The Diels-Alder reaction, a widely used transformation in organic synthesis, forms six-membered rings from a conjugated diene and a dienophile-frequently an alkene. Usually, these two reactants must be activated by catalysts or have complementary electronic properties to participate in the reaction. Phil S. Baran, Thomas J. Maimone, and Ana-Florina Voica of Scripps Research Institute have observed a catalyst-free Diels-Alder reaction between simple, nonactivated reactants at room temperature while synthesizing an intermediate en route to vinigrol, a natural product with antihypertensive and other biological activities (Angew. Chem. Int. Ed., DOI: 10.1002/anie.200800167). Vinigrol has a unique three-ring skeleton, which the team formed by strategically breaking a bond in a four-ring intermediate. The Diels-Alder reaction (shown) forms the four-ring intermediate from a bicyclic precursor. The team believes that the precursor's compact structure brings the reacting diene and alkene into proximity and promotes the cyclization. The rigidity of the resulting four-ring intermediate likely aids the subsequent bond-breaking step that forms vinigrol's three-ring skeleton, the authors write. They now hope to complete the synthesis of vinigrol from this skeleton.