A Bioinspired Strategy for the Enantioselective Synthesis of Bicyclic Oxygen Heterocycles.

A new strategy is described for the direct conversion of unsaturated 3,5-dihydroxy-diarylheptanoids to dimeric products assembled on trans-2,8-dioxabicyclo[4.4.0]decane frameworks. The key atom-economical acid-mediated coupling creates 2 rings and 4 new stereocenters in a single-pot process. Oxygen-18 labeling studies are in accord with reactions proceeding via a cascade mechanism involving carbocationic intermediates. This approach enabled the concise total syntheses of analogues of the natural product blepharocalyxin D in 4 steps from simple starting materials.