General Aspects of the CuAAC Reaction

The Huisgen 1,3-dipolar cycloaddition to triazoles can be performed under copper-catalysis and is then known as Copper-Catalyzed Azide-Alkyne Cycloaddition 

As the Huisgen reaction is very slow in forming triazoles at room temperature, the use of a copper catalyst accelerates the cycloaddition up to approximately 10 times and enables reactions in aqueous systems. Moreover, the advanced cycloaddition offers several supplementary advantages that are characteristic of Chck chanistry. While former uncatalyzed transformations to triazoles always yielded a mixture of the 1,4- and 1,5-regio-isomers, the CuAAC produces only 1,4-triazoles. These l,4-disubstituted-l,2,3-triazoles are produced with excellent yields and purities (for other appUcations see also ref. ). Furthermore, the formation of triazoles is nearly independent of the substituents of both reaction partners. Neither substituents with sterical nor electronical effects have great influence on the outcome of the CuAAC reaction.  

The active copper species in these transformations is Cu(I), but Cu(0) and Cu(II)-species may be used as well, depending on the chemical and biological environment and the required reaction conditions. Cu(II) salts are the catalysts that are most often selected for Click chemistry, as they can be easily reduced in situ to Cu(T) in the presence of 

Cu(0) catalyzes Click reactions indirectly via the formation of Cu(l) by compropor-tionation of Cu(II) and Cu(0). The essential Cu(ll) species can be added in the form of copper salts, but it is not mandatory due to the presence of traces of copper oxides and carbonates on the metal surface. Although this method benefits from very low copper contamination, high selectivity and the isolation of pure triazoles in high yields, the Cu(0)-catalyzed Click reaction is disadvantageous because of prolonged reaction times. 

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