Maras et al., 2010). 

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