Cycloaddition reactions are intermolecular pericyclic processes involving the formation of a ring from two independent conjugated systems through the formation of two new ?-bonds at the termini of the ?-systems. The reverse process is called

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Cycloaddition reactions are intermolecular
pericyclic processes involving the formation of a
ring from two independent conjugated systems
through the formation of two new ?-bonds at the
termini of the ?-systems. The reverse process
is called cycloreversion or is referred to as a
retro-reaction.
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Learning Objectives Part 2(ii)
Cycloaddition Reactions
CHM3A2 Introduction to FMOs
After completing PART 2(ii) of this course you
should have an understanding of, and be able to
demonstrate, the following terms, ideas and
methods. (i) A cycloaddition reaction involves
the formation of two ? bonds between the termini
of two independent ?-systems, resulting in ring
formation - or the reverse process. (ii) Cycloadd
ition reactions are stereospecific (e.g.
cis/trans isomers). The stereospecificity being
afforded by the suprafacial or antarafacial
nature of the approach of the two ?-units in the
transition state. (iii) The suprafacial or
antarafacial process involved in the ? bond
making process is controlled by the HOMO/LUMO
interactions of the two ?-systems in the
transition state. (v) Cycloaddition reactions
can be regioselective. The regioselectivity
cannot be predicted from the simple treatment
given to frontier molecular orbitals in this
course. However, generalisations can be made
from looking at classes of substituents (C, Z, X)
which are in conjugation with the ?-systems,
which allow us to predict the regioselectivity in
an empirical manner.
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The Questions FMO Theory Can Answer
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FMO Theory Explains Difference in Rates of
Cycloadditions
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FMO Theory Explains Stereospecificity of
Cycloadditions
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FMO Theory Explains Regiochemistry of
Cycloadditions
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Analysing Cycloaddition Reactions
The interaction is between the HOMO of one
p-system with the LUMO of the second p-system,
such that the energy difference is least.
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Terminology
SUPRAFACIAL
ANTARAFACIAL
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4n2 p Electron Cycloaddition Transition
States
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Suprafacial-Suprafacial Interaction 4n2 p
Electron Transition States
pXs pYs
HOMO
suprafacial
In-phase
Suprafacial
LUMO
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Diels-Alder Cycloaddition Reaction 6 p-Electron
Transition State
Suprafacial
p4s p2s
Suprafacial
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4n p Electron Cycloaddition Transition States
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Suprafacial-Antarafacial Interaction 4n p
Electron Transition States
HOMO
Suprafacial
pXs pYa
antarafacial
LUMO
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Why Ethene Does Not Dimerise 4 p-Electron
Transition State
Suprafacial
p2s p2s
Suprafacial
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Why Ethene Does Not Thermally Dimerise 4
p-Electron Transition State
Suprafacial
p2s p2s
Out-of-phase
In-phase
Suprafacial
Can not react via suprafacial/suprafacial
Interaction
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How About a Suprafacial/Antarafacial Interaction?
Suprafacial
p2s p2a
Antarafacial
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How About a Suprafacial/Antarafacial Interaction?
Suprafacial
p2s p2a
Antarafacial
In principle, suprafacial/antarafacial is
possible by FMO theory, however, it is
geometrically impossible
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The Diels-Alder Reaction In Detail
The Diels-Alder reaction is an extremely well
studied cycloaddition reaction, The reason for
this is that careful design of the diene
component and the ene component (the dienophile)
has led to a great insight into the reaction
mechanism.
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Diels-Alder Reaction Transition State Geometry
Suprafacial
Diene
HOMO y2
MESO
Dieneophile
LUMO y2
Suprafacial
p4s p2s
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Suprafacial
Diene
HOMO y2
Dieneophile
LUMO y2
Suprafacial
i.e. enantiomers
p4s p2s
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Enantiomer Formation
Top
Top
Bottom
Bottom
A pair of Enantiomers
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Enantiomer Formation
Top
Top
Bottom
Bottom
A pair of Enantiomers
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Normal Electron Demand in Diels-Alder
Cycloaddition Reactions
Dieneophile
Diene
Dieneophile
Diene
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Raising and Lowering the Energy of HOMO and LUMOS
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Diene HOMO/Dienophile LUMO Normal Electron
Demand
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Regiochemistry Issues in the Diels-Alder Reaction
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Substituents and Desymmetrisation of Orbitals
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Low Energy Transition State
High Energy Transition State
Small/Large
Large/Small
Small/Small
Large/Large Coefficient interaction
Despite more pronounced steric interactions
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Rules for Cycloadditions
Number of ?-Electrons Thermal
Photochemical ___________________________________
________________________________ 4n
sa ss 4n 2
ss sa (aa) __________________________
_________________________________________ s
suprafacial a antarafacial
Photochemical cycloaddition reactions are dealt
with in CHM3A2 in year 3
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Summary Sheet Part 2(ii) Cycloaddition
Reactions
CHM3A2 Introduction to FMOs
Cycloaddition reactions are intermolecular
pericyclic processes involving the formation of a
ring from two independent conjugated systems
through the formation of two new ?-bonds at the
termini of the ?-systems. The reverse process
is called cycloreversion or is referred to as a
retro-reaction. By far the best known example of
a cycloaddition is a Diels-Alder reaction. The
reverse process is known as a retro-Diels-Alder
reaction. Perhaps the simplest approach for
assessing the feasibility of a particular
cycloaddition uses frontier molecular orbital
theory. In the concerted cycloaddition of two
polyenes, bond formation at each terminus must be
developed to some extent in the transition state.
Thus, orbital overlap must occur simultaneously
at both termini. For a low energy concerted
process - an allowed reaction - to be possible,
such simultaneous overlap must be geometrically
feasible and must also be potential
bonding. There are two stereochemically
different ways in which new bonds can be formed
either to the same face of the ?-bond, i.e. in a
suprafacial way, or to opposite faces, i.e. in an
antarafacial way. The same definitions apply to
longer ? systems. Suprafacial, suprafacial (ss)
approach of two polyenes is normally sterically
suitable for efficient-orbital overlap. The
vast majority of concerted additions involves the
ss approach. However, this type of overlap will
only be energetically favourable when the HOMO of
one component and the LUMO of the other component
can interact in a bonding fashion at both
termini. Thus, these orbitals must be of the
correct phase of symmetry. In the Diels-Alder
reaction of a diene with a monoene, the HOMO and
LUMO of each reactant are of the appropriate
symmetry so that mixing of these orbitals will
result in simultaneous potential bonding
character between the terminal atoms. In
contrast, a similar ss approach of two olefins
does not lead to a stabilising interaction since
the HOMO and LUMO are of incompatible phase for
simultaneous bonding interaction to occur at both
termini. Thus, the initial approach of
reactants for a concerted ss addition is
favourable for a Diels-Alder reaction - which is
therefore an allowed process - but not for olefin
dimerisation, which is therefore disallowed.
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Exercise 1 4n2 p Cycloadditions
Explain the difference in the rates of reaction
of the two reaction shown right.
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Answer 1 4n2 p Cycloadditions
Explain the difference in the rates of reaction
of the two reaction shown right.
The difference in rates is a result of at least 2
factors.
Factor 2 Butadiene does not exist preferentially
in the reactive cis conformation, thus the
concentration of reactive conformations of
butadiene is always low.
Factor 1 The HOMO of cyclopentadiene is raised
relative to the HOMO of butadiene as a result of
the bridging methylene units I inductive effect,
thus the energy difference between the diene HOMO
and dieneophile LUMO is the least with
cyclopentadiene, and results in the greatest
HOMO/LUMO interaction (i.e. DE2ltltDE1).
Reactive Conformation
In contrast, the bridging methylene unit in
cyclopentadiene forces the diene moiety to exist
exclusively in the reactive conformation.
Reactive Conformation Locked
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Exercise 2 4n2 p Cycloadditions
Utilise FMOs to predict stereochemical outcome of
the Diels-Alder reaction shown right
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Answer 4n2 p Cycloadditions 2
Utilise FMOs to predict stereochemical outcome of
the Diels-Alder reaction shown right
MESO
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Exercise 3 4n2 p Cycloadditions
Predict the cycloaddition products formed from
the following pairs of starting materials. State
the number of p electrons involved and use the
pns/pna descriptor to describe each reaction.
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Answer 3 4n2 p Cycloadditions
Predict the cycloaddition products formed from
the following pairs of starting materials. State
the number of p electrons involved and use the
pns/pna descriptor to describe each reaction.
20C
4C, 3d

20C, 3d
Meso
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Exercise 4 4n2 p Cycloadditions
Utilse FMOs to rationalise the stereochemical
outcome of the cycloaddition reaction shown right
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Answer 4 4n2 p Cycloadditions
Utilse FMOs to rationalise the stereochemical
outcome of the cycloaddition reaction shown right
y4 Octatetraene (3 nodes, 9/4)
HOMO
s/s
Enantiomers
s/s
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Exercise 5 4n2 p Cycloadditions
Propose an arrow pushing mechanism for the
reaction shown right Utilse FMOs to rationalise
the stereochemical outcome. Identify a
regioisomer of the product.
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Answer 5 4n2 p Cycloadditions
Propose an arrow pushing mechanism for the
reaction shown right Utilse FMOs to rationalise
the stereochemical outcome. Identify a
regioisomer of the product.
The reaction requires forcing conditions because
the HOMO/LUMO gap is large
Dieneophile
"Diene"
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Exercise 6 4n2 p Cycloadditions
Propose an arrow pushing mechanism, reagents and
byproducts for the reaction shown right.
Additionally, identify any driving forces which
make the reaction proceed from starting material
to product.
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Answer 6 4n2 p Cycloadditions
Propose an arrow pushing mechanism, reagents and
byproducts for the reaction shown right.
Additionally, identify any driving forces which
make the reaction proceed from starting material
to product.
N
N
A retro-Diels-Alder
A Diels-Alder