I. Progress toward the total synthesis of guanacastepene A. II. Silyloxy-tethered methodology development: New applications in enyne metathesis and hydrosilylation chemistry

Guanacastepene A, the leading member of a structurally diverse family of diterpene natural products, was isolated from the extracts of an unidentified fungus. The discovery of its potent antibiotic activity as well as its previously unreported tricyclic architecture render guanacastepene A an attractive and formidable target for total synthesis. Efforts to construct guanacastepene A's novel tricyclic architecture, which includes two ring-junction quaternary methyl groups and an array of unsaturated and oxygen functionality, are discussed.; Organosilanes, such as silyl ethers and vinylsilanes, play an important and diverse role in organic chemistry. Silyl ethers are widely used as protecting groups for alcohols and also function as temporary tethers that adapt a variety of intermolecular reactions to more favorable intramolecular processes. In addition, vinyl silanes participate in palladium-catalyzed cross-coupling reactions and can be transformed into vinyl halides or carbon-oxygen species.; Given the broad utility of silyl ethers and vinyl silanes, we have investigated new methods for the catalytic synthesis of these highly versatile intermediates. We have shown that the well-known olefin metathesis complex Cl2(PCy 3)2Ru=CHPh is also an effective catalyst for the synthesis of silyl ethers and vinylsilanes through activation of the silicon--hydrogen bond. Silyl ethers are obtained from a variety of silanes by the dehydrogenative condensation with various alcohols as well as the hydrosilylation of aldehydes and ketones. During the hydrosilylation of terminal alkynes, up to complete formation of the Z-vinylsilane was observed. A second ruthenium catalyst, [RuCl2(p-cymene)]2, was employed for the synthesis of silyloxy-tethered enyne substrates via the dehydrogenative condensation between terminal alkenyl alcohols and alkynylsilanes. These useful building blocks undergo regioselective enyne ring-closing metathesis reactions to give the exo-siloxacycles exclusively. The silyloxy-tethered enyne ring-closing metathesis reaction was further developed into a concentration-dependent group-selective ring closure of alkynylsilyloxy-tethered dienynes. Additionally, we explored the activation of alkynylsilanes by Lewis base catalysis via the formation of pentacoordinate silicates. Treatment of select alkynylsilanes and carbonyl compounds with a catalytic amount of potassium tert-butoxide promotes an unexpected tandem alkynlation-trans-hydrosilylation sequence to yield oxasilacyclopentenes.