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% <i>ee</i> and 98:2 <i>dr</i> 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% <i>ee</i>. 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.