In general...
The Diels-Alder
Diels-Alder Reaction
Synthetic method for preparing
compounds containing a cyclohexene ring
+
conjugated
alkene
diene
(dienophile)
dienophile)
cyclohexene
via
transition state
Mechanistic features
concerted mechanism
new σ bond
[4+2] cycloaddition
+
pericyclic reaction
a concerted reaction that proceeds
through a cyclic transition state
Only the s-cis conformation of the diene
can react
diene
dienophile
transition
state
new σ bond
What makes a reactive dienophile?
dienophile?
The most reactive dienophiles have an
electron-withdrawing group (EWG
(EWG)) directly
attached to the double bond.
Typical EWGs
EWG
C
C
C
O
C
N
Example
O
H 2C
CH2 + H2C
CHCH
CH
CH
100°
100°C
O
CH
(100%)
Example
Example
O
H 2C
CHCH
CH2 + H2C
CH
CH
H 2C
O
CHC
CH2
O
O
CH
CH
(100%)
O
100°
100°C O
100°
100°C
via:
+
CH3
O
H 3C
O
(100%)
O
Example
H 2C
Acetylenic Dienophile
O
CHC
CH2
+
CH3
benzene
via:
O
H 2C
CHCH
O
H 3C
COCH2CH3
O
O
(100%)
CCOCH2CH3
100°
100°C
100°
100°C O
O
O
CH2 + CH3CH2OCC
O
O
H 3C
O
(98%)
COCH2CH3
O
O
Diels-Alder
Diels-Alder Reaction
Cis
Cis
C6H5
Stereospecific syn addition
H 2C
cis-trans relationship of substituents of alkene
is retained in the product
Only the s-cis
conformation of
the diene can
participate in a
Diels–Alder
reaction
The most reactive dienophiles have an
electron-withdrawing group (EWG
(EWG)) directly
attached to the double bond.
The most reactive dienes have an electrondonating (releasing) group (ERG
(ERG)) directly
attached to the double bond. Eg.
Eg. -OR
O
CHCH
CH2 +
C
C6H5
H
O
Trans
O
3<1<2
2<3<1
COH
H
H 2C
CHCH
CH2 +
C
C6H5
H
B)
D)
(racemic)
racemic)
COH
C6H5
A) 1 < 2 < 3
C) 3 < 2 < 1
H
H
Question
Rank the compounds below in order of
increasing rate of the Diels-Alder
Diels-Alder reaction.
C
H
Only product.
But, is it enantiomeric?
enantiomeric?
Trans
COH
only product
(racemic)
racemic)
COH
H
O
C
H
Stereospecific, concerted, syn addition:
Question
What is the product of the Diels-Alder
Diels-Alder reaction that
occurs between the reactants shown here?
A)
B)
C)
D)
Predict the reaction products:
2. Consider the charge distribution in each of the
reactants
1. Consider the alignment of the reactants
Question
Select the correct starting materials to make
the compound at the right through the
Diels-Alder
Diels-Alder reaction.
A)
C)
B)
D)
Cyclic dienes yield bridged bicyclic
Diels-Alder
Diels-Alder adducts.
Since only cis dienes can participate in Diels–Alder
reactions: 5- & 6- membered rings are ideal
O
COCH3
H
C
+
CH3OC
C
H
O
H
O
COCH3
H
COCH3
O
H
O
COCH3
H
O
COCH3
H
is the
same as
COCH3
H
COCH3
O
O
The π Molecular Orbitals
of
Ethylene and 1,3-Butadiene
Orbitals and Chemical Reactions
Orbitals and Chemical Reactions
A deeper understanding of chemical reactivity
can be modeled using frontier orbitals of the
reactants.
Electrons flow from the highest occupied
molecular orbital (HOMO) of one reactant to
the lowest unoccupied molecular orbital
(LUMO) of the other.
Reactants’ HOMO and LUMO
We can illustrate HOMO-LUMO interactions by
way of the Diels-Alder
Diels-Alder reaction between
ethylene and 1,3-butadiene.
We need only consider only the π electrons of
ethylene and 1,3-butadiene. We can ignore
the framework of σ bonds in each molecule.
MO Analysis of Diels-Alder
Diels-Alder Reaction
HOMO of 1,3-butadiene
HOMO of 1,3-butadiene
and LUMO of ethylene
are in phase with one
another
allows σ bond formation
between the alkene and
the diene
LUMO of ethylene (dienophile
(dienophile))
Two Possible Configurations of Bridged
Bicyclic Compounds
Secondary orbital overlap favors the endo product
formation
MO Analysis of Diels-Alder
Diels-Alder Reaction
A π Molecular Orbital Analysis
Inasmuch as electron-withdrawing groups
increase the reactivity of a dienophile,
dienophile, we
assume electrons flow from the HOMO of the
diene to the LUMO of the dienophile.
dienophile.
of the
Diels-Alder
Diels-Alder Reaction
MO Analysis of Diels-Alder
Diels-Alder Reaction
A "forbidden" reaction
HOMO of 1,3-butadiene
H 2C
H 2C
+
CH2
CH2
The dimerization of ethylene to give cyclobutane
does not occur under conditions of typical
Diels-Alder
Diels-Alder reactions.
LUMO of ethylene (dienophile
(dienophile))
A "forbidden" reaction
H 2C
H 2C
+
CH2
CH2
HOMO-LUMO
mismatch of two
ethylene molecules
precludes single-step
formation of two new
σ bonds
HOMO of
one ethylene
molecule
LUMO of
other ethylene
molecule