Copper catalysed azide-alkyne cycloaddition

CuAAC copper catalysed alkyne-azide cycloaddition... 

Mechanistic investigations of copper(I)-catalysed alkyne—azide cycloaddition reactions to form 1,2,3-triazoles 12THC(28)1. 

Mechanistic Investigations of Copper(I)-Catalysed Alkyne-Azide Cycloaddition Reactions... 

Chapter 1, Mechanistic Investigations of Copper(I)-Catalysed Alkyne-Azide Cycloaddition Reactions , by Buckley and Heaney is concerned with various mechanistic interpretations of thermal and metal-catalyzed reactions of organic azides and aUcynes, which result in the formation of 1,2,3-triazoles. 

A copper catalysed click (azide-alkyne cycloaddition) reaction has been used to prepare a fluorous-tagged TEMPO catalyst (Figure 7.20). TEMPO is a stable organic free radical that can be used in a range of processes. In this case, its use in metal-free catalytic oxidation of primary alcohols to aldehydes using bleach as the terminal oxidant was demonstrated. The modified TEMPO can be sequestered at the end of the reaction on silica gel 60 and then released using ethyl acetate for reuse in further reactions in this way the TEMPO was used four times with no loss in activity. 

Normally, copper-catalysed Huisgen cycloadditions work with terminal alkynes only. The formation of a Cu-acetylide complex is considered to be the starting point of the catalyst cycle. However, the NHC-Cu complex 18 was able to catalyse the [3-1-2] cycloaddition of azides 17 and 3-hexyne 23 (Scheme 5.6). 

Cycloaddition with Azides, Alkynes, Alkenes and Allenes. The copper-catalysed azide-alkyne cycloadditiOTi reaction is typically catalysed by simple, monometallic Cu(I) salts. However, the mechanism of catalysis was recently determined to involve a bimetalhc process. Similar bimetallic mechanisms have also been discovered in the cycloaddition of alkynes with alkenes, allenes and other alkynes using Au catalysts. This reaction is discussed for its broad application to many areas of chemistry and for the potential of bimetalhc catalyst design to enhance the reaction. 

Scheme 15.27 A simplified reaction scheme for copper-catalysed azide-alkyne cycloaddition.

Scheme 15.29 Copper-catalysed azide-alkyne cycloaddition employing a phosphine as the ligand.

The Cu(l) complex formed by a mesoionic carbene and a phenanthroline has been generated in situ to perform copper-catalysed azide-alkyne cycloaddition in alcoholic solvent and without the need for a reducing reagent. ... 

Iridium dimer complexes catalyse the 3 + 2-cycloaddition reactions of organic azides with bromoalkynes to furnish 1,5-disubstituted 4-bromo-1,2,3-triazoles in excellent yields under mild conditions. Ruthenium(II)-azido complexes undergo 3 + 2-cycloaddition reactions with strained cyclooctynes under ambient temperatures. No reaction was observed with non-activated terminal or internal alkynes under the same conditions. Dithioic acid copper catalysts (60) catalyse the 3 + 2-cycloaddition reaction of azides with alkynes to form 1,4-disubstituted-1,2,3-triazoles in various solvents and under various temperatures. Thermal Huisgen 3 + 2-cycloaddition reactions of azides and bis(trimethylsilyl)acetylene formed 4,5-bis(trimethylsilyl)-l/f-l,2,3-triazoles in low to high yields (15-95%). The Cu(I)-catalysed 3 + 2-cycloaddition... 

Regioselective ring expansion of alkynyl cyclopropanes to cyclobutenes has been reported via a copper-catalysed cycloaddition of an alkyne with an arylsulfonyl azide and a silver-catalysed carbene formation followed by ring expansion of a cyclopropyl carbene intermediate (Scheme 75)7° ... 

Scheme 26 A proposed mechanistic sequence for the copper-catalysed cycloaddition reaction based on the use of copper(II) acetate and 2-azidomethylp5Tidine with a terminal alkyne. We thank Dr Lei Zhu for providing Scheme 26, which is an amalgam of Schemes 17 and 18 in the paper Experimental Investigation on the Mechanism of Chelation-Assisted, Copper(II) Acetate-Accelerated Azide-AIkyne Cycloaddition by Kuang G-C, Guha PM, Brotherton WS, Simmons IT, Stankee LA, Nguyen BT, Clark RJ, Zhu L (2011) J Am Chem Soc 133 13984...

V. V. Rostovtsev, L. G. Green, V. V. Fokin, and K. B. Sharpless, A stepwise Huisgen cycloaddition process Copper(I)-catalysed regioselective ligation of azides and terminal alkynes, Angew. Chem. Int. Ed., 41 (2002) 2596-2599. 

Photochemically generated phosphonyl radicals are effeetive reducing agents for Cu VCu reduction in copper complexes. It has been shown that the obtained copper(i) species can rapidly catalyse atom transfer radical polymerisation and azide-alkyne cycloadditions in mild conditions, i.e. at ambient temperature and humidity, under an air atmosphere. 

Two additional examples serve to illustrate the complexity of copper(I)-catalysed azide-alkyne cycloaddition reactions and the dramatic effect that different ligands can have on the outcome of particular reactions. When the base ammonium carbonate was used in the reaction shown in Scheme 27, the normally... 

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