A new catalyst for a Pd catalyzed alder ene reaction. A total synthesis of (+)-cassiol

The scope of the palladium catalyzed cycloisomerization of enynes in an Alder ene type fashion that led to a new catalytic system was explored in the context of a synthetic strategy to the antiulcerogenic agent (+)-cassiol. In a model study, the effect of six-membered ring formation, the presence of a carbonyl group in the tether, and the steric hindrance of the alkene conspire to prevent the cycloisomerization under the ''standard'' conditions. Two variables proved key in the development of a new catalytic system that has proven to be effective, the absence of traditional ligands and the choice of acid. An effective synthesis of (+)-cassiol was accomplished in which this new reaction played a key. A lipase served to introduce the chirality, and a palladium(0) catalyzed reaction was important in elaborating a side chain. The final adjustment of oxidation level made advantageous use of a platinum catalyzed enone hydrosilyation.