Enantioselective synthesis of chiral tetrahydroisoquinolines by iridium-catalyzed asymmetric hydrogenation of enamines

Abstract

Chiral iridium complexes based on spiro phosphoramidite ligands are demonstrated to be highly efficient catalysts for the asymmetric hydrogenation of unfunctionalized enamines with an exocyclic double bond. In combination with excess iodine or potassium iodide and under hydrogen pressure, the complex Ir/(Sa,R,R)-3a provides chiral N-alkyltetrahydroisoquinolines in high yields with up to 98% ee. The L/Ir ratio of 2:1 is crucial for obtaining a high reaction rate and enantioselectivity. A deuterium labeling experiment showed that an inverse isotope effect exists in this reaction. A possible catalytic cycle including an iridium(III) species bearing two monophosphoramidite ligands is also proposed. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.