Heck reaction Neutral cycle

Many types of functional groups are tolerated in a Suzuki reaction, and the yields are often good to very good. The presence of a base, e.g. sodium hydroxide or sodium/potassium carbonate, is essential for this reaction. The base is likely to be involved in more than one step of the catalytic cycle, at least in the transmetal-lation step. Proper choice of the base is important in order to obtain good results." In contrast to the Heck reaction and the Stille reaction, the Suzuki reaction does not work under neutral conditions. 

Eberlin also studied the Heck reaction of aryltellurides [45] and Svennebring [19] reported the identification of three types of cationic, catalytic intermediates (Fig. 4A-C) in the microwave-assisted, phosphine-containing Heck arylation of electron rich olefins. In the latter case the authors support a Pd(0)/Pd(II) cycle as opposed to a Pd(II)/Pd(IV) cycle based on ESI-MS evidence for reduction of the palladium(II) precatalyst to Pd(0) by the ligand, and oxidative addition of the aryl substrate to a Pd(0) species. None of the expected Pd-bound olefin intermediates were observed however, this is often the case either because the olefin-bound species is neutral or because OA (oxidative addition) is the turnover-limiting step and the subsequent steps occur too quickly to be observed by the sampling method (in this case sampling included quenching and dilution of samples from a reaction vessel). 

The classical Heck reaction involves the Pd(0)-mediated coupling of alkenes with aryl and alkenyl halides at much more convenient laboratory conditions (Scheme 5.3). Hindered amines such as tri-n-butyl amine and triethyl amine are used as a base to neutralize HX produced as a by-product of the catalytic cycle. The Heck reaction has trans-selectivity. 

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. ... 

A tentative catalytic cycle for ligand-accelerated Mizoroki-Heck reactions is shown in Scheme 2.14. A pivotal feature of this mechanism is the requirement to have neutral complex 4 with a single ancillary ligand, as related coordinatively saturated species 1 or... 

The most common Mizoroki-Heck reaction mechanism is called the neutral mechanism, because its intermediates are uncharged. The catalytic cycle for the neutral manifold of the intramolecular Mizoroki-Heck reaction of alkenyl and aryl halides is shown in Scheme... 

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 regiochemical outcome of the Mizoroki-Heck reaction is furthermore affected by the (pseudo)haUde liberated in the oxidative addition step. Using aryl bromides or iodides, the reaction foUows the neutral pathway (left cycle. Scheme... 

Another of the standard palladium-catalyzed C—C bond formations is the Mizoroki-Heck reaction. This reaction is based on the palladium-catalyzed coupling of olefins with aryl or vinyl halides under basic conditions [21]. The catalytic cycle that is typically proposed for this reaction is outlined in Scheme 7.7. The first step of the reaction postulated in the mechanism is an oxidative addition of R -X to a Pd(0) complex. The next step is the insertion of the alkene to the Pd complex II. In order for this to be possible, an uncharged ligand has to break away giving a neutral Pd(II) complex that will be coordinated by the olefin. The insertion of the alkene into the Pd— bond results in the C C bond-forming step to give BO. Rotation around the C—C bond and 3-hydride elimination yields the new substituted olefin and intermediate 131. Regeneration of the active catalytic species occurs by the addition of a base. 

These fundamental steps of the catalytic cycle have been confirmed by stoichiometric reactions starting from isolated stable complexes, and by DFT calculations [11], Although many aspects of the Heck olefination can be rationalized by this textbook mechanism , it provides no explanation of the pronounced influence that counter-ions of Pd(II) pre-catalysts or added salts have on catalytic activity [12], This led Amatore and Jutand to propose a slightly different reaction mechanism [13]. They revealed that the preformation of the catalytically active species from Pd(II) salts does not lead to neutral Pd(0)L2 species a instead, three-coordinate anionic Pd(0)-complexes g are formed (Scheme 3, top). They also observed that on the addition of aryl iodides la to such an intermediate g, a new species forms quantitatively within seconds and the solution remains free of iodide and acetate anions. It may then take several minutes before the expected stable, four-... 

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