Oppenauer oxidation secondary alcohols

The widely used Moifatt-Pfltzner oxidation works with in situ formed adducts of dimethyl sulfoxide with dehydrating agents, e.g. DCC, AcjO, SO], P4O10, CCXTl] (K.E, Pfitzner, 1965 A.H. Fenselau, 1966 K.T. Joseph, 1967 J.G. Moffatt, 1971 D. Martin, 1971) or oxalyl dichloride (Swem oxidation M. Nakatsuka, 1990). A classical procedure is the Oppenauer oxidation with ketones and aluminum alkoxide catalysts (C. Djerassi, 1951 H. Lehmann, 1975). All of these reagents also oxidize secondary alcohols to ketones but do not attack C = C double bonds or activated C —H bonds. 

Chloral (trichloroacetaldehyde), CCI3CHO, oxidizes secondary alcohols to ketones in the presence of very active aluminum oxide (Woelm). This reaction seems to be superior to the Oppenauer oxidation, because it takes place at room temperature or at only slightly elevated temperatures [958, 959, 960],... 

Oppenauer oxidation In combination with p-nitrobenzaldehyde, (i-PrO) A1(0C0CF3) oxidizes secondary alcohols but not primary alcohols under the defined conditions (room temperature). 

The Meerwein-Ponndorf-Verley reduction of carbonyl compounds and the Oppenauer oxidation of alcohols, together denoted as MPVO reactions, are considered to be highly selective reactions. For instance, C=C double bonds are not attacked. In MPV reductions a secondary alcohol is the reductant whereas in Oppenauer oxidations a ketone is the oxidant. It is generally accepted that MPVO reactions proceed via a complex in which both the carbonyl and the alcohol are coordinated to a Lewis acid metal ion after which a hydride transfer from the alcohol to the carbonyl group occurs (Fig. 1) [1]. Usually, metal ec-alkoxides are used as homogeneous catalysts in reductions and metal t-butoxides in oxidations [1]. 

The Meerwein-Ponndorf-Verley reduction of aldehydes and ketones and its reverse, the Oppenauer oxidation of alcohols, are hydrogen-transfer reactions that can be performed under mild conditions and without the risk of reducing or oxidizing other functional groups [1]. The hydrogen donors are easily oxidizable secondary alcohols (e. g. i-PrOH) and the oxidants are simple ketones (e. g. cyclohexanone). Industrial applications of the MPVO reactions are found in the fragrance and pharmaceutical industries, for example. 

Secondary alcohols may be oxidised to the corresponding ketones with aluminium ferf.-butoxlde (or tsopropoxlde) In the presence of a large excess of acetone. This reaction Is known as the Oppenauer oxidation and Is the reverse of the Meerweln - Ponndorf - Verley reduction (previous Section) it may bo expressed ... 

Oppenauer reaction is oxidation of secondary alcohols to ketones using aluminium t-butoxide... 

The reduction of ketones to secondary alcohols and of aldehydes to primary alcohols using aluminum alkoxides is called the Meerw>ein-Ponndorf-Verley reduction. The reverse reaction also is of synthetic value, and is called the Oppenauer oxidation. ... 

The Oppenauer Oxidation. When a ketone in the presence of base is used as the oxidizing agent (it is reduced to a secondary alcohol), the reaction is known as the Oppenauer oxidation. This is the reverse of the Meerwein-Ponndorf-Verley reaction (16-23), and the mechanism is also the reverse. The ketones most commonly used are acetone, butanone, and cyclohexanone. The most common base is aluminum r r/-butoxide. The chief advantage of the method is its high selectivity. Although the method is most often used for the... 

Selective oxidation of allylic alcohols.1 This zircononcene complex when used in catalytic amount can effect an Oppenauer-type oxidation of alcohols, including allylic ones, in the presence of a hydrogen acceptor, usually benzaldehyde or cyclohexanone. This system oxidizes primary alcohols selectively in the presence of secondary ones. Thus primary allylic alcohols are oxidized to the enals with retention of the configuration of the double bond in 75-95% yield. The method is not useful for oxidation of propargylic alcohols. 

Oppenauer-type oxidation of secondary alcohols can be a convenient procedure for obtaining the corresponding carbonyl compounds. It was found recently [19], that Ir(I)- and Rh(I)-complexes of 2,2 -biquinoline-4,4 -dicarboxylic acid dipotassium salt (BQC) efficiently catalyze the oxidation of secondary alcohols with acetone in water/acetone 2/1 mixtures (Scheme 8.5). The reaction proceeds in the presence of Na2C03 and affords medium to excellent yields of the isolated ketones. The process is much faster in largely aqueous solutions, such as above, than in wet organic solvents in acetone, containing only 0.5 % water, low yields were observed (15 % vs. 76 % in case of cyclohexanol). 

The catalytic activity of Cp Ir(III) complexes in the Oppenauer-type oxidation of alcohols was considerably enhanced by the introduction of N-heterocyclic carbene ligands. Here, high turnover numbers (TONs) of up to 950 were achieved in the oxidation of secondary alcohols [40]. 

Hydrogen transfer reactions from an alcohol to a ketone (typically acetone) to produce a carbonyl compound (the so-caUed Oppenauer-type oxidation ) can be performed under mild and low-toxicity conditions, and with high selectivity when compared to conventional methods for oxidation using chromium and manganese reagents. While the traditional Oppenauer oxidation using aluminum alkoxide is accompanied by various side reactions, several transition-metal-catalyzed Oppenauer-type oxidations have been reported recently [27-29]. However, most of these are limited to the oxidation of secondary alcohols to ketones. 

The reverse reaction is known as the Oppenauer oxidation. Here aluminium tri tertiary but oxide and an involatile ketone such as cyclohexanone are used to oxidise any secondary alcohol to the corresponding ketone. 

Pyrrolizidine alcohols are readily oxidized. Stereoisomeric 1-hydroxymethylpyrrolizidines when oxidized with chromic acid afford stereoisomeric pyrrolizidine-1-carboxylic acids (see Section III, C).81,90 Secondary alcohols, when subjected to Oppenauer oxidation or chromic acid treatment, yield amino-ketones (cf. refs. 72, 77, and 81). 

Regardless of the veracity of the proposed assembling depicted in Figure 6.1, the fact remains that the catalyst 67 is highly efficient in the promotion of Oppenauer oxidations under mild conditions and have been employed in a very elegant way in oxidation-reduction transformations, in which in the same molecule a secondary alcohol is oxidized while an aldehyde is reduced with no addition of external redox reagents. 

Maruoka s group also developed the extremely active aluminium compound 68,38 which in a proportion as low as 1 mol% is able to promote the oxidation of alcohols with pivalaldehyde or acetone at room temperature. Oppenauer oxidations employing catalyst 68 succeed in a variety of secondary and primary alcohols, providing yields of aldehydes and ketones above 80% in a consistent way. Only lineal primary aliphatic alcohols fail to be cleanly oxidized to the corresponding aldehydes. 

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. 

An Oppenauer reaction produces the selective oxidation of a secondary alcohol, leading to a (3-hydroxyketone that suffers a retro-aldol condensation under the basic reaction conditions, resulting in the evolution of formaldehyde. 

Chloral or benzaldehyde in the presence of dehydrated alumina48 and Al(OtBu)3 in the presence of f-BuOOH,49 are oxidizing systems reminiscent of Oppenauer oxidations that can perform regioselective oxidations of secondary alcohols. 

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