Organic Chemistry II (PHCM

(PHCM 433)
Lecture 5: Addition to conjugated dienes
and Pericyclic reactions
Dr. Mohammad Abdel-
Abdel-Halim
Office : B5-
B5-133, mohammad.abdel-
[email protected]

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Assoc. Prof. Mohammad Abdel-
Abdel-Halim
 Learning Outcomes
• Compare the stability of dienes to that of aromatic compounds
• Highlight the difference between the addition to isolated dienes and conjugated
dienes.
• Highlight the difference between the transition states resulting from the 1,2-
addtion and 1,4- addition.
• Explain the difference between kinetic control and thermodynamic control of
reaction products.
• Define pericyclic reactions and their types and compare them with polar and
radical reactions
• Explain and predict the regiochemistry and the stereochemistry of Diels–Alder
reaction product .
• Order different dienes and dienophiles according to their reactivity in Diels–Alder
reaction.
• Design a synthetic plan to prepare Diels–Alder reaction product
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Assoc. Prof. Mohammad Abdel-
Abdel-Halim
 Addition to conjugated dienes

Two double bonds

separated by a
single bond

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Assoc. Prof. Mohammad Abdel-
Abdel-Halim
 Different Types of Dienes

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Assoc. Prof. Mohammad Abdel-
Abdel-Halim
 Conjugated Dienes :1,3
:1,3-
1,3-BUTADIENE
Bond Lengths of 1,3-Butadiene: the central bond of 1,3-butadiene is considerably shorter
than the single bond of ethane

the p orbitals of
1,3 -butadiene

The central carbon atoms of 1,3-butadiene are close enough for overlap to occur between
the p orbitals of C2 and C3. This overlap is not as great as that between the orbitals of C1
and C2 (or those of C3 and C4). The C2–C3 orbital overlap, however, gives the central bond
partial double-bond character and allows the four π electrons of 1,3-butadiene to be
delocalized over all four atoms 5
Assoc. Prof. Mohammad Abdel-
Abdel-Halim
 Conjugated Dienes :1,3
:1,3-
1,3-BUTADIENE
CONFORMATIONS OF 1,3-BUTADIENE
There are two possible planar conformations of 1,3-butadiene

s-cis conformation s-trans Conformation

less stable more stable

These are not true cis and trans forms since the s-cis and s-trans conformations of 1,3-
butadiene can be interconverted through rotation about the single bond (hence the prefix
s). The s-trans conformation is the predominant one at room temperature
2 3
s-cis conformation
less stable
H H steric interference
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of H atoms
Assoc. Prof. Mohammad Abdel-
Abdel-Halim
 Conjugated Dienes :1,3
:1,3-
1,3-BUTADIENE
Stability:
Conjugated alkadienes are thermodynamically more stable than isomeric isolated
alkadienes, this can be indicated by measuring heat of hydrogenation.
example 1 example 2

The extra stability of conjugated dienes

→ stronger central bond that they contain and
→ additional delocalization of the π electrons
heats of hydrogenation of 2 mol of 1-butene and 1
mol of 1,3-butadiene. that occurs in conjugated dienes 7

Assoc. Prof. Mohammad Abdel-

Abdel-Halim
 Electrophilic Attack on Conjugated Dienes: 1,2-
1,2- and 1,4-
1,4-Addition
Conjugated dienes undergo both 1,2- and 1,4-addition through an allylic intermediate that
is common to both
direct addition conjugate addition

2 2 2
1 4 1 4 1 4
1 equiv
3 3 3
The numbering is for the double bonds not IUPAC numbering

Less stable , formed more More stable, Internal double

rapidly at low temperature bond (disubstituted), formed at
conditions (cooling) high temperature conditions

'Kinetic' Product 'Thermodynamic' Product

NB. For the 1- and 2-positions or at the 1- and 4-positions, the:
numbers refer to the four carbons of the conjugated system. Thus,
the carbon in the 1-position is the sp2 carbon at one of the ends of
the conjugated system—it is not necessarily the first carbon in the
molecule.
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Assoc. Prof. Mohammad Abdel-
Abdel-Halim
 Electrophilic Attack on Conjugated Dienes: 1,2-
1,2- and 1,4-
1,4-Addition

Remember: secondary allylic primary allyic

Markovnikov's carbocatiom carbocatiom
rule
1 2 4 1 2 4
3 3

a proton adds to one of the terminal carbon atoms of 1,3-

butadiene to form the more stable carbocation

2 4
1 3

2 4
1 3

chloride ion forms a bond to one of the carbon atoms of the allylic cation that bears a partial positive
charge to give the 1,2-addition or gives the 1,4-addition product. 9
Assoc. Prof. Mohammad Abdel-
Abdel-Halim
 Electrophilic Attack on Conjugated Dienes: 1,2-
1,2- and 1,4-
1,4-Addition
Kinetic Control versus Thermodynamic Control of a Chemical Reaction: the way temperature
affects product distribution in a reaction that can take multiple paths.

kinetic
product

Thermodynamic
products

kinetic (or rate) control product . The favored Thermodynamic (or equilibrium) control
products in a reaction at lower temperature are products. The favored products at higher
those formed by the pathway having the smallest temperature in a reversible reaction are those
energy of activation barrier. (the 1,2- product) that are most stable. (the 1,4- product)
When the product mixture from the low temperature reaction is warmed to the higher temperature, the product
distribution becomes the same as when the reaction was carried out at high temperature—that is, the 1,4-product
predominates. 10
Assoc. Prof. Mohammad Abdel-
Abdel-Halim
 Electrophilic Attack on Conjugated Dienes: 1,2-
1,2- and 1,4-
1,4-Addition
both products have the The path to go to the 1,2 -addition product
same transition state goes through a lower-energy transition state
for the first step
and ends up at this higher-energy product.
To do the 1,4 -addition product, we go to a
higher-energy transition state, but then we
end up at a lower-energy product.

allylic carbocation

more stable product

with lower energy

transition state for formation of the 1,2-addition transition state for

product lower in energy, so Lower activation formation of the 1,4-addition
energy needed so faster reaction product higher in energy 11
Assoc. Prof. Mohammad Abdel-
Abdel-Halim
 Electrophilic Attack on Conjugated Dienes: 1,2-
1,2- and 1,4-
1,4-Addition

The 1,2-addtion product is faster to be formed, why ?

After H+ adds to the double bond, the bromide ion can form a bond with C-2 faster than it
can form a bond with C-4 simply because it is closer to C-2 than to C-4. So it is a
proximity effect that causes the 1,2-addition product to be formed faster. A proximity
effect is an effect caused by one species being close to another`.

closer C-2

H+ added
here

proximity effect
The Br- is closer to the added hydrogen
So closer to C2

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Assoc. Prof. Mohammad Abdel-
Abdel-Halim
 Electrophilic Attack on Conjugated Dienes: 1,2-
1,2- and 1,4-
1,4-Addition
The 1,2-addition product is always the kinetic product
However, 1,4-addition product is not always the thermodynamic product
Example 1 more stable

1,2 -addition product 1,4 -addition product

kinetic product &
Thermodynamic products
Have the same stability
neither is the thermodynamic product

Example 2

kinetic product
1,2 -addition product 1,4 -addition product
Approximately equal amounts of both products will be formed under conditions that cause the addition
reaction to be reversible 13
Assoc. Prof. Mohammad Abdel-
Abdel-Halim
 Pericyclic reactions
Pericyclic reactions are reactions involving cyclic transition states, the
electrons in one or more reactants are reorganized in a cyclic manner
electrons move in a concerted fashion (no intermediate)

Three types :
 Cycloaddition reactions
 Electrocyclic reactions
 Sigmatropic rearrangements

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Assoc. Prof. Mohammad Abdel-
Abdel-Halim
 cycloaddition reactions : Example Diels–
Diels–Alder reaction
In a cycloaddition reaction, two different π-bond-containing molecules react to form a cyclic
compound. Each of the reactants loses a π bond, and the resulting cyclic product has two new
σ bonds.
In a Diels–Alder reaction, a conjugated diene reacts with a compound containing a carbon–15
carbon double bond. The latter compound is called a dienophile because it “loves a diene.”

dienophile
two π electrons Transition state
conjugated diene
six delocalized π
four π electrons Cyclohexene product
electrons (aromatic
in character)
Diels–
Diels–Alder reaction is [4 + 2] cycloaddition reaction because four of the six π electrons that
participate in the cyclic transition state come from the conjugated diene and two come from
the dienophile. ([4 + 2] cycloadditions are promoted by heat energy)
Assoc. Prof. Mohammad Abdel-
Abdel-Halim
 cycloaddition reactions : Example Diels–
Diels–Alder reaction
The Diels–Alder reaction is an example of 1,4- addition reaction . it is simply the
1,4-addition of an electrophile and a nucleophile to a conjugated diene.
However, unlike the other 1,4-addition reactions—where the electrophile adds to the diene
in the first step and the nucleophile adds to the carbocation in the second step—the Diels–
Alder reaction is a concerted reaction: the addition of the electrophile and the addition of the
nucleophile occur in a single step.

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Assoc. Prof. Mohammad Abdel-
Abdel-Halim
 Oversimplification

E
Nu
Diene Dienophile

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Assoc. Prof. Mohammad Abdel-
Abdel-Halim
 Diels–
Diels–Alder reaction
The Dienophile R
Can be alkene R
or alkyne
Product has
two double bonds

Cyclohexadiene product

An EWG Increases the reactivity of the Dienophile: it withdraws electrons

from the dienophile’s double bond. This puts a partial positive charge on
the sp2 carbon that the π electrons of the conjugated diene. Thus, EWG
makes the dienophile a better electrophile.

better
electrophile18
Assoc. Prof. Mohammad Abdel-
Abdel-Halim
 Diels–
Diels–Alder reaction
The Diene
Diels–Alder reaction is favored by the presence of electron-releasing groups in the diene,
EDG increases the electron density on the diene (in Diels Alder reactions the diene acts as
the nucleophilic component) e.g. alkyl group or an ether group.

Example
O O

H 30 °C H Reaction
proceeds readily
under mild
conditions
Diene Dienophile
Yield 100 %
methyl EDG carbonyl EWG
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Assoc. Prof. Mohammad Abdel-
Abdel-Halim
 Diels–
Diels–Alder reaction
Regiochemistry : Predicting the Product When Both Reagents Are Unsymmetrically Substituted
In Diels–Alder reactions, only one product is formed (disregarding stereoisomers) if at least one
of the reacting molecules is symmetrically substituted.
If both the diene and the dienophile are unsymmetrically substituted two products are
possible. The products are constitutional isomers.

2 constitutional
isomers

rule is that 1,2 is

preferred over 1,3
Asymmetric Asymmetric product A
Diene Dienophile (1.2 product) product B (1,3)
Two products are possible because the reactants can align in two different ways

To determine the structure of

the second product, don’t
change the position of one of
the reactants and turn the
other upside down
this gives product A 20
Assoc. Prof. Mohammad Abdel-
Abdel-Halim this gives product B
 Diels–
Diels–Alder reaction
But which is the product formed product formed in greater yield in the previous reactions ?
Depends on the charge distribution in each of the reactants
donating electrons
by resonance withdrawing electrons
by resonance

resonance contributors of the diene resonance contributors of the dienophile

The partially positively charged carbon of the dienophile bonds preferentially to the partially
negatively charged carbon of the diene

rule is that 1,2

is preferred
over 1,3

joining up with the best electrophile, the most Nu site

Major product 21
Assoc. Prof. Mohammad Abdel-
Abdel-Halim
 Diels–
Diels–Alder reaction

2 constitutional
isomers

rule is that 1,4 is

Asymmetric Asymmetric product A product B preferred over 1,3
Diene Dienophile (1.3 product) (1,4 product)
Major product

Two products are possible because the reactants can align in two different ways

To determine the structure of

the second product, don’t
change the position of one of
the reactants and turn the
other upside down

this gives product A this gives product B

Major product
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Assoc. Prof. Mohammad Abdel-
Abdel-Halim
WHY?
 Diels–
Diels–Alder reaction
Conformation of the Diene

room temperature

The conjugated diene must be in an s-cis conformation because when it is in an s-trans

conformation, C-1 and C-4 are too far apart to react with the dienophile in a concerted
reaction

conjugated diene that is locked in

an s-trans conformation cannot
undergo a Diels–Alder reaction
because it cannot achieve the
required s-cis conformation.
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Assoc. Prof. Mohammad Abdel-
Abdel-Halim
 Diels–
Diels–Alder reaction
Conformation of the Diene
Cyclic diene: A conjugated diene that is locked in an s-cis conformation, such as 1,3-
cyclopentadiene, is highly reactive in a Diels–Alder reaction

diene locked
s-cis conformation
Endo Exo

When the diene is a cyclic compound, the product of a Diels–Alder reaction is

a bridged bicyclic compound (a compound that contains two rings that share
two nonadjacent carbons).
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Assoc. Prof. Mohammad Abdel-
Abdel-Halim
 Remember !

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Assoc. Prof. Mohammad Abdel-
Abdel-Halim
 Rank the following dienes from most reactive to least reactive in a Diels–
Alder reaction:

Answer:

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Assoc. Prof. Mohammad Abdel-
Abdel-Halim
 Diels–
Diels–Alder reaction
Exo and Endo Products
There are two possible configurations for substituted bridged bicyclic compounds,
because the substituent (R) can either point away from the double bond (the exo
configuration) or not point away from the double bond (the endo configuration)

The endo product is formed faster when the dienophile has a substituent with π electrons.
the increased rate of endo product formation is due to interaction between the π electrons
of the substituent and the π electrons of the ring, which stabilizes the transition state.
A substituent in the exo position cannot engage in such stabilizing interactions.
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Assoc. Prof. Mohammad Abdel-
Abdel-Halim
 Diels–
Diels–Alder reaction
RETROSYNTHETIC ANALYSIS OF THE DIELS–ALDER REACTION
To determine the reactants needed to synthesize a Diels-Alder product
1) locate the double bond in the product. The diene that was used to form the cyclic product had
double bonds on either side of this double bond, so draw in those double bonds and remove the
original double bond.
2) the new σ bonds are now on the other side of these double bonds. Deleting these σ bonds and
putting a π bond between the two carbons whose s bonds were deleted gives the needed reactants—
that is, the diene and the dienophile

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Assoc. Prof. Mohammad Abdel-
Abdel-Halim
 What diene and what dienophile should be used to synthesize
the following?

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Assoc. Prof. Mohammad Abdel-
Abdel-Halim
 References

• Organic Chemistry, 2nd edition, Clayden.

• Organic Chemistry, 12th edition, Solomons.
• Organic Chemistry, 4th edition, Bruice.
• Organic Chemistry, 4th edition, Carey.

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Assoc. Prof. Mohammad Abdel-
Abdel-Halim
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