Recent Applications of the Suzuki-Miyaura Cross-coupling to Complex Polycyclic Ether Synthesis

The ladder-shaped polycyclic ether marine natural products present formidable and challenging synthetic targets due to their structural complexity, and exceptionally potent biological activities. Over the past decade, however, the limited availability of these substances from natural sources has precluded detailed biological studies. There has been an urgent need for means to supply useful quantities of these natural products and their analogues by total synthesis. We have developed a highly convergent strategy for the rapid and efficient assembly of polycyclic ether arrays, which relies on the palladium-catalyzed Suzuki-Miyaura cross-coupling reaction of cyclic enol triflates or phosphates. The utility of this strategy has been demonstrated by its application to the convergent total synthesis of the polycyclic ether class of natural products.