Hydride acceptors, Oppenauer oxidation

Although the Mukaiyama oxidation is not in the top list of the most frequently used alcohol oxidants, the authors of this book have decided to pay full attention to this procedure because it succeeds in very sensitive organometallic compounds, where most other oxidants fail. The Mukaiyama oxidation operates via a somehow unique mechanism involving a hydride transfer from a metal alkoxide to a very good hydride acceptor, which resembles the Oppenauer oxidation. In variance with the Oppenauer oxidation, the Mukaiyama protocol involves much milder conditions and it does not promote as easily base-induced side reactions. 

In the Oppenauer oxidation, an activated carbonyl compound acts as a hydride acceptor in the selective oxidation of an alcohol to give a ketone. Krohn et al. (208) used SiCL-anchored Zr(OnPr)4 in combination with chloral ... 

A zirconium complex, bis(cyclopenta(Uenyl)zirconium(IV) hydride will function as a catalyst for the chemoselective Oppenauer oxidation of primary alcohols in the presence of a hydrogen acceptor (cyclohexanone, benzaldehyde or benzophenone). This method appears to be of some value, since it also allows for the selective monooxidation of primary (and secondary) diols (Scheme 3). 1,2-Diols are not cleaved under these conditions and retro-aldol reactions appear not to be a problem. 

The classical Meerwein-Ponndorf-Verley (MPV) process, named after the independent originators, can be illustrated by the reduction of crotonaldehyde (43) by aluminum isopropoxide (44) in isopropyl alcohol (equation 24). Aluminum isopropoxide transfers hydride reversibly to a carbonyl acceptor. Acetone is formed as a volatile side product, which can be removed during reaction. The reaction of equation (24) is forced even further to the right by the use of excess isopropyl alcohol. MPV reactions have been reviewed.In the Oppenauer variant of this reaction an alcohol is oxidized to a ketone, and acetone is used as hydride acceptor in the presence of a strong base like r-butoxide. This reaction was originally developed for the selective oxidation of sterols. The synthetic aspects of this procedure have also been reviewed. ... 

Carbonyl compounds act as hydrogen acceptors in the Oppenauer oxidation of alcohols to aldehydes or ketones. The reaction is based on hydride transfer from the alkoxide ion of the starting alcohol prepared in situ from anhydrous bases, aluminum isopropoxide, or, better still, tert-butoxide (equation 256). 

Reich, R., Keana, J. F. W. Oppenauer oxidations using 1-methyl-4-piperidone as the hydride acceptor. Synth, Common, 1972, 2, 323-325. 

The most extensive application of the Oppenauer oxidation has been in the oxidation of steroid molecules. The most common aluminum catalysts are aluminum /-butoxide, i-propoxide, and phenoxide. While only catalytic amounts of the aluminum alkoxide are theoretically required, in practice at least 0.25 mole of alkoxide per mole of alcohol is used. Acetone and methyl ethyl ketone have proved valuable hydride acceptors due to their accessibility and ease of separation from the product, whereas other ketones such as cyclohexanone and p-benzoquinone are useful alternatives, due to their increased oxidation potentials.4 Although the reaction can be performed neat, an inert solvent to dilute the reaction mixture can reduce the extent of condensation, and, as such, benzene, toluene, and dioxane are commonly utilized. Oxidation of the substrate takes place at temperatures ranging from room temperature to reflux, with reaction times varying from fifteen minutes to twenty-four hours and yields ranging from 37% to 95%. 

Although the traditional Oppenauer conditions utilized aluminum catalysts, alternative metal alkoxides, for example, chloromagnesium alkoxides, are competent in the transformation.3 In 1945, Woodward devised a new system, which involved the use of potassium r-butoxide, and benzophenone for the oxidation of quinine (29) to quinone (30).13 This was termed the modified Oppenauer oxidation. The traditional aluminum catalytic system failed in this case due to the complexation of the Lewis-basic nitrogen to the aluminum centre. The synthetic flexibility of this procedure was extended by the use of more potent hydride acceptors.46... 

As mentioned previously, one common sidereaction of the Oppenauer oxidation is the aldol condensation of the product with the hydride acceptor. Simultaneous Oppenauer oxidation-aldol condensations have therefore been employed toward the synthesis of a,p-unsaturated carbonyl compounds.3 For example, geraniol (34) in the presence of acetone and an aluminum alkoxide gave ionone (35) in good yield.58... 

Oppenauer oxidation. Using chloral as the hydride acceptor and Zr(OBu ) as a mediator, the oxidation is accomplished at room temperature (17 examples, 67-99%). 

The Oppenauer oxidation of alcohols using fluorenone (27) as a hydride acceptor may not proceed by the mechanism in which is delivered to the carbon of the carbonyl group. The following description remains a distinct possibility. 

The reverse of the Meerwein-Ponndorf-Verley reduction (Section 4.15.3), occurs when a ketone (as a hydride acceptor) in the presence of base is used as the oxidizing agent. It is reduced to a secondary alcohol (Scheme 2.7), and the reaction is known as Oppenauer Oxidation. ... 

The same research group also investigated sulfonylamino alumino bisphenoxides, one of their best MPV catalytic systems and tuned these compounds towards pure Oppenauer oxidation catalysis (Scheme 18.17). The aluminium alkoxides, generated in situ, very efficiently catalyse the oxidation of the test substrate carveol in toluene with 1.2 equiv of pivalde-hyde as hydride acceptor to give carvone in 94% yield (1 mol% catalyst, RT, 1 h). A wide range of alcohols including secondary aliphatic and benzylic... 

Following this, the group of Nguyen reported a highly active and practical Oppenauer oxidation system involving trimethylaluminium in catalytic amounts (10 mol%) and the relatively inexpensive and readily available 3-nitrobenzaldehyde or 2,4-dinitrobenzaldehyde (2 equivalents) as hydride acceptors, as shown in Scheme 18.20. This system, operated in toluene at room temperature, is able to selectively oxidise a variety of secondary alcohols with all l and aromatic substituents as well as primary alcohols, though primary alcohols react more slowly than secondary ones. This system delivers the corresponding ketones and aldehydes almost quantitatively. ... 

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