Divergent Method to trans-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 alpha-chiral aldimines using alkynyl/alkenyl Grignard reagents. The diastereoselectivity of alkenyl in C-6 position of 2-piperidinone was controlled by alpha-alkoxy substitution, while the alkynyl was controlled by the coordination of the alpha-alkoxy substitution and stereochemistry of sulfinamide. The utility of this straightforward cascade process is demonstrated by the asymmetric synthesis of the (-)-epiquinamide and (+)-swainsonine.