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

ABSTRACT

We completed the synthesis of dimeric high-oxidation-state securinega alkaloid flueggeacosine B via two synthetic routes from allosecurinine. The first-generation synthesis (seven overall steps) involved a Liebeskind-Srogl cross-coupling reaction for the union of two functionalized fragments, the organostannane and the thioester. As a means to further streamline the synthetic route, we have developed a visible-light-mediated Cu-catalyzed cross-dehydrogenative coupling (CDC) reaction between an aldehyde and an electron-deficient olefin. This enabled the second-generation synthesis of flueggeacosine B from allosecurinine in four overall steps. The newly developed CDC reaction paves a direct way to a conjugated dicarbonyl moiety, a ubiquitous structural moiety present in various natural products.