Reduction Meerwein Ponndorf-Verley reaction

Smis assisted version of this reduction has been reported. The Meerwein-Ponndorf-Verley reaction usually ... 

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. 

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. 

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... 

While the use of zeolites as catalysts for C=0 reduction with alcohols as a reductant goes back to the eighties, stereoselective versions of this reaction have been developed more recently. In this so-called MPV (Meerwein-Ponndorf-Verley) reaction, the reactant carbonyl compound and the reducing alcohol coordinate simultaneously on a Lewis acid centre. In the reduction of 4-t-butylcyclohexanone, the trans product would normally be thermodynamically favored. However, the cis alcohol isomer is economically much more interesting. Van Bekkum and coworkers discovered that in the constrained pores of an Al- or Ti-Beta zeolite, more than 95 % of the product has the cis configuration (59) ... 

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. 

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. 

The deviation from Cram s rule has been attributed to the cyclic nature of the transition state of the Meerwein-Ponndorf-Verley reaction129. The situation may be further complicated by hydride transfer from external aluminum isopropoxide units not involved in the cyclic six-mem-bered transition state49,5S-13°. These competitive mechanistic pathways (external vs internal hydride transfer) depend on the experimental conditions (concentrations of reactants etc.). These have also been observed in the reduction of cyclic 1,2-diones where an internal hydride transfer to the intermediate a-hydroxy ketones may be sterically hindered. In these cases the stereochemical outcome of Meerwein-Ponndorf-Verley reactions cannot be definitely predicted. 

This reaction was first reported concurrently by Meerwein and Schmidt and Verley in 1925, and by Ponndorf in 1926, respectively. It is an aluminum alkoxide-catalyzed reduction of carbonyl compounds (ketones and aldehydes) to corresponding alcohols using another alcohol (e.g isopropanol) as the reducing agent or hydride source. Therefore, it is generally known as the Meerwein-Ponndorf-Verley reduction (MPV) or Meerwein-Ponndorf-Verley reaction. Occasionally, it is also referred to as the Meerwein-Ponndorf reduction, Meerwein-Ponndorf reaction, or Meerwein-Schmidt-Ponndorf-Verley reaction. About 12 years later, Oppenauer reported the reversion of this reaction in which alcohols were reversely oxidized into carbonyl compounds. Since then, the interchanges between carbonyl compounds and alcohols in the presence of aluminum alkoxide are generally called the Meerwein-Ponndorf-Oppenauer-Verley reduction or Meerwein-Ponndorf-Verley-Oppenauer reaction." ... 

The main feature of the Meerwein-Ponndorf-Verley reaction pathway involves the coordination of both reactants to the Lewis-acid metal eentre and hydride transfer from the alcohol to the earbonyl group. Aluminium or titanium alkoxides are usually effective homogeneous catalysts. With tin-Beta catalyst, cyclohexanone reduction with 2-butanol led selectively to cyclohexanol at 100 °C. Ketone conversion was >95%, whereas silicon-Beta, Sn02/Si02 and SnCl4 -5H20 were inaetive under the same experimental conditions. Therefore, the activity is likely due to tetrahedral tin in the zeolite framework, and not to extra-framework tin or to leached tin. ... 

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. 

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... 

The Meerwein-Ponndorf-Verley (MPV) reduction is generally mediated by aluminum triiso-propoxide, Al(01Pr)3. In MPV reduction, reversible hydride transfer occurs via a six-membered transition state (Scheme 67). By removing acetone from the reaction system, the reversible reaction proceeds smoothly. The advantages of the reduction are the mildness of the reaction conditions, chemoselectivity, safety, operational simplicity, and its applicability to large-scale synthesis. It is reported that the addition of trifluoroacetic acid, significantly accelerates the reduction (Scheme 68) 304,305 in which case a catalytic amount of Al(0 Pr)3 is enough to complete the reaction. 

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

In the fourth and final chapter, Howard Haubenstock discusses asymmetric reduction of organic molecules. Within this general topic of wide and continuing interest, Haubenstock s chapter deals with chiral derivatives of lithium aluminum hydride, their preparation from suitable amino or hydroxy compounds, and their use in reducing carbonyl groups. Related reactions of the Meerwein-Ponndorf-Verley type or involving tri-alkylaluminum reagents are also presented. 

The Meerwein-Ponndorf-Verley reduction (reduction with aluminum alkoxides). Wilds, A.L., Org. Reactions 2, 178 (1944). 

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