Copper-catalyzed azide-alkyne cycloaddition synthesis

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. 

Diaz DD, Punnas Holzer P et al (2004) Click chemistiy in materials synthesis. 1. Adhesive polymers from copper-catalyzed azide-alkyne cycloaddition. Polym Sci Part A Polym Chem... 

A copolymer bearing proline and permethylated p-CD was used as catalyst in aldol condensation [23]. The linear copolymer bearing both pendant permethylated p-CD and proline groups was designed on the basis that the hydrophobic cavity of the CDs could approach the substrates close to the proline that acted as catalyst through host-guest interactions. The synthesis of the CD monomer was carried out by a copper-catalyzed azide-alkyne cycloaddition. The CD monomer was then polymerized with a protected hydroxyproline methacrylate to give the linear polymer with a monomer ratio proline/CD of 4.The Me-p-CD-Pro polymer was subsequently obtained after acid deprotection of proline (Scheme 2.9). 

Azide additions to a,P-unsatnrated systems are another method for the preparation of 1,2,3-triazoles. Cydoaddition of aryl azides to a,P-unsaturated aldehydes 88 in the presence of catalytic diethylamine and DBU afforded 1,4-disubstituted-l,2,3-triazoles 89 via an inverse electron-demand process (13CC10187). Michael addition of sodium azide with ethyhdene bisphospho-nates 90 in cydoaddition reactions via sonication afforded bisphosphono-1,2,3-triazoles 91 (13T4047).A one-pot protocol for the synthesis of 1,2,3-triazoles was prepared from unactivated alkenes with azidosulfenylation of the carbon-carbon double bond followed by the copper-catalyzed azide—alkyne cycloaddition (13JOC5031). 1,5-Disubstituted-l,2,3-triazoles 93 were synthesized from enamides 92 with tosyl azide (13AG(E)13265). Reaction of ethyl 3-(alkylamino)-4,4,4,-trifluoro-but-2-enoates 94 with mesyl azide in the presence of DBU afforded l,2,3-triazole-4-carboxylates 95 (13EJ02891). 

The functional groups from the starting monomers may be further modified either by click chemistry, such as thiol-ene, epoxy-amine reaction and copper catalyzed azide-alkyne cycloaddition. Authors also applied the Passerini synthesis pathway to a mixture of the three initial monomers to obtain a combined photodegradable polymer with triple functionality (P4) (Scheme 4). Reproduced with permission. Copyright 2014, American Chemical Society [3]. The photocleavable character may be determined by UV-Vis and gel permeation chromatography (GPC) techniques, when the polymers cleave into the corresponding ortho-nitrosobenzaldehydes and carboxylic acids. 

Spiteri C, Moses JE (2010) Copper-catalyzed azide-alkyne cycloaddition regioselective synthesis of 1,4,5-trisubstituted 1,2,3-triazoles. Angew Chem Int Ed 49(l) 31-33 Agalave SG, Maujan SR, Pore VS (2011) Click chemistry 1,2,3-triazoles as pharmacophores. Chem Asian J 6(10) 2696-2718... 

Triazoles are attractive compounds and widely used in materials, drugs, and bioconjugation chemistry [124-136]. 1,2,3-Triazoles could be synthesized by 1,3-dipolar cycloaddition of azides with alkynes under thermal conditions via the activation of C-H bond of alkyne [137-141]. The developments of Click reaction, copper-catalyzed azide-alkyne cycloaddition (CuAAC), provide an efficient pathway for the synthesis of 1,2,3-triazoles [142, 135, 143, 144]. They have been well reviewed and we don t discuss it in detail in this chapter. 

Copper catalyzed azide-alkyne cycloaddition (CuAAC reaction) is the well-known Huisgen [3+2] cycloaddition reaction of an azide with a terminal alkyne. The CuAAC gives a mild efficient reaction, which requires no protection groups, and no purification in many cases. Appukuttan et al. (2004) reported a one pot, three-component synthesis of various 1,4-substituted-l,2,3-triazoles using the corresponding... 

Copper-catalyzed azide-alkyne cycloaddition has been used to couple the phenazine luminescent probe and an Af,Af-bis(2-picolyl)amine moiety in a 75% yield by using copper acetate (0.01 mol%) and sodium ascorbate in CH3CN/H2O (10 1) [94]. The cycloaddition of l,3-diethynyl-6-fluoroisoquinohne with 1-(2-azidoethyl)pyrrohdine has been applied to the synthesis of a soluble click fluorescent chemosensor (Scheme 3.5). The molecule displays good sensitivity toward heavy and transition metal ions such as Fe ", or Cu in water at pH 7.0 [95]. 

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. 

To highlight the utility of the enantioselective azidation further, transformations of the resulting azides were carried out (Scheme 15.11). For example, an a-azido ester could be converted smoothly into a-amino ester by palladium-catalyzed hydrogenolysis, which may provide a useful method for the synthesis of highly substituted cx-amino acid derivatives. On the other hand, the copper-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC), as a click reaction, has been... 

Scheme 8.1 Examples of click reactions commonly employed in polymer synthesis and functionalization reactions, (a) Copper(I)-catalyzed azide alkyne cycloaddition reaction, (b) Diels-Alder [4 + 2] cycloaddition between anthracene derivatives and maleimides. (c) Hetero-Diels-Alder between a terminal electron-deficient thiocarbonylthio group of RAFT-generated polymers and an appropriate diene, (d) Ultrafast hetero-Diels-Alder reaction between a terminal electron-deficient thiocarbonylthio group of RAFT-generated polymers and a reactive cyclopentadiene. (e) Thiol-ene click chemistry.

Fig. 1 (a) Synthesis of 1,2,3-triazole by copper(l)-catalyzed azide-alkyne cycloaddition (CuAAC) and the CH X hydrogen bonds that form with neutral triazole and positively charged triazolium moieties, (b) Synthesis of iodotriazolium with halogen bonds... 

The synthesis of probe 75, via procedures similar to those reported previously with some modifications, is outlined in Scheme 18 [74]. Coupling compound 76, already described in the literature [75-77], with the bioactive ligand 77 gave compound 78, which was subsequently reacted with the fluorophore 79 to give probe 75 employing the copper-catalyzed [3 + 2] azide-alkyne cycloaddition [78]. 

Huorescent sensor 15 was prepared by employing a copper (I) catalyzed azide-alkyne [3-1-2] cycloaddition developed by Ham, enabling the synthesis of 1,2,3-triazole ring as predominantly the 1,4-regioisomer. At this point during the synthesis. X-ray quality crystals of the pinacol-protected intermediate 16 were obtained. The target sensor 15 was then obtained via a two-step deprotection of the pinacol ester. ... 

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