Meerwein-Ponndorf-Verley reduction catalytic

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. 

Evans reported an enantioselective Meerwein-Ponndorf-Verley reduction using a catalytic amount of chiral samarium complex 26 prepared from samarium (III) iodide and a chiral amino diol (Scheme 9.16) [34], Even when a partially resolved ligand (80% ee) was used, the enantiopurity of the resulting alcohol 27 reached 95% ee, which is the same value as that obtained when the enantiopure amino diol was used. 

Catalytic reduction of unsymmetrical ketones into alcohols by concomitant oxidation of 2-propanol to acetone (Meerwein-Ponndorf-Verley reduction, MPV), with rhodium... 

Catalytic Oppenauer oxidations (Eq. 28) and Meerwein-Ponndorf-Verley reductions (Eq. 29) were studied in detail [232,234]. The gadolinium derivative, employed in situ without elimination of LiCl, was reported to be ten times more reactive in the MPV reduction of cyclohexanone as the standard reagent Al(OiPr)3 [235]. 

Lanthanide alkoxide complexes have been shown to promote a number of useful chemical reactions, whereby the complex is used catalytically or applied in stoichiometric amount. One such reactions is the Meerwein-Ponndorf-Verley reduction (MPV) or the Oppenauer oxidation, depending on which component is the desired product (Equation 6.5). If the alcohol is the desired product, the reaction is viewed as Meerwein-Ponndorf-Verley Reduction [43]. 

A simultaneous reduction-oxidation sequence of hydroxy carbonyl substrates in the Meerwein-Ponndorf-Verley reduction can be accomplished by use of a catalytic amount of (2,7-dimethyl-l,8-biphenylenedioxy)bis(dimethylaluminum) (8) [33], This is an efficient hydride transfer from the sec-alcohol moiety to the remote carbonyl group and, because of its insensitivity to other functionalities, should find vast potential in the synthesis of complex polyfunctional molecules, including natural and unnatural products. Thus, treatment of hydroxy aldehyde 18 with 8 (5 mol%) in CH2CI2 at 21 °C for 12 h resulted in formation of hydroxy ketone 19 in 78 % yield. As expected, the use of 25 mol% 8 enhanced the rate and the chemical yield was increased to 92 %. A similar tendency was observed with the cyclohexanone derivative. It should be noted that the present reduction-oxidation sequence is highly chemoselective, and can be utilized in the presence of other functionalities such as esters, amides, rert-alco-hols, nitriles and nitro compounds, as depicted in Sch. 10. 

Although bidentate Lewis acids still remain poorly studied, it is increasingly difficult to dismiss them as esoteric reagents of mere academic interest because truly efficient and useful synthetic applications have recently appeared. The authors reported a new catalytic Meerwein-Ponndorf-Verley reduction [60,61 ] system based on the bidentate Lewis acid chemistry [62]. Treatment of benzaldehyde with (2,7-dimethyl-l,8-biphe-nylenedioxy)bis(diisopropoxyaluminum) (57) at room temperature instantaneously produced the reduced benzyl alcohol almost quantitatively (entry 2, Table 1-10). Moreover, even with 5 mol% of the catalyst 57 the reduction proceeds quite smoothly at room temperature to furnish benzyl alcohol in 81 % yield after 1 h (entry 3, Table 1-10). This remarkable efficiency can be ascribed to the double electrophilic activation of carbonyls by the bidentate aluminum catalyst (Scheme 1-21). 

Scheme 1-21. Catalytic Meerwein-Ponndorf-Verley reduction of carbonyl compounds with bidentate aluminum alkoxides.

A simultaneous reduction/oxidation sequence of hydroxy carbonyl substrates in the Meerwein-Ponndorf-Verley reduction can be accomplished by use of a catalytic amount of (2,7-dimethyl-l,8-biphenylenedioxy)bis(dimethylaluminum) (49). This represents an efficient hydride transfer from the sec-alcohol moiety to the remote carbonyl group and, due to its insensitivity to other functionalities, should find vast potential in the synthesis of complex polyfunctional molecules including both natural... 

An interesting example of catalytic domino reaction is the synthesis of an ether fragrance reported by Corma and Renz [343] using either Sn-beta or Zr-beta, although the latter is preferable, giving at 100 °C (8h) complete conversion with virtually 100% overall selectivity, while the Sn-beta is equally selective but less active. Figure 2.69 reports the scheme of this reaction. In a first step, the alcohol is produced by a Meerwein-Ponndorf-Verley reduction at 100 °C. 

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. 

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. 

Catalytic Asymmetric Meerwein-Ponndorf-Verley Reduction of Ketones... 

Scheme 13.38 Catalytic asymmetric Meerwein-Ponndorf-Verley reduction.

New methods of synthesis of samarium alkoxides catalytically active in Meerwein-Ponndorf-Verley reductions and Oppenauer oxidations resulted from careful reexamination of diiodosamarium-promoted alkylations of alddiydes (Namy et al., 1984). 

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. 

The use of Al(III) complexes as catalysts in Lewis acid mediated reactions has been known for years. However, recent years have witnessed interesting developments in this area with the use of ingeiuously designed neutral tri-coordinate Al(lll) chelates. Representative examples involving such chelates as catalysts include (1) asymmetric acyl halide-aldehyde cyclocondensations, " (2) asymmetric Meerwein-Schmidt-Ponndorf-Verley reduction of prochiral ketones, (3) aldol transfer reactions and (4) asymmetric rearrangement of a-amino aldehydes to access optically active a-hydroxy ketones. It is important to point out that, in most cases, the use of a chelating ligand appears critical for effective catalytic activity and enantioselectivity. 

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]. 

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. 

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