Meerwein-Ponndorf-Verley reaction mechanism

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... 

Within the mechanisms proceeding with substrate coordination to the metal, we can distinguish between insertion mechanisms, being characterized by the substrate insertion into the M—H bond (Scheme 4a), and in the particular case of the hydrogen-transfer reactions, a mechanism where the substrate and the hydrogen source (usually an alcohol) are both coordinated to the metallic center, commonly named the Meerwein-Ponndorf-Verley (MPV) mechanism (Scheme 5) (22-24). 

The Meerwein-Ponndorf-Verley reaction involves reduction of a ketone by treat-ment with an excess of aluminum triisopropoxide. The mechanism of the process is closely related to the Cannizzaro reaction in that a hydride ion acts as a leaving group. Propose a mechanism. 

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

The Meerwein-Ponndorf-Verley (MPV) reaction is an important route in the reduction of ketones with aluminum alkoxides (111). The mechanism has been... 

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]. 

Secondary alcohols may be oxidised to the corresponding ketones by the use of an aluminium alkoxide, frequently the t-butoxide, in the presence of a large excess of acetone (the Oppenauer oxidation). The reaction involves an initial alkoxy-exchange process followed by a hydride ion transfer from the so-formed aluminium alkoxide of the secondary alcohol by a mechanism analogous to that of the Meerwein-Ponndorf-Verley reduction (see Section 5.4.1, p. 520). 

Recent mechanistic studies on transition metal-catalysed hydrogen transfer reactions have been reviewed. Experimental and theoretical studies showed that hydrogen transfer reactions proceed through different pathways. For transition metals, hydridic routes are the most common. Within the hydridic family there are two main groups the monohydride and dihydride routes. Experimentally, it was found that whereas rhodium and iridium catalysts favour the monohydride route, the mechanism for ruthenium catalysts proceeds by either pathway, depending on the ligands. A direct hydrogen transfer mechanism has been proposed for Meerwein-Ponndorf-Verley (MPV) reductions.352... 

Kinetic studies of the Midland reduction confirmed that the reduction of aldehydes is a bimolecular process and the changes in ketone structure have a marked influence on the rate of the reaction (e.g., the presence of an EWG in the para position of aryl ketones increases the rate compared to an EDG in the same position). However, when the carbonyl compound is sterically hindered, the rate becomes independent of the ketone concentration and the structure of the substrate. The mechanism with sterically unhindered substrates involves a cyclic boatlike transition structure (similar to what occurs in the Meerwein-Ponndorf-Verley reduction). The favored transition structure has the larger substituent (Rl) in the equatorial position, and this model correctly predicts the absolute stereochemistry of the product. 

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)... 

Instead of using a complex metal hydride as the source of the hydride anion, the hydride anion may be donated from a carbon atom. In such a case, the reaction is called the Meerwein-Ponndorf-Verley reduction, or MPV reduction. In contrast to the reduction by a complex metal hydride, the MPV reduction is reversible. It is performed by heating aluminium isoproproxide with an excess of propan-2-ol. Two different routes compete one involves one molecule of the aluminium isoproproxide for each molecule containing a carbonyl group to be reduced, while the other route uses two. Suggest the mechanism that involves only one molecule of the aluminium compound. 

Kinetically controlled reaction conditions can also he employed in Meerwein-Ponndorf-Verley reductions11-78, but often appropriate control experiments to check the mechanism are lacking, for instance, determination of the ratio of stereoisomers with progressing reaction time. Low reaction temperatures, short reaction times and continuous removal of the carbonyl compound, e.g., acetone, favor kinetic reaction control. The mild conditions required for kinetic control can also be effected by a new variation of the Meerwein-Ponndorf Verley reaction11 in which three requirements are fulfilled ... 

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. 

Step 6 is the final step in the cellulose-to-lactic acid cascade, involving the isomerization of the 2-keto-hemi-acetal (here pyruvic aldehyde hydrate) into a 2-hydroxy-carboxyhc acid. This reaction is known to proceed in basic media following a Cannizzaro reaction with 1,2-hydride shift [111], Under mild conditions, Lewis acids are able to catalyze this vital step, which can also be seen as an Meerwein-Ponndorf-Verley reduction reaction mechanism. The 1,2-hydride shift has been demonstrated with deuterium labeled solvents [110, 112], Attack of the solvent molecule (water or alcohol) on pymvic aldehyde (step 5) and the hydride shift (step 6) might occur in a concerted mechanism, but the presence of the hemiacetal in ethanol has been demonstrated for pyruvic aldehyde with chromatography by Li et al. [113] andfor4-methoxyethylglyoxal with in situ CNMRby Dusselier et al. (see Sect. 7) [114]. 

Furukawa et al. (1961) suggested a mechanism for the stereoregular polymerizations. It is based on complexes presumed to be intermediates in well-known organic reactions, the Meerwein-Ponndorf-Verley reduction and the Tishchenko reaction (Fig. 17). The stereocontrol is thought to arise from steric effects owing to the tendency of metal alkoxides to associate by coordination between oxygen and metal. This steric interpretation is supported by work on the aluminum alcoholate reduction of substituted cyclohexanones. Jackman et al. (1949) found that the cis epimer is preferred if the ketone or alcoholate is hindered. 

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. 

Before considering the mechanism of this important variant of asymmetric hydrogen transfer, let us first look at earlier methods used in the field. Most of them were based on 2-propanol as the favourable organic source of hydrogen, and represent catalytic variants of the Meerwein-Verley-Ponndorf name reaction which uses large quantities of Al-isopropoxide at elevated temperatures (Scheme 11.7) [27, 28]. 

---