Oppenauer-oxidation of alcohols

Very recently, Maruoka s team developed two highly sophisticated and efficient aluminium compounds for the Oppenauer oxidation of alcohols. Thus, the complex aluminium phenoxide 67, containing two aluminium atoms, is able to catalyze in a quantity as low as 5 mol%—the oxidation of alcohols with pivalaldehyde at room temperature.37... 

The Oppenauer oxidation of alcohols (by a ketone in excess, with an aluminium alkoxide as catalyst) proceeds by hydride transfer through a cyclic transition state (7) in which a molecule of the alcohol and a molecule of the reagent ketone (e.g. acetone) are simultaneously coordinated to one aluminium atom [39]. The reaction actually establishes an equilibrium... 

Acetone, cyclohexanone, benzophenone, cinnamaldehyde, and other carbonyl compounds are hydrogen acceptors in the Oppenauer oxidation of alcohols to carbonyl compounds. The reaction is catalyzed by Raney nickel [961], aluminum alkoxides [962], tris(isopropoxide), or tris(tert-bu-toxide) as bases soluble in organic solvents [963, 964]. These dehydrogenations of alcohols to aldehydes and ketones require refluxing or distillations and have given way to dimethyl sulfoxide oxidations, which take place at room temperature. 

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). 

In fact, a variation of this reaction has been utilized in the well-known Meerwein-Ponndorf-Verley reduction of carbonyl compounds (reverse of Oppenauer oxidation of alcohols) by aluminum isopropoxide The reaction involves a six-centered transition state, wherein the P-hydride is delivered into an incoming carbonyl group [Eq. (6.86)]. The stereochemistry of this reaction has been studied in detail. ... 

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 most important side reaction in heterogeneously catalysed MPVO reactions is the acid-catalysed aldol condensation. Aldol products are usually observed during the Oppenauer oxidation of alcohols, when a surplus of ketone or aldehyde is used as the oxidizing agent and the solvent. The low amount of by-products formed when Ti-beta was used as the catalyst, demonstrates the advantage of the titanium system over Al-beta. This is probably caused by the much weaker Brpnsted acidity of the solvated titanium site [8] compared with the strong H -acidity of the aluminium site in Al-beta. As we have shown earlier Ti-beta has a high tolerance towards water, which further shows the catalytic potential of Ti-beta in MPVO reactions [9]. 

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. 

Raja. T Jyothi, TM Sreekumar, K Talawar, MB Santhanalakshmi, J Rao, BS. Calcined layered double hydroxides as basic heterogeneous catalysts for the Oppenauer oxidation of alcohols. Bulletin of the Chemical Society of Japan, 1999 72. 2117-2119. 

The Oppenauer oxidation of alcohols by ketones is a very selective oxidation reaction when the molecule to be oxidised contains other groups susceptible to oxidation. The opposite reaction, the Meerwein-Ponndorf-Verley reduction of ketones by alcohols is simply the reverse reaction. These conversions are catalysed by Lewis acids. These are typically metal tert-butoxides in solution,... 

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. 

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. 

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 Oxidation of Alcohols (Oppenauer-Type Oxidation)... 

Gabrielsson et al. reported the aerobic oxidation of alcohols catalyzed by a cationic Cp Ir complexes bearing diamine ligands such as bipyrimidine 10 (Scheme 5.8) [35], the mechanism of which is closely related to the Oppenauer-type oxidation mentioned above. In this reaction, the deprotonation of Ir hydrido species to afford Ir species, and the reoxidation of Ir to Ir by O2, are crucial. 

Meerwein-Pondorf-Verley reduction, discovered in the 1920s, is the transfer hydrogenation of carbonyl compounds by alcohols, catalyzed by basic metal compounds (e.g., alkoxides) [56-58]. The same reaction viewed as oxidation of alcohols [59] is called Oppenauer oxidation. Suitable catalysts include homogeneous as well as heterogeneous systems, containing a wide variety of metals like Li, Mg, Ca, Al, Ti, 2r and lanthanides. The subject has been reviewed recently [22]. In this review we will concentrate on homogeneous catalysis by aluminium. Most aluminium alkoxides will catalyze MPV reduction. 

Water-soluble catalysts for Oppenauer-type oxidation of alcohols can be achieved by adding functionalized salts of classical ligands such as dipotassium 2,2 -biquinoline-4,4 -dicarboxylate (BQC) to acetone-water mixtures. In this way, the catalyst system [ Ir(ix-Cl)(cod) 2]/BQC is highly efficient for the selective oxidation of a wide range of alcohols such as benzylic. 

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 number of zirconium compounds are able to catalyze Oppenauer oxidations. For example, zirconium dioxide, when properly conditioned, is able to promote the oxidation of alcohols in variable yields40 and it is reportedly superior than AI2O3. Other zirconium compounds able to induce Oppenauer oxidations in catalytic amounts include Cp2ZrH2,41 Cp2Zr(Oi-Pr)2,41b Zr(Oi-Bu)442 and Zr(0 -Pr)x on Si0242... 

Sometimes, reactions in which an alcohol is oxidized by hydride transfer to a metallic cluster, resulting in the formation of a metallic hydride that subsequently transfers a hydride to a sacrificial aldehyde or ketone, are described as Oppenauer oxidations.44 In the opinion of the authors, the name Oppenauer oxidation should be reserved for oxidation of alcohols in which a hydride is directly transferred from a metallic alkoxide to an aldehyde or ketone acting as oxidant. 

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. 

The oxidation of cholesteryl esters and low-density lipoproteins by free radicals has been reviewed.228 The use of bis(pentafluorophenyl)borinic acid as a strong Lewis acid allows efficient Oppenauer oxidation of allylic and benzylic alcohols using Bu CHO as oxidant.229 Saturated alcohols were only slowly oxidized and this allowed selective conversion of allylic alcohols in the presence of saturated alcohols. 

The addition of a-deprotonated alkyl halides to alkenes or carbonyl compounds can, because of the good leaving-group properties of halides, also lead to formation of cyclopropanes [292] or epoxides [187, 304, 306, 310], respectively. Because of the inherent instability of a-halo organometallic compounds, these intermediates should be handled carefully and on a small scale only. The ketone produced by the last reaction in Scheme 5.34 is probably formed by Oppenauer oxidation of the intermediate alcohol by the excess benzaldehyde [310],... 

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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