PALLADIUM-CATALYZED COUPLING OF OPTICALLY-ACTIVE AMINES WITH ARYL BROMIDES

The coupling of enantiomerically enriched amines with aryl bromides pr oduces the corresponding N-aryl derivatives. The choice of ligand in t he palladium-catalyzed coupling is critical to the formation of the an ilines without loss of enantiomeric purity. While LnPd (L = P(o-tolyl) (3)) successfully catalyzes the intramolecular aryl amination of alpha -subsituted optically pure amines, intermolecular coupling reactions w ith this catalyst system gives racemized products. In contrast, interm olecular N-arylations employing LnPd (L = (+/-)-BINAP) gives products in good yields with no erosion of enantiopurity. A mechanism for the o bserved racemization is proposed. The utility of the intramolecular pr ocess is demonstrated by the synthesis of 5, an intermediate in the fo rmal synthesis of 6, a potent ACE inhibitor.