Catalytic Nucleophilic Aromatic Substitution Amination of 2-Aminopyridines with Amines

Jiajia Chen; Hang Shi

doi:10.1055/a-2538-1289

Synlett, Table of Contents

Synlett 2025; 36(10): 1289-1294
DOI: 10.1055/a-2538-1289

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Catalytic Nucleophilic Aromatic Substitution Amination of 2-Aminopyridines with Amines

Authors

Jiajia Chen

^aKey Laboratory of Precise Synthesis of Functional Molecules of Zhejiang Province, School of Science, Westlake University, 18 Shilongshan Road, Hangzhou 310030, Zhejiang Province, P. R. of China
Hang Shi ∗

^aKey Laboratory of Precise Synthesis of Functional Molecules of Zhejiang Province, School of Science, Westlake University, 18 Shilongshan Road, Hangzhou 310030, Zhejiang Province, P. R. of China

^bInstitute of Natural Sciences, Westlake Institute for Advanced Study, 18 Shilongshan Road, Hangzhou 310024, Zhejiang Province, P. R. of China

Abstract

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Abstract

Nucleophilic aromatic substitution (S_NAr) is a powerful strategy for rapid functional group transformations and has been applied extensively in arene functionalization. Electrophilic transition-metal-enabled π-coordination activation has emerged as a unique approach for catalyzing S_NAr reactions of benzene derivatives. Traditionally, heteroarenes are considered resistant to π-coordination with transition metals because of preferential binding of the heteroatom to the metal. In our recent work, we demonstrated a π-coordination activation strategy for aminopyridines using a ruthenium(II) catalyst to enable S_NAr reactions with amines as nucleophiles. The transient η⁶-pyridine complex serves as an electrophile, facilitating pyridyl C–N bond cleavage, and providing access to a diverse array of pyridylamines. Additionally, this method enables the incorporation of chiral and ¹⁵N-labeled amines, expanding its synthetic utility.

1 Introduction

2 Amination of Aminopyridines via η⁶-Coordination Catalysis

3 Conclusions and Perspectives

Key words

S_NAr - 2-aminopyridines - η⁶-coordination - amination - catalysis

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References

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