Molecular Orbital Analysis of Diels-Alder reaction
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Review Diels-Alder reaction ?
Electron donating groups (e.g. -R, -OR) on diene promote reaction. Conclusion
diene = nucleophile
Electron withdrawing groups (e.g. -CO2R, -CN) on dienophile promote reaction.
Conclusion dienophile = electrophile
Nucleophile characterised by the HOMO
Electrophile characterised by the LUMO
Notice how the
phases of the
orbitals at C1 and
C4 of the HOMO
of butadiene match
the phases of the
orbitals of C1 and
C2 in the LUMO of
ethene (i.e. the
colours match).
This means there is
a favourable
bonding interaction
at each of these
positions, which
corresponds to the
positions where the
two new bonds
are formed.
Therefore the
reaction is said to
be a "symmetry
allowed" - this is
good news, since
we know the
reaction works !
Frontier - Molecular Orbitals
A useful molecular orbital model for analyzing pericyclic reactions has been proposed by
Kenichi Fukui of Japan. This frontier-orbital approach is based on the assumption that
bonds are formed by a flow of electrons from the highest occupied molecular orbital
(HOMO) of one reactant or participating bond to the lowest unoccupied molecular orbital
(LUMO) of another reactant or bond. To illustrate, consider the [4+2] cycloaddition of
1,3-butadiene and ethylene.to give cyclohexene. The pertinent molecular orbitals
involved in this reaction were described elsewhere, and the two combinations of HOMO
and LUMO are shown in the following diagram. Note that regardless of which
combination is examined, the terminal orbital phases match, indicating a bonding
interaction. Since the dienophile often has electron-withdrawing substituents and the
diene is usually electron rich, the electron flow pattern on the left seems to best
represent the course of most Diel-Alder reactions.
This frontier orbital approach to cycloaddition reactions is general, and is simple to apply
thanks to the alternation of terminal orbital phase relationships as a polyene changes
from a 4n electron system to a 4n + 2 electron system. By clicking on the above
diagram, these phase relationships will be displayed for HOMO and LUMO of polyenes
in both classes. Only the terminal orbital phases (colored in the diagram) are important
for frontier orbital analysis. The frontier orbital analysis of a [6s + 2s] cycloaddition
reaction will be demonstrated by clicking on the diagram a second time. An antibonding
node is present in both HOMO-LUMO combinations (one is shown), so this reaction is
orbital symmetry forbidden.
An additional feature of this treatment of cycloaddition reactions is its rationalization of
the tendency of Diels-Alder reactions of cyclic dienes to form endo adducts
preferentially. This was noted earlier, and is further illustrated in the following diagram.
The first two equations are straightforward examples of the endo predilection of
substituents or rings (colored green) attached to a bicyclic ring system. The third
equation shows a more subtile case of the same orientational factor, which essentially
favors that [4+2] transition state in which unsaturated substituents on the dienophile are
directed toward the diene double bonds. By clicking on this diagram, the secondary
orbital bonding interaction that stabilizes the endo transition state for a typical DielsAlder reaction will be displayed.
Not all cycloaddition reactions favor endo products. The predominant product from the
[6s + 4s] reaction shown earlier is the exo adduct. Frontier orbital analysis of this case
demonstrates that secondary orbital interaction destabilizes the endo transition state.
Endo - Exo Selectivity
When both the diene and the dienophile are suitably substituted, a stereochemical
feature arises because the reactants may approach each other in two distinct
orientations. The substituent on the dienophile may be directed away from the
diene (exo approach) or toward the diene (endo approach). This stereochemical
difference is often found with cyclic compounds. One very simple exemple is the
Diels-Alder addition of two cyclopentadiene(1) (Figure 3).
Figure 3 : Diels-Alder addition of two cyclopentadienes
1. Mechanisms
In most Diels-Alder reactions, when the product distribution is under kinetic
control, the endo adduct is preferentially, sometimes exclusively, formed. Several
hypotheses have been made to explain this selectivity :
o
o
o
Alder[5] proposed that endo addition was the consequence of a plane-toplane orientation of diene and dienophile with "maximum accumulation of
double bonds". Since this same orientation would promote stability in a
molecular complex, it has been suggested that complex formation between
the reactants may be responsible for preferential endo addition.
Woodward and Hoffmann[6] ascribe endo addition to interaction of
occupied orbitals with unoccupied orbitals, the endo transition state
conformation being favored by orbital symmetry relative to the exo
conformation. With the model of frontier orbitals, we have interaction of
HOMOs (Highest Occupied Molecular Orbitals) with LUMOs (Lowest
Unoccupied Molecular Orbitals). Those interactions are represented in
figure 4. The main interactions that will form the bonds are shown by
plain bold lines, the secondary interactions, responsible for the endo-exo
selectivity, are shown by small squiggly lines. We do not know if the
molecules approch so closely that the secondary interactions can be as
important as shown in figure 1.
Studies of Diels-Alder transition states can also give an explanation of this
selectivity[7]. The transition state in an asynchronous mechanism can be
described using several resonance structures (figure 5). One of this
resonance structure is a zwitterion. In the endo transition state, the
proximity of the two charges stabilizes this structure and thus favours the
endo addition.
For the addition of the two cyclopentadienes, the forming bond lengths are
2.183 Å and 2.119 Å in the exo transition state and 2.184 Å and 2.127 Å
in the endo transition state. This prove that the mechanism for this
addition is asynchronous, and that the endo transition state is more
assymetric, ie. the zwitterion resonance strucure is more favorized than in
the exo attack.
Exo-Attack
Endo-Attack
Figure 4 : HOMO-LUMO interactions in the Diels-Alder addition of two
cyclopentadienes
In the above figure :
o
o
Red lines represent single bonds
Yellow lines represens double
bonds
o
Hydrogen have been omitted
o
Red and yellow orbitals represent the
LUMOs
o
Blue and green orbitals represent the
HOMOs
exo Transition State
endo Transition State