Ponndorf-Verley Reduction

Reduction of aldehydes and ketones with aluminum isopropoxide 

The reduction of ketones to secondary alcohols and of aldehydes to primary alcohols using aluminum alkoxides is called the Meerw ein-Ponndorf-Verley reduction. The reverse reaction also is of synthetic value, and is called the Oppenauer oxidation.  

The aldehyde or ketone, when treated with aluminum triisopropoxide in isopropanol as solvent, reacts via a six-membered cyclic transition state 4. The aluminum center of the Lewis-acidic reagent coordinates to the carbonyl oxygen, enhancing the polar character of the carbonyl group, and thus facilitating the hydride transfer from the isopropyl group to the carbonyl carbon center. The intermediate mixed aluminum alkoxide 5 presumably reacts with the solvent isopropanol to yield the product alcohol 3 and regenerated aluminum triisopropoxide 2 the latter thus acts as a catalyst in the overall process  

Thus one of the transferred hydrogens conies from the aluminum reagent, and the other one from the solvent. In addition to the mechanism via a six-membered cyclic transition state, a radical mechanism is discussed for certain substrates.  

In order to shift the equilibrium of the reaction, the low boiling reaction product acetone is continuously removed from the reaction mixture by distillation. By keeping the reaction mixture at a temperature slightly above the boiling point of acetone, the reaction can then be driven to completion. 

Reduction of ketones to the corresponding alcohols using Al(0/-Pr)3 in isopropanol. 

Meerwein, H. Schmidt, R. Justus Liebigs Ann. Chem. 1925, 444, 221. Hans L. Meerwein, born in Hamburg Germany in 1879, received his Ph.D. at Bonn in 1903. In his long and productive academic career, Meerwein made many notable contributions in organic chemistry. 

Also known as Meisenheimer-Jackson salt, the stable intermediate for certain SNAr reactions. 

Meisenheimer complex (Meisenheimer-Jackson salt) Example 

Name Reactions, 4th ed., DOI 10.1007/978-3-642-01053-8 154, Springer-Verlag Berlin Heidelberg 2009 

Meerwein-Ponndorf-Verley reduction. In Name Reactions for Functional Group Transformations-, Li, J. J., Corey, E. J., Eds. John Wiley Sons Hoboken, NJ, 2007, pp 123-128. (Review). 

Name Reactions A Collection of Detailed Mechanisms and Synthetic Applications, DOI 10.1007/978-3-319-03979-4 167, Springer International Publishing Switzerland 2014 

Treatment of bicyclic epoxides with acid affords rearranged aldehydes. 

Nucleosides, Nucleotides Nucleic Acids 2000, 19, 619. 

Kurihara, T. Sakamoto, Y. Matsumoto, H. Kawabata, N. Harusawa, S. Yoneda, R. Chem. Pharm. Bull. 1994, 42, 475. 

Meerwein-Ponndorf-Verley reduction Oppenauer oxidation 

The currently accepted concerted mechanism that goes through a chairlike six-membered transition state was first proposed by Woodward. The special activity of aluminum alkoxides for the MVP reduction can be explained as a result of the activation of both the hydride donor and the hydride acceptor. For aromatic ketones the involvement of radicals was suggested, but for aliphatic carbonyl compounds there is no evidence for a SET mechanism.  

(i-PrOjsAI (large excess) /-PrOH (solvent), reflux, 5h 

The synthesis of the rare furochromone ammiol was achieved by R.B. Gammill starting from (methylthio)furochromone in four steps.The last step was the selective conversion of the aldehyde moiety of a six-membered 1,4-dicarbonyl compound using the MVP reduction. 

R = CH2Ph, CHPh2, CH2Ar, allyl R = alkyl with no (3-hydrogen, aryl R = H, alkyl, aryl R = alkyl with no p-hydrogen, aryi  

The reaction of aldehydes and ketones with aluminum isopropoxide is an equilibrium reaction which can be steered entirely in the desired direction by continuous removal of one of the products, e.g., acetone, from the reaction 

The aluminum isopropoxide is not only a catalyst but is actually the reducing agent.322 Experiments with aluminum alkoxides derived from alcohols deuter-ated on carbon323 showed that the hydrogen is transferred to the carbonyl group directly from the alkoxide without participation of the solvent thus the reaction can be carried out also in the absence of 2-propanol, by using aluminum isopropoxide in the molten state or in toluene or other hydrocarbon. 

Carbon-carbon double bonds oc9 / to the carbonyl group are not attacked, which contrasts with the results of other methods of reduction. Nitro groups, ester groups, and even activated halogen are unaffected. And a further advantage of the method is the generally good yields obtained. 

The Tishchenko reaction (see page 334) may take place as a side reaction to reduction of aldehydes, but for aliphatic aldehydes it is suppressed by using an excess of isopropoxide. Also the aldehyde may undergo an aldol condensation (see page 868) with itself or with the acetone produced. Recently the formation of 2-methyl-2,4-pentanediol as by-product was observed.361 These side reactions, however, occur only occasionally and in no way detract from the value of this method of reduction. 

The aluminum alkoxide is prepared by activating the surface of the metallic aluminum by HgCl2 or iodine and then dissolving it in the appropriate alcohol. 

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Benzhydrol (Diphenylcarbinol), (C HJ,CH OH, from Bettzo-phenone. The Meerwem-Ponndorf-Verley Reductions. 

Secondary alcohols may be oxidised to the corresponding ketones with aluminium ferf.-butoxlde (or tsopropoxlde) In the presence of a large excess of acetone. This reaction Is known as the Oppenauer oxidation and Is the reverse of the Meerweln - Ponndorf - Verley reduction (previous Section) it may bo expressed ... 

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 lithium aluminum hydride-aluminum chloride reduction of ketones is closely related mechanistically to the Meerwein-Ponndorf-Verley reduction in that the initially formed alkoxide complex is allowed to equilibrate between isomers in the... 

Knoevenagel reaction Knorr p3rrrole synthesis. Kolbe-Schmitt reaction Leuckart reaction Mannich reaction Mccrwein-Ponndorf-Verley reduction Michael reaction Oppenauer oxidation... 

We recently reported a modified Meerwein-Ponndorf-Verley reduction in which low-boiling alcohols such as EtOH and w-PrOH, but preferably i-PrOH, were used at temperatures near 225 °C in the absence of aluminum alkoxides [42]. The carbonyl moiety of an olefinic aldehyde such as cinnamaldehyde was reduced selectively to the alcohol without the carbon-carbon double bond being affected (Scheme 2.7). Since base was not present, aldol and Claisen-Schmidt condensations were avoided. 

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

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. 

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