The stereoselective formation of six-membered nitrogen heterocycles that contain an asymmetric quaternary carbon center was achieved through aza-annulation of beta-enamino amide substrates with activated acrylate derivatives. Condensation of a racemic beta-keto amide with an optically active primary amine, either (R)-alpha-methylbenzylamine or alpha-amino esters, generated the corresponding optically active tetrasubstituted secondary enamine, in which the enamine tautomer was stabilized through conjugation with an amide carbonyl. Treatment of the intermediate enamine with acryloyl chloride, acrylic anhydride, or sodium acrylate/ethyl chloroformate resulted in aza-annulation to give the corresponding delta-lactam with high diastereoselectivity (>96% de). For the variety of different beta-enamino amide substrate classes examined in this reaction, the optimum method for activation of the acrylate derivative was the use of EtO2CCl. When aza-annulation was performed with an alpha-acetamido-substituted acrylate derivative, the stereoselective formation of the quaternary carbon center was accompanied by poor selectivity for generation of the center alpha to the lactam carbonyl. Crystallographic analysis of one alpha-amido aza-annulation product was performed to identify the key structural features of these molecules.