What Is Meerwein-Ponndorf-Verley Reduction Reaction?
Discovered independently by Hans Meerwein, Wolfgang Ponndorf, and Albert Verley in the 1920s, Meerwein-Ponndorf-Verley (MPV) reduction is a reaction in which aldehydes or ketones are reduced to alcohols by isopropanol under the catalysis of aluminum isopropoxide. The reduction process provides excellent chemical selectivity and operates under mild conditions while remaining straightforward to perform. This reduction process fits both laboratory experiments and industrial manufacturing.
- Reagents: Aluminum alkoxide (commonly aluminum isopropoxide); Sacrificial alcohol (typically isopropanol).
- Reactants: Aldehydes or ketones.
- Products: Primary alcohols (from aldehydes) or secondary alcohols (from ketones).
- Reaction type: Reduction reaction.
- Related reaction: Oppenauer oxidation.
- Experimental tips:
a) Compared with the corresponding sodium and magnesium alcohol salts, aluminum alcohol salts are weak alcohol-aldehyde condensation reagents and are more suitable for MPV reduction.
b) Compared with aluminum ethoxide, aluminum isopropoxide has fewer side reactions and higher yields.
c) The MPV method can reduce both aliphatic aldehydes and ketones and aromatic aldehydes and ketones.
d) Compared with the acidic and catalytic reduction methods and catalytic addition methods, the MPV reduction catalyzed by aluminum isopropoxide has the characteristics of good chemical selectivity, and sensitive groups such as carbon-carbon double bonds, nitro groups, and halogens are not affected. For example, when crotonaldehyde is reduced by MPV reaction, the carbon-carbon double bond remains unchanged, and croton alcohol can be smoothly generated. When producing chloramphenicol, the MPV reaction only reduces the ketone carbonyl to a secondary alcohol, while the base is not reduced.
Fig 1. Meerwein-Ponndorf-Verley reduction reaction and its mechanism. [1]
Mechanism of Meerwein-Ponndorf-Verley Reduction
The process begins with both reactants forming complexes with aluminum atoms as Lewis acids before proceeding through a six-membered ring transition state which allows the transfer of the negative hydrogen from the α-carbon of the isopropoxide anion to the carbonyl group of the aldehyde or ketone. Simultaneously, the isopropoxide anion undergoes oxidation to acetone while the aldehyde or ketone experiences reduction to an alkoxide anion and then reacts with isopropanol to form the corresponding alcohol which results in the formation of a molecule of aluminum isopropoxide. In this reaction aluminum isopropoxide functions as a catalyst while isopropanol serves as the source of negative hydrogen.
Application Examples of Meerwein-Ponndorf-Verley Reduction
- Example 1: Timothy B. Boit et al. reported an experimental scheme for the MPV reduction of ketones under weak alkaline conditions. The transformation tolerates a variety of ketone substrates, including heterocycles containing O and S, is scalable, and shows potential as a platform for obtaining enantiomerically enriched products. [2]
- Example 2: Guodong Sun et al. reported an alternative scalable process for the synthesis of key intermediates of omarigliptin. In this synthetic strategy, the asymmetric synthesis relies on an initial diastereoselective alkylation and a subsequent aluminum-catalyzed substrate-controlled MPV reduction. This synthetic strategy has been successfully applied to multi-kilogram production. [3]
Fig 2. Synthetic examples via Meerwein-Ponndorf-Verley reduction reaction.
Related Products
References
- Jie Jack Li. Name Reactions-A Collection of Detailed Mechanisms and Synthetic Applications, Sixth Edition, 2021, 339-341.
- Boit, Timothy B., et al. Organic letters, 2019, 21(16), 6447-6451.
- Sun, Guodong, et al. Organic Process Research & Development, 2016, 20(12), 2074-2079.
