Total Synthesis of (+)-Epoxydictymene. Application of Alkoxy-Directed Cyclization to Diterpenoid Construction

TLDR: In this paper, an enantioselective synthesis of (+)-epoxydictymene (1) is reported, which efficiently constructs the strained oxabicyclo[3.0] octane subunit of 1.3.

Abstract: An enantioselective synthesis of (+)-epoxydictymene (1) is reported. Condensation of the enantiopure aldehydo ester 5 with (S)-3-isopropylcyclopentenyllithium proceeds selectively to afford 13. Once this lactone was methylenated with the Tebbe reagent, the newly formed allyl vinyl ether was induced into Claisen rearrangement under catalysis with triisobutylaluminum. Sequential hydroboration−oxidation of the resulting dicyclopentacyclooctenone derivative was followed by angular methylation and deoxygenation of the carbonyl functionality. Following epimerization at C-11, an α-hydroxyl was introduced regio- and stereoselectively. Some functional group manipulation led to 57 and 58, both of which underwent efficient cyclization to deliver the complete framework of the target molecule when irradiated with visible light in cyclohexane solution containing iodosobenzene diacetate and iodine. The generality of this key reaction, which efficiently constructs the strained oxabicyclo[3.3.0]octane subunit of 1, is dem...