dielsalder

The Diels-Alder reaction, named after Otto Diels and Kurt Alder, is a [4+2] cycloaddition between a conjugated diene and a dienophile that forms a cyclohexene ring. Discovered in 1928, it is one of the most versatile and widely used reactions in organic synthesis.

Mechanistically, the reaction is concerted and proceeds via a cyclic transition state in which both new bonds form in a single step. Frontier molecular orbital theory explains its electronic requirements: the HOMO of the diene interacts with the LUMO of the dienophile. Electron-rich dienes and electron-poor dienophiles react most readily. The diene must adopt the s-cis conformation to allow proper orbital overlap.

Regio- and stereochemistry are governed by substituents and orbital interactions. Substituents influence regioselectivity, and the endo rule often governs, with electron-withdrawing groups on the dienophile oriented underneath the forming ring due to secondary orbital interactions. Endo products predominate under many conditions, although exo outcomes can occur with steric or conformational effects.

Dienophile activation and variants expand the scope of the reaction. Lewis acids such as AlCl3 or TiCl4 can accelerate the reaction by lowering the dienophile's LUMO, enabling less reactive partners. Intramolecular Diels-Alder reactions create bicyclic frameworks and are valuable for building complex natural products and medicinally relevant molecules. The reaction also finds use in polymer chemistry via Diels-Alder polymerization and in asymmetric synthesis with chiral catalysts or auxiliaries to achieve enantioselectivity.

Limitations include sensitivity to temperature, solvent, and reaction conditions, and the retro-Diels-Alder reaction can occur upon heating, allowing rearrangements or simplification of products.