Old Haunts Revisited

Old Haunts Revisited

Author: ChemViews

The originally proposed synthesis of (+)-symbioimine involved a tandem diastereoselective exo intramolecular Diels−Alder (IMDA) cycloaddition/imine condensation of the (E)-enone. This approach was not developed due to:

  • literature precedents indicating that IMDA cycloadditions proceed preferentially through an endo rather than exo transition state
  • the nonconstrained exocyclic C-2 stereocenter controlling the π-facial selectivity for the cycloaddition.

Jason Chruma and co-workers, University of Virginia, USA, have revisited this approach and show that the exo-IMDA cyclization fails due to the all-E triene framework, but the desired cyclization may be achieved through an endo transition state. They note the need to constrain the Z-enone to prevent isomerization and that a single nonconstrained exocyclic stereocenter can control π-facial selectivity in this type of cyclization.

Using this methodology the team formed a range of synthetic precursors to epimeric analogues of (+)-symbioimine.

Original paper reporting the isolation and proposed synthesis:

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