1- Phenylethanols, aerobic oxidation

Figure 6.16. Aerobic oxidation of 1-phenylethanol catalysed by palladium complexes of a fluorous pyridine...

The application of ionic liquids as a reaction medium for the copper-catalyzed aerobic oxidation of primary alcohols was reported recently by various groups, in attempts to recycle the relatively expensive oxidant TEMPO [150,151]. A TEMPO/CuCl-based system was employed using [bmim]PF6 (bmim = l-butyl-3-methylimodazolium) as the ionic liquid. At 65 °C a variety of allylic, benzylic, aliphatic primary and secondary alcohols were converted to the respective aldehydes or ketones, with good selectiv-ities [150]. A three-component catalytic system comprised of Cu(C104)2, dimethylaminopyridine (DMAP) and acetamido-TEMPO in the ionic liquid [bmpy]Pp6 (bmpy = l-butyl-4-methylpyridinium) was also applied for the oxidation of benzylic and allylic alcohols as well as selected primary alcohols. Possible recycling of the catalyst system for up to five runs was demonstrated, albeit with significant loss of activity and yields. No reactivity was observed with 1-phenylethanol and cyclohexanol [151]. 

The significant influence of carboxylic acid on these reactions prompted a fundamental investigation into its role in the aerobic oxidation of 1-phenylethanol catalyzed by 44a (0.5 mol %) [80]. At low concentrations (<0.62 mol %), acetic acid has a beneficial effect on the reaction rate (Fig. 3a). Beyond this concentration, acetic acid exhibits an inhibitory effect. Acetic acid also influences the catalyst stability (Fig. 3b). In the absence of acetic acid, the reaction proceeds only to low levels of conversion. At 0.75 mol % acetic acid, the reaction begins with a high initial rate, but the time-course deviates from the expected first-order dependence on [alcohol] (Fig. 3b). The first-order dependence observed when [AcOH] is > 2mol% suggests that the catalyst is more stable (albeit somewhat less active) under these conditions. 

A milestone in the aerobic oxidation of alcohols was the report of Kaneda and CO workers describing the use of palladium supported on hydroxyapatite as a highly active and reusable soUd catalyst for the atmospheric-pressure aerobic oxidation of alcohols [98]. Hydroxyapatite is a synthetic calcium phosphate phase obtained reproducibly by precipitation starting from soluble calcium nitrate and ammonium hydrogenophosphate salts. The hydroxyapatite-supported palladium was water insensitive and exhibited unprecedentedly high turnover numbers for alcohol oxidation, particularly high for 1-phenylethanoL The catalyst showed a general activity for primary, secondary, ahphatic and aromatic alcohols. 

Fig. 23 Aerobic oxidation of 1-phenylethanol with bifunctional catalysts...

In 2010, Crabtree and co-workers reported P-alkylation reaction of 1-phenylethanol (2 mmol) with benzyl alcohol was achieved by using simple alkali base KOH (2 mmol) under transition-metal free aerobic conditions, giving the corresponding ketones and alcohols in 78 and 21 %, respectively (Scheme 43) [236]. The reaction proceeded by an Oppenauer oxidation of these alcohols to give the ketone and aldehyde. Subsequently, base-assisted aldol reaction followed by Meerwein— Ponndorf—Verley (MPV) reduction and isomerization gave the p-alkylated products. 

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