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

ABSTRACT

The (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.