What Is Carroll Rearrangement?
The Carroll rearrangement, a [3,3]-sigmatropic rearrangement reaction, represents a powerful, thermally driven transformation within the sigmatropic rearrangement repertoire, enabling the efficient conversion of β-keto allyl esters into γ,δ-unsaturated ketones. The reaction specifically targets allyl acetoacetates or analogous β-keto esters derived from allylic alcohols. Upon heating, these substrates undergo a concerted rearrangement followed by rapid decarboxylation, yielding γ,δ-unsaturated methyl ketones (or homologs) with high efficiency. Its key distinction from the closely related Claisen rearrangement lies in the decarboxylation step, which serves as the driving force and simplifies the product.
- Reagents: Base catalysts (e.g., aluminum isopropoxide).
- Reactants: β-Keto allyl esters (e.g., allyl acetoacetate).
- Products: γ,δ-Unsaturated ketones.
- Reaction Type: [3,3]-Sigmatropic rearrangement.
- Related Reactions: Claisen rearrangement, Cope rearrangement, Ireland-Claisen rearrangement.
- Application Note: Widely used industrially for synthesizing fragrance/terpenoid intermediates (e.g., farnesylacetone for vitamin E). Asymmetric versions with chiral Pd catalysts enable quaternary carbon center formation in natural product synthesis (e.g., cyanthiwigins).
Fig 1. Carroll rearrangement and its mechanism. [1]
Mechanism of Carroll Rearrangement
- Enolization: The acidic α-proton adjacent to both the carbonyl and ester group in the β-keto ester tautomerizes to the enol form.
- [3,3]-Sigmatropic Rearrangement (The Core Step): The enol allyl ester undergoes a concerted [3,3]-sigmatropic shift. This cyclic, synchronous reorganization involves the breaking of the C-O bond of the enol ester and the formation of a new C-C bond between the former enol carbon and the terminal allylic carbon. This step results in an intermediate γ,δ-unsaturated β-keto carboxylic acid. The rearrangement proceeds through a chair-like six-membered cyclic transition state, analogous to the Cope and Claisen rearrangements. Stereochemistry is transferred stereospecifically from the allyl moiety to the product chain.
- Keto-Enol Tautomerism & Decarboxylation (Pathway A): The initial product of the sigmatropic shift is an enol form of the β-keto acid. It rapidly tautomerizes to the more stable β-keto carboxylic acid. The β-keto acid intermediate is inherently unstable under the reaction conditions (heat). It readily undergoes loss of CO2 via a cyclic, concerted mechanism (often involving an enol intermediate), yielding the final γ,δ-unsaturated ketone. This irreversible decarboxylation provides the thermodynamic driving force for the overall reaction.
- In 1980, Isao Shimizu improved this reaction by using palladium (0) as a catalyst to generate an intermediate allyl cation/carboxylate anion organometallic complex, followed by decarboxylation and allylation, to achieve a Carroll rearrangement under mild conditions (Pathway B). [2]
Application Examples of Carroll Rearrangement
- Example 1: The Carroll rearrangement of β-keto esters derived from tertiary allylic alcohols, carried out under basic conditions and followed by the decarboxylation of the resulting β-keto acids, led to the formation of γ,δ-unsaturated methyl ketones characterized by various olefin geometries ranging from 100:0 to 1:1.8 E/Z, influenced by the steric requirements of the groups at the allylic position. [3]
- Example 2: Ryoichi Kuwano et al. described the preparation of allyl α-acetylamino-β-ketocarboxylates via asymmetric decarboxylation rearrangement (Carroll rearrangement). They employed a chiral modified palladium complex catalyst with a phosphine ligand to achieve optically active γ,δ-unsaturated α-amino ketones with an enantiomeric excess of up to 90%. [4]
Fig 2. Synthetic examples via Carroll rearrangement.
Related Products
References
- Jie Jack Li. Name Reactions-A Collection of Detailed Mechanisms and Synthetic Applications, Fourth Edition, 2014, 108-109.
- Shimizu, Isao, et al. Tetrahedron Letters, 1980, 21(33), 3199-3202.
- Jung, Michael E., et al. Tetrahedron letters, 2004, 45(1), 107-109.
- Kuwano, Ryoichi, et al. Chemical Communications, 2005, 31, 3951-3952.
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