Meerwein-Ponndorf-Verley-type reduction

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... 

Figure 1.26. Asymmetric Meerwein-Ponndorf-Verley-type reduction of ketones catalyzed by a Sm complex.

Meerwein-Ponndorf-Verley-Type Reduction Reduction of ketones by 2-propanol or related alcohols, known as Meerwein-Ponndorf-Verley (MPV) reduction, is promoted by various metal alkoxides, typically aluminum 2-propoxide [2a,d,281]. The C2 hydrogen of 2-propanol is transferred directly to the carbonyl carbon through a six-membered pericyclic transition state [284], Earlier, a stoichiometric quantity of a metal alkoxide was required for this purpose, but recently, lanthanide [285] and aluminum [286] complexes acting as excellent catalysts have been reported. 

A different approach that has been used is a ruthenium-catalyzed Meerwein-Ponndorf-Verley-type reduction of ketones using the silica-supported amino alcohol ligand 22 (Scheme 4.65). It was found necessary to cap the remaining free silica hydroxyl sites to alkylsilane derivatives to prevent catalyst deactivation. Initial studies found that slower flow rates resulted in lower ee because of equilibration back to the starting materials - after optimization, the best conditions were found to be 1400 pl/h providing a 95% conversion and 90% ee. The stability of the catalyst was investigated over time, during which a constant formation of 175 pmol/h was obtained only after a period of 7 days was some decrease in activity observed. The extended lifetime of the... 

Meerwein-Ponndorf-Verley-type reduction of carbonyl compounds and Oppe-nauer-type oxidation of allylic alcohols 69 proceed simultaneously imder the influence of a catalytic amount of Cp2ZrH2 (Eq. 28) [32a]. 

Cha, J. S., Park, J. H. Reaction of aldehydes and ketones with boron triisopropoxide. The Meerwein-Ponndorf-Verley type reduction of boron aikoxides. 1. Bull. Korean Chem. Soc. 2002, 23, 1051-1052. 

Tagliavini and Umani-Ronchi found that chiral BINOL-Zr complex 9 as well as the BINOL-Ti complexes can catalyze the asymmetric allylation of aldehydes with allylic stannanes (Scheme 9) [27]. The chiral Zr catalyst 9 is prepared from (S)-BINOL and commercially available Zr(0 Pr)4 Pr0H. The reaction rate of the catalytic system is high in comparison with that of the BINOL-Ti catalyst 4, however, the Zr-catalyzed allylation reaction is sometimes accompanied by an undesired Meerwein-Ponndorf-Verley type reduction of aldehydes. The Zr complex 9 is appropriate for aromatic aldehydes to obtain high enantiomeric excess, while the Ti complex 4 is favored for aUphatic aldehydes. A chiral amplification phenomenon has, to a small extent, been observed for the chiral Zr complex-catalyzed allylation reaction of benzaldehyde. 

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. 

A series of 2-substituted cyclohexanones was studied over a wide range of temperature in an attempt to optimize the diastereoselectivity of diisobutylaluminium phenoxides in the reduction of ketones.161 Hydride transfer dominates at high temperature, but a Meerwein-Ponndorf-Verley-type interconversion of the aluminium alcoholate intermediates (via the reactant ketone) is an important factor in diastereoselection at low temperature. 

Meerwein-Ponndorf-Verley type asymmetric reduction has also been accomplished with alkyloxy magnesium halides prepared from optically active alcohols. Optically active 2-octyloxy-2-d magnesium bromide reduced butyraldehyde to optically active n-butyl-1-d alcohol (Streitwieser, 1953). Reduction of benzaldehyde with 1-deuteroisobornyloxy magnesium halide produced optically active benzyl-l-d alcohol (Streitwieser and Wolfe, 1957 Streitwieser et al, 1959). 

The generality of schemes of this type is not clear, but it is an alternative to the e/H transfer sequences for a range of reactions in which oxidant-derived radical anions are found, including the Meerwein-Ponndorf-Verley reduction of diaryl ketones outlined above. 

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. 

Summary Meerwein-Ponndorf-Verley and Oppenauer reactions (MPVO) are catalysed by metal oxides which possess surface basicity or Lewis acidity. Recent developments include the application of basic alkali or alkaline earth exchanged X-type zeolites and the Lewis-acid zeolites BEA and [Ti]-BEA. The BEA catalysts show high stereoselectivity, as a result of restricted transition state selectivity, in the MPV reduction of substituted alkylcyclohexanones with i-PrOH. 

Aluminum alkoxides, particularly those formed from secondary alcohols, have been of interest to synthetic chemists since the mid-1920s due to their catalytic activity. Examples of these trialkoxides include aluminum isopropoxide (AIP) and aluminum sec-butoxide (ASB). They are easily prepared at lab or plant scale and provide highly selective reductions and oxidations under mild conditions. These reductions are termed Meerwein-Ponndorf-Verley (MPV) reactions after the chemists (1-3) who first investigated their utility. Because a MPV reaction are accuratelybe described as an equilibrium process, the reverse reaction (oxidation) can also be exploited. These associated reactions are termed Oppenauer oxidations (4). Meerwein-Ponndorf-Verley reductions and Oppenauer oxidations as well as other reaction types and applications will be discussed, but first some background is provided concerning structure, preparation, and characterization of aluminum isopropoxide and related compounds. 

This cleavage usually also provides, as a minor product, the ketone 3, formed by an intramolecular Meerwein-Ponndorf-Verley reduction and Oppenauer oxidation -Alkoxy ketones of this type (6) can be obtained as the major product by reduction of ketals (5) with diethylaluminum fluoride (1.2 equiv.) and pentafluorophenol (2.4 equiv.), (equation II). Note that the reduction is again effected with retention. 

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