Meerwein-Ponndorf-Verley MPV Reduction

The Michael addition/Meerwein-Ponndorf-Verley (MPV) reduction sequence developed by Node and coworkers is another easily implementable strategy for the... 

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-... 

Aluminum Alkoxides and the Meerwein-Ponndorf-Verley (MPV) Reduction... 

The Meerwein-Ponndorf-Verley (MPV) reduction [236] of carbonyl moieties to produce the corresponding alcohols is usually conducted under the influence of stoichiometric or excessive amounts of Al-based catalysts, in particular Al(0 Pr)3 ... 

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 tandem 1,4-addition-Meerwein-Ponndorf-Verley (MPV) reduction allows the reduction of a, /i-unsaturated ketones with excellent ee and in good yield using a camphor-based thiol as reductant.274 The 1,4-addition is reversible and the high ee stems from the subsequent 1,7-hydride shift the overall process is thus one of dynamic kinetic resolution. A crossover experiment demonstrated that the shift is intramolecular. Subsequent reductive desulfurization yielded fiilly saturated compounds in an impressive overall asymmetric reductive technique with apparently wide general applicability. 

Recent mechanistic studies on transition metal-catalysed hydrogen transfer reactions have been reviewed. Experimental and theoretical studies showed that hydrogen transfer reactions proceed through different pathways. For transition metals, hydridic routes are the most common. Within the hydridic family there are two main groups the monohydride and dihydride routes. Experimentally, it was found that whereas rhodium and iridium catalysts favour the monohydride route, the mechanism for ruthenium catalysts proceeds by either pathway, depending on the ligands. A direct hydrogen transfer mechanism has been proposed for Meerwein-Ponndorf-Verley (MPV) reductions.352... 

Zeolite BEA is a stereoselective and regenerable heterogeneous catalyst for the Meerwein Ponndorf Verley (MPV) reduction of 4-ZerZ-butylcyclohexanone to cA-4-/er/-butylcyclohexanol (Scheme 5.41), as demonstrated by Bekkum et The cM -isomer is very important in the fragrance industry and is very difficult to obtain by other methods. 

Reduction of ketones using 2-propanol or related alcohols is referred to as Meerwein-Ponndorf-Verley (MPV) reduction [2a, 2d, 87]. Historically, metal alkox-ides, typically aluminum 2-propoxide, have been used as stoichiometric promotors for this purpose. The hydrogen migration is conceived to occur through a direct, pericyclic mechanism involving a metal alkoxide and ketonic substrate... 

Bcrkani ct al. [222] proposed the transformation of an alcohol (cyclopenianol) in the presence of a ketone (cyclohexanone) as a model reaction to characterize the acidity and the basicity of oxide catalysts (Figure 3). Actually, it is a Meerwein-Ponndorf-Verley (MPV) reduction which will be discussed in section 5. The authors found a good correlation between basicity of NaCsX zeolites or K impregnated alumina and their activities for hydrogen transfer (monitored by cyclohexanol or cyclohexene production). On the other hand, the more acidic the catalyst, the higher the dehydration extent. 

One of the chemoselective and mild reactions for the reduction of aldehydes and ketones to primary and secondary alcohols, respectively, is the Meerwein-Ponndorf-Verley (MPV) reduction. The lifeblood reagent in this reaction is aluminum isopropoxide in isopropyl alcohol. In MPV reaction mechanism, after coordination of carbonyl oxygen to the aluminum center, the critical step is the hydride transfer from the a-position of the isopropoxide ligand to the carbonyl carbon atom through a six-mem-bered ring transition state, 37. Then in the next step, an aluminum adduct is formed by the coordination of reduced carbonyl and oxidized alcohol (supplied from the reaction solvent) to aluminum atom. The last step is the exchange of produced alcohol with solvent and detachment of oxidized alcohol which is drastically slow. This requires nearly stoichiometric quantities of aluminum alkoxide as catalyst to prevent reverse Oppenauer oxidation reaction and also to increase the time of reaction to reach complete conversion. Therefore, accelerating this reaction with the use of similar catalysts is always the subject of interest for some researchers. 

In 2010, Crabtree and co-workers reported P-alkylation reaction of 1-phenylethanol (2 mmol) with benzyl alcohol was achieved by using simple alkali base KOH (2 mmol) under transition-metal free aerobic conditions, giving the corresponding ketones and alcohols in 78 and 21 %, respectively (Scheme 43) [236]. The reaction proceeded by an Oppenauer oxidation of these alcohols to give the ketone and aldehyde. Subsequently, base-assisted aldol reaction followed by Meerwein— Ponndorf—Verley (MPV) reduction and isomerization gave the p-alkylated products. 

Although the Meerwein-Ponndorf-Verley (MPV) reduction was discovered over 80 years ago, it has not been until relatively recently that catalytic variants utilising chiral aluminium have been realised. " In 2002, the Nguyen group reported a practical, enantioselective catalytic MPV reduction. Isopropanol was used as the hydride source, and trimethylaluminium with (R)-BINOL as the catalyst (Scheme 19.54). ... 

Meerwein-Ponndorf-Verley (MPV) reduction is one of the most popular synthetic reactions with Al(Oi-Pr)3 [72, 73]. Since this reaction is reversible, retro reaction, which is known as Oppenauer oxidation, is also used [74, 75]. 

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