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CLICK CHEMISTRY
Alkynes and azides can undergo a Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC; 1st Generation Click Chemistry) to afford 1,4-disubstituted 1,2,3-triazoles. Developed by K. Barry Sharpless and Morton Meldal, this type of chemical transformation was quickly dubbed “Click Chemistry”. As alternative, the so-called strain-promoted azide-alkyne cycloaddition (SPAAC; 2nd Generation Click Chemistry) is widely utilized as copper-free click reaction. Besides, tetrazine ligation represents the option for a copper-free, rapid, and fully biorthogonal type of Click Chemistry based on an inverse electron-demand Diels-Alder (IEDDA; 3rd Generation Click Chemistry) cycloaddition reaction between a tetrazine and a strained alkene.
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