What Is Oppenauer Oxidation?
Oppenauer oxidation is the backwards version of Meerwein-Ponndorf-Verley reduction. It is a reaction in which the primary or secondary alcohols are oxidized to the aldehydes or ketones by acetone with aluminum tert-butoxide as catalyst. Other than the tert-butoxide aluminum as Lewis acid catalyst, aluminum isopropoxide, aluminum phenol etc. can also be used. Besides acetone, butanone and cyclohexanone can be used as oxidants too.
Nguyen et al. found that 3-nitrobenzaldehyde is an intense Oppenauer oxidant. With 10 mol% trimethylaluminum catalyzed, various primary or secondary alcohols easily get Oppenauer oxidation reaction. The respective aldehydes and ketones yield quantitative quantities in the majority of the cases and reaction time is only 0.5-2h.
Moreover, as catalysts for Oppenauer oxidation in addition to aluminum reagents, transition metal catalysts (ruthenium, iridium, etc.) are also useful. By way of illustration, with a catalyst of 0.1 mol% RuCl2(PPh3)3, aliphatic or aromatic secondary alcohols are easily oxidized in acetone to yield related ketones with a conversion yield of 80%-91%.
- Reagents: Aluminum tert-butoxide, aluminum isopropoxide, acetone or cyclohexanone.
- Reactants: Primary or secondary alcohols.
- Products: Aldehydes, ketones.
- Reaction type: Oxidation reaction.
- Related reactions: Meerwein-Ponndorf-Verley reduction.
Fig 1. Oppenauer oxidation reaction and its mechanism. [1]
Mechanism of Oppenauer Oxidation
Primary or secondary alcohols first undergo anion exchange with aluminum tert-butyl alcohol to generate the corresponding aluminum alcohol and a molecule of tert-butyl alcohol. Then acetone, as an oxidant, is complexed with the aluminum atom as a Lewis acid, and the negative hydrogen on the α-carbon in the alkoxy anion is transferred to the carbonyl group of acetone through a six-membered ring transition state. In this way, the alkoxide anion is oxidized to aldehyde or ketone, and acetone is reduced to isopropanol.
Reactivity of Oppenauer Oxidation
Oppenauer oxidation can oxidize both saturated and unsaturated alcohols. For instance, in aluminum isopropoxide, α-decalinol can be oxidized by acetone and derived as α-decalinone with high yield (1). In the presence of aluminum tert-butoxide, 6-methyl-nona-3,5,7-trien-2-ol can be easily oxidized with acetone to the corresponding ketone and the double bond is not affected (2).
For polyhydroxylated steroids, Oppenauer oxidation is regioselective, with the 3-hydroxyl group being oxidized more favorably (3).
The Oppenauer oxidation reaction has no effect on sensitive functional groups such as amino groups, acetal groups, and halogens in alcohol molecules. For example: under the catalysis of aluminum phenol, Yohimbine can be smoothly oxidized by cyclohexanone to obtain Yohimbinone in high yield, and the amino group in the molecule is not affected (4).
Fig 2. The reaction selectivity of Oppenauer oxidation for reactants with different functional groups. [2]
Application Examples of Oppenauer Oxidation
- Example 1: Ying Fu et al. developed a tandem triorganoaluminum addition-Oppenauer oxidation method for converting aromatic aldehydes to aromatic ketones. The triorganoaluminium reagents, prepared in situ demonstrate remarkable selectivity as organometallic compounds. Additionally, pinacolone has proven to be an effective oxidant in the tandem nucleophilic addition-Oppenauer oxidation process involving aromatic aldehydes. [3]
- Example 2: The work of Yohei Ogiwara et al. used indium (III) isopropoxide [In(OiPr)3] as a hydrogen transfer catalyst and pivalaldehyde as an oxidant to achieve the conversion of benzyl alcohol into aldehydes or ketones through Oppenauer oxidation. [4]
Fig 3. Synthetic examples via Oppenauer oxidation reaction.
Related Products
References
- Li, Jie Jack. Name Reactions: A Collection of Detailed Mechanisms and Synthetic Applications Sixth Edition, 2021, 412-414.
- Peiqiang Huang. Organic Name Reactions, Reagents and Rules, 2007, 190.
- Schobert, Rainer. Synthesis, 1987, 08, 741-742.
- Wang, Mengmeng, et al. Journal of medicinal chemistry, 2005, 48(10), 3649-3653.
