Variants of the prins cyclization for the synthesis of terpenoid spiroethers and oxabicyclo[3.3.1]nonane derivatives

J Org Chem. 2014 Nov 7;79(21):10123-31. doi: 10.1021/jo501755x. Epub 2014 Oct 23.

Abstract

Terpenoid spiroethers are abundant natural flavors with significant impact, particularly in the food industry. We present in this article the synthesis of new derivatives of the well-known flavors theaspirane and vitispirane using a variant of the Prins cyclization starting from α,β-unsaturated or heterocyclic ketones. When aromatic ketones were used as the starting materials for Lewis acid-mediated cyclizations, an alternative pathway involving a domino sequence of Prins cyclization, followed by an intramolecular Friedel-Crafts alkylation, gave benzoannelated oxabicyclo[3.3.1]nonane derivatives. Different reaction pathways may be triggered by the reaction temperature to give with good selectivity either tetrahydropyran derivatives as conventional Prins products or oxabicyclo[3.3.1]nonane derivatives.

MeSH terms

  • Bridged Bicyclo Compounds, Heterocyclic / chemical synthesis*
  • Bridged Bicyclo Compounds, Heterocyclic / chemistry
  • Catalysis
  • Cyclization
  • Ethers, Cyclic
  • Heterocyclic Compounds / chemical synthesis*
  • Heterocyclic Compounds / chemistry
  • Ketones / chemistry
  • Molecular Structure
  • Spiro Compounds
  • Terpenes / chemistry*

Substances

  • 2,8-dioxabicyclo(3.3.1)nonane
  • Bridged Bicyclo Compounds, Heterocyclic
  • Ethers, Cyclic
  • Heterocyclic Compounds
  • Ketones
  • Spiro Compounds
  • Terpenes
  • spiroether