Ligand‐Enabled Palladium(II)‐Catalyzed Enantioselective β‐C(sp3)−H Arylation of Aliphatic Tertiary Amides**

Abstract

AbstractAmide is one of the most widespread functional groups in organic and bioorganic chemistry, and it would be valuable to achieve stereoselective C(sp3)−H functionalization in amide molecules. Palladium(II) catalysis has been prevalently used in the C−H activation chemistry in the past decades, however, due to the weakly‐coordinating feature of simple amides, it is challenging to achieve their direct C(sp3)−H functionalization with enantiocontrol by PdIIcatalysis. Our group has developed sulfoxide‐2‐hydroxypridine (SOHP) ligands, which exhibited remarkable activity in Pd‐catalyzed C(sp2)−H activation. In this work, we demonstrate that chiral SOHP ligands served as an ideal solution to enantioselective C(sp3)−H activation in simple amides. Herein, we report an efficient asymmetric PdII/SOHP‐catalyzed β‐C(sp3)−H arylation of aliphatic tertiary amides, in which the SOHP ligand plays a key role in the stereoselective C−H deprotonation‐metalation step.