Iridium-Catalyzed Asymmetric Hydrogenation of Aryl α-Chloro-β-keto Esters and Aryl Alkyl Ketones

An efficient and enantioselective Ir/Huaphos-catalyzed asymmetric hydrogenation system has been developed for the dynamic kinetic resolution (DKR) of aryl α-chloro-β-keto esters, furnishing anti-α-chloro-β-hydroxy esters in >99% ee and 98:2 dr at an exceptional substrate-to-catalyst ratio (S/C = 20,000). The same system also enables asymmetric hydrogenation of aryl alkyl ketones, delivering chiral 1-aryl aliphatic alcohols in up to 99% yield and >99% ee. Gram-scale syntheses of key intermediates to diltiazem and aprepitant further demonstrate the utility of this method for the highly stereoselective preparation of valuable chiral building blocks.