Diastereoselective Heterogeneous Hydrogenation of Bicyclic Arenes Directed by Amines and Alcohols

The heterogeneous hydrogenation of aromatic compounds using supported metal catalysts is an efficient strategy to increase the three-dimensionality and molecular complexity of organic molecules. However, most heterogeneous hydrogenation methods lack stereoselectivity or rely upon the steric properties of the substrate for stereocontrol, which limit their predictability and generality for pharmaceutical synthesis applications. In this work, we develop two synthetic methods for the amine-and hydroxyl-directed hydrogenation of benzofused arenes using Rh/C and Pt 3 Cu/SiO 2 as heterogeneous catalysts, respectively. Mechanistic studies on the amine-directed reaction reveal that simultaneous adsorption of the amine and benzene functional groups to the Rh metal surface is extremely strong, outcompeting adsorption of the benzene or amine individually and enabling good turnover and high diastereoselectivity toward the amine-directed product. A broad scope of benzofused scaffolds are effective substrates, generating up to four stereocenters in a single step. The utility of the method is demonstrated in the synthesis of a novel chiral ligand, a pyridine bisoxazoline compound derived from perhydro- cis -aminoindanol, which shows enantioselectivity comparable to its aromatic counterpart in three model asymmetric reactions.