Studies on tandem Dienyne metathesis reaction and application to total synthesis.

Abstract

With the development of new metathesis catalysts, olefin metathesis has attracted much attention from the organic chemistry community and numerous synthetic strategies based on metathesis have been developed. On the other hand, enyne metathesis has not been developed as much. Therefore, our studies were focused on both intramolecular and intermolecular enyne metathesis. At first, the enyne proceeded well with internal olefins but produced E/Z diene mixture. Therefore, we investigated the stereoselective tandem enyne/diene-ene metathesis reaction. This concept extended to intermolecular and multicomponent reaction. Since the tandem enyne/diene-ene metathesis reaction produces several conjugated cyclodienes, the reaction could be coupled to the Diels-Alder reaction to form polycyclic compounds. Tandem ring-closing metathesis of dienynes using the $2^{nd}$ generation Grubbs catalyst was explored and turned out to be a useful method for synthesis of fused ring system. Though, the tandem metathesis reaction was strongly substrate dependent. Depending on the substrate, the reaction either did not proceed at all of leads to cyclopropanation products. Therefore, we developed an alternative route to the tandem metathesis reaction. The sequential reaction of dienyne using platinum chloride catalyzed rearrangement and metathesis reaction produced the same bicyclic ring system with wider applicability. The results were applied to the construction of core skeleton of Clavukerin C. In the next part, synthesis of Frondosin A using [5+2] cycloaddition reaction of oxidopyrylium ion as a key reaction was investigated. Frondosin A is as norsesquiterpenoid natural product, which has been found to exhibit biological activity. Among the various types of cycloaddition, [5+2] cycloaddition reaction of oxidopyrylium ion as a key reaction was used to assemble the functionalized bicyclo core using system stereoselectively. The reaction could construct the both of the core skeleton an...