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. 2024 Sep 6;14(17):12806-12813.
doi: 10.1021/acscatal.4c03858. Epub 2024 Aug 9.

Ligand-Controlled Nondirected meta- or para-C-H Olefination of Silyl-Protected Phenols

Guangrong Meng  1 , Jie-Lun Yan  1 , Nikita Chekshin  1 , Daniel A Strassfeld  1 , Jin-Quan Yu  1
Affiliations

Ligand-Controlled Nondirected meta- or para-C-H Olefination of Silyl-Protected Phenols

Guangrong Meng et al. ACS Catal. .

Abstract

Recent advances in ligand design have enabled Pd(II)-catalyzed non-directed C-H functionalization using arenes as the limiting reagent, but achieving catalyst control over the site-selectivity in these transformations remains a significant challenge. Instead, selectivity is typically governed by the inherent steric and electronic properties of the arene substrates or directing effects. Consequently, it can be difficult to selectively functionalize para-position of electron-deficient arenes and meta-positions of electron-rich arenes respectively. In this report, we demonstrate that the choice of ligand in a Pd(II)-catalyzed olefination can switch selectivity between the activated para- and deactivated meta-C-H bonds of silyl-protected phenols, highly enabling site-selective functionalization of either position with broad substrate scopes. Specifically, monodentate 2-pyridone ligands enable high-yielding olefination with the conventional para-selectivity, largely governed by the intrinsic electronic bias of the substrate, whereas a dual-ligand system consisting of a bidentate pyridine-pyridone ligand and a monodentate pyridine ligand reversed the site selectivity to favor olefination of the relatively electron-deficient meta-position. Mechanistic studies indicate that the dual ligand system selectively renders para-C-H palladation reversible, but not the meta-C-H palladation, thereby favoring the meta-C-H olefination of electron-rich arenes.

Keywords: C−H activation; ligand design; non-directed; olefination; palladium; phenols.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1.
Scheme 1.
Pd(II)-Catalyzed Site-Selective C−H Activation of Phenols
Scheme 2.
Scheme 2.
Mechanistic Studies
Scheme 3.
Scheme 3.
Studies on the Role of the Silyl Group
See this image and copyright information in PMC

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