The CuAAC: Principles, Homogeneous and Heterogeneous Catalysts, and Novel Developments and Applications

Abstract

The copper‐catalyzed azide/alkyne cycloaddition reaction (CuAAC) has emerged as the most useful “click” chemistry. Polymer science has profited enormously from CuAAC by its simplicity, ease, scope, applicability and efficiency. Basic principles of the CuAAC are reviewed with a focus on homogeneous and heterogeneous catalysts, ligands, anchimeric assistance, and basic chemical principles. Recent developments of ligand design and acceleration are discussed.

3D Printing of Core–Shell Capsule Composites for Post‐Reactive and Damage Sensing Applications

“…[ 17a–c ] The desired composites are based on PCL, containing 10–15 wt% azide(I)‐nanocapsules (Figures S2 and S3, Supporting Information) and a corresponding amount of TRGO, [ 17a ] able to catalyze a chemical reaction triggered by an external stimulus, as azides and alkynes are known to react in a “CuAAC‐click” reaction. [ 24 ] Two different trivalent monomers, one bearing azide groups (I), the other bearing alkyne groups (II), were separated by encapsulation methods and could then react after activation via a Cu(I)‐catalyzed Huisgen‐1,3‐dipolar cycloaddition under a formation of 1,4‐triazole crosslinked resin. [ 24,25 ] We aimed to transform the known mold based fabrication into a 3D‐printed‐based approach.…”

“…[ 24 ] Two different trivalent monomers, one bearing azide groups (I), the other bearing alkyne groups (II), were separated by encapsulation methods and could then react after activation via a Cu(I)‐catalyzed Huisgen‐1,3‐dipolar cycloaddition under a formation of 1,4‐triazole crosslinked resin. [ 24,25 ] We aimed to transform the known mold based fabrication into a 3D‐printed‐based approach. Since the final composite consisted of the PCL matrix, a graphene‐based TRGO catalyst (containing catalytic CuO 2 ‐nanoparticles), the azide(I)‐filled nanocapsules (200 nm), and a trivalent, reactive alkyne (II), we first probed changes in melt‐viscosity of the PCL melt at 80 °C upon addition of the catalyst in amounts of 1–5 wt% TRGO (Figure 2c).…”

Diversity Oriented Clicking (DOC): Divergent Synthesis of SuFExable Pharmacophores from 2‐Substituted‐Alkynyl‐1‐Sulfonyl Fluoride (SASF) Hubs

“…This trend is epitomized by the influence that 1,3-dipolar cycloaddition reactions have had on click chemistry, and most notably the azide-alkyne fusion reaction recognized [10] by Professor Rolf Huisgen. [11,12] Arguably, Huisgens early work on cycloaddi-tion chemistry has influenced the evolution of click chemistry more than any other; ultimately leading to the discovery of three high-profile breakthroughs: i) target accelerated in situ click chemistry as a tool for drug discovery; [13][14][15][16][17] ii) the regioselective stepwise copper-catalyzed Huisgen azide-alkyne cycloaddition (CuAAC) reaction [18,19] -a transformation with an unrivaled breadth of application; [3,[20][21][22] and iii) the strain-promoted Huisgen 1,3-dipolar cycloaddition reaction between azide-alkyne (SPAAC, 2004), [23,24] used ubiquitously in bioconjugation applications (Figure 1).…”

Diversity Oriented Clicking (DOC): Divergent Synthesis of SuFExable Pharmacophores from 2‐Substituted‐Alkynyl‐1‐Sulfonyl Fluoride (SASF) Hubs

“…This trend is epitomized by the influence that 1,3‐dipolar cycloaddition reactions have had on click chemistry, and most notably the azide–alkyne fusion reaction recognized by Professor Rolf Huisgen . Arguably, Huisgen's early work on cycloaddition chemistry has influenced the evolution of click chemistry more than any other; ultimately leading to the discovery of three high‐profile breakthroughs: i) target accelerated in situ click chemistry as a tool for drug discovery; ii) the regioselective stepwise copper‐catalyzed Huisgen azide–alkyne cycloaddition (CuAAC) reaction—a transformation with an unrivaled breadth of application; and iii) the strain‐promoted Huisgen 1,3‐dipolar cycloaddition reaction between azide–alkyne (SPAAC, 2004), used ubiquitously in bioconjugation applications (Figure ).…”