Rubottom oxidation
| Rubottom oxidation | |
|---|---|
| Named after | George M. Rubottom |
| Reaction type | Organic redox reaction |
| Identifiers | |
| Organic Chemistry Portal | rubottom-oxidation |
The Rubottom oxidation is a useful, high-yielding chemical reaction between silyl enol ethers and peroxyacids to give the corresponding α-hydroxy carbonyl product. The mechanism of the reaction was proposed in its original disclosure by A.G. Brook with further evidence later supplied by George M. Rubottom. After a Prilezhaev-type oxidation of the silyl enol ether with the peroxyacid to form the siloxy oxirane intermediate, acid-catalyzed ring-opening yields an oxocarbenium ion. This intermediate then participates in a 1,4-silyl migration (Brook rearrangement) to give an α-siloxy carbonyl derivative that can be readily converted to the α-hydroxy carbonyl compound in the presence of acid, base, or a fluoride source.
In 1974, three independent groups reported on the reaction now known as the Rubottom oxidation. A.G Brook from the University of Toronto, was the first to report the reaction on June 10, followed by A. Hassner from the University of Colorado, Boulder on Sept. 4, and G.M. Rubottom from the University of Puerto Rico on Sept. 24. There was a considerable amount of precedent for this type of chemistry in the literature leading up to the seminal publications in 1974. For instance, it was known as early as the 1930s that highly enolizable β-dicarbonyl compounds would react with peroxyacids, although it was not until the 1950s and 60s α-hydroxy β-dicarbonyl compounds were in fact the product.
There was also a considerable amount of work, led by A.G Brook, during the 1950s on elucidating the mechanisms of organosilicon migrations, which are now known as Brook Rearrangements. Finally, in March 1974, C.H. Heathcock from the University of California, Berkeley published a paper on the treatment of silyl enol ethers with ozone to give a carboxylic acid product via oxidative cleavage where silyl migrations were observed as side reactions and exclusively in the case of a bicyclic system.
Each of the seminal reports of the Rubottom oxidation featured the peroxyacid meta-chloroperoxybenzoic acid (mCPBA) as the oxidant in dichloromethane (DCM), in the case of Hassner and Brook, and hexanes for Rubottom. While the reaction has been tweaked and modified since 1974, mCPBA is still commonly used as the oxidant with slightly more variation in the solvent choice. Today, DCM is the most common solvent followed by various hydrocarbon solvents including pentane and toluene. Notably, the reaction proceeds at relatively low temperatures and heating beyond room temperature is not necessary. Low temperatures allow the standard Rubottom oxidation conditions to be amenable with a variety of sensitive functionalities making it ideal for complex molecule synthesis (See synthetic examples below). Silyl enol ether substrates can be prepared regioselectively from ketones or aldehydes by employing thermodynamic or kinetic control to the enolization prior to trapping with the desired organosilicon source (usually a chloride or triflate e.g. TBSCl or TBSOTf). As illustrated by the synthetic examples below, silyl enol ethers can be isolated prior to exposure to the reaction conditions, or the crude material can be immediately subjected to oxidation without isolation. Both acyclic and cyclic silyl enol ether derivatives can be prepared in this way and subsequently be used as substrates in the Rubottom oxidation. Below are some representative Rubottom oxidation products synthesized in the seminal papers.
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