Unified Synthesis of 10-Oxygenated <i>Lycopodium</i> Alkaloids: Impact of C₁₀-Stereochemistry on Reactivity

The pronounced impact of the C₁₀ stereochemistry on the successful construction of a polycyclic <i>Lycopodium</i> alkaloid scaffold has been explored. A wide range of reaction conditions and functionality were investigated to control a keto sulfone Michael addition to construct the C₇–C₁₂ linkage. An unexpected, overriding impact of the C₁₀ stereochemistry in stereoselectivity and reaction rate in the Michael addition was observed. Furthermore, divergent reactivity of a conformationally accelerated, intramolecular Mannich cyclization based on the C₁₀ stereochemistry was discovered. The successful execution of this synthetic route resulted in the total synthesis of all three known 10-oxygenated <i>Lycopodium</i> alkaloids: 10-hydroxylycopodine, paniculine, and deacetylpaniculine