Catalytic Nucleophilic Aromatic Substitution Amination of 2-Aminopyridines with Amines

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

Publikationsverlauf

Eingereicht: 27. Dezember 2024

Angenommen nach Revision: 12. Februar 2025

Accepted Manuscript online:
12. Februar 2025

Artikel online veröffentlicht:
01. April 2025

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