Chemistry 20
Lecture 8c
Chemistry E-2b: Lecture 1The
•
•
Diels-Alder Reaction
January 28, 2010
One of the
most powerful reactions
in organic
synthesis
is known as the Diels-Alder
Diels-Alder:
Dienes
and
Dienophiles
reaction, after Otto Diels and Kurt Alder. Here is an example. Can you “push arrows”?
The diene in the Diels-Alder reaction must react through the s-cis conformation. Why?
O
O
OMe
+
O
OMe
OMe
heat
diene
••
dienophile
(+/–)
cyclic 6-membered
transition state
What are
can the
youfrontier
say about
the reactivity
ofin
thethe
following
dienes
in Diels-Alder reactions?
What
orbitals
involved
Diels-Alder
reaction?
O
Me
Me
Me
Me
•
The dienophile in a Diels-Alder reaction is usually conjugated with an electronwithdrawing group: a carbonyl group or a nitrile. Why?
These are excellent dienophiles:
O
O
CN
CN
O
O
OMe
CN
NC
O
Reading: Section 15.3
1
16
Chemistry 20
Lecture 8c
Molecular Orbitals of Conjugated p-Orbitals
•
Is there any way to figure out, exactly, where the nodes will be in these conjugated
π-systems? Let’s find out where the nodes are for the orbitals of butadiene:
•
And how can we find the energies of the orbitals in these conjugated systems?
E = α − 2β
E=α
E = α + 2β
2
Chemistry 20
Lecture 8c
Diels-Alder: Dienes and Dienophiles
•
The diene in a Diels-Alder reaction must react through the s-cis conformation. Why?
Chemistry E-2b: Lecture 1
January 28, 2010
Diels-Alder: Dienes and Dienophiles
•
The diene in the Diels-Alder reaction must react through the s-cis conformation. Why?
•
What can you say about the reactivity of the following dienes in Diels-Alder reactions?
•
What can you say about the reactivity of the following dienes in Diels-Alder reactions?
O
Me
Me
Me
Me
•
The dienophile in a Diels-Alder reaction is usually conjugated with an electronwithdrawing group: a carbonyl group or a nitrile. These are excellent dienophiles:
O
O
CN
CN
O
O
OMe
CN
NC
3
O
Reading: Section 15.3
Chemistry E-2b: Lecture 1
Chemistry 20
Chemistry E-2b: Lecture 1
•
•
•
January 28, 2010
Lecture 8c
January 28, 2010
Diels-Alder: Stereochemistry
Diels-Alder
Stereochemistry:
Suprafacial
Diels-Alder:
Stereochemistry
The stereochemistry of the dienophile is preserved in the reaction. Predict the products
The
of the dienophile is preserved in the reaction. Predict the products of
of stereochemistry
the
following reactions:
The
stereochemistry
of the dienophile is preserved in the reaction. Predict the products
the
following
reactions:
of the following reactions:
CN
CN
+
+
CN
CN
CN
CN
+
+ NC
NC
••
•
The
thethe
diene
is is
preserved
inin
thethe
reaction.
Predict
thethe
products
of of
thethe
Thestereochemistry
stereochemistryofof
diene
preserved
reaction.
Predict
products
following
reactions:
following
reactions:of the diene is preserved in the reaction. Predict the products of the
The
stereochemistry
following reactions:
CN
+
+
CN
NC
NC
CN
+
+
CN
NC
NC
•
Reading: Section 15.3
We say that the Diels-Alder reaction is suprafacial in both components.
Reading: Section 15.3
17
417
Chemistry
Chemistry20
E-2b: Lecture 1
Lecture
8c
January
28, 2010
Diels-Alder
Stereochemistry:
Rule”
Diels-Alder:
Stereochemistry
and“Endo
Regiochemistry
••
When
thethe
endo
and
Whenrelevant
relevantthe
theendo
endodiastereomer
diastereomerisisfavored
favored(the
(the“endo
“endorule”).
rule”).Show
Show
endo
and
exo
products
of
the
following
Diels-Alder
reactions:
exo products of the following Diels-Alder reactions:
CN
+
CN
CN
+
CN
•
•
How can you remember the endo rule?
•
•
How can you remember the endo rule?
Finally, when there are two possible regioisomers that can be formed, the preferred
isomers usually have the substituents either ortho or para to one another (the “ortho/para
possiblefor
regioisomers
forfor
thethe
following
reactions,
and indicate the
Isrule”).
there aShow
good both
explanation
the endo rule
Diels-Alder
reaction?
preferred isomer.
+
CN
CN
+
CN
CN
+
Reading: Section 15.3
518
Chemistry 20
Lecture 8c
Diels-Alder Regiochemistry
•
•
Finally, when there are two possible regioisomers that can be formed, the preferred
Finally,
there
arethe
twosubstituents
possible regioisomers
can be
the preferred
isomerswhen
usually
have
either orthothat
or para
to formed,
one another
(the “ortho/para
isomers
usually
have
the
substituents
either
ortho
or
para
to
one
another
“ortho/para
rule”). Show both possible regioisomers for the following reactions, and(the
indicate
the
rule”).
Show
both
possible
regioisomers
for
the
following
reactions,
and
indicate
the
preferred isomer.
preferred isomer.
CN
+
CN
+
Reading: Section 15.3
•
We can explain the ortho/para rule by looking at resonance structures for electron
donating groups on the diene and electron withdrawing groups on the dienophile. Let’s
take a look…
18
CN
OMe
CN
OMe
MeO
CN
MeO
CN
6
Chemistry 20
Chemistry E-2b: Synthesis
Lecture 1
•
Lecture 8c
using the Diels-Alder Reaction
January 28, 2010
Provide a multistep synthesis for the desired product from the indicating starting
Synthesis
Using
the Diels-Alder
Reaction
materials. You may
use any inorganic
reagents plus any reagents
with four (4) carbons
or fewer. Pay careful attention to the specified stereochemistry in your answer. The
correctsynthesis
answer will
require
five
or fewer
Provide a multistep
for the
desired
product
fromsteps.
the indicating starting materials. You may use any
inorganic reagents plus any reagents with four (4) carbons or less. Pay careful attention to the specified
stereochemistry in your answer. The correct answer will require five or fewer steps.
Starting material: any compounds with 4 carbons or less.
HO
CN
HO
CN
Desired product
(as a racemic mixture)
7
19