Meerwein-Ponndorf-Verley oxidation

To meet the needs of the advanced students, preparations have now been included to illustrate, for example, reduction by lithium aluminium hydride and by the Meerwein-Ponndorf-Verley method, oxidation by selenium dioxide and by periodate, the Michael, Hoesch, Leuckart and Doebner-Miller Reactions, the Knorr pyrrole and the Hantzsch collidine syntheses, various Free Radical reactions, the Pinacol-Pinacolone, Beckmann and Arbusov Rearrangements, and the Bart and the Meyer Reactions, together with many others. 

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... 

Meerwein-Ponndorf-Verley Reduction and Oppenauer Oxidation... 

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. 

Alcohols have always been the major group of hydrogen donors. Indeed, they are the only hydrogen donors that can be used in Meerwein-Ponndorf-Verley (MPV) reductions. 2-Propanol (16) is most commonly used both in MPV reductions and in transition metal-catalyzed transfer hydrogenations. It is generally available and cheap, and its oxidation product, acetone (14), is nontoxic and can usually be removed readily from the reaction mixture by distillation. This may have the additional advantage that the redox equilibrium is shifted even more into the direction of the alcohol. As a result of sigma inductive electronic ef-... 

Apart from aluminium, many other metals were tested in Meerwein-Ponndorf-Verley reductions and Oppenauer oxidations during the early years of research on hydride transfer from alkoxides.26 A consensus was... 

Catalytic reduction of unsymmetrical ketones into alcohols by concomitant oxidation of 2-propanol to acetone (Meerwein-Ponndorf-Verley reduction, MPV), with rhodium... 

Meerwein-Ponndorf-Verley Reduction opposite of Oppenauer oxidation Synthesis 1994,1007 Organic Reactions 1944, 2,178... 

The aluminium-catalyzed hydride shift from the a-carbon of an alcohol component to the carbonyl carbon of a second component, which proceeds via a six-membered transition state, is referred to as the Meerwein-Ponndorf-Verley Reduction (MPV) or the Oppenauer Oxidation, depending on which component is the desired product. If the alcohol is the desired product, the reaction is viewed as the Meerwein-Ponndorf-Verley Reduction. 

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. 

Catalytic Oppenauer oxidations (Eq. 28) and Meerwein-Ponndorf-Verley reductions (Eq. 29) were studied in detail [232,234]. The gadolinium derivative, employed in situ without elimination of LiCl, was reported to be ten times more reactive in the MPV reduction of cyclohexanone as the standard reagent Al(OiPr)3 [235]. 

Aramendia, M. A., Borau, V., Jimenez, C., Marinas, J. M., Ruiz, J. R. and Urbano, F. J. Influence of the preparation method on the structural and surface properties of various magnesium oxides and their catalytic activity in the Meerwein-Ponndorf-Verley reaction, Appl. Catal., A, 2003, 244, 207-215. 

The generality of schemes of this type is not clear, but it is an alternative to the e/H transfer sequences for a range of reactions in which oxidant-derived radical anions are found, including the Meerwein-Ponndorf-Verley reduction of diaryl ketones outlined above. 

Both the Meerwein-Ponndorf-Verley reaction and the Cannizzaro reaction are hydride transfers in which a carbonyl group is reduced by an alkoxide group, which is oxidized. Note that each aluminum triisopropoxide molecule is capable of reducing three ketone molecules. 

A simultaneous reduction-oxidation sequence of hydroxy carbonyl substrates in the Meerwein-Ponndorf-Verley reduction can be accomplished by use of a catalytic amount of (2,7-dimethyl-l,8-biphenylenedioxy)bis(dimethylaluminum) (8) [33], This is an efficient hydride transfer from the sec-alcohol moiety to the remote carbonyl group and, because of its insensitivity to other functionalities, should find vast potential in the synthesis of complex polyfunctional molecules, including natural and unnatural products. Thus, treatment of hydroxy aldehyde 18 with 8 (5 mol%) in CH2CI2 at 21 °C for 12 h resulted in formation of hydroxy ketone 19 in 78 % yield. As expected, the use of 25 mol% 8 enhanced the rate and the chemical yield was increased to 92 %. A similar tendency was observed with the cyclohexanone derivative. It should be noted that the present reduction-oxidation sequence is highly chemoselective, and can be utilized in the presence of other functionalities such as esters, amides, rert-alco-hols, nitriles and nitro compounds, as depicted in Sch. 10. 

Meerwein-Ponndorf-Verley-type reduction of carbonyl compounds and Oppe-nauer-type oxidation of allylic alcohols 69 proceed simultaneously imder the influence of a catalytic amount of Cp2ZrH2 (Eq. 28) [32a]. 

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 classical Meerwein-Ponndorf-Verley (MPV) process, named after the independent originators, can be illustrated by the reduction of crotonaldehyde (43) by aluminum isopropoxide (44) in isopropyl alcohol (equation 24). Aluminum isopropoxide transfers hydride reversibly to a carbonyl acceptor. Acetone is formed as a volatile side product, which can be removed during reaction. The reaction of equation (24) is forced even further to the right by the use of excess isopropyl alcohol. MPV reactions have been reviewed.In the Oppenauer variant of this reaction an alcohol is oxidized to a ketone, and acetone is used as hydride acceptor in the presence of a strong base like r-butoxide. This reaction was originally developed for the selective oxidation of sterols. The synthetic aspects of this procedure have also been reviewed. ... 

---