Cycloadditions of azide and alkyne

A microwave-assisted three-component reaction has been used to prepare a series of 1,4-disubstituted-1,2,3-triazoles with complete control of regiose-lectivity by click chemistry , a fast and efficient approach to novel functionalized compounds using near perfect reactions [76]. In this user-friendly procedure for the copper(l) catalyzed 1,3-dipolar cycloaddition of azides and alkynes, irradiation of an alkyl halide, sodium azide, an alkyne and the Cu(l) catalyst, produced by the comproportionation of Cu(0) and Cu(ll), at 125 °C for 10-15 min, or at 75 °C for certain substrates, generated the organic azide in situ and gave the 1,4-disubstituted regioisomer 43 in 81-93% yield, with no contamination by the 1,5-regioisomer (Scheme 18). 

The kinetically driven copper(I)-catalyzed cycloaddition of azides and alkynes requires hours of reaction time to obtain quantitative yields [63]. However, in the case of no-carrier added radiochemical synthesis the ratio of reactants and catalysts differs considerably from that in traditional chemistry. In particular, the azide component and catalyst are in huge excess compared with the [18F]fluoroalkyne. The quantitative incorporation of [18F]fluoroalkyne could be achieved in 10 minutes when an optimized catalytic system was used [81]. Re versed-phase HPLC analysis of all 18F-labeled peptides showed only a single product, indicating that the reaction proceeded regioselectively to yield 1,4-disubstituted 1,2,3-triazoles as previously reported [64]. 

The discovery at the beginning of this century of the Cu(I) catalytic and re-gioselective effect in the 1,3-dipolar cycloaddition of azide and alkynes [5,6] has initiated a golden era for this cycloaddition reaction that has found multiple applications in biomedical science, organic synthesis, and material science [7,8]. A vast majority of these results involved the use of carbohydrates. The present review is focused on the recent advances concerning the non-catalytic and catalytic azide-alkyne conjugation in the carbohydrate field. 

The outstanding characteristics mentioned for both the imcatalyzed and the catalyzed reactions have led to the 1,3-dipolar cycloadditions of azide and alkynes being considered the most efficient reaction under the new concept of click chemistry [ 12], The term coined by Sharpless and coworkers refers to a modular synthetic approach based on a set of the most practical end rehable chemical reactions. These are wide in scope, highly efficient in terms of both conversion and selectivity under very mild and simple reaction conditions, and use simple product isolation procedures. An indicative parameter of the importance of the 1,3-dipolar cycloaddition of azide and alkyne as a prototype of a click chemistry reaction is the exponential number of applications based on this reaction that have appeared in the literature since the description in 2002 of the catalyzed version. Currently, it can be asserted that click chemistry and the Huisgen 1,3-dipolar cycloaddition of azides and alkynes are synonymous. 

Among the different reported methodologies for the covalent assembling of the constitutive modules of these polyvalent carbohydrate systems, the 1,3-dipolar cycloaddition of azides and alkynes have reached a relevant place in recent times because of the rehabihty, efficiency, and robustness of the... 

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-...

N-Heterocyclic carbene-copper(I) complexes in homogeneous catalysis, particularly, of [3 + 2] cycloaddition of azides and alkynes 07SL2158. 

Since the development of the cUck chemistry concept by Sharpless and coworkers [59], the well known Huisgen 1,3-dipolar cycloaddition of azides and alkynes to 1,4-disubstituted 1,2,3-triazoles [229] has regained much atten-... 

J.F. Lutz, 1,3-Dipolar cycloadditions of azides and alkynes a universal ligation tool in polymer and materials science, Angew. Chem. Int. Ed. EngL 46 (7) (2007) 1018—1025. 

A good example of a click chemistry reaction is the Huisgen 1,3-dipolar cycloaddition of azides and alkynes to give triazole linkages [ 16-18]. This reaction has been used in the synthesis of organic compounds [18-21], and more recently in the... 

Montmorilonitrile clay was also successfully used as a support for Cu(0) nanoparticles. Dutta et al. showed that the virgin montmorilonitrile clay-supported Cu(0) nanoparticles catalyzed the formation of 1,2,3-triazoles by 1,3-dipolar cycloaddition of azides and alkynes (Scheme 33) [54]. 

SCHEME 33 1,3-Dipolar cycloaddition of azides and alkynes catalyzed by Cu(0) nanoparticles. 

A. Kumar, S. Aerry, A. Saxena, A. De, S. Mozumdar, Copper nanoparticulates in guar-gum a recyclable catalytic system for the Huisgen [3 + 2]-cycloaddition of azides and alkynes without additives under ambient conditions. Green Chem. 14 (2012) 1298-1301. 

Similar 1,3-dipolar cycloadditions of azides and alkynes produce thermally stable, aromatic triazoles. Ma et al. prepared triazole 212 by pressure-accelerated cycloaddition of azide and alkyne in the crystalline state (present as salt 211) at room temperature (Scheme 51) [79]. Standard reaction conditions requires the use of copper catalyst. An analogous result was previously obtained by solvent-free pressurization (10 kbar, 2-4 h, RT) of aryl azides and tri-methylsilylacetylene by Zanirato and co-workers [79]. 

Copper complexes containing abnormal imidazolylidene 4 were successfully applied to the [3+2] dipolar cycloaddition of azides and alkynes. " Related abnormal imidazolylidene gold(i) complexes showed good activity in the hydration of alkynes. However, the precursor complex required activation with a silver salt, which is likely to lead to carbene transfer (see Section... 

Scheme 3.1 General 1,3-dipolar cycloaddition of azides and alkynes.

Copper-aluminum hydrotalcite (3 1) (Cu/Al-HT (3 1)) promotes the cycloaddition of azides and alkynes, without any sacrificial reducing agents and ligands, because of its ability to stabilize Cu(I) [43]. 

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