Diastereoselective synthesis of 4-hydroxypiperidin-2-ones via Cu(I)-catalyzed reductive aldol cyclization

4-Hydroxypiperidin-2-ories may be prepared in highly diastereoselective fashion using a Cu(I)-catalyzed reductive aldol cyclization of alpha,beta-unsaturated amides with ketones. Used in combination with proline-catalyzed asymmetric Mannich reactions, this methodology enables the enantioselective synthesis of more highly functionalized piperidin-2-ones and hydroxylated piperidines.