Sigmatropic

Rearrangement
Name: Anushka Sunam
Roll no. 001920101075
B.Sc. Chemistry
Paper: DSE/Chem/PR/04
UNIT: 604L-O
 Introduction

Sigmatropic Rearrangement in Organic Chemistry is a class of pericyclic reactions which are the
intramolecular reaction in which a sigma bond migrate from one position to another over an
unsaturated system. The name sigmatropic is the result of a compounding of the long-established
sigma designation from single carbon-carbon bonds and the Greek word tropos, meaning turn.
There is a rearrangement of pi-bonds to accommodate for the newly formed sigma bonds while the
total number of pi-bonds remains the same. The most commonly known examples of sigmatropic
rearrangement are Claisen Rearrangement, Cope Rearrangement and Walk Rearrangement

2
Classification of Sigmatropic Rearrangement:
Sigmatropic rearrangements are classified by two numbers within a bracket i.e, [i,j]
That refers to the relative positions of the atom or group involved in the migration

In sigmatropic rearrangement, the substrate can be divided into two parts: the Alkenyl (or polyalkenyl) chain and migrating
group. All substrates have at least one allylic carbon in an alkenyl chain for sigmatropic rearrangement.

Numbering of alkenyl chain is always started from Atom (H, C or heteroatom) of migrating group bonded with
the allylic carbon and this carbon is numbered-1 allylic carbon by σ (sigma) bond is always given number-1

3
Classification of Sigmatropic Rearrangement:

In the following example, atom-1 of the migrating group migrates on the atom-3 of the alkenyl chain.
Therefore, this rearrangement would be classified as a [1, 3] sigmatropic rearrangement

Following is an example of [1, 7] sigmatropic rearrangement:

4
Classification of Sigmatropic Rearrangement:

Now, is it always so that the first atom of the migrating group will be bonded to the alkenyl chain in the
rearrangement?

In this rearrangement atom-3 of the migrating group migrates on atom-3 of the alkenyl chain. Therefore, this
rearrangement is an example of [3, 3] sigmatropic rearrangement

5
Suprafacial and Antarafacial Processes
Since a sigmatropic reaction involves the migration of an s-bond across the p-electron system, there are two different
stereochemical courses by which the process may occur.

When migration pi- bonds get moved When migration pi- bonds get moved across the
across the same face of the conjugated opposite face of the conjugated system it is a
system it is a suparafacial process antarafacial process

Due to steric reasons, suprafacial migration is more common than antarafacial shifts. However, with the lengthening
of the conjugated system. Sometimes it is possible for a σ-bond to migrate to the opposite π electron face.

6
Suprafacial and Antarafacial Processes
In case of carbon shifts:

7
Theoretical Approach to Sigmatropic Rearrangement Reactions: FMO Approach

Thermally-induced sigmatropic rearrangement for a [1, 3] shift:

• For the purpose of analyzing the orbitals, it is assumed that the σ (sigma) bond connecting the migrating group to its
original position undergoes homolytic cleavage to yield two free radicals.

• This is not how the reaction takes place because the reaction is concerted. HOMO
• This assumption can be explained by the molecular orbitals approach.
The hypothetical cleavages is a hydrogen atom and an allyl free radical
And the ground state configuration for the propenyl radical is radical is Ѱ12Ѱ22

8
Theoretical Approach to Sigmatropic Rearrangement Reactions: FMO Approach
Under Photochemical Condition:

• [1, 3] sigmatropic shifts take place in the presence of UV light but examples are rare. Consider again what happens when a
molecule absorbs a photon.
• LUMO of ground state will become HOMO of the excited state known as photochemical HOMO

Under photochemical condition:

9
FMO Approach for Allowed and Forbidden Reactions

For [1,5] Sigmatropic Rearrangement

Mechanism:

The ground state electronic configuration of pentadienyl radical is Ѱ12Ѱ22 Ѱ3. Since HOMO ( Ѱ3 ) of this
radical has a similar sign on the terminal lobes, [ 1,5 ] suprafacial migration will be a thermally allowed
process

10
The first excited state of the pentadienyl radical has the configuration Ѱ12Ѱ22 Ѱ4 and the
symmetry characteristics of HOMO ( Ѱ4 ) are thus reversed ( C2 symmetry).

Thermal Reaction Photochemical Reaction

11
The Woodward–Hoffmann Generalized Rules

We may now summarize the

Woodward Hoffman Selection
Rule for symmetry allowed [1,n]
Sigmatropic Rearrangement. Here
a and s refer to antarafacial and
suprafacial respectively and r and
I to the retention and inversion of
configuration in the migrating
system

12
Types of Sigmatropic Rearrangement Reaction:
a) [i, j] shifts:
i. [1,2] shifts
ii. [1,3] shifts
iii. [1,5] shifts
iv. [1,7] shifts
b) [3,3] shifts:
i. Claisen rearrangement
ii. Aromatic Claisen rearrangement
iii. Cope rearrangement
iv. Oxy-Cope rearrangement
v. Carroll rearrangement
vi. Fischer indole synthesis
c) [5,5] Shifts
d) [2,3] shifts

13
Types of Sigmatropic Rearrangement Reaction: [1,j] shifts

[1,2] Shifts:
Often initialized by the formation of a reactive intermediate such as a carbocation or a carbanion to form a more stable
intermediate. Many name reactions involve a [1,2] shift such as Wagner-Meerwein, Beckmann, or Stevens rearrangement.

Wagner–Meerwein rearrangement: carbocation 1,2-rearrangement reactions in which a hydrogen, alkyl or aryl

group migrates from one carbon to a neighboring carbon. They can be described as cationic [1,2]-sigmatropic
rearrangements, proceeding suprafacially and with stereochemical retention. As such, a Wagner–Meerwein shift is
a thermally allowed pericyclic process.
The rearrangement was first discovered in bicyclic terpenes for example the conversion of isoborneol to camphene:

A Wagner-Meerwein rearrangement is any reaction in which the carbon skeleton of a reactant changes due to one or
more rearrangements involving carbocations
14
Types of Sigmatropic Rearrangement Reaction: [1,j] shifts
[1,3] Sigmatropic rearrangement:

Thermal [1,3] hydride shifts: The Mobius topology required in the transition state prohibits such a shift because it is
geometrically impossible.

Thermal [1,3] alkyl shifts: Geometry of the transition state is prohibitive, but an alkyl group can invert its geometry, and
therefore proceed via a suprafacial shift.

- Antarafacial [1,3] alkyl shift: symmetry allowed, Suprafacial [1,3] alkyl shift with inversion: symmetry allowed
geometrically impossible

Photochemical [1,3] shift: should proceed suprafacially; however, most are nonconcerted (have a diradical mechanism, to
15
which the Woodward-Hoffmann rules do not apply
Types of Sigmatropic Rearrangement Reaction: [1,j] shifts

[1,5] Sigmatropic rearrangement: involving the shift of 1 substituent (H, alkyl, or Ar) down 5 atoms of a π system.
Suprafacial thermal shifts are quite common, while antarafacial photochemical shifts are rarely observed.

16
In one particularly elegant experiment carried out in 1964, also by Roth, 1,3,5-cyclooctatriene was labeled at
carbons 7 and 8 with deuterium and then allowed to undergo many hydrogen shifts for a long time. When the
molecule undergoes [1,5] hydrogen shift, the D should migrate part of the time, and the H part of the time.
However, after a long time, the D should eventually scramble to all positions that have a 1,5-relationship. In
such a case, only carbons 3, 4, 7, and 8 would be partially deuterated

On the other hand, if the molecule undergoes successive [1,3] hydrogen (or deuterium) shifts, the
deuterium should be scrambled eventually to all positions

The experimental result was that, even after very long reaction
times, deuterium appeared only in the positions predicted by
the [1,5] shift.

17
[3,3] Sigmatropic Rearrangement: Claisen Rearrangement

1.

2.

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.
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. Trivalent organoaluminium reagents, such as trimethylaluminium, have
been shown to accelerate this reaction. Common Example: Discovered in 1912 by Rainer Ludwig Claisen, the Claisen
rearrangement is the first recorded example of a [3,3]-sigmatropic rearrangement. This rearrangement is a useful carbon-
carbon bond-forming reaction. An example of Claisen rearrangement is the [3,3] rearrangement of an allyl vinyl ether,
which upon heating yields a γ,δ-unsaturated carbonyl. The formation of a carbonyl group makes this reaction, unlike other
sigmatropic rearrangements, inherently irreversible.
18
Claisen Rearrangements in BIOLOGY
The enzyme Chorismate mutase catalyzes the Claisen rearrangement of chorismate ion to prephenate ion, a key intermediate in
the shikimic acid pathway (the biosynthetic pathway towards the synthesis of phenylalanine and tyrosine).

3
3 3 3 2
2 2 1
2

1 1
1

19
Variations of Claisen Rearrangement
Aromatic Claisen rearrangement
The first reported Claisen rearrangement is the [3,3]-sigmatropic rearrangement of an allyl phenyl ether to intermediate
1, which quickly tautomerizes to a 2-allylphenol

Meta-substitution affects the regioselectivity of this rearrangement. For example, electron withdrawing groups (such as
bromide) at the meta-position direct the rearrangement to the ortho-position (71% ortho product), while electron donating
groups (such as methoxy), direct rearrangement to the para-position (69% para product). Additionally, presence of ortho
substituents exclusively leads to para-substituted rearrangement products (tandem Claisen and Cope rearrangement).
Mechanism:
Step 1: Step 1 Step 2
An electrocyclic process. Push those electrons around the 6
membered ring.... Best appreciated by starting the electron
flow by having the aromatic C=C attacking the allyl C=C and
displacing an O leaving group.
Step 2:
Tautomerisation of the ketone (actually a dienone) to the more
20
stable aromatic enol, the phenol.
Variations of Claisen
[1, J] Sigmatropic Rearrangement
Rearrangements
One of the most useful sigmatropic rearrangements is the Claisen rearrangement
and all it’s variants

Also called the orthoester Claisen rearrangement, involves the reaction of allylic alcohol with an orthoester, often triethyl
orthoacetate, in the presence of a carboxylic acid such as propionic acid usually at lower temperatures. The intermediate
ketene acetal rearranges stereoselectivity

The Eschenmoser–Claisen rearrangement proceeds by heating allylic alcohols in the presence of N,N-dimethylacetamide
dimethyl acetal to form a γ,δ-unsaturated amide. This was developed by Albert Eschenmoser in 1964. Eschenmoser-Claisen
rearrangement was used as a key step in the total synthesis of morphine.

21
Cope Rearrangement- [3,3] Sigmatropic Rearrangement
The Cope rearrangement is an extensively studied organic reaction involving the [3,3]- sigmatropic rearrangement of 1,5-
dienes. It was developed by Arthur C. Cope. For example 3-methyl-1,5-hexadiene heated to 300°C yields 1,5-heptadiene. The
Cope rearrangement causes the fluxional states of the molecules in the bullvalene family.

The rearrangement is widely used in organic synthesis. It is symmetry-allowed when it is suprafacial on all
components. The transition state of the molecule passes through a boat or chair like transition state. An example of the
Cope rearrangement is the expansion of a cyclobutane ring to a 1,5-cyclooctadiene ring

In this case, the reaction must pass through the boat transition
state to produce the two cis double bonds. A trans double
bond in the ring would be too strained. The reaction occurs
under thermal conditions. The driving force of the reaction
is the loss of strain from the cyclobutane ring.
22
Mechanism: Although the Cope rearrangement is concerted and pericyclic, it can also be considered to go via a transition
state that is energetically and structurally equivalent to a diradical. This is an alternative explanation that remains faithful
to the uncharged nature of the Cope transition state while preserving the principles of orbital symmetry. This also explains
the high energy required to perform a Cope rearrangement. However, conformationally constrained systems like cis-1,2-
divinylcyclopropanes can undergo the rearrangement in the boat conformation

23
Cope Rearrangement- [3,3] Sigmatropic Rearrangement

1. 2.

3.

Reactions 1 and 2 (top row) demonstrate the stereospecificity of this reaction

Reaction 3: The diene reactant in the third reaction is drawn in an extended conformation. This molecule must assume a
coiled conformation (as above) before the [3,3] rearrangement can take place. The product of this rearrangement is an enol
which immediately tautomerizes to its keto form. Such variants are termed the oxy-Cope rearrangement, and are useful
because the reverse rearrangement is blocked by rapid ketonization.

24
Cope Rearrangement- [3,3] Sigmatropic Rearrangement

Cope rearrangements can be driven by the relief of strain, as illustrated by the following synthesis of the seaweed
pheromone, dictyopterene C found in several species of brown algae (Phaeophyceae)
The chemical formula of dictyopterene C' is 6-butylcyclohepta-1,4-diene.

Brown Algae
(Phaeophyceae)

25
Aza-Cope Rearrangement- [3,3] Sigmatropic Rearrangement

Nitrogen-containing 1,5-dienes undergo [3,3]-sigmatropic rearrangement just like the Cope rearrangement of 1,5-dienes.
Among these so-called aza-Cope rearrangements, the 3-aza version is sometimes referred to as the aza-Claisen
rearrangement. In well-designed systems, the 2-aza version is known to undergo the Mannich reaction sequentially, in which
case the reaction is called the aza-Cope/Mannich reaction.

26
Fisher Indole synthesis
Fisher Indole synthesis: It is a chemical reaction that involves a synthesis of the aromatic heterocycle indole from a
(substituted) phenylhydrazine and an aldehyde or ketone. This reaction takes place under acidic conditions.

Triptan Indometacin
27
References

https://www.ch.ic.ac.uk/local/organic/pericyclic/p1_sigma.html

https://www2.chemistry.msu.edu/faculty/reusch/VirtTxtJml/pericycl.htm#top1

Organic Reactions and their Mechanisms- P.S Kalsi

https://www.sciencedirect.com/topics/chemistry/vitamin-d2

https://en.wikipedia.org/wiki/Sigmatropic_reaction#:~:text=Sigmatropic%20rearrangements
%20are%20concisely%20described,location%20of%20the%20%CF%83%2Dbond
.

https://en.wikipedia.org/wiki/Claisen_rearrangement#Aromatic_Claisen_rearrangement

https://www.chem.ucalgary.ca/courses/353/Carey5th/Ch24/ch24-4-3.html

28
Conclusion

29