Divergent Total Synthesis of Tacaman Alkaloids: A Skeleton Reorganization Strategy

Herein, we present a divergent synthesis of tacaman alkaloids featuring a pivotal pentacyclic intermediate bearing an exocyclic trisubstituted olefin, accessed via a base-promoted intramolecular cyclopropanation/cyclopropane ring-opening/<i>oxa</i>-Michael cascade and a subsequent electrophilic halomethylation-<i>retro-aza</i>-Michael sequence. This versatile common intermediate enabled the regio- and diastereoselective functionalization of the trisubstituted olefin, affording the total syntheses of tacamonine, tabercamine K, and 19S-hydroxyapotacamine in good yields with excellent stereocontrol. Notably, the Mukaiyama-type hydration reaction was applied to achieve tunable stereochemistry at the C19 and C20 hydroxyl positions.