Alkynes 2 + 2 cycloaddition reactions

Gramlich PME, Wirges CT, Manetto A, Carell T (2008) Postsynthetic DNA modification through the copper-catalyzed azide-alkyne cycloaddition reaction. Angew Chem Int Ed... 

A variety of triazole-based monophosphines (ClickPhos) 141 have been prepared via efficient 1,3-dipolar cycloaddition of readily available azides and acetylenes and their palladium complexes provided excellent yields in the amination reactions and Suzuki-Miyaura coupling reactions of unactivated aryl chlorides <06JOC3928>. A novel P,N-type ligand family (ClickPhine) is easily accessible using the Cu(I)-catalyzed azide-alkyne cycloaddition reaction and was tested in palladium-catalyzed allylic alkylation reactions <06OL3227>. Novel chiral ligands, (S)-(+)-l-substituted aryl-4-(l-phenyl) ethylformamido-5-amino-1,2,3-triazoles 142,... 

A copper catalysed click (azide-alkyne cycloaddition) reaction has been used to prepare a fluorous-tagged TEMPO catalyst (Figure 7.20). TEMPO is a stable organic free radical that can be used in a range of processes. In this case, its use in metal-free catalytic oxidation of primary alcohols to aldehydes using bleach as the terminal oxidant was demonstrated. The modified TEMPO can be sequestered at the end of the reaction on silica gel 60 and then released using ethyl acetate for reuse in further reactions in this way the TEMPO was used four times with no loss in activity. 

Rodionov VO, Fokin VV, Finn MG. Mechanism of the ligand-free Cu-I-catalyzed azide-alkyne cycloaddition reaction. Angew. Chem. Int. Ed. 2005 44 2210-2215. 

Recently, Wittmann and co-workers reported the one-pot procedure for di-azo transfer and azide-alkyne cycloaddition reaction. As shown in Scheme 21 the divalent glycoconjugate 104 was obtained in excellent yield from amine 103 without the need for isolation of the azide intermediate. Similarly, Moses et al. reported on the efficient conversion of aromatic amines into 12 3-triazoles [75]. 

Scheme 9 Cooperatively catalysed azide-alkyne cycloaddition reaction with a second Cu metal centre participating during key intermediate steps...

Scheme 10 Highly efficient Cu(I) bimetallic catalysts (22 and 23) for the azide-alkyne cycloaddition reaction...

CuAAC Copper-catalyzed azide-alkyne cycloaddition reaction... 

Park, J.C., Kim, A.Y., Kim, J.Y., Park, S., Park, K.H. and Song, H. 2012. ZnO-CuO corebranch nanocatalysts for ultrasound-assisted azide-alkyne cycloaddition reactions. Chem. Commun. 48 8484-8486. 

Chemical modification of liposome surfaces via a copper-mediated [3-I-2] azide-alkyne cycloaddition reaction based on click chemistry and monitored by a colorimetric assay... 

To date, copper ions still remain the choice of metal catalyst for the azide-alkyne cycloaddition reaction, which generates 1,4-disubstituted 1,2,3-triazoles as the final product. Chemists have also studied the feasibility of other metals in catalyzing the azide-alkyne cycloaddition. For example, Hein and Fokin surveyed the complexes of all of the first-row transition elements, as well as complexes of Pd(0/II), Pt(II), Au(I/III), and Hg(II) ions, among others. However, none of these metal ions were found to produce triazoles in synthetically useful yields, and the effects of these... 

Presolski SI, Hong V, Cho S-H, Finn MG (2010) Tailored ligand acceleration of the cu-catalyzed azide-alkyne cycloaddition reaction practical and mechanistic implications. J Am Chem Soc 132 14570-14576... 

Xie F, Sivakumar K, Zeng Q et al (2008) A fluorogenic Cu(I) catalyzed azide-alkyne cycloaddition reaction of azidoanthracene derivatives. Tetrahedron 64 2906-2914... 

Likewise, Hirao et al. applied copper free chck chemistry for RNA functionalization via the 7-(2-thienyl)imidazo[4,5-b]pyridine (Ds) and pyrrole-2-carbalde-hyde (Pa) unnatural base pair [152], For this, an azide-modified Pa nucleobase (N3-Pa) was incorporated as triphosphate in a T7 in vitro transcription reaction using Ds as corresponding nucleobase in the DNA template (Fig. 3b, 2). Post-transcriptional modification was achieved using fluorescent dibenzocyclooctyne (DIBO) derivatives in a strain-promoted azide-alkyne cycloaddition reaction. Transcription and efficient site-specific labeling of a 260mer RNA was demonstrated. 

Thongh the high ef ciency, orthogonahty, and simplicity of CuAAC reactions have prompted rapid and extensive adoption of the method in the eld of macromolecular engineering, the use of copper is undesirable and a cause of concern in the context of biomaterials synthesis. This has generated interest in new metal-free azide-alkyne cycloaddition reactions (discussed below) which do not suffer from toxicity issues. 

Lai S, Diaz-Gonzalez S (2011) [CuBifPPhj) ] for azide-alkyne cycloaddition reactions imder strict click conditions. J Org Chem 76 2367-2373... 

Park et al. [61] synthesized ZnO-CuO core-branch hybrid NPs by copper oxide growth and controlled oxidation on ZnO nanospheres, and exhibited remarkable enhancement of catalytic activity and stability for ultrasound-assisted [3+2] azide-alkyne cycloaddition reactions imder ultrasonic irradiation (Scheme 5.19). The surface species of the catalysts were investigated by XPS with the core level of Cu 2p3 2 before and after the reaction. The peaks are deconvoluted into two peaks, where the peak at lower binding energy is attributed to Cu(l) and that at higher binding energy is attribnted to the Cu(ll) species. Before the reaction, the... 

In the BONCAT method, the cellular system of interest (cultured cells, tissue slices, or live animals) is pulse-labeled with a non-canonical amino acid that carries a reactive side chain. In our initial experiments, we used azidohomoalanine (Aha) as the label because Aha-Iabeled proteins can be selectively tagged with dyes or affinity reagents through copper-catalyzed or strain-promoted azide-alkyne cycloaddition reactions [34-36]. Tagged proteins can then be separated from other... 

In 2014, Ding et al. [70] reported an iridium-catalyzed azide-alkyne cycloaddition reaction (IrAAC) of electron-rich internal alkynes (Scheme 9.27). The reaction is highly regioselective in favor of the 1,5-isomer. 

Also, triazolobenzoazepines 42 are obtained in high yields in a one-pot azide/alkyne cycloaddition reaction, using 2-azidobenzoic acid andpropargylamines . ... 

An intramolecular azide/alkyne cycloaddition reaction to give the fused triazoloimida-zoles 44 is also observed using 43 . 

Click chemistry comprises a number of organic heteroatom coupling procedures that comply with the stringent criteria as defined by Sharpless (see also Chapter 2) (Kolb et al, 2001). Among these click reactions, the copper-catalyzed azide-alkyne cycloaddition reaction... 

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.

Copper-Catalyzed Azide-Alkyne Cycloaddition Reaction. 46... 

Since the first reaction was discovered by Reppe and Schweckendiek [4], numerous transition metals have been used to promote alkyne [2 + 2 + 2] cycloadditions [1]. The majority of attention has focused on group 9 and 10 transition elements, including Co, Rh, Ni, and Pd. In comparison to these precedents, [2 + 2 + 2] alkyne cycloaddition reactions involving group 8 metals have been relatively neglected. However, over the past decade, there has been significant progress in efficient and selective [2 + 2 + 2] alkyne cycloadditions catalyzed by ruthenium. In this section we review the synthesis of benzene derivatives via alkyne [2 + 2 + 2] cycloaddition both stoichiometrically and catalytically. 

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