The concise, highly stereoselective, substrate-controlled asymmetric total syntheses of both 2,5-trans- and 2,5-cis-tetrahydrofuranoid nematocidal oxylipids from the Australian brown algae Notheia anomala have been accomplished in a stereodivergent fashion. The highly stereoselective intramolecular amide enolate alkylation strategy provides access to both stereoisomers of the 3-hydroxy-2,5- disubstituted tetrahydrofuran core of these marine natural products through chelate and nonchelate control, which is driven by the C(3)-hydroxy protecting group. This approach offers an optional and highly stereoelective access to any of the eight possible stereoisomers of the 2,5-disubstituted-3-oxygenated tetrahydrofuran skeleton, an important structural feature which is present in many biologically active natural products.
