Bulky electron-rich monophosphin

Heterocyclic carbene ligands are strong a-electron donors with properties close to those of for instance PCy3. They form active catalysts with palladium for the Suzuki reaction of non-activated substrates [46], The ligands IMes and Ipr are shown in Figure 13.31. It would seem that mono-ligand species are needed, very similar to bulky, electron-rich monophosphines. 

In 2013, Feringa reported the palladium-catalyzed cross-coupling of organolithium reagents with aryl bromides and chlorides [29]. Pd or Pd° complexes are used associated with bulky electron-rich monophosphines (PfBu, Xphos) or electron-rich NHC ligands (PEPPSI-Ipent) (Scheme 19.24) that favor oxidative additions. 

Recently, the Xiao group has reported the Heck arylation of vinyl pyrrolidine III-92 with l-chloro-4-methoxybenzene (Scheme 4.70) [223]. Despite the use of a bulky electron-rich monophosphine HI-93, the a-arylated alkene is the major product. Altematevely, when a bidentate ligand is used under ionizing conditions, the a-product can be exclusively obtained from III-92 [224—228]. 

Mechanism of the Mizoroki-Heck Reaction when the Ligand is a Bulky and Electron-Rich Monophosphine... 

Barrios-Landeros and Hartwig [80a] have reported the mechanism of the oxidative addition of aryl bromides with Pd(0) complexes ligated by bulky electron-rich phosphines such as Pd°(Fc -P-t-Bu2)2 (Fc = aryl-substituted ferrocenyl). All Pd(0) complexes are found to react via a monophosphine complex Pd L in a dissociative mechanism, leading to the monophosphine T-shaped complex ArPdXL which may be stabilized by a weak agostic Pd-H bond (H from the ligand) [80b,c] (Scheme 1.52). The mechanism of the oxidative addition of PhBr to Pd°(P-r-Bu3)2 (P-t-Bus cone angle 182°, pKa = 11.4) is not reported. 

The efficiency of bulky and electron-rich phosphines in Mizoroki-Heck reactions seems to be due to their ability to generate monophosphine-Pd(O) or -Pd(II) complexes in each step of the catalytic cycle (Scheme 1.55). Steric factors are probably more important than electronic factors. One sees from Fu s studies that the last step of the catalytic cycle in which the Pd(0) complex is regenerated in the presence of a base may be rate determining. The role of this last step has been underestimated for a long time. Provided this step is favoured (e.g. with P-r-Bus as ligand and Cy2NMe as base), the oxidative addition of aryl chlorides would appear to be rate determining. However, Mizoroki-Heck reactions performed from the same aryl chloride with the same Pd(0) catalyst and same base but... 

The Mizoroki-Heck reaction is a subtle and complex reaction which involves a great variety of intermediate palladium complexes. The four main steps proposed by Heck (oxidative addition, alkene insertion, )3-hydride elimination and reductive elimination) have been confirmed. However, they involved a considerable number of different Pd(0) and Pd(Il) intermediates whose structure and reactivity depend on the experimental conditions, namely the catalytic precursor (Pd(0) complexes, Pd(OAc)2, palladacycles), the Ugand (mono- or bis-phosphines, carbenes, bulky monophosphines), the additives (hahdes, acetates), the aryl derivatives (ArX, ArOTf), the alkenes (electron-rich versus electron-deficient ones), which may also be ligands for Pd(0) complexes, and at least the base, which can play a... 

As far as the oxidative addition is concerned, two different mechanisms are proposed for this step a concerted mechanism and a nucleophihc attack mechanism. Calculations on the concerted mechanism show that the size of the phosphine does not significantly affect this process for monophosphine catalytic systems. In fact, it is experimentally shown that the rate constants for the oxidative addition depend more on the identity of the halide of the ArX electrophihc reactant than of the steiic bulk of the phosphine ligands. The nature of the phosphine ligand may affect this process not because of the oxidative addition elementary step itself (where the effect is rather small), but due to its own intrinsic capability of generating mono- or bisphosphine catalysts. The oxidative addition process in monophosphine systems are more favorable than in their bisphosphine counterparts. In fact, the most active phosphine ligands known are the bulky and electron-rich dialkylbiaryl phosphines developed by Buchwald s group. 

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