CuAAC Ligand Synthesis

Figure 2.11 Synthesis of an alkyne side functional polymer and introduction of azido sugar ligands via CuAAc. ...

Figure 2.13 Solid phase polymer synthesis of monodisperse sequence-defined glycooligomers using CuAAc to attach sugar ligands on the polymer backbone. to...

Kumar and co-workers reported an efficient ligand-free copper-catalyzed tandem azidealkyne cycloaddition (CuAAC), Ullmann-type C-N coupling, and intramolecular direct arylation in a single step for the synthesis of stmcturally complex and novel 1,2,3-triazole-fused imidazo-[l,2-a] pyridines 42 (Scheme 7.23) [84]. This protocol shows high generality and functional group tolerance, which provides a concise method for the preparation of fused triazoles derivatives. 

The position of copper(I) salts as quite soft Lewis acids has resulted in a significant number of publications where soft phosphorus- and sulfur-containing ligands have been used and shown to enhance the catalytic process in CuAAC reactions. A variety of phosphorus-containing ligands has been used to produce significant rate enhancements or improved efficiency in CuAAC reactions. Examples include the use of triphenylphosphine-copper(I) bromide [137] (e.g., in the synthesis of dendrimers [138]), phosphoramidites [139], and bis(triphenylphosphine)-copper(I) carboxylates [140]. In addition, triethylphosphite-copper(I) iodide complexes have been used in sugar chemistry [141]. 

Because of its modularity, high yields, simple reaction conditions, and purification procedures, the CuAAC has been especially suitable for the synthesis of a large number of modified nucleosides, nucleotides, and nucleic acids with a wide range of applications. Its use in biological systems was, for a while, limited by the inherent toxicity of Cu in cells. The use of Cu(I)-stabilizing ligand, but... 

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