We have studied a transannular Diels-Alder reaction catalyzed by SpnF, an enzyme identified as a Diels-Alderase by Liu and coworkers. Examination of PES revealed the presence of a bifurcation, indicating that the relevant TS is bis-pericylic. This bis-pericyclic TS leads directly to the Diels-Alder adduct and an unexpected [6+4] adduct. This [6+4] adduct can rearrange by a concerted Cope rearrangement into the more stable Diels-Alder adduct. Product formation in reactions involving a bifurcation is non-statistical; instead, the reaction is controlled by the distribution of energy in the vibrational modes of the reactant as it progresses past the transition state downhill toward the bifurcation. It is possible SpnF may alter this energy distribution as a means of affecting regiocontrol. Consequently, SpnF may exclusively form the [6+4] adduct via a pericyclic mechanism first described by Woodward and Hoffmann in 1965. The [6+4] adduct can then rearrange into the more stable Diels-Alder cycloadduct.

Computational investigation of the mechanism of an enzyme-catalyzed transannular Diels-Alder reaction: Is SpnF really a [6+4]ase?

245th National Meeting (2013)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.