Variants of the Prins Cyclization for the Synthesis of Terpenoid Spiroethers and Oxabicyclo[3.3.1]Nonane Derivatives

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.