Synthesis of Dimeric Securinega Alkaloid Flueggeacosine B: From Pd-Catalyzed Cross-Coupling to Cu-Catalyzed Cross-Dehydrogenative Coupling

We completed the synthesis of dimeric high-oxidation-state securinega alkaloidflueggeacosine B via two syntheticroutes from allosecurinine. Thefirst-generation synthesis (seven overall steps) involved a Liebeskind-Srogl cross-coupling reactionfor the union of two functionalized fragments, the organostannane and the thioester. As a means to further streamline the syntheticroute, we have developed a visible-light-mediated Cu-catalyzed cross-dehydrogenative coupling (CDC) reaction between analdehyde and an electron-deficient olefin. This enabled the second-generation synthesis offlueggeacosine B from allosecurinine infour overall steps. The newly developed CDC reaction paves a direct way to a conjugated dicarbonyl moiety, a ubiquitous structuralmoiety present in various natural products.

Automated summary

In this study, we successfully synthesized dimeric high-oxidation-state securinega alkaloid Flueggeacosine B via two synthetic routes. The second-generation synthesis was more streamlined and a new reaction was developed to provide a direct pathway for the synthesis of compounds with a conjugated dicarbonyl moiety.