Home Daniel A. Singleton Research Publications Group Pictures JOC
Many of the current projects of group members employ isotope effects to study reaction mechanisms. One example is Jennifer Hirschi’s project to study the mechanism of the enzyme-catalyzed cyclization of squalene oxide, the key step in the biosynthesis of steroids. The fascinating reaction forms four rings in a single chemical step. How are those rings formed, all at once or one at a time? Jen is going to find out. How? By measuring where there are carbon kinetic isotope effects in the process.
An example of a current project is Ziggy Wang’s study of the Diels-Alder reaction of acrolein with methyl vinyl ketone. This reaction produces a mixture of products, yet only one transition state can be found theoretically for the cycloaddition. Without considering dynamic effects, theory would predict only one product! Ziggy has studied the reaction both experimentally and theoretically, and is developing an understanding of what factors determine the product ratio in such reactions. This will be critical, as we believe that many common reactions have their selectivity determined by dynamics effects.
Only one transition state can be found, yet the reaction produces two products!
Bryson Ussing has found that dynamic effects change the basic ideas with which we understand reaction mechanisms. In the decomposition of diazonium ions in water to afford phenols, the two conventional mechanistic possibilities are an SN1 mechanism, involving an aryl cation (path a) and a concerted front-side displacement (path b, described here as SN2Ar). Under some conditions, there is unambiguous evidence for an intermediate, supporting the SN1 mechanism. However, some observations and recent theoretical studies have favored a concerted transition state as in the SN2Ar.
We first used isotope effects to tell us what theoretical structures are reasonable models for the actual reaction - the recent theoretical studies had modeled bulk water with a single water molecule and this was shown to be highly inaccurate. Dynamics trajectories were then started from defensible transition structures. Some trajectories formed the product quickly, some slowly, but often the trajectories often afforded long-lived aryl cation intermediates. Intriguingly, the nucleophilic water molecule involved at the transition state does not necessarily end up in the product.
Chad Christian has found that dynamic effects are important in the ene cyclization of enyne-allenes, and again the results shatter conventional mechanistic ideas. This reaction is mechanistically on the borderline between stepwise and concerted processes. A conventional mechanistic study would try to decide whether it is one, or the other, or perhaps a mixture of the two. With dynamic effects, however, there are more choices. In this particular case, only one transition structure may be located for the initial cyclization, and the minimum energy path through this transition structure goes directly to the product. The transition state would thus be described as “concerted.” However, dynamic trajectories passing through this transition structure often lead to an intermediate diradical. Thus, a reaction can have a concerted transition state and a stepwise mechanism.
Contact Information Department of Chemistry Texas A&M University