A highly diastereoselective approach for the synthesis of trans-4-hydroxy-5-substituted 2-pyrrolidinones has been developed through an intramolecular cascade process of α-chiral aldimines using alkyl, aryl, alkynyl, and alkenyl Grignard reagents. The stereochemistry at the C-5 position of 2-pyrrolidinone after reaction with alkyl, aryl, and alkenyl Grignard reagents was solely controlled by α-alkoxy substitution. For alkynyl Grignard reagents, the stereochemistry was controlled by coordination of the α-alkoxy substitution and the stereochemistry of the sulfinamide. The utility of this one-pot cascade protocol is demonstrated by the asymmetric synthesis of streptopyrrolidine 5 and 3-epi-epohelmin A 3-epi-6.