Aryl chlorides palladium® chloride

Aryl chlorides Aryl chlorides will substitute alkenes only under very special conditions, and then catalyst turnover numbers are generally not very high. Palladium on charcoal in the presence of triethylphos-phine catalyzes the reaction of chlorobenzene with styrene,58 but the catalyst becomes inactive after one use.59 Examples employing an activated aryl chloride and highly reactive alkenes, such as acrylonitrile, with a palladium acetate-triphenylphosphine catalyst in DMF solution at ISO C with sodium acetate as base react to the extent of only 51% or less.60 Similar results have been reported for the combination of chlorobenzene with styrene in DMF-water at 130 C, using sodium acetate as the base and palladium acetate-diphos as a catalyst.61 Most recently, a method for reacting chlorobenzene with activated alkenes has been claimed where, in addition to the usual palladium dibenzilideneacetone-tri-o-tolylphosphine catalyst, nickel bromide and sodium iodide are added. It is proposed that an equilibrium concentration of iodobenzene is formed from the chlorobenzene-sodium iodide-nickel bromide catalyst and the iodoben-zene then reacts in the palladium-catalyzed alkene substitution. Moderate to good yields were reported from reactions carried out in DMF solution at 140 C 62... 

Unlike aryl chlorides, acyl chlorides are quite reactive, although not often used. Oxidative addition of palladium(O) to the acid chloride 5.44 generates an acyl palladium(II) complex 5.46 (Scheme 5.12). This may undergo decarbonylation or not prior to alkene insertion depending on the reaction conditions, and the substrate structure (Schemes 5.13 and 5.14). Acid chlorides are more reactive than aryl bromides and selective coupling at the two positions of p-bromobenzoyl chloride 5.53 with different alkenes is possible (Scheme 5.15). ... 

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... 

Hydrogenolysis of aryl and alkenyl halides and triflates proceeds by the treatment with various hydride sources. The reaction can be explained by the transmetallation with hydride to form palladium hydride, which undergoes reductive elimination. Several boro hydrides are used for this purpose[680], Deuteration of aromatic rings is possible by the reaction of aryl chlorides with NaBD4681]. 

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. 

HECK REACTIONS OF ARYL CHLORIDES CATALYZED BY PALLADIUM/TRI-tert-BUTYLPHOSPHINE (E)-2-METHYL-3-PHENYLACRYLIC ACID BUTYL ESTER AND (E)-4-(2-PHENYLETHENYL)BENZONITRILE... 

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. 

We have investigated the arylation of different primary or secondary amines with different aryl chlorides or bromides in heterogeneous or homogeneous catalysis conditions using palladium(O) or palladium(II) derivatives (Fig. 5). 

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]. 

However, the Buchwald-Hartwig reaction with NHCs as hgands is not limited to palladium. Nickel has also been successfully employed in this catalytic amination. In situ procedures have been described for the coupling of aryl chlorides [163] and tosylates [164] and, more interestingly, anisoles [165]. The use of well-defined Ni(0) catalysts has also been studied [166] (Scheme 6.49). 

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]. 

Palladium NHC systems for the hydrodehalogenation of aryl chlorides and bromides and polyhalogenated aromatic substrates originate from about the same time as the first reports on Ni chemistry, and show many similarities. Initial efforts showed that the combination of PdCdba) (2 mol%), one equivalent of imidazolium chloride and KOMe produced an effective system for the reduction of 4-chlorotolu-ene, especially upon use of SIMes HCl 2 (96% yield of toluene after 1 h at 100°C) [7]. Interestingly, higher ligand to metal ratios severely inhibited the catalysis with only 7% yield of toluene achieved in the same time in the presence of two equivalents of SIMes HCl 2. Variation of the metal source (Pd(OAc)2, Pd(CjHjCN)jClj), alkoxide (NaOMe, KO Bu, NaOH/ ec-BuOH) or imidazolium salt (IMes HCl 1, IPr HCl 3, lAd HCl, ICy HCl) all failed to give a more active catalyst. 

Kotschy et al. also reported a palladium/charcoal-catalyzed Sono-gashira reaction in aqueous media. In the presence of Pd/C, Cul, PPI13, and z -Pr2NH base, terminal alkynes smoothly reacted with aryl bromides or chlorides, such as 2-pyridyl chloride, 4-methylphenyl bromide, and so on, to give the expected alkyne products in dimethyl-acetamide (DMA)-H20 solvent. Wang et al. reported an efficient cross-coupling of terminal alkynes with aromatic iodides or bromides in the presence of palladium/charcoal, potassium fluoride, cuprous iodide, and triph-enylphosphine in aqueous media (THF/H20, v/v, 3/1) at 60°C.35 The palladium powder is easily recovered and is effective for six consecutive runs with no significant loss of catalytic activity. 

The generated palladium chlorides possessing phosphinous acid ligands were found to be remarkably active and efficient catalysts in the presence of bases for a variety of cross-coupling reactions of aryl halides with aiylboronic... 

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. 

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