Oppenauer oxidation, named after , is a gentle method for selectively oxidizing secondary alcohols to ketones. The reaction is the opposite Meerwein–Ponndorf–Verley reduction. The alcohol is oxidized with aluminium isopropoxide in excess acetone. This shifts the equilibrium toward the product side. The oxidation is highly selective for secondary alcohols and does not oxidize other sensitive functional groups such as amines and sulfides. Though primary alcohols can be oxidized under Oppenauer conditions, primary alcohols are seldom oxidized by this method due to the competing aldol condensation of aldehyde products. The Oppenauer oxidation is still used for the oxidation of acid labile substrates. The method has been largely displaced by oxidation methods based on chromates (e.g. pyridinium chlorochromate) or dimethyl sulfoxide (e.g. Swern oxidation) or Dess–Martin oxidation due to its use of relatively mild and non-toxic reagents (e.g. the reaction is run in acetone/benzene mixtures). The Oppenauer oxidation is commonly used in various industrial processes such as the synthesis of steroids, hormones, alkaloids, terpenes, etc. Mechanism In the first step of this mechanism, the alcohol (1) coordinates to the aluminium to form a complex (3), which then, in the second step, gets deprotonated by an alkoxide ion (4) to generate an alkoxide intermediate (5). In the third step, both the oxidant acetone (7) and the substrate alcohol are bound to the aluminium. The acetone is coordinated to the aluminium which activates it for the hydride transfer from the alkoxide. The aluminium-catalyzed hydride shift from the α-carbon of the alcohol to the carbonyl carbon of acetone proceeds over a six-membered transition state (8). The desired ketone (9) is formed after the hydride transfer. Advantages An advantage of the Oppenauer oxidation is its use of relatively inexpensive and non-toxic reagents. Reaction conditions are mild and gentle since the substrates are generally heated in acetone/benzene mixtures. Another advantage of the Oppenauer oxidation which makes it unique to other oxidation methods such as pyridinium chlorochromate (PCC) and Dess–Martin periodinane is that secondary alcohols are oxidized much faster than primary alcohols, thus chemoselectivity can be achieved. Furthermore, there is no over oxidation of aldehydes to carboxylic acids as opposed to another oxidation methods such the Jones oxidation. Modifications Wettstein-Oppenauer reaction In the Wettstein-Oppenauer reaction, discovered by Wettstein in 1945, Δ 5–3β-hydroxy steroids are oxidized to Δ 4,6-3-ketosteroids with benzoquinone as the hydrogen acceptor. This reaction is useful in that it affords a one-step preparation of Δ 4,6-3-ketosteroids.