Heck mechanistic cycle

Other metals can catalyze Heck-type reactions, although none thus far match the versatility of palladium. Copper salts have been shown to mediate the arylation of olefins, however this reaction most probably differs from the Heck mechanistically. Likewise, complexes of platinum(II), cobalt(I), rhodium(I) and iridium(I) have all been employed in analogous arylation chemistry, although often with disappointing results. Perhaps the most useful alternative is the application of nickel catalysis. Unfortunately, due to the persistence of the nickel(II) hydride complex in the catalytic cycle, the employment of a stoichiometric reductant, such as zinc dust is necessary, however the nickel-catalyzed Heck reaction does offer one distinct advantage. Unlike its palladium counterpart, it is possible to use aliphatic halides. For example, cyclohexyl bromide (108) was coupled to styrene to yield product 110. 

The Heck reaction,5 sometimes also mentioned with cross-coupling reactions, deserves distinction not only for being mechanisticly different but also for its synthetic importance. In the catalytic cycle depicted in Figure... 

Indolizines were arylated under similar conditions selectively in the 3-position (6.90.). A detailed mechanistic study of the transformation revealed that in this reaction the arylpalladium species, formed in the first step of the catalytic cycle, is attached to the indolizine core in an electrophilic substitution step, which is followed by reductive elimination. The presence of alternate routes such as Heck-type insertion, oxidative addition of the C-H bond, or transmetalation were excluded on the basis of experimental evidence.121... 

Fig. 16.35 (part II). Heck coupling of an aryltriflate with acrylic acid methyl ester under "classical," conditions mechanistic analysis of the catalytic cycle, starting with the catalyt-ically active Pd(0) complex F (for the formation of F see Figure 16.35, part I). The elementary steps 1 and 2 correspond to those in the Figures 16.12, 16.18, 16.25 and 16.27. The further course of the reaction is described in the text. 

The mechanism of the Heck reaction is not fully understood and the exact mechanistic pathway appears to vary subtly with changing reaction conditions. The scheme shows a simplified sequence of events beginning with the generation of the active Pd catalyst. The rate-determining step is the oxidative addition of Pd into the C-X bond. To account for various experimental observations, refined and more detailed catalytic cycles passing through anionic, cationic or neutral active species have been proposed. ... 

Mechanistically, all catalytic systems, including heterogeneous catalysts, pal-ladacydes and pincers operate through the formation of soluble Pd(0) nanoparticles in solution. In the catalytic cycle the aryl halide oxidatively adds to the palladium atoms at the rim, leading to the formation of an anionic aryl-palladium dihalide complex, or possibly its dimer. This anionic species then completes the Heck cycle. 

Apart from their high catalytic activity in the Heck reaction, palladium pincer-catalyzed C-C cross-coupling reactions are of particular interest from mechanistic points of view. While classical Pd°/Pd cycles and mechanisms in which the palladium center of pincer-type cross-coupling catalysts does not change its oxidation state and has in most cases been excluded to be operative [23], considerable... 

Mechanistic studies performed with Freeh s pincer catalyst in the Heck reaction excluded catalytic cycles with the involvement of homogeneous palladium(O) species, as indicated by the results obtained from the (recently developed) dibenzyl-test, which is directly applicable under the reactions conditions applied [24aj. Dibenzyl formation was - in contrast to Heck reactions catalyzed by palladium(O) complexes of type [Pd(PR3)2, where Pd /Pd" cycles are operative - not detectable by gas chromatography-mass spectrometry (GC/MS) when reaction mixtures of aryl bromide, olefin, benzyl chloride ( 10 mol% relative to aryl bromide), catalyst, and base were thermally treated. On the other hand, experimental observations, such as quantitative poisoning experiments with metallic mercury and CS2, which were shown to eflfidently inhibit catalysis, as well as analysis of the reaction profiles showed sigmoidal-shaped kinetics with induction periods and hence indicated that palladium nanoparticles are the catalytically active form... 

The base is required to regenerate the active Pd(0)L2, which enters a new catalytic cycle, A more detailed presentation of the Mizoroki-Heck cycle, including two of the possible mechanistic pathways using bidentate ligands [16], is presented in Figure 3,1,... 

A detailed discussion of the current understanding of the mechanism of the Mizoroki-Heck reaction can be found in earUer chapters of this book and in several excellent reviews [7]. Two mechanistic pathways, typically termed neutral and cationic, have been proposed to account for the differences in reactivity and enantioselectivity observed in asymmetric Mizoroki-Heck cycUzations of unsaturated trillates and halides. These pathways differ in the degree of positive charge and the number of available coordination sites assignable to the palladium(II) intermediates of the catalytic cycle. Because catalytic asymmetric Mizoroki-Heck cyclizations are typically carried out with bidentate Ugands, these pathways will be illustrated with a chelating diphosphine Ugand. 

The main steps of the mechanism proposed by Heck have been further on confirmed. New ligands (diphosphines, carbenes, bulky monophosphines, polyphosphines) and new precatalysts (P,C-palladacycles) were introduced all along the last 50 years. Mechanistic investigations revealed that depending on the experimental conditions, the catalytic cycle may involve intermediate palladium complexes whose structure differs from the original ones proposed by Heck. 

It has been observed that reductive elimination can also occur for aryl-Pd-carbene complexes. Such complexes were investigated in mechanistic studies on Heck coupling and catalyst decomposition routes. Reductive elimination products with direct imidazolium-aryl coupling were observed and in one case fully characterized. Such products provide direct evidence of the Heck coupling mechanism and of intermediates in the catalytic cycle. Important mechanistic studies on the oxidative addition of aryl chlorides to a 14-electron Pd(0)(carbene)2 complex have demonstrated that oxidative addition occurs via a dissociative process and this step is probably the rate-determining step in the amination of aryl chlorides. Aryl-carbene reductive coupling was observed in this study of the amination reaction, and directly coupled aryl-imidazolium compounds were isolated. A further study on an (aryl)Pd(carbene) complex has also demonstrated that such complexes undergo facile reductive elimination to form aryl-imidazolium salt. ... 

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