Recent Progress of Cu-Catalyzed Azide-Alkyne Cycloaddition Reactions (CuAAC) in Sustainable Solvents: Glycerol, Deep Eutectic Solvents, and Aqueous Media

Abstract

This mini-review presents a general overview of the progress achieved during the last decade on the amalgamation of CuAAC processes (copper-catalyzed azide-alkyne cycloaddition) with the employment of sustainable solvents as reaction media. In most of the presented examples, the use of water, glycerol (Gly), or deep eutectic solvents (DESs) as non-conventional reaction media allowed not only to recycle the catalytic system (thus reducing the amount of the copper catalyst needed per mole of substrate), but also to achieve higher conversions and selectivities when compared with the reaction promoted in hazardous and volatile organic solvents (VOCs). Moreover, the use of the aforementioned green solvents also permits the improvement of the overall sustainability of the Cu-catalyzed 1,3-dipolar cycloaddition process, thus fulfilling several important principles of green chemistry.

Investigation of Base-free Copper-Catalysed Azide–Alkyne Click Cycloadditions (CuAAc) in Natural Deep Eutectic Solvents as Green and Catalytic Reaction Media

“…Even if this protocol needed longer reaction times compared to the ones reported in literature with non-catalytic DESs, [50] the lower temperatures used and the reducing and the basic behavior of the investigated NADESs (with the same quantitative yields observed) promote this protocol as relevant in CuAAc transformations.…”

“…[44][45][46][47][48][49] CuAAc click reactions have been explored and analyzed in many different green solvents and reaction media, including DESs. [50] The investigated liquids (choline chloride/glycerol, D-sorbitol/urea and L-carnitine/urea), used in the presence of a base and of CuI, promoted the cyclization with excellent yields, comparable with those observed using the conventional volatile organic solvents, showing also excellent recycle capabilities.…”

Investigation of Base-free Copper-Catalysed Azide–Alkyne Click Cycloadditions (CuAAc) in Natural Deep Eutectic Solvents as Green and Catalytic Reaction Media

“…[44][45][46][47][48][49] CuAAc click reactions have been explored and analyzed in many different green solvents and reaction media, including DESs. 50 The investigated liquids (choline chloride/glycerol, D-sorbitol/urea and L-carnitine/urea), used in the presence of a base and of CuI, promoted the cyclization with excellent yields, comparable with those observed using the conventional volatile organic solvents, showing also excellent recycle capabilities.…”

Recent Trends and Prospects in the Copper‐Catalysed “on Water” Reactions

“…On this account, “click reactions” in water medium deserves special attention and is more likely to have wider applications in chemical biology. Nebra and Garcia‐Alvarez have presented a mini review describing the current progress in CuAAC performed in non‐hazardous solvents like glycerol, deep eutectic solvents and water [61] . The triazole formation is triggered by two main factors: Stability of the N 1 ‐N 2 bond and protonation of the cuprated triazole [62]…”