Ruthenium-Catalyzed Azide Alkyne Cycloaddition Reaction: Scope, Mechanism, and Applications

Abstract

The ruthenium-catalyzed azide alkyne cycloaddition (RuAAC) affords 1,5-disubstituted 1,2,3-triazoles in one step and complements the more established copper-catalyzed reaction providing the 1,4-isomer. The RuAAC reaction has quickly found its way into the organic chemistry toolbox and found applications in many different areas, such as medicinal chemistry, polymer synthesis, organocatalysis, supramolecular chemistry and the construction of 2 electronic devices. This review discusses the mechanism, scope and applications of the RuAAC reaction, covering the literature during the last 10 years. CONTENTS

Ruthenium‐Catalyzed Azide–Thioalkyne Cycloadditions in Aqueous Media: A Mild, Orthogonal, and Biocompatible Chemical Ligation

“…[13] In contrast to the CuAAC, which encompasses dinuclear copper intermediates such as I and II, [14] the ruthenium-promoted reaction involves intermediate species like III,w hich evolve into IV by oxidative cyclometalation, and eventually to the triazole products.…”

“…[10] Several azide-alkyne cycloadditions using metals other than copper have been described in recent years, [11] but only the ruthenium variant (RuAAC) [12] has shown am eaningful scope (Scheme 1b). [13] In contrast to the CuAAC, which encompasses dinuclear copper intermediates such as I and II, [14] the ruthenium-promoted reaction involves intermediate species like III,w hich evolve into IV by oxidative cyclometalation, and eventually to the triazole products.…”

“…[16,13] Recent data suggest that some ruthenium complexes can promote the process in water, but the reactions require thermal activation and present alimited scope. [17] Herein, we demonstrate that certain ruthenium(II) complexes can indeed catalyze the cycloaddition between azides and alkynes in water, and at room temperature.Importantly, …”

“…[10] Several azide-alkyne cycloadditions using metals other than copper have been described in recent years, [11] but only the ruthenium variant (RuAAC) [12] has shown am eaningful scope (Scheme 1b). [13] In contrast to the CuAAC, which encompasses dinuclear copper intermediates such as I and II, [14] the ruthenium-promoted reaction involves intermediate species like III,w hich evolve into IV by oxidative cyclometalation, and eventually to the triazole products. [15] In keeping with this scenario,the RuAAC, essentially developed in organic solvents,t olerates disubstituted alkynes but can produce mixtures of regioisomers.Probably,the notion that it is not compatible with water and air atmospheres has precluded more biofocused investigations.…”

“…[15] In keeping with this scenario,the RuAAC, essentially developed in organic solvents,t olerates disubstituted alkynes but can produce mixtures of regioisomers.Probably,the notion that it is not compatible with water and air atmospheres has precluded more biofocused investigations. [16,13] Recent data suggest that some ruthenium complexes can promote the process in water, but the reactions require thermal activation and present alimited scope. [17] Herein, we demonstrate that certain ruthenium(II) complexes can indeed catalyze the cycloaddition between azides and alkynes in water, and at room temperature.Importantly, At the outset, we were inspired by areport of Jia, Sun, and co-workers on an iridium-promoted azide-thioalkyne cycloaddition.…”