Stereoselective substrate-controlled asymmetric syntheses of both 2,5-cis- and 2,5-trans-tetrahydrofuranoid oxylipids: Stereodivergent intramolecular amide enolate alkylation

Article abstract of DOI:10.1002/anie.201600637

The concise, highly stereoselective, substrate-controlled asymmetric total syntheses of both 2,5-cis- and 2,5-trans-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 C3-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. Two from one: The title reaction leads to both isomers of the tetrahydrofuranoid nematocidal oxylipids in a stereodivergent fashion from a common intermediate. Each of the stereoisomers results from exploiting either chelate or nonchelate control in the reaction. PMB=para-methoxybenzyl, TIPS=triisopropylsilyl.