CH 111: Organic Chemistry

Molecular Orbitals: Pericyclic Reactions

Santosh J. Gharpure
Room No. 440
Department of Chemistry,
IIT Bombay, Powai
Mumbai – 400076
e-mail: sjgharpure@chem.iitb.ac.in
sjgharpure@gmail.com
Phone: 2576 7171
Cell: 9167948171
1
 Learning Outcomes

At the end of this module you should be able to….

• Construct π–molecular orbitals for conjugated polyenes

• Explain the reactivity of molecules and reaction

outcomes based on MO Theory

• Predict the stereochemical outcome of the pericyclic

reaction under the given reaction condition
 Molecular Orbital Theory
Molecular Bonds – formed when two atoms are
brought from infinity close to each other
Molecular orbitals - obtained by combining the
atomic orbitals (AO) on the atoms
How do the AOs combine?
Think of the wave nature of electrons
MO2 Destructive (higher energy)

AO AO

MO1 Constructive (lower energy)

Energy
 Examples of Mixing

σ σ* Rows A & B
Axial overlap
σ MO
σ σ*

Row C
Lateral overlap
π π* π MO
Column A Column B
Constructive Destructive
Bonding MO Antibonding MO
 More on σ Orbitals

• No nodes along the internuclear axis (Ignore AO nodes e.g. of p orbital)

• Symmetric along the axis

 Types of Orbitals – Ethylene (C=C)

s*
Antibonding MO
ABMO
H H p*
H H

Ignore C-H p
bonds Bonding MO
BMO
s

Hückel – The sigma framework can be

neglected!!
 Ethylene – Simplified MO picture

The σ – framework neglected as it is in the nodal plane of the p atomic

orbitals
Nodal Plane (nodes) Phase inversion
(node)

(  c11 - c22

LUMO - Lowest
Increasing Unoccupied MO
Energy of
2 x * MO
Orbitals

(  c11 + c22

HOMO - Highest
-MO Occupied MO

Qualitative Picture – Hückel’s MO

Applying to Larger Conjugated Systems

Molecular Orbital Picture

Let us look at the π-bonding interactions closely
The σ – framework neglected as it is in the nodal plane

interact π/ MOs

n n

Qualitative Picture – Hückel’s MO

 MO Construction Acyclic Conjugated Polyenes

antibonding MOs
Energy

n AO Non bonding

bonding MOs

Lowest energy MO 0 nodes,

next MO 1 node
nth MO (n-1) nodes
The nodes are placed symmetrically
When n is even – n/2 bonding and n/2 antibonding MOs exist
When n is odd – (n-1)/2 bonding, 1 non-bonding and (n-1)/2 antibonding MOs exist
 Butadiene MOs

Ψ4 = c1φ1 - c2φ2 + c3φ3 - c4φ4

Write the
wave Ψ3 = c1φ1 - c2φ2 - c3φ3 + c4φ4
equation for LUMO
Energy

each MO

Write the Ψ2 = c1φ1 + c2φ2 - c3φ3 - c4φ4

energy for HOMO
each MO
Ψ1 = c1φ1 + c2φ2 + c3φ3 +
c4φ4
 MOs of Larger Conjugated Polyenes

• The lowest energy orbital is always symmetric with respect to the

principal mirror plane

• The energy of the MO increases as the no: of nodes increases

Eg. ψ1 - 0 nodes
ψ2 - 1 node
ψn - n-1 nodes
Again: Remember to ignore the nodes of the AO

• When you draw MOs place the nodes symmetrically

Draw the MOs of Hexatriene

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 A Small Activity

• Go to www.menti.com –
• Use code 8164588
Happy answering 
 MOs of Hexatriene

ψ6

ψ
5

ψ4
Energy

ψ3

ψ2

ψ1
 MOs – See any patterns?

ψ6
ψ4

ψ2 ψ5

LUMO ψ3
ψ4
LUMO LUMO
Energy

ψ3

ψ2 HOMO
ψ1 ψ
HOMO 2

HOMO ψ1
ψ1

2p 4p 6p
Draw the MOs of Allyl Cation

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 MOs of Allyl System

ψ3

Antibondin
g
Energy

ψ2

Non-
bonding
ψ1

2e⁻ 3e⁻ 4e⁻

Bondi
ng Catio Radic Anion
n al
Summary: Acyclic Conjugated Systems

What is the trend in HOMO-LUMO gap?

Generalizations for Acylic Polyenes

The lowest energy orbital is always symmetric with respect to the

principal mirror plane

The number of nodes increases by ONE on going from one orbital to

the next higher energy orbital

Nodes must be symmetrically located with respect to the central

mirror plane

In systems with an odd number of atoms, the antisymmetric levels

always have a node at the central carbon atom.

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Broad Classification: Organic Reactions
 Polar Mechanism

E+ + Nu_ E Nu

 Radical Mechanism

. + . A B
A B

 Concerted Reactions
All the bonding changes occur at the same time and in a single
step – No intermediates involved !

Pericyclic reactions – Concerted reactions that occur through a

cyclic transition state
 Significance of Orbital Energies

Nucleophiles have higher energy filled nonbonding orbitals

(Ready to donate electrons to suitable electrophiles)
e.g., nonbonding MO in NH3 that contains the lone pair of
electrons is responsible for the nucleophilic nature of the
molecule

Electrophiles are characterized by lower energy unfilled

H
nonbonding orbitals
H

e.g., empty nonbonding MO in BF3 or CH3+ H

Electron Rich to Electron poor

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Possible HOMO-LUMO Combinations

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 Explanation of Reactions Through Molecular
Orbitals

1. non bonding orbital + atomic orbital: SN1

(nBr)2 (nC)0

2. non bonding orbital + antibonding orbital (σ*): SN2

(nO)2 (σ*C-Br )0 28
Pericyclic Reactions: Factors to Consider
• The number of electrons involved has a profound
influence on reactivity

• Pericyclic reactions are stereospecific

• Reactions behave differently depending on the

conditions used (i.e. thermal versus photochemical
conditions)

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 Classification of Pericyclic Reactions
1) Electrocyclic reactions (Ring opening and ring closing)

2) Cycloaddition reactions (cycloreversion)

O O Reagents -
+ S S
3) Cheletropic reactions
O O Heat () or
Light (h)

4) Sigmatropic rearrangement

H H
5) Group transfer reactions
 Class 1- Electrocyclic Reactions
Cyclization of a conjugated polyene (ring closing)
• Outermost π bonds converted to σ bond and π bonds
reorganized
• Classified based on the number of π electrons
highlighted in red

6 e⁻ system
Conjugated triene cyclohexadiene

4 e⁻ system

Conjugated diene cyclobutene

Reverse process (ring opening)

Striking Feature – Electrocyclic Reactions
Stereochemistry - Highly stereospecific

hn D

syn
(2E,4Z)-2,4-hexadiene
(2E,4E)-2,4-hexadiene

hn D

anti
(2E,4Z)-2,4-hexadiene (2E,4E)-2,4-hexadiene
4n system
Orbital Interactions – Electrocyclic Reactions
Two possibilities

Dis
rota
tory

Outermost orbitals
Same symmetry

t or y Bonding interaction
rota
Con Symmetry allowed

Outermost orbitals
Opposite symmetry
The lobes of the reactant MOs must of the correct sign (phase)
for bonding to occur in the transition state leading to product
 Understanding Stereospecificity
Frontier Molecular Orbitals (FMO) Theory
Stereochemistry of an electrocyclic reaction is determined by the
symmetry of the polyene HOMO

Thermal Reactions - Ground state HOMO

Photochemical Reactions – Excited state is the HOMO

LUMO hn HOMO
Excited state

HOMO
 FMO Explanation – Butadiene
Stereospecificity
Butadiene – 4 e⁻ system
Thermal reaction - HOMO is π2

con rotation

bonding

Photochemical reaction - HOMO is π3

dis rotation

bonding
Is applicable to any 4n system
 Revisiting Stereospecificity
h 

syn
(2E,4Z)-2,4-hexadiene
dis
(2E,4E)-2,4-hexadiene con

h 

anti
(2E,4Z)-2,4-hexadiene
dis con(2E,4E)-2,4-hexadiene

4 e⁻ system
Steps to Understand Stereospecificity
Any 4n system

Thermal conditions
• Draw ground state HOMO for butadiene
• Determine mode of closure

Photochemical conditions
• Draw excited state HOMO for butadiene
• Determine mode of closure
 Stereospecificity- Revisited

CH3
CH3 CH3
h 
H
H
CH3 con dis CH3
CH3
(2E,4Z,6E)-2,4,6-octatriene
CH3
CH3 CH3
h 
H
CH3 CH3 CH3
H
(2E,4Z,6Z)-2,4,6-octatriene

con dis

6n system
 Woodward-Hoffman Rules
A pericyclic reaction can take place only if the symmetries of
the reactant (R) MOs are the same as the symmetry of the
product (P) MO
Based on electron count the same rules apply for the ring
opening
System Mode of Allowedness of the
(no of rotation reaction
electrons) Thermal Photochemical

4n con allowed forbidden

4n dis forbidden allowed

4n+2 con forbidden allowed

4n+2 dis allowed forbidden

Electrocyclic Reaction: Torquoselectivity

• Donor substituents prefer con–out mode

• p acceptor substituents prefer con–in mode

43
Electrocyclic Reaction: Torquoselectivity

44
 Some Examples
CH3 Ph
Ph CH3
Ph Ph
Ph  Ph  CH3
CD3 Ph Ph
Ph Ph Ph
CD3
Ph CD3

OMe OMe
Me Me
 h

Me
OMe OMe
Me
Examples of torquoselectivity
Ph Ph Ph
Ph
H ?
Δ
H dis
Ph
Ph
 More Examples
Thermal isomerization of benzocyclobutene to ortho quinodimethane


Thermal valence isomerization of cycloheptatriene-norcaradiene

H
H

(X)n (X)n

H
H
Interesting examples
OMe
Me OMe Me
 h

Me OMe
OMe Me
Selectivity in rotation – called as torquoselectivity
More Practice Problems
 Synthetic Applications
H H

oxidation

H H

Δ Δ
? ? ?
Con Dis

H H

HO OH HO OH
HO OH
 Cycloaddition Reactions
Involves the addition of two (or more) molecules to form a ring
by transferring electrons from π bonds to form σ bonds

[2π + 2π] [4π + 2π]

[4π + 4π] [4π + 6π]

O

Classified by the number of π electrons interacting

(shown in red)
 Ease of Reaction
Ease with which a cycloaddition takes place thermally
depends on number of π electrons involved
Δ
[4π + 2π] Occurs readily

Diels-Alder a widely used reaction in organic synthesis

Δ
[2π + 2π] Does not occur easily

hν
+ Occurs

Why is this so ??
 Interactions – Cycloaddition Reactions
Cycloadditions involve facial interactions and not
side by side interactions

One face of 4π system

One face of 2π system

 CYCLOADDITION REACTIONS:
The Stereochemical issues
In a cycloaddition, a pi system may be attacked in one of
two distinct ways.
• If the pi system is attacked from the same face, then
the reaction is suprafacial on that component.
• If the system is attacked from opposite faces, then the
reaction is antarafacial on that component.

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 FMO Treatment of [2+2] Cycloaddition reaction
• Consider the reaction between two ground state
ethylene molecules in which both of them undergo
reaction in a suprafacial mode.
• HOMO of one ethylene interacts with LUMO of other
ethylene.
Consider [2 + 2] cycloaddition: Thermal activation [ p2s + p2s ]

57
58
FMO Treatment of [2+2] Cycloaddition reactions:
Photochemical Activation

62
 [4π + 2π]

Diene Dienophile
(2 double (likes diene)
bonds)

For this course – Dienes – electron rich

Dienophile – electron deficient

‘Normal’ electron demand Diel’s Alder Reactions

Typically: HOMO – e⁻ rich compd LUMO – e⁻ deficient compd

In this case diene – HOMO and dienophile - LUMO

 FMO Explanation – [4π + 2π]
Thermal Conditions

LUMO (dienophile)

Matching Matching
symmetry symmetry

HOMO (diene)

Suprafacial [4πs + 2πs]

Easy for thermal 4πs + 2πs cycloaddition to occur

What about photochemical 4π + 2π cycloaddition?
 Selection Rules for Cycloaddition

System Mode of Allowedness of the reaction

(total no. of addition
electrons)
Thermal Photochemical

4n s/s forbidden allowed

4n s/a allowed forbidden

4n+2 s/s allowed forbidden

4n+2 s/a forbidden allowed

(n = natural number)
Since s/a mode is difficult to achieve mainly the s/s
mode is observed
 [2+2] Cycloaddition Reactions:
Intramolecular [2p+2p] Photocycloadditions

+?

Combination of [4+2] and [2+2] cycloaddition leads to strained cage shaped molecules
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 4π + 2π Cycloaddition
Diels-Alder Reaction


+

diene dienophile adduct

Thermal cycloaddition between a cisoid conjugated diene and a dienophile

Discovered by Otto Diels and Kurt Alder (Nobel prize 1950)

Diels Alder
 Reactivity - Diels-Alder Reaction
Requirement
Diene should be in a cisoid (s-cis) conformation

Transoid dienes are unreactive

Normally isomerization possible

Unreactive as transoid structure is locked

 [4π + 2π]

Diene Dienophile
(2 double (likes diene)
bonds)

For this discussion – Dienes – electron rich

Dienophile – electron deficient

‘Normal’ electron demand Diels-Alder Reactions

 Effect of Substituent on Reactivity
Electron releasing groups (or alkyl groups) - Raise HOMO and LUMO energy

Electron withdrawing groups - Lower HOMO and LUMO energies

Improve Decrease ERG on diene

D-A rate HOMO-LUMO
gap EWG on dienophile

ΔE1 ΔE2 < ΔE1

ΔE2
More efficient
reaction

CHO Me

E
Diene Dienophile Dienophile Diene
 One Minute Paper

Compare the order of reactivity

Me for these
CHOdienes

Me CHO

> > > >

Planar Alkyl – Not planar EWG –

Constrained HOMO inc. Near s-cis HOMO dec.
s-cis
 Cis-Rule in Diels-Alder Reactions
Suprafacial Interaction

Cis dienophile Adduct with cis substituents

Trans dienophile Adduct with trans substituents

COOH COOH
+
COOH COOH

major product - syn

COOH COOH
+
HOOC COOH

major product - anti

Rule holds true for dienes as well !

 Cis Rule

R R H R COOEt R H
COOEt COOEt COOEt
H + H +
H COOEt R COOEt
COOEt R H COOEt H R
R H

R R R R
HCOOEt H HCOOEt H
H H COOEt R R COOEt
R R H H
EtOOC COOEt EtOOC COOEt
Visualizing [4+2] Cycloaddition
Visualizing [4+2] Cycloaddition: Another View
Diels Alder reaction – Highly Stereospecific

R
R
COOH COOH
+
HOOC COOH
R
R

R R
R
COOH COOH
COOH
+
COOH COOH
COOH
R R
R

major product
 Alder’s Endo Rule
Dienophile approaches the diene preferentially in the endo mode so as to allow
maximum spatial overlap of the unsaturated centers of the diene and
dienophile
R R
R
COOH COOH COOH
+ +
COOH COOH COOH
R R
R
Endo product Exo product

R R R R

H H H H
H H H H H H COOH
HOOC
R R H R R COOH
H COOH
COOH H H
HOOC HOOC H
H COOH

Endo approach - Favoured Exo approach

[4+2] Cycloaddition Reactions:The Alder Endo Rule

Excellent endo selectivity for maleic anhydride

86
 Let us try to write the products
H COOH H
H
+
COOH
H COOH
COOH

HOOC H COOH
H
O + H
H COOH COOH

OMe OMe
O H O

O O
+
H O
O Me
Me

CH3 CH3
CHO CHO
+
 Regioselectivity
CH3 CH3 CH3
CHO CHO
+
CHO
Major Product

X X X
Y Y
+ +
Y
Favoured

X Y X X Y
+ +
Y
Favoured
 Let us try to write the product

Me 

MeOOC

Intra-molecular
O

+ OMe
RO
O2N

Don’t get confused: Remember the basics 

 More Problems
O
What is the product?
O
Ph  O
? ?
Ph

What is the mechanism?

 Synthetic Utility
O H H O
O H
H
+

O O O HH
endo cis-anti-cis
O
H O
H O
 h
+
[4 + 2] [2 + 2]
O
O O

O
O
9
several
xylene steps
+ O
reflux 83 %
10
O
triptycene
Synthesis of Basketene

H O
H H
 H O h O
+ O H
O O
H O
O O

basketene
Synthesis of Endiandric acid
 Recap - [4π + 2π] Cycloaddition
Reactivity Selectivity
• Cis-rule – Relative stereochem
• S-Cis Conformation required diene or dienophile
R COOEt R H
COOEt
H +
H COOEt
required COOEt R H
R

• Endo-rule - Relative stereochem

• ERG – Diene (HOMO) diene-dienophile
• Regioselectivity
EWG – Dienophile (LUMO)
out CH3 CH3 syn
ERG OHC CHO
+ in

EWG
MeO CHO MeO
+
CHO