Asymmetric Hydrogenation of Quinoxalines

In 2003, Henschke and coworkers described asymmetric hydrogenation of 2 methylquinoxaline with Noyori s catalyst RuCl2(diphosphine)(diamine). In most case, moderate enantioselectivities and excellent conversions were obtained within 20h with S/C 1000/1 [45]. The combination of Xyl HexaPHEMP and (S,S) DACH afforded the best enantioselectivity (73% ee) with full conversion. 

Recently, Chan prepared Ir PQ Phos complex and applied it to the catalytic enantioselective hydrogenation of 2 methylquinoxaline [8], and up to 80% ee was obtained in THF with full conversion in the presence of I2. 

---

Chiral NHC-Ru complexes have been successfully involved in the asymmetric hydrogenation of quinoxalines. Complete conversions have been achieved but ees remained under 90%. 

Binol-derived phosphoroamidite PipPhos (19) has been successfully used as a ligand for the Ir-catalyzed asymmetric hydrogenation of 2- and 2,6-substituted quinolines [39], 2- and 2,6-substituted quinoxalines [40], and IV-aryl imines [41] (Fig. 16). 

BIS(TERT-BUTYLMETHYLPHOSPfflNO)QUINOXALINE (QuinoXP ) AS A LIGAND FOR RHODIUM-CATALYZED ASYMMETRIC HYDROGENATION OF PROCHIRAL AMINO ACID AND AMINE DERIVATIVES... 

ASYMMETRIC HYDROGENATION OF METHYL (E)-3-ACETYLAMINO-2-BUTENOATE CATALYZED BY Rh(I)-(R,R)-2,3-BIS(tert-BUTYLMETHYLPHOSPHINO)QUINOXALINE... 

Recent advances in asymmetric hydrogenation of heteroaromatic compounds (quinoxaline, pyridine, and furan derivatives) 05CJO634. 

Chiral NHC ligands allowed the challenging asymmetric hydrogenation of the carbo-cyclic ring of quinoxalines, yielding enantioenriched 5,6,7,8-tetrahydroquinoxalines with an enantiomeric ratio of up to 94 6 in the presence of n-hexane and toluene in the presence of KOBu ... 

Recently, the first example of asymmetric hydrogenation of thiophenes and benzothiophenes was reported by Glorius and coworkers (Scheme 3.12) [31]. High levels of reactivities (up to 99%) and enantioselectivities (up to 98% ee) were achieved by in situ generation of the catalyst from 23 and [Ru(COD)(2-methylallyl)2]. Qrmpared to the reduction of quinoxalines and benzofurans. 

SCHEME 13.19 Asymmetric homogeneous hydrogenation of quinoxalines catalyzed by ruthenium A-heterocyclic carbene complexes. 

Fan et al. have successfully developed an efficient metal/ Bronsted acid (261) relay catalysis system for highly enantioselective hydrogenation of quinoxalines (374) through a convergent asymmetric disproportionation of dihydroquinoxalines (375) to chiral tetrahydroquinoxalines (377) with up to 94% ee (Scheme 99). ... 

---