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Discovery of a Formal Dyotropic Rearrangement during Acid-Mediated Dioxabicyclo[4.2.1]nonanone Formation.

Yoshimitsu HashimotoWang-Yeuk KongDean Joseph Tantillo
Published in: Organic letters (2024)
A new reaction mechanism for the construction of dioxabicyclo[4.2.1]nonanone skeletons via a cation cascade has been proposed and examined by DFT and ab initio computations. This mechanism features the following steps: (1) intramolecular Friedel-Crafts-type cyclization with a methyl oxocarbenium cation formed by carboxylate disconnection, (2) electron-rich aromatic ring assisted methoxide loss followed by lactone formation, and (3) stepwise dyotropic rearrangement resulting in skeletal isomerization from a dioxabicyclo[3.2.2]nonanone to the dioxabicyclo[4.2.1]nonanone product observed experimentally. The high regioselectivity and driving force for the overall rearrangement were rationalized, and Lewis and Brønsted acid mediated reactivities were compared.
Keyphrases
  • ionic liquid
  • small molecule
  • single molecule
  • molecular docking
  • high throughput
  • density functional theory
  • single cell