Formal Synthesis of Ezetimibe Using a Proline-mediated, Asymmetric, Three-component Mannich Reaction

The formal total synthesis of ezetimibe was accomplished using a proline-mediated, asymmetric, three-component Mannich reaction as the key step. The two stereogenic centers on the β-lactam skeleton of ezetimibe were controlled by the syn-selective asymmetric Mannich reaction, followed by isomerization.