Diels-Alder reaction

Also known as: Diels-Alder cycloaddition

The Diels-Alder reaction is an organic reaction used to convert a conjugated diene and a dienophile to a cyclic olefin under thermal conditions. This is a concerted process where bonds are forming and breaking at the same time and the reaction belongs to a class of reactions termed "cycloaddition". The Diels-Alder reaction is by far the most famous 'name reaction' and it is extensively used in natural product synthesis. When predicting the regiochemistry and stereochemistry of the product, things to consider are the electronic character of the substitutes on the diene and dienophile, the partial charges formed, and the orientation of the starting materials when they approach each other.^[1][2][3]

• Kinetics
• Molecular Orbital Theory
• Regiochemistry
• Stereochemistry
• Predictions

The Diene must be in the s-cis conformation for the reaction to occur.

Conformational lock can play a major role in this reaction diene is locked in the s-trans conformation and can not react diene is locked in the s-cis conformation and reacts faster

Molecular Orbitals with the same sign must overlap during the cycloaddition.

Normal electron-demand Diels-Alder reaction.

Inverse electron-demand Diels-Alder reaction.

Note:
Only the approach of the dienophile from the bottom has been shown. The top approach is just as valid as the molecular orbitals align, having the same sign Most Diels-Alder reactions are normal electron demand reactions as their HOMO-LUMO energy difference is often lower than the reverse electron demand reactions. This reaction can be further sped up by EDGs on the diene which raise the energy of its HOMO and EWGs on the dienophile which lower the energy of the LUMO of the dienophile in turn lowering the energy barrier for this reaction.

Regiochemistry of the Diels-Alder reaction can be predicted using partial charges.

partial charges align 1,2 product partial charges do not align partial charges do not align partial charges align 1,4 product

Stereochemistry of the Diels-Alder reaction can be predicted by the "Endo rule".

endo products (major products) exo products (minor products) The endo products are kinetically favoured and are the major products they are however less stable than the exo thermodynamic products endo product kinetic product OMe and the COMe R group are facing the same side of the forming ring attack of the dienophile from the top side yields the other stereoisomer exo product thermodynamic product The OMe and COMe groups are facing opposite sides of the forming ring attack of the dienophile from the top side yields the other stereoisomer

Using the same rationale as previously, the outcome of the following reactions can be explained.

In the following examples we will be working with normal electron demand Diels-Alder reactions and for simplicity we have arbitrarily chosen OMe as the EDG and COMe as the EWG.

1,4 endo products (major products) cis products trans products Z olefin E olefin