By the Oppenauer oxidation

Most terpene-based citral (5) produced is based on the catalytic oxidative dehydrogenation of nerol (47) and geraniol (48), or by the Oppenauer oxidation of nerol and geraniol (123—125). 

The oxidation of 2-ethylhexan-l-ol to 2-ethyl-hexanal by the Oppenauer oxidation with aliphatic aldehydes such as acetaldehyde, propionaldehyde, and isobutyr-aldehyde has been investigated with gas-phase reactants and MgO as the catalyst (196). Reaction with propionaldehyde was found to be an effective synthetic route for 2-ethylhexanal preparation, whereas with acetaldehyde and isobutyraldehyde a gradual catalyst deactivation in a flow reactor was observed. 

A selective oxidation of a secondary alcohol is achieved by the Oppenauer oxidation of a sterol. A primary alcohol is partially transformed in an aldehyde that condenses in situ with cylohexanone employed as oxidant. 

By the same series of reactions, tetrahydroalstonine (LXXXI) has been related to dihydrocorynantheane (46), but this time by reversal of the configuration at C-20 by the Oppenauer oxidation on the open-chain alcohol, the configuration /3 equatorial being the more stable. 

Dihydro-i/< -codeinone is obtained in 40 per cent, yield by the Oppenauer oxidation of dihydroallo-with phosphorus pentachloride gives 8-chloro- and 1 8-dichlorodihydrocodide, which are also produced in the same way from dihydro-i/ -codeine-A thionyl chloride effects chlorination in the aromatic nucleus only. With phosphorus tribromide it apparently suffers replacement of the hydroxyl group by bromine, loss of hydrogen bromide, and demethylation, as the product is desoxymorphine-D [240] (see Chap. VIII). 

Cod binone and 1-bromocodeinone [xix, R = H] and [xix, R = Br] have been prepared by the Oppenauer oxidation of codeine [xx, R = H] and 1-bromocodeine [xx, R = Br] respectively using potassium if-butoxide and benzophenone. On reduction with lithium aluminium hydride these two ketones are converted into codeine [3]. 

Ring C was investigated through a-dihydrocaranone (LXX), prepared by the Oppenauer oxidation of a a-dihydrocaranine. The ketone showed carbonyl absorption at 5.87 p, characteristic of a cyclohexanone. A neutral by-product of the oxidation was shown to be LXXI, the isolation of which provided additional evidence for the 1-hydroxyl group of caranine. Finally, LXX formed an enol acetate in wMch the double bond was conjugated with the aromatic ring. 

The oxidation of a hydroxyl group by an aluminum alkoxide-catalyzed hydrogen exchange with a receptor carbonyl compound is known as the Oppenauer oxidation. For oxidation of steroidal alcohols the reaction is generally... 

It has been found that 17/S-ureidoandrost-5-en-3/S-oI could not be oxidized by the Oppenauer method probably because an insoluble complex is formed. G. E. Arth and T. Jefopolus, unpublished results. 

There are also reactions in which hydride is transferred from carbon. The carbon-hydrogen bond has little intrinsic tendency to act as a hydride donor, so especially favorable circumstances are required to promote this reactivity. Frequently these reactions proceed through a cyclic TS in which a new C—H bond is formed simultaneously with the C-H cleavage. Hydride transfer is facilitated by high electron density at the carbon atom. Aluminum alkoxides catalyze transfer of hydride from an alcohol to a ketone. This is generally an equilibrium process and the reaction can be driven to completion if the ketone is removed from the system, by, e.g., distillation, in a process known as the Meerwein-Pondorff-Verley reduction,189 The reverse reaction in which the ketone is used in excess is called the Oppenauer oxidation. 

The reversible reduction of aldehydes or ketones to the corresponding alcohols using aluminum alkoxides such as aluminum isopropoxide (Al[OCH(CH3)2]3), the reducing alcohol usually being isopropyl alcohol (Le., RCOR + CH3CH(0H)CH3 RCH(OH)R + CH3C0CH3). The reaction is facilitated by the removal of acetone by distillation". This reaction has served as a model for metal-ion-dependent hydride transfer reactions catalyzed by certain enzymes. The reverse reaction is known as the Oppenauer oxidation . ... 

The Oppenauer oxidation of cholesterol to A4-cholesten-3-one of m.p. 77-79° in 70-93% yield has been reported in these volumes.10 Isomerization of As-cholesten-3-one by a mineral acid or a base has been conducted satisfactorily only on a micro scale 6 the method of isomerization with oxalic acid has been reported.3... 

The available experimental data supports a mechanism for the Oppenauer oxidation, involving an initial complexation of a carbonyl group with the aluminium from an aluminium alkoxide, followed by a rate-determining hydride transfer via a six-membered transition state.22... 

The Woodward modification of the Oppenauer oxidation is occasionally used on substrates that fail to be oxidized under the standard protocol,27 although it possesses the serious limitation of the strongly basic medium generated by potassium f-butoxide. 

Secondary alcohols may be oxidised to the corresponding ketones by the use of an aluminium alkoxide, frequently the t-butoxide, in the presence of a large excess of acetone (the Oppenauer oxidation). The reaction involves an initial alkoxy-exchange process followed by a hydride ion transfer from the so-formed aluminium alkoxide of the secondary alcohol by a mechanism analogous to that of the Meerwein-Ponndorf-Verley reduction (see Section 5.4.1, p. 520). 

Acetone in conjunction with benzene as a solvent is widely employed. Alternatively cyclohexanone as the hydrogen acceptor, coupled with toluene or xylene as solvent, permits the use of higher reaction temperatures and consequently the reaction time is considerably reduced the excess of cyclohexanone can be easily separated from the reaction product by steam distillation. Usually at least 0.25 mol of aluminium alkoxide per mol of secondary alcohol is employed. However, since an excess of alkoxide has no detrimental effect, the use of 1 to 3 mol of alkoxide is desirable, particularly as water, either present in the reagents or formed during secondary reactions, will remove an equivalent quantity of the reagent. It is recommended that 50 to 200 mol of acetone or 10 to 20 mol of cyclohexanone be employed. Other oxidisable groups are usually unaffected in the Oppenauer oxidation and the reaction has found wide application in the steroid field. 

Carboxamidation of RLi or RMgX.1 This reaction can be effected by reaction of RLi (or RMgX) with DMF to give a hemiaminal a followed by an Oppenauer oxidation. The second step requires the presence of a magnesium alkoxide such as magnesium 2-ethoxyethoxide 1, Mg(OCH2CH2OC2H5)2, either as a catalyst for the oxidation or for stabilization of a, possibly as a mixed cluster. 

The reaction between an aluminum alkoxide and a ketone can be reversed. This is the basis of the Oppenauer oxidation of a secondary alcohol to the ketone.44 8 The aluminum derivative of the alcohol is prepared by mOans of aluminum t-butoxide and is oxidized with a large excess of acetone or cyclohexanone. 

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