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

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.

Automated summary

This review article traces the evolution of Woodward's mechanistic thinking from proposing a charge-transfer mechanism to developing the Woodward-Katz two-stage concerted mechanism and orbital symmetry control. Research by Houk in Woodward's lab tested the theory's predictions. Modern calculations have confirmed Woodward's descriptions of cyclopentadiene dimerization mechanism and the discovery of ambimodal or bis-pericyclic transition states. Hoffmann's Coda reflects on the joy of following the cycloaddition story from Woodward's youth to trajectory simulations today.