Total Synthesis of (+)-Dactylolide. Studies on the Cascade Cyclization Reactions of Epoxides/Polyepoxides Initiated by Single Electron Transfer

摘要

The total synthesis of the marine macrolactone (+)-dactylolide was achieved in a highly convergent and efficient way (Scheme I). The route involves the coupling of two functionalized fragments of the molecule, an ¦Á,¦Â-unsaturated aldehyde and a 1,3-syn-diol, to form a cyclic ¦Á,¦Â-unsaturated cyclic acetal. Both enantiopure fragments arise from asymmetric vinylogous Mukaiyama aldol reactions. The key transformations in this synthesis include a sequential Peterson olefination/Prins cyclization reaction to construct the 2,6-cis-disubstituted-4-methylenetetrahydropyran core efficiently and stereoselectively, a Mislow-Evans selenoxide-selenate [2,3] sigmatropic rearrangement to transpose allylic alcohol transposition and an intramolecular Horner-Emmons macrocyclization.A systematic study on the cascade cyclizations of epoxides/polyepoxides initiated by single electron transfer has been carried out (Scheme II). Four monoepoxides and six diepoxides were tested. The results showed that the bicyclo[3.1.0] epoxonium ion intermediates formed in the cyclization favor 5-exo-cyclization in the nonpolar solvent (1,2-dichloroethane) while in the polar solvent (CH3CN), they prefer 6-endo-selectivity. However, the bicyclo[4.1.0] epoxonium ion intermediates usually give 7-endo regiochemical selectivity in the presence of substitution-induced bias. However, without the substituent effect, 6-exo and 7-endo-cyclizations are two competitive pathways.