Diels-Alder Reaction II
 A diene and dienophile undergo a cycloaddition
 Prototype reaction: butadiene and ethylene [4n+2]p-addition
+
diene
dienophile
“aromatic TS”
cyclo-adduct
 In order for the aromatic transition state to form, the diene
has to be s-cis conformation (cisoid)
s-cis
DHf= 73.16 kJ/mol
s-trans
72.54 kJ/mol
+ CH2=CHCOCH3
s-trans
s-cis
DHf= 79.12 kJ/mol
N.R.
40.53 kJ/mol
 Substituents on the diene and the dienophile can have
a significant effect on their reactivity and therefore the
conditions required to carry out the reaction
200oC
+
O
O
CH3
140oC
CH3
+
O
+
O
CH3
30oC
CH3
 Strategically placed donor and acceptor groups both
seem to facilitate the reaction
 Explanation (simplified version)
Energy
LUMO
LUMO
LUMO
LUMO
LUMO
HOMO
HOMO
LUMO
HOMO
HOMO
HOMO
O
HOMO
O
 Acceptor groups lower the orbital energies for the HUMO and the LUMO orbital
because they reduce the electron-density in the p-system
 Donor groups raise the orbital energies for the HUMO and the LUMO orbital
because they increase the electron-density in the p-system
 Thus, placing a donor in the diene and an acceptor in the dienophile (or vice versa
 inverse electron-demand) is most effective in decreasing the HUMO-LUMO gap,
which directly relates to the activation energy for the reaction
 Diels-Alder reactions are stereoselective because they
are concerted for most parts (=all bonds are broken and
formed at the same time)
 The stereochemistry of the diene and the dienophile are
retained in the cyclo-adduct
O
H
 Cis to cis
+
H
H
CH3
CH3
CH3
CH3
H O
O
O
 Trans to trans
H
H
O
CH3
+
H3C
O
CH3
CH3
H
O
H O
 For many Diels-Alder reactions, a high degree of regioselectivity is
observed favoring six-membered rings with 1,2- or 1,4-substitution
R
R
R
X
X
+
X
major
X
minor
X
+
R
R
R
X
minor
major
 Example: Reaction of 1-methoxybutadiene (R=OMe) and methyl
vinyl ketone (X=COCH3)
O
O
Resonance contributors
of the diene
O
O
Resonance contributors
of the dienophile
 If a bicycle is formed in the reaction, an endo or an exo
product can be formed in the reaction depending on
the temperature
 Endo product
R
R
H
+
R
R
R
H
R
 Exo product
+
R
R
R
R
R
H
R
H
 Which product is preferentially formed highly depends
on the reaction conditions
 Low temperature: endo product
 High temperature: exo product
 Example: Maleic anhydride and cyclopentadiene
 Exo approach
 This product is usually thermodynamically more stable
O
O
O
LU MO
O
O
C
O
O
H
HOMO
O
H C
 Endo approach
 This product is formed at lower temperatures because of
the secondary orbital interaction (in red) which lower the
activation energy for the endo pathway
O
C
O
LU MO
O
O
O
LU MO
H
C
O
O
H C
C
O
O
HOMO
HOMO
 The activation energies for the endo and the exo pathway are different resulting
different rates of reaction
Y=
Eact( 1)
Eact( 2)
Eact( 3)
Eact( 4)
A+B
Energy
Y
X=
H
O
HC
C O
O
O
CO
HC
H O
A=
(start)
X
Endo
(Kin etic Product)
Exo
DHf= -293.3 kJ/mol (AM1)
DHf= -300.7 kJ/mol (AM1)
(T herm ody nam ic Pro duct)
Reactant
O
B=
O
Reactant
rxn coordinate
O
 The endo pathway has the lower activation energy and is therefore favored
at low temperatures (=kinetic control)
 The endo-product can be converted to the exo-product by heating (T=190 oC,
1.5 hrs) because the reaction is reversible (=thermodynamic control)
 At high temperatures (T=206 oC), an almost equimolar mixture of the endo
and the exo-product is obtained from the reaction of dicyclopentadiene with
maleic anhydride
 The simplest reaction would be the reaction of ethylene
with itself
+
no lig ht
at r.t.
?
 Experience tells us that this reaction does not take place
 Ethylene has only two p-electrons
p
LUMO
p
HOMO
 The combination of the HUMO
and LUMO of ethylene leads to
one bonding and one anti-bonding Energy
antibonding
interaction, which cancel
each out other energetically
+
bonding
XXX
no reaction
 The next case would be the reaction of ethylene with butadiene
+
 This reaction seems to proceed with low yields (~20 %)
p
anti-bonding
orbitals
p3
LUMO
p2
HOMO
Energy
bonding
orbitals
p
 Butadiene has four p-electrons, which means that the two lowest
p-orbitals are filled making p2 the HOMO and p3 the LUMO
 Either combination leads to the formation of two new
bonding interactions and no anti-bonding interactions
bonding
bonding
LUMO
HOMO
Cycloadduct
HOMO
bonding
bonding
LUMO
 The cyclo-adduct is formed in this reaction
 Reactions that involve [4n+2]p-electrons are allowed
thermodynamically speaking (D)
 Reactions that involve [4n]p-electrons often require
photochemically activation (hn)