Copper-Catalyzed Asymmetric Hydrogenation of Aryl and Heteroaryl Ketones

High throughput screening enabled the development of a Cu-based catalyst system for the asymmetric hydrogenation of prochiral aryl and heteroaryl ketones that operates at H-2 pressures as low as 5 bar. A ligand combination of (R,S)-N-Me-3,5-xylyl-BoPhoz and tris(3,5-xylyl)phosphine provided benzylic alcohols in good yields and enantioselectivities. The electronic and steric characteristics of the ancillary triarylphosphine were important in determining both reactivity and selectivity.