Ponndorf-Meerwein-Verley method

For the synthesis of (+)-citronellol (6), the mixed pinenes were catalytically hydrogenated to give (-)-cis-pinane (7) which was pyrolysed to (-)-citronellene. Application of the Ziegler reaction with aluminium hydride proceeded selectively at the more reactive disubstituted double bond and following atmospheric oxidation and aqueous work-up, (+)-citronellol was isolated identical with that derived by the reduction of natural citronellal by the Ponndorf-Meerwein-Verley method (ref.9) as shown. 

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. 

It was noticed as early as 1925 that alkoxides of calcium, magnesium and particularly aluminum could catalyze the reduction of aldehydes by ethanol as shown in equation (65).242,243 Removal of very volatile acetaldehyde is easily achieved to drive the reaction to the right. In 1926, Ponndorf devised a method in which both aldehydes and ketones could be reduced to alcohols by adding excess alcohol and aluminum isopropoxide.244 Such reductions are today referred to as Meerwein-Ponndorf-Verley reactions. Although alkoxides of a number of metals, e.g. sodium, boron, tin, titanium and zirconium, have been used for these reactions, those of aluminum are by far the best. 

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]. 

The Meerwein-Ponndorf-Verley procedure has largely been replaced by reduction procedures that use lithium aluminum hydride, sodium borohydride or derivatives thereof. The Meerwein-Ponndorf-Verley reduction however has the advantage to be a mild and selective method, that does not affect carbon-carbon double or triple bonds present in the substrate molecule. 

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... 

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. 

Mannich reaction, 1, 10 7, 3 Meerwein arylation reaction, 11, 3 24, 3 Meerwein-Ponndorf-Verley reduction, 2, 5 Mercury hydride method to prepare radicals, 48, 2... 

The Meerwein-Ponndorf-Verley reaction is a useful method for the reduction of carbonyl groups to alcohols. Most typically, aluminium isopropoxide is used as a reducing agent. The acetone produced can be easily removed by distillation, thus driving the equilibrium reaction in the desired direction. When the carbonyl compound was refluxed... 

The synthetic method (a) is the regioselective reduction of an a,/ -unsaturated aldehyde or ketone (Section 5.18.2, p. 798), which is most conveniently effected by the Meerwein-Ponndorf-Verley procedure (Section 5.4.1, p. 520). The further disconnection shown of the a, -carbonyl compound is a retro-aldol condensation (Section 5.18.2, p. 799) however it should be emphasised that other routes to the unsaturated carbonyl compound, such as the Horner-Emmons reaction (Section 5.18.2, p. 799), may also be feasible. 

This mild and specific method of reducing carbonyl compounds became known as the Meerwein-Ponndorf-Verley reduction 4 and in the next decade was used successfully in a number of instance, particularly... 

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. 

Meerwein-Ponndorf-Verley reductions. Zirconocene or hafnocene can catalyze reduction of carbonyl compounds with isopropanol. This method is useful for preferential reduction of keto aldehydes to hydroxy ketones and of a,(i-enones or -enals to allylic alcohols.1... 

The reduction of a carbonyl compound containing an additional functional group is a common practice. If the other group is easily reduced, best results are frequently obtained by the Meerwein-Ponndorf-Verley reaction (method 80). The following paragraphs, however, describe certain useful selective reductions. 

Zeolite BEA is a stereoselective and regenerable heterogeneous catalyst for the Meerwein Ponndorf Verley (MPV) reduction of 4-ZerZ-butylcyclohexanone to cA-4-/er/-butylcyclohexanol (Scheme 5.41), as demonstrated by Bekkum et The cM -isomer is very important in the fragrance industry and is very difficult to obtain by other methods. 

Yu and coworkers reported that use of PrSBEt2 as an additive accelerates the chiral Zr-catalyzed asymmetric allylation reaction and suppresses the concomitant Meerwein-Ponndorf-Verley reduction. The presence of the additive is thought to dissociate the product from the reaction complex and to regenerate the chiral catalyst [28]. This method was further extended to asymmetric propargylation with allenyltributylstannane by the same group [19]. In contrast, Taghavini and Umani-Ronchi and their group have shown that an enantioselective allylation of... 

Aldrich, ( )-DlP-Chloride]31. These latter two reagents are complementary with respect to enantiomeric excesses obtainable from various ketones (- j-DIP-Chloride is especially effective in the reduction of hindered acetylenic ketones37. Various chiral reducing agents have been compared38 and in recent reviews 30,39 the stereochemistry of Meerwein-Ponndorf-Verley reductions has been discussed in connection with other reduction methods. 

Meerwein-Ponndorf-Verley reduction of ketones to secondary alcohols proceeds analogously to that of aldehydes, although usually more slowly. The method cannot, however, be used for ketones such as j8-keto esters or / -diketones that have a strong tendency to enolize, since they form aluminum enolates which are not reduced such compounds are preferably reduced by sodium borohydride, by potassium borohydride, or catalytically. 

Method II, The Meerwein-Ponndorf-Verley reaction A solution of 3 g of acetylferrocene in 300 mL of isopropyl alcohol was passed through a tube of diameter 25 mm and length 700 mm filled with activated AI2O3 for 3 h at a pressure of 900 to 1300 Pa and 200-210 °C. From the condensate 2.3 g of vinylferrocene was isolated and chromatographed via a column with AI2O3, hexane was used as the eluent. After evaporation of the solvent, 1.95 g of the metallomonomer was obtained (70% of the yield). 

The development of the CrOs-pyridine complex and the DMSO-based systems has decreased the number of instances in which older oxidation techniques are used. One such method, the Oppenauer oxidation is the reverse of the Meerwein-Ponndorf-Verley reduction (Chapter 3). It involves heating the alcohol to be... 

Metals other than ruthenium also have the potential to produce diverse DKR methods. But although some rhodium, iridium and aluminium complexes are known to catalyse the racemisation of alcohols, only a few have proved to be compatible with enzymatic reactions. In 1996, Williams and colleagues demonstrated the compatibility of enzymes and rhodium complexes by reporting the first example of racemisation of a secondary alcohol through rhodium-catalysed Oppenhauer oxidation/Meerwein Ponndorf Verley reduction with concomitant acylation of one enantiomer with a lipase from Pseudomonas fluorescens (PFL) (Scheme 4.45). ... 

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