Highly Stereodivergent Construction of a C-Symmetric ,- and ,-2,6-Dioxabicyclo[3.3.0]octane Framework by Double Intramolecular Amide Enolate Alkylation: Total Synthesis of (+)-Laurenidificin and (+)-Aplysiallene.

The highly stereoselective construction of C-symmetric ,- and ,-2,6-dioxabicyclo[3.3.0]octane (fused -tetrahydrofuran) skeletons and has been accomplished via a novel stereodivergent double intramolecular amide enolate alkylation of common cyclization substrate through the judicious choice of "chelate" versus crown ether-promoted "nonchelate" control. Application of this methodology has provided access to substrate-controlled concise total syntheses of (+)-laurenidificin () and (+)-aplysiallene (-), which possess /- and /-fused bis-tetrahydrofuran cores, respectively.