The Claisen rearrangement (not to be confused with the Claisen condensation) is a powerful carbon-carbon bond-forming chemical reaction discovered by Rainer Ludwig Claisen. The heating of an allyl vinyl ether will initiate a [3,3]-sigmatropic rearrangement to give a g,d-unsaturated carbonyl.

Discovered in 1912, the Claisen rearrangement is the first recorded example of a [3,3]-sigmatropic rearrangement.
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== Mechanism ==
The Claisen rearrangement is an exothermic (about 84 kJ mol-1), concerted pericyclic reaction which according to the Woodward-Hoffmann rules shows a suprafacial reaction pathway. Crossover experiments eliminate the possibility of the rearrangement occurring via an intermolecular reaction mechanism and are consistent with an intramolecular process, now understood as a [3,3]-electrocyclic reaction.
There are substantial solvent effects in the Claisen reactions. More polar solvents tend to accelerate the reaction to a greater extent. Hydrogen-bonding solvents gave the highest rate constants. For example, ethanol/water solvent mixtures give rate constants 10-fold higher than sulfolane.
Trivalent organoaluminium reagents, such as trimethylaluminium, have been shown to accelerate this reaction.


== Variations ==


=== Aromatic Claisen rearrangement ===
The aromatic variation of the Claisen rearrangement is the [3,3]-sigmatropic rearrangement of an allyl phenyl ether to an intermediate which quickly tautomerizes to an ortho-substituted phenol.

Meta-substitution affects the regioselectivity of the ortho rearrangement. With the meta constituent in the 3rd position, electron withdrawing functional groups, such as bromide, move the side-chain to the 2nd position (71% of products) while electron donating groups, such as methoxy, shift it to the 6th position (69% of products). If ortho-position is substituted then reaction goes to para position with retention in configuration.

Additionally if an aldehyde or carboxylic acid occupies the substituted position the allyl side-chain displaces the group, releasing it quantitatively as carbon monoxide or carbon dioxide respectively.


=== Bellus-Claisen rearrangement ===
The Bellus-Claisen rearrangement is the reaction of allylic ethers, amines, and thioethers with ketenes to give g,d-unsaturated esters, amides, and thioesters.


=== Eschenmoser-Claisen rearrangement ===
The Eschenmoser-Claisen rearrangement proceeds from an allylic alcohol to a g,d-unsaturated amide, and was developed by Albert Eschenmoser in 1964.

Mechanism:


=== Ireland-Claisen rearrangement ===

The Ireland-Claisen rearrangement is the reaction of an allylic acetate with strong base (such as Lithium diisopropylamide) to give a g,d-unsaturated carboxylic acid. The actual rearrangement occurs from the enolate of the ester--this is the structural analog of the simple alkene in the original Claisen rearrangement.

Mechanism:


=== Johnson-Claisen rearrangement ===
The Johnson-Claisen rearrangement is the reaction of an allylic alcohol with an orthoester containing a deprotonatable alpha carbon (e.g. triethyl orthoacetate) to give an g,d-unsaturated ester.

Mechanism:


=== Photo-Claisen rearrangement ===
The photo-Claisen rearrangement is closely related to the photo-Fries rearrangement, proceeding by a similar mechanism. Aryl ethers undergo the photo-Claisen, while the photo-Fries is experiences by aryl esters.


== Hetero-Claisens ==


=== Aza-Claisen ===
An iminium can serve as one of the pi-bonded moieties in the rearrangement.


=== Chromium oxidation ===
Chromium can oxidize allylic alcohols to alpha-beta unsaturated ketones on the opposite side of the unsaturated bond from the alcohol. This is via a concerted hetero-Claisen reaction, although there are mechanistic differences since the chromium atom has access to d- shell orbitals which allow the reaction under a less constrained set of geometries.


=== Chen-Mapp reaction ===
The Chen-Mapp reaction also known as the [3,3]-Phosphorimidate Rearrangement or Staudinger-Claisen Reaction installs a phosphite in the place of an alcohol and takes advantage of the Staudinger reduction to convert this to an imine. The subsequent Claisen is driven by the fact that a P=O double bond is more energetically favorable than a P=N double bond.


=== Overman rearrangement ===

The Overman rearrangement (named after Larry Overman) is a Claisen rearrangement of allylic trichloroacetimidates to allylic trichloroacetamides.

Overman rearrangement is applicable to synthesis of vicinol diamino comp from 1,2 vicinal allylic diol.


=== Zwitterionic Claisen rearrangement ===
Unlike typical Claisen rearrangements which require heating, zwitterionic Claisen rearrangements take place at or below room temperature. The acyl ammonium ions are highly selective for Z-enolates under mild conditions.


== Claisen rearrangement in nature ==
The enzyme Chorismate mutase (EC 5.4.99.5) catalyzes the Claisen rearrangement of chorismate ion to prephenate ion, a key intermediate in the shikimic acid pathway (the biosynthetic pathway towards the synthesis of phenylalanine and tyrosine).


== References ==


== See also ==
Carroll rearrangement
Cope rearrangement