Evolution of the Diels–Alder Reaction Mechanism since the 1930s: Woodward, Houk with Woodward, and the Influence of Computational Chemistry on Understanding Cycloadditions

Abstract This review article describes the evolution of Woodward's mechanistic thinking, beginning in the late 1930s and early 1940s with his proposal of a charge‐transfer mechanism for the Diels–Alder reaction, eventually leading to the Woodward–Katz two‐stage concerted mechanism in 1959, and then to its mechanistic solution in terms of orbital symmetry control. Houk′s research in the Woodward labs, testing the predictions of this theory, is described. Subsequent modern calculations with quantum mechanics and molecular dynamics simulations have shown that Woodward indeed had perfectly described not only the cyclopentadiene dimerization mechanism, but a new class of transition states now known as ambimodal or bis‐pericyclic transition states. In recent years, the Houk group has found that ambimodal reactions are operative in the [6+4] cycloaddition. Molecular dynamics simulations of many Diels–Alder and ambimodal cycloadditions provide a time‐resolved picture of how these reactions occur. Lastly, Roald Hoffmann provides a Coda in which he describes his joy in “being taken along the journey” of the cycloaddition story from Woodward's youth to today's trajectory simulations.