Click chemistry dipolar

Although beyond the scope of the present discussion, another key realization that has shaped the definition of click chemistry in recent years was that while olefins, through their selective oxidative functionalization, provide convenient access to reactive modules, the assembly of these energetic blocks into the final structures is best achieved through cydoaddition reactions involving carbon-het-eroatom bond formation, such as [l,3]-dipolar cydoadditions and hetero-Diels-Al-der reactions. The copper(i)-catalyzed cydoaddition of azides and terminal alkynes [5] is arguably the most powerful and reliable way to date to stitch a broad variety... 

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). 

Kappe and co-workers proposed an application of a microwave-assisted Huisgen 1,3-dipolar cycloaddition of terminal acetylenes and azides 70, imder Cu(I) catalysis, as an example of click chemistry to obtain a collection of... 

By combining several click reactions, click chemistry allows for the rapid synthesis of useful new compounds of high complexity and combinatorial libraries. The 2-type reaction of the azide ion with a variety of epoxides to give azido alcohols has been exploited extensively in click chemistry. First of all, azido alcohols can be converted into amino alcohols upon reduction.70 On the other hand, aliphatic azides are quite stable toward a number of other standard organic synthesis conditions (orthogonality), but readily undergo 1,3-dipolar cycloaddition with alkynes. An example of the sequential reactions of... 

Click chemistry has been particularly active in various fields this year. For example, ample applications of click chemistry have been seen in carbohydrate chemistry. Various /weiido-oligosacchardies and amino acid glycoconjugates were synthesized via an intermolecular 1,3-dipolar cycloaddition reaction using easily accessible carbohydrate and amino acid derived azides and alkynes as building blocks <06JOC364>. The iterative copper(I)-catalyzed... 

Scheme 7.1 Click chemistry synthesis of 1,4-disubstituted-l,2,3-triazoles by a 1,3-dipolar cycloaddition reaction of organic azides with terminal acetylenes.

Click chemistry has been used extensively since its introduction in organic chemistry, due to the high efficiency and technical simplicity of the reaction [40]. The most popular click reaction has been the copper-catalyzed dipolar cycloaddition of a terminal alkyne and an azide to form... 

A specific peptide sequence for nuclear targeting (NLS) has been conjugated to gold NRs via click chemistry. In particular, a thiol with an azide end group has been reacted via Huisgen 1,3-dipolar cycloaddition to an alkyne-terminated NLS peptide and then anchored to CTAB-protected gold NRs.250... 

Click chemistry can also be efficiently combined with p,CP. 1,3-Dipolar cycloadditions where alkynes and azides react to give triazoles can serve as a good example for the reaction conducted under stamp confinement.111 Usually this reaction... 

The discovery of copper catalysis in 1,3-dipolar cycloadditions of terminal alkynes to azides (click chemistry) in 2002 <2002AGE2596, 2002JOC3057> has revolutionized the field . It is not only that the catalyzed reactions proceed faster under mild conditions, but full regioselectivity of the products is also achieved. Terminal alkynes generate only 1,4-disubstituted triazoles. A brief outline of the reaction mechanism is given in Scheme 253 . Some aspects of this new methodology are discussed in a review <2007ALD7>. 

Click chemistry also found applications in peptides and peptidomimetics. Alkyne-azide cycloaddition between two peptide strands provided an efficient convergent synthesis of triazole ring-based P-tum mimics <07CC3069>. The synthesis of a-substituted prolines has been accomplished by microwave-assisted Huisgen 1,3-dipolar cycloaddition between azides and orthogonally protected a-propynyl proline in the presence of Cu(I) sulfate <07SL2882>. The synthesis of new trifluoromethyl peptidomimetics with a triazole moiety has been reported <07TL8360>. 

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]. 

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