An allylic rearrangement or allylic shift is an
organic reaction
Organic reactions are chemical reactions involving organic compounds. The basic organic chemistry reaction types are addition reactions, elimination reactions, substitution reactions, pericyclic reactions, rearrangement reactions, Mechanistic Organ ...
in which the
double bond
In chemistry, a double bond is a covalent bond between two atoms involving four bonding electrons as opposed to two in a single bond. Double bonds occur most commonly between two carbon atoms, for example in alkenes. Many double bonds exist betw ...
in an
allyl
In organic chemistry, an allyl group is a substituent with the structural formula , where R is the rest of the molecule. It consists of a methylene bridge () attached to a vinyl group (). The name is derived from the scientific name for garlic, ...
chemical compound shifts to the next carbon atom. It is encountered in
nucleophilic substitution
In chemistry, a nucleophilic substitution is a class of chemical reactions in which an electron-rich chemical species (known as a nucleophile) replaces a functional group within another electron-deficient molecule (known as the electrophile). The ...
.
In reaction conditions that favor a
SN1 reaction mechanism, the intermediate is a
carbocation
A carbocation is an ion with a positively charged carbon atom. Among the simplest examples are the methenium , methanium and vinyl cations. Occasionally, carbocations that bear more than one positively charged carbon atom are also encountere ...
for which several
resonance structure
In chemistry, resonance, also called mesomerism, is a way of describing Chemical bond, bonding in certain molecules or polyatomic ions by the combination of several contributing structures (or ''forms'', also variously known as ''resonance stru ...
s are possible. This explains the product distribution (or product spread) after recombination with
nucleophile
In chemistry, a nucleophile is a chemical species that forms bonds by donating an electron pair. All molecules and ions with a free pair of electrons or at least one pi bond can act as nucleophiles. Because nucleophiles donate electrons, they are ...
Y. This type of process is called an S
N1' substitution.
Alternatively, it is possible for nucleophile to attack directly at the allylic position, displacing the leaving group in a single step, in a process referred to as S
N2' substitution. This is likely in cases when the allyl compound is unhindered, and a strong
nucleophile
In chemistry, a nucleophile is a chemical species that forms bonds by donating an electron pair. All molecules and ions with a free pair of electrons or at least one pi bond can act as nucleophiles. Because nucleophiles donate electrons, they are ...
is used. The products will be similar to those seen with S
N1' substitution. Thus reaction of 1-chloro-2-butene with
sodium hydroxide
Sodium hydroxide, also known as lye and caustic soda, is an inorganic compound with the formula NaOH. It is a white solid ionic compound consisting of sodium cations and hydroxide anions .
Sodium hydroxide is a highly caustic base and alkali ...
gives a mixture of 2-buten-1-ol and 3-buten-2-ol:
:
![AllylicRearrangementReaction](https://upload.wikimedia.org/wikipedia/commons/2/2b/AllylicRearrangementReaction.png)
Nevertheless, the product in which the OH group is on the primary atom is minor. In the substitution of 1-chloro-3-methyl-2-butene, the secondary 2-methyl-3-buten-2-ol is produced in a yield of 85%, while that for the primary 3-methyl-2-buten-1-ol is 15%.
In one
reaction mechanism
In chemistry, a reaction mechanism is the step by step sequence of elementary reactions by which overall chemical change occurs.
A chemical mechanism is a theoretical conjecture that tries to describe in detail what takes place at each stage of ...
the
nucleophile
In chemistry, a nucleophile is a chemical species that forms bonds by donating an electron pair. All molecules and ions with a free pair of electrons or at least one pi bond can act as nucleophiles. Because nucleophiles donate electrons, they are ...
attacks not directly at the electrophilic site but in a conjugate addition over the double bond:
:
![SN2 accent reaction mechanism](https://upload.wikimedia.org/wikipedia/commons/d/d1/SN2_accent_reaction_mechanism.png)
This is usual in allylic compounds which have a bulky leaving group in S
N2 conditions or bulky non-leaving substituent which give rise to significant steric hindrance, thereby increasing the conjugate substitution. This kind of reaction is termed S
N1' or S
N2', depending on whether the reaction follows S
N1-like mechanism or S
N2-like mechanism. Similar to how there are S
N1' and S
N2' analogues for S
N1 and S
N2 reactions respectively, there also is an analogue for S
Ni, that being the S
Ni', applicable for reactions betwixt allylic compounds and reagents like SOCl
2.
Scope
The synthetic utility can be extended to substitutions over
butadiene
1,3-Butadiene () is the organic compound with the formula (CH2=CH)2. It is a colorless gas that is easily condensed to a liquid. It is important industrially as a precursor to synthetic rubber. The molecule can be viewed as the union of two viny ...
bonds:
:
![Lawton reaction](https://upload.wikimedia.org/wikipedia/commons/b/b7/Lawton_reaction.png)
:''Reaction in
methanol
Methanol (also called methyl alcohol and wood spirit, amongst other names) is an organic chemical and the simplest aliphatic alcohol, with the formula C H3 O H (a methyl group linked to a hydroxyl group, often abbreviated as MeOH). It is a ...
and catalyst
diisopropylethylamine
''N'',''N''-Diisopropylethylamine, or Hünig's base, is an organic compound and an amine. It is named after the German chemist Siegfried Hünig. It is used in organic chemistry as a base. It is commonly abbreviated as DIPEA, DIEA, or ''i''-Pr2N ...
''
In the first step of this
macrocyclization
Macrocycles are often described as molecules and ions containing a ring of twelve or more atoms. Classical examples include the crown ethers, calixarenes, porphyrins, and cyclodextrins. Macrocycles describe a large, mature area of chemistry.
...
the
thiol
In organic chemistry, a thiol (; ), or thiol derivative, is any organosulfur compound of the form , where R represents an alkyl or other organic substituent. The functional group itself is referred to as either a thiol group or a sulfhydryl gro ...
group in one end of ''1,5-pentanedithiol'' reacts with the butadiene tail in 1 to the
enone 2 in an allylic shift with a
sulfone
In organic chemistry, a sulfone is a organosulfur compound containing a sulfonyl () functional group attached to two carbon atoms. The central hexavalent sulfur atom is double-bonded to each of two oxygen atoms and has a single bond to each of ...
leaving group In chemistry, a leaving group is defined by the IUPAC as an atom or group of atoms that detaches from the main or residual part of a substrate during a reaction or elementary step of a reaction. However, in common usage, the term is often limited t ...
which reacts further with the other end in a
conjugate addition reaction
Nucleophilic conjugate addition is a type of organic reaction. Ordinary nucleophilic additions or 1,2-nucleophilic additions deal mostly with additions to carbonyl compounds. Simple alkene compounds do not show 1,2 reactivity due to lack of polarit ...
.
In one study the allylic shift was applied twice in a ring system:
:
![Double Lawson reaction](https://upload.wikimedia.org/wikipedia/commons/3/3d/Double_Lawson_reaction.png)
In this reaction sequence a
Jacobsen epoxidation
The Jacobsen epoxidation, sometimes also referred to as Jacobsen-Katsuki epoxidation is a chemical reaction which allows enantioselective epoxidation of unfunctionalized alkyl- and aryl- substituted alkenes. It is complementary to the Sharpless e ...
adds an
epoxy
Epoxy is the family of basic components or cured end products of epoxy resins. Epoxy resins, also known as polyepoxides, are a class of reactive prepolymers and polymers which contain epoxide groups. The epoxide functional group is also coll ...
group to a
diene
In organic chemistry a diene ( ) (diolefin ( ) or alkadiene) is a covalent compound that contains two double bonds, usually among carbon atoms. They thus contain two alk''ene'' units, with the standard prefix ''di'' of systematic nomenclature. ...
which serves as the leaving group in reaction with the
pyrazole
Pyrazole is an organic compound with the formula C3H3N2H. It is a heterocycle characterized by a 5-membered ring of three carbon
Carbon () is a chemical element with the symbol C and atomic number 6. It is nonmetallic and tetravalent
...
nucleophile. The second nucleophile is
methylmagnesium bromide expulsing the pyrazole group.
An S
N2' reaction should explain the outcome of the reaction of an
aziridine
Aziridine is an organic compound consisting of the three-membered heterocycle . It is a colorless, toxic, volatile liquid that is of significant practical interest. Aziridine was discovered in 1888 by the chemist Siegmund Gabriel. Its derivati ...
carrying a methylene bromide group with
methyllithium
Methyllithium is the simplest organolithium reagent with the empirical formula CH3Li. This s-block organometallic compound adopts an oligomeric structure both in solution and in the solid state. This highly reactive compound, invariably used in so ...
:
:
![AziridineAllylicRearrangement](https://upload.wikimedia.org/wikipedia/commons/0/02/AziridineAllylicRearrangement.png)
In this reaction one equivalent of
acetylene
Acetylene (systematic name: ethyne) is the chemical compound with the formula and structure . It is a hydrocarbon and the simplest alkyne. This colorless gas is widely used as a fuel and a chemical building block. It is unstable in its pure ...
is lost.
Examples of allylic shifts:
*
Ferrier rearrangement
The Ferrier rearrangement is an organic reaction that involves a nucleophilic substitution reaction combined with an allylic shift in a glycal (a 2,3-unsaturated compound, unsaturated glycoside). It was discovered by the carbohydrate chemist Robert ...
*
Meyer–Schuster rearrangement The Meyer–Schuster rearrangement is the chemical reaction described as an acid-catalysis, catalyzed rearrangement reaction, rearrangement of secondary and tertiary propargyl alcohols to α,β-unsaturated ketones if the alkyne group is internal and ...
SN2' reduction
In one adaptation called a S
N2' reduction a formal
organic reduction
Organic reductions or organic oxidations or organic redox reactions are redox reactions that take place with organic compounds. In organic chemistry oxidations and reductions are different from ordinary redox reactions, because many reactions carr ...
on an allyl group containing a good
leaving group In chemistry, a leaving group is defined by the IUPAC as an atom or group of atoms that detaches from the main or residual part of a substrate during a reaction or elementary step of a reaction. However, in common usage, the term is often limited t ...
is accompanied by a rearrangement. One example of such reaction is found as part of a
taxol total synthesis
Paclitaxel total synthesis in organic chemistry is a major ongoing research effort in the total synthesis of paclitaxel (Taxol). This diterpenoid is an important drug in the treatment of cancer but, also expensive because the compound is harveste ...
(ring C):
:
The
hydride
In chemistry, a hydride is formally the anion of hydrogen( H−). The term is applied loosely. At one extreme, all compounds containing covalently bound H atoms are called hydrides: water (H2O) is a hydride of oxygen, ammonia is a hydride of ...
is
lithium aluminium hydride
Lithium aluminium hydride, commonly abbreviated to LAH, is an inorganic compound with the chemical formula Li Al H4. It is a white solid, discovered by Finholt, Bond and Schlesinger in 1947. This compound is used as a reducing agent in organic ...
and the leaving group a
phosphonium salt
In polyatomic cations with the chemical formula (where R is a hydrogen or an alkyl, aryl, or halide group). These cations have tetrahedral structures. The salts are generally colorless or take the color of the anions.
Types of phosphonium c ...
. The product contains a new
exocyclic
In organic chemistry, an alicyclic compound contains one or more all-carbon rings which may be either saturated or unsaturated, but do not have aromatic character. Alicyclic compounds may have one or more aliphatic side chains attached.
The s ...
double bond. Only when the
cyclohexane
Cyclohexane is a cycloalkane with the molecular formula . Cyclohexane is non-polar. Cyclohexane is a colorless, flammable liquid with a distinctive detergent-like odor, reminiscent of cleaning products (in which it is sometimes used). Cyclohexan ...
ring is properly substituted will the proton add in a ''
trans
Trans- is a Latin prefix meaning "across", "beyond", or "on the other side of".
Used alone, trans may refer to:
Arts, entertainment, and media
* Trans (festival), a former festival in Belfast, Northern Ireland, United Kingdom
* ''Trans'' (film ...
'' position with respect to the adjacent
methyl
In organic chemistry, a methyl group is an alkyl derived from methane, containing one carbon atom bonded to three hydrogen atoms, having chemical formula . In formulas, the group is often abbreviated as Me. This hydrocarbon group occurs in many ...
group. A conceptually related reaction is the
Whiting reaction
The Whiting reaction is an organic reaction converting a propargyl diol into a diene using lithium aluminium hydride.
This organic reduction has been applied in the synthesis of ''fecapentaene''.protecting groups are tetrahydropyranyl and TBSMS ...
forming dienes.
Electrophilic allyl shifts
Allyl shifts can also take place with
electrophile
In chemistry, an electrophile is a chemical species that forms bonds with nucleophiles by accepting an electron pair. Because electrophiles accept electrons, they are Lewis acids. Most electrophiles are positively charged, have an atom that carries ...
s. In the example below the
carbonyl
In organic chemistry, a carbonyl group is a functional group composed of a carbon atom double-bonded to an oxygen atom: C=O. It is common to several classes of organic compounds, as part of many larger functional groups. A compound containing a ...
group in
benzaldehyde
Benzaldehyde (C6H5CHO) is an organic compound consisting of a benzene ring with a formyl substituent. It is the simplest aromatic aldehyde and one of the most industrially useful.
It is a colorless liquid with a characteristic almond-like odor. ...
is activated by
diboronic acid
A boronic acid is an organic compound related to boric acid () in which one of the three hydroxyl groups () is replaced by an alkyl or aryl group (represented by R in the general formula ). As a compound containing a carbon–boron bond, membe ...
prior to reaction with the allyl alcohol (see:
Prins reaction
The Prins reaction is an organic reaction consisting of an electrophilic addition of an aldehyde or ketone to an alkene or alkyne followed by capture of a nucleophile or elimination of an H+ ion. The outcome of the reaction depends on reaction c ...
):
[The active catalyst system in this reaction is a combination of a ]palladium
Palladium is a chemical element with the symbol Pd and atomic number 46. It is a rare and lustrous silvery-white metal discovered in 1803 by the English chemist William Hyde Wollaston. He named it after the asteroid Pallas, which was itself na ...
pincer compound and ''p''-toluenesulfonic acid, the reaction product is obtained as a single regioisomer and stereoisomer
In stereochemistry, stereoisomerism, or spatial isomerism, is a form of isomerism in which molecules have the same molecular formula and sequence of bonded atoms (constitution), but differ in the three-dimensional orientations of their atoms in ...
:
References
{{Organic reactions
Rearrangement reactions
Reaction mechanisms