title: General asymmetric hydrogenation of 2-alkyl- and 2-aryl-substituted quinoxaline derivatives catalyzed by iridium-difluorphos: unusual halide effect and synthetic application.
abstract: A general asymmetric hydrogenation of a wide range of 2-alkyl- and 2-aryl-substituted quinoxaline derivatives catalyzed by an iridium-difluorphos complex has been developed. Under mild reaction conditions, the corresponding biologically relevant 2-substituted-1,2,3,4-tetrahydroquinoxaline units were obtained in high yields and good to excellent enantioselectivities up to 95%. With a catalyst ratio of S/C = 1000 and on a gram scale, the catalytic activity of the Ir-difluorphos complex was maintained showing its potential value. Finally, we demonstrated the application of our process in the synthesis of compound (S)-9, which is an inhibitor of cholesteryl ester transfer protein (CETP).
authors.affiliation: ENSCP Chimie ParisTech, Laboratoire Charles Friedel (LCF), 75005 Paris, France.
authors.forename: Damien
authors.initials: D
authors.lastname: Cartigny
authors.forename: Farouk
authors.initials: F
authors.lastname: Berhal
authors.forename: Takuto
authors.initials: T
authors.lastname: Nagano
authors.forename: Phannarath
authors.initials: P
authors.lastname: Phansavath
authors.forename: Tahar
authors.initials: T
authors.lastname: Ayad
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Genêt
authors.forename: Takashi
authors.initials: T
authors.lastname: Ohshima
authors.forename: Kazushi
authors.initials: K
authors.lastname: Mashima
authors.forename: Virginie
authors.initials: V
authors.lastname: Ratovelomanana-Vidal
mesh_terms: D002384:Catalysis; D053480:Cholesterol Ester Transfer Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis* / Q000737:chemistry; D006865:Hydrogenation; D007495:Iridium / Q000737:chemistry*; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D011810:Quinoxalines / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D053480:Cholesterol Ester Transfer Proteins; D006845:Hydrocarbons, Fluorinated; D009942:Organometallic Compounds; D011810:Quinoxalines; D007495:Iridium