Catalyst Meerwein- Ponndorf-Verley-Oppenauer

Very recently the Meerwein-Ponndorf-Verley-Oppenauer (MPVO) reaction has been exploited for the racemization of alcohols using inexpensive aluminum-based catalysts. Combination of these complexes with a lipase (CALB) results in an efficient DKR of sec-alcohols at ambient temperature. To increase the reactivity of the aluminum complexes, a bidentate ligand, such as binol, is required. Also, specific acyl donors need to be used for each substrate [31] (Eigure 4.9). 

Meerwein-Ponndorf-Verley-Oppenauer catalysts typically are aluminum alkox-ides or lanthanide alkoxides (see above). The application of catalysts based on metals such as ytterbium (see Table 20.7, entries 6 and 20) and zirconium [85, 86] has been reported. 

Based on the catalytic activity of aluminum alkoxides in the Meerwein-Ponndorf-Verley-Oppenauer reaction, Berkessel et al. envisioned that aluminum complexes can act as alcohol racemization catalysts [32]. Aluminum alkoxide complexes generated from a 1 1 mixture of AlMes and a bidentate ligand such as binol or 2,2 -biphenol were effective catalysts for alcohol racemization. At room temperature, 10mol% of the aluminum catalyst racemized 1-phenylethanol completely within 3h in the presence of 0.5 equiv. of acetophenone. The aluminum catalysts were... 

Zeolite Titanium Beta A selective catalyst in the Meerwein-Ponndorf-Verley-Oppenauer reactions. 

Meerwein-Ponndorf-Verley-Oppenauer (MPVO) reactions are usually mediated by metal alkoxides such as Al(0/-Pr)3. The activity of these catalysts is related to their Lewis-acidic character in combination with ligand exchangeability. The mechanism of these homogeneous MPVO reactions proceeds via a cyclic six-membered transition state in which both the reductant and the oxidant are co-ordinated to the metal center of the metal alkoxide catalyst (Scheme 1). The alcohol reactant is co-ordinated as alkoxide. Activation of the carbonyl by co-ordination to Al(III)-alkoxide initiates the hydride-transfer reaction from the alcoho-late to the carbonyl. The alkoxide formed leaves the catalyst via an alcoholysis reaction with another alcohol molecule, usually present in excess [Ij. 

Zr compounds are also useful as Lewis acids for oxidation and reduction reactions. Cp2ZrH2 or Cp2Zr(0 Pr)2 catalyze the Meerwein-Ponndorf-Verley-type reduction and Oppenauer-type oxidation simultaneously in the presence of an allylic alcohol and benzaldehyde (Scheme 40).170 Zr(C)1 Bu)4 in the presence of excess l-(4-dimethylaminophenyl) ethanol is also an effective catalyst for the Meerwein-Ponndorf-Verley-type reduction.1 1 Similarly, Zr(0R)4 catalyze Oppenauer-type oxidation from benzylic alcohols to aldehydes or ketones in the presence of hydroperoxide.172,173... 

The most common catalysts for the Meerwein-Ponndorf-Verley reduction and Oppenauer oxidation are Alm and Lnm isopropoxides, often in combination with 2-propanol as hydride donor and solvent. These alkoxide ligands are readily exchanged under formation of 2-propanol and the metal complexes of the substrate (Scheme 20.5). Therefore, the catalytic species is in fact a mixture of metal alkoxides. 

The development of aluminium-based catalysts for the asymmetric Meerwein-Schmidt-Ponndorf-Verley-Oppenauer (MSPVO) reduction/oxidation systems is reviewed with emphasis on the mechanistic understanding of the origin for activity and selectivity in monometallic catalysts.252... 

Creyghton, E. J., Huskens, J., van der Waal, J. C. and van Bekkum, H. Meerwein-Ponndorf-Verley and Oppenauer reactions catalysed by heterogeneous catalyst. Stud. Surf. Sci. Catal., 1997, 108, 531. 

Meerwein-Ponndorf-Verley reduction was efficiently and selectively achieved by use of l-(4-dimethylaminophenyl)ethanol as the reducing alcohol (2-4 equiv.) and Zr(0-/-Bu)4 (0.2 equiv.) as the catalyst [32b]. Oppenauer oxidation was selectively achieved by using chloral (1.2-3 equiv.) as the hydrogen acceptor and Zr(0-t-Bu)4 (0.2 equiv.) as the catalyst [32c]. 

The Oppenauer Oxidation. When a ketone in the presence of an aluminum alkoxide 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 (19-36) and the mechanism is also the reverse. The ketones most commonly used are acetone, butanone, and cyclohexanone. The most common base is aluminum ferf-butoxide. The chief advantage of the method is its high selectivity. Although the method is most often used for the preparation of ketones, it has also been used for aldehydes. An iridium catalyst has been developed for the Oppenauer oxidation, and also a water-soluble iridium catalyst An uncatalyzed reaction under supercritical conditions was reported. 

Oppenauer oxidation. The bidentate aluminum species and pivalaldehyde constitute an oxidizing system for secondary alcohols. The bis(diisopropoxyaluminum) analog is a highly efficient catalyst for the Meerwein-Ponndorf-Verley reduction. 

Zeolite titanium beta has been tested in the liquid- and gas-phase Meerwein-Ponndorf-Verley reduction of cyclohexanones and the Oppenauer oxidation of cyclohexanols. A high selectivity towards the thermodynamically unfavourable cis-alcohol was observed, which has been ascribed to transition-state selectivity in the pores of the zeolite. Under gas-phase conditions the dehydration of alcohols to cycloalkenes is observed as a side reaction. The catalyst was found to be active even in the presence of water and ammonia. 

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]. 

Meerwein-Ponndorf-Verley and Oppenauer reactions catalysed by heterogeneous catalysts... 

Summary Meerwein-Ponndorf-Verley and Oppenauer reactions (MPVO) are catalysed by metal oxides which possess surface basicity or Lewis acidity. Recent developments include the application of basic alkali or alkaline earth exchanged X-type zeolites and the Lewis-acid zeolites BEA and [Ti]-BEA. The BEA catalysts show high stereoselectivity, as a result of restricted transition state selectivity, in the MPV reduction of substituted alkylcyclohexanones with i-PrOH. 

Aluminium isopropoxide is a Lewis acid and it is also a good catalyst for the Oppenauer oxidation and Meerwein-Ponndorf-Verley reduction reactions. In the presence of a ketone, it will oxidise d-isomenthol to d-isomenthone (Oppenauer oxidation). The hydrogen atom on C-4 is now enolisable and therefore epimerisation can occur, catalysed by the aluminium isopropoxide acting as a Lewis acid. This will give /-menthone. This can now be reduced (Meerwein-Ponndorf-Verley reduction) to /-menthol by an alcohol and aluminium isopropoxide. The ketone and alcohol for the redox reactions could be the menthols/ menthones themselves or traces of acetone/isopropanol in the aluminium isopropoxide. Obviously, the reactions shown in Figure 4.28 are all reversible. The equilibrium will eventually be driven over completely to /-menthol since the latter is the most thermodynamically favoured of all of the isomeric components in the system. 

One of the chemoselective and mild reactions for the reduction of aldehydes and ketones to primary and secondary alcohols, respectively, is the Meerwein-Ponndorf-Verley (MPV) reduction. The lifeblood reagent in this reaction is aluminum isopropoxide in isopropyl alcohol. In MPV reaction mechanism, after coordination of carbonyl oxygen to the aluminum center, the critical step is the hydride transfer from the a-position of the isopropoxide ligand to the carbonyl carbon atom through a six-mem-bered ring transition state, 37. Then in the next step, an aluminum adduct is formed by the coordination of reduced carbonyl and oxidized alcohol (supplied from the reaction solvent) to aluminum atom. The last step is the exchange of produced alcohol with solvent and detachment of oxidized alcohol which is drastically slow. This requires nearly stoichiometric quantities of aluminum alkoxide as catalyst to prevent reverse Oppenauer oxidation reaction and also to increase the time of reaction to reach complete conversion. Therefore, accelerating this reaction with the use of similar catalysts is always the subject of interest for some researchers. 

Metal alkoxides are known to act as potential catalysts (Chapter 7, Section 4) and this property has been utilized successfully in organic syntheses. Before dealing with the Tischtchenko, Meerwein-Ponndorf-Verley, and Oppenauer oxidation reactions, it is worth briefly mentioning the Cannizzaro reaction which appears to be the main basis... 

In a different vein and as already pointed out in Chapter 8 (Scheme 8.6), the Meerwein-Ponndorf-Verley reduction is the reverse of the Oppenauer oxidation of aldehydes and ketones, and it is only a change of solvent that dictates whether the reaction that occurs is an oxidation or a reduction.The same catalyst is used. Scheme 9.19 is the reverse of Scheme 8.6. Thus, it is now suggested that the carbonyl oxygen of cyclohexen-3-one displaces an isopropoxy group (2-propoxy [ OCH(CH3)2]) from the catalyst, aluminum isopropoxide [Al(0-iPr)3].Then, after intramolecular hydride transfer, propanone (acetone, CH3COCH3) is lost by displacement from aluminum by the solvent, 2-propanol (isopropanol [CH3CH(OH)CH3]), and finally, the cyclo-... 

Scheme 9.19. A representation of the Meerwein-Ponndorf-Verley reduction of cyclohexen-3-one using aiuminum isopropoxide catalyst. The reaction is the reverse of that seen as the Oppenauer Oxidation (Scheme 8.6). See (a) Meerwein, H. Schmidt, R. Liebigs Ann. Chem., 1925, 444, 221 (b) Ponndorf, W. Angew. Chem., 1926,39,138 (c) Verley, A. Bull. Soc. Chim. Fr., 1925,37,537, and Oppenauer, R. V. Red. Trav. Chim. Pays-Bas, 1937,56,137.

The Meerwein-Ponndorf-Verley reduction is a reversible reaction and the reverse pathway was reported in detail a couple of years later by Oppenauer who selectively oxidised hydroxyl functions into ketones or aldehydes with the help of acetone or cyclohexanone as proton quencher (oxidant) and aluminium tert-butoxide as catalyst (other common oxidants are acetaldehyde, anisaldehyde, benzaldehyde, benzophenone and cinnamalde-hyde). This mild oxidation method was in many cases used in the synthesis of steroids and terpenoids. 

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