Phenols copper-catalyzed arylations

Scheme 1.5 Copper-catalyzed arylation of phenol (16) (Ullmann, 1905).

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. 

The copper-catalyzed reactions of aryl bromides were more effectively conducted with the hindered phenols 2,6-dimethylphenol (64) and 2-phenylphenol (65) as additive than with ethylene glycol. These reactions were conducted at 100 °C instead of 80 °C, as for the reactions of aryl iodides. Moreover, amine in large excess as solvent was required (equation 63). 

Copper-catalyzed couplings of phenols with aryl halides. 2-(3 ,4 -Dimethyl-phenoxy)benzoic acid ... 

Scheme 4.2 Plausible mechanism for copper-catalyzed crosscouplings of aryl boronic acids with phenols.

Copper-catalyzed C-O, C-N, and C-S Coupling. While there is an extensive variety of palladium catalysts for C(aryl)-X bond formation (X = 0, N, and S), copper corrqtlexes have recently gained renewed popularity in these coupling processes. Use of the (CuOTf)2. benzene complex allows the formation of diaryl ethers from aryl bromides or iodides and phenols in very good yields (76-93%) (eq 121). The reaction occurs in toluene in the presence of cesium carbonate as the base and a catal)4ic quantity of ethyl acetate whose role is probably to increase the solubility of the copper species. In the case of less reactive phenols, yields can be increased by the addition of a stoichiometric amount of carboxylic acid. A slight modification of these conditions has been used in the key diaryl ether formation in the synthesis of verbenachalcone. ... 

Some of these drawbacks have been overcome by the recent developments in copper-catalyzed cross-coupling reactions. Buchwald and coworkers reported the coupling of variety of phenols with aryl bromides in the presence of Cs COj (Scheme 20.34) [89]. The less reactive phenols required an equivalent amount of 1-naphthoic acid and molecular sieves to facilitate the transformation. Under these conditions, the reaction of unactivated aryl halides and less reactive or hindered phenols can be achieved. 

A sequential one-pot synthesis of unsymmetrical aryl urea derivatives was developed by arylation of N-substituted cyanamides under metal-free conditions, followed by a second N-arylation under copper-catalyzed conditions [96]. Chen and Chen devised the arylation of pyridine N-oxides with At21X via initial O-arylation followed by a 1,3-radical rearrangement to o-pyridinium phenolates, and arylation of pyridine N-amidates delivered o-pyridinium anilines (Scheme 5d) [97]. 

A copper-catalyzed process converts aryl iodides and bromides into phenols in pure water using TBAB as a phase-transfer catalyst [48]... 

Newman et al. reported an approach to 2-bromobenzofurans using an intramolecular copper catalyzed C—O coupling of gm-dibromovinyl phenols (Scheme 24.29, disconnection D-2 and Scheme 24.31) [115]. This process is directly analogous to their palladium-catalyzed route to indoles via gem-dihalovinylaniline precursors (Scheme 24.3). Like the indole synthesis, further development of this chemistry has focused on harnessing the synthetic potential of the second bromine atom. To this end, several research groups have reported routes incorporating a tandem direct arylation leading to 2-aryl [116] and heteroaryl [27,117] benzoxazoles. 

The aryl ether formation was, until the late 1990s, the domain of copper-catalyzed processes, namely the Ullmann reaction. Around 15 years ago, Hartwig and Buchwald independently discovered the palladium-catalyzed alkoxylation of aryl halides with phenols. Later, these reactions were extended to aliphatic alcohols and to hydroxide as nucleophiles (vide infra. Scheme 5-159). The mechanism of the reductive elimination has been elucidated on isolated complexes. ... 

Synthesis of benzoxazines through aziridine ring opening followed by intramolecular C—N bond formation was reported by Sekar and co-workers. " In this approach, a domino ring opening of A -Ts aziridines 332 with o-iodo-phenols 333 followed by copper-catalyzed intramolecular C(aryl)-N(amide) bond formation in the presence of ethyl-enediamine ligand has been established to afford the resultant product 334 in excellent yield (Scheme 40.73). The trans selectivity was confirmed by H NMR spectroscopy and single crystal X-ray analysis. 

Entry 5 involves metallic copper as a catalyst and is probably a metal-catalyzed reaction (see Section 11.3). The reaction is carried out with excess phenol without solvent. Entries 6 and 7 are cases of C-arylation, both using 2,4-dinitrochlorobenzene. 

It is worth noting that the Ullmann-Goldberg condensation of aryl halides with phenols and anilines worked efficiently in the presence of copper in water.50 For example, the coupling of 2-chlorobenzoic acid with 4-chlorophenol (K2C03/pyridine/copper powder) gave 2-(4-chlorophenoxy)carboxylic acid (Eq. 6.23).51 The Cu(I)-catalyzed transformation of 2-bromobenzoic acid into salicylic acid has also been studied in aqueous media (Eq. 6.24).52... 

It is well established that metallic copper or copper salts efficiently catalyze N- and O-arylation reaction using pentavalent and trivalent organobismuth compounds [5-9, 24]. The C-arylation reaction of phenols and active methylene compounds using pentavalent organobismuth compounds are usually mediated by a base. However, in some cases, copper catalysts mediate C-arylation using pentavalent organobismuth compounds. 

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... 

The scope of the Cu-catalyzed cycloaddition between propargylamines and electron-deficient olefins in the presence of catalytic amounts of a copper salt was subsequently expanded to a one-pot, three-component coupling strategy involving phenols as third components [65]. In this case, reactive Michael acceptors such as ethyl 2-aryl- or alkylsulfonyl cinnamates 57 are involved in the process. This sequence leading to 3(4)-phenoxymethyl pyrrolidines 60 and their isomeric pyrrolidines 61 comprises of the relay process of... 

Arylations. Copper(II) acetate catalyzes the reaction of arylboronic acids with phenols and amines (including imidazole and amides) to provide diaryl ethers (e.g., for synthesis of thyroxine) and arylamines, respectively. The reactions are quite erratic, although some preparatively useful cases have been found. 

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