Ruthenium-Catalyzed Chemo- and Enantioselective Hydrogenation of Isoquinoline Carbocycles

A chemoselective hydrogenation of isoquinoline carbocycles was achieved by using the catalyst prepared from Ru(methallyl)₂(cod) and trans-chelate chiral ligand PhTRAP. The unique chemoselectivity achieved in this hydrogenation could be ascribed to the trans-chelation of the chiral ligand. The procedure for preparing the catalyst strongly affects the reproducibility of the carbocycle hydrogenation. Various 5-, 6-, 7-, and 8-substituted isoquinolines were selectively hydrogenated at their carbocycles to afford 5,6,7,8-tetrahydroisoquinolines as major products in high yields with moderate or good enantioselectivities. Some mechanistic studies suggested that the stereogenic center was created during the initial addition of H₂ to the aromatic ring in the hydrogenation of 5-substituted isoquinolines. In other words, the stereochemical control was accompanied by the dearomatization.