Cycloaddition reactions strain-promoted

The reaction of methylenecyclopropanes with transition metal complexes is well known to promote a catalytic a-ir cycloaddition reaction with unsaturated compounds, in which a trimethylenemethane complex might exist71-76. Recently, much interest has been focused on the interaction of strained silicon-carbon bonds with transition metal complexes. In particular, the reaction of siliranes with acetylene in the presence of transition metal catalysts was extensively investigated by Seyferth s and Ishikawa s groups77-79. In the course of our studies on alkylidenesilirane, we found that palladium catalyzed reaction of Z-79 and E-79 with unsaturated compounds displayed ring expansion reaction modes that depend on the (Z) and (E) regiochemistry of 79 as well as the... 

To date, four bioorthogonal reactions have been used to label glycans on cells and in lysates hydrazone/oxime formation with ketones, thiol alkylation with maleimides, Staudinger ligation of azides with triaryl phosphines, and copper-catalyzed or strain-promoted [3+2] cycloadditions of alkynes and azides (Figure 5) (25, 26, 32, 34, 35). While each reaction has been used extensively, most recent applications have employed azido- or alkynyl-sugars due to their superior metabolic incorporation and efficient ligations. 

Figure 5. Bioorthogonal reactions on sugars, A. Ketones react with hydrazides to give hydrazones. B. Thiols undergo Michael Reaction with maleimides. C, Azides undergo Staudinger ligation with phosphines or D. strain-promoted or copper catalyzed [3 2] cycloaddition with all nes. E. Alkynes undergo copper-catalyzed [3- 2] cycloaddition with azides.

In many instances, the entropic assistance provided in the intramolecular Diels-Alder reaction is sufficient to promote azadiene participation in Diels-Alder reactions.12 The incorporation of the azadiene system, or dienophile, into a reactive or sensitive system, e.g., heterocumulene or strained olefin, allows a number of specialized azadiene Diels-Alder reactions. Many such examples may represent stepwise, polar [4 + 2] cycloaddition reactions. 

Fig. 10.3-20 Metal-free bioconjugation using a strain-promoted [3 + 2] dipolar cycloaddition reaction. This reaction is accelerated by the relief of ring strain in the transition state as the alkyne carbons become sp2 hybridized.

POC-click is formed by thermo-cross-linking the mixture of pre-POC-N (azide-containing POC prepolymer) and pre-POC-Al (alkyne-containing POC prepolymer) the process applies synchronous binary cross-link mechanism, esterification, and thermal click reaction, and the residual azide groups on the surface of POC-click film or scaffold paved the way of surface bioconjugation through strain-promoted alkyne-azide cycloaddition (SPAAC), another copper-free click reaction. 

Recent advances and applications of strain-promoted alkyne-nitrone cycloaddition reactions in bio-orthogonal labeling (14COCB81) and of natural isoxazoline derivatives in the field of anticancer research (14EJM121) were reviewed. 

A one-step Lewis acid-catalysed intermolecular 4- -3-cycloaddition of aromatic a,)3-unsaturated aldehyde and ketones (105) with epoxides (106) formed seven-membered oxacycles (107) under mild conditions (Scheme 34).The effect of oxygen-, sulfur-, and halogen-substituents on the reactivity of nitrogen-stabilized oxyallyl cations in 4- -3-cycloaddition reactions has been extensively investigated. Aza-oxyallyl cationic intermediates react with cyclopentadiene and furan via an aza-4 -I- 3-cycloaddition reaction to form bicyclic cycloadducts in moderate yields. The intramolecular formal 4- -4-cycloaddition of conjugated enynes with an e-deflcient cyclobutene (108) yielded a strained six-membered cyclic allene (109) that isomerized to a 1,3-cyclohexadiene (110). This intermediate underwent a thermal or acid-promoted six-electron electrocyclic ring opening to yield a 2,4,6-cyclooctatrienone (111) (Scheme 35). ... 

Strain-promoted azide-alkyne cycloaddition (SPAAC), since its inception in 2004, has firmly established itself as a powerful click chemistry tool. The commercial access of starting materials, its ease of operation, the nowadays practical reaction... 

From the cycloaddition reaction standpoint, the photo-generated reactive species suitable for both 1,3-dipolar cycloaddition reactions and Diels-Alder reactions have been studied in the literature. In this review, we will focus our discussion on four cycloaddition reactions (1) 1,3-dipolar cycloaddition between aUcenes and photogenerated nitrile imines (2) 1,3-dipolar cycloaddition between aUcenes and photogenerated nitrile ylides (3) photoinduced hetero Diels-Alder reactions and (4) photoinduced strain promoted azide-alkyne cycloaddition (Scheme 3). It is... 

Fig. 1 Cycloaddition reactions employed in nucleic acid labeling with reporter groups (green star). A Cu -mediated azide-alkyne cycloaddition (CuAAC) of a terminal alkyne with an azide. B Strain-promoted azide-alkyne cycloaddition (SPAAC) of an azide with a cyclooctyne derivative. C Staudinger ligation of an azide with a phosphine derivative (not a cycloaddition reaction, see below). D Norbornene cycloaddition of a nitrile oxide as 1,3-dipole and a norbornene as dipolarophile. E Inverse electron-demand Diels- Alder cycloaddition reaction between a strained double bond (norbornene) and a tetrazine derivative. F Photo-cUck reaction of a push-pull-substituted diaiyltetrazole with an activated double bond (maleimide)...

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. 

Shelbourne M, Chen X, Brown T, El-Sagheer AH (2011) Fast copper-free click DNA ligation by the ring-strain promoted alkyne-azide cycloaddition reaction. Chem Commun 47(22) 6257-6259. doi 10.1039/clccl0743g... 

Describe the main criteria that should be satis ed for a reaction to be called a click reaction How would you justify the inclusion of the following reactions into the pantheon of click reactions (a) Copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reactions (b) strain-promoted azide-alkyne coupling (SPAAC) reactions (c) Diels-Alder (DA) cycloaddition reactions (d) thiol-ene (TE) reactions and (e) thiol-yne (TY) reactions ... 

Figure 14.5 Reaction scheme of copper-free strain-promoted azide-alkyne cycloaddition. The reaction occurs because of the interaction between functionahzed polymer with azide (blue) and the triple bond (red) of the reactive cyclooctyne, in absence of any catalysts.

Staudinger-based ligation techniques, oxime/hydrazone formation, or strain-promoted azide-allq ne cycloaddition reactions/ To be able to specifically address a particular protein target, or other moieties, these reactions use chemical groups that are not typically found in natural systems. 

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