Oppenauer Oxidation
Table of Contents
Oppenauer oxidation is an organic reaction that converts secondary alcohols into ketones. It is the reverse of the Meerwein–Ponndorf–Verley reduction. [1–4]
The reaction is named after Austrian chemist Rupert Viktor Oppenauer, who reported it in 1937.
General Reaction
The general reaction is shown in the image below. [1–5]
Because the reaction is reversible, acetone is often used in excess to shift the equilibrium toward formation of the ketone product.
Mechanism
Acetone acts as the hydride acceptor. The alcohol first forms a substrate-derived aluminum alkoxide, after which acetone coordinates to the same aluminum center. This arrangement positions the reacting groups for direct hydride transfer from the α-carbon of the substrate-derived alkoxide to the carbonyl carbon of acetone. [1–5]
The mechanism can be summarized in three steps:
Step 1: Formation of the Substrate-Derived Aluminum Alkoxide
The secondary alcohol undergoes ligand exchange with aluminum isopropoxide to form a substrate-derived aluminum alkoxide. Isopropanol is released in this reversible step.
R1R2CH−OH + Al(OiPr)3 ⇌ Al(OiPr)2(O−CHR1R2) + iPrOH
This equation is a simplified representation of the aluminum-containing species.
Step 2: Coordination of Acetone
Acetone coordinates to the same aluminum center through its carbonyl oxygen. This brings the carbonyl carbon of acetone close to the hydrogen attached to the carbon bearing the substrate alkoxide group.
Step 3: Hydride Transfer and Product Release
The coordinated reactants pass through a six-membered cyclic transition state. Hydride is transferred directly from the carbon that originally bore the hydroxyl group to the carbonyl carbon of acetone.
During this process:
- the substrate alkoxide forms a carbonyl group, producing the ketone;
- acetone is reduced to an isopropoxide ligand attached to aluminum.
No free hydride ion is released. The hydride moves directly from the substrate to acetone within the cyclic transition state.
The ketone product is then released, leaving the acetone-derived isopropoxide attached to aluminum. This regenerates aluminum isopropoxide, Al(OiPr)3.
Aqueous Workup
During the subsequent aqueous workup shown in the figure, aluminum isopropoxide is hydrolyzed. Water protonates an isopropoxide ligand, releasing 2-propanol and replacing that ligand with a hydroxyl group. The first hydrolysis step can be represented as:
Al(OiPr)3 + H2O ⟶ iPrOH + Al(OH)(OiPr)2
Further hydrolysis of the remaining isopropoxide ligands may occur when additional water is present.
