Regioselectivity in Diels-Alder reactions

Reaction of 2-methoxybuta-1,3-diene and acrylonitrile

It is possible to tell which product is formed by considering the molecular orbitals of the reactants.

The regioselectivity of the reaction can be determined by working out where the largest coefficient of the HOMO lies in the diene and the largest coefficient of the LUMO lies in the dienophile. The reagents come together in the orientation where these ‘largest’ coefficients can overlap.

• The largest coefficient of the HOMO is found where electrophilic attack on the diene is most favoured.
• Electrophilic attack at the end carbons of a diene gives the most stable allyl cation – thus the largest component of the HOMO is on these end carbons.
• When the two ends are different we consider where electrophilic attack is most favoured to tell us which end carbon has the largest component of the HOMO.

• Attack from the end nearest OMe is most favoured because then the OMe stabilises the carbocation product.
• The largest coefficient of the HOMO is found at the end of the diene where electrophilic attack is most favoured, or put another way, where the diene will act as a nucleophile.

• The largest coefficient of the LUMO is found where the dienophile acts as an electrophile.

• Nucleophilic attack occurs at the position where the cyano group can delocalise the charge.
• This is where the largest coefficient of the LUMO is.

Combining the two ends gives the product that is formed.

To see this reaction in 3D click here.

J. Sauer, Angew. Chemie Int. Ed. English, 1967, 6, 16–33.