Claisen rearrangement

Claisen rearrangement
Named after	Rainer Ludwig Claisen
Reaction type	Rearrangement reaction
Identifiers
Organic Chemistry Portal	claisen-rearrangement
RSC ontology ID	RXNO:0000148

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 γ,δ-unsaturated carbonyl.

The Claisen rearrangement

Discovered in 1912, the Claisen rearrangement is the first recorded example of a [3,3]-sigmatropic rearrangement.^[1]^[2]^[3]

Many reviews have been written.^[4]^[5]^[6]^[7]

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.^[8]^[9]

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.^[1]^[2]

Trivalent organoaluminium reagents, such as trimethylaluminium, have been shown to accelerate this reaction.^[10]^[11]

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.

The Claisen rearrangement

Meta-substitution affects the regioselectivity of the ortho rearrangement.^[12]^[13] 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.^[14]

Aromatic Claisen with ortho-position substituted

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.^[15]^[16]

Bellus–Claisen rearrangement

The Bellus–Claisen rearrangement is the reaction of allylic ethers, amines, and thioethers with ketenes to give γ,δ-unsaturated esters, amides, and thioesters.^[17]^[18]^[19]

The Bellus–Claisen rearrangement

Eschenmoser–Claisen rearrangement

The Eschenmoser–Claisen rearrangement proceeds from an allylic alcohol to a γ,δ-unsaturated amide, and was developed by Albert Eschenmoser in 1964.^[20]^[21]

The Eschenmoser-Claisen rearrangement

Mechanism:^[14]

Eschenmoser–Claisen 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 γ,δ-unsaturated carboxylic acid.^[22]^[23]^[24] The actual rearrangement occurs from the enolate of the ester—this is the structural analog of the simple alkene in the original Claisen rearrangement.

The Ireland–Claisen rearrangement

Mechanism:^[14]

Ireland Enolate Claisen 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 γ,δ-unsaturated ester.^[25]

The Johnson–Claisen rearrangement

Mechanism:^[14]

Johnson–Claisen 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.^[26]

Hetero-Claisens

Aza–Claisen

An iminium can serve as one of the pi-bonded moieties in the rearrangement.^[27]

An example of the Aza–Claisen 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.^[28]^[29]

File:ClaisenOx.png

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.^[30]

The Mapp reaction

Overman rearrangement

The Overman rearrangement (named after Larry Overman) is a Claisen rearrangement of allylic trichloroacetimidates to allylic trichloroacetamides.^[31]^[32]^[33]

The Overman rearrangement

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.^[34]^[35]

The zwitterionic Claisen rearrangement