Exploratory studies toward the synthesis of the peroxylactone unit of plakortolides

Our efforts in construction the 1,2-dioxane ring of plakortolides through two approaches are described. The first one involved as a key step an acid catalyzed 6-endo ring closure of beta-hydroperoxy trans-epoxides directed by a vinyl group adjacent to the epoxide function. By this route, an advanced intermediate of plakortolides was obtained in six steps and 35% overall yield. The second approach featured a 1,2-dioxane ring forming by a double opening of bis-epoxides by ethereal hydrogen peroxide. This reaction did not proceed in the expected sense and exclusive formation of hydroperoxy tetrahydropyran derivatives was observed via a tandem oxacyclization-hydroperoxidation sequence. (C) 2012 Elsevier Ltd. All rights reserved.