DOI: 10.1002/adsc.201000530 Non-Magnetic and Magnetic Supported Copper(I) Chelating Adsorbents as Efficient Heterogeneous Catalysts and Copper Scavengers for Click Chemistry Alicia Megia-Fernandez, a Mariano Ortega-MuÇoz, a Javier Lopez-Jaramillo, a Fernando Hernandez-Mateo, a and Francisco Santoyo-Gonzalez a, * a Departamento de Quimica Organica, Facultad de Ciencias, Instituto de Biotecnología, 18071 Granada, Spain Fax: (+ 34)-958243186; phone: (+ 34)-958248087; e-mail: fsantoyo@ugr.es Received: July 5, 2010; Revised: September 9, 2010; Published online: December 7, 2010 Supporting information for this article is available on the WWW under http ://dx.doi.org/10.1002/adsc.201000530. Abstract: Novel supported chelating adsorbents bearing diverse multidentate nitrogenated ligands with strong copper(I) affinities are easily prepared in non-magnetic and magnetic variants using silica and silica-coated magnetite nanoparticles as suitable sup- ports and the aza-Michael-type addition of vinyl sul- fones as the ligation tool. These adsorbents are ver- satile materials with applications in the copper-cata- lyzed alkyne-azide cycloaddition (CuAAC) click chemistry where their complexation abilities enable them to act either as heterogeneous click catalysts when used in their complexed form or as copper(I) scavengers when used in their uncomplexed form. In the first instance, they proved to be robust and effi- cient heterogeneous catalysts to promote click reac- tions using extremely low doses and showing negligi- ble copper leaching, particularly in the case of the silica-based non-magnetic adsorbents, allowing a simple operational protocol for their rapid and easy removal by filtration or magnetic decantation and showing good recyclability properties. In their un- complexed form, the non-magnetic chelating adsorb- ents are very efficient copper scavengers that are able to remove any traces of metal contamination and that can be applied in tandem with any hetero- geneous supported copper(I) catalysts or as stand- alone copper removing system in any click protocol allowing the isolation of metal-free clicked com- pounds. Keywords: chelates; click chemistry; heterogeneous catalysis; magnetic nanoparticles; scavenger Introduction The discovery of the catalytic effect of Cu(I) in the 1,3-dipolar cycloaddition reaction of azides with al- kynes (CuAAC) [1] was a milestone in the develop- ment of the click chemistry concept [2] that has estab- lished this process as the most reliable “click” reac- tion. [3] A prolific research activity in this area during the last decade has led to the development of a ple- thora of protocols where the use of different Cu(I) sources for homogeneous catalysis constitutes the bulk of the reported applications on many research fields that have benefited from the high reliability of CuAAC reactions. The introduction of new variants to further improve the efficiency of the reaction has determined an outstanding level of development for this ligation methodology. In particular, the use of Cu(I) complexes with nitrogen-based ligands as click catalysts or mediators was revealed [4] shortly after the discovery of the CuAAC coupling [5] and was shown to both enhance the reaction rate and to protect the in- herent thermodynamic instability of Cu(I) species from oxidation under aerobic and/or aqueous condi- tions. In addition, the application of microwave irradi- ation has demonstrated its utility to increase the reac- tion rate and to improve yields with a dramatic reduc- tion of reaction times being observed in most proto- cols. [6] Despite the pivotal role played by Cu(I) in click cy- cloaddition reaction of azides and alkynes, the use of this metal is not without drawbacks, especially those related to contamination of clicked products with toxic metal which becomes an issue of utmost impor- tance particularly in bioconjugation and in biomedical and pharmaceutical applications of click chemistry. [7] Nowadays, several approaches have been used to 3306  2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Adv. Synth. Catal. 2010, 352, 3306 – 3320 FULL PAPERS