Diaryl ethers, formation

The Pd-catalyzed intermolecular C—O bond formation has also been achieved [105-108]. Novel electron-rich bulky phosphine ligands utilized by Buchwald et al. greatly facilitated the Pd-catalyzed diaryl ether formation [109], When 2-(di-tert-butylphosphino)biphenyl (95) was used as the ligand, the reaction of triflate 93 and phenol 94 elaborated diaryl ether 96 in the presence of Pd(OAc)2 and K3PO4. The methodology also worked for electron-poor, neutral and electron-rich aryl halides. 

Cyclic amide 100 was iV-Boc deprotected and coupled with the tripeptide 102 (Scheme 20) t47l subsequent diaryl ether formation led to an 8 1 mixture of (P)- and (M)-104 with the natural D-O-E isomer predominating. This stands in contrast to the Nicolaou process (Section 16.7.2), in which the unnatural isomer predominated at this step. Removal of protecting groups led to vancomycin aglycon (105). 

Total synthesis of a selective thyromimetic SK FL-94901 (76) was accomplished by diaryl ether formation from symmetrical or unsymmetrical diaryliodonium salts. 

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],... 

Scheme 1. Diaryl ether formation from para-carbonyl activated phenolates and arylfluorides or triflates.

Scheme 2. Diaryl ether formation by ortho-activation. a) Methods of Eicher et al. and Zhu et al., (R1 = 4-CHO, 4-C02Me, 4-CH2CH(NHBoc)C02Me R2 = 2-OMe-4-CHO, 2,3-(0Me)2-4-C02Me, 4-CH2CH(NHBoc)C02Me),...

Another phenoxide activating approach published by Buchwald et al. [18] is based on the reaction of cesium phenoxides with aryl bromides or iodides in the presence of catalytic amounts of copper(I) triflate and ethyl acetate in refluxing toluene (Scheme 3b). In certain cases equimolar amounts of 1-naphthoic acid have been added in order to increase the reactivity of the phenoxide. The authors assume the formation of a cuprate-like intermediate of the structure [(ArO)2Cu] Cs+ as the reactive species. In addition, diaryl ether formation between phenols and aryl halides has been achieved using a phosphazene base forming naked phenoxide in the presence of copper bromide in refluxing toluene or 1,4-dioxane [19]. 

Besides, an enzymatic approach has been developed by Sih and his group by using an oxidative coupling of tyrosine or hydroxyphenylglycine units by hydrogen peroxide in the presence of peroxidases followed by a subsequent reduction step (Scheme 4). Yields in general are moderate and sometimes low. Dependent on the pH of the medium, diaryl ether formation is accompanied by more or less C-C-coupling reactions. 

Scheme 4. Enzymatic diaryl ether formation. X = F, Cl, Br X = Cl, Br, H R = CH2CH(NHAc)C02H, (CH2)2NHAc, CH(NHAc)C02Me.

A much more detailed discussion of the most recent developments in inter- and intramolecular diaryl ether formation can be found in the literature [23]. 

Buchwald and co-workers disclosed that the palladium-catalyzed diaryl ether formation can be performed with a 6/Pd-based system [152]. These reactions are accomplished using a mild base such as K3PO4, and with electron-poor aryl bromides, the reactions proceed in good to excellent yield, Eq. (194). 

Olivera, R., SanMartin, R., Dominguez, E. A novel palladium-catalyzed intramolecular diaryl ether formation. Tetrahedron Lett. 2000,41, 4357 360. 

As mentioned above, bromine substituents promote the diaryl ether formation, while iodine substitutions prefer to produce diaryls. The ab initio calculations indicate that the O-radicals are stable in bromo derivatives, in contrary to the C-radicals in the iodo derivative, although solvent effects were not taken into consideration. Accordingly, the... 

Ebisawa, M., Ueno, M., Oshima, Y. and Kondo, Y. (2007) Synthesis of dictyomedins using phosphazene base catalysed diaryl ether formation. Tetrahedron Letters, 48, 8918-8921. 

Table 9.9 Copper/ligand catalyzed diaryl ether formation from aryl halides and phenols.

Room temperature diaryl ether formation for some special substrates has been observed by Ma and coworkers (Scheme 9.5). This may result from the combination of an ortho-subshtuent (directed by an amido group) and ligand effects [55]. These mild reaction conditions showed excellent prospects in the total synthesis of some important natural products. 

Inter-Intra Tandem Processes Involving Pd-Catalyzed a-Arylation of Carbonyl Compounds with 1,2-Dibromoarenes. 1,2-Dibromoarenes have been shown to undergo Pd-catalyzed inter-intra tandem processes leading to the formation of cyclic compounds, as summarized in Scheme 28. In some examples, however, the cyclization process itself does not actually involve Pd-catalyzed a-arylation. It instead involves either an interesting diaryl ether formation (Sect, in.3.3) or intramolecular Heck reaction (Sect. IV.2.2). 

Another approach to heterogeneous Cu-catalyzed diaryl ethers calls for use of copper-in-charcoal (Cu/C), preferably with a 10-15 wt% loading of the metal into the support. All diaryl ether formations using Cu/C (5 mol% vs. substrate) have been run at high temperatures (180-200 °C) using either conventional heating in a Teflon... 

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. ... 

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