Computational Exploration of the Mechanism of Critical Steps in the Biomimetic Synthesis of Preuisolactone A, and Discovery of New Ambimodal (5+2)/(4+2) Cycloadditions

Computational studies with omega B97X-D density functional theory of the mechanisms of the steps in Trauner's biomimetic synthesis of preuisolactone A have elaborated and refined mechanisms of several unique processes. An ambimodal transition state has been identified for the cycloaddition between an o-quinone and a hydroxy-o-quinone; this leads to both (5 + 2) (with H shift) and (4 + 2) cycloaddition products, which can in principle interconvert via alpha-ketol rearrangements. The origins of periselectivity of this ambimodal cycloaddition have been investigated computationally with molecular dynamics simulations and tested further by an experimental study. In the presence of bicarbonate ions, the deprotonated hydroxy-o-quinone leads to only the (5 + 2) cycloaddition adduct. A new mechanism for a benzilic acid rearrangement resulting in ring contraction is proposed.

Automated summary

Computational studies using omega B97X-D density functional theory have revealed and refined the mechanisms of unique processes in Trauner's biomimetic synthesis of preuisolactone A. The research identified an ambimodal transition state for the cycloaddition between o-quinone and hydroxy-o-quinone, leading to both (5 + 2) and (4 + 2) cycloaddition products. A new mechanism for benzilic acid rearrangement resulting in ring contraction was proposed based on the study.