4.3 1,3-Dipolar Cycloadditions of Alkenes

Click reactions between 1,3-dipoles and alkenes are appealing due to their versatility, which goes beyond simple conjugation applications and the synthesis of five-membered heterocycles. Leveraging various 1,3-dipoles and alkenes, photoactivatable, highly reactive, and “click to release” systems have been developed. In this article, we explore the wide range of reactivities, selectivities, and applications offered by this class of cycloadditions.

2.1 Introduction to CuAAC

The basic principles of the copper-catalyzed azide–alkyne cycloaddition reaction (CuAAC), widely considered to be the first click reaction, are described. This involves amongst others the concept of click reactions, the mechanism of CuAAC, the synthesis and reactivity of organic azides and acetylenes, an overview of most commonly used copper(I) catalysts and ligands, the properties of 1,2,3-triazoles and their resemblance to amides, and a general overview of the scope and limitations of this reaction.

6.1 Thiol–Ene/Yne Click Reactions: A Powerful Tool Toward Diversity-Oriented Synthesis

The clickable addition reaction between thiols and unsaturated compounds leading to the generation of (branched/linear) thioethers or (branched/linear) vinyl sulfides is known as the hydrothiolation reaction. Based upon the nature of unsaturation, i.e. double bond or triple bond, hydrothiolation reactions are classified as thiol–ene and thiol–yne click reactions, respectively. These reactions have emerged as a powerful and widely used strategy for the generation of carbon–sulfur bonds due to several associated benefits including versatile synthetic procedures, wide functional-group tolerance, high atom economy with few to no byproducts, and simple purification. The hydrothiolation reactions have numerous trapping applications in the fields of polymer chemistry, nanoengineering, pharmaceuticals, natural products, and perhaps most importantly in medicinal chemistry for the synthesis of many drugs and bioactive molecules.

Organocatalytic Silicon-Free SuFEx reactions for modular synthesis of sulfonate esters and sulfonamides

Sulfur(VI) fluoride exchange (SuFEx) click chemistry provides a powerful tool for rapid construction of modular connections. Here, we report a novel catalytic silicon-free SuFEx reaction with sulfonyl fluorides. Under the catalysis of 10 mol% N-heterocyclic carbene (NHC), a range of phenols and alcohols react with different sulfonyl fluorides to afford sulfonate esters in 49-99% yields. In addition, Under the relay catalysis of 10 mol% N-heterocyclic carbene and 10 mol% 1-hydroxybenzotriazole (HOBt), a variety of primary and secondary amines react with different sulfonyl fluorides to produce sulfonamides in 58%-99% yields. More than 140 sulfonylated products, including 17 natural product derivatives have been prepared through this method. Mechanism study showed that NHCs might act as a carbon-centered Brønsted base to catalyse the SuFEx click reactions via the formation of hydrogen bonding with phenols or alcohols.

An Overview on the Performance of 1,2,3-Triazole Derivatives as Corrosion Inhibitors for Metal Surfaces

This review accounts for the most recent and significant research results from the literature on the design and synthesis of 1,2,3-triazole compounds and their usefulness as molecular well-defined corrosion inhibitors for steels, copper, iron, aluminum, and their alloys in several aggressive media. Of particular interest are the 1,4-disubstituted 1,2,3-triazole derivatives prepared in a regioselective manner under copper-catalyzed azide-alkyne cycloaddition (CuAAC) click reactions. They are easily and straightforwardly prepared compounds, non-toxic, environmentally friendly, and stable products to the hydrolysis under acidic conditions. Moreover, they have shown a good efficiency as corrosion inhibitors for metals and their alloys in different acidic media. The inhibition efficiencies (IEs) are evaluated from electrochemical impedance spectroscopy (EIS) parameters with different concentrations and environmental conditions. Mechanistic aspects of the 1,2,3-triazoles mediated corrosion inhibition in metals and metal alloy materials are also overviewed.

Click reaction in the synthesis of dendrimer drug-delivery systems

: Drug delivery systems are technologies designed for the targeted delivery and controlled release of medicinal agents. Among the materials employed as drug delivery systems, dendrimers have gained increasing interest in recent years because of their properties and structural characteristics. The use of dendrimer-nanocarrier formulations enhances the safety and bioavailability, increases the solubility in water, improves stability and pharmacokinetic profile, and enables efficient delivery of the target drug to a specific site. However, the synthesis of dendritic architectures through convergent or divergent methods has drawbacks and limitations that disrupt aspects related to design and construction and consequently slow down the transfer from academia to industry. In that sense, the implementation of click chemistry has been received increasing attention in the last years, because offers new efficient approaches to obtain dendritic species in good yields and higher monodispersity. This review focuses on recent strategies for building dendrimer drug delivery systems using click reactions from 2015 to early 2021. The dendritic structures showed in this review are based on β-cyclodextrins (β-CD), poly(amidoamine) (PAMAM), dendritic poly (lysine) (PLLD), dimethylolpropionic acid (bis-MPA), phosphoramidate (PAD), and poly(propargyl alcohol-4-mercaptobutyric (PPMA).

A Family of Externally-Functionalised Coordination Cages

New synthetic routes are presented to derivatives of a (known) M8L12 cubic coordination cage in which a range of different substituents are attached at the C4 position of the pyridyl rings at either end of the bis(pyrazolyl-pyridine) bridging ligands. The substituents are (i) –CN groups (new ligand LCN), (ii) –CH2OCH2–CCH (containing a terminal alkyne) groups (new ligand LCC); and (iii) –(CH2OCH2)3CH2OMe (tri-ethyleneglycol monomethyl ether) groups (new ligand LPEG). The resulting functionalised ligands combine with M2+ ions (particularly Co2+, Ni2+, Cd2+) to give isostructural [M8L12]16+ cage cores bearing 24 external functional groups; the cages based on LCN (with M2+ = Cd2+) and LCC (with M2+ = Ni2+) have been crystallographically characterised. The value of these is twofold: (i) exterior nitrile or alkene substituents can provide a basis for further synthetic opportunities via ‘Click’ reactions allowing in principle a diverse range of functionalisation of the cage exterior surface; (ii) the exterior –(CH2OCH2)3CH2OMe groups substantially increase cage solubility in both water and in organic solvents, allowing binding constants of cavity-binding guests to be measured under an increased range of conditions.