Copper-Catalyzed Transformations

Click chemistry is now a popular concept, more specifically when it is used to indicate a copper-catalyzed cycloaddition reaction between alkyl or aryl azides and terminal alkynes. Due to the fact that Cu(I) catalysts dramatically accelerate the original Hiiisgen thermal reaction with perfect control of the mechanistic pathway to lead only to l,4-disubstituted-l,2,3-triazoles, the copper-catalyzed azide-alkyne cycloaddition (CuAAC) reaction has become one of the most representative examples of click chemistry. It was proposed that this reaction proceeds first through the formation of a copper(l)-acetyhde from a copper(I) catalyst and a terminal alkyne, followed by cycloaddition with a copper(l)-bound azide to generate a triazolyl copper(I) complex, which is released by protonation of the Cu—C bond. 

Recently, it was demonstrated that the CuAAC reaction of sulfonyl or phosphoryl azides with terminal alkynes could form reactive ketenimine species 85, which could 

SCHEME 5.56 Cu(I)-catalyzed formation of the ketenimine intermediate from sulfonyl azide and terminal aUcyne. 

SCHEME 5.57 Cu(I)-catalyzed three-component cascade reaction of sulfonyl azides, terminal alkynes, and nucleophiles. 

SCHEME 5.58 Three-component synthesis of substituted iminocoumarins 90. 

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Intramolecular oxonium ylide formation is assumed to initialize the copper-catalyzed transformation of a, (3-epoxy diazomethyl ketones 341 to olefins 342 in the presence of an alcohol 333 . The reaction may be described as an intramolecular oxygen transfer from the epoxide ring to the carbenoid carbon atom, yielding a p,y-unsaturated a-ketoaldehyde which is then acetalized. A detailed reaction mechanism has been proposed. In some cases, the oxonium-ylide pathway gives rise to additional products when the reaction is catalyzed by copper powder. If, on the other hand, diazoketones of type 341 are heated in the presence of olefins (e.g. styrene, cyclohexene, cyclopen-tene, but not isopropenyl acetate or 2,3-dimethyl-2-butene) and palladium(II) acetate, intermolecular cyclopropanation rather than oxonium ylide derived chemistry takes place 334 ). 

Extensive research in the field led to the publication of several reviews and monographs in the field. The place of our book in this niche is to provide an overview of the developments in the application of palladium, nickel and copper catalyzed transformations in the preparation and functionalization of heterocyclic compounds. Although preference was given to recent results, important examples of earlier (pioneering) works are also included in this monograph. 

It includes the steam reforming of methane over a nickel catalyst to synthesis gas followed by the copper-catalyzed transformation of the latter to methanol (see Section 3.5.1). Finally, formaldehyde is produced by oxidative dehydrogenation of methanol. 

Many of the copper-mediated transformations summarized in the previous sections of this chapter can also be performed efficiently with catalytic amounts of copper salts or reagents. Indeed, some of the copper-catalyzed reactions have been discovered before the development of stoichiometric organocopper reagents. The focus of the last decade has been put on new copper-catalyzed transformations (e.g., conjugate reductions) and in particular on the discovery of chiral copper catalysts for highly enantioselective 1,4-addition and S -substitution reactions of prochiral substrates. 

N-HeterocycHc carbene—copper-catalyzed transformations of carbon dioxide 13CS3395. 

The lone pair in the T] -pyrrolyI ligands is the most basic site in V azolyl complexes, and is the site of protonation and electrophilic attack. Novel planar chiral catalysts have been prepared, based on the azaferrocene unit, and these complexes have been used for asymmetric nucleophilic catalysis. One example of such a complex is shown on the left in Figure 4.5. Some linked versions of azaferrocenes possessing C synunetry create an unconventional chiral environment. The ligand on the right in Figure 4.5 has been used for several asymmetric copper-catalyzed transformations. ... 

Scheme 2.169 Copper-catalyzed transformations of 2-(g e7n-dibromovinyl)phenols.

Potassium aryltrifluoroborate salts are excellent coupling partners for free or protected NH-indoles at the C-2 position the palladium- and copper-catalyzed transformation takes place under mild conditions, in air, at room temperature. Furthermore, conditions were developed for the coupling of indoles with aryl boronic acids, employing Pd(OAc)2 as the catalyst and a copper salt or O2 as the oxidant. ... 

Scheme 3.12 Copper catalyzed transformation of aryl alkyl ketones to amides with NaNa...

Flow chemistry [149] as a versatile tool for the synthesis of triazoles has been reviewed. Catalyst-free continuous-flow reactions between azides and further dipolarophiles complement the copper-catalyzed transformations and have been proven to be convenient for the synthesis of diversely substituted triazoles. The safety aspects associated with the handling of azides have been recognized as one of the most important driving forces behind the advent of continuous-flow processes for triazole synthesis. Better heat-transfer characteristics and increased mixing efficiency can be accounted for an improved safety profile as well as for the elimination of common by-products such as diacetylenes and bis-triazoles. 

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