Aryl chlorides palladium complexes

Diisopropyl- and l,3-dimesityl-3,4,5,6-tetrahydropyrimidin-2-ylidene ligands and complexes of Pd(ii) have been synthesized. The complexes were obtained via an Ag-carbene transfer reaction with PdCl2(NGMe)2 and X-ray structures determined. The complexes were found to be extremely effective in Heck coupling reactions with aryl bromides but much less so with aryl chlorides. Palladium complexes of the triazole-based carbenes, 1,4-dimethyl-l,2,4-triazolin-2-ylidene, and chelating l,T-methylenebis(4-alkyl-l,2,4-triazolin-2-ylidene) have been synthesized by... 

Parrish and Buchwald30 performed couplings with a polystyrene-supported biphenyl-phosphine palladium complex between aryl halides and either amines (entry 24) or boronic acids (entry 25). The resin-bound complex is analogous to the corresponding homogeneous compound and is effective for couplings to unactivated aryl halides, including aryl chlorides. The complex is air-stable and retains activity after recovery without apparent loss of palladium. 

Finally, the acyclic amino(aryl)carbene palladium complex 26 (see Figure 5.7) gave high conversions in the coupling of aryl bromides with morpholine at ambient temperature. For pyridyl chloride substrates, higher temperatures (70 °C) were required in order to achieve an appreciable 73% yield. ... 

Palladium(II) complexes provide convenient access into this class of catalysts. Some examples of complexes which have been found to be successful catalysts are shown in Scheme 11. They were able to get reasonable turnover numbers in the Heck reaction of aryl bromides and even aryl chlorides [22,190-195]. Mechanistic studies concentrated on the Heck reaction [195] or separated steps like the oxidative addition and reductive elimination [196-199]. Computational studies by DFT calculations indicated that the mechanism for NHC complexes is most likely the same as that for phosphine ligands [169], but also in this case there is a need for more data before a definitive answer can be given on the mechanism. 

Scheme 78) [89]. Aryl chlorides with activating as well as deactivating substituents could also be coupled under the same conditions in high yields, ranging from 60% to 95%, within 30-60 min of microwave irradiation. The process does not require an inert atmosphere. The increased conversion observed with the addition of the ionic liquid reveals that it might have an additional function besides simply acting as a molecular irradiator . It cannot be excluded for instance that carbene palladium complexes are formed in situ and implicated in the catalytic cycle. 

Independently, Caddick et al. reported microwave-assisted amination of aryl chlorides using a palladium-N-heterocyclic carbene complex as the catalyst (Scheme 99) [lOlj. Initial experiments in a domestic microwave oven (reflux conditions) revealed that the solvent is crucial for the reaction. The Pd source also proved very important, since Pd(OAc)2 at high power in DMF gave extensive catalyst decomposition and using it at medium and low power gave no reaction at all. Pd(dba)2/imidazohum salt (1 mol% catalyst loading) in DME with the addition of some DMF was found to be suitable. Oil bath experiments indicated that only thermal effects are governing the amination reactions. 

Cazin and co-workers recently reported on the use of the well-defined dimer complexes [Pd( a-C1)(C1)(NHC)]2 that are commercially available, and perform exceedingly well in the Suzuki-Miyaura reaction involving aryl chlorides [108]. The Cazin group has also recently disclosed well-defined mixed NHC/phosphite palladium systems of the type [PdCl2(NHC) P(OR)3j], enabling the Suzuki-Miyaura of aryl chlorides at 0.1 mol% Pd loading [109]. 

Fagnou and co-workers reported on the use of a palladium source in the presence of different phosphine ligands for the intramolecular direct arylation reaction of arenes with bromides [56]. Later, they discovered that new conditions employing palladium complex 27 promoted the direct arylation of a broad range of aryl chlorides to form six- and five-membered ring biaryls including different functionalities as ether, amine, amide and alkyl (Scheme 7.11) [57]. 

A palladium catalyst with a less electron-rich ligand, 2,2-dipyridyl-methylamine-based palladium complexes (4.2), is effective for coupling of aryl iodides or bromides with terminal alkynes in the presence of pyrrolidine and tetrabutylammonium acetate (TBAB) at 100°C in water.37 However, the reactions were shown to be faster in NMP solvent than in water under the reaction conditions. Palladium-phosphinous acid (POPd) was also reported as an effective catalyst for the Sonogashira cross-coupling reaction of aryl alkynes with aryl iodides, bromides, or chlorides in water (Eq. 4.18).38... 

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. 

Activated aryl chlorides, which are close in reactivity to unactivated aryl bromides, underwent reaction with the original P(o-tol)3-ligated catalyst.58 Nickel complexes, which catalyze classic C—C bond-forming cross-couplings of aryl chlorides, 9-64 also catalyzed aminations of aryl chlorides under mild conditions.65,66 However, the nickel-catalyzed chemistry generally occurred with lower turnover numbers and with a narrower substrate scope than the most efficient palladium-catalyzed reactions. 

Indoles, pyrroles, and carbazoles themselves are suitable substrates for palladium-catalyzed coupling with aryl halides. Initially, these reactions occurred readily with electron-poor aryl halides in the presence of palladium and DPPF, but reactions of unactivated aryl bromides were long, even at 120 °C. Complexes of sterically hindered alkylmonophosphines have been shown to be more active catalysts (Equation (25)). 8 102 103 In the presence of these more active catalysts, reactions of electron-poor or electron-rich aryl bromides and electron-poor or electron-neutral aryl chlorides occurred at 60-120 °C. Reactions catalyzed by complexes of most of the /-butylphosphines generated a mixture of 1- and 3-substituted indoles. In addition, 2- and 7-substituted indoles reacted with unhindered aryl halides at both the N1 and C3 positions. The 2-naphthyl di-t-butylphosphinobenzene ligand in Equation (25), however, generated a catalyst that formed predominantly the product from A-arylation in these cases. 

A variety of triazole-based monophosphines (ClickPhos) 141 have been prepared via efficient 1,3-dipolar cycloaddition of readily available azides and acetylenes and their palladium complexes provided excellent yields in the amination reactions and Suzuki-Miyaura coupling reactions of unactivated aryl chlorides <06JOC3928>. A novel P,N-type ligand family (ClickPhine) is easily accessible using the Cu(I)-catalyzed azide-alkyne cycloaddition reaction and was tested in palladium-catalyzed allylic alkylation reactions <06OL3227>. Novel chiral ligands, (S)-(+)-l-substituted aryl-4-(l-phenyl) ethylformamido-5-amino-1,2,3-triazoles 142,... 

Utilizing more reactive discrete palladium-N-heterocyclic carbene (NHC) complexes (for example, Pd(carb)2) or in situ generated palladium/imidazolium salt complexes (1 mol% ligand A), Caddick and coworkers were able to extend the rapid amination protocols described above to electron-rich aryl chlorides (Scheme 6.61) [128],... 

Recently, the groups of Fu and Buchwald have coupled aryl chlorides with arylboronic acids [34, 35]. The methodology may be amenable to large-scale synthesis because organic chlorides are less expensive and more readily available than other organic halides. Under conventional Suzuki conditions, chlorobenzene is virtually inert because of its reluctance to oxidatively add to Pd(0). However, in the presence of sterically hindered, electron-rich phosphine ligands [e.g., P(f-Bu)3 or tricyclohexylphosphine], enhanced reactivity is acquired presumably because the oxidative addition of an aryl chloride is more facile with a more electron-rich palladium complex. For... 

Because of their convenient preparation from palladium(II) salts and stable NHC-precursors (vide supra), paUadium(ll) complexes were first examined as potential catalysts for Heck-type reactions. Due to the high thermal stability, temperatures up to 150°C can be used to activate even less reactive substrates, like, e.g., aryl chlorides. Inunobilization of such catalysts has been shown recently (vide infra) ... 

In sharp contrast to the observations with mixed palladium(II) complexes, the mixed palladium(O) complex 64 showed inferior activity in all tested reactions as compared to 63, rendering this catalyst useless for the activation of aryl chlorides. 

For nickel(O) complexes prepared from Ni(r -cod)2 and an excess of the free NHC, it was shown that they exhibit outstanding catalytic activity in the Kumada-Corriu reaction at room temperature toward unreactive substrates like aryl chlorides and even aryl fluorides.Again, an essential element of these catalysts is the need for sterically demanding NHC ligands as observed for the palladium catalysts. 

The push-spectator stabilization system enables one to employ various alkyl groups with different types of steric environment, which differentiate amino(alkyl) carbenes dramatically from the NHCs as ligands. Taking advantage of their steric and electronic properties, Bertrand et al. nicely demonstrated the utility of CAACs as ligands in the palladium catalyzed a-arylation of ketones. Depending on the nature of the aryl chloride used, dramatic differences were observed in the catalytic activity of Pd-complexes with CAACs featuring different types of steric environment [36]. 

The choice of an ionic liquid was shown to be critical in experiments with [NBuJBr (TBAB, m.p. 110°C) as a catalyst carrier to isolate a cyclometallated complex homogeneous catalyst, tra .s-di(ri-acetato)-bis[o-(di-o-tolylphosphino) benzyl] dipalladium (II) (Scheme 26), which was used for the Heck reaction of styrene with aryl bromides and electron-deficient aryl chlorides. The [NBu4]Br displayed excellent stability for the reaction. The recycling of 1 mol% of palladium in [NBu4]Br after the reaction of bromobenzene with styrene was achieved by distillation of the reactants and products from the solvent and catalyst in vacuo. Sodium bromide, a stoichiometric salt byproduct, was left in the solvent-catalyst system. High catalytic activity was maintained even after the formation of visible palladium black after a fourth run and after the catalyst phase had turned more viscous after the sixth run. The decomposition of the catalyst and the formation of palladium... 

A number of modified reaction conditions have been developed. One involves addition of silver salts, which activate the halide toward displacement.94 Use of sodium bicarbonate or sodium carbonate in the presence of a phase-transfer catalyst permits especially mild conditions to be used for many systems.95 Tetraalkylammonium salts often accelerate reaction.96 Solid-phase catalysts in which the palladium is complexed by polymer-bound phosphine groups have also been developed.97 Aryl chlorides are not very reactive under normal Heck reaction conditions, but reaction can be achieved by inclusion of triphenylphosphonium salts with Pd(OAc)2 or PdCl2 as the catalyst.98... 

In early studies, it was observed that when the NHG was already attached to the metal center, reaction times were shortened since the time for the deprotonation of the salt and coordination to the metal center was no longer required. The use of well-defined systems also allows for a better understanding of the actual amount of stabilized palladium available in the system. Herrmann reported on two similar Pd(0) complexes bearing two carbenes, 37 and 38. The latter was used in 2002 as the first example of coupling of aryl chlorides (activated and unactivated) with arylboronic acids at room temperature, in high yields, and reaction times between 2 and 24 h in the presence of GsF as base. 

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