Pericyclic Reactions
Pericyclic reactions: Bonding changes occur through reorganization of electron pairs within a closed loop of interacting orbitals
In order for a reaction to be pericyclic the bonding changes must be concerted, therefore bond formation and bond cleavage occur simultaneously
If stepwise then the reaction is not pericyclic
The extent of bond formation or breakage need not be equivalent at a given point along the
reaction coordinate only that the process are both occurring simultaneously
Concerted ≠ Synchronous
What importance does knowledge of pericyclic reactions impart?
Allows prediction about whether a reaction will proceed and also allows prediction about stereochemical control
338 Pericyclic Reactions
All pericyclic reactions have a transition state with a continuous loop of electrons in a cycle
The symmetry characteristics of the orbitals in the cycle thus determine the selection rules
Chemists R.B. Woodward and Roald Hoffmann developed “rules” to predict when pericyclic reactions can occur with low energy barriers (allowed reactions) or when they have high energy barriers (forbidden reactions)
* Called Woodward-Hoffmann rules
There are four types of reactions that are considered pericyclic:
Electrocyclic
(reactions were the first type the Woodward-Hoffmann rules were developed to explain)
Cycloadditions
(including cheletropic – cycloadditions where one reactant is through a single atom)
Sigmatropic
Group Transfer
339 Pericyclic Reactions
Examples of each type of reaction:
Electrocyclic
Cyclic ring either opens up or closes
Cycloaddition
NO2
NO2
Two compounds react to form a ring
Sigmatropic
Bond(s) migrate over a
conjugated system
Group Transfer
H
H
H
H
Transfer atoms from one group to another
All pericyclic reactions will have a defined stereochemistry depending upon number of electrons involved in the process
340 Electrocyclic Reactions
We will begin to look at how to predict pericyclic reactions by considering the ring closure in an electrocyclic reaction
When this E,E-2,4-hexadiene ring closes in an electrocyclic reaction, potentially two different stereoisomers are obtained
What intrigued Woodward, however, is that only one of these stereoisomers is obtained when the reaction is run experimentally (and there is always only one product whenever any butadiene system ring closes)
If only one is obtained, how to predict which is favored instead of needing to run the
experiment for every new compound?
Today it seems more obvious due to the better understanding of orbital interactions in
reactions, but the approach is to always consider that the reaction must be occurring through
a molecular orbital, so if we can write the HOMO for the compound this must dictate how
341 the reaction proceeds
Electrocyclic Reactions
We have already learned how to draw a simple Hückel HOMO for butadiene
HOMO of butadiene
In the electrocyclic ring closure, the two terminal atoms react to form the new sigma bond
New σ bond
In order to form a bond, only orbitals of like sign can interact, therefore the symmetry of the
butadiene HOMO will dictate how the terminal atoms must move to form a bond
In order to form a bond,
the two orbitals must spin
in the same direction (both clockwise as shown)
If orbitals move in same
direction it is called
conrotatory (CON), if different directions then
disrotatory (DIS)
342 Electrocyclic Reactions
Thus a butadiene system will close in a CONROTATORY motion
An unsubstituted butadiene will generate the same cyclobutene upon ring closure whether it undergoes a CON or DIS ring closure, but a substituted butadiene yields different stereoisomers
FAVORED
Which is favored?
Would just need to perform a CON ring closure to determine preferred product
In the E,E-2,4-hexadiene
compound, the methyl groups are pointing
away from each other
H3C
H3 C
CH
3
CH3
A CON motion thus places the
methyl groups on opposite sides
of the ring, therefore the trans
product is favored
343 Electrocyclic Reactions
Any size conjugated system could form a ring through an electrocyclic reaction, a pericyclic
reaction needs an orbital on each atom of the ring interacting but size is not limited
Consider hexatriene
Would once again need to consider the HOMO for the hexatriene (which was already determined with Hückel)
Once again the terminal
atoms combine to form
the new σ bond
Compounds can be categorized by the number of
electrons in system on the preferred electrocyclic rotation
4n systems
4n+2 systems
With hexatriene, a CON rotation gives the
wrong bonding scheme, need a DIS rotation instead
CONROTATORY
DISROTATORY
344 Electrocyclic Reactions
By the principle of microscopic reversibility, the ring opening reactions must proceed
through the same symmetry motions as the ring closing
Therefore in ring opening, a 4n system opens through a CON motion while a 4n+2 system opens through a DIS motion
(methyl groups pointed in
same direction at both
double bonds)
Therefore consider a CON
motion for this cyclobutene
ring opening with methyl
groups starting on same side
Product yields are due to
symmetry of ring opening,
not stability of product!
CH3
CH3
CH3
CH3
When this compound does a ring
opening through a CON motion,
the methyl groups in product
point in the same direction
Δ
99.9%
0.005%
345 Electrocyclic Reactions
With a CON ring opening with cyclobutene, the ring could open in two different ways (both terminal atoms rotating clockwise or both terminal atoms rotating counterclockwise)
A C
B
B D
C
A
D
A D
B C
Both rotate clockwise
Both rotate counterclockwise
Which product will be favored?
Orbital symmetry does not distinguish between these two structures, they both are possible
When there is a difference in sterics, however, one product can be preferred
H3 C H
H H
Δ
H3 C
CH3
favored
346 Electrocyclic Reactions
Electrocyclic reactions can occur in ring opening reactions involving loss of a leaving group
OCH3
CH3OH
Cl
The ring can aid in the
leaving group departing
Cl
As cyclopropane ring
opens up, an allyl cation
is formed
Cl
There are 2 electrons
involved in this process,
Back lobe of
therefore ring opening is
C-Cl bond
disrotatory
Rotate view so looking
The C-C bond anti to
at the bond breaking
leaving group, aids in
(and C-Cl bond is
leaving group departing
behind in view)
The bond breaks only in the disrotatory motion that moves electrons towards the back lobe of the C-Cl bond that is breaking
347 Electrocyclic Reactions
Will not have bond break in other possible disrotatory motion because this motion would not aid in leaving group departing
Cl
Cl
Back lobe of
C-Cl bond
Also disrotatory, but
when electrons move
this way do not break
C-Cl bond
Knowing this motion, predict which of the following two isomers will react faster
krel
Cl
Cl
348 Electrocyclic Reactions
Cyclopropanes can open up in an electrocyclic reaction to aid in leaving groups at other sites,
consider this bicyclic compound
Disrotatory
(still 2 e’s)
OCH3
CH3OH
Rotate towards
back lobe
TsO
Can thus make predictions about relative rates for isomers of this structure
krel
H
H
TsO
TsO
H
H
349 Electrocyclic Reactions
Ring constraints can impact rates of normal electrocyclic ring opening reactions
Consider a cyclobutene ring opening when included in a bicyclic compound
4 e’s, therefore CON
H
H
200˚C
Would generate a trans double
bond, but ring is 10 carbons,
so Bredt’s rule is not violated
420˚C
H
H
Ring is 3 carbons shorter
Observed product is cis-cis
1,3-cycloheptadiene
Obtain forbidden pathway due to the allowed electrocyclic ring opening would violate Bredt’s rule (by placing trans alkene in 7 membered ring), thus reaction occurs at much higher temperature
350 Electrocyclic Reactions
Photochemically an electron is promoted into a higher energy molecular orbital
When considering a butadiene system, this means the symmetry of the HOMO changes
A
A
S
S
hν
A
A
S
S
The HOMO is antisymmetric (A) in
ground state, therefore need CON
Upon photolysis, HOMO changes
to symmetric, thus need DIS
351 Electrocyclic Reactions
Upon photolysis, therefore, the motion changes compared to the thermal process
For an electrocyclic reaction
# of electrons
Thermal (Δ)
Photochemical (hν)
4n
CON
DIS
4n+2
DIS
CON
Allows reactions that to occur that would be impossible under opposite conditions
H
H
This compound can form
readily under photolysis
hν
Δ
DIS
CON
H
H
Highly strained, does not form
352 Cycloaddition Reactions
We have already briefly discussed cycloaddition reactions when looking at a Diels-Alder
reaction in the discussion on molecular orbital theory
A similar orbital consideration needs to be undertaken by considering the HOMO of one reactant interacting with the LUMO of the second (in a cycloaddition there are two molecules reacting, unlike an electrocyclic where a single
compound either forms a ring or opens a ring)
Typically the butadiene component reacts through the HOMO and the ethylene reacts through the LUMO
LUMO of ethylene
HOMO of butadiene
Reaction is symmetry allowed
If the symmetry was not correct, then it would be symmetry forbidden by
Woodward-Hoffmann rules
To increase the rate of a Diels-Alder reaction, the energy difference between the HOMO of butadiene and the LUMO of ethylene needs to be lowered
353 Cycloaddition Reactions
Cycloadditions are further characterized by the allowed symmetry of addition
If the orbitals react on the same side of a plane, then the addition is suprafacial (S), if the orbitals react on the opposite sides of a plane, then the addition is antarafacial (A) Suprafacial addition
Suprafacial addition
A Diels-Alder reaction is thus formally a [4πS + 2πS] addition
354 Cycloaddition Reactions
When an alkene HOMO reacts with an alkene LUMO, however, the suprafacial reaction will not be symmetry allowed
HOMO
of alkene
LUMO
of alkene
Suprafacial addition
Suprafacial addition
[2πS + 2πS]
forbidden
But an antarafacial addition is allowed
In a four membered ring
this orientation is hard to
reach, therefore rate of
reaction is slow but the
stereochemistry is allowed
[2πS + 2πA]
allowed
Antarafacial addition
Suprafacial addition
355 Additional Problems
Are the following observations allowed according to orbital symmetry conservation rules?
1)
H
H
CO2CH3
CO2CH3
Δ
CO2CH3
CO2CH3
4 electron electrocyclic ring opening, under thermal conditions need to proceed with CONROTATORY ring opening
H H
H3CO2C CO2CH3
H
R
H
R
CO2CH3
=
CO2CH3
Therefore this reaction is allowed thermally (it would, however, be forbidden photochemically)
356 Additional Problems
2)
hν
6 electrons involved, photochemical electrocyclic reaction will be CONROTATORY
H
H
H
H
A photochemical opening will thus generate a trans double bond in the ring (not the compound shown above) so it is forbidden by Woodward-Hoffmann rules (it would be allowed thermally)
357 Additional Problems
3)
H
O
Δ
O
O
H
O
Reaction shown is a 4 electron electrocyclic ring closing reaction, therefore under thermal conditions this should be a CONROTATORY ring closure
H
H
O
O
O
H
O
In a conrotatory ring closure, the two hydrogens would move to opposite sides of the bicyclic ring junction, not the compound shown so thermally this is a forbidden process (it is allowed photochemically)
358