## 3 Discrete Cu(I/II) Complexes
### Polymeric Organic Supports from Natural Sources  
As noted already in Section 2.6, chitosan, the biodegradable polymer obtained by deacetylation of chitin, is still attracting much interest as catalyst support in view of its low cost, inoffensive nature, and prompt adsorption of metal ions by surface hydroxy and amino groups. After early contributions by [PERSON] et al. [176], the use in CuAAC of CS-Cu(I/II) complexes was examined recently by [PERSON] et al. and by [PERSON] et al. [177; 178]. In both studies the supported polymeric catalysts were obtained by suspending CS in the solution of a proper Cu(I/II) salt, followed by filtration or centrifugation, washing, and drying of the insoluble material. Characterization of the solid indicated an appreciable copper content (5.1 wt % by ICP-AES), but no signals pertinent to crystalline forms were observed by XRD. The former group tested CS-CuSO\({}_{4}\), at low catalyst loading (0.4 mol % of Cu) in water, in CuAAC between alkyl azides and aliphatic or aromatic alkynes (Scheme 1). On the contrary, the latter focused on the three-component CuAAC reaction between aromatic boronic acids, sodium azide, and aromatic alkynes (Scheme 2d). Also in this case water proved to be the solvent of choice, but the experiments involved the use of considerably larger amounts of catalyst (typically 10 mol % of CS-CuSO\({}_{4}\)). Under the said conditions good to excellent yields (71%-99%) were attained in both studies in 4-12 h at r.t. The CS-supported catalyst could be recovered by decantation and reused, albeit with variable degrees of success depending upon the specific reaction: With preformed azides, essentially quantitative yields were obtained in five initial runs and constant, yet reduced values (28%), were recorded in five additional reaction cycles carried out at five-fold larger S/C ratio. On the contrary, with boronic acids an appreciable reduction of yield was observed in the initial 5 cycles (90% \(\rightarrow\) 79%), which appears to mirror quite closely the progressively larger losses of insoluble material along the reaction series (approximate 18% of the initial amount after the 5 th reaction cycle).  
Cuttlebone, the rigid structural component of the cuttlefish body, is an hybrid material composed of calcium carbonate (aragonite form), proteins, and \(\beta\)-chitin [179]. In view of the complexing/reducing properties of the latter component, [PERSON] et al. explored the use of cuttlebone as a support for CuAAC catalytic systems [180]. Because XPS analysis of the solid obtained by treating powdered cuttlebone with CuCl\({}_{2}\) in water confirmed the presence of copper in the Cu(I)/Cu(II) mixed oxidation state, the material was tested directly in the three-components CuAAC reaction of benzyl bromide and phenylacetylene. Strangely enough, bare cuttlebone displayed some catalytic activity itself but, as expected, the reaction rate in the presence of metal-loaded material proved significantly higher. Best results were attained by using 8.5 mol % of the supported copper catalyst in water at 40 \({}^{\circ}\)C, conditions under which the CuAAC multi-component reaction of other reactive bromides led to good triazole yields (72%-95%) within 5-80 min. Recovery by filtration and washing with different solvents allowed the reuse of the catalytic material in seven reaction cycles. This led to observe some decrease of substrate conversion and product yield (100% \(\rightarrow\) 90% and 95% \(\rightarrow\) 85%, respectively) and the reduction of the metal loading on the cuttlebone support (1.77 mmol\(\cdot\)g\({}^{-1}\)\(\rightarrow\) 1.54 mmol\(\cdot\)g\({}^{-1}\)). In spite of this, the measured amount of leached copper was found to be relatively modest, with reported levels in selected isolated triazole products ranging between 37 ppm and 46 ppm.