1,2,3 triazole Huisgen cycloaddition

The NHCs have been used as ligands of different metal catalysts (i.e. copper, nickel, gold, cobalt, palladium, rhodium) in a wide range of cycloaddition reactions such as [4-1-2] (see Section 5.6), [3h-2], [2h-2h-2] and others. These NHC-metal catalysts have allowed reactions to occur at lower temperature and pressure. Furthermore, some NHC-TM catalysts even promote previously unknown reactions. One of the most popular reactions to generate 1,2,3-triazoles is the 1,3-dipolar Huisgen cycloaddition (reaction between azides and alkynes) [8]. Lately, this [3h-2] cycloaddition reaction has been aided by different [Cu(NHC)JX complexes [9]. The reactions between electron-rich, electron-poor and/or hindered alkynes 16 and azides 17 in the presence of low NHC-copper 18-20 loadings (in some cases even ppm amounts were used) afforded the 1,2,3-triazoles 21 regioselectively (Scheme 5.5 Table 5.2). 

The reaction chosen to connect the tethers in situ was the Huisgen azide-alkyne cycloaddition (Scheme 10.5). The Huisgen cycloaddition forms 1,2,3-triazoles as a nearly 1 1 mixture of regioisomers (10.28 and 10.29). The reaction is slow at room temperature. However, if the azide and alkyne are positioned ideally, such as when bound in close proximity by AChE, then the reaction occurs at room temperature. 

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). 

Glycosyl triazoles have been prepared from glycosyl azides by different authors [146,147] using Cu(I)-catalysed Huisgen cycloaddition. The same reaction has been employed for the preparation of polyvalent glycoconjugate clusters (Scheme 35). For example, treatment of 0-protected glucopyranosyl... 

The second step is the copper(l)-catalyzed azide-alkyne cycloaddition (CuAAC). CuAAC produces only 1,4-disubstituted-1,2,3-triazoles at room temperature in excellent yields. Formally, it is not a 1,3-dipolar cycloaddition and thus should not be termed a Huisgen cycloaddition. 

They also employed 7V-heterocyclic carbene (NHC)-modified silica particles as efficient and recyclable ligands for the Huisgen cycloaddition (Scheme 4.2) (Li et al., 2008). A variety of 1,2,3-triazoles were generated in high yields from various organic azides and alkynes. 

Synthesis of 1,2,3-Triazoles Using Charcoal-Based Cu Catalysts Huisgen cycloaddition can also be promoted by charcoal-based Cu catalysts (Lipshutz and Taft, 2006 Sharghi et al., 2009b Alonso et al., 2010). Despite their low cost, most of these catalytic systems suffer from high reaction temperatures and the difficulty to reuse. 

For some selected examples, see (a) Y. Perez-Fuertes, J. E. Taylor, D. A. TickeU, M. F. Mahon, S. D. Bull, T. D. James, J. Org. Chem. 2011, 76, 6038-6047. Asymmetric Strecker synthesis of a-arylglycines. (b) J. R. Donald, R. R. Wood, S. F. Martin, ACS Comb. Sci. 2012,14,135-143. Application of a sequential multicomponent assembly process/Huisgen cycloaddition strategy to the preparation of libraries of 1,2,3-triazole-fused 1,4-benzodiazepines, (c) L. Y. V. Mendez, V.V. Kouznetsov, Curr. Org. Chem. 2013, 10, 969-973. First girgensohnine analogs prepared through InClj-catalyzed Strecker reaction and their bioprospection. 

Wu Y-M, Deng J, Fang X, Chen Q-Y (2004) Regioselective synthesis of fluoroalkylated-1,2,3-triazoles by Huisgen cycloaddition. J Fluorine Chem 125 1415—1423... 

The synthesis of 1,2,3-triazoles has been routinely achieved using click chemistry approach. The main advantages of this methodology include high specificity, efficiency, simple reaction workup procedures, and good product yields. The reaction involves copper(I) catalyzed 1,3-dipolar cycloaddition (Huisgen cycloaddition) between an... 

In 2009, Miura et al. reported an elegant assembly of pyrroles 38 from alkynes and A-sulfonyl-1,2,3-triazoles 36 (Scheme 12.16) [18,19]. The reaction proceeded at 100 °C in the presence of a nickel catalyst and aluminum co-catalyst to afford substituted pyrroles 38. It is worth mentioning that the starting material 36 can be produced readily by the copper-catalyzed azide-alkyne Huisgen cycloaddition. The reaction is thought to be initiated by tautomerization of the triazole to an a-iminodiazo compound, which reacts with Ni(0) to give a nickel carbenoid and then the azanickelacycle 37. Subsequent alkyne insertion to the azanickelacycle and reductive elimination lead to the formation of 38. 

The synthesis of triazoles by 1,3-dipolar cycloaddition between azides and alkynes has been extensively studied recently with numerous synthetic applications in the field of click chemistry. However, the Huisgen cycloaddition between azides 39 and alkenes 40 (Scheme 41.9) although less studied offers interesting opportunities for the stereoselective formation of C N bonds in the context of natural products synthesis. The triazolines 41 thus formed are in fact good precursors of aziridines via ring contraction and expulsion of N2. 

Since the renaissance of the [3-1-2] Huisgen cycloaddition [249], the azide group has attracted many attention because its condensation with alkynes, leading to 1,2,3-triazole derivatives, is one of the most powerful tools to reach these compounds which found various applications, for example, as pharmaceuticals, agrochemicals, or dyes. 

The Huisgen cycloaddition reaction of azides with alkynes to produce triazoles was used to produce HA hydrogels and to encapsulate yeast cells during crosslinking. In this method, azide and alkyne functional groups were installed on HA using EDC chemistry. The hydrogel... 

The classical thermal 1,3-dipolar cycloaddition that involves azides and alkynes (either terminal or internal) derivatives is known as the Huisgen cycloaddition and gives access to 1,2,3-triazoles as a mixture of 1,4- and 1,5-regioisomers (Scheme 3.1) [3]. Regiospecific couplings to furnish the 1,4-disubstituted 1,2,3-triazoles are promoted by copper(I) salts as faster procedures (more than 100 times faster). 

Ag(I) acetylide has been thought to catalyze the Huisgen cycloaddition however, the addition of copper(I) salts is required to accomplish the cycloaddition and to obtain 1,4-disubstituted 1,2,3-triazoles [63]. Despite this, homogeneous complexes of type [Ag (L2)(X )]catalyze the acetylene-azide cycloaddition. When Af,Af-diisopropyl(2-diisopropylphosphanyl)benzamide was used as ligand, the reaction conditions based on 2-2.5 mol% of catalyst, for 24 h, at 90 C in toluene lead to conversions higher than 99% [64]. 

The synthesis of 1,4-disubstituted 1,2,3-triazoles is often carried out by a conventional Huisgen cycloaddition between azides and terminal alkynes. 

The Cu(I)-catalyzed Huisgen [3 + 2] dipolar cycloaddition was also utilized by Van der Eycken and co-workers to obtain a new class of glycopep-tidomimetics based on the 1,2,3-triazole ring system 78 starting from glu-copyranosyl azide 75 and the pyrazinone compound 76 (Scheme 26) [58]. 

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