Ligand-Enabled Pd(II)-Catalyzed Enantioselective β-C(sp³)-H Arylation of Aliphatic Tertiary Amides.

Abstract

Amide is a widespread functional group in organic and bioorganic chemistry, and it is valuable to achieve stereoselective C(sp³)-H functionalization in amide molecules. Pd(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 Pd(II) catalysis. 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 could also provide an ideal solution to enantioselective C(sp³)-H activation in simple amides. Herein, we report an efficient asymmetric Pd(II)/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.