Azide-alkyne cycloaddition copper-catalyzed

Sharpless and coworkers pubhshed a paper in 2002 (Rostovtsev et al., 2002) where the formation of 1,23-triazoles by the Cu(l)-catalyzed Huisgen 1,3-dipolar cycloaddition reaction between alkyl/aryl azides and non-activated alkynes was described as a chck reaction in contrast to the purely thermal (imcatalyzed) azide-alkyne chck reaction which refers to the 13-dipolar cycloaddition reaction between alkyl/aryl azides and strongly activated alkynes. The Cu(l)-catalyzed 

The mechanism of the CuAAC reaction was rst proposed by Meldal (Tomoe et al., 2002) and Sharpless (Rostovtsev et al., 2002) and later veri ed by computational methods by Sharpless (Himo et al., 2005) in a series of papers. The proposed catalytic cycle based on a concerted mechanism via a Cu-acetylide intermediate is shown in Fig. 12.7. The most effective variant of the catalyzed 1,3-dipolar azide-alkyne cycloaddition system uses terminal alkynes in combination with copper sulfate and sodium ascorbate. The sodium ascorbate reduces copper sulfate to Cu(I), which forms a Cu-acetylide by reaction with the terminal alkyne via an initial r-complex formation. The copper acetyhde formed is considerably more reactive toward the azide so that a rate enhancement of the 1,3-dipolar cycloaddition results (Englert et al., 2005). 

Though in case of the azide-alkyne 13-dipolar cycloaddition process, exclusively Cu(l) catalysts have been used (in 0.25-2 molcatalysts (Ru, Ni, Pd, and Pt salts) have also been employed. For Cu(l) catalysts, most methods directly use Cu(T) salts, while other methods generate Cu(I) by reduction of Cu(ll) salts with sodium ascorbate or metallic copper. The catalyzed cycloaddition reaction is experimentally simple, perfecdy rehable, quantitative, proceeds well in aqueous solutions under ambient conditions without protection from oxygen, requires only stoichiometric 

Hawker and Wooley (Joralemon et al., 2005) later extended the CnAAC reaction to prepare dendrimers in a divergent fashion. The divergent method of synthesis generally involves serial 

These reactions have also been performed in ionic liquids, as reported by Wang and Yan [71]. The system Cul/amino 

SCHEME 337 1,4-Substituted 1,2,3-triazoles synthesis using a silica-immobilized copper-based catalyst. 

SCHEME 3.38 Synthesis of 1,4-substituted 1,2,3-tiiazoles by CuAAC in ionic liquid media. 

This methodology was subsequently applied to the synthesis of related amidine compounds [74], including phosphorus amidines [75], benzoxazoline-amidines [76], and benzimidazoles [77], 

These Cn-catalyzed MCRs were further extended with the incorporation of different nucleophiles such as water [78], 

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Gramlich PME, Wirges CT, Manetto A, Carell T (2008) Postsynthetic DNA modification through the copper-catalyzed azide-alkyne cycloaddition reaction. Angew Chem Int Ed... 

Diaz, D.D., Punna, S., Holzer, P., Mcpherson, A.K., Sharpless, K.B., Fokin, V.V. and Finn, M.G. (2004) Click chemistry in materials synthesis. 1. Adhesive polymers from copper-catalyzed azide-alkyne cycloaddition. J. Polym. Sci. Polym. Chem., 42, 4392. 

Copper-Catalyzed Azide-Alkyne Cycloaddition (CuAAC)... 

Copper-catalyzed azide-alkyne cycloaddition producing only 1,4-disub-stituted-1,2,3-triazoles at room temperature in excellent yields 07AA7. 

Rinaldi L, Martina K, Baricco F, Rotolo L, Cravotto G. Solvent-free copper-catalyzed azide-alkyne cycloaddition under mechanochemical activation. Molecules 2015 20 2837 9. 

Diaz DD, Punnas Holzer P et al (2004) Click chemistiy in materials synthesis. 1. Adhesive polymers from copper-catalyzed azide-alkyne cycloaddition. Polym Sci Part A Polym Chem... 

CuAAC Copper-catalyzed azide-alkyne cycloaddition... 

Advancements in the mechanistic understanding of the copper-catalyzed azide—alkyne cycloaddition 13BJ02715. 

Hein, J. E. and Fokin, V. V. 2010. Copper-catalyzed azide-alkyne cycloaddition (CuAAC) and beyond New reactivity of copper(I)acetylides. Chem. Soc. Rev. 39(4) 1302-1315. 

Hong V, Presolski SI, Ma C, Finn MG (2009) Analysis and optimization of copper-catalyzed azide-alkyne cycloaddition for bioconjugation. Angew Chem Int Ed 48 9879-9883... 

Copper-catalyzed azide-alkyne cycloaddition (CuAAC) is one of the most powerful click reactions. The only disadvantage is that the copper is toxic to certain cells [90]. Despite efforts to make the copper complexes more biocompatible [91, 92], the breakthrough was achieved by the Bertozzi group [93] through harnessing the ring strain present in cyclooctyne to accelerate the reaction. A variety of cyclooctynes and one cycloheptyne have subsequently been reported [94, 95]. 

A copolymer bearing proline and permethylated p-CD was used as catalyst in aldol condensation [23]. The linear copolymer bearing both pendant permethylated p-CD and proline groups was designed on the basis that the hydrophobic cavity of the CDs could approach the substrates close to the proline that acted as catalyst through host-guest interactions. The synthesis of the CD monomer was carried out by a copper-catalyzed azide-alkyne cycloaddition. The CD monomer was then polymerized with a protected hydroxyproline methacrylate to give the linear polymer with a monomer ratio proline/CD of 4.The Me-p-CD-Pro polymer was subsequently obtained after acid deprotection of proline (Scheme 2.9). 

Figure 14.15 Copper-catalyzed azide-alkyne cycloaddition reaction of arginine-glydne-...

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