A Brief Description on Pericyclic Reactions

(Student reference)
 Pericyclic Reactions
Peri= periphery, around
Cyclic= following a circular path or forming a cycle

Definition: Pericyclic reaction is defined as a thermal or photochemical induced

reaction involving a stereospecific, (rather highly stereoselective) concerted cyclic shift
of the electrons. The reactant is converted to a product typically by a cyclic
conjugated transition state (T.S) either thermally or photochemically.
The first key term concerted implies to no intermediate since bond breaking
and bond making takes place simultaneously. The second key point cyclic shift of
electrons signifies a kind of reaction that occurs around the periphery of a molecule
following a typical involvement of π-orbital via a circular pathway. It rules out either
homolytic/heterolytic cleavage or radical/ionic pathway.

There are three major classes of pericyclic reactions. Besides, Group transfer
reaction is accounted as another class of pericyclic reactions.

Characteristics features of Pericyclic reactions

1. A concerted pathway via a single cyclic conjugated T.S where lack of evidence in
isolation of intermediate like free radical, carbocation etc. rather the bond
breaking and bond making takes place synchronously.
 2. Cyclic shift of electrons as a result of in general participation of p/π-orbital with
some extent to σ-bond: A reorganization of electron pairwise within the close
loop of interacting orbitals (around cyclic).
3. Usually unaffected by acids or bases, the change of solvent polarity, catalyst
(exception in Diels-Alder cycloaddition reaction accelerated by Lewis acid catalyst)
and radical initiator or change in structural motif of the molecule.
4. No nucleophilic or electrophilic reagents are required.
5. No such ionic or radical pathway.
6. Highly stereoselective in nature.
7. Most of the reactions are equilibrium processes in which direction of equilibrium
depends on the enthalpy and entropy of the reacting species. Large decrease in
entropy or loss of degree of freedom illustrates the rigid transition state (e.g D.A
reaction ΔS≠ = —150 to —200 JK-1mole-1 and in sigmatropic reaction ΔS≠ = —50
JK-1mole-1) and with a low enthalpy of activation reflecting the exothermic nature
of the reaction.
8. They follow Woodward-Hoffmann rule of “Conservation of Orbital Symmetry”
which states that the orbital symmetry should be maintained through out the
reaction i.e before and after the reaction the orbital symmetry of both the
reactant and product should be conserved. Thus, it is an orbital symmetry
controlled reaction. The pericyclic reaction excludes any usual nucleophilic-
electrophilic selective transformation of stereoheterotopic faces and ligand
discrimination by intramolecular symmetry.
Source/ Influencing factor/Mode of activation
1. Heat or Thermal (Δ)
2. Light or Photochemical (hγ)
Non- Influencing factor
1. Polar/Non polar solvents.
 2. Radical initiator or inhibitor.
3. Catalysis (except Diels-Alder cycloaddition reaction).

Criteria for Pericyclic Reaction

1. Mode of activation. (Δ/ hγ)
2. Number of p/π-orbital participatiion [4nπ or (4n+2)π]
3. Stereochemical outcome (stereospecific or stereoselective).
Advantages of Pericyclic Reaction
(a) Generation of variety of new carbon-carbon σ-bond (due to reorganization of
p/π-bond).
(b) Less probabilities of formation of unwanted side products. (due to concerted
cyclic process and unreacted or unaffected by the influence of solvent or any
reagent). So, it is straight forward, non-complicated and anticipated reaction.
(c) The reaction is highly stereospecific in nature. (due to concerted orbital
symmetry controlled process).
(d) Enormous application in biosynthesis.
(e) Non conventional energy source e.g. the cycloreversal of cyclobutane to two
ethelene molecule is accompanied by liberation of heat.

hy

Evidence for the concertedness of Pericyclic reaction

Point 1: Although small, an inverse secondary kinetic isotope effects was observed for
the following diene and the dienophile when the deuterium substitution on the four
carbon atoms changes from trigonal to tetrahedral as the reaction proceeds. It was
experimentally found a geometrically related (kD/kH)2 = (kD2/kH) [not arithmetically
related, (kD2/kH) = 2(kD/kH) —1] to the isotope effects at both deuterated ends
indicating both ends are formed simultaneously.
Point 2: Bimolecular reactions account for inherently high negative entropies of
activation (ΔS≠). Exceptionally high negative ΔS≠ (typically in the range of —150 to
—200 J K—1 mol—1) for Diels-Alder (D.A) reactions or cycloaddition reactions
reveals a favourable alignment with compact transition structure of two components
only if both bonds can form at the same time.
Point 3: The rates of D.A reactions are slightly increased by a factor of only 10 upon
the change in the polarity of the solvents or with large change in dipole moment
from 2.3 to 39 in contrast to several orders of magnitude for stepwise ionic
cycloaddition reactions.
Point 4: The dienophile tetracyanoethylene reacts significantly much faster rate with
butadiene than 1,1-dicyanoethylene which can’t be rationalized by ionic stepwise
pathway.

Q. What is the difference between S N2 reaction and pericyclic reaction although both
literally proceed in stereospecific concerted manner?
SN2 reaction constitutes a transition state of non-isolable intermediate that
may be linear or cyclic transition state where the HOMO of nucleophilic approach
must be exactly opposite to that of LUMO of leaving group. A stereospecific product
having inversion of configuration is expected to result in SN2 reaction. On the other
side, Pericyclic reaction is an orbital symmetry controlled reaction with non-isolable
intermediate via cyclic conjugated transition state which demands stereospecific
product by virtue of suprafacial or anatarafacial or HOMO-LUMO interaction.
Woodward-Hoffmann Selection Rule
Let us take an example in which maleic anhydride reacts butadiene
spontaneously but not with ethelene under thermal condition.
O O

O O

O O
O O

O O

O O
In order to explain the phenomenon, we need to consider the Woodward-
Hoffmann selection rule.
In a Pericyclic reaction, the set of in phase atomic orbitals (A.Os) to form
molecular orbitals (M.Os) of reactants are transformed into corresponding in phase
set of M.Os of the products by conserving the symmetry of the orbitals throughout
the reaction in a concerted manner via symmetry allowed low energy transition state.
This is called as woodward-Hoffmann rule of “Conservation of Orbital Symmetry”.
This clearly indicates that the orbital symmetry should be maintained through out the
reaction i.e before and after the reaction the orbital symmetry of both the reactant
and product should be conserved. Hence, Pericyclic reaction can be attributed as
orbital symmetry controlled reaction.
Maintaining the principle of conservation of orbital symmetry, a Pericyclic
reaction can be visualized as reorganization of electron (pairwise) with in a close loop
of interacting orbitals through symmetry allowed concerted process.
Selective transformation of organic reaction is based on
(a) Stereoheterotopic faces
(b) Stereoheterotopic ligand
 These are distinguished by intramolecular symmetry or overall symmetry of
the molecule. But, the Pericyclic Reaction relies on the interactive molecular orbitals
(M.Os), not as a whole molecular symmetry.
The basic difference between pericyclic chemistry with heterocyclic or alicyclic
reaction is that the pericyclic reaction is guided by “Rule of Conservation of Orbital
Symmetry” proposed by Woodward and Hoffman. In addition to this, the former
involves a cyclic concerted process with the help of p/π-orbital and the mode of
activation must be either thermal or photochemical. No other reagents are associated
with the pericyclic reaction.
To explain the stereochemistry of the product, three fundamental approaches
have to be considered-
1. Correlation of orbitals in relation to symmetry should be preserved (W. H
principle).
2. Aromaticity or anti aromaticity of T.S by Hückel Molecular orbital theory.
3. Fronteir Molecular Orbital (FMO) approach: HOMO-LUMO interactions.
Most of the pericyclic reactions, of course not all, are little influenced by
Coulombic forces e.g. the rates of D.A reactions are little affected by polarity of the
solvent. We can therefore expect that the major factor influencing the reactivity will
be the size of the Frontier orbital interaction represented by energy expression from
Klopman and Salem’s perturbation of orbital symmetry. Thus, FMO approach among
three fundamental approaches is most widely applicable in Pericyclic reaction.
Class of Pericyclic Reactions
Pericyclic Reaction

Electrocyclic Cycloaddition Sigmatropic Ene

(Ring closure/opening) Rearrangements
 Electrocyclic Reaction
An intramolecular pericyclic reaction where reversible concerted cyclic shift of
electrons occurs by virtue of ring closing with the formation of new σ-bonds across
the ends of conjugated acyclic π-electrons of polyene or breaking of ring to form
acyclic analogue from its corresponding cyclic framework, is typically termed as
Electrocyclic reaction. The reaction can be best way represented by the following
diagram;

(K)pi

a new sigma bond

is formed

new
(K-2)pi
sigma bond one sigma bond
is broken

The reaction is activated either by heat or by UV-light. The reaction follows

the principle of microscopic reversibility. The reaction sequence can be explained by
three fundamental approaches;
(a) Correlation of orbital symmetry of terminal lobes of interacting orbitals
(b) Perturbation of M.O theory or HMO theory of aromaticity or anti aromaticity in
T.S
(c) FMO approach of HOMO-LUMO interactions of orbital energy states.
Conditions for Electrocyclic Reaction
1. Symmetry of terminal orbitals in conjugated π-system has to be considered.
2. Terminal p-orbitals form σ-bond by maintaining phase distribution of lobes
after rotation.
3. Two possible ways of the rotation of lobes or p-orbitals: (a) Conrotation
motion (b) Disrotation motion.
 4. Movement of the groups or substituents attached to terminal lobes
according to the lobe’s movements which bring about the stereochemistry of the
resultant product.
5. Conrotation or disrotation should follow Woodward –Hoffmann principle
of orbital symmetry and will be favoured if the process is devoid of any steric
crowding and generation of strain in the molecule.

Example of electrocyclic reactions and their stereochemical significance of two

modes of ring opening/closing are illustrated through thermal and photochemical
transformations of isomeric 3,4-dimethylcyclobutenes and isomeric 5,6-
dimethylcyclohexa-1,3-dienes. The stereochemistry of the substituents depends on
the mode of activation and the mode of rotation of terminal orbitals

Let us consider a butadiene system (4nπ) as s-cis conformation where the

terminal groups are considered as ‘in’ group (concave face of the arc) and ‘out’ group
(convex face of the arc).
 in

out
out
out

in in Enantiomers
Conrotation C2 -orbital symmetry
in Symmetry allowed
out Thermal
in phase overlap out
2HOMO
in
Thermal in
Disrotation

Symmetry forbidden out

Out of phase overlap
out
Photochemical
Conrotation in
out

out
in Enantiomers
Disrotation m- orbital symmetry
in Symmetry allowed
Photochemical
in in
out in phase overlap

3HOMO in
out

out

If the termini rotates in the same direction i.e. either both clockwise or both
anticlockwise, is called Conrotatary motion. Here both ‘in-in’ and ‘out-out’ groups
are in trans relationship. If the termini rotates in the opposite direction i.e. one in
clockwise and another in anticlockwise or vice-versa, is called Disrotatary motion.
Here both ‘in-in’ and ‘out-out’ groups are in cis relationship. In both cases the
enantiomeric mixtures are formed. Enantiomers have equal energies and hence
enantiomeric pathways have identical energies. The enantiomeric excess depends on
the movements of the termini offering the in phase orbital overlap.
 During conrotation C2 symmetry has been maintained whereas for disrotation
mirror plane (m) symmetry has been followed for 4nπ system. But the situation is
exactly reversed in case of (4n+2)π system. It should be kept in mind that in both
cases HOMO orbitals do participate in the conrotation or disrotation pathway which
in turn regulates the stereochemical outcome.

Pictorial Representation: FMO Approach

According to Frontier Molecular Orbital approach, the valence π-electrons in

the HOMO orbital of polyene system dictates the course of the Pericyclic Reaction.
Similarly the valence π-electrons in the HOMO orbital of cyclo-polyene system also
regulate the course of the pericyclic reaction. Therefore, combination of above
HOMO orbital participation ultimately leads to a bonding interaction. The selection
of HOMO participation obviously depends on the mode of activation.
Let us consider a photochemical electrocyclic ring closure reaction of 1,3
butadiene to cyclobutene derivative. The pictorial representation is shown below.

Me
But
hy But
Me
disrotation
H H
But Me
Path-A in phase H H
trans-trans H
symmetry allowed bonding overlap H
HOMO
3

H H

hy H
H
disrotation
H H
But Me
Path-B But
But in phase
trans-trans symmetry allowed Me Me
bonding overlap
HOMO
3

Which pathway is more favourable, Path-A or Path-B?

Both the Path A and Path B are symmetry allowed process and is represented
by [σ2S + π2S] interaction where ‘S’ stands for suprafacial interaction. The FMO
suggests the both pathways are facilitated by suprafacial in phase bonding interaction
leading to symmetry allowed process. Although enantiomeric mixture is formed but
the Path-A is slightly enegetically more favourable than Path-B since during T.S the
bulky substituents tBu and Me groups tend to move towards inward direction in Path-
B although both of the pathways results syn conformation. But such impact is even
more pronounced while considering reverse reaction i.e. Electrocyclic ring opening.
Then it will be observed that inward movements of arrows can be better pathways
than outward movements of arrows because the later constitutes a bulk effect as a
result of direct confrontation in T.S due to close proximity of tBu and Me groups. This
makes Path-Y although symmetry allowed process but not observed due to
thermodynamically almost impossible situation to take place.

Me
But
hy
disrotation H H
But Me
But Me
Path-X H H
H in phase H
symmetry allowed outward movement of groups
bonding overlap trans-trans
thus feel no steric croweding
Pi* HOMO

H H

hy
H H
disrotation But But Me
Me H
Path-Y H
in phase cis-cis
But Me intward movement of groups
bonding overlap symmetry
allowed thus feel serious steric croweding,
Pi* HOMO but not observed so very unfavourable pathway

Thermal induced cyclization uses ground state ψ3 as HOMO which has m-

symmetry. So, the mode of thermal cyclisation is disrotatory motion. Photochemical
induced cyclization uses excited state ψ4 as HOMO which has C2-symmetry. So,
conrotatory motion is the mode of photo-induced cyclisation. For ring opening
reaction, the similar energy of HOMO orbital, the symmetry element and mode of
reaction would be followed.
 In case of 6π i.e [(4n+2)π] system, the same situation happens as that found in
4π system. Here both Path-A and Path-B have equal probabilities during thermal
induced ring closing reaction. Because of similar type of steric interaction may occur
at T.S, their formation of either pathway is statistically favourable. However, the
photochemical pathway is both kinetically and thermodynamically unfavourable
compared to that of thermal process because Path-D clearly shows a bulk atmosphere
during the course of the reaction.
Thermal (4n+2)pi system

COOR
COOR
Ar H
Thermal
ROOC Disrotation
Ar
HOMO Path-A H Ar
3
anti-enantiomers

Ar H Ar
Ar
Thermal
ROOC Disrotation

HOMO Path-B COOR COOR H

3

Photochemical (4n+2)pi system

COORAr COOR
Ar Ar
Photochemical
Conrotation
ROOC
HOMO Path-C H H
4

syn-enantiomers

H H
Ar
Photochemical
Conrotation
ROOC
Path-D ROOC Ar
HOMO COOR Ar
4
Allylic carbocationic system
THERMAL

MeOOC Et

MeOOC MeOOC Et
Et

H H
Thermal
Disrotation in phase
MeOOC Et symmetry allowed bonding overlap

H H
HOMO
1
Thermal
Conrotation out of phase
symmetry Forbidden antibonding overlap MeOOC Et COOMe Et
Even more favourable process
MeOOC due to all suprafacial interaction
leadind to greater extent of bond strength

Et PHOTOCHEMICAL

MeOOC MeOOC H

H Et
Photochemical Et
Conrotation in phase
MeOOC Et symmetry allowed bonding overlap

H Et
HOMO
2
Photochemical
Disrotation out of phase
symmetry Forbidden antibonding overlap MeOOC Et COOMe H
Bothsteps are equally favourable
MeOOC Et due to enegetically equivalent steps

Q. What is the driving force for allylic cation or pentadienyl cation to undergo
Electrocyclic Ring closure reaction?
Ans: Generally less conjugated carbocations undergo in Electrocyclic ring closing
reaction. The formation of ring from allylic or pentadienayl cation increase the strain
in the ring as well as decrease the stabilization of carbocation. In spite of that such
reactions undergo due to gain in extra carbon-carbon σ-bond which compensate the
destabilization energy.
FMO of butadiene

FMO of hexatriene

The following table provides a correlation among the entire factors associated
with Elecrocyclic Reaction.
No. of π Mode of Reactants Product
Symmetry Pathway
electrons activation stereochemistry Stereochemistry
trans-trans
trans
4nπ C2(s) Thermal(Δ) Conrotation cis-cis
trans-cis cis
trans-trans
Photochemical cis
4nπ m(s) Disrotation cis-cis
(hγ)
trans-cis trans
trans-trans
cis
(4n+2)π m(s) Thermal(Δ) Disrotation cis-cis
trans-cis trans
trans-trans
Photochemical trans
(4n+2)π C2(s) Conrotation cis-cis
(hγ)
trans-cis cis

Thermal electrocyclic reactions involving a total number of electrons that can

be expressed in the form (4nþ2) are disrotatory, and thermal electrocyclic reactions in
which the total number of electrons can be expressed in the form (4n) are
conrotatory. Some examples of electrocyclic reaction are shown below.
 Ex 1: A representative of various types of electrocyclic reactions is illustrated.

Ex 2: The reaction below is photo-induced conrotatory mode of reaction in

which reactant comprises (4n + 2)π electrons with ψ4* excited HOMO having C2-
symmetry.

Ex 3: The following disrotatory mode of conversions of hexatriene [(4n + 2)π

electrons system] are observed in thermal condition.

Ex 4: The following reactions represent double electrocyclic ring closure

reaction. The first involves (4n)π electrons, resulting a conrotatory motion while the
second cyclization has (4n + 2)π electrons showing disrotatory motion.
 Ex 5: Octatetraene produces 7,8-dimethyl cycloocta-1,3,5-triene upon
photochemical disrotatory ring closure followed by thermal disrotatory
electrocyclization to yield fused ring.

Ex 6: Under thermal conditions, cyclooctatetraene preferentially undergoes a

6π-electron disrotatory electrocyclization whereas under photochemical conditions,
cyclooctatetraene preferentially undergoes a 4π-electron disrotatory
electrocyclization. However, both form only the cis-isomer.

Ex 7: Compound II and III are formed by the ring opening via thermal
conrotation and disrotatory electrocyclization respectively. Compound III undergoes
[1,5] hydrogen shift to yield IV.

Ex 8: [16]-annulene isomerizes both thermally through two cis-fused 6-

membered double disrotatory closure and photochemically through two trans-fused
6-membered double conrotatory closure.
 Ex 9: It is usual for a photochemical reaction to favour the less stable isomer of
an equilibrium. For instance, the conjugated diene absorbs UV light, but the bicyclic
compound does not, hence, the photochemical reaction favours the latter.

Ex 10: The allowed thermal conrotatory process would give a highly strain
molecule containing a trans double bond within a small ring.

Ex 11: (2Z, 4Z, 6Z)-2, 4, 6-cyclooctatrione first isomerizes photochemically to

(2E, 4Z, 6Z)-2, 4, 6-cyclooctatrienone, which then cyclises thermally to cis-bicyclo
[4, 2, 0]octa-3, 6-dien-2-one by a conrotatory process.

Ex 12: Thermal isomerization of cis-bicyclo [6, 2, 0] deca-2, 9-diene gives (1E,

3Z, 5Z)-1, 3, 5-cyclodecatriene.

Ex 13: In bicycloheptane, a conrotatory reaction is virtually impossible since it

would put trans double bond in the seven membered ring. Rather a forbidden
disrotatory reaction occurs at high temperature (≈ 400 oC).
 Ex 14: Since the ring fusion as well as double bond within the ring is the low
energy cis arrangement, a conrotatory ring opening is expected to give strained trans
double bond within 8-membered ring. It is thermodynamically unfavourable. The
reaction thus needs a high temperature to resulting in the formation of another
isomer.

Ex 15: Stereoisomeric pentadienyl cations give stereoiosmeric cyclopentenyl

cations in conrotatory reactions. The reactions are fully stereospecific. In contrary, for
cyclopentenyl anion that disrotatory opens to allow two H’s moving outward.

Ex 16: In case of constrained systems, the photochemical reaction can easily

lead to a product thermodynamically much higher in energy than the starting
material; but nevertheless they are thermally stable. Because the bicyclic ketone (first
reaction) lost is not only strained but it lost the partial aromaticity of tropone and
similar loss of aromaticity for dihydroanthracene from cis-stilbene.
 Ex 17: Disrotatory ring opening of various cyclopropyl halide results three
different shapes of allyll cations: W-shaped, sickle shape and U-shaped which largely
retain their conformation at low temperature as obvious from 1H NMR spectroscopy.
These recations demonstrate torqueoselectivity. It defines that the direction of
disrotatory ring opening is determined by which side of the ring the halide leaves
from as shown from contrast between the products from the cyclopropyl halides. The
former opens the two –CH3 groups moving outwards as thermodynamically preferred
direction. However, later shun thermodynamics to open as U-shaped geometry.

Ex 18: There is another example of Torquoselectivity as the predisposition of a

given R substituent for a given conrotatory motion. Steric factors cause a preference
for the larger group to move outward. It is observed that π-donor substituents prefer
con-out mode whereas π-acceptor substituents prefer con-in mode.

Ex 19: The trans isomer of 2,3-ditertiary butyl cyclopropanone readily

isomerizes at 80 oC whereas the cis isomer does not because the disrotatory ring
opening required for isomerization is sterically prevented for cis isomer.
 Ex 20: Thermal isomerization of Ph-substituted dienes occurs via cyclobutene
intermediate following a thermally allowed conrotatory electrocyclization.

Ex 21: The trans-stilbine isomerizes to cis-stilbine (I) under photochemically.

On irradiation of cis-stilbine provides dihydrophenanthrene (II) by conrotatory
cyclization.

Ex 22: A beautiful illustration of the synthesis of ergosterol involves

electrocyclic reaction under irradiation by light.
 Ex 23: Vitamin D3 (cholecalciferol) is produced through the action of UV
irradiation on its precursor 7-dehydrocholesterol.

Typical examples of electrocyclic reactions

1.

2.

3.

4.

5.

6.

7.
 8.

9.

10.

11.

12.

Q.1. Compare to allylic cation, pentadienyl cation undergoes faster rate of

electrocyclic ring closure reaction while the situation is completely reversed in case of
allylic anion compared to pentadienyl anion. Logically explain the fact.
Q.2. The endo isomer of 7-chloro bicycle [4,1,0] heptane reacts 10,000 times more
faster rate than that of its corresponding exo-isomer. Account for the fact.
Q.3. Explain the following phenomena with proper mechanistic details.
Ph Ph
Ph
K1
H
H NC
Ph
NC H
K1
42
H K2
H
Ph
H
K2 Ph
NC
H Ph
Ph
NC
H
Q.4. Which one of the following reaction is feasible according to pericyclic rules?
Cl
Cl
Cl
H endo chlorine eliminates
H through inward rotation
producing cis double bond
Cl
Cl
Cl

H exo chlorine eliminates

H through outward rotation
producing trans double bond

Q.5. Account for the following observation of thermal three membered electrocyclic
ring opening reaction.

OTs
endo tosyl eliminates
through inward rotation
producing cis double bond
H

OTs H
H
exo tosyl eliminates
through inward rotation
producing trans double bond

Q6. The endo isomer of 6-chloro bicycle [3,1,0] hexane undergoes facile reaction to
produce 3-chloro hexane upon heating for 3hrs at 125 0C, while the exo-isomer
remain unaffected even at drastic condition. Account for the fact.

Q7. The endo isomer of 7-chloro bicycle [4,1,0] heptane reacts 10,000 times more
faster rate than that of its corresponding exo-isomer. Account for the fact.

Q8. The rate of solvolysis of endo isomer of 8-bromo bicycle [5,1,0] octane by silver
perchlorate in acetone –water mixture produces trans cyclo allylic alcohol. The exo-
isomer on same reaction condition results cis cyclo allylic alcohol. Account for the
fact.
Q. Cyclobutene to 1,3 butadiene conversion thermally favours in the direction of
diene system whereas the reverse occurs at longer wavelength. However, hexatriene to
1,3 cyclohexadiene conversion is both thermally and photochemically favourable
compared to its correspondind reverse reaction. But the situation looks completely
reversed if the electrocyclic equilibrium of benzocyclobutene is taken into
consideration. Explain the above observation.

Ans: Due to small member of carbocycle as well as presence of internal double bond,
cyclobutene becomes highly strained and its energy is higher than that of butadiene.
Naturally, according to law of themodynamics, cyclobutadiene to butadiene
conversion occurs smoothly under thermal condition. The reverse reaction invokes
high energy thermal process, rather presence of more conjugation in butadiene
absorbs a particular (quantized) light energy at longer wave length to bring about
apparently non favourable process.
However, the energy difference between cyclohexadiene and hexatriene is very
less as cyclohexadiene does not contain as much strain and also have one more σ-
bond. Due to comparatively lower energy of cyclohexadiene, the interconversion to it
from hexatriene proceeds spontaneously at thermal condition. Again we know that a
photochemical reaction proceeds at much faster rate than thermal condition if there is
more and more number of double bond. Therefore, it is clear that such above
transformation becomes kinetically faster if allowed under photochemical condition.
The electrocyclic equilibrium shifts towards cyclobutane direction not towards
diene system because the benzocyclobutane to butadiene produces a non-aromatic,
unstable xylene like compound. Therefore, aromatic to non-aromatic conversion is
both kinetically and thermodynamically impossible.
 CYCLOADDITION REACTIONS
Definition
A concerted cyclic shift of two separate π-electron systems in which a ring is
produced with the formation of two new σ-bonds is termed as Cycloaddition
reaction. The reaction is activated either by heat or by UV-light. The reaction follows
the principle of microscopic reversibility. The reaction sequence can also be explained
by three fundamental approaches; (a) correlation of orbital symmetry of terminal
lobe of interacting orbitals (b) perturbation of M.O theory or HMO theory of
aromaticity or anti aromaticity in T.S (c) FMO approach of HOMO-LUMO
interaction of corresponding orbital energy state. The reverse reaction of
cycloaddition is called cycloreversion.

Conditions for Cycloaddition Reaction

1. The symmetry of those orbitals w.r.t terminal conjugated π-system of two
separate polyene system has to be considered.
2. Always the terminal p-orbitals of both polyene which are going to form σ-
bond must overlap by maintaining the in phase distribution of of lobes after
rotation.
3. The groups or substituent attached to terminal lobes also moves according to
the lobe’s movements. This brings about the stereochemistry of the resultant
product.
4. HOMO of the one polyene interact effectively with LUMO of other polyene
forming both endo and exo product where endo product is kinetically more
stable.
5. That cycloaddition will be favoured which follows the Woodward –Hoffmann
principle of orbital symmetry. The involvement of any steric crowding or
generation of strain in the product molecule will avoid the subsequent
mechanism.
Source/ Influencing factor/Mode of activation:
1. Heat or Thermal (Δ)
2. Light or Photochemical (hγ)
Criteria for Cycloaddition Reaction:
1. Mode of activation. (Δ/ hγ)
2. Number of p/π-orbital participates. [4nπ or (4n+2)π]
3. Stereochemical outcome (wthether stereospecific or stereoselective).
4. The nature of orbitals undergoing change (σ or π).

Here Woodward-Hoffmann suggested that if the reaction would take place

through same face of a π-system, the reaction is said to be Suprafacial (s) to that of π-
system and if the reaction occurs through opposite face of a π-system, the reaction is
said to be Antarafacial (a) to that of π-system. For example (supra)-ethylene and
(supra) cis-2-butene yields cis-1,2-dimethyl cyclobutane whereas (supra)-ethylene
and (antara) cis-2-butene yields trans-1,2-dimethyl cyclobutane.

Pictorial Representation
 Diene in the s-cis conformation undergoes Diels-Alder reaction because C-1
and C-4 of the diene is close enough to react through a cyclic transition state. In s-
trans conformation, the T.S would be strain.

Dienes with an enforced coplanar s-cis conformation are exceptionally reactive

in Diels-Alder reaction. The reactivity of diene depends on the rigidity (locked
conformation in cyclic form), coplanarity and the concentration of the s-cis
conformation in the equilibrium mixture.

The following acyclic dienes are very unstable in s-cis form owing to severe
steric hindrance. Cyclic dienes of permanent s-trans conformation are unable to adopt
s-cis conformation and thus will not undergo Diels-Alder reaction.
 Approaching π—bonds and pair them up in a lower energy symmetric and a
higher energy antisymmetric combination can be classified based on symmetry of
orbitals w.r.t an imiginary plane.

The Diels-Alder reaction which is suprafacial on both components, a plane of

symmetry bisects the bond between C-2 and C-3 of the diene and the π bond of the
dienophile. If any substituents cause the diene or dienophile unsymmetrical, they do
not necessarily disturb the symmetry of the orbitals that are involved directly.

In the transition structure, the π bond between C-2 and C-3 has sharply

formed (66%) and likewise, the σ bonds are little formed (22%). The π bonds in the

dienophile and the diene seems not so weakened (32% and 22%, respectively). A late
transition structure is accounted by the larger changes in the π-bonding in the diene

and an early transition structure implies the small changes in the σ bonding and in the

π-bonding of the dienophile. This asynchronicity reflects the sum of the

HOMO(diene)/HOMO(dienophile) interactions and substantial contributions from
both FOIs.
Molecular orbitals from combination of σ orbitals (left) and σ* (right)

Primary and Secondary Orbital interaction

Parallel approach of
Anti-Parallel approach of cyclopentadiene and
cyclopentadiene and maleic anhydride
maleic anhydride
a
a This approach
Tail
Tail brings two orbitals HOMO
HOMO in close proximity
Head
Head

Head Supra-Supra Tail

Primary interaction
Tail a Head
O
O LUMO
O O
LUMO O
O
a
[4s+2s]
Secondary orbital
Endo-suprafacial interaction Exo-suprafacial
[4s+2s] a No secondary interaction

Both the cyclopentadiene and maleic anhydride can interact to each other w.r.t
C2 symmetry orbital under thermal condition. Their approach is either in parallel
direction or in anti-parallel direction as shown in the figure. Both the approaches are
basically supra-supra addition where in phase bonding overlap takes place. The
antiparallel approach leads to endo product whereas parallel approach exerts exo
product. The endo product is formed as kinetically controlled product (KCP) which
occurs at low temperature while the exo addition is produced as thermodynamically
controlled product (TCP) at comparatively higher temperature. The reason is that
there is an additional orbital interaction between non-terminal lobes of both diene
and carbonyl lobes of dienophile which strengthen the net overlap. This interaction
enables lowering in activation barrier and faster the reaction rate. Therefore, such
interaction which stabilizes the endo addition is known as secondary orbital
interaction. Since exo product is formed due to parallel approach of two π-systems, so
the lobes involving secondary orbital interaction are far apart from each other. Hence,
the secondary orbital interaction is virtually absent in exo product. The endo product
can be converted to exo product at high temperature (190 0C) but the reverse can not
be possible.

OPh antarafacial interaction

D
Secondary orbital interaction

Endo group

MeO

Me Exo group

Supra- interaction

Supra-antara orbital interaction

The above supra-antara interaction leads to a bonding with highly strained

system. Hence the reaction is symmetry forbidden reaction.
The exo product is more stable than the endo product for steric reasons. Since
the reaction is concerted, the transition state for exo product formation must be less
crowded than the transition state for endo product formation. In practice, it has been
found that the endo product is more stable than the expected exo product. This
clearly confirms that the transition state of endo product should be more stable than
that of the exo product due to some other factors which overwhelms steric
consideration. This factor is known as secondary orbital interaction. In endo transition
state the double bonded carbon of dienophile is directed to the inside of diene ring
where the there can be interaction between back diene orbitals and orbitals on the
substituents (C≡N) in dienophile. Such interaction is absent in case of exo orientation
as dienophile is directed away from the cyclic diene conjugated system.
 Substituents is out of cavity or
Substituents is cis to bridge carbon

NC H
Secondary
interaction
CN CN
H
Exo Endo
40% 60%
Endo T.S

Substituents extends
into concane cavity or
Exo T.S substituents is trans to
bridge carbon

Point to be noted:
1. For two component system the maximum number of mode of
addition=2n=22=4. (ss, sa, as, aa).
2. ss mode means parallel approach of orbital whereas sa, as, aa indicates
orthogonal approach of orbitals.
3. Terminal group retains its configuration in suprafacial approach while it is
inverted in antarafacial approach.
4. Both endo and exo addition occurs through ss mode depending on the
substitution pattern.
5. Favourable as well as facile pathways is shown when [π 4
S + π2S] is greater
than [π 4a + π2a].
6. Always s-cis conformation reacts in cycloaddition reaction because in s-
trans conformation the terminal lobes are anti to each other.
7. Any bulky group or ring at the termini will retard the rate.
8. The rate of cycloaddition reaction depends on the energy difference
between HOMO and LUMO orbital. The electron releasing group enhances the
HOMO energy of diene and electron withdrawing group lowers the LUMO
energy of dienophile except for cycloaddition reaction with reverse electron
demand.
Energies of frontier orbitals
C- (extra conjugation)
Raises the energy of the HOMO and lowers the energy of the LUMO.
Z- (an electron-withdrawing group)
Slightly lowers the energy of the HOMO and substantially lowers the energy of
the LUMO.
X- (an electron-donating group)
Substantially raises the energy of the HOMO and slightly raises the energy of
the LUMO.
Frontier orbital energies (eV) of alkenes and dienes (1 eV = 23 kcal = 96.5 kJ).

Frontier orbital energies are experimentally measured by photoelectron spectra

for the occupied orbitals, and a combination of electron affinity measurements,
charge transfer spectra and polarographic reduction potentials for the unoccupied
orbitals. Frontier orbital energies provide a clear idea about the rate of cycloaddition
reactions by considering lower energy difference between HOMO and LUMO. The
size of the orbital coefficients seldom influences in the frontier orbitals energies.
Rather the relative sizes of the coefficients are principally used to account for
regioselectivity.
Butadiene reacts with ethylene at high temperature (165 oC), high pressure to
give a low yield of cyclohexene. The rate becomes little faster with acrolein (at 150
oC) in terms taking less time at the same temperature. Introducing a second Z-
substituent (EWG) such as methylenemalonate or maleic anhydride increases the rate
even more that eventually reacts at room temperature.
An X-substituent (ERG) diene on C-1 or C-2 such as trans-piperylene,
isoprene or methoxybutadiene increases the rate further with acrolein at 130 oC. In
contrast to times and temperatures, the yield of the isolated product (here say 80 %)
is a reliable way of measuring relative rates.

Cause: In order to explain the rate of the reaction, the proper selection of HOMO and
LUMO for either of diene or dienophile is essential. Considering two pathways, the
direction of the reaction and rate depend on the smaller energy difference between
HOMO-LUMO either of diene or dienophile. Normally, a Diels-Alder reaction is
characterized by the interaction of HOMO-diene (9.1 eV) and LUMO-dienophile (0
eV) with energy difference = 9.1 eV as compared to 11.9 eV arising from LUMO-diene
(1.0 eV) and HOMO-dienophile (10.9 eV). Thus, a faster reaction is associated with
more electron-withdrawing group in dienophile comprising low-lying LUMO such as
tetracyanoethylene. This enables smaller the separation of the HOMO-diene and the
LUMO-dienophile. The combination of X-substituent HOMO-diene (raising energy)
and Z-substituted LUMO-dienophile produces relatively lower energy gap of 8.5 eV.
That is why, in above example, the energy separation between the HOMO of
butadiene and the LUMO of a Z-substituted dienophile is less than that between the
HOMO of butadiene and the LUMO of ethylene.

Frontier orbital interactions for Diels-Alder reactions

Diene with electron-withdrawing Z-substituents reacting with dienophiles with

electron-donating X-substituents are said to be Diels-Alder reactions with inverse
electron demand. Following examples represent this idea, although are not common.
 Cause: Suppose the electron density is supplied from from the diene. Since one
node is there, the ψ2 HOMO of diene ensures the flow of electrons that are

concentrated at the sides where the σ—bonds are formed in lieu of concentrated in

the centre of the diene (left). In case of inverse electron demand, the major supply of
electrons comes from the ψ1 HOMO of dienophile which consists of no node.
Consequently, it interacts with ψ3 diene LUMO even more strongly with lowe
activation barrier.

Normal Diels-Alder reaction Inverse electron demand

HOMO(diene)/LUMO(dienophile) LUMO(diene)/HOMO(dienophile)

In both examples (above), R = ERG raises the HOMO of dienophile that

becomes closer to LUMO of diene containing EWG. It helps strong HOMO-LUMO
interactions.
If two dienes one having a EWG and another with ERG are allowed to react,
diene with EWG always acts as dienophile while diene with ERG behaves as diene.
Regioselectivity of Diels-alder reactions
Regioselectivity refers to the orientation of a cycloaddition.
Methoxybutadiene reacts with acrolein to give more of the ‘ortho’ adduct than of the
‘meta’ adduct.

Cause: The coefficients of the atomic orbitals undergoing new σ—bond formation

should be the concern of regioselectivity. The combination HOMO-diene and the

LUMO-dienophile gives Eact, Er –Es = 8.5 eV (left) predominantly, as compared to the
reverse where Er – Es = 13.4 eV (right).

Let the square of the terminal coefficients on X be x and (x+n), and let the
square of the coefficients on Y be y and (y+m).
Large-large/small-small interaction [xy+(x+n)(y+m)] > Large-small/small-large
interactions [x(y+m)+(x+n)y]. substracting gives the value nm. Therefore, former
interaction is greater as long as n and m are of the same sign.

It is important to note that the large-large interaction precedes over the small-
small interaction (third figure). It indicates that the transition structure of an

unsymmetrical Diels-Alder reaction is itself unsymmetrical where two σ bonds are

formed to different extents. Despite the fact, the reaction is still concerted, with both
bonds forming at the same time, but it is not synchronous.
Drawing curly arrows and creating canonical structures to express the logic that
C-4 of the diene is a nucleophilic carbon and C-3/ of the acrolein an electrophilic
carbon works well for the reaction between ERG-diene and EWG of dienophile.
However, this is not applicable to all.

Clearly the valence bond argument is not good enough, rather the frontier
orbital interactions. For instance, the curly arrows reflect that both C-4 of the diene
carboxylic acid and C-3/ of acrylic acid are expected to be electrophilic which repels
due to partial positive charges. The expected adduct would be the ‘meta’ adduct. In
contrary, the mainly the ‘ortho’ adduct were isolated.

The ‘ortho’ adduct is also consistent with smaller HOMO-LUMO energy gap.
It is assumed that the orbitals are polarized with marginally higher coefficient on C-4
in the diene-HOMO which stems from the hexatriene-like character of the
conjugated system. As a result, the counter-intuitive combination with bonding
between C-4 and C-3/ is achieved.
Examples that obey ‘ortho-para’ rule

Exception of ‘ortho-para’ rule

The rule breaks when both diene (at C-1 and C-2 position) and dienophile
contain ERG (X substituent). It yields a substantial yield of ‘meta’ adduct with
reasonable loss of regioselectivity partly because of high temperature reactions.

Hyperconjugation of the C-2 methyl group through the double bond with the
carbonyl group attached to C-3 can reduce the electron-withdrawing effect of that
carbonyl group. The C=C orbital is more polarised by the C-2 carbonyl which is the
guiding factor than by the C-3 carbonyl.

2-aryl substituent is usually less effective in polarising the coefficient at of

frontier orbital at C-2 position than that at C-1 which eventually explains the
observed regioselectivity.
 Based on the frontier orbital coefficients of tropone, the regioselectivity arises
while reacts to various dienophiles.

Typical [4+2] cycloadditions occur after electrocyclic ring closure.

A transformation is shown using cycloaddition reaction as intermediate.

The Stereoselectivity of Diels-Alder Reactions
Three stereochemical issues related to product formation for cycloaddition:
1. cis/trans product formation w.r.t stereochemistry of starting diene and
dienophile
2. exo/endo products based on secondary HOMO-LUMO interactions
3. Regioselectivity measured by the relative size of terminal orbital lobes

OUT-ENDO-CIS Rule:
out = refers to the orientation of a group on the termini of diene
endo = refers to the substituents (usually EWG) on the dienophile
cis = refers to stereochemical relationship of two groups in the product
In order to determine product stereochemistry in D.A reaction Out-Endo-Cis
rule is applied provided the interaction is supra-supra.
out
ou t in out in
gem z z
Z (ENDO)
in gem
[4+2] gem
in trans trans
O UT-ENDO -CIS
cis cis
trans cis out in out in
out
M ajor product

Therefore, out group on diene and endo group in dienophile are in cis in the
product. Generally most electron withdrawing group in dienophile has been
considered as endo group. Similarly OUT-EXO-TRANS, IN-ENDO-TRANS, IN-
EXO-CIS are also can be applied.

OMe
1. 2. O H OEt
OUT MeO H Me OEt
H COOEt Me
COOEt O
H
ENDO H
ENDO H

OUT Me
Ph
3. COOH Me
OUT Ph H
COOH
H
H ENDO

COOH
COOH Ph H
OUT Ph

The stereochemical finding for Diels-Alder reactions relies on Alder’s endo rule
in which the favoured transition structure includes electron-withdrawing substituents
in the more hindered environment under the diene unit. This gives kinetically
favourable endo product at lower temperature with additional secondary orbital
interactions. Long heating equilibrates this isomer with the thermodynamically
favoured exo adduct by a retro-cycloaddition pathway.

Secondary interactions determines the regioselectivity of a Diels-Alder reaction

Transition structure for Transition structure f or

formation of an 'ortho' adduct formation of a 'meta' adduct

The possibility for an electrostatic or Coulombic repulsive effect occurs in the

exo transition structure. Such effect, in turn, has the greater propensity for forming
the endo isomer. A Coulombic attraction favours exo attack both kinetically and
thermodynamically in case of furan react with cyclopropenone.
Energy profile diagram

Effect of Lewis Acids on Diels-Alder Reactions

Lewis acids exert a strong catalysing effect in Diels-Alder reactions both as
faster reaction rate and stereo/regioselectivity of the reactions.
Site selectivity of Diels-Alder Reactions
In cycloadditions, site selectivity is a pair of regioselectivity of a polyfunctional
molecule having multiple sites in which the counterpart of another molecule reacts.
The adduct obtained from anthracene arises due to product stability by achieving two
isolated benzene ring and the largest coefficients in the HOMO at the 9,10-positions.

The dimerisation of hexatriene is another example of site selectivity. The

former retains a conjugated diene system and is likely to be lower in energy than the
latter. The former product is thermodynamically favoured.
 Among the four isomers (A-D), isomer (A) is more reactive for the highest
HOMO energy and it remains in equilibrium in very low extent. The smallest energy is
between the diene-HOMO of (C) and the dienophile-LUMO of (D). The reverse
variation suffers from steric hindrance. The product has always endo selectivity.

A B C D
Periselectivity

[4+6] favoured path [2+4] Less-favoured path

Periselectivity is a special case of site-selectivity which considers whether whole

of the conjugated array of electrons or a large part of it, or only a small part of it is
involved in pericyclic reaction. Periselectivity decides [4+6] cycloaddition adduct
between cyclopentadiene and tropone prefers over [2+4] cycloaddition although
both are thermodynamically much different in energy. Rather, the frontier orbitals
indicate that the longer conjugated system of the tropone is more reactive than the
shorter. The largest coefficients of the LUMO of tropone are at C-2 and C-7. It results
the bonding to these sites with lower energy more than bonding to C-2 and C-3.
Rates, Regioselectivity and Site selectivity of 1,3-Dipolar Cycloadditions
1,3-dipolar cycloaddtions is faster rate of concerted cycloaddition reaction
between 1,3-dipole (like diazomethane, nitrone, ozone) with high-energy HOMOs
and low energy –LUMO alkenes (dipolarophiles) carrying electron-withdrawing
substituents. Frontier orbital interactions resemble this reaction with normal Diels-
Alder reactions. The reaction of diazomethane or phenyl azide with methyl acrylate
shows the regioselectivity.

A smaller separation between the HOMO of the dipole and the LUMO of the
dipolarophile is called dipole-HO controlled and between the LUMO of the dipole
and the HOMO of the dipolarophile is called dipole-LU controlled. The
regioselectivity of of 1,3-dipolar cycloadditions are shown below. The smallest energy
separation (7.8 eV) is with X-substituted dipolarophiles implies a dipole-LU-
controlled reactions. Conversely, regioselectivity for phenyl azide reacting with a Z-
substituted alkene is dipole-HO-controlled regiochemistry with ELUMO – EHOMO = 9.5
eV (compared to dipole-LU-controlled regiochemistry ELUMO – EHOMO = 10.7 eV).
 Overall ozonolysis reaction exhibits regioselectivity. The first step has no
regiochemistry; the second step is a cycloreversion, but the third stage the
cycloaddition of a ketone oxide to a carbonyl group, is highly regioselective.

The site selectivity of 1,3-dipolar cycloadditions is analogous to the Diels-Alder

reactions.

[4+2] cycloaddition of cations

[4+6] Cycloadditions
An explanation for the stereochemistry of [4+6] cycloadditions underlies
secondary orbital interactions. The reaction between cyclopentadiene and tropone
produces thermodynamically favoured exo adduct with favourable exo transition
structure. Frontier orbitals indicate a repulsive interaction (wavy lines) between C-3,
C-4 on the tropone and C-2 on the diene (and between C-5 and C-6 on the tropone
and C-3 on the diene) in the endo transition structure.
[8+2] cycloadditions

[14+2] Cycloadditions
[14+2] Cycloaddition of heptafulvalene (HOMO) with tetracyanoethylene
(LUMO) involves an antiaromatic transition state. The reaction is termed as [π14a +
π2s] and is thermally allowed process. This is possible because heptafulvalene is flexible
enough not to lose the conjugation through seven double bonds.

Cycloaddition with multiple components

Ketene cycloaddition
Ketenes undergo faster cycloadditions with double bonds to give
cyclobutanones. It uses the interaction between the LUMO of the ketene and the
HOMO of the ketenophile. The conjugation of the C—Cl bonds with the carbonyl
group of the ketene will lower, by negative hyperconjugation, the energy of the
LUMO, which is more or less π*CO. A C or X substituent on the alkene raises the
energy of its HOMO, and the energy separation between the frontier orbitals is
reduced.

The regioselectivity in the reaction between cyclopentadiene and

dichloroketene giving the cyclobutanone is explained by the overlap from the large
LUMO coefficient on the central atom of the ketene and the larger coefficient in the
HOMO of the diene at C-1.
 Both HOMO(ketone)/LUMO(ketene) and LUMO(ketone)/HOMO(ketene)
interactions lead to the same conclusions about regioselectivity.
Retro Diels alder reaction

Forbidden reactions

[4+2], [4+6] and [8+2] cycloaddition are commonplace. Burtadiene dimerizes

following [4+2] cycloaddition reactions, not by [2+2] or [4+4] pathway. The simplest
answer is 6-membered ring is easiest to form energetically than that of 4 or 8
membered ring due to ring starin or little probability to get two ends close. This
argument does not apply to the reaction between ethylene and maleic anhydride. To
get 4-membered ring with lower energy, a high kinetic barrier has to overcome. Thus,
a total number of [4n+2] electron involved in cycloaddition reaction is thermally
allowed; but not 4n number of electron system. Thus, the selection rule of orbital
symmetry proposed by Woodward Hoffmann is justified. They are accomplished by
photochemical means.
Photochemical cycloadditions
Cycloaddtion by photoactivation considers the first electronically excited state.
Since photoactivation puts so much energy into the molecule, many pathways
including self and crossdimerization are available in the first electronically excited
state. This is accentuated by the observation that photo induced Diels-alder reactions
are very rare.

[2+2] Cycloaddition [6+6] cycloaddition

All cycloadditions are not pericyclic

The reaction of enamine with methyl vinyl ketone provides hetero Diels Alder
adduct. However, the product is cycloadduct, the reaction is not included in pericyclic
because of isolation of zwitter ionic intermediate due to stepwise reaction. Even, the
nucleophilic enamine reacts readily with either electrophilic methyl vinyl ketone or
methyl acrylate gives different types of adducts.
Cheletropic reactions
The stereospecific and suprafacial insertion of carbine into double bond
(alkene) is known as Cheletropic reaction.

Intramolecular cycloaddition reaction

When diene and the dienophile are part of the same molecule, such type of
molecule gives Diels-Alder reaction known as intramolecular Diels-Alder reaction.

Q. Explain the following.

Diene
Dienophile 13 13
12 10 Me O
8 6 4 2 1 Me O
13 1 OMe OMe 1
11 11 2 11 OMe
9 7 5 3
O H
10 3 10
H H

a a
HOMO LUMO
Ans: It is an example of intramolecular cycloaddition reaction or intramolecular
Diels-alder reaction which takes places under thermal activation following orbital
symmetry rules. The formation of the product follows ‘Out-Endo-Cis’ rule with
supra-supra interaction. The (4n+2)π cycloaddition reaction occurs after adopting a
suitable conformation necessary for cycloaddition. The driving force of the product
may be the formation of stable 6-fused-7 membered ring with trans trans
stereochemistry at the fused junction chiral centre.

Typical examples on cycloadditions

Examples 1

Examples 2
The following table gives a correlation among the entire factors associated with
Cycloaddition Reaction:
No. of Reactants Product
Mode of
total π e- Symmetry Interaction Feasibility stereoche Stereoche
activation
involved mistry mistry
Symmetry trans-trans
Supra-supra trans
Thermal allowed cis-cis
4nπ m(s)
(Δ) Symmetry
Supra-antara trans-cis cis
Forbidden
Symmetry trans-trans
Supra-supra cis
Photoche allowed cis-cis
4nπ C2(s)
mical(hγ) Symmetry
Supra-antara trans-cis trans
Forbidden
Symmetry trans-trans
Supra-supra cis
Thermal allowed cis-cis
(4n+2)π C2(s)
(Δ) Symmetry
Supra-antara trans-cis trans
Forbidden
Symmetry trans-trans
Supra-supra trans
Photoche allowed cis-cis
(4n+2)π m(s)
mical(hγ) Symmetry
Supra-antara trans-cis cis
Forbidden
 Sigmatropic Rearrangement
Definition:
Sigmatropic rearrangement is defined as the intramolecular migration of an
allylic σ-bond or atom or group or ligand along with an σ-bond from a migration
origin to the terminus of a polyene system through reorganization of π-bonds. This
process is concerted involving simultaneous breaking of one σ-bond with the
formation of new σ-bond and rearrangements of π-bonds. The numbers of π-bonds
remain unchanged.
Classification of sigmatropic rearrangement:
The sigmatropic rearrangement can be represented by [i,j] shift where i and j
are defined as the centre of migration origin and centre of migration terminus
respectively. The difference of sigmatropic rearrangement from electrocyclic and
cycloaddition reaction is that the later are classified by the number of π electrons
involved in the cyclic transition state without migration of bonds.

Migration
terminus
2
H 2
H 1 H 1 3 H
3
HD H H
1,3 shift D
1 H
Migration
Origin Migrating
group

Basic Features and Conditions for Sigmatropic rearrangement:

1. The symmetry of migrating orbital which migrates from migratory origin to
migratory terminus must be in same phase and suprafacial.
2. Suprafacial in phase interaction of lobes must take place by maintaining a
reliable orientation and certain distance between migratory origin and
terminus.
3. Depending on the way of migration, stereochemical features would be
resulted. If the migratory group is chiral, the configuration of the chiral centre
 will depend on the total number of electron involves during the process [4n or
(4n+2)].
4. HOMO of either migrating group and LUMO rest of the residue or vice-
versa has to be considered in order to get symmetry allowed kinetically and
thermodynamically more stable product.
5. That sigmatropic rearrangement will be favoured which follows the
Woodward –Hoffmann principle of orbital symmetry. The involvement of any
steric crowding or generation of strain in the product molecule will avoid the
subsequent mechanism.
Source/ Influencing factor/Mode of activation:
1. Heat or Thermal (Δ)
2. Light or Photochemical (hγ)
Criteria for Sigmatropic reaction:
1. Mode of activation. (Δ/ hγ)
2. Total number of electron participates. [4n or (4n+2)]π
3. Stereochemical outcome (stereospecific, stereoselective).
4. The nature of orbitals interacting (σ and π).

Representative examples of various types of sigmatropic rearrangement

Me
Tol S Tol
Me
S O O
1,3 shift 2,3 shift

O OH

3,3 shift
1,4 shift

H
NH2
Me Me H2 N NH2
D D
Me Me
Me 1,5 shift 5,5 shift
H Me
H2 N

Ar Ar

D 1,7 shift D 7,7 shift

Ar Ar
D R D
R
Case I: [1,3] Sigmatropic shift
A thermal [1,3] Sigmatropic shift is illustrated below.

F.M.O interaction HOMO

Suprafacial out of phase

Ph Ph but Antarafacial in phase
H
Me H Ph interaction with
Me LUMO
Me H retention of configuration,
S so symmetry fobidden path

Ph
H
H
Ph
H Me
Ph Me Me
R
Suprafacial in phase
interaction with
inversion of configuration,
so symmetry allowed path

Orbital symmetry considers that the suprafacial path is thermally symmetry

forbidden while antarafacial path might be followed; but it is geometrically impossible.
Therefore, thermal [1,3] shift is very unlike. The process should be symmetry allowed
under photochemical condition. However, the examples for 1,3 shift in photochemical
process are rare. Because, when photon is absorbed by the molecule, the LUMO of the
ground state will become HOMO of the excited state known as photochemical
HOMO. Such situation is very unlikely.

Ex-1: A thermal ring expansion (left) with antarafacial [1,3] shift while a
reversible suprafacial [1,3] shift (right) with retention of configuration in the
migrating group are observed.

Ex-2: The reaction involves [1,3] sigmatropic shift under thermal conditions
which is characterized by suprafacial with inversion at the migrating apical carbon.
 Ex-3: [1,3] suprafacial shift of an alkyl group proceeds with inversion at the
migrating center at high temperature (300 oC).

[1,4] Sigmatropic shift

[1,4] Sigmatropic shift involves allylic cation. The example is the degenerate
rearrangement of bicyclic cation in which the bridge moves around perimeter of the
five membered ring. The endo and exo —Me-groups remain unaltered from
spectroscopic point of view.

Case II: [1,5] Sigmatropic shift

A thermal [1,5] Sigmatropic shift is illustrated below.
Antarafacial path is out of
F.M.O interaction phase interaction with
inversion of configuration,
HOMO so symmetry fobidden path

Ph Ph
H Ph H
Me H
Me LUMO Ph Ph Me
Me H S
S Me H
Suprafacial in phase
interaction with
retention of configuration,
so symmetry allowed path
 Among all possibilities of sigmatropic migration, always 1,5 shift occurs due
both symmetrically and geometrically favourable migration. H’s and alkyl groups
migration favours suprafacial [1,5] shift. The [1,5] sigmatropic shift results symmetry
allowed suprafacial migration with retention of configuration.

Stereochemistry of migration

Suprafacial migration renders R-configuration at C-5 and E-configuration at

C-1 (left) whereas antarafacial migration yields S-configuration at C-5 and E-
configuration at C-2 (right).

Ex-4: The structures of the dienes present in the reaction mixture via
sequential thermal [1,5] suprafacial sigmatropic H and D—shifts.

Ex-5: The isomers of monosubstituted cycloheptatriene are interconvertible

following successive suprafacial [1,5] ‘H shifts. This reaction involving [1,5] ‘H shifts is
reasonably slower than that of cyclopentadienes. In contrary, photochemically [1,5]
‘H shifts occurs only in open chain system where the migration can be antarafacial.
 Ex-6: Isomeric methylcycloheptadienes (1—4) are in a thermal equilibration as
a result of successive [1,5] ‘H shifts.

Ex-7: Both thermally allowed [1,5] H and D—shifts shows the scrambling of
deuterium label of 1-deuteroindene.

Ex-8: The deuterium labeling is found consistent with thermal suprafacial [1,5]
deuterium shift for optically active 1-deuterio-1-methyl-3-tert-butylindene. Three
products were obtained as optical active.

Ex-9: The given molecule represents fluxtionality. The fluxionality of the σ

(sigma) bonded atom in cyclopentadienide involves migration.
 Ex-10: Both reactions involve a suprafacial [1,5] deuterium shift under thermal
condition.

Ex-11: A relatively less stable diene with exocyclic double bonds is switched to a
stable diene containing endocyclic double bond by [1,5] H-shift.

Ex-12: The isomers of 1,4-di(cycloheptatrienyl)benzene are interconverted by

thermal [1,5] and photochemical [1,7] suprafacial sigmatropic hydrogen shifts.

Ex-13: Only suprafacial [1,5] hydrogen shift is thermally allowed for the
conversion into toluene.
 Ex-14: Suprafacial [1,5] H shift of Z-cyclodeca1,2,4 triene followed by an 6π
electrocyclic ring closure in disrotatory manner yield bicycle[4,4,0] deca2,4-diene.

Ex-15: S-(+)-α-phellandrene loses its optical activity on distillation owing to

spontaneous and geometrically favourable [1,5] H shift of chiral hydrogen within the
molecule.

Ex-16: An 6π electrocyclic disrotatory ring closure followed by suprafacial [1,5]

H shift results 7-fused-4 to stable 6-fused-5 membered ring.

Ex-17: Three successive thermal suprafacial [1,5] sigmatropic shifts including

one σ—bond and two hydrogens occurs with retention of configuration.

Ex-18: The given compound shows only a singlet for the methyl group in 1H
NMR. Because the [1, 5] migration of hydrogen takes place in the preference to the
methyl group and the migration is so fast at room temperature that only a singlet is
observed for the methyl group.
Ex-19: Walk rearrangement of norcaradiene with [1,5] shifts

Ex-20: Isomerization of substituted cycloheptatrienes takes place through

sequences of [1,5] sigmatropic rearrangements and electrocyclic reactions.

Case III: [1,7] Sigmatropic shift

A thermal [1,7] Sigmatropic shift is illustrated below.
F.M.O interaction
HOMO
Antarafacial in phase
interaction with
retention of configuration,
Ph H but suprafacial out of
Me Ph Ph
H phase interaction, so
S Me LUMO Me H symmetry fobidden path

Ph
H H H Ph
Me Me
Me Suprafacial in phase
Ph interaction with R
inversion of configuration,
so symmetry allowed path
 Thermally [1,7] shift although is suprafacial symmetry forbidden process, it
occurs due to achievement of favourable geometry.
Ex-21: Unlike [1,3] shift, antarafacial migration is allowed for [1,7] hydrogen
shift since the geometrical restrictions on antarafacial T.S of [1,7] hydrogen shift is not
as severe as in the [1,3] shift case due to flexibility of a π-system of seven carbon
atoms.

Ex-22: The thermal equilibrium between precalciferol (previtamin D2) and

calciferol (vitamin D2) is illustrated by [1,7] Hydrogen shift.

[2,3] Sigmatropic shift: Wittig rearrangement [σ2S+ω2S+π2S]

[3,3] Sigmatropic shift
Cope rearrangements
A [3,3] sigmatropic rearrangement of 1,5-dienes under thermal condition is
called the Cope rearrangement. The reaction proceeds through a 6-membered cyclic
T.S. The Cope rearrangement is a reversible process; the equilibrium mixture has a
great proportion of the thermodynamically stable isomer. It is an intramolecular
process because rearrangement of a mixture of two different hexa-1,5-dienes does not
lead to the formation of cross products.

Ex-23: In [3,3] sigmatropic shifts, a chair-like transition state is energetically

preferred to a boat-like structure. Rearrangement of the meso diene through such a
transition state then would give the cisetrans isomer while in the case of the
rearrangement of the racemic mixture the trans-trans isomer is the major product
 Ex-24: The following examples represent [3,3] shift mostly via a suitable chair
conformation.
 Ex-25: Diyne system can be thermally activated to suprafacial [3,3] sigmatropic
shift via reactive allene intermediate which allows thermal electrocyclic ring closing
reaction through conrotatory mode to furnish conjugated exocyclic double bond.

Claisen rearrangement
The Claisen rearrangement is an typical example of [3,3] sigmatropic
rearrangement; for instance, the conversion of allyl vinyl ether to pent-4-enal or an
allyl phenyl ether to an ortho-substituted phenol on heating.

Ex-26: The mechanism of Claisen rearrangement for various isomers is shown

in chair like T.S. Most favorable geometry arises in case of two larger methyl
substituents in the pseudoequatorial position (E,E) in the transition state. The order
of increasing rates toward the Claisen rearrangement is E,E > Z,E ≈ E,Z > Z,Z.
 Ex-27: Citral is formed by following [3,3] sigmatropic rearrangement.

Ex-28: Ireland-Claisen rearrangement

The β-ketoesters can rearrange to β-ketoacids following a [3,3] shift which is

decarboxylated to give γ, δ-unsaturated ketone. This rearrangement is known as
 Ex-29: Kimel-Cope rearrangement.

Ex-30: A typical example for anionic oxy-Cope rearrangement is depicted by

converting allyl alcohol to anion and then [3,3] shift occurs.

Ex-31: The following molecules do not exhibit Cope rearrangement.

[5,5] Sigmatropic shift

Ex-32:

Ex-33:Benzidine rearrangement
An acid-catalyzed rearrangement of hydrazobenzenes involving [5,5]
sigmatropic shifts proceeds suprafacially through 10-membered T.S.
Hückel-Mobius rule in Sigmatropic rearrangements
According to Hückel-Mobius rule, a thermal sigmatropic rearrangement take
places via aromatic T.S whereas photochemical sigmatropic rearrangement proceeds
via antiaromatic T.S.

No. of
Mode of Product
allylic πe- Interaction Feasibility
activation Stereochemistry

Thermal Suprafacial Symmetry allowed Retention

4nπ
(Δ) Antarafacial Symmetry Forbidden Inversion
Photochemic Antarafacial Symmetry allowed Inversion
4nπ
al(hγ) Suprafacial Symmetry Forbidden Retention
Thermal Antarafacial Symmetry allowed Inversion
(4n+2)π
(Δ) Suprafacial Symmetry Forbidden Retention
Photochemic Suprafacial Symmetry allowed Retention
(4n+2)π
al(hγ) Antarafacial Symmetry Forbidden Inversion
Q. Why are HOMO-LUMO interactions so significant in order to prove concerted
reaction and how the two approaches FMO and Woodward Hoffmann rule are
rational in this concern?
Ans: The electrons in HOMO of a molecule are considered to be in the outer shell
orbital. The energy required to expel those electrons will be less as they are already in
higher energy level. LUMO is the unoccupied lowest energy orbital where electron can
be transformed with the expense of least energy. Thus, least energy is expensed to
remove electrons from HOMO and subsequent accommodation into LUMO. It
makes smallest energy difference between HOMO and LUMO to ensure strong
bonding. The Frontier Molecular Orbital (FMO) interactions of HOMO-LUMO must
be abided by symmetry allowed process according Woodward-Hoffmann selection
rule of orbital symmetry. Thus, a pericyclic reactivity can be understood in terms of
FMO theory and the outcome of reactions can be predicted using the Woodward-
Hoffmann rules.

References
1. Fleming, I. Molecular Orbitals and Organic Chemical Reactions, Reference
Edition, John Wiley & Sons, Ltd, UK, 2010.
2. Fleming, I. Pericyclic Reactions, Oxford Science Publication, Astrazeneca, UK.
3. Kumar, S., Kumar, V., Singh, S.P, Pericyclic Reactions A Mechanistic and
Problem-Solving Approach, Academic Press, Elsevier, UK, 2016.
4. Singh, J., Singh, J. Photochemistry and Pericyclic Reaction, New Academic
Science Limited, 3rd Ed., UK, 2012.
5. Carey, F., Sundberg, R. Advanced Organic Chemistry, Part A: Structure and
Mechanisms, 4th Ed, Kluwer Academic Publishers, USA, 2000.