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

01 November 2022, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


Amide 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. 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 served as 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.


Pd catalysis
Ligand design
Aliphatic tertiary amides
Asymmetric C(sp3)-H activation

Supplementary materials

Supporting Information
Detailed experimental procedure, characterization data, XRD structures, details for DFT computation, and NMR spectra for the synthesized compound.


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