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.