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

Hong Zhang, Alexander J.E. Novak, Cooper S. Jamieson, Xiao Song Xue, Shuming Chen, Dirk Trauner, K. N. Houk

Research output: Contribution to journalArticlepeer-review

Abstract

Computational studies with ωB97X-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 α-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.

Original languageEnglish (US)
JournalJournal of the American Chemical Society
DOIs
StateAccepted/In press - 2021

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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