Asymmetric Hydrogenation of Cyclic Imines and Enamines: Access to 1,5-Benzodiazepine Pharmacophores

Abstract

A new strategy towards the pharmacologically relevant class of dihydro-1,5-benzodiazepines was developed by applying a rhodium-catalyzed asymmetric hydrogenation. The approach represents an efficient protocol providing access to the optically active products in excellent yields (up to 99%) and with high enantioselectivities (up to 92% ee). The versatility of the methodology was demonstrated by a broad substrate scope including alkyl, aryl, and heteroaryl substituents as well as halides. Furthermore, investigations regarding the reaction mechanism were performed and unraveled a preferred reaction of the tautomeric enamine in the rhodium-catalyzed asymmetric hydrogenation.