General Asymmetric Hydrogenation of 2-Alkyl- and 2-Aryl-Substituted Quinoxaline Derivatives Catalyzed by Iridium-Difluorphos: Unusual Halide Effect and Synthetic Application

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).