Recent Advances in Copper-Based Solid Heterogeneous Catalysts for Azide–Alkyne Cycloaddition Reactions

Abstract

The copper(I)-catalyzed azide−alkyne cycloaddition (CuAAC) reaction is considered to be the most representative ligation process within the context of the “click chemistry” concept. This CuAAC reaction, which yields compounds containing a 1,2,3-triazole core, has become relevant in the construction of biologically complex systems, bioconjugation strategies, and supramolecular and material sciences. Although many CuAAC reactions are performed under homogenous conditions, heterogenous copper-based catalytic systems are gaining exponential interest, relying on the easy removal, recovery, and reusability of catalytically copper species. The present review covers the most recently developed copper-containing heterogenous solid catalytic systems that use solid inorganic/organic hybrid supports, and which have been used in promoting CuAAC reactions. Due to the demand for 1,2,3-triazoles as non-classical bioisosteres and as framework-based drugs, the CuAAC reaction promoted by solid heterogenous catalysts has greatly improved the recovery and removal of copper species, usually by simple filtration. In so doing, the solving of the toxicity issue regarding copper particles in compounds of biological interest has been achieved. This protocol is also expected to produce a practical chemical process for accessing such compounds on an industrial scale.

Copper supported silica-based nanocatalysts for CuAAC and cross-coupling reactions

“…Furthermore, metals like Ru, Ag, Au, Ir, Ni, Zn, and Ln have also been used to catalyze azide-alkyne cycloaddition reactions for the regioselective synthesis of 1,4or 1,5-disubstituted or 1,4,5-trisubstituted triazoles (Scheme 1a), which depend on reagents (e.g., aliphatic or aromatic) and the selected conditions for a CuAAC reaction, as summarized in Scheme 1b. 47 Fokin et al 48 reported direct evidence for a binuclear Cu intermediate's involvement and a number of stages involving Cu (I) -aryl intermediates have been proposed in Scheme 2a and b. During this mechanism, two Cu atoms are required to formation of the active cycloaddition complex and their relation was described.…”

“…, aliphatic or aromatic) and the selected conditions for a CuAAC reaction, as summarized in Scheme 1b. 47…”

Decade Advances of NaN3 in Three‐component Reactions

“…1,3‐Dipolar cycloaddition reaction of organic azides and alkynes has gained considerable attentions [11a–k] . 1,2,3‐Triazole scaffolds are major products.…”

On the mechanochemical synthesis of C-scorpionates with an oxime moiety and their application in the copper-catalyzed azide–alkyne cycloaddition (CuAAC) reaction

“…This was publicly recognized with the award of Nobel Prize in Chemistry to Morten Meldal, Carolyn R. Bertozzi and K. Barry Sharpless in 2022. [5][6][7][8] Researchers in this area have focused on developing more sustainable conditions by seeking greener solvents and copper precursors that can generate copper(I) efficiently, while decreasing or eliminating the need for reducing agents and bases.…”