Diastereo- and Enantioselective Synthesis of Structurally Diverse Succinate, Butyrolactone, and Trifluoromethyl Derivatives by Iridium-Catalyzed Hydrogenation of Tetrasubstituted Olefins

A highly efficient iridium N,P-ligand-catalyzed asymmetric hydrogenation of functionalized tetrasubstituted olefins lacking a directing group has been developed. Various structural diverse chiral succinate derivatives were obtained in high yields and excellent enantio- and diastereoselectivities (up to 99% ee) using 0.5-1.0 mol % catalyst loadings. This stereoselective reaction is applicable for the synthesis of chiral acyclic molecules (up to >99% ee) having two contiguous stereogenic centers and is compatible with various aromatic, aliphatic, and heterocyclic systems, a variety of functional groups of different electronic nature. Furthermore, this asymmetric protocol allows a short enantioselective route to the butyrolactone building block, an intermediate in the synthesis of anticancer agent BMS-871 and pharmaceuticals (2S)-(-)-Verapamil and (2S)-(-)-Gallopamil.