Gold(III)-Catalyzed Cyclizations to Form Saturated Oxygen Heterocycles

Gold catalysis has emerged over the past decade as an important methodology in the construction of organic molecules. Cationic gold complexes are robust, versatile, selective and efficient catalysts that can be used to enhance the electrophilicity of C-C unsaturated bonds. A current area of investigation is the use of gold to activate allylic alcohol/ether moieties for intramolecular SN2' nucleophilic attack to form oxygen heterocycles. We have discovered that sterically bulky, electron-withdrawing oxygen leaving groups drastically improved reaction efficiency, and bulky leaving groups in combination with substrate substituents enhanced diastereomeric ratios in the oxygen heterocycle products. These reactions proceeded smoothly in the presence of many functional groups to consistently afford high diastereoselectivity. This methodology was attempted in the synthesis complex spirocyclic ether structures, and used in progress towards total synthesis of the natural product (±)-centrolobine.