[Rh(CO)2Cl]2 is as an effective catalyst for endoselective cyclizations and cascades of epoxy-(E)-enoate alcohols, thus enabling the synthesis of oxepanes andoxepane-containing polyethers from di- and trisubstituted epoxides. Syntheses of the ABC and EF ring systems of (−)-brevisin via all endo-diepoxide-opening cascades using this method constitute a formal total synthesis and demonstrate the utility of this methodology in the context of the synthesis of marine ladder polyether natural products.