Divergent Method to <i>trans</i>-5-Hydroxy-6-alkynyl/alkenyl-2-piperidinones: Syntheses of (−)-Epiquinamide and (+)-Swainsonine

An efficient diastereoselective approach to access trans-5-hydroxy-6-alkynyl/alkenyl-2-piperidinones has been developed through nucleophilic addition of α-chiral aldimines using alkynyl/alkenyl Grignard reagents. The diastereoselectivity of alkenyl in C-6 position of 2-piperidinone was controlled by α-alkoxy substitution, while the alkynyl was controlled by the coordination of the α-alkoxy substitution and stereochemistry of sulfinamide. The utility of this straightforward cascade process is demonstrated by the asymmetric synthesis of the (−)-epiquinamide and (+)-swainsonine.