Copper-catalyzed azide–alkyne cycloaddition (CuAAC) is a widely utilized, reliable, and straightforward way for making covalent connections between building blocks containing various functional groups. It has been used in organic synthesis, medicinal chemistry, surface and polymer chemistry, and bioconjugation applications. Despite the apparent simplicity of the reaction, its mechanism involves multiple reversible steps involving coordination complexes of copper(I) acetylides of varying nuclearity. Understanding and controlling these equilibria is of paramount importance for channeling the reaction into the productive catalytic cycle. This tutorial review examines the history of the development of the CuAAC reaction, its key mechanistic aspects, and highlights the features that make it useful to practitioners in different fields of chemical science.

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Copper-catalyzed azide–alkyne cycloaddition (CuAAC) and beyond: new reactivity of copper(I) acetylides

Heterocycles constitute the largest and the most diverse family of organic compounds Among them, aromatic heterocycles represent structural motifs found in a great number of biologically active natural and synthetic compounds, drugs, and agrochemicals Moreover, aromatic heterocycles are widely used for synthesis of dyes and polymeric materials of high value 1 There are numerous reports on employment of aromatic heterocycles as intermediates in organic synthesis 2

Although, a variety of highly efficient methodologies for synthesis of aromatic heterocycles and their derivatives have been reported in the past, the development of novel methodologies is in cuntinious demand Particlularly, development of new synthetic approaches toward heterocycles, aiming at achieving greater levels of molecular complexity and better functional group compatibilities in a convergent and atom economical fashions from readily accessible starting materials and under mild reaction conditions, is one of a major research endeavor in modern synthetic organic chemistry Transition metal-catalyzed transformations, which often help to meet the above criteria, are among the most attractive synthetic tools

Several excellent reviews dealing with transition metal-catalyzed synthesis of heterocyclic compounds have been published in literature during recent years Many of them highlighted the use of a particular transition metal, such as gold,3 silver,4 palladium,5 copper,6 cobalt,7 ruthenium,8 iron,9 mercury,10 rare-earth metals,11 and others Another array of reviews described the use of a specific kind of transformation, for instance, intramolecular nucleophilic attack of heteroatom at multiple C–C bonds,12 Sonogashira reaction,13 cycloaddition reactions,14 cycloisomerization reactions,15 C–H bond activation processes,16 metathesis reactions,17 etc Reviews devoted to an application of a particular type of starting materials have also been published Thus, for example, applications of isocyanides,18 diazocompounds,19 or azides20 have been discussed In addition, a significant attention was given to transition metal-catalyzed multicomponent syntheses of heterocycles21 Finally, syntheses of heterocycles featuring formation of intermediates, such as nitrenes,22 vinylidenes,23 carbenes, and carbenoids24 have also been reviewed

The main focus of the present review is a transition metal-catalyzed synthesis of aromatic monocyclic heterocycles The organization of the review is rather classical and is based on a heterocycle, categorized in the following order: (a) ring size of heterocycle, (b) number of heteroatoms, (c) type of heterocycle, and (d) a class of transformation involved A brief mechanistic discussion is given to provide information about a possible reaction pathway when necessary The review mostly discusses recent literature, starting from 200425 until the end of 2011, however, some earlier parent transformations are discussed when needed

Transition Metal-Mediated Synthesis of Monocyclic Aromatic Heterocycles

Intramolecular Cross-Linking Methodologies for the Synthesis of Polymer Nanoparticles.

(Chemical Equation Presented) 4-Substituted 1-(N-sulfonyl)-1,2,3-triazoles are selectively obtained by using the Cu-catalyzed azide-alkyne cycloaddition reaction with sulfonyl azides. Performing the reaction at 0°C in chloroform in the presence of 2,6-lutidine and Cul as the catalyst effectively prevents the ketenimine pathway and provides convenient access to N-sulfonyltriazoles in good to excellent yields.

Copper‐Catalyzed Synthesis of N‐Sulfonyl‐1,2,3‐triazoles: Controlling Selectivity

Electrochemical nanoarchitectonics and layer-by-layer assembly: From basics to future

Data on the synthetic routes to substituted 1,2,3-triazoles, including those containing functional groups, based on cyclisation of various nitrogen compounds published during the last 15 years are described. Examples of using new triazole derivatives in agrochemistry, medicine and engineering are given.

https://iopscience.iop.org/article/10.1070/RC2005v074n04ABEH000893/pdf

1,2,3-Triazole and its derivatives. Development of methods for the formation of the triazole ring

A novel pyrazolylpyrimidine ligand (L) and its complex CuLCl(2) were prepared and structurally characterized. The simultaneous crystallization of three polymorphs of CuLCl(2), green (G), emerald green (EG) and orange (O), was discovered. The molecular structures vary only slightly between the three forms. The Cu atom forms four coordinate bonds with the two N and two Cl atoms, and a shortened Cu...H contact with an H atom of the phenyl ring in L. The structural difference between polymorphs was analyzed with the boundary surfaces of molecular Voronoi-Dirichlet polyhedra. The difference in colour of the polymorphs is likely to be due to the different pi-pi stackings. There is no stacking in the G modification, but EG and O polymorphs demonstrate face-to-face and slipped stacking, resulting in dimers and infinite chains, respectively. The EG and O polymorphs are packed according to the hexagonal close-packing motif, while in G no special topology is found.

Three differently coloured concomitant polymorphs: synthesis, structure and packing analysis of (4-(3',5'-dimethyl-1H-pyrazol-1'-yl)-6-methyl-2-phenylpyrimidine)dichlorocopper(II).

Unexpected Transformations of 4-Azido-2-(2’-hydroxyphenyl)-5-ethoxycarbonyl-pyrimidine: the Formation of 4-Hydroxyamino-2-(2’-hydroxyphenyl)- 5-ethoxycarbonylpyrimidine and Ethyl 3-(2’-Hydroxybenzoylamino)- 2-(1” H-tetrazol-5” -yl)acrylate

Intramolecular Cyclization in 4-Azido-5-ethoxycarbonyl-2-(2′-hydroxyphenyOpyrimidine: Synthesis and Properties of 3-Ethoxy-6-(2′-hydroxyphenyl)isoxazolo[3,4-d]pyrimidine

Victor P. Krivopalov

Papers

1,2,3-Triazole and its derivatives. Development of methods for the formation of the triazole ring

Three differently coloured concomitant polymorphs: synthesis, structure and packing analysis of (4-(3',5'-dimethyl-1H-pyrazol-1'-yl)-6-methyl-2-phenylpyrimidine)dichlorocopper(II).

Unexpected Transformations of 4-Azido-2-(2’-hydroxyphenyl)-5-ethoxycarbonyl-pyrimidine: the Formation of 4-Hydroxyamino-2-(2’-hydroxyphenyl)- 5-ethoxycarbonylpyrimidine and Ethyl 3-(2’-Hydroxybenzoylamino)- 2-(1” H-tetrazol-5” -yl)acrylate

Intramolecular Cyclization in 4-Azido-5-ethoxycarbonyl-2-(2′-hydroxyphenyOpyrimidine: Synthesis and Properties of 3-Ethoxy-6-(2′-hydroxyphenyl)isoxazolo[3,4-d]pyrimidine

1,2,3‐Triazole and Its Derivatives. Development of Methods for the Formation of the Triazole Ring