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.