Chemistry Cu l -promoted Azide-Alkyne Cycloaddition

Click Chemistry Cu(l)-Promoted Azide-Alkyne [3 + 2] Cycloaddition 

3-dipolar cycloaddition reactions to unsaturated carbon-carbon bonds have been known for quite some time and have become an important part of strategies for organic synthesis of many compounds (Smith and March, 2007). The 1,3-dipolar compounds that participate in this reaction include many of those that can be drawn having charged resonance hybrid structures, such as azides, diazoalkanes, nitriles, azomethine ylides, and aziridines, among others. The heterocyclic ring structures formed as the result of this reaction typically are triazoline, triazole, or pyrrolidine derivatives. In all cases, the product is a 5-membered heterocycle that contains components of both reactants and occurs with a reduction in the total bond unsaturation. In addition, this type of cycloaddition reaction can be done using carbon-carbon double bonds or triple bonds (alkynes). 

Click chemistry reactions historically are done at elevated temperatures, and sometimes elevated pressures, to increase the rate of reaction and make the yield of heterocycle formation acceptable. However, it was discovered that in the presence of Cu(I), the reaction kinetics are 

The functional groups used for click chemistry conjugations are completely unreactive toward biological molecules and virtually free of side reactions, which otherwise would cause reagent 

Another source for Cu(I) in the click reaction is to use elemental copper metal filings, which generate Cu(I) ion in solution slowly by oxidation. This last option, however, is considerably slower in generating the necessary Cu(I) than the other methods and will result in reactions needing to be done for at least 24 hours. 

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