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A sigmatropic reaction in
organic chemistry Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, and reactions of organic compounds and organic materials, i.e., matter in its various forms that contain carbon atoms.Clayden, ...
is a pericyclic reaction wherein the net result is one σ-bond is changed to another σ-bond in an uncatalyzed intramolecular reaction. The name ''sigmatropic'' is the result of a compounding of the long-established sigma designation from single
carbon Carbon () is a chemical element with the symbol C and atomic number 6. It is nonmetallic and tetravalent—its atom making four electrons available to form covalent chemical bonds. It belongs to group 14 of the periodic table. Carbon mak ...
–carbon bonds and the Greek word ''tropos'', meaning turn. In this type of rearrangement reaction, a substituent moves from one part of a π-bonded system to another part in an intramolecular reaction with simultaneous rearrangement of the π system. True sigmatropic reactions are usually uncatalyzed, although Lewis acid
catalysis Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...
is possible. Sigmatropic reactions often have transition-metal catalysts that form intermediates in analogous reactions. The most well-known of the sigmatropic rearrangements are the ,3
Cope rearrangement The Cope rearrangement is an extensively studied organic reaction involving the ,3sigmatropic rearrangement of 1,5-dienes. It was developed by Arthur C. Cope and Elizabeth Hardy. For example, 3-methyl-hexa-1,5-diene heated to 300 °C yield ...
,
Claisen rearrangement The Claisen rearrangement is a powerful carbon–carbon bond-forming chemical reaction discovered by Rainer Ludwig Claisen. The heating of an allyl vinyl ether will initiate a ,3sigmatropic rearrangement to give a γ,δ-unsaturated carbonyl, ...
, Carroll rearrangement, and the Fischer indole synthesis.


Overview of sigmatropic shifts


Woodward–Hoffman sigmatropic shift nomenclature

Sigmatropic rearrangements are concisely described by an order term ,j'', which is defined as the
migration Migration, migratory, or migrate may refer to: Human migration * Human migration, physical movement by humans from one region to another ** International migration, when peoples cross state boundaries and stay in the host state for some minimum le ...
of a σ-bond adjacent to one or more π systems to a new position (i−1) and (j−1)
atom Every atom is composed of a nucleus and one or more electrons bound to the nucleus. The nucleus is made of one or more protons and a number of neutrons. Only the most common variety of hydrogen has no neutrons. Every solid, liquid, gas, ...
s removed from the original location of the σ-bond. When the sum of i and j is an even number, this is an indication of the involvement of a neutral, all C atom chain. An odd number is an indication of the involvement of a charged C atom or of a heteroatom lone pair replacing a CC double bond. Thus, ,5'' and ,3'' shifts become ,4'' and ,3'' shifts with heteroatoms, while preserving symmetry considerations.
Hydrogen Hydrogen is the chemical element with the symbol H and atomic number 1. Hydrogen is the lightest element. At standard conditions hydrogen is a gas of diatomic molecules having the formula . It is colorless, odorless, tasteless, non-toxic ...
s are omitted in the third example for clarity. : A convenient means of determining the order of a given sigmatropic rearrangement is to number the atoms of the bond being broken as atom 1, and then count the atoms in each direction from the broken bond to the atoms that form the new σ-bond in the product, numbering consecutively. The numbers that correspond to the atoms forming the new bond are then separated by a comma and placed within brackets to create the sigmatropic reaction order descriptor. : In the case of hydrogen atom migrations, a similar technique may be applied. When determining the order of a sigmatropic shift involving a hydrogen atom migration it is critical to count across all atoms involved in the reaction rather than only across the closest atoms. For example, the following hydrogen atom migration is of order ,5 attained by counting counterclockwise through the π system, rather than the ,3order designation through the ring CH2 group that would mistakenly result if counted clockwise. : As a general approach, one can simply draw the transition state of the reaction. For a sigmatropic reaction, the transition state will consist of two fragments, joined together by the forming and breaking σ-bonds. The sigmatropic reaction is named as a 'i'',''j''sigmatropic rearrangement (''i'' ≤ ''j'') if these two fragments consist of ''i'' and ''j'' atoms. This is illustrated below, with the relevant fragments shown in color. :


Suprafacial and antarafacial shifts

In principle, all sigmatropic shifts can occur with either a retention or inversion of the geometry of the migrating group, depending upon whether the original bonding lobe of the migrating atom or its other lobe is used to form the new bond. : In cases of stereochemical retention, the migrating group translates without rotation into the bonding position, while in the case of stereochemical inversion the migrating group both rotates and translates to reach its bonded conformation. However, another stereochemical transition effect equally capable of producing inversion or retention products is whether the migrating group remains on the original face of the π system after rebonding or instead transfers to the opposite face of the π system. If the migrating group remains on the same face of the π system, the shift is known as
suprafacial Antarafacial ( Woodward-Hoffmann symbol a) and suprafacial (s) are two topological concepts in organic chemistry describing the relationship between two simultaneous chemical bond making and/or bond breaking processes in or around a reaction center ...
, while if the migrating group transfers to the opposite face is called an antarafacial shift, Woodward, R.B.; Hoffmann, R. The Conservation of Orbital Symmetry. Verlag Chemie Academic Press. 2004. . which are impossible for transformations that occur within small- or medium-sized rings. :


Classes of sigmatropic rearrangements


,3shifts


Thermal hydride shifts

In a
thermal A thermal column (or thermal) is a rising mass of buoyant air, a convective current in the atmosphere, that transfers heat energy vertically. Thermals are created by the uneven heating of Earth's surface from solar radiation, and are an example ...
,3
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 ...
shift, a hydride moves three atoms. The
Woodward–Hoffmann rules The Woodward–Hoffmann rules (or the pericyclic selection rules), devised by Robert Burns Woodward and Roald Hoffmann, are a set of rules used to rationalize or predict certain aspects of the stereochemistry and activation energy of pericyclic rea ...
dictate that it would proceed in an antarafacial shift. Although such a shift is symmetry allowed, the Mobius
topology In mathematics, topology (from the Greek words , and ) is concerned with the properties of a geometric object that are preserved under continuous deformations, such as stretching, twisting, crumpling, and bending; that is, without closing ...
required in the
transition state In chemistry, the transition state of a chemical reaction is a particular configuration along the reaction coordinate. It is defined as the state corresponding to the highest potential energy along this reaction coordinate. It is often marked ...
prohibits such a shift because it is geometrically impossible, which accounts for the fact that
enol In organic chemistry, alkenols (shortened to enols) are a type of reactive structure or intermediate in organic chemistry that is represented as an alkene ( olefin) with a hydroxyl group attached to one end of the alkene double bond (). The t ...
s do not isomerize without an acid or base
catalyst Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...
.Miller, Bernard. ''Advanced Organic Chemistry''. 2nd Ed. Upper Saddle River: Pearson Prentice Hall. 2004. :


Thermal alkyl shifts

Thermal alkyl ,3shifts, similar to ,3hydride shifts, must proceed antarafacially. Here the geometry of the transition state is prohibitive, but an
alkyl group In organic chemistry, an alkyl group is an alkane missing one hydrogen. The term ''alkyl'' is intentionally unspecific to include many possible substitutions. An acyclic alkyl has the general formula of . A cycloalkyl is derived from a cycloalk ...
, due to the nature of its orbitals, can invert its geometry, form a new bond with the back lobe of its sp3 orbital, and therefore proceed via a suprafacial shift. These reactions are still not common in open-chain compounds because of the highly ordered nature of the transition state, which is more readily achieved in
cyclic Cycle, cycles, or cyclic may refer to: Anthropology and social sciences * Cyclic history, a theory of history * Cyclical theory, a theory of American political history associated with Arthur Schlesinger, Sr. * Social cycle, various cycles in s ...
molecules. :


Photochemical ,3shifts

Photochemical ,3shifts should proceed through suprafacial shifts; however, most are non-concerted because they proceed through a
triplet state In quantum mechanics, a triplet is a quantum state of a system with a spin of quantum number =1, such that there are three allowed values of the spin component, = −1, 0, and +1. Spin, in the context of quantum mechanics, is not a mechanical r ...
(i.e., have a
diradical In chemistry, a diradical is a molecular species with two electrons occupying molecular orbitals (MOs) which are degenerate. The term "diradical" is mainly used to describe organic compounds, where most diradicals are extremely reactive and i ...
mechanism, to which the Woodward-Hoffmann rules do not apply).


,5shifts

A ,5shift involves the shift of 1 substituent (hydride, alkyl, or
aryl In organic chemistry, an aryl is any functional group or substituent derived from an aromaticity, aromatic ring, usually an aromatic hydrocarbon, such as phenyl and naphthyl. "Aryl" is used for the sake of abbreviation or generalization, and "Ar ...
) down 5 atoms of a π system. Hydrogen has been shown to shift in both cyclic and open-chain compounds at temperatures at or above 200 ˚C. These reactions are predicted to proceed suprafacially, via a Hückel-topology transition state. : Photoirradiation would require an antarafacial shift of hydrogen. Although rare, there are examples where antarafacial shifts are favored: : In contrast to hydrogen ,5shifts, there have never been any observed ,5alkyl shifts in an open-chain compound. Several studies have, however, been done to determine rate preferences for ,5alkyl shifts in cyclic systems:
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 containi ...
and
carboxyl In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxylic ...
> hydride>
phenyl In organic chemistry, the phenyl group, or phenyl ring, is a cyclic group of atoms with the formula C6 H5, and is often represented by the symbol Ph. Phenyl group is closely related to benzene and can be viewed as a benzene ring, minus a hydrogen ...
and
vinyl Vinyl may refer to: Chemistry * Polyvinyl chloride (PVC), a particular vinyl polymer * Vinyl cation, a type of carbocation * Vinyl group, a broad class of organic molecules in chemistry * Vinyl polymer, a group of polymers derived from vinyl ...
>> alkyl. Alkyl groups undergo ,5shifts very poorly, usually requiring high temperatures, however, for
cyclohexadiene Cyclohexadiene may refer to: * 1,3-Cyclohexadiene, * 1,4-Cyclohexadiene, See also * Benzene or its theoretical isomer ''1,3,5-Cyclohexatriene'' * Cyclohexene Cyclohexene is a hydrocarbon with the formula C6H10. This cycloalkene is a colorle ...
, the temperature for alkyl shifts isn't much higher than that for carbonyls, the best migratory group. A study showed that this is because alkyl shifts on cyclohexadienes proceed through a different mechanism. First the ring opens, followed by a ,7shift, and then the ring reforms electrocyclically: : This same mechanistic process is seen below, without the final electrocyclic ring-closing reaction, in the interconversion of lumisterol to vitamin D2.


,7shifts

,7sigmatropic shifts are predicted by the Woodward–Hoffmann rules to proceed in an antarafacial fashion, via a Mobius topology transition state. An antarafacial ,7'' shift is observed in the conversion of
lumisterol Lumisterol is a compound that is part of the vitamin D family of steroid compounds. It is the (9β,10α) stereoisomer of ergosterol Ergosterol (ergosta-5,7,22-trien-3β-ol) is a sterol found in cell membranes of fungi and protozoa, serving man ...
to vitamin D2, where following an electrocyclic ring opening to previtamin D2, a methyl hydrogen shifts. : Bicyclic nonatrienes also undergo ,7shifts in a so-called walk rearrangement, which is the shift of
divalent In chemistry, the valence (US spelling) or valency (British spelling) of an chemical element, element is the measure of its combining capacity with other atoms when it forms chemical compounds or molecules. Description The combining capacity, ...
group, as part of a three-membered ring, in a
bicyclic molecule In chemistry, a bicyclic molecule () is a molecule that features two joined rings. Bicyclic structures occur widely, for example in many biologically important molecules like α-thujene and camphor. A bicyclic compound can be carbocyclic (all ...
. :


,3shifts

,3sigmatropic shifts are well studied sigmatropic rearrangements. The Woodward–Hoffman rules predict that these six-
electron The electron ( or ) is a subatomic particle with a negative one elementary electric charge. Electrons belong to the first generation of the lepton particle family, and are generally thought to be elementary particles because they have no ...
reactions would proceed suprafacially, via a Hückel topology transition state.


Claisen rearrangement

Discovered in 1912 by
Rainer Ludwig Claisen Rainer Ludwig Claisen (; 14 January 1851 – 5 January 1930) was a 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 u ...
, the Claisen rearrangement is the first recorded example of a ,3sigmatropic rearrangement. This rearrangement is a useful
carbon Carbon () is a chemical element with the symbol C and atomic number 6. It is nonmetallic and tetravalent—its atom making four electrons available to form covalent chemical bonds. It belongs to group 14 of the periodic table. Carbon mak ...
-carbon
bond Bond or bonds may refer to: Common meanings * Bond (finance), a type of debt security * Bail bond, a commercial third-party guarantor of surety bonds in the United States * Chemical bond, the attraction of atoms, ions or molecules to form chemica ...
-forming
reaction Reaction may refer to a process or to a response to an action, event, or exposure: Physics and chemistry *Chemical reaction *Nuclear reaction * Reaction (physics), as defined by Newton's third law *Chain reaction (disambiguation). Biology and m ...
. An example of Claisen rearrangement is the ,3rearrangement of an allyl vinyl
ether In organic chemistry, ethers are a class of compounds that contain an ether group—an oxygen atom connected to two alkyl or aryl groups. They have the general formula , where R and R′ represent the alkyl or aryl groups. Ethers can again be ...
, which upon heating yields a γ,δ-unsaturated carbonyl. The formation of a carbonyl group makes this reaction, unlike other sigmatropic rearrangements, inherently irreversible. :


=Aromatic Claisen rearrangement

= The ortho-Claisen rearrangement involves the ,3shift of an allyl phenyl ether to an intermediate which quickly tautomerizes to an ortho-substituted
phenol Phenol (also called carbolic acid) is an aromatic organic compound with the molecular formula . It is a white crystalline solid that is volatile. The molecule consists of a phenyl group () bonded to a hydroxy group (). Mildly acidic, it ...
. : When both the ortho positions on the
benzene Benzene is an organic chemical compound with the molecular formula C6H6. The benzene molecule is composed of six carbon atoms joined in a planar ring with one hydrogen atom attached to each. Because it contains only carbon and hydrogen atoms ...
ring are blocked, a second ,3rearrangement will occur. This para-Claisen rearrangement ends with the tautomerization to a tri-substituted phenol. :


Cope rearrangement

The Cope rearrangement is an extensively studied organic reaction involving the ,3sigmatropic rearrangement of 1,5-dienes. It was developed by Arthur C. Cope. For example, 3,4-dimethyl-1,5-hexadiene heated to 300 °C yields 2,6-octadiene. :


=Oxy-Cope rearrangement

= In the oxy-Cope rearrangement, a
hydroxyl In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydro ...
group is added at C3 forming an enal or enone after
keto-enol tautomerism In organic chemistry, alkenols (shortened to enols) are a type of reactive structure or intermediate in organic chemistry that is represented as an alkene ( olefin) with a hydroxyl group attached to one end of the alkene double bond (). Th ...
of the intermediate enol: :


Carroll rearrangement

The Carroll rearrangement is a rearrangement reaction in
organic chemistry Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, and reactions of organic compounds and organic materials, i.e., matter in its various forms that contain carbon atoms.Clayden, ...
and involves the transformation of a β- keto allyl
ester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides a ...
into a α-allyl-β-ketocarboxylic acid. This organic reaction is accompanied by decarboxylation and the final product is a γ,δ-allylketone. The Carroll rearrangement is an adaptation of the
Claisen rearrangement The Claisen rearrangement is a powerful carbon–carbon bond-forming chemical reaction discovered by Rainer Ludwig Claisen. The heating of an allyl vinyl ether will initiate a ,3sigmatropic rearrangement to give a γ,δ-unsaturated carbonyl, ...
and effectively a decarboxylative allylation. :


Fischer indole synthesis

The Fischer indole synthesis is a
chemical reaction A chemical reaction is a process that leads to the IUPAC nomenclature for organic transformations, chemical transformation of one set of chemical substances to another. Classically, chemical reactions encompass changes that only involve the pos ...
that produces the aromatic
heterocycle A heterocyclic compound or ring structure is a cyclic compound that has atoms of at least two different elements as members of its ring(s). Heterocyclic chemistry is the branch of organic chemistry dealing with the synthesis, properties, and ...
indole Indole is an aromatic heterocyclic organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other c ...
from a (substituted)
phenylhydrazine Phenylhydrazine is the chemical compound with the formula . It is often abbreviated as . It is also found in edible mushrooms. Properties Phenylhydrazine forms monoclinic prisms that melt to an oil around room temperature which may turn yellow ...
and an
aldehyde In organic chemistry, an aldehyde () is an organic compound containing a functional group with the structure . The functional group itself (without the "R" side chain) can be referred to as an aldehyde but can also be classified as a formyl grou ...
or ketone under acidic conditions. The reaction was discovered in 1883 by Hermann Emil Fischer. : The choice of acid catalyst is very important. Brønsted acids such as HCl, H2SO4,
polyphosphoric acid A phosphoric acid, in the general sense, is a phosphorus oxoacid in which each phosphorus (P) atom is in the oxidation state +5, and is bonded to four oxygen (O) atoms, one of them through a double bond, arranged as the corners of a tetrahedron. ...
and
p-toluenesulfonic acid ''p''-Toluenesulfonic acid (PTSA or ''p''TsOH) or tosylic acid (TsOH) is an organic compound with the formula CH3 C6H4 SO3H. It is a white extremely hygroscopic solid that is soluble in water, alcohols, and other polar organic solvents. The CH3C ...
have been used successfully. Lewis acids such as boron trifluoride,
zinc chloride Zinc chloride is the name of inorganic chemical compounds with the formula ZnCl2 and its hydrates. Zinc chlorides, of which nine crystalline forms are known, are colorless or white, and are highly soluble in water. This salt is hygroscopic and e ...
, iron(III) chloride, and
aluminium chloride Aluminium chloride, also known as aluminium trichloride, is an inorganic compound with the formula . It forms hexahydrate with the formula , containing six water molecules of hydration. Both are colourless crystals, but samples are often contam ...
are also useful catalysts. Several reviews have been published.


,5Shifts

Similar to ,3shifts, the Woodward-Hoffman rules predict that ,5sigmatropic shifts would proceed suprafacially, Hückel topology transition state. These reactions are rarer than ,3sigmatropic shifts, but this is mainly a function of the fact that molecules that can undergo ,5shifts are rarer than molecules that can undergo ,3shifts. :


,3shifts

An example of a 2,3-sigmatropic rearrangement is the 2,3-Wittig rearrangement: :


Walk rearrangements

The migration of a divalent group, such as O, S, N–R, or C–R2, which is part of a three-membered ring in a bicyclic molecule, is commonly referred to as a walk rearrangement. This can be formally characterized according to the Woodward-Hofmann rules as being a (1, n) sigmatropic shift. An example of such a rearrangement is the shift of substituents on tropilidenes (1,3,5-cycloheptatrienes). When heated, the pi-system goes through an electrocyclic ring closing to form bicycle ,1,0eptadiene (norcaradiene). Thereafter follows a ,5alkyl shift and an electrocyclic ring opening. : Proceeding through a ,5shift, the walk rearrangement of norcaradienes is expected to proceed suprafacially with a retention of stereochemistry. Experimental observations, however, show that the 1,5-shifts of norcaradienes proceed antarafacially. Theoretical calculations found the ,5shift to be a
diradical In chemistry, a diradical is a molecular species with two electrons occupying molecular orbitals (MOs) which are degenerate. The term "diradical" is mainly used to describe organic compounds, where most diradicals are extremely reactive and i ...
process, but without involving any diradical minima on the
potential energy surface A potential energy surface (PES) describes the energy of a system, especially a collection of atoms, in terms of certain parameters, normally the positions of the atoms. The surface might define the energy as a function of one or more coordinat ...
.Kless, A.; Nendel, M.; Wilsey, S.; Houk, K. N. '' J. Am. Chem. Soc.'', 1999, ''121'', 4524.


See also

* 2,3-sigmatropic rearrangement * NIH shift *
Frontier molecular orbital theory In chemistry, frontier molecular orbital theory is an application of MO theory describing HOMO/LUMO interactions. History In 1952, Kenichi Fukui published a paper in the ''Journal of Chemical Physics'' titled "A molecular theory of reactivity i ...


References

{{Reflist Reaction mechanisms Rearrangement reactions