Synthetic applications of Z-selective ruthenium-based olefin metathesis catalysts

Abstract

The first report of Z-selective macrocyclizations using a ruthenium-based metathesis catalyst is described. Selectivity for Z-- macrocycles is consistently high for a diverse set of substrates bearing different functional groups and comprised of various ring sizes. The same catalyst was employed for the Z-selective ethenolysis of a mixt. of E and Z macrocycles, providing the pure Eisomers. These methodologies were successfully applied to the construction of several olfactory macrocycles, as well as the backbone of cytotoxic alkaloid natural products. Conditions were also optimized for a series of challenging cross metathesis reactions using the same catalyst system, and subsequently exploited in the synthesis of a family of lepidopteran insect pheromones. A detailed mechanistic study probing the origin of the stereoselectivity in these challenging transformations is currently underway, and will also be discussed in detail.