Enantioselective Reduction of Nitrogen‐Based Heteroaromatic Compounds

Abstract

Optically active amines are fundamentally important synthetic intermediates and structural components of biologically active natural products, drugs, and pharmaceuticals. Asymmetric hydrogenation of nitrogen-based heteroaromatic compounds is one of the most attractive and efficient approaches to enantiomerically pure amines, especially for numerous saturated or partially saturated chiral cyclic amines, whose synthesis by direct cyclization is often difficult. In the past decades, some progresses have been achieved in the hydrogenation of nitrogen-containing heteroaromatic compounds [1]. For example, quinolines, quinoxalines, pyridines, indoles, and pyrroles have been hydrogenated successfully with over 90% enantiomeric excess (ee). In this chapter, we focus on the synthesis of chiral amines via enantioselective hydrogenation of nitrogen-based heteroaromatic compounds. Asymmetric Hydrogenation of Quinolines Ir-and Ru-Catalyzed Asymmetric Hydrogenation of QuinolinesAmong these studies on asymmetric hydrogenation of nitrogen-based heteroaromatic compounds, the hydrogenation of quinolines was studied extensively and elaborately. In 2003, Zhou and coworkers reported the first highly enantioselective hydrogenation of quinolines with high enantioselectivities [2]. They employed [Ir(COD)Cl] 2 /MeO-BiPhep as catalyst using iodine as additive, while the hydrogenation reaction could not take place in the absence of iodine. Their studies showed that this reaction was highly solvent dependent, and toluene was the best solvent.Subsequently, some commercially available chiral bidentate phosphine ligands were tested for the asymmetric hydrogenation of quinolines, and (S)-MeO-BiPhep was the best ligand with 94% ee (Scheme 10.1). The optimal conditions are [Ir(COD) Cl] 2 /MeO-BiPhep/I 2 in toluene at 700 psi H 2 .

Application of Phosphine-Phosphite Ligands in the Iridium Catalyzed Enantioselective Hydrogenation of 2-Methylquinoline

“…The catalytic asymmetric hydrogenation of quinolines to produce optically active tetrahydro-quinolines is a very interesting reaction due to the importance of the resulting products. For instance, chiral tetrahydroquinolines are ubiquitous products in Nature ( Figure 1 ) which exhibit, in addition, a wide range of biological properties of interest to the pharmaceutical industry [ 6 , 7 , 8 , 9 , 10 , 11 , 12 ]. A variety of catalytic systems, mostly based on Ir complexes and chiral chelating ligands with either equivalent( C 2 symmetric) or non equivalent ( C 1 symmmetric) coordinating functions, have provided satisfactory results for this transformation.…”