Heck reaction with bidentate phosphines

Scheme 6-29 The cationic and neutral manifold.s of the Heck reaction with bidentate phosphines.

The mechanism of the Heck reaction (Scheme la) with bidentate phosphine ligands is generally thought to follow the four-step catalytic cycle shown in Scheme lb, with the individual steps being A) oxidative addition of 1 to the Pd°... 

Extended X-ray absorption fine stmcture (EXAFS) analysis has been employed recently for the investigation of the role of colloids in catalysis. For Heck reactions with Herrmarm s paUadacycle or with [Pd(OAc)2]/P(tert-Bu)3, no indication of formation of coUoidal palladium was found [44]. By contrast, Koningsberger and co-workers found that in aUyHc amination with allylpalladium complexes with bidentate phosphine Hgands, from the early stages of the reaction onward, deactivation occurs by formation of di- and trinuclear clusters, which aggregate to larger clusters and finally to palladium black [45]. 

A short five-step synthesis of a bifuran, namely ( )-2,2 -bis(diphenylphosphino)-3,3 -binaphtho[2,l-I>]furan (BINAPFu) from naphthofuranone via a low-valent titanium-mediated dimerization was reported. The newly developed resolution procedure for phosphines was utilized to provide the optically active bidentate phosphine ligands (BINAPFu), which consistently outperforms BINAP in the asymmetric Heck reaction between 2,3-dihydrofuran and phenyl triflate . Another way in which a benzofuranone can be converted into benzo[7 ]furan is by treatment of the former with 1-BU2AIH at -78°C followed by an acidic work up <00TL5803>. 

A variety of chiral phosphine ligands are frequently used for asymmetric Heck reactions. The oxidative insertion is favored by basic ligands whereas bidentate ligands with a small bite angle enable good to excellent chirality transfer (>90 % ee). Some selected ligands which meet these requirements for asymmetric Heck reactions are shown in the margin. 

The intramolecular asymmetric Heck reaction has featured in the synthesis of complex heterocyclic compounds. Bidentate ligands, such as diphosphines (especially BINAP) and phosphine—oxazolines, have been used as a chiral ligand of the asymmetric Heck reaction. Imbos et al. demonstrated that the mono-dentate phosphoramidite 513 was an effective ligand for the asymmetric Heck reaction of the prochiral cyclohexadienone 511 (Scheme 153).227 The reaction of 511 in the presence of catalytic amounts of Pd-(OAc)2 and the chiral phosphoramidite 513 gave the 4a-methoxy-4a//-benzo[c]chromen-2(6E/)-one 512 in 71% yield with 96% ee. By contrast, the reaction of... 

DFT calculations by Rosch and cowoikers [74] showed that for PhPdCl(P Cb) complexes, where the bidentate hgand P Cb is a monophosphine Unked to an NHC, the reaction with an alkene proceeds via dissociation of the more labile phosphine that is, via a neutral Cb-linked ArPdX complex (Scheme 1.48). Later on, bidentate P Cb ligands generated in situ from phosphine-imidazohum salts proved to be efficient in Mizoroki-Heck reactions employing aryl bromides - even deactivated ones, as pioneered by Nolan and coworkers [Iq, 75]. Interestingly, the DFT calculations have paved the way to fhiitful experiments. 

It appears reasonable to predict that ArPdX(Cb)(PR3) complexes generated in the oxidative addition of ArX to Pd°(Cb)(PRj) would dissociate to ArPdX(Cb), which reacts with the alkene. Such a dissociation of the phosphine must be even easier than the intramolecular dissociation of the phosphine in the bidentate P Cb ligand proposed above. This is probably why mixed complexes Pd°(Cb)(PR3) are more efficient than Pd°(Cb)2 in Mizoroki-Heck reactions performed from aryl bromides [71, 76], even if they are less reactive than Pd°(Cb)2 in the oxidative addition. Indeed, the high stability of the Cb-Pd(II) bond combined with the easy dissociation of the phosphine in ArPdX(Cb)(PR3) favours the complexation/insertion of the alkene. 

Typed Mizoroki-Heck reactions require mild conditions. Partial or full dissociation of bidentate ligands is not expected to require very high temperatures (cf. discussion of various SRPC), at which type 4 precatalysts would simply turn into yet another SRPC. Indeed, Shaw and Perera [149] showed that (L)PdCl2 complexes with various bidentate phosphines (including dppf, dppe and dppp) make useful precatalysts for Mizoroki-Heck... 

A catalytic cycle arising from the common precatalyst mixture of Pd(OAc)2 and PPhs, termed the anionic pathway, has recently been proposed [ 14]. This pathway involves anionic palladinm(O) and palladium(II) intermediates in which the acetate anion is coordinated with palladinm in the catalytically active species persisting after oxidative addition. The anionic pathway has not been invoked or thoroughly explored for enantioselective intramolecular Mizoroki-Heck reactions. However, it may become more significant based on recent studies with Pd(OAc)2 and bidentate phosphine ligands for which the palladium(n) species is only formed in the presence of added acetate ion [15]. 

In 2008, Portnoy s group [76] reported the use of bidentate phosphine ligands immobilized to Wang polystyrene beads with polyether dendron spacers, which formed active catalysts for the Heck-Mizoroki reaction when treated with Pd(dba)2 (Figure 1.21). Two series of immobilized palladium catalysts were investigated, one series termed Gn-I was prepared by incubating the... 

Other highly active palladium chloride-based catalysts include di-2-pyridylmethylamine-based paUadium, tr(WM-bidentate pyridine, and PdCl2/phosphinous acid complexes. Typical examples are shown in Scheme 2. This section is concerned with the coupling reactions of aryl chlorides using the above PdCh-based catalysts. Chloro arenes are cheap to manufacture and therefore play a vital role as intermediates in the chemical industry. The low reactivity of chlorides is usually attributed to the strength of the C-Cl bond. Remarkable progress has been achieved since 1998 in the development of palladium-based catalysts that can in fact accomplish cross-couplings and Heck reactions. ... 

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