Asymmetric Hydrogenation of Quinoxalines with Diphosphinite Ligands: A Practical Synthesis of Enantioenriched, Substituted Tetrahydroquinoxalines

Abstract

Leicht zugänglich ist ein chiraler Iridium‐(H8‐Binapo)‐Katalysator, der die hoch enantioselektive Hydrierung von Chinoxalinen bei hohen Substrat/Katalysator‐Verhältnissen von 100 bis 20 000 vermittelt. Die neue Methode dient als praktischer Ansatz für die Synthese optisch aktiver Tetrahydrochinoxalin‐Derivate (siehe Schema; cod=1,5‐Cyclooctadien).

Asymmetric Organocatalytic Tandem Cyclization/Transfer Hydrogenation: A Synthetic Strategy for Enantioenriched Nitrogen Heterocycles

“…A number of metal‐catalyzed [Eq. (1)]4a–j and one organo‐catalyzed asymmetric hydrogenation reactions [Eq. (2)]4k have been established by using either hydrogen gas or a Hantzsch ester (HEH) as hydride source.…”

Enantioselective Synthesis of Alcohols and Amines by Iridium‐Catalyzed Hydrogenation, Transfer Hydrogenation, and Related Processes

“…[57] This catalyst system had high activity (up to TOF 5620 h À1 and TON 18140), affording outstanding results with heteroaromatic substrates. A similar catalytic system with (S)-54 was used for the hydrogenation of quinoline derivatives affording ee values in the range of 87-97 %.…”

Iridium‐Difluorphos‐Catalyzed Asymmetric Hydrogenation of 2‐Alkyl‐ and 2‐Aryl‐Substituted Quinoxalines: A General and Efficient Route into Tetrahydroquinoxalines

“…In sharp contrast, asymmetric hydrogenation of challenging 2-aryl-substituted quinoxalines has scarcely been explored. The rare examples reported so far are limited to 2-phenylquinoxaline, 2-benzoA C H T U N G T R E N N U N G [1,3]diA C H T U N G T R E N N U N G oxolequinoxaline and 2-o'-MeO-phenylquinoxaline with ee values up to 84% ee using (R)-H 8 -Binapo, [13] up to 86% using (S)-PipPHOS, [14] and up to 65% ee using (R)-SegPhos. [15] We were interested in pursuing a research program on the iridium-promoted asymmetric hydrogenation of heteroaromatic compounds, and report herein the first general, highly efficient, catalytic asymmetric hydrogenation of a broad range of 2-aryl-substituted quinoxalines.…”

“…[10,11] Chan et al reported in 2006 the use of PQ-Phos ligands with ee up to 80% for asymmetric hydrogenation of MeQ, [12] and later, in 2009, an efficient Ir/H 8 -binapo system for asymmetric hydrogenation of 2-alkyl-substituted quinoxalines derivatives with 85 to 96% ee at low catalyst loading. [13] Simultaneously, de Vries, Feringa and Minnaard described an iridium-based catalyzed hydrogenation of 2-and 2,6-substituted quinoxalines using the monodentate phosphoramidite PipPhos ligand and piperidine hydrochloride as an additive with ee ranging from 75 to 96%. [14] However, these catalytic systems are mostly limited to 2-alkyl-substituted quinoxalines.…”