Cycloadditions copper catalyzed azide-alkyne

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],... 

Following reports of efficient Cu(I)-catalyzed alkyne/azide cycloaddition on solid phase and in solution by Meldal [42] and Sharpless [43], respectively, the formerly obscure Huisgen reaction soared to prominence as a versatile tool for covalent chemical ligation. The so-called click reaction can be catalyzed by a number of copper sources in a variety of media (Equation 9.14). 

For an example of such interaction in the TS of non-catalyzed alkyne/azide cycloaddition (click reaction), see Gold, B., Shevchenko, N. E., Bonus, N., Dudley, G. B., Alabugin, 1. V. (2012). Selective Transition State Stabihzation via Hyperconjugative and Conjugative Assistance Stereoelectronic Concept for Copper-Free Click Chemistry. The Journal of Organic Chemistry, 77(1), 75-89. 

Liang L, Astruc D (2011) The copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) click reaction and its applications. An overview. Coord Chem Rev 255 2933-2945... 

Copper(I)-Catalyzed Alkyne-Azide Cycloaddition (CuAAC) on Nucleic Acids... 

The copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) reaction [1] (Fig. lA) has been extensively employed for the site-specific labeling of oligonucleotides with various reporter groups [3,4, 7, 9,12-16], ligating DNA strands [17, 18], cross-linking complementary strands [19], for surface functionalization [20] and for the formation of bimetallic Ag-Au nanowires from DNA templates [21], Selected examples are described in the following section. 

Currently, copper-catalyzed and copper-free alkyne-azide cycloadditions are the most widely applied cycloaddition reactions for the modification of biomolecules. We developed an approach based on the combination of CuAAC or strain-promoted copper-free variants with enzymatic tailing (and optional enzymatic hgation), which allows the convenient postsynthetic introduction of an azide into existing unmodified RNA strands (chemically or enzymatically synthesized or even isolated from biological sources) at a desired position, and the subsequent functionalization with a wide variety of commercially available or self-synthesized functional alkynes [16c]. 

SCHEME 10.3 Synthesis of Stoddart s rotaxane 3 templated using charge transfer donor-acceptor interactions and stoppered dioxynaphthalene using copper-catalyzed alkyne-azide cycloaddition (CuAAC). 

Subramanian P, Rudolf GC, Kaliappan KP (2016) Recent trends in copper-catalyzed C-H amination routes to biologically important nitrogen scaffolds. Chem Asian J 11(2) 168-192 Hassan S, Muller TJJ (2015) Multicomponent syntheses based upon copper-catalyzed alkyne-azide cycloaddition. Adv Synth Catal 357(4) 617-666... 

Lu, Wang et al. developed an efficient preparation of dihydropyrimidin-4-ones from readily available AT-(prop-2-yn-l-yl)amides and sulfonyl azides using Cul as catalyst (Scheme 8.108). This cascade reaction includes copper-catalyzed alkyne-azide cycloaddition, formation and intramolecular nucleophilic addition of ketenimine, and subsequent rearrangement. The C(sp)-H bond was activated through copper-catalyzed alkyne-azide cycloaddition process in this reaction [182]. 

Chapter 1, Mechanistic Investigations of Copper(I)-Catalysed Alkyne-Azide Cycloaddition Reactions , by Buckley and Heaney is concerned with various mechanistic interpretations of thermal and metal-catalyzed reactions of organic azides and aUcynes, which result in the formation of 1,2,3-triazoles. 

The copper-catalyzed alkyne-azide cycloaddition is a very useful methodology for the preparation of triazole libraries. Thus, a library of triazole amphiphiles with a variety of functional polar heads and hydrophobic or superhydrophobic tails [97], a 96-product-sized library of 1,2,3-triazoles from organic azides and terminal alkynes [98], and a small hbrary of triazole-conjugated coumarins have been synthesized [99]. 

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

A microreview on the copper(I)-catalyzed alkyne-azide click cycloadditions from a mechanistic and synthetic perspective has been written <06EJO51>. 

Disubstituted 1,2,3-triazoles are exclusive products of copper catalyzed 1,3-dipolar cycloadditions of terminal alkynes to azides. A variety of substituents can be introduced in this way. Many examples of such reactions are discussed in Section 5.01.9. 

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. 

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. 

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... 

Functionalized 1,2,3-triazoles 86 and 87 were prepared by [2 + 3] cycloadditions of resin-bound a-azido esters 85 with substituted alkynes <02TL4059>. Regiospecific copper(I)-catalyzed 1,3-dipolar cycloadditions of resin-bound alkynes 88 with azides afforded solid-supported 1,2,3-triazoles 89, which were ligated further to give 1,4-substituted-1,2,3-triazole peptide compounds <02JOC3057>. 

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." ... 

A recent very flexible approach for the preparation of TSOS has been published by Liebscher [34], It relies on a two step procedure with one so-called click chemistry step, which is a regioselective copper catalyzed [3 + 2] Huisgen cycloaddition between an azide and a terminal alkyne, followed by quatemarisation of resulting triazoles. Both reagents can be functionalized prior to cyclisation and furthermore such triazolium synthesis can tolerate a large variety of substituents owing to its chemoselectivity (Fig. 14). 

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