Azides and alkynes

After the optimization of these conditions, by adding an azide to the input stream it was possible to synthesize a range of substituted triazoles in a heterogeneously catalysed three-component reaction (Scheme 18). After the CFC, the stream was passed through a column containing a resin-immobilized copper-based catalyst, which was used in a previous work by the same authors to successfully catalyze the formation of triazoles from alkynes and azides [44]. An immobilized thiourea-containing cartridge was subsequently used to remove any leached Cu catalyst. In a similar way as for the alkynes production, the series of resins was used to purify the product. 

Perez-Balderas F, Ortega-Munoz M, Morales-Sanfrutos J et al (2003) Multivalent neogly-coconjugates by regiospecific cycloaddition of alkynes and azides using organic-soluble copper catalysts. Org Lett 5( 11) 1951—1954... 

Click chemistry can also be efficiently combined with p,CP. 1,3-Dipolar cycloadditions where alkynes and azides react to give triazoles can serve as a good example for the reaction conducted under stamp confinement.111 Usually this reaction... 

The most important syntheses in this group consist of the thermal 1,3-dipolar cycloaddition <65CB4014, 67CB2494) of azides to alkynes, which is, of course, one of the most versatile routes to l//-l,2,3-triazoles. A wide range of substituents can be incorporated into the alkyne and azide components. 

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. 

A one-pot, copper-catalyzed formation of fully decorated triazoles was recently demonstrated by Ackermann. In the first step, a copper-catalyzed click reaction produces triazoles from alkynes and azides. In the second step, a direct, copper-catalyzed... 

Huisgen 1,3-dipolar cycloaddition (click reaction) between terminal alkynes and azides is a highly efficient approach for the post modification of polymers. This technique is tolerant to a wide rage of reaction conditions and functional groups allowing fast coupling reactions under simple reaction conditions with... 

Regiospecific catalytic cydoaddition of alkynes and azides using copper complexes as soluble organic catalysts enables the preparation of divalent and mul-... 

Figure 10 Carbohydrate microplate arrays prepared by the noncovalent immobilization of azide-derivatized carbohydrates to microtiter plates via a 1,3-dipolar cycloaddition reaction between alkynes and azides. Carbohydrates displaying terminal azides can be captnred on microtiter plate surfaces through a terminal alkyne attached to a long, ahphatic tether and screened directly on the microtiter plate surface.

Scheme 14 Triazole-linked ubiquitin conjugate with post-translationally installed alkyne and azide. POI protein of interest...

Variations in monomer and catalyst stoichiometry, reaction time or temperature all proved unsuccessful in triggering the formation of the dipolar cycloaddition product. The use of excess cucurbituril led only to quantitative isolation of the pseudorotaxanes derived from 1 and 2 (Fig. 1.38). We speculated that our initial monomer design must have been flawed. The choice of a six-carbon spacer to maximize recognition of the monomer by cucurbituril may be the cause of the catalytic inhibition. We hypothesized that the pseudorotaxanes derived from cucurbituril and monomers 1 and 2 must form much faster than any possible ternary complex and that the essentially perfect fit of each monomer inside cucurbituril would prevent the simultaneous encapsulation of alkyne and azide moieties by a third cucurbituril with the correct conformation required for catalysis. 

A one-pot synthesis of macrocycles by a domino three-component reaction and [3+2] cycloaddition was investigated by Zhu et aL [99]. By combining three appropriately designed simple substrates, a programmed sequence involving an a-isocyano acetamide-based three-component reaction followed by a copper-catalyzed cycloaddition of alkyne and azide took place to afford macrocycles 119 in moderate to good yields (Scheme 26). 

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