A detailed study of the diastereoselective catalytic hydrogenation of 6-hydroxytetrahydroisoquinoline-(3R)-carboxylic ester intermediatesElectronic supplementary information (ESI) available: Synthesis of substrates, analytical methods, hydrogenation procedures, details of kinetic model. See DOI: 10.1039/c2cy20251d

A key step towards a highly-selective antagonist of ionotropic glutamate receptors entails the diastereoselective arene hydrogenation of an enantiopure tetrahydroisoquinoline. An extensive screen using parallel reactors was conducted and led to the discovery of several Pd/C catalysts giving high yield and improved diastereoselectivity from 75 : 25 to 95 : 5. A detailed kinetic study of the best system was performed and supports the reduction occuring in two-steps. High facial selectivity in the aromatic hydrogenation of a tetrahydroisoquinoline system allowed a 40% yield improvement in a drug candidate synthesis.