Click resins

Soutullo, M.D., Odom, C.I., Wicker, B.F., Henderson, C.N., Stenson, A.C., and Davis, J.H., Reversible CO2 capture by unexpected plastic- resin-, and gel-like ionic soft materials discovered during the combi-click generation of a TSIL library, Chem. Mater., 19, 3581-3583, 2007. 

Lober S, Rodriguez-Loaiza P, Gmeiner P (2003) Click linker efficient and high-yielding synthesis of a new family of SPOS resins by 1,3-dipolar cycloaddition. Org Lett 5 1753-1755... 

In order to avoid the limitation of the use of the anchoring step as a source of diversity to prepare libraries of supported ligands containing the same type of aminoalcohol as 195, click chemistry was employed. This more convenient and efficient technique is a copper(I)-catalyzed cycloaddition between an alkyne and an azide [137]. Aminoalcohol-derived alkynes 199 were prepared by reaction of 194 with different bromine reagent. The reaction between these alkynes and a variety of azido resins with different degree of functionalization (f= 0.74 - 2.25 mmol Ns/g) was performed to afford the supported-ligands 200 (Scheme 83). 

Several heterogeneous catalysts have been shown to effect related multicomponent couplings. These include cross-linked polymeric ionic liquid material-supported copper (Cu-CPSIL), silica-dispersed CuO (CuO/Si02), and imidazolium-loaded Merrifield resin-supported copper (Cu-PSIL), all of which can be used in water at room temperature to arrive at 1,4-disubstituted-1,2,3-triazoles from alkyl halides, NaNs, and terminal alkynes. Each can be filtered and reused several times with minimal loss of efficacy. Multistep flow synthesis, specifically including generation of underused vinyl azides and their subsequent click conversions to vinyl triazoles, has also been reported. ... 

Solid-phase click chemistry in organic solvents (e.g., DMF and THF) works well, seemingly independent of the support Resins such as polystyrene and polyethylene glycol (PEGA) attest to tolerance to both nonpolar and polar types. As outlined in the original Meldal el al. papers, novel triazole-containing polypeptides... 

In several cases, modified TentaGel resins were chosen as the supports because they could swell in a variety of solvents and efficiently promote the click reactions while simultaneously stabilizing the Cu(I) species against oxidation (Chan and Fokin, 2007 Suzuka et al, 2010). In addition, hardly any Cu leaching was observed and the resin could be efficiently reused. However, the catalytic activity was unsatisfactory due to the low Cu loading on the supports. Thus, the scope of their application is limited to a certain degree (Dervaux and Du Prez, 2012). 

Another inventive extension of click chemistry is the concept of cUck-resins that promote solid phase supported reactions to work under nearly perfect conditions, fulfilling the requirements of click chemistry [32, 33]. This approach has enabled the assembly of a library of carboxylic arene bioisoesters, with the general formula V [34] as potential dopamine D4 receptor ligands [35]. In essence, the authors completed parallel synthesis of bioactive tert-amines V, utilizing triazolyl-methylacrylate 7 as a linker. The product was readily generated from the commercial azidomethyl substituted polystyrene 5 and propargyl acrylate 6 via Cu(I) catalyzed 1,3-dipolar cycloaddition (Scheme 15.4). 

Scheme 15.4 Click chemistry on a resin, applied to the synthesis of bioactive rert-amines V...

A 1,2,3-triazole-based solid-phase click linker was developed with an aldehyde functionality or a regenerative Michael acceptor (REM) functionality (Figure 11.1). In addition, a chiral pyrrolidine catalyst was grafted to the resin with a 1,2,3-triazole linker, enabling enantioselective Michael addition of ketones to nitroolefins... 

S. Lober, P. Gmeiner, Click chemistry on solid support synthesis of a new REM resin and application for the preparation of tertiary amines. Tetrahedron, 2004, 60, 8699-8702. 

Yujing Li is pursuing her PhD in the School of Materials Science and Engineering at ECUST. Her current research interests include click chemistry, novel rigid polytriazole resins and their composites. 

SCHEME 25 Heterogeneous copper catalysts supported on chelate resins catalyzing Click reaction. 

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