Arylation of phenol

This adds to other reports of intra- and intermolecular arylations of phenolic derivatives (Equations (145)-( 147)). 124,124a 124c... 

The rhodium-catalyzed arylation of phenols with aryl halides occurs in the presence of phosphinites [PR2(OAr)] as a co-catalyst (Equation (59)).66 The phosphorus atom coordinates to the rhodium atom to facilitate the electrophilic substitution with the rhodium(m) species at the ortho-pos i on. 

The arylation of phenols also proceeds smoothly. Even the sterically overcrowded 3,5-di- r/-butylphcnol 17 reacts with 2,4,6-trimethoxyphenyllead triacetate 18 to furnish compound 19, which is isolated in 87% yield, together with 10% of the monoarylation product (Equation (6)). 

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],... 

He and Wu have developed a method for the arylation of phenols using aryl iodides and bromides [104], The coupling between 4-f-bulyl-iodobenzene and phenol was conducted both thermally and with directed microwave heating, affording 74% and 90% yields respectively at the same reaction temperature (195 °C). Unfortunately, the authors report the protocol to be mismatched with the less expensive aryl chlorides (Scheme 35). 

Scheme 3. Possible mechanistic sequences for the catalytic arylation of phenol.

Barolo, S.M., Teng, X., Cuny, G.D. and Rossi, R.A. (2006) Syntheses of aporphine and homoaporphine alkaloids by intramolecular ortho-arylation of phenols with aryl halides via SRn1 reactions in liquid ammonia. Journal of Organic Chemistry, 71, 8493—8499. 

Radical arylations of phenols differ in some respects from those of phenolates (Scheme 37). First, the decreased nucleophilicity of the phenol, such as 100, allows the use of unmasked aryl diazonium chlorides 101 as radical sources. Given that an efficient reductant is present in the reaction mixture and that the diazonium salt is added slowly, biphenyl alcohols 102 can be prepared in moderate to good yields [153,154]. In this way, the concentration of the salt 101 is kept low at any time and homocoupling reactions (addition of the aryl radical to diazonium ions) as well as azo coupling to the phenol 100 can be successfully overcome. 

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-... 

In general, the rate of the reaction of arylation of phenols by aryllead triacetate increases with the electron density of the phenolic substrate. When pyridine is used as a base, no reaction takes place with electron-poor phenols, such as 2,6-dichlorophenol or 2,6-dichloro-4-nitrophenol.45 45a However, the reaction of the sodium salt of perfluorophenol 43 with phenyllead triacetate under more forcing conditions led to a range of products the product of >rtfe -arylation, the 6-aryl-2,4-cyclohexadienone 44 together with minor amounts of the product of / zra-arylation 45 and the unsymmetrical diaryl ether 46 (Equation (43)).69... 

Methods for the arylation of phenols have been more successful than analogous reactions of aliphatic alcohols since the Pd (II) phenoxide intermediate is unable to undergo unwanted -hydride elimination. Hartwig and co-workers first reported the use of a DPPF/Pd-catalyst to prepare diaryl ethers in 1997 [151]. The system was particularly effective with electron-deficient aryl bromides and electron-rich phenols, Eq. (192). 

The reaction is considered to involve two mechanistic patterns i.e.,the reactions of arylpalladium intermediates with (a) phenolates at the ortho-positions, this being similar to the a-arylation of ketones (see Sect. 2.2 and Scheme 4), and with (b) thus formed biphenyl-2-ols as in Eq. (56). While the latter proceeds in both DME and xylene, the use of the less polar solvent is essential for the former to occur effectively. However, the intramolecular cyclization of halophenyl-linked phenols is known to occur in DMA [ 122]. It is worth noting that 0-arylation of phenols to give diaryl ethers occurs when bulky phosphine ligands are used (Eq. 60) [26-28]. This may imply that in the aryl(aryloxy)palladium intermediates, reductive elimination to give the ethers is enhanced by the ligands (Scheme 4). 

In these reactions, coordination of the functional groups to Pd(II) species in the medium with liberation of proton appears to be the key, as in the arylation of phenolic compounds and aryl ketones (see Sects. 3.2.1 and 3.2.2). It should be... 

Arylations of phenols using aryl-lead-triacetate51) or other lead triesters, probably give aryl lead intermediates first52). Only alkyl substituted phenols have been reported. 

Evans, D. A., Katz, J. L., West, T. R. Synthesis of diaryl ethers through the copper-promoted arylation of phenols with arylboronic acids. An expedient synthesis of thyroxine. Tetrahedron Lett. 1998, 39, 2937-2940. 

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. 

Three types of pentavalent arylbismuth derivatives can be used for the arylation of phenols. They derive from the triaryl, the tetraaryl and the pentaaryl series. The C-arylation of phenolic compounds can be performed by triarylbismuth carbonate, the presence of a base being not mandatory. It can also be realized by a variety of pentavalent triarylbismuth compounds and tetraarylbismuthonium salts, both in the presence of a base, in various solvents (methylene chloride, benzene, toluene or... 

In the case of the arylation of phenols or amides, no or very low-yielding arylation reactions took place in the absence of a tertiary amine. The mechanism of these two systems does not involve free... 

Table 7.1 Arylation of phenols with 4-methoxyphenyllead triacetate (15) and pyridine.l23...

C-Arylation of phenols and naphthols with arylbismuth(V) compounds... 

Scheme 22 Rh-catalyzed C-H ortho arylation of phenols by Bedford et al. [114, 116]...

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