Synthesis of Taranabant

Significance

Taranabant is a potential selective inverse agonist of the cannabinoid-1 receptor which is implicated in the regulation of feeding behaviour. Hence, taranabant is being developed for the treatment of obesity. The synthesis depicted incorporates three key features: (1) a simple highly stereoselective synthesis of the vinyl tosylate (A → B); (2) an efficient synthesis of a tetrasubstituted enamide by palladium-catalyzed amidation (B → D); and (3) a highly efficient asymmetric hydrogenation to create two adjacent stereogenic centers in a single step (E → G).