1. Chapter 22 Pericyclic Reactions
concerted
cyclic transition state of breaking and forming bonds
no electrophiles, nucleophiles, or radicals
very stereospecific
energy supplied by
heat, Δ, thermolysis or pyrolysis or
light, hν, photolysis
Now we are going to look at a new type of reaction.
We have seen an example in Chapter 20, decarboxylation of a β-ketoester.

2. Let’s look at another example that shows the amazing stereoselectivity of these reactions.
The reaction is completely stereospecific in both directions.
Furthermore, the photochemical reaction has the opposite stereochemistry.

3. conrotation: end carbons rotate in the same direction
Let’s look at the stereochemistry in more detail.
The reaction simply requires that the end C’s rotate so that their p orbitals can overlap to form the new sigma bond.
Two different rotations occur in the thermal reaction and the photochemical reaction. The rotation in the thermal reaction is called conrotation.
conrotation: end carbons rotate in the same direction

4. disrotation: end carbons rotate in opposite directions
The rotation in the photochemical reaction is called disrotation.
There is no obvious reason why one rotation should be preferred to the exclusion of the other. Nor is the reason why the thermal reaction prefers conrotation and the photochemical reaction prefers disrotation apparent.
disrotation: end carbons rotate in opposite directions

5. theoretical explanation (1965) developed by
R. B. Woodward and R. Hoffmann
and
K. Fukui
Fukui and Hoffmann shared the 1981 Nobel Prize
in chemistry for this work.
Woodward died in 1979, so he did not share in this Nobel prize because it is not given posthumously. However, he had already won a Nobel Prize in 1965 for his work in the area of organic synthesis. Had he lived a little longer, he would have undoubtedly won a second Nobel, making him one of the few scientists to attain this honor. Woodward is thought to be the greatest organic chemist of the 20th century by many people.
Both theories explain whether the transition state is favorable by examining how the reactant MO’s are converted to the product MO’s in the reaction. So we need to look at the MO’s.

6. MO Theory for Conjugated Molecules
The number of MO’s equals the number of AO’s
combining to form them.
The energies of the MO’s are symmetrically placed
about the energy of an isolated p orbital
(arbitrarily taken as zero energy).
The energy of an MO increases as the number of nodes
increases.
Nodes are symmetrically placed in a molecule.
We developed MO theory for localized MO’s in Chapter 3 and added some information about delocalized MO’s in Chapters 15 and 16. We need to know how the pi MO’s of a conjugated system are arranged in energy and where the nodes are located in each MO in order to use them in understanding pericyclic reactions.

7. Let’s see how these rules are applied by looking at some examples.
We’ll start with ethene. We did the pi MO’s for it in Chapter 3. There are two pi MO’s, symmetrically placed about zero energy (the energy of a p orbital). The bonding MO has no node and the antibonding MO has one node.
Now consider 1,3-butadiene. Four p orbitals combine to form four MO’s. Note the HOMO and the LUMO.

8. Let’s try 1,3,5-hexatriene.
If we shine light on the compound, an electron is excited to a higher energy antibonding MO. This changes the HOMO and the LUMO.

9. frontier MO’s = HOMO and LUMO
We will also have to deal with some systems which have an odd number of orbitals.
In general, all odd orbital systems have a nonbonding MO with nodes passing through the even numbered carbons.
To determine whether a pericyclic reaction is favorable, we need to evaluate how the energies of the electrons change as the pericyclic reaction proceeds. If the electrons are in MO’s that increase in energy, then the reaction should be unfavorable. But if the occupied MO’s remain at the same energy, or decrease, then the reaction should be favorable.
Woodward and Hoffmann used the symmetry of the placement of nodes to determine which reactant MO was converted to which product MO. Fukui showed that we can concentrate on the frontier MO’s, the HOMO and the LUMO. Fukui’s method is a little simpler, so that’s the one we’ll use.
The best way to see how everything works is to do some examples.
frontier MO’s = HOMO and LUMO

10. Electrocyclic Reactions
forms a sigma bond between the end atoms of a series
of conjugated pi bonds
Pericyclic reactions are broken into three classes. We’ll look at electrocyclic reactions first.
product has one more sigma bond and one less pi bond than reactant

11. Overlap of orbitals where new bond is formed must be
conrotation
Overlap of orbitals where new bond is formed must be
favorable (bonding) in the HOMO.
Here is the thermal conversion of (2E,4E)-hexadiene to trans-3,4-dimethylcyclobutene.
The HOMO for 1,3-butadiene is π2. It has one node.

12. Let’s look at disrotation.

13. In the photochemical reaction an electron is excited from π2 to π3
In the photochemical reaction an electron is excited from π2 to π3*, so the HOMO is now π3*. It has two nodes.

14. Let’s try a triene.
The HOMO is π3, which has two nodes. Therefore disrotation is preferred.
Conrotation is forbidden.
In the photochemical reaction, there is one more node in HOMO, so conrotation is the allowed pathway.
You can probably see, each time we add a C=C, the HOMO has one more node, so the preference changes from con to dis or from dis to con.

15. This reaction is thermally forbidden.
Let’s do an odd orbital system.
Is this reaction allowed or forbidden?
There are five MO’s. There are six electrons in these MO’s, so π3nb is the HOMO.
The reaction is proceeding by conrotation.
HOMO = π3nb
This reaction is thermally forbidden.

16. If HOMO has an odd number of nodes (π2, π4, π6 ...)
the thermal reaction proceeds with conrotation.
If HOMO has an even number of nodes (π1, π3, π5 ...)
the thermal reaction proceeds with disrotation.
Number of Electron Pairs Disrotation Conrotation
Odd thermally photochemically
allowed allowed
Even photochemically thermally
We can generalize.

17. Let’s use the table to predict the result of this reaction.
We have been analyzing this reaction from the other direction, that is, a diene closing to a cyclobutene. But the analysis works for either direction of any reaction. This reaction involves two pairs of electrons (even), so the thermally allowed reaction is conrotation. Both methyl groups are trans in the diene product.

18. Examples of Electrocyclic Reactions
allowed in either direction
two electron pairs (even)
Let’s look at some actual examples of electrocyclic reactions.
This will open to a butadiene.
thermally allowed reaction is conrotation
equilibrium favors the butadiene product
no angle strain

19. put light selectively into diene
(dienes absorb longer wavelength, lower energy light)
The reverse process, conversion of a butadiene to a cyclobutene, can be accomplished photochemically.
Disrotation results in the H’s being cis.
The product is stable under these reaction conditions. Cyclobutene does not absorb light so it cannot disrotate back because that is thermally forbidden. Conrotation is thermally allowed, but gives a trans double bond in the ring. This product is too strained to form.
At higher temperatures, the product does open, probably by a nonconcerted path.
disrotation is photochemically allowed

20. 6 electrons (3 pairs) odd, so disrotation is thermally allowed
Norcaradiene cannot be isolated because its conversion to cycloheptatriene is fast at room temperature and its concentration in the equilibrium mixture is very low because of ring strain.
The last example is similar, but here the product (5 and 6 membered rings) is more stable than the reactant (9 membered ring).

21. 4 pairs
3 pairs

22. Cycloaddition Reactions
two molecules cyclized product
two pi bonds converted to two sigma bonds
The second type of pericyclic reactions is called cycloadditions.
classified according to the number of pi electrons in each component

23. thermal [2+2] cycloaddition reaction
photochemical [2+2] cycloaddition reaction
only one component is excited
Cycloaddition reactions can be viewed as involving electrons flowing from the HOMO of one component to the LUMO of the other. Thus, to be allowed, the overlaps of the HOMO and LUMO must both be bonding where the new bond are formed.
Let’s do an example. Consider the thermal [2+2] cycloaddition. The HOMO of one component is π. The LUMO of the other is π*.
The thermal [2+2] cycloaddition is forbidden.
Let’s look at the photochemical reaction. It is important to note that only one component is excited in a photochemical reaction. Because excited states have extremely short lifetimes, the chances of two excited molecules colliding are exceedingly small.

24. thermal [4+2] cycloaddition reaction
We’ll picture electrons as flowing from the HOMO of the diene to the LUMO of the alkene, although analysis either way gives the same results.
The HOMO of the diene is π2, which has one node.
The LUMO of the alkene is π*, which also has one node.
We can generalize. If we add another pi bond to one component, we add one more node to the HOMO or LUMO. This reverses the signs at one terminus and reverses the selection rule. So a [2+2] is photochemically allowed, a [4+2] is thermally allowed, a [4+4] is photochemically allowed, etc. Or in terms of number of electron pairs:
Number of Electron Pairs Allowed Cycloaddition
Odd Thermal
Even Photochemical

25. The Diels-Alder Reaction (a [4+2] Cycloaddition)
1950 Nobel Prize in chemistry
very useful, makes a six-membered ring
with excellent control of stereochemistry
The [4+2] cycloaddition was a very important reaction long before this theory was developed.
Here is the simplest example. The yield is not too good in this particular example.
Better yields are obtained if the diene and the dienophile are substituted with groups of opposite polarity, EWG’s on one and EDG’s on the other. Most of the examples have the EWG’s on the dienophile. Here are some examples of good dienophiles.

26. syn addition on both components
stereochemistry:
syn addition on both components
So let’s look at some examples.

27. conformation of the diene
Now let’s analyze the 3-D shape of the diene. It must be planar for conjugation, but there are two possibilities.
These conformations are in equilibrium. The s-trans is more stable in this case because it has less steric strain.
Only the s-cis can react. The ends are too far apart in the s-trans. The more s-cis that is present at equilibrium, the more reactive the diene is.
unreactive
diene is held s-trans
more s-cis present
This diene is about 10x
more reactive.

28. Cyclopentadiene is a very reactive dienophile
Cyclopentadiene is a very reactive dienophile. It dimerizes spontaneously upon storage. One molecule reacts as the diene and a second as the dienophile.
To use cyclopentadiene in a reaction, dicyclopentadiene is heated to just below its boiling point to establish the equilibrium. The lower boiling cyclopentadiene distills off and is kept cold and used as soon as possible.
This introduces a new aspect to the reaction, the stereochemical relationship between the diene and the dienophile.
The newly formed cyclohexene ring has a one carbon bridge connecting positions 1 and 4.
Groups that are cis to this bridge are called exo, and those that are trans are called endo.

29. Usually, substituents on the dienophile, if they have pi bonds, are found to be endo in the adduct.
This is postulated to result from favorable interactions of orbitals on C-2 and C-3 of the diene with the orbitals on the groups attached to the dienophile.

30. When both the diene and the dienophile are unsymmetrically substituted, regioisomeric products are possible. In the first example, with the diene substituted on C-1, the “ortho-like” product is favored rather than the “meta-like” product. The stereochemistry results from endo addition. The H on the blue C is located where the bridge was in cyclopentadiene. So the ester substituent is trans to this H, or cis to the amine.
In the second example, with the diene substituted on C-2, the “para-like” product is preferred rather than the “meta-like” product. There is no stereochemistry in this case.

31. intramolecular reactions are favorable
Here are some additional examples.
The central ring of anthracene can act as a dienophile because the product has not lost much resonance energy.
Intramolecular Diels-Alder reactions can be used to make multiring systems.

32. The dienophile can be an alkyne.
Atoms other than C can be part of the diene or the dienophile.

33. Other Cycloaddition Reactions
[2+2] cycloadditions
photochemically allowed
Photochemical [2+2] cycloadditions are probably the best way to make four-membered rings.

34. a [8+2] cycloaddition = 5 electron pairs
Carbonyl groups will also add to alkenes.
Cycloadditions to form rings larger than 6-membered are less common because they are entropically unfavorable. However, if the ends are held in closer proximity, then the cycloaddition can occur. Here is an example. The N holds the blue C’s close together, so a 5-membered ring is formed. However, in terms of the pi system, a 10-membered ring is formed.
a [8+2] cycloaddition = 5 electron pairs
thermally allowed

35. Sigmatropic Rearrangements
intramolecular migration of a group along a conjugated pi system
The final type of pericyclic reactions is called sigmatropic rearrangements. A sigma bond between the migrating group and the atom next to a pi bond is broken and a new sigma bond is formed at the other end of the pi system.
Let’s look at this from an orbital perspective.

36. 1. find the sigma bond broken in the reaction
To classify:
1. find the sigma bond broken in the reaction
2. assign number 1 to both atoms of this bond
Sigmatropic rearrangements are classified according to the number of bonds separating the migration origin and the migration terminus in each component. Let’s see how to do it for the reaction we just saw.
3. number atoms of each component up to
where new sigma bond is formed
4. designate rearrangement by the numbers of the atoms
where the sigma bond is formed in the product

37. Both components can have pi bonds.

38. thermal [1,3] sigmatropic rearrangement
photochemical
To determine whether a sigmatropic rearrangement is allowed or forbidden, imagine breaking the sigma bond to form two radicals. (But remember, the reaction is concerted.) Examine the overlaps of the HOMO’s of each radical at the migration origin and the migration terminus. If both interactions are bonding, then the reaction is allowed.
Let’s try this with the [1,3] sigmatropic rearrangement.
The thermal [1,3] sigmatropic rearrangement is forbidden.
For the photochemical reaction, use the LUMO of the ground state allyl radical.

39. [1,5] sigmatropic rearrangement
For the photochemical reaction, use the next MO (π4*), which has one more node. So math signs at the end p orbital interchange, resulting in a antibonding interaction.
The [1,5] sigmatropic rearrangement is photochemically forbidden.

40. [3,3] sigmatropic rearrangement

41. Again, you can probably see that the MO’s for the photochemical reaction have one more node, so one interaction will be changed from bonding to antibonding and the photochemical reaction is forbidden.

42. [1,3] 4 electrons, 2 pairs, photochemically allowed
[1,5] and [3,3] 6 electrons, 3 pairs, thermally allowed
Number of Electron Pairs Allowed Sigmatropic
Rearrangement
Odd Thermal
Even Photochemical
We can generalize.
Note that these are the same rules as for cycloadditions.

43. Examples of Sigmatropic Rearrangements
The [1,3] sigmatropic rearrangement is photochemically allowed.
Let’s look at some examples of sigmatropic rearrangements.
Although the second reaction is highly exothermic, it does not occur at room temperature because the [1,3] sigmatropic rearrangement is thermally forbidden.

44. The [1,5] sigmatropic rearrangement is thermally allowed.
The half-life for the rearrangement of the methylcyclopentadiene isomers is about 1 hr at 20oC.

45. [3,3] Sigmatropic rearrangements are thermally allowed.
Cope rearrangement
The most important sigmatropic rearrangements are the [3,3] rearrangements.
The reaction is allowed in both directions, so the reactants are in equilibrium with the products. The position of the equilibrium is controlled by the stabilities of the compounds.
The more highly substituted alkene is a little more stable.
The product is more stable in the second example because of less ring strain.
The product is more stable in the third example because it is stabilized by conjugation.

47. Claisen rearrangement
spontaneous
enolization
The oxygen analog of the Cope rearrangement is called the Claisen rearrangement. Many of the examples involve aromatic ethers.

49. Rearrangements to Electron-Deficient Centers
one electron pair (odd)
thermally allowed
pinacol rearrangement
Carbocation rearrangements can be classified as [1,2] sigmatropic rearrangements.
There are some useful carbocation rearrangements.

50. Let’s look at the mechanism of the pinacol rearrangement.

52. Beckmann rearrangement
Similar rearrangements to N are known. The Beckmann rearrangement converts an oxime to an amide.
Rearrangement is concerted with water leaving because N+ is very unstable.

53. The Beckmann rearrangement is used to make caprolactam from cyclohexanone. Caprolactam is used to make nylon 6.

54. Hofmann Rearrangement
Here is a similar rearrangement to N called the Hofmann rearrangement. The carbonyl C of an amide is lost as CO2 to give an amine with one less C.
Let’s look at the mechanism for this reaction.
The carbonyl C of an isocyanate is a very reactive electrophile and reacts rapidly with water and base to give a carbamic acid. Carbamic acids are unstable and spontaneously lose carbon dioxide to give an amine.

55. Baeyer-Villiger Rearrangement
A similar rearrangement to electron deficient oxygen is known.
A ketone is treated with a peracid to produce an ester.
Let’s look at the mechanism for this reaction.
First, the peracid reacts as a nucleophile with the carbonyl carbon electrophile to form an analog of a hemiacetal.

56. Summary For disrotatory electrocyclic reactions, cycloadditions, and
sigmatropic rearrangements:
Number of Electron Pairs Allowed Reaction
Odd Thermal
Even Photochemical
The rules for conrotatory electrocyclic are reversed.

57. Here are the pericyclic reactions that are encountered most often.

58. Here are the electron-deficient rearrangements that were covered in this chapter.