Meerwein–Ponndorf–Verley reduction

The Meerwein–Ponndorf–Verley (MPV) reduction in

Figure 1, Exchange of carbonyl oxidation states in the presence of aluminium isopropoxide.

The MPV reduction was independently discovered by Albert Verley and the team of

The MPV reduction is believed to go through a catalytic cycle involving a six-member ring transition state as shown in Figure 2. Starting with the aluminium alkoxide 1, a carbonyl oxygen is coordinated to achieve the tetra coordinated aluminium intermediate 2. Between intermediates 2 and 3 the hydride is transferred to the carbonyl from the alkoxy ligand via a pericyclic mechanism. At this point the new carbonyl dissociates and gives the tricoordinated aluminium species 4. Finally, an alcohol from solution displaces the newly reduced carbonyl to regenerate the catalyst 1.

Figure 2, Catalytic cycle of Meerwein–Ponndorf–Verley reduction

Each step in the cycle is reversible. The reaction is driven by the thermodynamic properties of the intermediates and the products. Several other mechanisms have been proposed for this reaction, including a radical mechanism as well as a mechanism involving an aluminium hydride species. The commonly accepted direct hydride transfer is supported by experimental and theoretical data.^[6]

Chemoselectivity

One of the great draws of the Meerwein–Ponndorf–Verley reduction is its chemoselectivity. Aldehydes are reduced before ketones allowing for a measure of control over the reaction. If it is necessary to reduce one carbonyl in the presence of another, the common carbonyl protecting groups may be employed. Groups, such as alkenes and alkynes, that normally pose a problem for reduction by other means have no reactivity under these conditions.^[7]

Stereoselectivity

The aluminium based Meerwein–Ponndorf–Verley reduction can be performed on

One method of achieving the asymmetric MPV reduction is with the use of chiral hydride donating alcohols. The use of chiral alcohol (R)-(+)-sec-o-bromophen-ethyl alcohol gave 82%ee (percent

Figure 3, Transition states of MPV reduction with a chiral alcohol

The use of an intramolecular MPV reduction can give good enantiopurity.^[9] By tethering the ketone to the hydride source only one transition state is possible (Figure 4) leading to the asymmetric reduction. This method, however, has the ability to undergo the reverse Oppenauer oxidation due to the proximity of the two reagents. Thus the reaction runs under thermodynamic equilibrium with the ratio of the products related to their relative stabilities. After the reaction is run the hydride-source portion of the molecule can be removed.

Figure 4, Transition state of intramolecular MPV reduction

Chiral

Figure 5, MPV reaction with chiral ligand

Scope

Several problems restrict the use of the Meerwein–Ponndorf–Verley reduction compared to the use of other reducing agents. The stereochemical control is seriously limited. Often a large amount of aluminium alkoxide is needed when using commercial reagent, and there are several known side reactions.

While commercial aluminium isopropoxide is available, the use of it often requires catalyst loadings of up to 100-200 mol%. This hinders the use of the MPV reduction on scale. Aluminium alkoxides made in situ from

Work has been done in the use of lanthanides and transition metals for the Meerwein–Ponndorf–Verley reduction. Both ruthenium and samarium have shown high yields and high stereoselectivity in the reduction of carbonyls to alcohols.^[13][14] The ruthenium catalyst has been shown, however, to go through a ruthenium hydride intermediate. The Meerwein–Ponndorf–Verley reduction has also been effected with synthetically useful yield by plutonium (III) isopropoxide.^[15]

The standard MPV reduction is a homogeneous reaction several heterogeneous reactions have been developed.^[16]

See also

• Oppenauer oxidation
• Carbonyl reduction

References