Engineering Chemistry III Prof. S.

Sankararaman

Pericyclic Reactions
Definition:

1. Concerted reaction that proceed via a cyclic transition state

2. No distinct intermediates in the reaction

3. Bond forming and bond breaking steps are simultaneous but not necessarily

synchronous

Classification:

1. Electrocyclic ring closing and ring opening reaction

2. Cycloaddition and Cycloreversion reaction

3. Sigmatropic Rearrangements

4. Chelotropic Reaction

5. Group transfer Reaction

Methods of Analyzing Pericyclic Reaction

1. Orbital symmetry correlation method

(Woodward, Hoffmann, Longuet-Higgins and Abrahamson)
2. The frontier orbital method
(Woodward, Hoffmann and Fukui)
3. Transition state aromaticity method
(Dewar and Zimmerman)

Woodward-Hoffmann Rules: Predicts the allowedness or otherwise of pericyclic reactions

under thermal and photo- chemical conditions using the above methods. Therefore a basic

understanding of molecular orbitals of conjugated polyene systems and their symmetry

properties is essential to apply the above methods.

Indian Institute of Technology Madras

Engineering Chemistry III Prof. S. Sankararaman

Constructing MO diagram of polyene systems:

1. Although there are C-C and C-H sigma bonds present in the molecule, the π MOs

can be constructed independently of them. Although there may be a change in the

hybridization of carbon atoms during the course of a pericyclic reaction, the MO

levels of the sigma framework are relatively unaffected.

2. For a conjugated polyene system containing n (n = even) π electrons, there will be

n/2 π bonding molecular orbitals that are filled MOs and n/2 antibonding MOs that

are empty in the ground state electronic configuration of the molecule.

3. The lowest energy MO has zero nodes, the next higher one has one node and the

second higher has two nodes and so on.

The nth MO will have (n-1) nodes.

4. The nodal points are found at the most symmetric points in a MO.

In other words, no MO can be symmetric as well as antisymmetric at the same time

with respect to any existing molecular symmetry element. For example the π2 MO

of butadiene has a node at the center of the bond connecting C2 and C3. It is

incorrect to assign this node to the center of the bond connecting C1 and C2.

node node

π2
Correct π2
Incorrect

Indian Institute of Technology Madras

Engineering Chemistry III Prof. S. Sankararaman

Formation of MOs of butadiene from MOs of ethylene

π*
π∗

π4

π3

π π
π1

π4
ethylene butadiene ethylene

Indian Institute of Technology Madras

Engineering Chemistry III Prof. S. Sankararaman

MOs of ethylene Butadiene and hexatriene

π6

π4 π5

π∗

antibonding
π4
π3

bonding π3

π2

π π2

π1

π1

Indian Institute of Technology Madras

Engineering Chemistry III Prof. S. Sankararaman

Frontier orbital method:

Highest occupied MO (HOMO) – filled

Lowest unoccupied MO (LUMO) – empty
Analysis based on the interaction of HOMO of one Component and LUMO of the other
component.
If HOMO-LUMO interaction leads to bonding then the reaction is allowed. If not it is
forbidden.
HOMO-LUMO gap is important. The closer it is the faster the reaction.

ELECTROCYCLIC REACTIONS

1. Cyclization of an acyclic conjugated polyene system

2. The terminal carbons interact to form a sigma bond

3. Cyclic transition state involving either 4n electrons or 4n+2 electrons.

(1)

(2)

Electrocyclization of butadiene (4n) and hexatriene (4n+2)

Indian Institute of Technology Madras

Engineering Chemistry III Prof. S. Sankararaman

Modes of ring closing/ring opening reactions - Stereochemistry

H3C CH3
conrotatory disrotatory H CH3
H CH3 (3)
H H CH3 H H3C H
cis trans
Z, E

H3C H
conrotatory disrotatory H H
H H (4)
H CH3 CH3H3C H3C CH3
trans cis
Z, Z

H CH3
conrotatory disrotatory H H
(5)
H3C CH3
H3C H H H H3C CH3
trans E, E cis

Indian Institute of Technology Madras

Engineering Chemistry III Prof. S. Sankararaman

Frontier orbital method for electrocyclic reactions

conrotation

π2 HOMO of butadiene bonding interaction bonding orbital

in the TS

disrotation

antibonding interaction
π2 HOMO of butadiene in the TS
antibonding orbital

disrotation

bonding interaction bonding orbital

π3 HOMO of hexatriene in the TS

conrotation

antibonding interaction
π3 HOMO of hexatriene in the TS antibonding orbital

Indian Institute of Technology Madras

Engineering Chemistry III Prof. S. Sankararaman

disrotation

HOMO of excited
state butadiene bonding interaction bonding orbital
in the TS

conrotation

HOMO of excited antibonding interaction antibonding orbital

state butadiene in the TS

conrotation

bonding orbital

HOMO of excited bonding interaction

state hexatriene in the TS

disrotation

antibonding orbital

HOMO of excited antibonding interaction

state hexatriene in the TS

Indian Institute of Technology Madras

Engineering Chemistry III Prof. S. Sankararaman

Woodward – Hoffmann rules for electrocyclic reactions

System Mode of reaction Allowedness of the reaction

(no of electrons) Thermal Photochemical

4n conrotatory allowed forbidden

4n disrotatory forbidden allowed

4n+2 conrotatory forbidden allowed

4n+2 disrotatory allowed forbidden

Four-membered Ring Systems:

The synthesis of cyclobutene was first reported by Willstätter. The thermal ring opening of
cyclobutene occurs readily at 150 oC to give 1,3-butadiene.

o
150 C

Thermal isomerization of cyclobutene to 1,3-butadiene

The stereochemistry of the ring opening has been studied systematically in detail by
Vogel and Criegee even before the theory of pericyclic reactions and Woodward-
Hoffmann rules were developed. The electrocyclic ring opening of 3,4-disubstitued
cyclobutenes yield products arising from the conrotatory mode of ring opening with high
stereospecificity as illusrated below.

Indian Institute of Technology Madras

Engineering Chemistry III Prof. S. Sankararaman

H
Me Me
H Me
150 oC Me
H H
Me Me
Me
Me
only E, Z isomer
Me H
Me Me
H Me Me
150 oC H Me
Me H Me
Me Me Me
H
Me H
only Z, Z isomer E, E isomer
not formed

COOMe
Ph COOMe
Me 70 oC Ph
Me
Me COOMe
Ph Ph
COOMe
Me

Stereochemistry of thermal electrocyclic ring opening of cyclobutenes.

Thermal isomerization of the highly substituted dienes shown below takes place through
the formation of the cyclobutene intermediate by a conrotatory pathway. None of the
symmetry disallowed disrotatory products were formed even after 51 days at +124 oC
which allowed the estimation of a lower limit of 7.3 kcal/mole of energy difference
between the conrotatory and disrotatory modes of reaction.

10

Indian Institute of Technology Madras

Engineering Chemistry III Prof. S. Sankararaman

Stereoselective thermal isomerization of 1,3-butadiene derivatives.

CH3 Ph
Ph CH3
Ph Ph
Ph Ph CH3
CD3 Ph Ph
Ph Ph Ph
CD3
Ph CD3

Ph CH3
Ph Ph
CH3 Ph
or
CD3 Ph
Ph Ph
Ph CD3
o
51 days at 140 C

The photochemical ring closing of butadiene and E,E and Z,E-hexa-2,4-diene has been
studied by Srinivasan and the reaction follows the disroatory mode as predicted by the
Woodward-Hoffmann rules.
hν

253 nm

hν

hν

Photochemical electrocyclization of 1,3-butadiene derivatives.

Benzocyclobutene is another well studied 4 electron system and the electrocyclic ring
opening gives a very reactive intermediate, namely ortho quinodimethane.

11

Indian Institute of Technology Madras

Engineering Chemistry III Prof. S. Sankararaman

Thermal isomerization of benzocyclobutene to ortho quinodimethane.

Stereoselective thermal isomerization of benzocyclobutene derivatives

Ph H CN
Ph
rt Ph TCNE CN
CH2Cl2 CN
Ph con CN
meso Ph H Ph
quantitative
Ph Ph H CN
Ph
rt TCNE CN
CH2Cl2 CN
Ph con CN
racemic Ph Ph H
quantitative

Examples of thermal and photochemical electrocyclic reaction of cyclohexadiene-

hexatriene system are abundant in the literature.] According to the Woodward-Hoffmann
rules this six electron system is predicted to undergo disrotatory cyclization under
thermal and conrotatory ring closure under photochemical conditions. Isomeric
octatrienes conform to the above predictions and undergo stereospecific
electrocyclization as shown below.
Stereospecific electrocyclic ring closure of isomeric hexa-1,3-5-trienes.

Me

150 oC
Me
H
H dis
Me
Me
H
o Me
Me 150 C
H dis
Me
Me

12

Indian Institute of Technology Madras

Engineering Chemistry III Prof. S. Sankararaman

The photochemical reaction proceeds by a conrotatory ring closure / opening mode and in
general a photostationary state is reached consisting of an equilibrium mixture of both the
hexatriene and cyclohexadiene (shown below).

Stereospecific thermal ring closure of triphenylhexatrienes.

Ph Ph Ph
80 oC
Ph
H
H dis
92 % Ph
Ph
Ph H Ph Ph Ph
o Ph
Ph 110 C 110 oC H
H dis dis Ph
> 90 % Ph > 90 %
Ph H

Photochemical electrocyclic ring opening / closure of cyclohexdiene / hexatriene

systems

Me
Me
H hν
H dis
Me
Me
Ph Ph Me
Me hν H
H
Me
Ph Ph Me

Ph Ph H
Me hν Me
H
Me
Ph Ph Me

13

Indian Institute of Technology Madras

Engineering Chemistry III Prof. S. Sankararaman

CYCLOADDITION REACTIONS

1. Reaction of two components to form a cyclic compound

2. Ring forming reactions
3. Pericyclic type – both components are π systems
4. Intramolecular and intermolecular versions

Classification
Based on the number of π electrons involved in each component
The numbers are written within a square bracket e.g. [2π + 2π], [2π + 4π] etc

EXAMPLES OF CYCLOADDITION REACTIONS

[2π + 2π]
+

[4π + 2π]

[4π + 4π]

[4π + 6π]
O

[14π + 2π]

NC CN H H
NC CN
CNCN
NC CN

14

Indian Institute of Technology Madras

Engineering Chemistry III Prof. S. Sankararaman

Stereochemistry of cycloaddition reactions

Suprafacial and antarafacial approaches to a π bond

suprafacial antarafacial
approach approach

syn addition anti addition

It is necessary to specify with respect to each π component whether the approach is

suprafacial or antarafacial

The cycloaddition of ethylene to form cyclobutane is a [2πs + 2πs] process. The thermal
Diels-Alder reaction is a [4πs + 2πs] process

Frontier Orbital Method:

HOMO-LUMO interaction for a [2πs+2πs] cycloaddition.

LUMO LUMO

anti bonding both bonding

HOMO HOMO
[ethylene]*

[2πs + 2πs] [2πs + 2πs]

thermally forbidden photochemically allowed

15

Indian Institute of Technology Madras

Engineering Chemistry III Prof. S. Sankararaman

HOMO-LUMO interaction for a [4πs+2πs] cycloaddition

LUMO HOMO
butadiene [butadiene]*

HOMO anti
LUMO
bonding
ethylene ethylene

[4πs + 2πs]
photochemically forbidden

HOMO
butadiene

LUMO
ethylene

[4πs + 2πs]
thermally allowed

Concerted [2π+2π] cycloaddition reactions of alkenes

1. Convenient way to form cyclobutanes

2. Reaction occurs from singlet excited π-π* state
3. Triplet sensitizer is required to form T1 state
4. Acyclic alkenes undergo competing cis-trans isomerization

16

Indian Institute of Technology Madras

Engineering Chemistry III Prof. S. Sankararaman

5. Reaction is generally suprafacial-suprafacial additon and hence highly

stereospecific

Photochemical [2π + 2π] Cycloadditions:

The concerted photochemical [2π + 2π] cycloaddition reaction is suprafacial on both of
the π systems. The dimerization of cis- and trans-2-butene have been reported to take
place in a highly stereospecific manner. The structure of the four possible isomers are
given in Scheme below. The original 2-butene fragment in the product is shown by thick
lines. Only two isomers namely the cis-syn-cis (syn) and the cis-anti-cis (anti) isomer are
formed when pure cis 2-butene was photolysed in the liquid state. Similarly when pure
trans-2-butene was photolysed it gave only trans-anti-trans and cis-anti-cis isomers. The
fourth isomer, namely cis-anti-trans, was formed only when a mixture of cis- and trans-
2-butene was photolysed. This experiment clearly points to the fact that the reaction is
highly stereospecific and suprafacial in each of the reacting partners.

Photochemical cycloaddition reactions of cis- and trans-2-butene.

hν
+
direct

anti / syn = 0.8

hν +
direct

hν
+ + the above products
direct

Chapman has reported an efficient photochemical cross addition of trans-stilbene with

tetramethylethylene with high quantum yield (Φ = 1.0) and high stereospecificity. The
inverse dependence of the rate of cycloaddition with temperature provided evidence for
an exciplex formation.

17

Indian Institute of Technology Madras

Engineering Chemistry III Prof. S. Sankararaman

Photochemical cross addition of trans-stilbene and tetramethylethylene

Ph
Ph
hv
+ Via exciplex, Φ = 1.0
Ph
Ph

[2π+2π] Photocycloadditions of cyclic alkenes

hν
+

H
H
hν
acetone
H
H
H H
H H
hν
+
H H
sens = PhCOCH3 H H
12 : 88

Synthesis of cage structures by photochemical cycloaddition

H
H hν
cyclohexane
62 %

H O hν
H acetone O
O
O basketene
O
O

MeO OMe O

1. hν
2. H+
pentaprismane

18

Indian Institute of Technology Madras

Engineering Chemistry III Prof. S. Sankararaman

Diels-Alder Reaction:
Thermal cycloaddition between a cisoid conjugated diene and a dienophile, usually a
olefin or an acetylene
Six membered ring is formed
It is a concerted [4πs + 2πs ] addition

R1
*
CHR3 *
+
CHR4 *
*
R2

Diels-Alder Diene

s-cisoid s-transoid

conjugated transoid dienes transoid cisoid

>> > >

Order of reactivity of cyclic conjugated dienes

19

Indian Institute of Technology Madras

Engineering Chemistry III Prof. S. Sankararaman

Dienophiles:

CN CN NC CN NC CN

CN NC CN

O
COOCH3 COOCH3 COCH3
O

O COOCH3

O
O
N
N-Ph
N
O O

The “cis” rule :

COOEt

R HH O O O R R H
O
COOEt
COOEt
O
COOEt
R HH O R R H
R = Me, Ph
COOEt

O R R H
R HH O O O COOEt
COOEt
O
R COOEt
H RH O H R

R = Me, Ph

20

Indian Institute of Technology Madras

Engineering Chemistry III Prof. S. Sankararaman

Me

Me H
H
COOH
COOH Me
COOH COOH
H Me COOH
COOH
Me H

Me H
COOH COOH
H Me HOOC
COOH
H COOH
COOH
Me H

Alder’s “endo” rule (secondary orbital interactions):

rt
H
+ H

O
rt H
+ O HO

O O
O

HOMO

O
LUMO O O

21

Indian Institute of Technology Madras

Engineering Chemistry III Prof. S. Sankararaman

Regioselectivity in Diels-Alder reaction:

R R R
R' R'
+ +
R'
"ortho" "meta"

R R' R R' R
+ +
R'
"meta" "para"

Diels-Alder reactions are highly ortho/para selective.

The regioselectivity in Diels-Alder reactions is exemplified below

R R R
X X
Δ
+
X
R X ortho meta
Me COOMe 89 : 11
OAc COOMe 100 : 0
OMe COOMe 100 : 0
OMe CN 100 : 0
OMe CHO 100 : 0

R X R R X
Δ
+ +
X
R X para : meta
Me COOMe 80 : 20
Me CHO 100 : 0
OMe COMe 100 : 0
OMe CHO 100 : 0

22

Indian Institute of Technology Madras