Transition-Metal-Catalyzed C―H Bond Functionalization of Amines via Transient Directing Group Strategies

Ying Kang, Zhuoqi Li, Shiming Fan, Shouxin Liu

Prog Chem ›› 2026, Vol. 38 ›› Issue (5) : 870-887.

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Abbreviation (ISO4): Prog Chem      Editor in chief: Jincai ZHAO

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Prog Chem ›› 2026, Vol. 38 ›› Issue (5) : 870-887. DOI: 10.7536/PC20250811
Review

Transition-Metal-Catalyzed C―H Bond Functionalization of Amines via Transient Directing Group Strategies

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Abstract

Amines serve as crucial structural units in pharmaceuticals, functional materials, and natural products, and their efficient synthesis has always been a core topic in organic chemistry research. In recent years, transition-metal-catalyzed C―H bond activation has emerged as a highly efficient strategy for constructing complex amine derivatives. The core challenge in amine C―H bond functionalization lies in directing the transition metal to selectively cleave the target C―H bond. Direct use of the native amine group as directing groups often leads to catalyst deactivation and side reactions such as β-hydride elimination. While covalently linked directing auxiliaries enable precise activation, they require additional installation and removal steps, reducing synthetic efficiency. The recently developed transient directing group (TDG) strategies achieves selective activation of C―H bonds through reversible binding between the directing group and the substrate. This approach not only allows precise targeting of the desired C―H bond but also eliminates the need for pre-installation and removal of directing groups, significantly enhancing the atom economy and step economy of the reactions. This review systematically summarizes the progress in transition-metal-catalyzed C―H bond functionalization of amines via transient directing group strategies over the past decade. It focuses on the development and structural characteristics of different types of transient directing groups, and provides a detailed analysis of their applications in arylation, alkynylation, fluorination, oxidation, thiolation, and sulfonylation reactions. Additionally, the review discusses current limitations in the field, including reaction types, cost control, reaction conditions, and stereoselectivity, and prospects future directions such as the design of novel transient directing groups and the construction of new catalytic systems.

Contents

1 Introduction

2 Types and design strategies of transient directing groups

3 TDG-directed C―H functionalization of amines

3.1 Glyoxylic acid-type TDG-directed C―H functionalization of amines

3.2 Salicylaldehyde-type TDG-directed C―H functionalization of amines

3.3 2-Hydroxynicotinaldehyde-directed C―H functionalization of amines

3.4 Aza-aryl aldehyde-type TDG-directed C―H functionalization of amines

3.5 2-Benzoyl-4-chlorotrifluoromethanesulfonanilide directed selective arylation of amines

3.6 Acetal-type TDG-directed C―H functionalization of amines

3.7 Carbon dioxide-directed C―H functionalization of amines

3.8 Pivalaldehyde-directed C―H functionalization of amines

4 Conclusion and outlook

Key words

transient directing group / C―H activation / amine / transition metal / imine / functionalization

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Ying Kang , Zhuoqi Li , Shiming Fan , et al. Transition-Metal-Catalyzed C―H Bond Functionalization of Amines via Transient Directing Group Strategies[J]. Progress in Chemistry. 2026, 38(5): 870-887 https://doi.org/10.7536/PC20250811

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Funding

National Natural Science Foundation of China(21978067)
Natural Science Foundation of Hebei Province(H2020208030)
Excellent Going Abroad Expert’s Training Program in Hebei Province(201940)
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