Cycloaddition click

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]. 

Figure 14.8 Use of the copper(l)-mediated alkene-azide 1,3-cycloaddition ("click" chemistry) in both organic solvent and aqueous solvent systems. The aqueous system, with in situ generation of copper(l) from copper(II), is less sensitive to oxygen.

Very recently, Pericas reported a new strategy to immobihze trans-4-hydroxypro-line onto an insoluble Merrifield-type polymer by exploiting Cu(I)-catalyzed 1,3-dipolar cycloaddition ( click chemistry ) [42]. The supported catalyst 25 was successfully employed in the a-aminoxylation of ketones and aldehydes (Scheme 8.13). Under the optimized reaction conditions (20mol%/cat, 2 equiv. ketone, DMF, 23 °C, 3 h), the reaction of cyclohexanone with nitrosobenzene catalyzed by 25 gave the product in 60% yield and 98% ee (Scheme 8.13 Equation a). It should be noted that the reaction rates of cyclic ketones with supported catalyst are faster than those reported with (S)-proline. The use of a supported catalyst allowed for a simplification of the work-up procedure, as the product could often be obtained after simple filtration of the catalyst and evaporation of the solvents. Furthermore, 25 was recycled up to three times without any decrease in either the chemical and/or stereochemical efficiency. 

Huisgen 1,3-dipolar cycloaddition (click reaction) between terminal alkynes and azides is a highly efficient approach for the post modification of polymers. This technique is tolerant to a wide rage of reaction conditions and functional groups allowing fast coupling reactions under simple reaction conditions with... 

A series of 1,2,3-triazoles have been prepared using a Cu-catalyzed Huisgen [2+3] dipolar cycloaddition (click) reaction. The required azide was generated in situ from the corresponding halide and sodium azide (Scheme 4.7). Microwave irradiation dramatically reduced the reaction times from hours to minutes without affecting the 1,4-regioselectivity of the reaction. Since triazole products often crystallize readily... 

Synthesis of triazoles and tetrazoles by 1,3-dipolar cycloaddition ( click chemistry ) in bioconjugate chemistry 06CJ01640. 

Generality of this mechanochemical protocol was demonstrated in one-pot, two-step synthesis of triazole (Scheme 3.102). The first synthetic step, 1,3-dipolar cycloaddition ( click reaction ) of 4-iodobenzyl azide with phenyl acetylene employing copper powder (1 equiv.) was complete in lOmin and follows the synthetic procedure described in chapter Cycloaddition Reactions [67], Ullmann Af-arylation of tiiazole 371 with ethylenediamine in optimized reaction conditions provided the corresponding W-arylated triazole 372 in 56% yield, albeit reaction required 2h of ball milling to complete. 

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. 

Diels—Alder cycloaddition click chemistry 13CJ01437. 

Keywords Nucleic acid Cycloaddition Click chemistry CuAAC LEDDA Metabolic labeling... 

In the first section of this chapter, the different cycloaddition/click chemistries already used for modifying nucleic acids are summarized. The subsequent sections contain selected applications and themes where cycloaddition reactions are a central element of studies on nucleic acids. 

Figure 11 Mixing water-soluble polysaccharide derivatives 20 and 21 in a 1 1 ratio in the presence of Cu(I) led to rapid gelation of water because of the cross-linking of the polymers resulted from 1,3-dipolar cycloaddition (click) reaction.

Stoddart et al reported a redox-switchable a-CD-based [2]rotaxane R16 (Figure 16) via cycloaddition Click reaction, wherein an a-CD first incorporates a TTF unit of the dumbbell to form pseudorotaxane, and then employs a threading-followed-by-stopping approach via the copper(l)-actalyzed azide-alkyne cycloaddition (yield 23%). The host O -CD ring is preferred to rest on the TTF station. After the oxidation of TTF to its radical cation or to its dication, a-CD moves onto the 1,2,3-triazole ring unit. The redox-switchable process of rotaxane R16 is reversible as reported. This is the first example of redox-switchable CD-based [2]rotaxanes. 

Dendritic nanoreactor 1 was also employed as a recyclable micellar nanoreactor, stabilizer, and activator of Cu -catalyzed alkyne—azide cycloaddition click reaction, CuAAC reaction, in the presence of a very low amount (only 0.1%) of Cu (hexabenzyltren) Br (tren = triaminoethylantine) catalyst, 4, in aqueous media (Fig. 6.24) [60]. 

YA(j 14] Yagci Y, Tasdelen M.A., Jockusch S., Reduction of Cu(ll) by photochemically generated phosphonyl radicals to generate Cu(l) as catalyst for atom transfer radical polymerization and azide-alkyne cycloaddition click reactions . Polymer, vol. 55, pp. 3468-3474, 2014. 

There are four different chemical reactions that have been used to crosslink polymers with peptide sequences (Fig. 6.8) (i) amide bond formation (ii) Michael-type addition (iii) Huisgen cycloaddition (click reaction) and (iv) radical polymerisation. The amide bond formation follows typical solid phase peptide synthesis (SPPS) protocols and does not require functionalisation of the termini of the peptide sequence. Fluorenyhnethoxycarbonyl (Fmoc) protection of the N-terminus allows attachment of the peptide sequence to an amine-bearing polymer. After removal of the Fmoc group, the amine-terminated peptide-polymer conjugate can be reacted with a second polymer bearing carboxylic acid functionalities using the same coupling chemistry (Maier et al, 2011). For Michael-type additions the peptide... 

Johnson, J.A., Firm, M.G., Koberstein, J.T., and TUrro, N.J. (2008) Construction of Unear polymers, dendrimers, networks, and other polymeric architectures by copper-catalyzed azide-alkyne cycloaddition click chemistry. Macromolecular Rapid Communications, 29,1052. 

In a recent report, star polymers having an azide functional motif were cOTijugated to alkyne-containing DNA using an azide-alkyne cycloaddition click reaction. When a star polymer DNA hybrid was mixed with another star polymer DNA... 

Huisgen 1,3-dipolar cycloaddition (click chemistry) to form the 1,2,3-triazole ring (Scheme 50(a)). ... 

Singh MS, Chowdhury S, Koley S (2016) Advances of azide-alkyne cycloaddition-click chemistry over the recent decade. Tetrahedron 72(35) 5257-5283... 

A tris-triazoloethylamine capsule 202 of this type with high xenon and radon affinity has been prepared in [140] using copper-catalyzed 1,3-cycloaddition click reaction of appropriate alkyne- and azide-containing syntones by Scheme 2.124. 

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