Stereocontrolled synthesis of cyclic ethers by intramolecular hetero-Michael addition. 4. Enantiomeric synthesis of substituted and fused oxepanes

Abstract

The use of an intramolecular hetero-Michael addition of enantiomerically enriched 7-alkoxy-4-benzoyloxy-2,3-unsaturated esters for the synthesis of endo-substituted oxepanes is described. The stereochemistry in the cyclization step is governed by the geometry of the double bond in the unsaturated ester and the presence of a Z-double bond in the linear chain is required in order to achieve good yields. The synthesis of the fused oxepane-tetrahydropyran nucleus of marine polyether toxins with absolute control of all the stereocentres is described.