Applications CuAAC reaction

The CuAAC reaction has been applied to a remarkable array of problems in synthetic chemistry, chemical biology, materials science, and other fields. A comprehensive or even representative list is beyond the scope of this chapter. Instead, we will highlight two examples involving metallic copper as the source of CuAAC catalyst. While decidedly not typical in the body of CuAAC applications in the literature, we believe that this most convenient form of this inexpensive metal should receive greater attention in azide-aUcyne ligation reactions. We also hope that these examples will give the reader some indication of the facility with which the CuAAC process can be applied. 

Numerous applications of the CuAAC reaction reported during the last several years have been regularly reviewed [5-12], and are continously enriched by investigators in many fields. 

On the basis of the wide catalytic applications of NHC transition metal complexes [25], Nolan and coworkers have thoroughly studied the catalytic activity in CuAAC reactions of well-defined copper(I) complexes with general formula [CuX(NHC)]. Organic solvents, mixtures of EtOH/water, and pure water have been used as reaction media. In particular, it has been reported that complexes [CuBr(SIMes)] (1 in Fig. 15.1, SIMes=iVAf-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene)) and [CuI(IAd)] (2 in Fig. 15.1, IAd=iVAf-adamantyl imidazol-2-ylidene) show a remarkable activity for the synthesis of a... 

Miguel et al. [56], in 2011, reported the application of triazole bridges created from the CuAAC reaction for the preparation of donor-acceptor conjugates, bearing zinc(II)porphyrins and fuUerenes (ZnP-Tri-Cgg), designed for artificial photosynthetic applications. It was found that the triazole bridge is excellent for efficient photoinduced electron transfer between a remote electron donor and acceptor moiety. 

Scheme 9.22 Use of the CuAAC reaction for the synthesis of triazole-Cinchona hybrids for catalysis and medicinal applications, as described by Burke and coworkers (P.C. Barrulas, L. Alves, AJ. Burke, unpMished results) [60],...

In addition to the broad application of the CuAAC reaction, other types of highly efficient click reactions were used for the synthesis of star-shaped polymers. Tunca and coworkers used the Diels-Alder click reaction for the preparation of 3-arm star-shaped polymers using furan protected maleimide end-fiinctionalized PEO, PMMA or PtBuA and trianthracene functional linking agents (Dag et al., 2008). However, the resulting yields are comprised between 82 and 93% depending on the coupled polymer, the reaction conditions are more drastic than those used in CuAAC. 

Due to the high cytotoxicity of Cu(I) ion and the difficulty in completely removing it after the CuAAC reaction, it becomes highly desirable to promote the [2-1-3] cycloaddition between the acetylene and the azide under Cu ion-free conditions. In this coimection, Kiser reported the in situ preparation of cross-linked hydrogels by using a Cu(I)-free Huisgen cycloaddition between an azide-functionalized methacrylate polymer 37 and an activated diacetylene 38 (Scheme 11) [51]. However, even with 38 as the activated dipolarophile, the rate of cross-linking was still too slow (10% completion in 49 h at 24°C) to be useful in most in situ applications. 

Thus far, our focus has been on polymers that are prepared via the CuAAC reaction or those that bear clickable units primarily at the chain ends in this section, we focus on another important application of CuAAC reaction, namely side-chain clickable polymers. These are polymers that bear either pendant propargyl or azide groups and can be clicked, post-polymerization, to access a wide variety of polymeric structures one example that was earlier described was the dendronized... 

Another important applications of CuAAC reaction is its utility in surface modifications of a variety of substrates using small molecules and for the preparation of densely grafted polymeric brushes. The first demonstration of surface modification using click chemistry was by Collman et al., they utilized a m-azido alkanethiol, along with a simple alkanethiol, to first modify the surface of a gold-coated electrode by the formation of a self-assembled monolayer (SAM) and subsequently used CuAAC reaction with a suitable Ferrocene derivative... 

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