Rh-Catalyzed reductive Mannich-type reaction and its application towards the synthesis of (±)-ezetimibe.

An effective synthesis for syn-ß-lactams was achieved using a Rh-catalyzed reductive Mannich-type reaction. A rhodium-hydride complex (Rh-H) derived from diethylzinc (Et2Zn) and a Rh catalyst was used for the 1,4-reduction of an α,ß-unsaturated ester to give a Reformatsky-type reagent, which in turn, reacted with an imine to give the syn-ß-lactam. Additionally, the reaction was applied to the synthesis of (±)-ezetimibe, a potent ß-lactamic cholesterol absorption inhibitor.