Ketones Meerwein-Ponndorf-Verley reduction

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... 

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 ... 

As shown in Figure 1.26, a chiral Sm(III) complex catalyzes asymmetric reduction of aromatic ketones in 2-propanol with high enantioselectivity. Unlike other late-transition-metal catalysis, the hydrogen at C2 of 2-propanol directly migrates onto the carbonyl carbon of substrate via a six-membered transition state 26A, as seen in the Meerwein-Ponndorf-Verley reduction. ... 

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

In this way, an aldehyde or ketone could be reduced to the corresponding alcohol after hydrolysis of the resulting aluminium alkoxide. This reaction is known as the Meerwein-Ponndorf-Verley reduction. 

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

The aluminium-catalyzed hydride shift from the a-carbon of an alcohol component to the carbonyl carbon of a second component, which proceeds over a six-membered transition state, is named Meerwein-Ponndorf-Verley-Reduction (MPV) or Oppenauer Oxidation (OPP) depending on the isolated product. If aldehydes or ketones are the desired products, the reaction is viewed as the Oppenauer Oxidation. 

Among the hydrogen transfer reactions, the Meerwein-Ponndorf-Verley reduction and its counterpart, the Oppenauer oxidation, are undoubtedly the most popular. These are well-established selective and mild redox reactions and they have been studied extensively [4, 5]. Nevertheless, traditional Meerwein-Ponndorf-Verley-Oppenauer (MPVO) reactions have some drawbacks, as they usually suffer from poor reactivity of the traditional Al(OiPr)3/iPrOH system, for which continuous removal of the produced acetone is necessary in order to shift the equilibrium between reduction of the ketone and oxidation of the donor alcohol. 

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. 

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... 

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. 

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. 

Only one study has suggested the formation of an actinide(IID alkoxide (-OR) compound in which R is an alkyl. A recent investigation of the reactivity of Pu wo-propoxide, prepared in situ from the reaction of Pu[N(SiMe3)2]3 and three equivalents HOPr , indicates that the trivalent alkoxide complex is an effective catalyst in the Meerwein-Ponndorf-Verley reduction of ketones by isopropanol. ... 

Kinetic studies of the Midland reduction confirmed that the reduction of aldehydes is a bimolecular process and the changes in ketone structure have a marked influence on the rate of the reaction (e.g., the presence of an EWG in the para position of aryl ketones increases the rate compared to an EDG in the same position). However, when the carbonyl compound is sterically hindered, the rate becomes independent of the ketone concentration and the structure of the substrate. The mechanism with sterically unhindered substrates involves a cyclic boatlike transition structure (similar to what occurs in the Meerwein-Ponndorf-Verley reduction). The favored transition structure has the larger substituent (Rl) in the equatorial position, and this model correctly predicts the absolute stereochemistry of the product. 

Meerwein-Ponndorf-Verley reduction The reduction of aldehydes and ketones by metal alkoxides to the corresponding alcohols 280... 

Okano, T., Matsuoka, M., Konishi, H., Kiji, J. Meerwein-Ponndorf-Verley reduction of ketones and aldehydes catalyzed by lanthanide tri-2-propoxides. Chem. Lett. 1987, 181-184. 

Node, M., Nishide, K., Shigeta, Y., Shiraki, H., Obata, K. A Novel Tandem Michael Addition/Meerwein-Ponndorf-Verley Reduction Asymmetric Reduction of Acyclic a,P-Unsaturated Ketones Using A Chiral Mercapto Alcohol. J. Am. Chem. Soc. 2000, 122,1927-1936. 

The Meerwein-Ponndorf-Verley reduction of carbonyl compounds and the Oppenauer oxidation of alcohols, together denoted as MPVO reactions, are considered to be highly selective reactions. For instance, C=C double bonds are not attacked. In MPV reductions a secondary alcohol is the reductant whereas in Oppenauer oxidations a ketone is the oxidant. It is generally accepted that MPVO reactions proceed via a complex in which both the carbonyl and the alcohol are coordinated to a Lewis acid metal ion after which a hydride transfer from the alcohol to the carbonyl group occurs (Fig. 1) [1]. Usually, metal ec-alkoxides are used as homogeneous catalysts in reductions and metal t-butoxides in oxidations [1]. 

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. 

Kinetically controlled conditions are not easily maintained in the Meerwein-Ponndorf-Verley reduction of less reactive a,/ -unsaturated or hindered ketones and the thermodynamically more stable equatorial alcohols become the major products. Thus, Meerwein-Ponndorf-Verley reduction of 5a-cholest-l-ene-3-one using aluminum isopropoxide in isopropanol is reduced to a 1 9 mixture of 3a- and 3/ -alcohols180 (see also ref 181) [d.r. [(3S)/(3/ )] 10 90. ... 

In many cases, bridged polycyclic ketones react relatively slowly in the Meerwein-Ponndorf-Verley reduction and the thermodynamic equilibrium is obtained using aluminum isopropoxide in boiling isopropanol. The equilibrium depends on the substituents (see refs 5, 183 and 184). 

The Meerwein-Ponndorf-Verley reduction of aldehydes and ketones and its reverse, the Oppenauer oxidation of alcohols, are hydrogen-transfer reactions that can be performed under mild conditions and without the risk of reducing or oxidizing other functional groups [1]. The hydrogen donors are easily oxidizable secondary alcohols (e. g. i-PrOH) and the oxidants are simple ketones (e. g. cyclohexanone). Industrial applications of the MPVO reactions are found in the fragrance and pharmaceutical industries, for example. 

The Meerwein-Ponndorf-Verley reduction is so named because of the simultaneous and independent contributions from the labs of Meerwein, Ponndorf and Verley. The first report to appear in the literature was from Meerwein and Schmidt in 1925 who showed that an aldehyde could be reduced to a primary alcohol by Al(OEt)3 in an ethanolic medium.4 Independently, Verley demonstrated that butyraldehyde could be reduced by geraniol and Al(OEt)3.5 The following year, Ponndorf extended this reaction to include the reduction of ketones by using an easily oxidized secondary alcohol, such as i-PrOH, as the hydride source and Al(Oi-Pr)3 as the metal catalyst.6... 

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. 

A route to chiral alcohols from enones relies on stereoselective hydride transfer (Meerwein-Ponndorf-Verley reduction) from the isobomeol moiety after the substrates are attached to the monoterpene skeleton through Michael reaction with a 10-thiol group. Aromatic ketones are reduced by the system of t-BuOK- -PrOH and 91. ... 

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