In discussing ring forming reactions, I have only talked so far about reactions in which one ring bond is formed. At this point, we need to consider an alternative type - cycloaddition reactions, where two bonds are formed and the ring is constructed from two fragments. An extremely important example is the Diels-Alder reaction, which has an aromatic transition state. (V&S 600-607). Cycloaddition reaction are one example of a special class of reactions called pericyclic. Other examples of pericyclic reactions are electrocyclic reactions, sigmatropic reactions, and (a reaction you’ve already met) ester pyrolysis (V&S 607-612, 1006-1008, C &S A595-640)

The transition state for a Diels-Alder reaction in which addition is syn (suprafacial) is isoconjugate with benzene, and so is aromatic (F 16, 32). However, the transition states for 2p + 2p cycloaddditions are isoconjugate with the antiaromatic cyclobutadiene so they are forbidden if addition is syn (suprafacial) (F 18) to both reactants. A deeper understanding can be obtained from the correlation diagrams(F 34-39). In Diels-Alder reactions, the bonding orbitals of the starting materials are transformed smoothly into those of the products, but in 2p + 2p cycloaddditions, one of the orbitals of the starting materials has the wrong symmetry to transform to a bonding orbital in the product (it correlates with an anti-bonding orbital).On the other hand 2p + 2p cycloaddditions are allowed as photochemical processes - this is best understood by means of state correlation diagrams (F 39).

The Diels-Alder reaction (a 4p + 2p cycloaddition) is a very important synthetic method for cyclohexanes, mainly because the stereochemistry of the products are so well controlled (V&S 518-525, C&S A625-633, C&S B284-300).

1. The diene must be cisoid (this refers to the conformation about the single bond).
2. Addition is always syn (or cis) to the diene.
3. Addition is always syn (or cis) to the alkene (the dienophile).
4. Endo-addition is often the fastest reaction (kinetic control), although the endo-product is often the less stable than the exo (F 21). N.B. "endo" has a different meaning here to that used in Baldwin's rules.

The best way to visualise these rules is to think of the diene and the alkene approaching one another in parallel planes:-

In synthetic applications, this is obviously just as important as the stereochemistry. For a 2-substituted butadiene, it is found that the product is mainly "para", not "meta".

For a 1-substituted butadiene, the major product has the "ortho", rather than "meta" orientation.

Diels-Alder reactions are concerted, but it is likely that formation of the strongest bond runs ahead of formation of the second bond, and thus determines the regiochemistry. The transition state may therefore resemble a biradical in which this bond has formed completely. One way to analyse the regiochemistry is therefore to consider the four possible biradical intermediates which might be formed by making only one bond and to decide which is the most stable.

One resonance form for each biradical is shown below:-

The radical centre derived from the alkene is stabilised by the alkene substituent (in this case a CH₃CO group; all substituents stabilise radicals relative to hydrogen). The radical derived from the diene is always allylic, but it gains extra stability from the substituent (methyl in this case) when that is on a carbon which has radical character. The conclusion is that the biradical shown below is the most stable:-

An alternative way to understand the regiochemistry is to look at the frontier orbitals, and this will be done after using FMO theory to consider reactivity on the Diels-Alder reaction.

The simplest Diels-Alder reaction of ethene with 1,3-butadiene is not efficient and requires high temperatures. Reaction rates are increased if the dienophile has electron-withdrawing substitutents e.g. maleic anhydride (2nd year experiment), and the diene has electron-donating substituents (e.g. alkyl groups). This is known as the "normal" Diels-Alder reaction. These reactions are often catalysed by Lewis acids, which complex with the Z substituents, making them even more electron-withdrawing.

Less commonly, you can also get a rapid reaction between an electron-poor diene and an electron-rich alkene; this is called an "inverse electron demand" Diels-Alder reaction.

In order to understand this pattern of reactivity it is useful to use FMO theory (F 33). The FMOs of dienophiles and dienes with various types of substituent are shown over the page. Note that:

C is an alkyl group or conjugating group like Ph

Z is an electron-withdrawing group (e.g. CN)

X is a heteroatom with lone pairs, like OR or NR₂).

The effects of C, Z, and X groups on the energies of the HOMOs and LUMOs are described in F 49-51.

The most favourable reactions are ones with strongest FMO interactions between appropriate HOMOs and LUMOs (smallest energy gaps - wiggly lines below).

The FMO approach can also be used to understand regiochemistry. In the early stages of a Diels-Alder reaction, the strongest interaction will be between the centres with the highest coefficients on the most important pair of interacting orbitals (F 52-55). It can be seen from the diagrams above that this predicts ortho-regiochemistry for 1-substituted butadienes and para-orientation for 2-substituted butadienes, just like the radical approach described earlier.