Arylation of alcohols

The comparison of several nickel catalyst for the arylation of alcohols with arylbromide has been performed, in the same conditions of time, temperature and base, using different oxygen, phosphorus and nitrogen ligands. The yields for each catalyst, shown in the table (Fig. 9) range from 5 to 80 %. 

These results point out, for the arylation of alcohols, a better activity of the nickel catalysts in comparison to the copper analogs. That might be probably connected to the harder character of nickel(II) complexes in comparison to the copper analogs. 

Fig. 11. Influence of the base on the Nickel catalyzed arylation of alcohols...

A new comparison of the copper and nickel catalysts (Fig. 12) on the arylation of alcohols, using potassium carbonate as base, shows once again the superiority of the nickel catalyst (70 % against 40 % for the copper catalyst). 

Fig. 12. Comparison of the Copper and Nickel catalysis on the arylation of alcohols...

Now using the best experimental conditions, it was possible to investigate raughly the scope and limitations of the arylation of alcohols regarding both the substrates the alcohol on one hand and the arylbromide on the other one (Fig. 13). 

Ethers are widely used in solid-phase synthesis, either as linkers for alcohols or as target compounds. Almost all reported solid-phase syntheses of ethers are O-alkyla-tions or O-arylations of alcohols, which differ only in the type of alkylating/arylating agent used and in the precise reaction conditions. This section covers mainly syntheses of acyclic ethers. Preparations of cyclic ethers are considered in Chapter 15. 

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. 

The catalytic effect of copper salts on the 0-arylation of alcohols has been observed, but its synthetic importance remains limited. 7 jhe formation of 2-iodo-2 -acetoxybiphenyl (30) by reaction of the biphenyleneiodonium sulfate (29) with sodium acetate in boiling glacial acetic acid was quantitative when the reaction was catalysed by copper salts.(see 5.1.4.2) In the case of phenols, the (9-arylation by diaryliodonium salts is preferentially performed in a weakly basic medium (generally triethylamine) in the presence of copper bronze in dichloromethane or methanol at room temperature or at mild temperatures (around 50 C). Under these conditions, the 0-aryl ethers are obtained easily in good yields. l ... 

Arylation of alcohols, phenols and 1,3-dicarbonyl compounds with organobismuth(V) compounds... 

Scheme 5.44. 0-Arylation of alcohols and phenols with Ar,Bi(OAc)2 in the presence of Cu or Cu(OAc)2.

To improve the results of the amines arylation, several experiments were carried out on the catalytic system. Concerning the solvent for example, the 2-methoxyethanol was used in place of the usual 1,2-dimethoxyethane in order to reach a better solubility of the nickel(II) precursors but, in this case, besides the expected arylated amines, the reactions afford also some amounts of the 2-methoxyethoxyarene. The literature does not mention such arylation of alcohol catalyzed by nickel complexes accordingly, it was interesting to investigate this new way for the synthesis of alkylarylethers. 

In order to compare the new nickel catalytic system with the classical copper catalysis used for the arylation of alcohols (ref. 16), several experiments were performed with various copper catalysts (eqn. 5) (Table 5). 

To improve the nickel catalyzed arylation of alcohols and to reach a lower temperature and/or a shorter time as well as a smaller ratio of catalyst, the influence of the base was investigated more thoroughly, using the bromobenzene as arylating agent (in order to avoid any secondary reaction on the cyano group of the p-bromobenzonitrile used in the preliminary investigations) (eqn. 6) (Table 6). 

Using the best operating conditions previously determined but with a half quantity (3.5 %) of the nickel complexe, the scope of the arylation of alcohols was roughly investigated by changing the alcohol and the arylating agent (eqn. 7) (Table 7). 

Table 7. Influence of the substrate on the bipy2NiBr2 catalyzed arylation of alcohols (eqn. 7)... 

Pd(0)-Catalyzed Reactions of sp Organic Halides and Pseudohalides 3.7.4.2 Arylation of Alcohols... 

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