Mechanism of Diels-Alder reaction

Diels-Alder reaction

This reaction was discovered by two German chemists named Otto Diels and Kurt Alder. Conjugated dienes undergo a cycloaddition reaction with multiple bonds to form unsaturated six-membered rings. This reaction involves the 1,4-addition of a diene and a dienophile. This reaction proved to be of great importance as yield was 100% and hence they received the Nobel Prize in 1950.






Reaction mechanism
The Diels-Alder reaction is a thermal cycloaddition whose mechanism involves the sigma-overlap of the pi-orbitals of the two unsaturated systems. There is not a single mechanism for all Diels-Alder reaction. At first approximation, we can divide them into two classes:

1.Synchronous and symmetrical (concerted) mechanisms when the two new bonds are formed simultaneously. In the transition state, the two forming bonds have the same lengths. The combination of ethylene and butadiene is one example.
2.Multistage (non-concerted) and asynchronous mechanisms. The transition state is a di-radical, one bond being formed, the other not.

Real mechanisms are a mixture of these two extremes, one bond being more properly formed and thus shorter than the other.
















To have an idea of the mechanism and to calculate the activation energy of a reaction, we have to find its transition state, using a gradient minimization. The transition state of the Diels-Alder addition of butadiene and ethylene shows that it looks like the reactants. It is called an early transition state.
Typically, the Diels-Alder reaction works best when either the diene is substituted with electron donating groups (like -OR, -NR2, etc) or when the dienophile is substituted with electron-withdrawing groups (like -NO2, -CN, -COR, etc).

Conformational requirements of the diene
One quirk of the Diels-Alder reaction is that the diene is required to be in the s-cis conformation in order for the Diels-Alder reaction to work. The s-cis conformation has both of the double bonds pointing on the same side of the carbon-carbon single bond that connects them. In solution, the carbon-carbon single bond in the diene that connects the two alkenes is constantly rotating, so at equilibrium there is usually some mixture of dienes in the s-trans conformation and some in the s-cis conformation. The ones that are at that moment in the s-trans conformation do not react, while the ones in the s-cis conformation can go on to react.






Because of the Diels-Alder's requirement for having the diene in a s-cis conformation, dienes in rings react particularly rapidly because they are "locked" in the s-cis conformation. Unlike dienes in open chains in which there is usually some proportion of the diene in the unreactive s-trans conformation, dienes in rings are held in the reactive conformation at all times by the constraints of the ring, making them react faster.







Stereochemistry of Diels-Alder reaction
If the dienophile is disubstituted (substituted twice), there is the possibility for stereochemistry in the product. In the Diels-Alder reaction, you end up with the stereochemistry that you started with. In other words, if the substituents started cis (on the same side) on the dienophile, they end up cis in the product. If they started trans (opposite sides) on the dienophile, they end up trans in the product.