Cross couplings mechanism/coupling cycle

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 mechanism of the Sonogashira reaction has not yet been established clearly. This statement, made in a 2004 publication by Amatore, Jutand and co-workers, certainly holds much truth [10], Nonetheless, the general outline of the mechanism is known, and involves a sequence of oxidative addition, transmetalation, and reductive elimination, which are common to palladium-catalyzed cross-coupling reactions [6b]. In-depth knowledge of the mechanism, however, is not yet available and, in particular, the precise role of the copper co-catalyst and the structure of the catalytically active species remain uncertain [11, 12], The mechanism displayed in Scheme 2 includes the catalytic cycle itself, the preactivation step and the copper mediated transfer of acetylide to the Pd complex and is based on proposals already made in the early publications of Sonogashira [6b]. 

Consequently, to narrow the definition a bit further, we will adhere to Negishi s suggestion and define cross-coupling reactions as those that follow some variation of the mechanism depicted in Scheme 1 (where Mt is a transition metal, L is an ancillary hgand see Ancillary Ligand), and n is the oxidation state of the reduced metal in the catalytic cycle). This mechanism is supported by stoichiometric studies on isolated metal complexes (mostly where Mt = Pd, n = 0, L = triphenylphosphine) thought to be the intermediates in this cycle. 

The palladium-catalyzed cross-coupling reaction of a vinyl or aryl stannane with an arylhalogenide or -triflate is known as a Stille reaction. The mechanism of this Stille reaction is outlined below The palladium precatalyst loses two ligands and forms the catalytic species 36. The catalytic cycle starts with the oxidative addition of the catalytic species 36 into the carbon-triflate bond of 23 forming complex 41, which, however, does not undergo the required transmetallation step with stannane 22. Therefore, the triflate ion is... 

The mechanism of the cross-coupling reaction should follow the well-accepted catalytic cycle [1]. Namely, (1) Pd(0)L2 catalyst, generated by an unclear pathway, undergoes... 

The mechanism of the Sonogashira cross-coupling follows the expected oxidative addition-reductive elimination pathway. However, the structure of the catalytically active species and the precise role of the Cul catalyst is unknown. The reaction commences with the generation of a coordinatively unsaturated Pd species from a Pd " complex by reduction with the alkyne substrate or with an added phosphine ligand. The Pd " then undergoes oxidative addition with the aryl or vinyl halide followed by transmetallation by the copper(l)-acetylide. Reductive elimination affords the coupled product and the regeneration of the catalyst completes the catalytic cycle. 

The mechanism of palladium/aryl halide amination is very closely related to that of cross coupling, with displacement of the halide on palladium (or copper or nickel) by an amine or A-anion instead of the trans-metallation step. In the case of Cu and Ni catalysis, it may proceed through M(0)-M(11) or M(l)-M(lll) cycles. 

The general reaction mechanism has been shown to involve typical steps for cross-coupling [98, 113]. Oxidative addition of an aryl halide generates a Pd(II) species that undergoes transmetalation to form a Pd(II)-thiolate. C-S reductive elimination provides the aryl sulfide and regenerates the Pd(0) catalyst. More recently, Hartwig reported a detailed mechanistic analysis of the Pd/Josiphos system derived from different Pd precursors. The dominant Pd species were found to be off the catalytic cycle, which accounted for differences in rates between stoichiometric and catalytic reactions [114]. Thioketones are also effective thiolate nucleophiles for C-S bond formation. The reaction involves tandem Pd-catalyzed thioenolate alkylation, followed by 5-arylation (8) [102]. Presumably, the arylation process proceeds by a similar mechanism to related Pd-catalyzed transformations. 

The mechanism of palladium-catalysed cross-coupling starts, as in the Heck reaction, with oxidative addition of the halide or triflate to the initial palladium(O) phosphine complex to form a palladium(ll) species. But the next step is new it is a transmetallation, so-called because the nucleophile (Ri) is transferred from the metal in the organometallic reagent to the palladium and the counterion (X=hallde or triflate) moves in the opposite direction. The new palladium(ll) complex with two organic ligands undergoes reductive elimination to give the coupled product and the palladium(O) catalyst, ready for another cycle. 

This review provides a compilation of the most well-known catalytic reactions related to organo-palladium chemistry. The references have been covered up to November 1995. The mechanisms are generally described with respect to the data in the literature and by the use of information found mainly in publications. For each catalytic cycle, the chemical parameters are listed and one or more related references are given. As an example, for the cross-coupling reactions between RX and R M, the identity of R, R, X, and M parameters are defined. The references which are quoted contain at least one example of these parameters. A few palladium-catalyzed reactions are not reported in this review because of insufficient data concerning the mechanism or because the reaction affords a complex mixture of products. 

Some fundamental inorganic chenustry that is important for understanding which complexes will undergo the aromatic C—and C—O bond-forming processes will be presented before the catalytic transformations. First, the three reaction types involved in the catalytic cycle to form arylanunes are similar to those found in the catalytic cycle for C—C bond formation oxidative addition of aryl halide to Pd(0) complexes, transmetallation that converts an arylpalladium halide complex to an arylpaUadium amido complex, and reductive elimination to form a C—or C—O bond. The oxidative addition step is identical to the addition that initiates C—C bond-fomting cross-couplings,f f but the steps that form the arylpalladium amido complexes and that produce the arylamine product are different. The mechanism for these steps is discussed after presentation of the scope of the amination process. 

Hemnann et have indicated that the standard palladacycle trans-di(fju-acetato)-bis[o-(di-o-tolylphosphino)benzyl]-dipaUadium(II) (A) might be a catalyst precursor to active palladium(O) complexes (Scheme 41). In other words, the palladacycle may act as a thermally stable reservoir for the real catalytic species, which is released by heterolytic Pd—C bond cleavage and is activated by subsequent reduction. If this is the acmal case a tfaditional catalytic cycle via Pd(0)/Pd(II) has to be postulated also with palladacycles. In addition, for cross-coupling and amination reactions there is strong evidence for the reduction mechanism of phosphapaUadacycle A into a Pd(0) species.f ... 

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