What Is Claisen Rearrangement?
The Claisen rearrangement, named after its discoverer Rainer Ludwig Claisen (1912), stands as a fundamental and powerful carbon-carbon bond-forming reaction within the realm of pericyclic chemistry. It belongs specifically to the class of [3,3]-δ-rearrangements. At its core, the reaction involves the thermal isomerization of an allyl vinyl ether to yield a γ,δ-unsaturated carbonyl compound. This transformation is characterized by its concerted mechanism (bond breaking and forming occur simultaneously), stereospecificity (stereochemical information in the starting material is transferred to the product), and high atom economy. It serves as a vital tool for constructing complex molecular architectures, particularly in natural product synthesis.
- Reagents: Lewis acid.
- Reactants: Allyl vinyl ether, allyl phenyl ether, allyl alcohol + vinyl ether precursor, allyl aryl ether, substituted allyl phenyl ethers.
- Products: γ,δ-Unsaturated carbonyl compounds, ortho-Allyl phenol (o-ALLYL-ArOH).
- Reaction Type: [3,3]-δ rearrangement.
- Related Reactions: Cope rearrangement, Carroll reaction, Johnson-Claisen rearrangement, Ireland-Claisen rearrangement, Aza-Claisen rearrangement, Thio-Claisen rearrangement.
Fig 1. Claisen rearrangement and its mechanism. [1]
Mechanism of Claisen Rearrangement
The Claisen [3,3]-σ single bond rearrangement involves heating or using a Lewis acid to transform allyl vinyl ethers into γ,δ-unsaturated carbonyl compounds via an early six-membered chair transition state. In acyclic systems, larger substituents prefer equatorial positions to minimize unfavorable 1,3-biaxial interactions. If the reaction does not favor chair formation, it may progress through a boat transition state instead.
- Concertedness: No ionic or radical intermediates are formed; all bond changes happen in a single step.
- Stereospecificity: The stereochemistry of the allyl system (E/Z geometry of the double bond, chirality of substituents) is transferred through the envelope of the transition state to the newly formed chiral centers in the product. For acyclic systems, the reaction usually proceeds with high syn diastereoselectivity relative to the migrating allyl group.
Thio-Claisen Rearrangement and Aza-Claisen Rearrangement
When the heteroatom in the reaction substrate is sulfur and nitrogen, the [3,3]-σ migration is called Thio-Claisen rearrangement and Aza-Claisen rearrangement, respectively. Compared with the classic Claisen rearrangement reaction, the Thio-Claisen rearrangement reaction of allylphenyl sulfide often requires a higher temperature. The ortho-allylthiophenol anion generated in the reaction is easy to undergo SN2 substitution reaction with the raw material to obtain a bis-allylated by-product. The Thio-Claisen rearrangement reaction of aliphatic sulfur-containing substrates is the opposite. The rearrangement reaction can occur under the mild conditions of the classic Claisen rearrangement reaction. [2]
Aza-Claisen rearrangement involves the rearrangement of allylic imidates or enolates derived from allylic amines, leading to γ,δ-unsaturated amides. It is important for nitrogen-containing molecules. It is the [3,3]-σ rearrangement of N-allyl-N-arylamine, and requires to be carried out at 250~300℃ and is often accompanied by by-products. Similarly, the conditions required for aliphatic amino-containing substrates are also relatively drastic. [3]
Fig 2. Variations of Claisen rearrangement.
Application Examples of Claisen Rearrangement
- Example 1: Asymmetric Claisen rearrangement: Christopher Uyeda et al. used a hydrogen bond donor catalyst (N,N'-diphenylguanidine ion combined with a non-coordinating BArF counterion) to achieve a variety of highly enantioselective catalytic Claisen rearrangement reactions. [4]
- Example 2: Saki Ito et al. reported a total synthesis of the anticancer natural product termicalcicolanone A. In the final stage of the synthesis, they introduced the prenyl group via a regioselective Claisen rearrangement. [5]
Fig 3. Synthetic examples via Claisen rearrangement.
Related Products
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| 1746-13-0 |  | Allyl Phenyl Ether | Inquiry |
| 1126-20-1 |  | 2-(Allyloxy)phenol | Inquiry |
| 28752-82-1 |  | 2-Allyloxybenzaldehyde | Inquiry |
| 33148-47-9 |  | 4-(Allyloxy)benzonitrile | Inquiry |
| 2079-53-0 |  | 1-[4-(ALLYLOXY)PHENYL]ETHANONE 95% | Inquiry |
| 222840-95-1 |  | 3-Allyloxyphenylboronic acid | Inquiry |
| 19530-43-9 |  | 2-(Allyloxy)-1-naphthaldehyde | Inquiry |
| 64506-49-6 |  | Sofalcone | Inquiry |
| 3917-15-5 |  | ALLYL VINYL ETHER | Inquiry |
References
- Jie Jack Li. Name Reactions-A Collection of Detailed Mechanisms and Synthetic Applications, Sixth Edition, 2021, 91-93.
- Kwart, H., et al. The Journal of Organic Chemistry, 1974, 39(11), 1575-1583.
- Bennett, Gregory B. Synthesis, 1977, 09, 589-606.
- Uyeda, Christopher, et al. Journal of the American Chemical Society, 2008, 130(29), 9228-9229.
- Ito, Saki, et al. Organic Letters, 2019, 21(8), 2777-2781.
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