Revisiting the Gold-Catalyzed Dimerization of 2-Ethynylanilines: A Room-Temperature and Silver-Free Protocol for the Synthesis of Multifunctional Quinolines

Dedicated to Professors Vèronique Michelet and Virginie Ratovelomanana-Vidal with friendship and respect for their contributions to transition-metal catalysis.

Abstract

A room temperature and silver-free protocol for the formation of quinolines from 2-ethynylanilines through a dimerization event was achieved using a dinuclear gold catalyst, Au₂(BIPHEP)(NTf₂)₂. The reaction is inherently modular, allowing for the incorporation of peripheral substituents at any site of the quinoline product. The reaction is readily applied to other heterocyles also as exemplified by the preparation of naphthyridines. Competition reactions to determine the reactivity of dissimilar alkynes demonstrated that the product ratio of dimerization vs intermolecular addition is rather dependent on the electronic nature of aryl substituent on the alkynes. However, control experiments with substrates possessing internal alkynes resulted in cycloisomerization instead of expected dimerization, which is indicative of possible steric influence of the alkyne terminus in the reaction outcome.

Key words

2-ethynylanilines - dimerization - quinolines - atom-economy - dinuclear gold complex - silver-free approach - competition reactions

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