Phenolates as Nucleophiles

With regards to the scope of the reachon with respect to the phenolate, donor substituents and halogen were tolerated, and even sterically hindered lithium 

The reaction of lithium phenoxide with cirmamyl methyl carbonate at 50 °C gave excellent selectivities, if the reaction time was less than about 20 h. However, longer reaction times led to a fall in both regioselectivity and enantioselectivity, which indicated that the reaction is reversible. 

Phenolates were used as nucleophiles for kinetic resolutions by Carreira and coworkers [42] these authors used a catalyst which was prepared from [lr(COE)2Cl]2 and the chiral bicycle(2.2.2)octadiene L8 (cf. Section 9.2.5). 

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Many synthetic reactions involving phenols as nucleophiles are carried out m the presence of sodium or potassium hydroxide Under these conditions the phenol is con verted to the corresponding phenoxide ion which is a far better nucleophile... 

If 1-alkyl- or l-aryl-l,2-dihydro-X -phosphorins 147 (obtained by Method B, p. 78) are oxidized with mercuric acetate in the presence of alcohols or phenols as nucleophiles, it is possible to isolate X -phosphorins 156 in which the phosphorus bears a carbon substituent besides an alkoxy or phenoxy group (Markl ° ). 

Biaryls were obtained by C-alkylation using 2,6-di-tert-butyl phenolate as nucleophile with/rara-chlorobenzonitrile and 2-chloro-5-cyanopyridine676. Bromobenzonitriles and bro-mocyanopyridines have been employed in a study in which it was demonstrated that these compounds can be successfully used to arylate monoanions of / -dicarbonyl compounds677. 

Resols are obtained as a result of alkaline catalysis and an excess of formaldehyde. A resol molecule contains reactive methylol groups. Heating causes the reactive resol molecules to condense to form large molecules, without the addition of a hardener. The function of phenols as nucleophiles is strengthened by ionization of the phenol, without affecting the activity of the aldehyde. 

The Breslow intermediates are quite unstable toward oxidative conditions, providing acyl imidazolinium species that can acylate several nucleophiles or suffer 1,4-conjugated additions. Gois et al. disclosed the oxidative esterification of aldehydes using an iron/NHC catalytic system to prepare benzoic and cinnamic esters using phenols as nucleophiles (Scheme 26.11)... 

In most of their reactions phenols behave as nucleophiles and the reagents that act on them are electrophiles Either the hydroxyl oxygen or the aromatic ring may be the site of nucleophilic reactivity m a phenol Reactions that take place on the ring lead to elec trophilic aromatic substitution Table 24 4 summarizes the behavior of phenols m reac tions of this type... 

Homoenolate Protonation The p-protonation of homoenolates has been observed by Scheidt and co-workers, resulting in a redox transformation of enals to afford saturated esters 48. This process is catalysed by the NHC derived from imidazolium salt 46 and utilises phenol as a proton source [14]. A range of primary and secondary alcohols, and phenol itself, are competent nucleophiles with which to trap the acylazolium intermediate 47 generated by protonation (Scheme 12.8). 

Alkali phenolates were superior to ammonium phenolates as pro nucleophiles. 

Jacobsen et al. [48], in 1997 for the first time demonstrated KR of racemic terminal epoxides with water as nucleophile for the production of optically pure epoxides and corresponding 1,2-diols. Since then, various other nucleophiles viz., carboxylic acids, phenols, thiols, amines, carbamates and indols were used in KR to produce optically pure epoxides with concomitant production of corresponding enantioenriched l,2-bifimctional moieties [49-52]. 

ARO reaction with phenols and alcohols as nucleophiles is a logical extension of HKR of epoxides to synthesize libraries of stereochemically defined ring-opened products in high optical purity. To this effect Annis and Jacobsen [69] used their polymer-supported Co(salen) complex 36 as catalyst for kinetic resolution of epoxides with phenols to give l-aiyloxy-2-alcohols in high yield, purity and ee (Scheme 17). Conducting the same reaction in the presence of tris(trifluoromethyl)methanol, a volatile, nonnucleophilic protic acid additive accelerates KR reaction with no compromise with enantioselectivity and yield. Presumably the additive helped in maintaining the Co(III) oxidation state of the catalyst. 

And what about an alternative product There are two lines of thought, and the most obvious is that the reaction is repeated, since we are using a dibromide as substrate. Alternatively, we could consider one of the other resonance forms of the phenolate anion as nucleophile. This would generate a C-alkylated phenol. In the majority of cases, C-alkylation is not observed, in that the preferred resonance structure has charge on the electronegative oxygen. 

Benzene radical-cation is formed at the anode and reacts with water as a nucleophile to form phenol as an intermediate. Phenol is more readily oxidised than benzene and is converted to 1,4-dihydroxybenzene. Further oxidation of this in the anode chamber leads to quinone. 

When arenediazonium tetrafluoroborates 7 are not isolated but decomposed in water or aqueous tetrafluoroboric acid, water competes with the tetrafluoroborate anion as nucleophile so that phenols 8 are formed (30- 50 % yield) together with the fluoroarenes 1 (40-55 % yield).179... 

The telomerization of dienes in a two-phase system was first described in a patent (100). Water was used as the solvent for the catalyst, with sulfonated phosphane ligands providing the water solubility. Water, alcohols, phenols, acids, amines, and acetylacetic add were used as nucleophiles. 

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],... 

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