Meerwein-Ponndorf-Verley-Oppenauer reaction

Scheme 20.6 Mechanism of the Meerwein-Ponndorf-Verley-Oppenauer reaction.

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... 

The racemization mechanism of sec-alcohols has been widely studied [40, 41]. Metal complexes of the main groups of the periodic table react through a direct transfer of hydrogen (concerted process), e.g., aluminum complexes in the Meerwein-Ponndorf-Verley/Oppenauer reaction. However, racemization catalyzed by transition metal complexes occurs via a hydrogen transfer process through metal hydrides or metal dihydrides as intermediates (Scheme 5.21) [42]. 

Namy, J. L., Souppe, J., Collin, J., Kagan, H. B. New preparations of lanthanide aikoxides and their catalytical activity in Meerwein-Ponndorf-Verley-Oppenauer reactions. J. Org. Chem. 1984,49, 2045-2049. 

Kow, R., Nygren, R., Rathke, M. W. Rate enhancement of the Meerwein-Ponndorf-Verley-Oppenauer reaction in the presence of proton... 

Otvos, L., Gruber, L., Meisel-Agoston, J. The Meerwein-Ponndorf-Verley-Oppenauer reaction. I. Investigation of the reaction mechanism with radiocarbon. Racemization of secondary alcohols. Acta Chim. Acad. Sci. Hung. 1965,43, 149-153. 

Klomp, D., Maschmeyer, T., Hanefeld, U., Peters Jeep, A. Mechanism of homogeneously and heterogeneously catalysed meerwein-ponndorf-verley-oppenauer reactions for the racemisation of secondary alcohols. Chemistry (Weinheim an der Bergstrasse, Germany)... 

This reaction was first reported concurrently by Meerwein and Schmidt and Verley in 1925, and by Ponndorf in 1926, respectively. It is an aluminum alkoxide-catalyzed reduction of carbonyl compounds (ketones and aldehydes) to corresponding alcohols using another alcohol (e.g isopropanol) as the reducing agent or hydride source. Therefore, it is generally known as the Meerwein-Ponndorf-Verley reduction (MPV) or Meerwein-Ponndorf-Verley reaction. Occasionally, it is also referred to as the Meerwein-Ponndorf reduction, Meerwein-Ponndorf reaction, or Meerwein-Schmidt-Ponndorf-Verley reaction. About 12 years later, Oppenauer reported the reversion of this reaction in which alcohols were reversely oxidized into carbonyl compounds. Since then, the interchanges between carbonyl compounds and alcohols in the presence of aluminum alkoxide are generally called the Meerwein-Ponndorf-Oppenauer-Verley reduction or Meerwein-Ponndorf-Verley-Oppenauer reaction." ... 

The Meerwein-Ponndorf-Verley/Oppenauer reaction [1] induced by air-oxidised samarium(II) iodide has been found to be a means to directly isomerise aldohexopyranoses into ketohexopyranoses. ladonisi and co-workers [2] report-... 

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). 

Among the hydrogen transfer reactions, the Meerwein-Ponndorf-Verley reduction and its counterpart, the Oppenauer oxidation, are undoubtedly the most popular. These are well-established selective and mild redox reactions and they have been studied extensively [4, 5]. Nevertheless, traditional Meerwein-Ponndorf-Verley-Oppenauer (MPVO) reactions have some drawbacks, as they usually suffer from poor reactivity of the traditional Al(OiPr)3/iPrOH system, for which continuous removal of the produced acetone is necessary in order to shift the equilibrium between reduction of the ketone and oxidation of the donor alcohol. 

Yager, B. J., Hancock, C. K. Equilibrium and kinetic studies of the Meerwein-Ponndorf-Verley-Oppenauer (MPVO) reaction. J. Org. Chem. 1965, 30, 1174-1179. 

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. 

Aluminum alkoxides, particularly those formed from secondary alcohols, have been of interest to synthetic chemists since the mid-1920s due to their catalytic activity. Examples of these trialkoxides include aluminum isopropoxide (AIP) and aluminum sec-butoxide (ASB). They are easily prepared at lab or plant scale and provide highly selective reductions and oxidations under mild conditions. These reductions are termed Meerwein-Ponndorf-Verley (MPV) reactions after the chemists (1-3) who first investigated their utility. Because a MPV reaction are accuratelybe described as an equilibrium process, the reverse reaction (oxidation) can also be exploited. These associated reactions are termed Oppenauer oxidations (4). Meerwein-Ponndorf-Verley reductions and Oppenauer oxidations as well as other reaction types and applications will be discussed, but first some background is provided concerning structure, preparation, and characterization of aluminum isopropoxide and related compounds. 

CLASSIC MEERWEIN-PONNDORF-VERLEY-OPPENAUER (MPVO) REACTIONS... 

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. 

Berkessel and coworkers reported the DKR of secondary alcohols based on the Meerwein-Ponndorf-Verley-Oppenauer (MPVO) reaction (Scheme 5.24) [40]. Trimethylaluminum (AlMej) was employed for the in situ generation of aluminum... 

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... 

Secondary alcohols may be oxidised to the corresponding ketones with aluminium /erl.-butoxide (or tsopropoxide) in the presence of a large excess of acetone. This reaction is known as the Oppenauer oxidation and is the reverse of the Meerwein - Ponndorf - Verley reduction (previous Section) it may be expressed ... 

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... 

More recently, Lnm alkoxides were shown to have much higher catalytic activity in this reaction, which allowed their use in only catalytic amounts [6, 7]. Later, however, much higher reactivities for Alln-catalyzed Meerwein-Ponndorf-Verley and Oppenauer (MPVO) reactions have also been achieved with dinuc-lear Alnl complexes [8,9] and with Alln alkoxides generated in situ [10]. Several reviews on the MPVO reactions have been published [11-14],... 

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