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Chem3x11 Lecture 13

Incomplete Friday Jun 1

This last lecture is about two other classes of pericyclic reactions, namely cycloadditions and sigmatropic rearrangements.

(Back to the main teaching page)

Key concepts

  • Cycloadditions and sigmatropic rearrangements are governed by similar orbital considerations to those we've already seen

Cycloadditions

Cycloadditions are pericyclic reactions where two components come together to give a cyclic compounds. The best-known example is the Diels-Alder reaction. The reaction occurs between a diene (with 4 π electrons) and a dienophile (with 2 π electrons); we talk of this reaction being a [4 + 2] cycloaddition. Three π bonds and a σ bond in the starting materials become one π bond and five σ bonds in the product.

Scheme 1: Typical Diels-Alder Reactions
Scheme 1: Typical Diels-Alder Reactions

Again, there are no intermediates, just a cyclic transition state. The stereochemistry of the starting materials is carried through to the products, as can be seen by the above example. We need to explain why this is, as well as explaining other things about the reaction.

General Orbital Requirements for a Diels-Alder Reaction

As for electrocyclic processes, the lobes of the MOs on the interacting atoms need to be in phase. We should look at the frontier orbitals of the two reagents. Looking at the diene and dienophile drawn on paper, it's not clear which interaction is most energetically likely, but it turns out the HOMO of the diene interacts with the LUMO of the dienophile. (The other interaction is symmetry-allowed, but the orbitals are often quite far apart in energy and do not dominate the interaction unless the electronics of the reagents are unusual, giving what are called "inverse electron demand Diels-Alder reactions" which we don't cover.)

Scheme 2: General Diels-Alder Orbital Reactions
Scheme 2: General Diels-Alder Orbital Reactions

You'll notice that the two components approach and interact using MO lobes that are on the same face of each. i.e. the diene uses two lobes on one face and the dienophile uses two lobes on one face. This is a suprafacial-suprafacial interaction. The interaction between diene and dienophile is very sensitive to what's attached to the different systems. The simplest DA reaction on paper is very hard to get to go, but small steric and electronic changes to the structures of the reagents means the reaction can go very quickly.

Scheme 3: Influence of Reagent Structure on the Ease of a DA Reaction
Scheme 3: Influence of Reagent Structure on the Ease of a DA Reaction

The activation of the dienophile in the case above is electronic in origin. If we are to promote a cycloaddition, we need the frontier orbitals (of the right symmetry) to be close in energy - that provide the greatest energetic benefit when the new bonds are formed.

Scheme 4: Orbitals Close in Energy Produce the Greatest Energetic Benefit from the Interaction
Scheme 4: Orbitals Close in Energy Produce the Greatest Energetic Benefit from the Interaction

Usually a DA reaction employs an electron-rich diene. If it's electron-rich, it has a high energy HOMO. It thus helps if we have a low energy LUMO to go along with this HOMO, and we can achieve that by making the dienophile electron poor. The simplest way to do that is attach a group that is electron-withdrawing to the π system, for example a conjugated carbonyl group. Obviously the interacting orbitals are the ones shown here, and this diagram should bring some questions to your mind about the three-dimensional nature of this interaction, which is the cool thing we'll get to in a moment.

Scheme 5: The Interacting Orbitals of the DA Reaction in Scheme 3
Scheme 5: The Interacting Orbitals of the DA Reaction in Scheme 3

The other (more obvious) way to accelerate a cycloaddition is to arrange the diene in an orientation that promotes the reaction. This is why you typically see fast DA reaction employ cyclic compounds like cyclopentadiene.

Scheme 6: "Steric Activation" of a DA Reaction Through the Use of a Cyclic Diene
Scheme 6: "Steric Activation" of a DA Reaction Through the Use of a Cyclic Diene

The Stereochemistry of the Diels-Alder Reaction

There are two ways the diene and dienophile can approach each other - either "end-to-end" where there is the minimum of steric interaction between reagents, and the minimum of steric crowding in the product, or "folded over" where the two components approach sandwich-style.

Scheme 7: Thermodynamic vs Kinetic Products in the DA Reaction
Scheme 7: Thermodynamic vs Kinetic Products in the DA Reaction

When you perform a DA reaction and tune the conditions so that the reaction just goes (i.e. a high enough temperature to see conversion) you find the product you get is the "folded-over" product which we call the endo isomer. This is the kinetic product. Given that all cycloadditions are reversible, we can heat the reaction more to see if we get another product, and sure enough we do. The thermodymanic product is actually the other isomer, the exo isomer. The question is, what controls this?

If we draw out the interacting MOs in full, rather than just the end lobes of the p system, we see an extra feature. In the diagram below, note that the MO for the dienophile now includes the two carbonyl groups attached. When we include those in our MO diagram, and construct the LUMO, we find that some of the orbitals present interact with the right symmetry. These secondary orbital interactions do not give rise to new bonds, but are stabilising of the transition state and accelerate the reaction to the endo isomer. Ultimately, though, the steric congestion in the endo isomer is unfavourable compared to the less sterically congested exo isomer and the thermodynamic product will be obtained, if we push the reaction hard.

Scheme 8: Secondary Orbital Interactions Give Rise to the Kinetic DA Product
Scheme 8: Secondary Orbital Interactions Give Rise to the Kinetic DA Product

Brief Note on Photochemical Cycloaddition Reactions

We don't cover these in much detail here, but the arguments are similar to the ones we saw with electrocyclic reactions. The selectivity changes between thermal cycloadditions (those we've been looking at so far) and photochemical ones. To see why, let's look at a cycloaddition reaction that looks reasonable on paper, but doesn't actually proceed - the reaction of ethene with itself to give cyclobutane. The problem is one of orbital symmetry and geometrical constraint. The required HOMO and LUMO interaction can't happen because one of the alkenes can't "reach round" the side of the other. More formally, the interaction needs to the antarafacial, but a suprafacial interaction is imposed by geometry.

Scheme 9: The Cyclization of Alkenes with Themselves Occurs in the Presence of Light, not Heat
Scheme 9: The Cyclization of Alkenes with Themselves Occurs in the Presence of Light, not Heat

Here's an example of a real case:

Scheme 10: A Real Photochemical Cycloaddition Reaction
Scheme 10: A Real Photochemical Cycloaddition Reaction


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