Claisen Rearrangement

What is Claisen Rearrangement?

Claisen rearrangement is an organic chemical reaction that offers a powerful method in the formation of carbon-carbon bonds. The reactant of this reaction – allyl vinyl ether, is converted into a gamma, delta-unsaturated carbonyl compound when subjected to heat or a Lewis acid.

The Claisen rearrangement reaction is named after its discoverer, the German chemist Rainer Ludwig Claisen, who discovered it in 1912. This reaction belongs to the “sigmatropic rearrangement” category of reactions wherein the mechanism of the reaction is concerted (i.e. all the bonds break and form simultaneously).

An interesting fact about this reaction is that it was the first ever recorded example of a [3,3]- sigmatropic rearrangement reaction.

An example for the Claisen rearrangement reaction of an allyl vinyl ether is given below.

Claisen Rearrangement Reaction

Claisen Rearrangement Example for Allyl Vinyl Ether

The reaction can also be performed with allyl phenyl ethers. In this rearrangement, the regioselectivity is affected by the meta-substitution. The [3,3]-sigmatropic rearrangement of the allyl phenyl ether gives an intermediate. This intermediate now undergoes tautomerization to give a phenol which is substituted at the ortho position. An example for the [3,3]-sigmatropic rearrangement of an allyl phenyl ether is given below.

Claisen Rearrangement Example

Claisen Rearrangement Example for Allyl Phenyl Ethers

Mechanism of Claisen Rearrangement

This rearrangement reaction has an exothermic nature. As discussed earlier, the reaction mechanism is concerted. The reaction kinetics of this rearrangement reaction is of the first order. The reaction is accelerated by polar solvents. Hydrogen-bonding solvents provide further acceleration of reaction speed and greater rate constants.

1. Allyl Vinyl Ethers

Here, heat is the catalyst of the reaction. When the allyl vinyl ether is subjected to heat, it forms a transition state. Now, a [3,3]-sigmatropic rearrangement takes place leading to the formation of the required gamma,delta-unsaturated carbonyl compound product.

This mechanism is illustrated below.

Claisen Rearrangement Mechanism

Claisen Rearrangement Mechanism Allyl Vinyl Ether

2. Allyl Phenyl Ethers

The electrons are pushed around the six-membered ring in an electrocyclic process. The resulting dienone now undergoes tautomerization to give its aromatic enol form. This form is more stable than the dienone form. The required compound is therefore formed.

This mechanism can be illustrated as follows.

Claisen Rearrangement Mechanism

Claisen Rearrangement Mechanism Allyl Phenyl Ethers

Thus, the required gamma,delta-unsaturated carbonyl compounds are generated from the Claisen rearrangement of allyl vinyl ethers or allyl phenyl ethers.

Variations of Claisen Rearrangement

In addition to the classical allyl vinyl ether rearrangement, several variations have been developed which improve the synthetic value of the Claisen rearrangement with respect to the preparation of the parent compounds, reaction conditions and stereoselectivity.

The most popular variants are tabulated below.

Aromatic Claisen rearrangement The [3,3]-sigmatropic rearrangement of aryl allyl ethers is called the aromatic Claisen rearrangement. The transition state structures for the aromatic Claisen rearrangement have been calculated by the molecular orbital method.
Bellus–Claisen rearrangement It is the cycloaddition of ketene and allylic ether. The presence of unsaturated ester in the product mixture along with the expected product led to the rationale which forms zwitterionic intermediate resulting from the trapping of ketene by the ether oxygen.
Eschenmoser–Claisen rearrangement Condensation of with allylic alcohols followed by loss of a second equivalent of methanol gives ketene N, O-acetals, which undergo 3,3-sigmatropic rearrangement to afford γ,δ-unsaturated amides. It proceeds at lower temperatures with higher yields.
Ireland–Claisen rearrangement This method is widely used in the synthesis of a diverse range of natural products and other targets because of the ease of preparation of the allylic ester reactants and the ability to control the E/Z geometry.
Johnson–Claisen rearrangement This method is also called the orthoester Claisen rearrangement, involves the reaction of allylic alcohol with an orthoester, often triethyl orthoacetate, in the presence of a carboxylic acid such as propionic acid usually at lower temperatures. The intermediate ketene acetal rearranges stereoselectivity.
Photo-Claisen rearrangement Photo-Claisen rearrangement is a relatively new concept in photochemistry. It is a novel approach to the total synthesis of kendomycin makes use of the photo-Fries rearrangement as a key step.

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