Hydrogenation Meerwein-Ponndorf-Verley reduction

Transfer Hydrogenation Including the Meerwein-Ponndorf-Verley Reduction... 

As shown in Figure 1.26, a chiral Sm(III) complex catalyzes asymmetric reduction of aromatic ketones in 2-propanol with high enantioselectivity. Unlike other late-transition-metal catalysis, the hydrogen at C2 of 2-propanol directly migrates onto the carbonyl carbon of substrate via a six-membered transition state 26A, as seen in 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. 

Zeolites are not typically used in Lewis acid type catalysis due to the absence of Lewis acid centers in zeolites. This is due to the coordination of the Al-site to four lattice-oxygens in a perfect zeolite framework. It has, however, been shown for zeolite Beta that the aluminum atom can reversibly move between a framework Brpnsted acid site and a framework-grafted Lewis-acid site.70 Accordingly, Creyghton et al. showed that zeolite Beta is active in the Meerwein-Ponndorf-Verley reduction (MPV) of ketones (scheme 4).71 In this reaction a hydrogen hydride transfer reaction between an alcohol and a ketone takes place. 

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 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. 

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. 

A clean hydrogen-transfer reduction of aldehydes and ketones to the corresponding alcohols has been reported. In a typical experiment, propan-2-ol is employed as reductant and solvent in an autoclave at 220-230°C and 4-5MPa. Although formally similar to Meerwein-Ponndorf-Verley reduction, the reaction requires no catalyst, which tends to cut down on side-products. 

Fig. 8.36. As the asymmetric center of citronellal is unaffected by the reactions, all of the isopulegol and menthol isomers formed have the correct stereochemistry at Cl of the /i-menthane skeleton. There are therefore two strategies for recycling unwanted isomers. The first is to purify the ( )-isopulegol (172) by crystallization and recycle (178-180) back to citronellal by pyrolysis [221, 223, 224]. The second is to hydrogenate the mixture, separate the (—)-menthol by crystallization and treat the remainder with aluminium isopropoxide, which converts all of them, by Oppenauer oxidation, enoliza-tion, reketonization and Meerwein-Ponndorf-Verley reduction, to (—)-menthol, which is the thermodynamically most stable isomer (225).

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-... 

The Meerwein-Ponndorf-Verley reaction is a classic method for ketone/ aldehyde carbonyl group reduction, which involves at least 1 equivalent of aluminum alkoxide as a promoter. In this reaction, the hydrogen is transferred from isopropanol to the ketone/aldehyde substrate, so the reaction can also be referred to as a transfer hydrogenation reaction. 

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