CHEM 351, Spring 2016
Principles of Organic Chemistry II Lab
Prof. T. Nalli, WSU
Learning from Molecular Models - The Diels-Alder Cycloaddition Reaction
Textbook Reference – Smith - chapter 16.12-16.14
Overview
This work sheet introduces the Diels-Alder 4+2 cycloaddition reaction of a diene with a
dienophile to form a cyclohexene ring. Models will demonstrate the geometric requirements
for the diene, the stereospecificity of the reaction, and the endo selectivity principle.
Introduction
A Diels-Alder reaction in its simplest form is shown below. Although this specific reaction does
not work well, it will be useful to examine it with models so that some basic principles can be
learned.
(1)
diene
dienophile
cycloadduct
Characteristics of Diels-Alder Reactions
1. Identify the bonds broken and formed in a Diels-Alder reaction. (Use eq 1 as an example.)
Based on the bond strengths of these bonds are Diels-Alder reactions ordinarily exothermic or
endothermic?
Bonds broken = both pi bonds of diene + the pi bond of the dienophile
Bonds formed = the pi bond of the cyclohexene + two sigma bonds
3 weak pi bonds broken – (2 strong sigma bonds + 1 weak pi) = exothermic!
Several lines of experimental evidence (the instructor will present some of these in the lab)
indicate that the Diels-Alder reaction has a concerted mechanism (a single step).
2. Use curved arrows to show electron flow in the above Diels-Alder reaction (eq 1).
3. Using dotted lines to represent partial bonds, draw a representation of the transition state of
a Diels-Alder reaction. Identify some unique characteristics of this TS.
The TS has six pi electrons delocalized around a ring in an unbroken loop of p orbitals.
Thus, it can be considered to be aromatic.
Geometric Requirement for the Diene in a Diels-Alder Reaction
Make models of the reactants, 1,3-butadiene (the diene) and ethene (the dienophile), and of
the product, cyclohexene (the cycloadduct). Notice that the diene has two different planar
conformers that result from rotation of the C-C single bond. It is well established that the
planar conformations are the energy minima for single bond rotation in 1,3-butadiene.
4. Draw these two planar conformations showing all hydrogens.
H
H
H
H
H
H H
H
H
H
H H
5. Draw a PE diagram for rotation of the C2-C3 bond in 1,3-butadiene.
6. Why are the planar conformations energy minima?
For delocalization/resonance to stabilize the molecule the p-orbitals on carbons 2 and 3 need
to be able to overlap with each other. As the C2-C3 bond rotates the molecule out of planarity
these orbitals become unable to overlap. (See above drawings under number 5).
One of the butadiene conformations is referred to as the s-cis conformer and the other as the
s-trans conformer.
7. Why would it be improper to simply refer to these conformations as cis and trans?
Because cis and trans refer to configurations of a molecule that are not interconvertible by
single bond rotation, e.g., cis and trans 2-butene. The structures we are examining here quickly
interconvert at room temperature and represent two conformers of the same compound not
different compounds. They cannot be separated from each other.
Try to simulate the basic Diels-Alder reaction (eq 1) using your models. First try the s-cis
conformer of the diene, then try the s-trans conformer. Remember that the mechanism is
concerted, so all bonds being formed have to be formed simultaneously.
8. Which conformation of the diene works better in your attempted simulation? Can you
generalize as to what types of dienes (conformation wise) are most reactive in Diels-Alder
reactions?
The s-cis works better because the 1 and 4 carbons are close enough to get within bonding
distance of the dienophile both at the same time. The s-trans does not work at all because the
1 and 4 carbons are too far apart to react in a concerted fashion with the dienophile.
Now make models and examine the s-cis conformations of the three stereoisomers of 2,4hexadiene shown below.
trans, trans
cis, cis
cis, trans
9. Draw each of the above molecules in its s-cis conformation. (They are all shown as s-trans
above.)
H
H
H3C
H
CH3
H H
H
H
H
CH3
CH3 H
H
H
H
CHH33C
10. In which isomer is the s-cis conformation least strained? Explain.
The s-cis conformation is least strained in the trans, trans isomer. There is little steric strain
between the internal Hs on C1 and C4.
11. In which isomer is the s-cis conformation most strained? Explain.
The s-cis conformation is most strained in the cis, cis isomer. There is excessive steric strain
between the internal methyls on C1 and C4.
12. Which isomer has the highest population of its molecules existing as s-cis.?
The trans, trans has the highest population of its molecules existing as s-cis because it is the
least strained relative to the other conformer (the s-trans) that it is in equilibrium with. Thus,
the equilibrium constant that governs bond rotation is most favorable toward s-cis in the trans,
trans isomer.
13. Predict the order of reactivity of the 2,4-hexadiene stereoisomers in Diels-Alder reactions.
A diene cannot react in a Diels Alder reaction unless it can exist as s-cis. Thus the order of
reactivity is (from most reactive to least reactive) trans, trans > cis, trans >> cis, cis. (The cis,
cis won’t react at all because of excessive steric strain making its s-cis conformation
impossible.)
14. 1,3-Cyclopentadiene and 1,3-cyclohexadiene are particularly reactive dienes. Explain. Which
do you think is more reactive?
They are both particularly reactive because they are both locked into s-cis arrangements, and
therefore the carbons at C1 and C4 are always close enough to bond simultaneously to a
dienophile. Cyclopentadiene is more reactive because the smaller ring holds the end carbons
even closer together making simultaneous bonding even more feasible. In addition,
cyclopentadiene has more angle strain that is partly relieved by the hybridization changes that
occur in a Diel Alder reaction.
Stereospecificity with Respect to the Diene
Now consider the reaction of each of the dienes just prepared with ethylene to form 3,6dimethylcyclohexene.
15. Show an equation for this reaction (neglecting stereochemistry) in the space below.
+
Note that the product of the above reaction can exist as a cis or a trans isomer. Simulate the
reaction with models as before, remembering it is concerted,
16. Which isomer(s) of the product would be formed if the cis, cis isomer of the diene reacted
with ethene? (cis, trans, or both?) cis
17. Which isomer(s) of the product would be formed if the trans, trans isomer of the diene
reacted with ethene? (cis, trans, or both?) cis
18. Which isomer(s) of the product would be formed if the cis, trans isomer of the diene reacted
with ethene? (cis, trans, or both?) trans
19. Summarize your findings with respect to questions #16-18 using chemical equations to show
the structures of the reactants and products in these three reactions.
+
+
+
Notice that each stereoisomer of the reactant diene gives a specific stereoisomer of the
product. A reaction of this type is called a stereospecific reaction. Diels-Alder reactions are
stereospecific in that the stereochemistry of the diene is maintained.
Stereospecificity with Respect to the Dienophile
Now take the methyl groups off your hexadiene models reforming the original butadiene
model that we were working with at the start of the lab. Substitute the methyl groups for
hydrogens on your ethene model so that you now have a model of cis-2-butene.
Simulate a Diels-Alder reaction of cis-2-butene with 1.3-butadiene to form 4,5dimethylcyclohexene. Note that this product can exist as a cis or a trans isomer.
20. Which isomer(s) of the product would be formed by this reaction? (cis, trans, or both?) cis
Repeat the previous simulation using trans-2-butene.
21. Which isomer(s) of the product would be formed this reaction? (cis, trans, or both?) trans
22. Summarize your findings with respect to questions #20 and 21 using chemical equations to
show the structures of the reactants and products in these two reactions.
+
+
What you have just seen is that Diels-Alder reactions are also stereospecific in the sense that
the stereochemistry of the dienophile is maintained.
Endo Selectivity
1,3-Cyclopentadiene is so reactive as a diene that it reacts with another molecule of itself to
form a compound commonly called dicyclopentadiene (see equation below). In this reaction,
one molecule of the cyclopentadiene plays the role of the diene, while the other acts as the
dienophile. (This reaction happens readily at room temperature. Therefore, pure samples of
1,3-cyclopentadiene to be used for other purposes need to be prepared just before use as they
do not keep well.)
diene
dienophile
Make two models of 1,3-cyclopentadiene and simulate the Diels-Alder reaction described
above. You should note well that there are two distinct possibilities for how the diene and
dienophile approach each other in this reaction. To see these, focus on the double bond that is
not involved in the reaction (in the dienophile). Picture the diene to be approaching from on
top of the dienophile. The non-reacting double bond can either be directly below C2 and C3 of
the diene (endo approach) or it can be closer to the CH2 of the diene (exo approach) as
depicted below.
Now make models of the resulting dicyclopentadiene products, both exo and endo, and
examine them for any kinds of strain present.
23. Draw structural representations of the exo and endo isomers showing clearly the
stereochemical aspects that distinguish them.
endo
exo
H
H
H
H
24. Which isomer of dicyclopentadiene is less strained? Explain why by diagraming strain
interactions in the structures you drew above. The endo is more strained by about 1 kcal/mol.
25. The endo product is usually the predominant product (usually on the order of 80-90%). Given
this fact, is the reaction under thermodynamic or kinetic control? Kinetic control. The reaction is
very exothermic (see page 1), therefore there is generally not enough energy (even at elevated
temperatures) for the products to get over the Ea’s for the reverse reaction. Thus, the adducts
do not revert to reactants and do not have opportunity to equilibrate.
26. Draw out approximations of the transition states for both endo and exo approach by copying
the above diagrams and drawing in the p orbitals of the reacting pi bonds.
27. Use the transition state diagrams you just drew to explain why endo products are formed
faster than exo products.
The endo TS is more stable due to extra pi orbital overlap between the back end of the diene
(C2 and C3 of the diene) and the pi substituent of the dienophile (C3 and C4 of the dienophile).
In the above diagrams the red lines represent the start of orbital overlap that will eventually
end up as the new sigma bonds in the product. The blue lines represent the additional orbital
overlap in the endo that stabilizes the TS (and speeds the reaction).
Additional Questions
Give the structure of the main product of each of the following Diels-Alder reactions. Make
sure to show the stereochemistry of the products when unambiguous.
CN
O
+
NC
O
O
O