Cross-coupling catalytic cycle

Scheme 2 depicts a general cross-coupling catalytic cycle involving organic dihalides. Although the oxidative addition step is proposed to be reversible in some cross-coupling reactions [18], it is generally considered to be irreversible in many... 

Scheme 19 Suzuki cross-coupling catalytic cycle [96, 97]...

A number of alternative Pd(I) dimers have also been prepared and applied in catalysis [33a, 36]. Compared to the well-studied Pd(0)/Pd(II) sequences, the reactivities at (or derived from) Pd(I)-Pd(I) are not well understood [37]. The dimer itself could act as a catalytically active species, and dinuclear cross-coupling catalysis cycles might be undergone (see Figure 4.6). Alternatively, the Pd(I) dimer might function as a precatalyst to the active Pd(0) species. This could occur via disproportionation of the dimer, or alternatively, the complex might be reduced to Pd(0) or even anionic Pd(0)XL . Lastly, if homolytic scission of the dimer were to take place, mononuclear Pd(I) radicals could also be formed (see Figure 4.6). 

Carbon-carbon bond formation reactions and the CH activation of methane are another example where NHC complexes have been used successfully in catalytic applications. Palladium-catalysed reactions include Heck-type reactions, especially the Mizoroki-Heck reaction itself [171-175], and various cross-coupling reactions [176-182]. They have also been found useful for related reactions like the Sonogashira coupling [183-185] or the Buchwald-Hartwig amination [186-189]. The reactions are similar concerning the first step of the catalytic cycle, the oxidative addition of aryl halides to palladium(O) species. This is facilitated by electron-donating substituents and therefore the development of highly active catalysts has focussed on NHC complexes. 

In summary, these results demonstrate that air-stable POPd, POPdl and POPd2 complexes can be directly employed to mediate the rate-limiting oxidative addition of unactivated aryl chlorides in the presence of bases, and that such processes can be incorporated into efficient catalytic cycles for a variety of cross-coupling reactions. Noteworthy are the efficiency for unactivated aryl chlorides simplicity of use, low cost, air- and moisture-stability, and ready accessibility of these complexes. Additional applications of these air-stable palladium complexes for catalysis are currently under investigation. 

Palladium-catalyzed carbon-carbon cross-coupling reactions are among the best studied reactions in recent decades since their discovery [102, 127-130], These processes involve molecular Pd complexes, and also palladium salts and ligand-free approaches, where palladium(O) species act as catalytically active species [131-135]. For example, the Heck reaction with aryl iodides or bromides is promoted by a plethora of Pd(II) and Pd(0) sources [128, 130], At least in the case of ligand-free palladium sources, the involvement of soluble Pd NPs as a reservoir for catalytically active species seems very plausible [136-138], Noteworthy, it is generally accepted that the true catalyst in the reactions catalyzed by Pd(0) NPs is probably molecular zerovalent species detached from the NP surface that enter the main catalytic cycle and subsequently agglomerate as N Ps or even as bulk metal. 

The mechanism of a typical cross-coupling reaction catalyzed by Pd° or Ni° complexes can be represented by a standard catalytic cycle (Scheme 1, shown for Pd ancillary ligands not given, for simplicity). 

The ideal ligand for the cross-coupling reactions should satisfy the requirements of all stages of the catalytic cycle. In practice this is unlikely, as these requirements are not parallel. A careful compromise between various factors is necessary for any particular realization of cross-coupling chemistry. The path of reasoning should be similar for both Pd- and Ni-catalyzed processes however, since very little information is available concerning Ni catalysis, only Pd catalysis will be discussed here. 

The reductive elimination/oxidative addition is of practical importance in catalytic cycles, for example the rhodium/methyl iodide catalysed carbonylation of methanol. In organic synthesis the palladium or nickel catalysed cross-coupling presents a very common example involving oxidative addition and reductive elimination. A simplified scheme is shown in Figure 2.19 [17],... 

Palladium-catalyzed cross-coupling reaction of organostannanes with organic halides, triflates, etc. For the catalytic cycle, see Kumada coupling on page 345. 

Figure 3.48. Catalytic cycle of Ni/49-catalyzed as5mimetric cross-coupling of vinyl bromide with secondary alkyl Grignard reagents.

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... 

As the entry of the aryl halide into the catalytic cycle is analogous to the cross-coupling reactions, the scope and limitations in the choice of this... 

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