Sigmatropic reaction

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A sigmatropic reaction in organic chemistry is a pericyclic reaction wherein the net result is one bond is changed to another -bond in an uncatalyzed intramolecularprocess.[1] The
name sigmatropic is the result of a compounding of the long-established sigma designation from
single carboncarbon bonds and the Greek word tropos, meaning turn. In this type of rearrangement
reaction, a substituent moves from one part of a -bonded system to another part in an
intramolecular reaction with simultaneous rearrangement of the system. True sigmatropic
reactions are usually uncatalyzed, although Lewis acid catalysis is possible. Sigmatropic reactions
often have transition-metal catalysts that form intermediates in analogous reactions. The most wellknown of the sigmatropic rearrangements are the [3,3] Cope rearrangement, Claisen
rearrangement,Carroll rearrangement and the Fischer indole synthesis.
Contents
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1Overview of sigmatropic shifts

o

1.1WoodwardHoffman sigmatropic shift nomenclature

1.2Suprafacial and antarafacial shifts

2Classes of sigmatropic rearrangements

2.1[1,3] Shifts

2.1.1Thermal hydride shifts

2.1.2Thermal alkyl shifts

2.1.3Photochemical [1,3] shifts

2.2[1,5] Shifts

2.3[1,7] Shifts

2.4[3,3] Shifts
2.4.1Claisen rearrangement

2.4.2Cope rearrangement

2.4.1.1Aromatic Claisen rearrangement

2.4.2.1Oxy-Cope rearrangement
2.4.3Carroll rearrangement

2.4.4Fischer indole synthesis

2.5[5,5] Shifts

2.6[2,3] shifts

2.7Walk rearrangements

3See also

4References

Overview of sigmatropic shifts[edit]

WoodwardHoffman sigmatropic shift nomenclature[edit]
Sigmatropic rearrangements are concisely described by an order term [i,j], which is defined as
the migration of a -bond adjacent to one or more systems to a new position (i1) and
(j1) atoms removed from the original location of the -bond.[2] 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, [1,5] and [3,3] shifts become [1,4]and [2,3] shifts with heteroatoms, while
preserving symmetry considerations. Hydrogens 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 -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.[3]

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 [1,5], attained by counting counterclockwise through the

system, rather than the [1,3] order designation through the ring CH 2 group that would mistakenly
result if counted clockwise.

Suprafacial and antarafacial shifts[edit]

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.[3]

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 system after rebonding
or instead transfers to the opposite face of the system. If the migrating group remains on the same
face of the system, the shift is known assuprafacial, while if the migrating group transfers to the
opposite face is called an antarafacial shift,[2] which are impossible for transformations that occur
within small- or medium-sized rings.

Classes of sigmatropic rearrangements[edit]

[1,3] Shifts[edit]
Thermal hydride shifts[edit]
In a thermal [1,3] hydride shift, a hydride moves three atoms. The WoodwardHoffmann rules dictate
that it would proceed in an antarafacial shift. Although such a shift is symmetry allowed,
the Mobius topology required in the transition state prohibits such a shift because it is geometrically
impossible, which accounts for the fact that enols do not isomerize without an acid or base catalyst.[3]

Thermal alkyl shifts[edit]

Thermal alkyl [1,3] shifts, similar to [1,3] hydride shifts, must proceed antarafacially. Here the
geometry of the transition state is prohibitive, but an alkyl group, 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 systems because of the highly
ordered nature of the transition state, which is more readily achieved in cyclic molecules.[3]

Photochemical [1,3] shifts[edit]

Photochemical [1,3] shifts should proceed through suprafacial shifts; however, most are nonconcerted because they proceed through a triplet state (i.e., have a diradicalmechanism, to which
the Woodward-Hoffmann rules do not apply).[3]

[1,5] Shifts[edit]
A [1,5] shift involves the shift of 1 substituent (H, R or Ar) down 5 atoms of a system. Hydrogen
has been shown to shift in both cyclic and open chain systems at temperatures at or above 200 C.
[3]

These reactions are predicted to proceed suprafacially, via a Huckel-topology transition state.

Photoirradiation would require an antarafacial shift of hydrogen. Although rare, there are examples
where antarafacial shifts are favored:[4]

In contrast to hydrogen [1,5] shifts, there have never been any observed [1,5] alkyl shifts in an openchain system.[3] Several studies have, however, been done to determine ratepreferences for [1,5]
alkyl shifts in cyclic systems: carbonyl and carboxyl> hydride> phenyl and vinyl>> alkyl.[5][6]

Alkyl groups undergo [1,5] shifts very poorly, usually requiring high temperatures, however,
for cyclohexadienes, the temperature for alkyl shifts isnt 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 [1,7] shift, and then the ring
reforms electrocyclically:[7]

This same mechanistic process is seen below, without the final electrocyclic ring-closing reaction, in
the interconversion of lumisterol to vitamin D2.

[1,7] Shifts[edit]
[1,7] sigmatropic shifts are predicted by the WoodwardHoffmann rules to proceed in an antarafacial
fashion, via a Mobius topology transition state. An antarafacial [1,7] shift is observed in the
conversion of lumisterol to vitamin D2, where following an electrocyclic ring opening to previtamin D2,
a methyl hydrogen shifts.[8]

Bicyclic nonatrienes also undergo [1,7] shifts in a so-called walk rearrangement,[9] which is the shift
of divalent group, as part of a three-membered ring, in a bicyclic molecule.

[3,3] Shifts[edit]
[3,3] sigmatropic shifts are well studied sigmatropic rearrangements. The WoodwardHoffman rules
predict that these six electron reactions would proceed suprafacially, via a Huckel topology transition
state.
Claisen rearrangement[edit]
Main article: Claisen rearrangement

Discovered in 1912 by Rainer Ludwig Claisen, the Claisen rearrangement is the first recorded
example of a [3,3]-sigmatropic rearrangement.[10][11][12] This rearrangement is a useful carboncarbon bond-forming reaction. An example of Claisen rearrangement is the [3,3] rearrangement of
an allyl vinyl ether, which upon heating yields a ,-unsaturated carbonyl. The formation of a
carbonyl group makes this reaction, unlike other sigmatropic rearrangements, inherently irreversible.

Aromatic Claisen rearrangement[edit]

The ortho-Claisen rearrangement involves the [3,3] shift of an allyl phenyl ether to an intermediate
which quickly tautomerizes to an ortho-substituted phenol.

When both the ortho positions on the benzene ring are blocked, a second ortho-Claisen
rearrangement will occur. This para-Claisen rearrangement ends with the tautomerization to a trisubstituted phenol.

Cope rearrangement[edit]
Main article: Cope rearrangement
The Cope rearrangement is an extensively studied organic reaction involving the [3,3] sigmatropic
rearrangement of 1,5-dienes.[13][14][15] It was developed by Arthur C. Cope. For example 3,4-dimethyl1,5-hexadiene heated to 300 C yields 2,6-octadiene.

Oxy-Cope rearrangement[edit]
Main article: Oxy-Cope rearrangement
In the Oxy-Cope rearrangement, a hydroxyl group is added at C3 forming an enal or enone
after Keto-enol tautomerism of the intermediate enol:[16]

Carroll rearrangement[edit]
Main article: Carroll rearrangement
The Carroll rearrangement is a rearrangement reaction in organic chemistry and involves the
transformation of a -keto allyl ester into a -allyl--ketocarboxylic acid.[17] Thisorganic reaction is
accompanied by decarboxylation and the final product is a ,-allylketone. The Carroll
rearrangement is an adaptation of the Claisen rearrangement and effectively a decarboxylative
allylation.

Fischer indole synthesis[edit]

Main article: Fischer indole synthesis
The Fischer indole synthesis is a chemical reaction that produces
the aromatic heterocycle indole from a (substituted) phenylhydrazine and
an aldehyde or ketone under acidicconditions.[18][19] The reaction was discovered in 1883 by Hermann
Emil Fischer.

The choice of acid catalyst is very important. Bronsted acids such as HCl, H2SO4, polyphosphoric
acid and p-toluenesulfonic acid have been used successfully. Lewis acids such as boron
trifluoride, zinc chloride, iron(III) chloride, and aluminium chloride are also useful catalysts.
Several reviews have been published.[20][21][22]

[5,5] Shifts[edit]

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

[2,3] shifts[edit]
An example of an 2,3-sigmatropic rearrangement is the 2,3-Wittig rearrangement:

Walk rearrangements[edit]
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. [23] An
example of such a rearrangement is the shift of substituents on tropilidenes (1,3,5cycloheptatrienes). When heated, the pi-system goes through an electrocyclic ring closing to form
bicycle[4,1,0]heptadiene (norcaradiene). Thereafter follows a [1,5] alkyl shift and an electrocyclic ring
opening.

Proceeding through a [1,5] shift, 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.[24] Theoretical calculations found the [1,5] shift to
be a diradical process, but without involving any diradical minima on the potential energy surface.[25]