A detailed study of the diastereoselective catalytic hydrogenation of 6-hydroxytetrahydroisoquinoline-(3R)-carboxylic ester intermediates

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.