Aerobic primary alcohol

Acetobacter bacteria oxidatively convert wine to vinegar through an aerobic fermentation of ethanol (a primary alcohol) into acetic acid (a carboxylic acid) ... 

A breakthrough was reported by Stack and co-workers in 1998 (212) who reported the first biomimetic catalytic system for the oxidation of primary alcohols by air. Independently, in the same year Chaudhuri, et al. (216) reported efficient aerobic oxidation of primary and secondary alcohols by the dinuclear catalyst [Cu2 2(Ls )2]C12 (216). Next, we will briefly review the salient features of these two systems. 

Figure 33. Catalysts J and K for the aerobic oxidation of primary alcohols (218, 219).

Recently, two reports (218, 219) appeared showing that (iminosemiqui-nonato)copper(II) complexes also catalyze the aerobic oxidation of primary alcohols (ethanol, benzyl alcohol) to the corresponding aldehydes and H202. Complexes J and K shown in Fig. 33 have been isolated as active catalysts and the former has been characterized by X-ray crystallography. Detailed mechanistic studies have been performed that again show the close resemblance to GO. 

Aerobic oxidation of primary alcohols to aldehydes and secondary alcohols to ketones was accomplished in ionic liquids (bmim, l-butyl-3-methyl-imidazolium cation) as RuCl2(PPh3)j/(bmim)V80°C RuClj or [RuCl Cp-cymene)] were also used... 

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]. 

Jiang N, Ragauskas AJ (2005) Copper(II)-catalyzed aerobic oxidation of primary alcohols to aldehydes in ionic liquid [bmpy]PF6. Org Lett 7(17) 3689-3692... 

The nitroxyl-based systems are the most important and widely investigated homogeneous catalysts for the aerobic and non-aerobic oxidation of alcohols [9]. The different mechanisms with persistent (Scheme 1) and nonpersistent (Scheme 2) nitroxyl radicals is reflected in the selectivity of primary alcohol oxidation. Several... 

Unfortunately, even using this optimized procedure, we were not able to improve the conversion of primary alcohols into the corresponding aldehydes. However, close examination of the oxidation behavior of several primary aliphatic alcohols revealed intriguing features (Table VII). Whilst poor conversion of 1-decanol 23 to decanal 24 was achieved (Table VII, Entry 1), dibenzyl leucinol 25 and Boc-prolinol 27 were quantitatively transformed into the corresponding aldehydes (Table VII, Entries 2 and 3). The enhanced reactivity of 25 and 27 could be due either to an increased steric effect at the a-carbon center, to an electronic influence of the a-nitrogen substituent or to a combination of both. To test the importance of steric hindrance, the aerobic oxidation of cyclohexane methanol 29 and adamantane methanol 31 was carried out. Much to our surprise, oxidation of 29 afforded 30 in 70% conversion (Table VII, Entry 4) and transformation of 31 to 32 proceeded with 80% conversion (Table VII, Entry 5). Clearly increased substitution at the a-position favors the oxidation of primary aliphatic alcohols, although the conversions are still not optimum. 

Copper-Catalysed Aerobic Oxidation of Selected Primary Alcohols... 

These conditions were next applied to the aerobic oxidation of a variety of primary alcohols. A selection of pertinent examples is displayed in Table IX. 

Other ruthenium-based catalysts for the aerobic oxidation of alcohols have been described where it is not clear if they involve oxidative dehydrogenation by low-valent ruthenium, to give hydridoruthenium intermediates, or by high-valent oxoruthenium. Masutani et al. [107] described (nitrosyl)Ru(salen) complexes, which can be activated by illumination to release the NO ligand. These complexes demonstrated selectivity for oxidation of the alcoholic group versus epoxidation, which was regarded as evidence for the intermediacy of Ru-oxo moieties. Their excellent alcohol coordination properties led to a good enantiomer differentation in the aerobic oxidation of racemic secondary alcohols (Fig. 19) and to a selective oxidation of primary alcohols in the presence of secondary alcohols [108]. 

Nearly any primary alcohol serves as a substrate with the exception of methanol and ethanol. Ferricyanide (17, 18), porphyrexide (18), and hexachloroiridate(IV) (18) can replace oxygen as oxidant. Hexachloro-iridate(IV) is consumed to the exclusion of oxygen in aerobic mixtures. When hexachloroiridate(IV) and H202 serve as oxidant and reductant respectively, the normal reaction, vis-a-vis H202, is reversed, and oxygen is produced (18). 

Recently, an alternative to the catalytic system described above was reported [204]. The new catalytic procedure for the selective aerobic oxidation of primary alcohols to aldehydes was based on a CunBr2(Bpy)-TEMPO system (Bpy=2,2 -bipyridine). The reactions were carried out under air at room temperature and were catalyzed by a [copper11 (bipyridine ligand)] complex and TEMPO and base (KOtBu) as co-catalysts (Fig. 4.70). 

The final oxidation step of the primary alcohol at C-l in L-Srb requires acetone protection, which is carried out in a standard textbook way in the presence of an excess of sulfuric acid. The oxidation at C-l has been accomplished in a number of ways [147] it seems that nowadays aerobic oxidation in the presence of palladium or platinum is preferred. Deprotection, requiring additional sulfuric acid, affords 2KLG, which is transformed into ASA via esterification and lac-tonization. Alternatively, the diacetone derivative of 2KLG can be converted directly into ASA by treatment with HC1 in an organic solvent. 

It has been shown [9] that the copper-dependent oxidase enzyme, laccase, in combination with TEMPO or derivatives thereof, is able to catalyze the aerobic oxidation of the primary alcohol moieties in starch (Fig. 10.2). There is currently considerable commercial interest in laccases for application in pulp bleaching (as a replacement for chlorine) in paper manufacture and remediation of phenol-containing waste streams [10]. 

Chaudhuri, P., Hess, M., Weyherm.ller, T., and Wieghardt, K., 1999, Aerobic Oxidation of Primary Alcohols by a New Mononuclear Cu(II)-Radical Catalyst, Angew. Chem., Int. Ed. Engl. 38 1095nl098. 

PS has also been used in the copper catalysed aerobic oxidation of primary alcohols (Scheme 9.3). The selective oxidation of primary alcohols into aldehydes can be complicated by overoxidation to carboxylic acids or even decomposition products. These side reactions were not observed in PS, and a high turnover frequency (>31 h ) was achieved. The product could be easily isolated by extraction into -pentane and the PS catalyst-containing phase could be recycled three times. 

Oxidation of primary alcohols. Selective aerobic oxidation of RCH OH to... 

Oxidation of alcohols. The pernithenate salt is an excellent catalyst for aerobic oxidation of alcohols to aldehydes and ketones in the presence of 4A molecular sieves. The use of a polymer-supported ammonium perruthenat is perhaps an improvement, with good discrimination in the oxidation in favor of primary alcohols. Another versioif specifies a system containing CuCl and 2-aminopyridine also. 

An aerobic version of the TPAP oxidation has been developed [47] and adapted by the Ley group to PSP [48]. This method was applied by this group in the aforementioned total synthesis of epothilone C [22]. The synthesis of the thiazole fragment (Scheme 4.8) requires the oxidation of primary alcohol 33 to the corresponding aldehyde 34. This was achieved using catalytic PSP under an oxygen atmosphere. 

The selective aerobic oxidation of primary alcohols to aldehydes, but not secondary alcohols to ketones, is reminiscient of the chemistry catalyzed by the Cu-dependent enzyme, galactose oxidase (39). Similarly, the Cu-binding P-amyloid protein relevant to Alzheimer s disease promotes aerobic oxidation of cholesterol, a primary alcohol (cholesterol oxidase activity) (40). The Cu-dependent amine oxidases catalyze the aerobic oxidation of amines to aldehydes (41), the hydration products of imines. Each of these enzymes that promotes aerobic oxidation of primary alcohols and amines to the same products as Ni(TRISOX) catalyze the net reaction in Equation 1. If the net reactions... 

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