Cycloaddition click azide-alkyne

CuO nanostructures of variable shapes CuO nanospheres (5-10 run), CuO nanorods (WXL = 24-27 nmxl24-140 run) and CuO nanowires (WXL= 8-10 nmx230-270 nm) have been synthesised to study the effect of shape of the catalyst on the Cu(I)-catalyzed click azide-alkyne cycloaddition. Cu(I) species were generated in situ by the reduction of CuO nanostructures in the presence of sodium... 

A copper catalysed click (azide-alkyne cycloaddition) reaction has been used to prepare a fluorous-tagged TEMPO catalyst (Figure 7.20). TEMPO is a stable organic free radical that can be used in a range of processes. In this case, its use in metal-free catalytic oxidation of primary alcohols to aldehydes using bleach as the terminal oxidant was demonstrated. The modified TEMPO can be sequestered at the end of the reaction on silica gel 60 and then released using ethyl acetate for reuse in further reactions in this way the TEMPO was used four times with no loss in activity. 

An extensive review of the use of copper(I) complexes as catalysts in click azide—alkyne 3 + 2-cycloadditions has been presented. The polytriazole ligand tris(2- 4-[(dimethylamino)methyl]-l/f-l,2,3-triazol-l-yl ethyl)amine (DTEA) has... 

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). 

Besides short ELPS, longer ELPs have also been conjugated to synthetic polymers. In one approach, Cu(I)-catalyzed azide-alkyne cycloaddition click chemistry was applied. For this purpose, ELPs were functionalized with azides or alkynes via incorporation of azidohomoalanine and homopropargyl glycine, respectively, using residue-specific replacement of methionine in ELP via bacterial expression [133]. More recently, an alternative way to site-selectively introduce azides into ELPs was developed. Here, an aqueous diazotransfer reaction was performed directly onto ELP[V5L2G3-90] using imidazole-1-sulfonyl azide [134]. 

Another important click reaction is the cycloaddition of azides. The addition of sodium azide to nitriles to give l//-tetrazoles is shown to proceed readily in water with zinc salts as catalysts (Eq. 11.71).122 The scope of the reaction is quite broad a variety of aromatic nitriles, activated and nonactivated alkyl nitriles, substituted vinyl nitriles, thiocyanates, and cyanamides have all been shown to be viable substrates for this reaction. The reaction of an arylacetylene with an azide in hot water gave 1,4-disubstituted 1,2,3-triazoles in high yields,123 while a similar reaction between a terminal aliphatic alkyne and an azide (except 111 - nitroazidobenzcnc) afforded a mixture of regioisomers with... 

Click Chemistry Cu1-promoted Azide—Alkyne [3 + 2] Cycloaddition... 

Click Chemistry CU(l)-Promoted Azide-Alkyne [3+2] Cycloaddition... 

Another route involves a palladium-copper-catalyzed tandem carbon-carbon formation/cycloaddition sequence (Equation 12) <2005TL8531>. Notably, cycloadditions of azide to the internal alkynes failed under click chemistry reaction conditions <2003DDT1128>. Cyclization under oxidative conditions has been reported from dithioacetal 163 (Equation 13) <1996TL3925>. The formation of 164 as a single diastereoisomer has been explained by stereoelectronic effects. 

Another approach for the synthesis of networks relies on the polycondensation of multifunctionalized polyesters with the appropriate multifunctionalized agent, provided that one of the partner is at least tri-functionalized. Toward this end, several reaction have been reported, such as the Michael addition of amines onto acrylates [184], the coupling of ketones and oxyamines [185], the click copper(II)-catalyzed azide-alkyne cycloaddition [186], and esterification reactions [25, 159, 187]. Interestingly, if esterification reactions are used, the crosslinks are then degradable. 

Duran Pachon, L., van Maarseveen, J.H. and Rothenberg, G. (2005) Click chemistry copper clusters catalyze the cycloaddition of azides with terminal alkynes. Adv. Synth. Catal., 347, 811. 

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. 

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... 

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>. 

Various miidazo[l,5-a]imidazoles (35), itnidazo[l,5-a] pyridines (36), and iniidazo[5,l-a]isoquinolmes (37), important ligands or precursors to pharmaceuticals," can be constructed via copper-catalyzed heterocyclization of Schiff s bases. A stepwise cycloaddition between azides and terminal alkynes is also catalyzed by copper salts in what has now been termed click chemistry, producing 1,4-disubstituted triazoles (38) in excellent yields." ... 

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]. 

Evans, R. A. (2007) The rise of azide-alkyne 1,3-dipolar click cycloaddition and its application to polymer science and surface modification. Aust. J. Chem., 60, 384—395. 

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