Copper-Catalyzed Azide-Alkyne Cycloaddition CuAAC

Copper-Catalyzed Azide-Alkyne Cycloaddition (CuAAC) 

Catalysis Without Precious Metals. Edited by R. Morris Bullock 2010 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN 978-3-527-32354-8 

Numerous appUcations of the CuAAC reaction reported during the last several years have been regularly reviewed [7-13], and are continually enriched by investigators in many fields [14]. We focus here on the fundamental aspects of the CuAAC process and on its mechanism, with an emphasis on the qualities of copper that enable this unique mode of reactivity. 

Copper catalyzed azide-alkyne cycloaddition (CuAAC) 

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B. Copper catalyzed azide-alkyne cycloaddition (CuAAC)... 

Copper-Catalyzed Azide-Alkyne Cycloaddition (CuAAC) Cul (5 mol%)... 

Hein, J. E. and Fokin, V. V. 2010. Copper-catalyzed azide-alkyne cycloaddition (CuAAC) and beyond New reactivity of copper(I)acetylides. Chem. Soc. Rev. 39(4) 1302-1315. 

Copper-catalyzed azide-alkyne cycloaddition (CuAAC) is one of the most powerful click reactions. The only disadvantage is that the copper is toxic to certain cells [90]. Despite efforts to make the copper complexes more biocompatible [91, 92], the breakthrough was achieved by the Bertozzi group [93] through harnessing the ring strain present in cyclooctyne to accelerate the reaction. A variety of cyclooctynes and one cycloheptyne have subsequently been reported [94, 95]. 

CLICK COPPER CATALYZED AZIDE-ALKYNE CYCLOADDITION (CuAAC) IN AQUEOUS MEDIUM... 

Copper-catalyzed azide-alkyne cycloaddition (CuAAC) has been widely used in the post-glycosylation of pre-formed polymers, for which the protected aUcyne monomers can be first polymerized by various LRP strategies followed by removal of trimethylsilyl (TMS) protection groups using tetrabutylammonium fluoride (TBAF)/ acetic acid for click reaction with azido functional sugars (Fig. 3) [59, 60]. This approach avoids the use of hazardous azide-functionalized monomers and utilizes the diversity of well-documented azido functional sugars [59]. 

The orthogonal modification of a-alkyne, m-azido heterotelechelic polystyrene via sequential nitrile oxide-alkyne and azide-alkyne Huisgen cycloadditions was reported by the group of Lutz [36]. Alternatively, Su et al. reported a sequential triple chck modification of polyhedral oligomeric silsesquioxanes (POSS), involving strain-promoted azide-alkyne cycloaddition (SPAAC), copper-catalyzed azide-alkyne cycloaddition (CuAAC), and thiol-ene click coupling (TECC) [37]. 

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. 

Click chemistry is now a popular concept, more specifically when it is used to indicate a copper-catalyzed cycloaddition reaction between alkyl or aryl azides and terminal alkynes. Due to the fact that Cu(I) catalysts dramatically accelerate the original Hiiisgen thermal reaction with perfect control of the mechanistic pathway to lead only to l,4-disubstituted-l,2,3-triazoles, the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction has become one of the most representative examples of click chemistry. It was proposed that this reaction proceeds first through the formation of a copper(l)-acetyhde from a copper(I) catalyst and a terminal alkyne, followed by cycloaddition with a copper(l)-bound azide to generate a triazolyl copper(I) complex, which is released by protonation of the Cu—C bond. 

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... 

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