Copper I -catalyzed azide-alkyne

Scheme 6.221 Copper (I [-catalyzed azide-alkyne ligation.

For certain substrates, Fokin, Van der Eycken, and coworkers subsequently discovered that the azidation and ligation steps can be carried out in a one-pot fashion, thereby simplifying the overall protocol (Scheme 6.222) [397]. This procedure eliminates the need to handle organic azides, as they are generated in situ. Other applications of microwave-assisted copper(I)-catalyzed azide-alkyne ligations ( click chemistry ) have been reported [398],... 

Copper(I)-catalyzed azide-alkyne cycloaddition as a selective bioconjugation technique... 

Speers AE, Adam GC, Cravatt BF (2003) Activity-based protein profiling in vivo using a copper(I)-catalyzed azide-alkyne [3+2] cycloaddition. J Am Chem Soc 125 4686-4687... 

Wang Q, Chan TR, Hilgraf R, Fokin VV, Sharpless KB, Finn MG. Bioconjugation by copper(I)-catalyzed azide-alkyne [3 4- 2] cycloaddition. J. Am. Chem. Soc. 2003 125 3192-3193. 

Scheme 4.3 Copper(i)-catalyzed azide-alkyne click reaction in ILs.

Dabco-based ionic liquids have been recently used, together other basic and neutral ILs, in the copper(i)-catalyzed azide-alkyne click reaction (Scheme 4.3). The model cycloaddition of a sugar azide with a sugar acetylene has been carried out in ten ILs. With one exception, in all investigated ILs the reaction afforded exclusively the 1,4-disubstituted triazole, namely a triazole-linked C-dis-accharide, in high yields. 

Q. Wang, T.R. Chan, R. Hilgraf, V.V. Fokin, K.B. Sharpless, M.G. Finn, Bioconjugation by copper(I)-catalyzed azide-alkyne... 

The turning point for the above mentioned 1,3-dipolar cycloaddition occurred with the independent discovery that copper(I) not only promotes the speed of the reaction (often referred to as click reaction), but also improves regioselectivity. The copper(I)-catalyzed azide alkyne cycloaddition (CuAAC) of terminal alkenes with organic azides to yield 1,4-disubstituted 1,2,3-triazoles discovered by Meldal [51] and Sharpless [50] exhibits remarkably broad scope and exquisite selectivity [59,60]. The most prominent application of click reactions in recent years has been in drug research [61,62],... 

The alkynyl functionality of alkynones 1 is perfectly suited for subsequent copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) in the sense of an MCR (2015ASC(357)617). A microwave-assisted three-component reaction of aroyl chlorides 4, TMS-substituted acetylene (5a), and benzyl azide (10a) consisting of modified Sonogashira cross-coupling I, desilylation, and CuAAC furnishes 4-disubstituted 1,2,3-triazoles 11 in moderate to excellent yields (Scheme 5) (201 OOL(12)4936). 

Wang W, Hong SL, Tran A, Jiang H, Triano R, Liu Y, Chen X, Wu P (2011) Sulfated ligands for the copper(I)-catalyzed azide-alkyne cycloaddition. Chem-Asian J 6(10) 2796-2802. doi 10.1002/ asia.201100385... 

Fig. 1 Proposed intermediates of CuAAC with one or two copper atoms [41]. CuAAC copper(I)-catalyzed azide-alkyne cycloaddition...

Fig. 7 CuAAC reaction for studying protein lipidation and lipidation-induced protein-protein interactions. Schematic representation for studying (a) protein S-palmitoylation using an alkyne-tagged lipid probe alk-16 and the CuAAC reaction, and (b) S-palmitoylation-induced protein irotein interactions using a multifunctional lipid probe X-alk-16 [97, 98]. CuAAC copper(I)-catalyzed azide-alkyne cycloaddition, UV ultraviolet...

Zhou Z, Fahmi CJ (2(X)4) A fluorogenic probe for the Copper(I)-catalyzed azide-alkyne ligation reaction modulation of the fluorescence emission via (n,ji )- (n,n ) inversion. J Am Chem Soc 126 8862 863... 

Describe the main criteria that should be satis ed for a reaction to be called a click reaction How would you justify the inclusion of the following reactions into the pantheon of click reactions (a) Copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reactions (b) strain-promoted azide-alkyne coupling (SPAAC) reactions (c) Diels-Alder (DA) cycloaddition reactions (d) thiol-ene (TE) reactions and (e) thiol-yne (TY) reactions ... 

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. ... 

Although the azide-alkyne [3+2] cycloaddition (cf. Chapter 9) is known in carbohydrate chemistry for more than 50 years, its application for the preparation of glycoconjugates became particularly attractive with the development of the copper(I)-catalyzed variant by Meldal and Sharpless. The copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) enables the regioselective formation of 1,4-disubstituted 1,2,3-triazoles under very mild conditions even in a biological context. However, the cellular toxicity of the copper catalyst precludes applications wherein cells must remain viable. Therefore, as an alternative... 

Naturally, what is said to constitute an ultrarapid and mild reaction is rather subjective as it can be very system specific. For example, the use of the copper(I) catalyzed azide-alkyne... 

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.

Sinnwell, S., Inglis, A.J., Stenzel, M.H., and Bamer-KowoUik, C. (2008b) Access to three-arm star block copolymers by a consecutive combination of the copper(I)-catalyzed azide-alkyne cycloaddition and the RAFT hetero Diels-Alder concept. Macromolecular Rapid Communications, 29,1090. 

Geng J, Lindqvist J, Mantovani G, Haddleton DM (2008) Simultaneous copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) and living radical polymerization. Angew Chem Int Ed 47(22) 4180 183... 

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