CuAAC

The synthesized CPMV-alkyne 42 was subjected to the CuAAC reaction with 38. Due to the strong fluorescence of the cycloaddition product 43 as low as 0.5 nM, it could be detected without the interference of starting materials. TMV was initially subjected to an electrophilic substitution reaction at the ortho-position of the phenol ring of tyrosine-139 residues with diazonium salts to insert the alkyne functionality, giving derivative 44 [100]. The sequential CuAAC reaction was achieved with greatest efficiency yielding compound 45, and it was found that the TMV remained intact and stable throughout the reaction. 

An improved strategy using microwave-assisted synthesis, involving a gallic acid core and copper-catalyzed [3+2] cycloaddition (CuAAc), afforded a series of glyco-dendrons.329 The straightforward synthesis of this series of glycodendrons was... 

A. Vecchi, B. Melai, A. Marra, C. Chiappe, and A. Dondoni, Microwave-enhanced ionothermal CuAAC for the synthesis of glycoclusters on a calix[4] arene platform, J. Org. Chem., 73 (2008) 6437-6440. 

Campidelli et al. have synthesized interesting linear and hyperbranched porphyrin polymers from CNTs via copper-catalyzed alkyne-azide cycloaddition (CuAAC) [122], Zinc porphyrin monomers containing an azide group and one or three alkyne groups were synthesized and chemically bound to alkyne functionalized SWCNTs via CuAAC. Depending upon the number of alkyne functionalities either linear (single alkyne) or dendrimer-like (triple alkyne) porphyrin polymers were produced (Fig. 5.9) [122],... 

CuAAC copper catalysed alkyne-azide cycloaddition... 

Hijazi, I., et al., Formation of Linear and Hyperbranched Porphyrin Polymers onto Carbon Nanotubes via CuAAC Grafting from" Approach. Journal of Materials Chemistry, 2012. 22(39) p. 20936. 

Keywords 1,2,4/1,2,3-Triazoles CuAAC cycloaddition Antimicrobial activity... 

The Cu -catalysed azide alkyne 1,3-dipolar cycloaddition (CuAAC) click chemistry has also been used to synthesize a library of a,/ -D-glucopyranosyl triazoles (iii). The synthesized triazoles proved to be potential glycosidase inhibitors [15]. 

Dedola S, Hughes DL, Nepogodiev SA et al (2010) Synthesis of a- and ) -D-glucopyranosyl triazoles by CuAAC click chemistry Reactant tolerance, reaction rate, product structure and glucosidase inhibitory properties. Carbohydr Res 345 1123-1134... 

C C CU AAC C CU -3 Possible 10-nucleotide sequence for synthesis of G-rich lagging strand S -CUAAT c cUAAC i-, ... 

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

Numerous appUcations of the CuAAC reaction reported during the last several years have been regularly reviewed [7-13], and are continually enriched by investigators in many fields [14]. We focus here on the fundamental aspects of the CuAAC process and on its mechanism, with an emphasis on the qualities of copper that enable this unique mode of reactivity. 

Scheme 10.1 Thermal cycloaddition of azides and alkynes usually requires prolonged heating and results in mixtures of both 1,4- and 1,5-regioisomers (A), whereas CuAAC produces only 1,4-disubstituted-...

A wide range of experimental conditions for the CuAAC have been employed since its discovery, underscoring the robustness of the process and its compatibility with most functional groups, solvents, and additives, regardless of the source of the catalyst. The most commonly used protocols and their advantages and limitations are discussed below, and representative experimental procedures are described at the end of this chapter. 

Scheme 10.2 A Oxidative coupling byproducts in the CuAAC reactions catalyzed excess of the catalyst reactions with...

Scheme 10.3 CuAAC-accelerating ligands of choice tris(l,2,3-triazolyl)methyl amine (TBTA), water-soluble analogues 11, sulfonated bathophenanthroline 12, tris(benzimidazole)methyl amine (TBiA) 13, and hybrid ligand 14.

Scheme 10.4 One-pot syntheses of triazoles from halides at (A, B) sp - and (q sp - carbon centers. Reaction B was performed in a flow reactor in 0.75 mm diameter Cu tubing with no added CuAAC catalyst.

Whatever the details of the interactions of Cu with alkyne during the CuAAC reaction, it is clear that Cu-acetylide species are easily formed and are productive components of the reaction mechanism. Early indications that azide activation was rate-determining came from the CuAAC reaction of diazide 15, shown in Scheme 10.5, which afforded ditriazole 17 as the predominant product, even when 15 was used in excess [113]. The same phenomenon was observed for 1,1-, and 1,2-diazides, but not for 1,4-, 1,5-, and conformationally flexible 1,3-diazide analogues. The dialkyne 18, in contrast to its diazide analogue 15, gave statistical mixtures of mono- and di-triazoles 19 and 20 under similar conditions. Independent kinetics measurements showed that the CuAAC reaction of 16 was slightly slower than that of 15, ruling out the intermediacy of 16 in the efficient production of 17. The Cu-triazolyl precursor 21 is, therefore, likely to be converted to 17 very rapidly. 

The initial computational treatment of the CuAAC focused on the possible reaction pathways available to mononuclear copper(l) acetylides and organic azides propyne and methyl azide were chosen for simplicity [23]. The key bond-making steps are shown in Scheme 10.6. Formation of Cu-acetylide 16 (step A) was calcu-... 

Scheme 10.6 (A) Early proposed catalytic cycle for the CuAAC reaction based on DFT calculations. (B) Introduction of a second copper(l) atom favorably influences the energetic profile of the reaction (L-H2O in DFT calculations). At the bottom are shown the optimized structures for dinuclear Cu...

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