Computations on Pericyclic Reactions Reveal the Richness of Ambimodal Transition States and Pericyclases

Abstract

The pericyclic reaction concept was developed by Woodward and Hoffmann 56 years ago, before accurate quantum mechanical calculations of organic reaction pathways were possible. Since then, computational methods such as density functional theory and coupled-cluster methods have been formulated, and computer speeds have increased a hundred trillion (10 11 )-fold. The subtleties and timings of bond formation in reactions have been established by high-accuracy quantum mechanical calculations. The field of pericyclic reactions has been enriched by understanding of the borderline between concerted pericyclic reactions and stepwise reactions. Higher-order pericyclic reactions, involving more than six electrons, have ambimodal transition states that can form two, three, or even four products. In addition, while only imagined in the last century, the fact that enzymes can catalyze many pericyclic reactions has been repeatedly established in the 21 st century, aided enormously by computational studies.

Collective Synthesis of Illudalane Sesquiterpenes via Cascade Inverse Electron Demand (4 + 2) Cycloadditions of Thiophene S,S-Dioxides

“…Caramella later revisited this phenomenon computationally and clarified the bifurcating nature of the transition state, as distinct from the Cope rearrangement pathway that connects the products . A number of other cycloadditions have since been reported that proceed through “bipericyclic” ambimodal pathways, in which two distinct products are formed from the bifurcation point …”

Fifty Years of a Dispute. A Triptych: Why Woodward?**

“…[17] In today's parlance, Woodward and Katz were describing a Diels-Alder mechanism incorporating dynamically-stepwise reaction trajectories by way of highly asynchronous concerted transition states. [66,[75][76][77] Decades later, this interpretation has been revealed. For example, using high level quantum mechanical calculations, Houk et al found a time gap of 130 fs between the time the two bonds form in the dimerization of cyclopentadiene.…”

“…[75] Asynchronous transition states are now being reported frequently. [76,[79][80][81] Of course, ultimately molecular orbital theory would play an important role in the derivation of the Woodward- 9) revealed the structure of ferrocene [82] and thereby corrected the literature reported structure. [83,84] Shortly thereafter, Woodward et al reported the aromatic properties of this sandwich compound.…”

Kinetic Analysis of a Reaction Path Network Including Ambimodal Transition States: A Case Study of an Intramolecular Diels–Alder Reaction

“…When dynamical bifurcations occur, an ensemble of trajectories passing through a single TS, called ambimodal TS, bifurcates to multiple minima. 15,16 Dynamical bifurcations were initially found in theoretical studies 17−32 and have since been reported for various organic, organometallic, and biochemical reactions. 33 Dynamical bifurcations cannot be studied by analyses based on an IRC path, which connects one reactant and one product minimum.…”

“…In particular, dynamical bifurcation , is the most important factor because it has a significant impact on the actual yields. When dynamical bifurcations occur, an ensemble of trajectories passing through a single TS, called ambimodal TS, bifurcates to multiple minima. , Dynamical bifurcations were initially found in theoretical studies − and have since been reported for various organic, organometallic, and biochemical reactions. − …”