Catalysis click

Keywords Alkyne Azide Catalysis Click chemistry Copper(I) Ligands... 

Keywords Catalysis Click chemistry Metallosupramolecular chemistry... 

Kappe and co-workers proposed an application of a microwave-assisted Huisgen 1,3-dipolar cycloaddition of terminal acetylenes and azides 70, imder Cu(I) catalysis, as an example of click chemistry to obtain a collection of... 

Inhibition can be reversible when it simply complexes at the active site preventing further catalysis. The active enzyme under these conditions can be recovered by dialysis. Another form of inhibition is the irreversible type where the active enzyme cannot be recovered by dialysis. A variant of this type of inhibition is suicide inhibition a substrate of the enzyme reacts at the active site to yield an irreversible inhibitor which then reacts directly with groups at the active site [18]. A technique, in situ click chemistry , is related to that of suicide inhibition and involves click chemistry components which complex at the active site of an enzyme and combine to form femtomolar inhibitors. The technique can be used to synthesise inhibitors or by selection from a library of click chemistry components to search structure space of the inhibitor for the drug target [ 19]. 

Figure 7.18 Representative in situ Click chemistry reaction analysis by HPLC-SIM-MS the triazole product is indicated by the dashed line, (a) Triazole products obtained by conventional synthesis with Cu(l) catalysis, (b)-(d) Microfuidic device reactions performed at 37 °C for 40 h (b) in the presence of CA II, (c) in the presence ofCA II and potent CA inhibitor to block the CA active site and (d) in the absence of CA II. (e) Reaction performed at 37° C for 40 h in microtitre plate. Reproduced with permission from Wang,., Sui, C., Mocharla, V.P., Lin, R.J., Phelps, M.E., Kolb, H.C. and Tseng, H.-R., Integrated microfluidics for parallel screening of an in situ click chemistry library. Angewandte Chemie International Edition 2006, 45, 5276-5281. Copyright Wiley-VCH Verlag GmbH.

The discovery of copper catalysis in 1,3-dipolar cycloadditions of terminal alkynes to azides (click chemistry) in 2002 <2002AGE2596, 2002JOC3057> has revolutionized the field . It is not only that the catalyzed reactions proceed faster under mild conditions, but full regioselectivity of the products is also achieved. Terminal alkynes generate only 1,4-disubstituted triazoles. A brief outline of the reaction mechanism is given in Scheme 253 . Some aspects of this new methodology are discussed in a review <2007ALD7>. 

Triazoles are generally prepared by the cycloaddition of an alkyne with an azide, which can be promoted thermally or by metal catalysis. This cycloaddition reaction of an azide and an alkyne is a typical Click reaction, that is, a highly efficient and reliable general reaction that can be used for linking moieties for various purposes, such as in combinatorial chemistry. Opinion is divided on whether Click is a useful or necessary concept but it seems to have become associated, almost synonymously, but incorrectly, solely with this triazole synthesis. 

Another chemoselective ligation reaction is the [2 + 3] cycloaddition between an azide and an alkyne. This reaction has been discovered by Huisgen and was lately named click-reaction by Sharpless and Meldal [180, 181]. Whereas the Huisgen 1,3-dipolar cycloaddition leads to two isomeric triazole products at high temperature, click chemistry is performed under the catalysis of Cu(I), thus changing the reaction mechanism from a concerted to a step-wise route and resulting in the formation of the 1,4-substituted triazole as the only product, usually isolated in high yields [174, 182-186],... 

A somewhat different but mechanistically related reaction is the [2 -f 3] cycloaddition of a functionalized alkyne or nitrile to an azide to form a disubstituted triazole (120) or tetrazole ring (121, 122), linking the respective functionalities irreversibly (Scheme 14b). This click chemistry was used by Sharpless and co-workers (120) in 2001 as a tool to probe biochemical catalysis and substrate activation. The ease of the Cu(I)-catalyzed reaction has created a true explosion (120-160) of simple coupling-functionalization chemistry of all types of biochemical components (sugars, DNA, proteins, enzymes, substrates, inhibitors) (131, 135, 136, 139, 142, 155, 157-160), polymers (126, 134, 140, 147, 154),... 

S.2.2.4. Triazoles from Azides. Cycloadditions of this type constitute a valuable synthetic route to the triazole ring system. This is shown in Scheme 5.30. This combination dates back to the early work of Huis-gen, but in more recent times it was discovered to be subject to catalysis by Cu(I) compounds. The reactions are fast under mild conditions, have high regiospecificity, and occur in a variety of solvents including water. In addition, reaction products are easily isolated. Reactions with these characteristics have become known as comprising click chemistry this term was coined by K. B. Sharpless. The first and most commonly used reaction referred to by this name is indeed the azide-alkyne cycloaddition, and new interest has developed in triazole hemistry since the discoveiy of the copper catalysis. In addition to its use in organic... 

Last but not least, the versatility of zeolites is demonstrated by exchanging the acidic proton with deuteron which enables investigation of interesting mechanisms related to catalysis and by exchanging the proton with transition metal cations, such as Cu(I), and opens new areas of enviromnentaUy friendly organic chemistry. For these reasons, we are including in this chapter acidic-zeolite catalysed reactions from our own work which can be best understood as examples of confinement effects superelectrophilic, Cu(I) catalysed Click chemistry, and specific H/D exchange reactions. 

In the last decade, the combination of CRP techniques and newly found or reinvented highly effective and selective organic reactions termed as the click chemistry has been demonstrated to be a versatile tool for the specific constmction of novel functional macromolecules [28]. In 2001, Sharpless et al. [29] introduced the term click chemistry with its famous representative, the cycloaddition of azides with alkynes under copper catalysis. He defined a click reaction with a set of criteria The reaction must be modular, wide in scope, give very high yields, generate only inoffensive byproducts that can be removed by nonchromatographic methods, and be stereospecific (but not... 

Synthesis of 1,2,3-Triazoles Using Silica Gel-Supported Cu Catalysts Silica-based supports are easily available and environmentally benign. They have been widely utilized for heterogeneous Cu catalysis, which opens up new opportunities for the synthesis of greener clicked compounds. Wang s group immobilized a... 

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