Total Synthesis of (+)-Paucidactine D.

The first total synthesis of (+)-paucidactine D () is detailed from the pentacyclic intermediate . The approach features two bridging cyclizations with the first being a SmI-mediated intramolecular C21-C2 free radical cyclization to access the highly substituted bicyclo[2.2.2]octane core ring system. A subsequent intramolecular S2 displacement reaction was used to establish the C11-O bond of the bridging C11-OC(O)-C3 six-membered lactone. Central to the assemblage of the underlying skeleton of is a powerful [4 + 2]/[3 + 2] cycloaddition cascade of 1,3,4-oxadiazole , which provided the highly functionalized pentacyclic ring system in one step as a single diastereomer. The efforts combined with our past studies now represent the divergent total syntheses of members of eight distinct naturally occurring alkaloid classes from the same common intermediate , with each implementing a different late-stage core strategic bond formation.