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PERICYCLIC REACTIONS NOTES
They are reactions in which “all first order changes in bonding relationships takes place in concert on a closed curve” (Woodward & Hoffmann).
More simply, the term “pericyclic” covers all concerted reactions involving a cyclic flow of electrons through a single transition state. These reactions do not involve ions, free radicals and any catalyst. The reactions occur in thermal and photochemical conditions where molecular orbital symmetry is of great concern. Pericyclic reactions are highly stereospecific.
Pericyclic reactions can be predicted and controlled to a great degree, which makes them very useful in synthesis.
There are broadly four classes of pericyclic reaction:
Sigmatropic – These are unimolecular isomerisations, and involve the movement of a s-bond from one position to another. An illustration would be the first step of the Claisen Rearrangement:
Note the nomenclature of this reaction, being described as a [i,j] shift. For example, this following is a [1,7] shift:
Electrocyclic – These are unimolecular. They are characterised by ring opening or closing with a s- bond forming at one end. Ring closing is more common, since this is formation of a s-bond at the expense of a p-bond, but ring strain can lead to opening. Two examples are:
Cycloaddition – This is the largest class of pericyclic reaction. It is characterised by two fragments coming together to form two new s-bonds in a ring. Some examples are Diels-Alder and Ozonolysis reactions, which are described below.
Chelotropic reactions are a specific type of cycloaddition, where the two bonds are made or broken at the same atom. The classic example of this is carbene addition to a double bond.
Group Transfer – There are only a few of these reactions, the most common of which is the ene reaction (see further down). They resemble [1,5] sigmatropic shifts, since a s-bond moves, and they also resemble Diels-Alder, but replacing a p-bond with a s-bond.
Huckel Molecular Orbitals for Linear p -Systems
- Count the contributing p-orbitals. Total = n.
- Count the electrons held in these orbitals; two for each double bond, two for a carbanion or lone pair, one for an unpaired electron, zero for a carbocation. Total = m.
- For n contributing p-orbitals there will be n molecular orbitals.
- Draw n horizontal lines stacked on top of each other to represent the molecular orbitals and feed in the m electrons two at a time from the bottom (lowest energy) up (highest energy).
- Identify the HOMO, the LUMO, and, for radicals, the SOMO. These are the Frontier Molecular Orbitals (FMOs).
- Each molecular orbital yk is considered to be a linear combination of atomic orbitals fi [ where i designates the atom position with the p-system (an integer in the range 1-n) ].
Aromatic Transition State All thermally induced pericyclic reactions have transition structures involving a total of 4n+2 electrons. This explanation in terms of an aromatic transition state can be extended to cover all situations (including those involving antarafacial thermal reactions) using Frontier Orbitals.
Frontier Molecular Orbitals These are the HOMO of one component and LUMO of the other
The above diagram shows a [2+2] addition – not allowed due to the repulsion (antibonding effects of opposite sign of wavefunction). The other two show a [4+2] addition (the difference is the LUMO and HOMO are reversed – still both allowed). Note that barrier to [2+2] addition is only present when both bonds are trying to form at the same time – stepwise is allowed, but not pericyclic.
An alternative would be for the upper lobe of the C 1 in the [2+2] addition to interact. This would represent an antarafacial reaction, which is allowed. However, this requires a long
The number of nodes increases by one on going to the next higher MO and, in general, the number of nodes within a particular MO (yk) is k-1. In a linear p-system if the number of nodes is Even then the terminal orbital coefficients will be of Equal sign (i.e. both positive or both negative); if the number of nodes is Odd the terminal coefficients will be of Opposite sign.
p-MOs for Allyl Systems [n=3, m=2 (cation), 3 (radical), 4 (carbanion) ]
Orbital Symmetry Control in Electrocyclic Ring Opening of Cyclobutenes
consider the p-orbitals that comprise the s-bond as this bond breaks; there are two modes of rotation of the methyl groups as the reaction proceeds (neglect the possibility of the two methyl groups swinging towards each other). In the first case both the bonds rotate in the same direction; this is conrotatory ring opening. Throughout this process the molecule retains a two-fold axis of rotation (the axis passes through the plane of the molecule and through the breaking s-bond).
in the second case the bonds rotate in opposite directions – disrotatory ring opening – and the molecule retains a plane of symmetry throughout (the plane is perpendicular to the plane of the molecule and passes through the breaking s-bond).
The orbitals directly-involved in the cyclobutene and butadiene product are designated as symmetric (S) or antisymmetric (A) with respect to these symmetry operations; rotation about C 2 for the conrotatory case and reflection in m 1 in the disrotatory case. Orbitals of like symmetry are then correlated with one another, as follows.
Correlation Diagrams
Correlation Diagram for Electrocyclic Ring Opening of Cyclobutenes
In the conrotatory mode all bonding orbitals in the cyclobutene correlate with bonding orbitals of the diene; this is thermally allowed (“favoured” is a better term). In the disrotatory mode one of the bonding orbitals correlates with an anti-bonding orbital; this is thermally forbidden (“disfavoured”).
Correlation Diagram for the Diels-Alder Reaction
In this reaction a plane of symmetry m 1 is preserved throughout the process (perpendicular to the molecular planes of both diene and dienophiles and passing through the double bond of the dienophiles and the central single bond of the diene) therefore the orbitals are designated S or A after reflection in this plane. In the product there are two new equivalent s-bonds which are not proper symmetry combinations with respect to the plane m 1 ; they have therefore to be taken as s 1 + s 2 and s 1 - s 2 combinations as shown:
For thermal reactions the significant interactions are as shown:
Component A Component B
Unoccupied MO Unoccupied MO
Occupied MO Occupied MO
For photochemical reactions in which one molecular component (A) has been excited:
When the occupied MOs in one component lie lower in energy than the unoccupied MOs in the second component (the usual situation) the stabilising interaction will be greater when these orbitals are closer in energy; this implies that the dominant interactions will be between the FMOs, i.e. the HOMO, the LUMO, the LSOMO, and the HSOMO as follows:
HSOMOA ↔ LUMOB LSOMOA ↔ HOMOB Photochemical Reactions
HOMOA ↔ LUMOB LUMOA ↔ HOMOB Thermal Reactions
The interacting orbitals must possess phase properties that allow only bonding interactions; overlap of opposite orbital phases is antibonding and unfavourable.
Woodward-Hoffmann Rules
- A ground state pericyclic change is symmetry-allowed when the total number of (4q+2)s and (4r)a components is odd.
- A photochemical pericyclic change is symmetry-allowed when the total number of (4q+2)s and (4r)a components is even.
q and r are integers and the subscripts s and a denote suprafacial and antarafacial respectively.
The components of the cycloaddition are obviously the two separate electron systems (molecules) coming together. Looking at these components, we have to then consider:
- How many electrons?
- Suprafacial or antarafacial?
- Which can be expressed as 4q+2 and which as 4r?
Suprafaci al and antarafacial refer to modes of bond formation that are respectively on the same face and on opposite faces of a molecular component.
A pericyclic reaction in which 2 separate conjugated, overlapping arrays of orbitals combine. Cycloadditions proceed by way of a cyclic transition state, and 2 sigma bonds are formed during the course of the reaction. A suprafacial process ("s") is one in which the bonds made or broken lie on the same face of the orbital array undergoing reaction. In an antarafacial process ("a"), the newly formed or broken bonds lie on opposite faces of the reacting orbital array. Woodward-Hoffmann Rules for Cycloadditions Stereochemical Course: Electrons Thermal Mode Photochemical Mode 4n + 2 [s + s] [s + a] 4n [s + a] [s + s]
Because an s-orbital has no nodal properties all its reaction modes are suprafacial.
For example, the Diels-Alder has two components, one of 4 electrons and one of 2. They
Constructive overlap is complete whichever way round we take the HOMO and LUMO interactions. The reaction is suprafacial with respect to both components, therefore it is a [p (^4) s + (^) p (^2) s] cycloaddition and is thermally allowed by the W-H Rules (and photochemically disallowed) as mentioned earlier.
The reaction above would be very, very slow however. Electron-donating groups on the diene and electron-withdrawing groups on the dienophile greatly accelerate it. Also, the more powerful the electron-donating or withdrawing substituents, the more regioselective the reaction (see below).
Note that the diene must have the cis conformation to react – a trans diene would lead to a trans double bond forming in a ring, which is too high in energy to occur.
As with all pericyclic reactions, the path is determined by thermodynamics. Thus, studying the reverse retro-Diels-Alder reaction can often make determining the product easier.
Stereoselectivity
There are two possible ways of attacking suprafacially, and these are described as ENDO and EXO. This usually governs speed of the reaction (since both are allowed by the rules above) and is affected mostly by substituents present. The two approaches can be illustrated:
The favoured transition structures are those with electron-withdrawing substituents in the more hindered environment, but these are thermodynamically less favoured. This can be explained by looking at the Frontier Orbital approach, best depicted as:
The bold line shows an additional bonding interaction in the endo form which favours this route.
This leads to kinetic vs. thermodynamic control, depending on conditions. For example, the endo rule would suggest that at 0oC in ether:
However, refluxing in THF leads to further reaction of the above product, first by retro-Diels-Alder and then re-addition to form the thermodynamic product:
Endo-Selectivity The preference for kinetic formation of the endo- adduct (which is less stable than the exo- adduct) has been described deceptively convincingly by “secondary orbital overlap”. This is a stabilising interaction of in-phase orbitals in the transition state that does not lead to new bonds. In cases where the reaction readily reverses – for example with stable dienes such as furans – the thermodynamically preferred exo- adducts are usually obtained.
Energies
- Electron withdrawing groups ( Z , e.g. carbonyl) lower both the HOMO and LUMO.
- Electron donating groups ( X , e.g. methoxy) raise both the HOMO and LUMO.
- Merely conjugating groups that do not significantly withdraw or donate electron density ( C , e.g. C=C, Ph) raise the HOMO and lower the LUMO, i.e. they reduce the HOMO-LUMO gap.
Coefficients Qualitative pictures of the dienophiles (derived from experiment and theoretical combinations of ideal substituents) depict top views of the p-system with larger circles representing larger coefficients.
in all substituted cases the coefficient on the b-carbon is larger in the HOMO; in the LUMO the b coefficient is larger for Z and C cases, smaller for X cases.
For dienes there are size generic cases (only the coefficients of the terminal positions are shown):
The diene HOMO-dienophile LUMO interaction usually dominates; for 1-substituted dienes the larger HOMO coefficient is at the remote terminal carbon; for 2-substituted dienes the larger HOMO coefficient is at the closer terminal carbon.
Taking the second example above, a 1-Z-substituted diene reacts with a Z- substituted dienophile, i.e.
The same result would be predicted if the diene LUMO and dienophile HOMO had been considered.
Lewis Acid Catalysis Diels-Alder reaction are usually accelerated by Lewis Acid catalysis and an increase in the regio- and stereoselectivity is often observed.
Rate Enhancement
Improved Regioselectivity
Adding a Lewis Acid results in reversible complexation to Lewis basic sites. Complexation to the dienophile increases the electron withdrawing ability of the activating substituent; the LUMO is lowered and the HOMO(diene)- LUMO(dienophile) gap decreases resulting in a more favourable transition state and a faster reaction.
Complexation of the Z substituent on the dienophile imparts some of the orbital characteristics of an allyl cation, and the coefficients are altered accordingly:
There is a larger difference between the orbital coefficients in the LUMO which results in an enhancement of the regioselectivity.
Lewis Acid complexation also enhances the endo- selectivity of Diels-Alder reactions, but arguments involving favourable secondary interactions may not be valid; increasing
with the C-H bonds and oxygen lone pairs is significant: molecular orbital calculations show the FMOs to have the form shown:
Because the terminal carbon atom in the C=C bond is the site of a node (a zero orbital coefficient) in the LUMO the significant interaction of the second alkene component’s HOMO must be with the next available unoccupied MO (NLUMO) if bonding to that carbon is to be achieved. Thus the orbital picture for the cycloaddition looks like:
This [p (^2) s + (^) p (^2) a] orientation has further consequences:
- in reactions with an unsymmetrical alkene the less sterically demanding C=O part of the ketene will be oriented above the larger alkene substituents;
- if an unsymmetrical ketene (R 1 R 2 C=C=O) reacts with an alkene the favoured transition state will have the larger of the two substituents oriented away from the plane of the alkene;
- applying the rule of favoured bonding between atoms bearing larger orbital coefficients allows the regioselectivity of the process to be predicted.
A useful example that illustrates all of these points is the reaction between chloroketene and cyclopentadiene which reacts to give a single [2+2] cycloadduct, the regiochemistry being dictated by the large NLUMO coefficient on the ketene central carbon and a large HOMO coefficient on the terminal carbon of the butadiene substructure in cyclopentadiene.
But it not be as “simple” as this. Recent experimental and theoretical work showed that, at least for the case of diphenyl ketene and cyclopentadiene the reaction is not a genuine [2+2] cycloaddition but a stepwise process consisting of Diels-Alder reaction following by a Claisen rearrangement (see below).
In this reaction mode, just the C=O bond of the ketene is involved in the first (regio- and stereochemistry dictating) step, therefore the diene HOMO may usefully interact with the ketene LUMO. The ketene can orient itself with the large group away from the plane of the diene to result in a specific stereochemistry in the adduct. Subsequent Claisen rearrangement (a [3,3] sigmatropic process which is suprafacial in all components) gives rise to the same product that we predict on the basis of a [2+2] cycloaddition:
It is too early to say whether this is the preferred mode in the majority of ketene “[2+2]” cycloadditions.
Vinyl Cations
Related to ketene cycloadditions are the group of cycloadditions with vinyl cation intermediates, e.g. the reaction of allene with hydrogen chloride:
Vinyl cations, like ketenes, have two p-orbitals at right angles to each other, and overlap can develop to each simultaneously, just as with ketenes. In a sense, a ketene is merely a special case of a vinyl cation, with the carbonyl group a highly stabilised carbocation.
1,3-Dipolar [3+2] Cycloadditions
A side-on approach can accommodate simultaneous HOMO-LUMO overlap in either combination. This is a [p (^2) s + (^) w (^2) a] process:
Both of these processes are essentially irreversible; reversible Chelotropic reactions are seen in the chemistry of sulphur dioxide; in this case orientation of SO 2 is head- on (in contrast to carbenes). Extrusion of SO 2 occurs from episulphones during the Ramberg-Backlund alkene synthesis.
Reaction with 1,3-dienes is reversible; the sulphones are useful precursors for controlled formation of dienes.
This is suprafacial with respect to both diene and sulphur atom, [p (^4) s + (^) w (^2) s]. The extrusion process is disrotatory.
With trienes the extrusion process dominates but considering the reverse process the reaction must be antarafacial with respect to the alkene p-system and suprafacial with respect to the sulphur atom, [p (^6) a + (^) w (^2) s]. This results in conrotatory ring opening during the extrusion with the result that certain bicyclic sulphones undergo SO 2 extrusion extremely slowly (probably via diradical mechanism):
Electrocyclic Reactions
These are pericyclic processes in which a ring is formed or opened in an intramolecular way. Woodward & Hoffmann provided an early (workable) means for predicting the stereochemistry of these processes (a simplification of the correlation diagram approach discussed earlier).
This modifies the Woodward-Hoffmann Rules slightly, since this con/dis consideration must be added. Basically, all thermal reactions involving 4n+
electrons are allowed if disrotatory, and all thermal reactions involved 4n are allowed if conrotatory. Photochemical reactions are then the opposite.
In this analysis the mode of rotation is determined by the phase properties of the HOMO (in the ring closure process). Thus, although cyclobutene opens thermally to butadiene, its mode of ring opening is inferred by analysing the reverse process.
The HOMO for the thermal case is y 2 (one-node); that for the photochemical case is
