The Claisen rearrangement is a powerful
carbonCarbon is the chemical element with symbol C and atomic number 6. As a member of group 14 on the periodic table, it is nonmetallic and tetravalent—making four electrons available to form covalent chemical bonds...
-carbon
bondA chemical bond is an interaction between atoms or molecules and allows the formation of polyatomic chemical compounds. A chemical bond is the attraction caused by the electromagnetic force between opposing charges, either between electrons and nuclei, or as the result of a dipole attraction...
-forming
chemical reactionA chemical reaction is a process that leads to the transformation of one set of chemical substances to another. They are studied by chemists under a field of science called chemistry. Chemical reactions can be either spontaneous, requiring no input of energy, or non-spontaneous, often coming about...
discovered by
Rainer Ludwig ClaisenRainer Ludwig Claisen was a famous German chemist best known for his work with condensations of carbonyls and sigmatropic rearrangements. He was born in Cologne as the son of a jurist and studied chemistry at the university of Bonn , where he became a member of K.St.V. Arminia...
. The heating of an
allylAn allyl group is an alkene hydrocarbon group with the formula H2C=CH-CH2-. It is made up of a vinyl group, CH2=CH-, attached to a methylene -CH2. For example allyl alcohol has the structure H2C=CH-CH2OH. Another example of a simple...
vinylA vinyl compound is any organic compound that contains a vinyl group , −CH=CH2. These are derivatives of ethene, CH2=CH2, with one hydrogen atom replaced with some other group...
etherEther is a class of organic compounds that contain an ether group — an oxygen atom connected to two alkyl or aryl groups — of general formula R–O–R. A typical example is the solvent and anesthetic diethyl ether, commonly referred to simply as "ether"...
will initiate a
[3,3]-sigmatropic rearrangementA sigmatropic reaction in organic chemistry is a pericyclic reaction wherein the net result is one σ-bond is changed to another σ-bond in an uncatalyzed intramolecular process. The name sigmatropic is the result of a compounding of the long-established sigma designation from single carbon-carbon...
to give a γ,δ-unsaturated carbonyl.
Discovered in 1912, the Claisen rearrangement is the first recorded example of a [3,3]-sigmatropic rearrangement.
Many reviews have been written.
The Claisen rearrangement (and its variants) are
exothermicIn thermodynamics, the term exothermic describes a process or reaction that releases energy usually in the form of heat, but also in the form of light , electricity , or sound. Its etymology stems from the Greek prefix ex- and the Greek word thermein...
(about 84 kJ/mol), concerted pericyclic reactions which according to the
Woodward-Hoffmann rulesThe Woodward–Hoffmann rules devised by Robert Burns Woodward and Roald Hoffmann are a set of rules in organic chemistry predicting the stereochemistry of pericyclic reactions based on orbital symmetry. These include electrocyclic reactions, cycloadditions, and sigmatropic reactions...
show a suprafacial reaction pathway.
There are substantial
solventA solvent is a liquid, solid, or gas that dissolves another solid, liquid, or gaseous solute, resulting in a solution.The most common solvent in everyday life is water. Most other commonly-used solvents are organic chemicals. These are called organic solvents...
effects in the Claisen reactions.
The Claisen rearrangement is a powerful
carbonCarbon is the chemical element with symbol C and atomic number 6. As a member of group 14 on the periodic table, it is nonmetallic and tetravalent—making four electrons available to form covalent chemical bonds...
-carbon
bondA chemical bond is an interaction between atoms or molecules and allows the formation of polyatomic chemical compounds. A chemical bond is the attraction caused by the electromagnetic force between opposing charges, either between electrons and nuclei, or as the result of a dipole attraction...
-forming
chemical reactionA chemical reaction is a process that leads to the transformation of one set of chemical substances to another. They are studied by chemists under a field of science called chemistry. Chemical reactions can be either spontaneous, requiring no input of energy, or non-spontaneous, often coming about...
discovered by
Rainer Ludwig ClaisenRainer Ludwig Claisen was a famous German chemist best known for his work with condensations of carbonyls and sigmatropic rearrangements. He was born in Cologne as the son of a jurist and studied chemistry at the university of Bonn , where he became a member of K.St.V. Arminia...
. The heating of an
allylAn allyl group is an alkene hydrocarbon group with the formula H2C=CH-CH2-. It is made up of a vinyl group, CH2=CH-, attached to a methylene -CH2. For example allyl alcohol has the structure H2C=CH-CH2OH. Another example of a simple...
vinylA vinyl compound is any organic compound that contains a vinyl group , −CH=CH2. These are derivatives of ethene, CH2=CH2, with one hydrogen atom replaced with some other group...
etherEther is a class of organic compounds that contain an ether group — an oxygen atom connected to two alkyl or aryl groups — of general formula R–O–R. A typical example is the solvent and anesthetic diethyl ether, commonly referred to simply as "ether"...
will initiate a
[3,3]-sigmatropic rearrangementA sigmatropic reaction in organic chemistry is a pericyclic reaction wherein the net result is one σ-bond is changed to another σ-bond in an uncatalyzed intramolecular process. The name sigmatropic is the result of a compounding of the long-established sigma designation from single carbon-carbon...
to give a γ,δ-unsaturated carbonyl.
Discovered in 1912, the Claisen rearrangement is the first recorded example of a [3,3]-sigmatropic rearrangement.
Many reviews have been written.
Mechanism
The Claisen rearrangement (and its variants) are
exothermicIn thermodynamics, the term exothermic describes a process or reaction that releases energy usually in the form of heat, but also in the form of light , electricity , or sound. Its etymology stems from the Greek prefix ex- and the Greek word thermein...
(about 84 kJ/mol), concerted pericyclic reactions which according to the
Woodward-Hoffmann rulesThe Woodward–Hoffmann rules devised by Robert Burns Woodward and Roald Hoffmann are a set of rules in organic chemistry predicting the stereochemistry of pericyclic reactions based on orbital symmetry. These include electrocyclic reactions, cycloadditions, and sigmatropic reactions...
show a suprafacial reaction pathway.
There are substantial
solventA solvent is a liquid, solid, or gas that dissolves another solid, liquid, or gaseous solute, resulting in a solution.The most common solvent in everyday life is water. Most other commonly-used solvents are organic chemicals. These are called organic solvents...
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,
ethanolEthanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug, best known as the type of alcohol found in alcoholic beverages and in modern thermometers. Ethanol is one of the oldest recreational drugs...
/
waterWater is an ubiquitous chemical substance that is composed of hydrogen and oxygen and is essential for all known forms of life.In typical usage, water refers only to its liquid form or state, but the substance also has a solid state, ice, and a gaseous state, water vapor or steam. Water covers 71%...
solvent mixtures give rate constants 10-fold higher than
sulfolaneSulfolane is a clear, colorless liquid commonly used in the chemical industry as an extractive distillation solvent or reaction solvent. Sulfolane was originally developed by the Shell Oil Company in the 1960s as a solvent to purify butadiene...
.
[1][2]
Trivalent organo
aluminiumAluminium or aluminum is a silvery white and ductile member of the boron group of chemical elements. It has the symbol Al; its atomic number is 13. It is not soluble in water under normal circumstances....
reagents, such as
trimethylaluminiumTrimethylaluminium is the chemical compound with the formula Al26, abbreviated as Al2Me6, 2 or the abbreviation TMA...
, have been shown to accelerate this reaction.
Aromatic Claisen rearrangement
The aromatic variation of the
Claisen rearrangement is the
[3,3]-sigmatropic rearrangementA sigmatropic reaction in organic chemistry is a pericyclic reaction wherein the net result is one σ-bond is changed to another σ-bond in an uncatalyzed intramolecular process. The name sigmatropic is the result of a compounding of the long-established sigma designation from single carbon-carbon...
of an
allylAn allyl group is an alkene hydrocarbon group with the formula H2C=CH-CH2-. It is made up of a vinyl group, CH2=CH-, attached to a methylene -CH2. For example allyl alcohol has the structure H2C=CH-CH2OH. Another example of a simple...
phenyl
etherEther is a class of organic compounds that contain an ether group — an oxygen atom connected to two alkyl or aryl groups — of general formula R–O–R. A typical example is the solvent and anesthetic diethyl ether, commonly referred to simply as "ether"...
to an intermediate which quickly tautomerizes to an ortho-substituted
phenolPhenol, also known as carbolic acid, is a toxic, white crystalline solid. Its chemical formula is C6H5OH and its structure is that of a hydroxyl group bonded to a phenyl ring, making it an aromatic compound.-Phenols:...
.
If ortho position is substituted then reaction goes to para position with retention in configration.
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.
Eschenmoser-Claisen rearrangement
The
Eschenmoser-Claisen rearrangement proceeds from an allylic alcohol to a γ,δ-unsaturated amide, and was developed by
Albert EschenmoserAlbert Eschenmoser is a Swiss chemist working at the ETH Zurich and The Scripps Research Institute.His work together with Lavoslav Ružička on terpenes and the postulation of squalene cyclization to form lanosterol improved the insight into steroid biosynthesis.In the early 1960s, Eschenmoser began...
in 1964.
Ireland-Claisen rearrangement
The
Ireland-Claisen rearrangement is the reaction of an
allylicAn allyl group is an alkene hydrocarbon group with the formula H2C=CH-CH2-. It is made up of a vinyl group, CH2=CH-, attached to a methylene -CH2. For example allyl alcohol has the structure H2C=CH-CH2OH. Another example of a simple...
acetateAn acetate, or ethanoate, is either a salt or ester of ethanoic acid.In chemistry, the abbreviation Ac refers to the acetyl group. The anion and the functional group may be written as −OAc and AcO−, or OAc respectively...
with strong base (such as
Lithium diisopropylamideLithium diisopropylamide is the chemical compound with the formula [
2CH]
2NLi. Generally abbreviated LDA, it is a strong base used in organic chemistry for the deprotonation of weakly acidic compounds. The reagent has been widely accepted because it is soluble in non-polar...
) to give a γ,δ-unsaturated
carboxylic acidCarboxylic acids are organic acids characterized by the presence of a carboxyl group, which has the formula -COH, usually written -COOH or -CO2H. Carboxylic acids are Brønsted-Lowry acids — they are proton donors. Salts and anions of carboxylic acids are called...
.
Johnson-Claisen rearrangement
The
Johnson-Claisen rearrangement is the reaction of an
allylicAn allyl group is an alkene hydrocarbon group with the formula H2C=CH-CH2-. It is made up of a vinyl group, CH2=CH-, attached to a methylene -CH2. For example allyl alcohol has the structure H2C=CH-CH2OH. Another example of a simple...
alcoholIn chemistry, an alcohol is any organic compound in which a hydroxyl group is bound to a carbon atom of an alkyl or substituted alkyl group. An important group of acohols is formed by the simple acyclic alcohols, the general formula for which is C
nH
2n+1OH...
with trimethyl orthoacetate to give a γ,δ-unsaturated
esterEsters are chemical compounds derived by reacting an oxoacid with a hydroxyl compound such as an alcohol or phenol. Esters are usually derived from an inorganic acid or organic acid in which at least one -OH group is replaced by an -O-alkyl group, and most commonly from carboxylic acids and...
.
Aza-Claisen
An
iminiumAn iminium salt or cation in organic chemistry has the general structure [R1R2C=NR3R4]+ and is as such a protonated or substituted imine . It is an intermediate in many organic reactions such as the Beckmann rearrangement,...
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 Ligation 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 rearrangementThe Overman rearrangement is a chemical reaction that can be described as a Claisen rearrangement of allylic alcohols to give allylic trichloroacetamides through an imidate intermediate. The Overman rearrangement was discovered in 1974 by Larry Overman....
(named after Larry Overman) is a Claisen rearrangement of allylic trichloroacetimidates to allylic trichloroacetamides.
Zwitterionic Claisen rearrangement
Unlike typical Claisen rearrangements which require heating, zwitterionic Claisen rearrangements take place at or below room temperature. The
acylAcyl group|rightAn acyl group is a functional group derived by the removal of one or more hydroxyl groups from an oxoacid. In organic chemistry, the acyl group is usually derived from a carboxylic acid. It therefore has the formula RCO, where R represents an alkyl group that is attached to the CO...
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
chorismateChorismic acid, more commonly known as its anionic form chorismate, is an important biochemical intermediate in plants and microorganisms...
ion to
prephenatePrephenic acid, more commonly known by its anionic form prephenate, is an intermediate in the biosynthesis of the aromatic amino acids phenylalanine and tyrosine.It is synthesized by a [3,3]-sigmatropic Claisen rearrangement of chorismate....
ion, a key intermediate in the
shikimic acidShikimic acid, more commonly known as its anionic form shikimate, is an important biochemical intermediate in plants and microorganisms. Its name comes from the Japanese flower shikimi , from which it was first isolated....
pathway (the
biosyntheticBiosynthesis is an enzyme-catalyzed process in cells of living organisms by which substrates are converted to more complex products. The biosynthesis process often consists of several enzymatic steps in which the product of one step is used as substrate in the following step...
pathway towards the synthesis of
phenylalaninePhenylalanine is an α-amino acid with the formula HO
2CCHCH
2C
6H
5. This essential amino acid is classified as nonpolar because of the hydrophobic nature of the benzyl side chain. The codons for
L-phenylalanine are UUU and UUC...
and
tyrosineTyrosine or 4-hydroxyphenylalanine, is one of the 20 amino acids that are used by cells to synthesize proteins. It is a non-essential amino acid with a polar side group...
).