Meerwein-Pondorf-Verley , ketone

The mechanism of the Meerwein-Pondorf-Verley reaction is by coordination of a Lewis acid to isopropanol and the substrate ketone, followed by intermolecular hydride transfer, by beta elimination [41]. Initially, the mechanism of catalytic asymmetric transfer hydrogenation was thought to follow a similar course. Indeed, Backvall et al. have proposed this with the Shvo catalyst [42], though Casey et al. found evidence for a non-metal-activation of the carbonyl (i.e., concerted proton and hydride transfer [43]). This follows a similar mechanism to that proposed by Noyori [44] and Andersson [45], for the ruthenium arene-based catalysts. By the use of deuterium-labeling studies, Backvall has shown that different catalysts seem to be involved in different reaction mechanisms [46]. 

Finally, /i-hydrogen transfer is the key step in the Meerwein-Pondorf-Verley (MPV) reduction of ketones by alcohols, catalyzed by aluminium alkoxides and many other catalysts. In that case, competition is not an issue, since polymerization is usually not thermodynamically favourable. The accepted mechanism for this reaction is direct transfer of the hydride from alkoxide to ketone. 

Aluminium Alkoxides and Ketones Meerwein-Pondorf-Verley Reduction... 

The Oppenauer oxidation. When a ketone in the presence of base is used as the oxidizing agent (it is reduced to a secondary alcohol), the reaction is known as the Oppenauer oxidation,95 This is the reverse of the Meerwein-Pondorf-Verley reaction (6-25), and the mechanism is also the reverse. The ketones most commonly used are acetone, butanone, and cyclohexanone. The most common base is aluminum f-butoxide. The chief advantage of the method is its high selectivity. Although the method is most often used for the preparation of ketones, it has also been used for aldehydes. 

Aluminum methoxide Al(OMe)3 is a solid which sublimes at 240 °C in vacuum. Aluminum isopropoxide melts in the range 120-140 °C to a viscous liquid which readily supercools. When first prepared, spectroscopic and X-ray evidence indicates a trimeric structure which slowly transforms to a tetramer in which the central Al is octahedrally coordinated and the three peripheral units are tetrahedral.162,153 Intramolecular exchange of terminal and bridging groups, which is rapid in the trimeric form, becomes very slow in the tetramer. There is MS and other evidence that the tetramer maintains its identity in the vapour phase.164 Al[OCH(CF3)2]3 is more volatile than Al[OCH(Me)2]3 and the vapour consists of monomers.165 Aluminum alkoxides, particularly Al(OPr )3, have useful catalytic applications in the synthetic chemistry of aldehydes, ketones and acetals, e.g. in the Tishchenko reaction of aldehydes, in Meerwein-Pondorf-Verley reduction and in Oppenauer oxidation. The mechanism is believed to involve hydride transfer between RjHCO ligands and coordinated R2C=0— A1 groups on the same Al atom.1... 

An intriguing chiral samarium complex for the Meerwein-Pondorf-Verley (MPV) reduction of ketones has been reported by Evans.100 The soluble catalyst, prepared as indicated in Figure 46, promoted the asymmetric MPV reduction of aryl methyl ketones in up to 97% ee with as little as 5 mol % loading (Figure 47). 

The Oppenauer oxidation can also afford a convenient alternative to more traditionally used oxidants. Oxidation of quinine (13) using benzophenone and KO/Bu gave the ketone in excellent yield (Figure 3.14) other oxidants were less effective [27]. This reaction can be viewed as an Oppenauer oxidation or a Meerwein-Pondorf-Verley reduction, depending on whether one considers the oxidation or the reduction to be the primary reaction. A magnesium-catalyzed Meerwein-Pondorf-Verley reduction was determined to form significant amounts of impurities in a Grignard reaction [28]. 

The reaction of a chiral alkene with borane in the proper stoichiometry may afford alkyl boranes R BH2 or dialkyl boranes R BH, where R is a chiral ligand. Attempts to achieve highly selective reductions of ketones using such reagents have met with little success, however. Trialkyl boranes R3B were first reported to reduce aldehydes and ketones (under forcing conditions) in 1966 by Mikhailov [50]. Mechanistic studies (summarized in ref. [46]) showed that there are two limiting mechanisms for the reduction of a carbonyl compound by a trialkylborane, as shown in Scheme 7.4 a pericyclic process reminiscent of the Meerwein-Pondorf-Verley reaction (Scheme 7.4a), and a two step process that involves dehydro-... 

Meerwein-Pondorf-Verley reduction is the hydrogenation in which alcohols are used as a source of hydrogen, and one of the hydrogen transfer reactions. M-P-V reduction of aldehydes, ketones and esters are efficiently catalyzed by hydrous Zr02 catalyst[18]. In these reactions, 2-propanol is the best for hydrogen source. 

An enantioselective version of the Meerwein-Pondorf-Verley (MPV) reaction was developed by Nguyen and coworkers (331-333). A combination of (i )-(- -)-2,2 -dihydroxy-l,l -biphenyl ((i )-(- -)-binol) and AlMes, in a 1 1 ratio, catalyzes the ATH of alkyl/aryl ketones, with 2-propanol as the hydride source. Reductions can be achieved in high yield (up to 99%) and enantioselectivity (up to 80% ee). 

The intermediate formed in the aluminum isopropoxide (AI[OCH(CH3)2]s) (Meerwein-Pondorf-Verley) reduction of aldehydes and ketones. Hydrolysis produces the corresponding alcohol. See this Chapter (Reduction). 

As is apparent (Table 26.33), the reduction of methylcyclohexanones (entries 1, 2, 4, 6, and 7) requires longer reaction times to achieve satisfactory conversions. This results in the equilibration of epimeric alcohols, leading to higher formation of more stable alcohols (entries 6 and 7). The isomerization is because of the intermolecular hydride transfer, which is similar to Meerwein-Pondorf-Verley reduction of ketones with aluminum alkoxides (Scheme 26.8). 

Transfer hydrogenation of ketones has its origin in Meerwein—Pondorf-Verley reduction which appeared in the mid-1920s, where the use of stoichometiic aluminium isopropoxide allowed for hydrogen transfer from propan-2-ol to a ketone [17-19], and was later introduced in its asymmetric version by Doering and Young... 

M = main group metal, e.g. Al Fig. 1 Meerwein—Pondorf—Verley reduction of ketones... 

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