4. Claisen Rearrangement
History
The Claisen rearrangement (not to be confused with the Claisen condensation) is discovered by Rainer
Ludwig Claisen 1912. [1]
Definition
The heating of an allyl vinyl ether will initiate a [3, 3]-sigma tropic rearrangement to give a γ, δ-unsaturated
carbonyl. [2]
Examples
This reaction is used for the rearrangement of allyl vinyl ether and allyl aryl ether like allyl phenyl ether..[3]
5. Mechanism of reaction:
The mechanism of this reaction closely resembles that of the Diels-Alder reaction.
Proton Tatumerism is expected in this reaction, where a proton is removed from one site in
the molecule and placed at a different nearby sit. [4]
1. Allyl vinyl ether:
Breakage of central C- C Bond and rearrangement of two 3 carbon allyl fragment through an
intermediate state. [5]
2. Allyl phenyl ether:
An electro cyclic process pushes those electrons around the six membered rings.
The resulting dienone now undergoes tautomerization to give more stable aromatic phenol.
Thus, the required compound is formed. [6]
6. Step 1.
An electro cyclic process pushes those electrons around the six membered rings.
Step 2.
Tautomerization of the dienone to give more stable aromatic phenol.
7. Variations of Claisen Rearrangement
In addition to the classical allyl vinyl ether rearrangement, several variations have been developed
which Compounds, reaction conditions and stereo selectivity. [7]
1. Ireland–Claisen rearrangement
The Ireland–Claisen rearrangement is the reaction of an allylic carboxylate with a strong base
(such as lithium disopropylamide) to give a γ, δ-unsaturated carboxylic acid.
The rearrangement proceeds via silylketene acetal, which is formed by trapping the lithium
enolate with chlorotrimethylsilane. [8]
Example:
8. 2. Johnson-Claisen rearrangement
Also known as: ortho ester Claisen rearrangement
The Johnson-Claisen rearrangement is an organic reaction where an allylic alcohol is heated
with trialkyl orthoacetate under mild acidic conditions to produce a γ, δ-unsaturated ester.
The reaction begins with protonation of one of the alkoxide groups of the orthoacetate. [10]
Example:
10. 3. Eschenmoser-Claisen Rearrangement
In 1964 the Swiss chemist Albert Eschenmoser reported that allylic or benzylic alcohols heated in
the presence of N, N-dimethylacetamide dimethyl acetal.
This generated a γ, δ-unsaturated amide with a high level of stereo specificity, and today this
transformation has become known as the Eschenmoser - Claisen rearrangement. [11]
Example:
Synthetic Applications:
i. Synthesis of o-Eugenol:
Since aryl allyl ethers can be easily prepared, the rearrangement is employed to prepare various
kinds of compounds, e.g.
11. ii. Synthesis of Prephenate :
The enzyme chorismate mutase catalysis the Claisen rearrangement of chorismate to
Prephenate, a key intermediate in the shikimate pathway.
