Copper‐Catalyzed Asymmetric Arylation of α‐Substituted Cyanoacetates Enabled by Chiral Amide Ligands

Abstract

AbstractThe (S)‐nobin‐embodied picolinamide and L‐hydroxyproline‐derived amide are effective ligands for Cu‐catalyzed enantioselective coupling reaction of (hetero)aryl iodides with α‐alkyl substituted cyanoacetates. This arylation reaction gave α‐(heteroaryl)‐α‐alkyl cyanoacetates in good to excellent enantioselectivities (up to 95 % ee). A variety of functionalized (hetero)aryl and alkyl groups could be introduced to the quaternary center and therefore provided a valuable tool for preparing enantioenriched compounds with an all‐carbon quaternary center tethered with convertible functional groups. The size of both α‐alkyl and ester groups was proven as the key factor for asymmetric induction.