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

Rongxing Zhang, Qinghai Zhou, Xin Wang, Lanting Xu, Dawei Ma

2023Angewandte Chemie International Edition24 citationsDOI

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.

Topics & Concepts

AlkylChemistryAmideArylCatalysisEnantioselective synthesisOrganic chemistryDenticityCombinatorial chemistryMedicinal chemistryMetalAsymmetric Synthesis and CatalysisAdvanced Synthetic Organic ChemistryCatalytic C–H Functionalization Methods
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