Copper catalytic cycle

The original Sonogashira reaction uses copper(l) iodide as a co-catalyst, which converts the alkyne in situ into a copper acetylide. In a subsequent transmeta-lation reaction, the copper is replaced by the palladium complex. The reaction mechanism, with respect to the catalytic cycle, largely corresponds to the Heck reaction.Besides the usual aryl and vinyl halides, i.e. bromides and iodides, trifluoromethanesulfonates (triflates) may be employed. The Sonogashira reaction is well-suited for the synthesis of unsymmetrical bis-2xy ethynes, e.g. 23, which can be prepared as outlined in the following scheme, in a one-pot reaction by applying the so-called sila-Sonogashira reaction ... 

It is noteworthy that metallic copper or cuprous bromide used under nitrogen atmosphere shows only a very short induction time. This last result points out the inhibitor role of the oxygen of the air atmosphere and most likely the important role taken either by reduced species or by radical intermediates in the catalytic cycle. 

According to these conclusions, it is possible to propose a catalytic cycle (Fig. 20) involving no radical species, but a copper(I) complex with the classical oxidative addition, nucleophilic substitution and reductive elimination resulting lastly in the arylated nucleophile. 

The catalytic cycle of laccase includes several one-electron transfers between a suitable substrate and the copper atoms, with the concomitant reduction of an oxygen molecule to water during the sequential oxidation of four substrate molecules [66]. With this mechanism, laccases generate phenoxy radicals that undergo non-enzymatic reactions [65]. Multiple reactions lead finally to polymerization, alkyl-aryl cleavage, quinone formation, C> -oxidation or demethoxylation of the phenolic reductant [67]. 

The presence of Cu(i) or Cu(n) salts in the aforementioned reactions is critical. It is believed that organozinc reagents undergo transmetallation with copper species to yield more reactive complexes.301 A proposed301 catalytic cycle (Scheme 118) suggests that the alkyl group transferred to the enone from the copper metal in a bimetallic intermediate 207. 

Cu(0) species. Alternatively, the Cu(n) species may first undergo oxidation by an external oxidant (or internal redox process) to a Cu(m) intermediate, and then undergo reductive elimination to provide the product and a Cu(i) species. Re-oxidation to Cu(n) would then, in theory, complete the catalytic cycle, but in practice, most reactions of this type have been performed with stoichiometric amounts of the copper reagent. 

PhI=NTs in MeCN affords a copper species that is indistinguishable by ultraviolet-visible (UV-vis) spectroscopy from an identical solution derived from Cu(OTf)2. Given the strong oxidizing nature of PhI=NTs, it seems likely that both catalysts proceed through a Cu(II) species. Beyond this, little can be said with certainty. If nitrenoid formation proceeds by a two-electron oxidation of the catalyst, one would need to invoke Cu(IV) as an intermediate in this process (77). This issue is resolved if one invokes the intervention of a bimetallic complex in the catalytic cycle. However, attempted observation of a nonlinear effect revealed a linear relationship between ligand enantiopurity and product ee (77, 78). 

A priori, an allenyl cuprate intermediate might account for the observed products. However, the reaction was carried out in two stages with only 5mol% of CuBr. Thus, if a cuprate intermediate was the reactive species, a theoretical yield of 5% would have been expected. However, the reaction did not take place in the absence of the copper catalyst. Accordingly, a catalytic cycle was proposed in which the initial dibutyl cuprate effects a well precedented SN2 displacement on the vinyloxirane,... 

Fig. 10.1. Proposed catalytic cycle of copper-catalyzed conjugate addition.

A C-Cu bond is a stable covalent bond, and is difEcult to cleave by itself [93]. After charge transfer from cuprate(I) to substrate, however, cleavage of the resulting R-Cu bond becomes easy. The reductive elimination reaction regenerates RCu , which may take part in further catalytic cycles. Thus, in copper-... 

In summary, the copper ion transfers an electron from the unsaturated substrate to the diazo-nium cation, and the newly formed diazonium radical quickly loses nitrogen. The aryl radical formed attacks the ethylenic bond within the active complexes that originated from aryldiazo-nium tetrachlorocuprate(II)-olefin or initial arydiazonium salt-catalyst-olefln associates and yields >C(Ar)-C < radical. The latter was detected by the spin-trap ESR spectroscopy. The formation of both the cation-radical [>C=C<] and radical >C(Ar)-C < as intermediates indicates that the reaction involves two catalytic cycles. In the other case, radical >C(Ar)-C < will not be formed, being consumed in the following reaction ... 

While the mechanisms of these reactions have not been investigated in detail, it is likely that an intermediate copper(I) alkynyl is formed, which undergoes an alkynyl-halide exchange with the metal halide, resulting in the formation of the transition metal cr-alkynyl complex and a Cu(I) halide, which completes the catalytic cycle (Scheme l), ... 

Fig. 6. Suggested changes in the coordination at tte copper (xntre upon anion binding and during the catalytic cycle of Cu—Za superoxide dismutase...

On the basis of DFT calculations, a catalytic cycle involving a copper vinylidene intermediate has been proposed (Scheme 9.22) [44]. The reaction is initiated by copper acetylide (138) formation. Sharpless and coworkers next invoke an unusual [3 + 3]-cycloaddition that would be forbidden by orbital symmetry, were it not stepwise. Coordination of an azide to complex 138 generates a zwitterionic complex (139). Internal nucleophilic attack of the acetylide moiety of 139 on the electrophilic... 

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