Huisgen cycloaddition

The conversion of CO2 to industrially useful compounds has been a challenge for synthetic chemists and has attracted more and more interest [78]. Recently, significant progress has been made in the application of SIL catalysis in the coupling of epoxides with CO2. 

It was demonstrated that both homogeneous and a silica-supported hexaalkyl-guanidinium chloride were effective catalysts for fixation of COj to carbonate without solvent, and that the silica-supported catalyst had the great advantage of being easily recovered and reused [79]. 

A siUca-SIL [BMIM]BF4 material was synthesized [80]. The catalyst proved to be an efHdent heterogeneous catalyst for solventless synthesis of cyclic carbonates from epoxides and CO2 under supercritical conditions, which required no additional organic solvents either for the reaction or for the separation of product. High yields with excellent selectivity were obtained. Moreover, the catalyst could be easily 

The immobilized IL-zinc chloride catalyst system was also reported [81], which was very efficient in chemical fixation of CO2 to form cyclic carbonates under mild condihons in high TOP. The synthesis of five-membered cychc carbonate from aUyl glycidyl ether (AGE) and CO2 was reported using immobilized imidazolium IL on silica, which was also proved to be an effective heterogeneous catalyst for the solventless synthesis of cyclic carbonate [82]. Then, MCM-41 was used as the support to immobihze ILs and the resulting material showed excellent activities for CO2 insertion reactions [83]. 

The IL 3-butyl-l-vinylimidazolium chloride ([VBIMJCl) and the cross-linker DVB were copolymerized to prepare a highly cross-linked PSIL, in which [VBIMJCl was covalently anchored on DVB-cross-linked polymer matrix. The catalytic performance of the PSIL was investigated, and the PSIL was very active, selective, and stable for the cycloaddition of CO2 to epoxides, and could be easily separated from the products and reused [88]. 

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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). 

Normally, copper-catalysed Huisgen cycloadditions work with terminal alkynes only. The formation of a Cu-acetylide complex is considered to be the starting point of the catalyst cycle. However, the NHC-Cu complex 18 was able to catalyse the [3-1-2] cycloaddition of azides 17 and 3-hexyne 23 (Scheme 5.6). 

Ramachary, D.B. Barbas, C.R III (2004) Towards Organo-Click Chemistry Development of Organocatalytic Multicomponent Reactions Through Combinations of Aldol, Wittig, Knoevenagel, Michael, Diels-Alder and Huisgen Cycloaddition Reactions. Chemistry A European Journal, 10, 5323-5331. 

The 1,3-dipolar eyeloaddition, also known as the Huisgen cycloaddition, is a elassie reaetion in organic chemistry consisting in the reaetion of a dipolar-ophile with a 1,3-dipolar compound that allows the produetion of various five-membered heteroeyeles. This reaction represents one of the most productive fields of modern synthetic organic chemistry. Most dipolarophiles are alkenes, alkynes, and molecules possessing related heteroatom functional... 

The reaction of 1,2,3-triazolium-l-aminides 3 with propiolate esters led to fluorescent 2,5-dihydro-1,2,3-triazine derivatives 4 in one pot, involving a Huisgen cycloaddition followed by a sequence of rearrangements <06JOC5679 06TL1721>. These reactions can be carried out in acetone, in water, or under solvent-free conditions. 

V. V. Rostovtsev, L. G. Green, V. V. Fokin, and K. B. Sharpless, A stepwise Huisgen cycloaddition process Copper(I)-catalysed regioselective ligation of azides and terminal alkynes, Angew. Chem. Int. Ed., 41 (2002) 2596-2599. 

H. Isobe, K. Cho, N. Solin, D. B. Werz, P. H. Seeberger, and E. Nakamura, Synthesis of fullerene glycoconjugates via a copper-catalyzed Huisgen cycloaddition reaction, Org. Lett., 9 (2007) 4611-4614. 

Finally, several groups have reported irreversible chemistries that work selectively in the presence of proteins or even whole cells. These include the Huisgen cycloaddition recently improved by Sharpless and others,1146-481 chemical ligation,1491 the formation of oximes or hydrazones and the Staudinger ligation.1501... 

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. 

The Huisgen Cycloaddition (or 1,3-Dipolar Cycloaddition) is the reaction of a dipolarophile with a 1,3-dipolar compound that leads to 5-membered (hetero)cycles. Examples of dipolarophiles are alkenes and alkynes and molecules that possess related heteroatom... 

The reaction has been modified to a more regioselective, copper-catalyzed stepwise process by the Sharpless group, which is no longer a classic Huisgen Cycloaddition. Another approach prefers the use of a directing electron withdrawing group, which is removable later ... 

Figure 3.42 a General reaction scheme for the thermal Huisgen cycloaddition b the copper-catalyzed reaction between phenyl propargyl ether (phenyl 2-propynyl ether) and benzyl azide. The catalytic reaction is performed in the presence of a reductant (sodium ascorbate) and gives just one of the product isomers in high yield. 

Rostovtsev, V.V., Green, L.G., Fokin, V.V., and Sharpless, K.B. (2002). A stepwise huisgen cycloaddition process copper(I)-catalyzed regioselective hgation of azides and terminal alkynes Angew Chem Int Ed 33 45. 

Cycloaddition reactions between azides and alkynes—exemplified by the Huisgen 1,3-dipolar cycloaddition—have tremendous potential for the development of biomolecules and have been employed for conjugation of sugars to peptides [184]. Drawbacks of the Huisgen cycloadditions, however, are poor regioselectivity and incompatibility with physiological conditions. These limitations, which hinder MOE applications in living cells, were first overcome by cop-... 

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). 

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