Heck bromobenzene activation

Reetz et al. 16) were the first to recover and recycle a dendritic catalyst through a precipitation procedure. The dimethylpalladium complex of the phosphine-functionalized DAB-dendr-[N(CH2PPh2)2]i6 dendrimer (la) is an active catalyst for the Heck reaction of bromobenzene and styrene to give trara-stilbene (89% trans-stilbene and 11% 1,1-diphenylethylene, at a conversion of 85—90%, Scheme 8). 

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... 

The influence of high pressure on the Heck reactions of selected alkenyl and aryl halides, respectively, i.e., 1-iodocyclohex-l-ene, iodobenzene, bromobenzene, with methyl acrylate has been investigated and the activation parameters of these reactions determined [142], Two different catalyst cocktails were used in this study, the classical system (Pd(OAc)2, NEtg, PPhg) and the one reported by Herrmann, Beller and others [16] (la). The temperature-dependent and the pressure-dependent rate coefficients both follow the order PhI/Pd(OAc)2 > 1-iodocyclohexene/Pd(OAc)2 > Phl/la > PhBr/la and the activation enthalpies as well as the activation entropies exhibit the trend 1-iodocyclohexene/Pd(OA)2 < Phl/Pd(OAc)2 < Phl/la < PhBr/la. The absolute values of the activation volumes, which were ascertained from the pressure-dependent rate coefficients, increase as follows l-iodocyclohexene/Pd(OAc)2 < PhI/Pd(OAc)2 Phl/la < PhBr/la. Under high pressure, the lifetime of the active palladium catalyst and thereby the turnover numbers are greatly enhanced [88]. 

Influence of Pd dispersion and reduction degree. The catalytic results summarized in Table 1 illustrate that all parameters investigated are of importance for the activity in the Heck reaction. All catalysts show conversions between 45 and 90 % of bromobenzene (after 20 hours) and high selectivities to -stilbene (> 90 %) no dehalogenation of bromobenzene occuned in any experiment (Table 1). 

Figure 2 investigation of activity and Pd leaching as a function of time Heck coupling of bromobenzene with styrene reaction conditions bromobenzene (200 mmol), styrene (300 mmol), sodium acetate (240 mmol), 1.0 mol% Pd, catalyst 3W, DM Ac (200 mL) T = 140 °C styrene was added last after catalyst, solvent, and bromo benzene had reached 140 °C. 

Multiple catalyst use. The dramatic decrease in Pd dispersion during the reaction should lead to a significant decrease in catalytic activity, when the catalyst is re-used in the same Heck reaction. This was in fact found in recycling studies with catalyst 3W in Heck couplings of bromobenzene with styrene. The conversion after 6 hours with the recycled methylene chloride washed catalyst is roughly 50 % of fresh 3W. A second recycling of the Pd/C catalyst decreases the reaction rate further and resulted in very low conversion (4 % after 6 hours). For higher or close to complete conversions reaction times of 20 hours or more are necessary. Re-used catalysts exhibit low activities comparable to other (fresh)... 

Table 6 Con arison of activity and reaction conditions for heterogeneous and homogeneous catalysts in the Heck reaction of bromobenzene (Figure 1, R = H)...

CPG material was used as support instead of silica gel for a Heck/SAPC system [6]. There, iodobenzene was coupled with different olefins. The dependencies of different substrates and different bases on the activity were examined. The system was active for several types of olefins. The reactivity of the aryl hahdes was comparable to that of the homogeneous catalysis. Iodides reacted easily, while bromobenzene was converted inefficiently. No reaction occurred using chlorobenzene. With EtjN as base, the highest conversions were achieved. However, leaching of palladium was observed and an /Z mixture of products was isolated. When the amine was replaced by KOAc, the Heck reaction gave selectively the -isomer. No leaching was observed (detection limit approx. 0.1 ppm), but the conversion dropped to 80%. The catalytic system with KOAc as base was successfully used for five consecutive rims, with an overall TON of > 1,200. In all cases, conversion ranged from 70 to 80% and 100% selectivity of the -isomer was achieved. 

The Pd is leaching and is redeposited at the end of the reaction, which provides an excellent recovery of the precious metal from the reaction mixture. The precipitation of the catalyst at the end of the reaction significantly changes its state and decreases its activity, however, making its re-use unattractive. Kohler et al. also showed that optimization of the Pd/C catalyst (temperature, solvent, base and Pd loading) allows turnover frequencies (TOFs) of up to 9000 to be reached and Pd concentration down to 0.005 mol% to be developed for the Heck reaction of unac-tivited bromobenzene at 140 °C [44]. The turnover numbers (TONs) are surpassed, however, by those of the best homogeneous catalysts. 

When Nowotny et al. immobilised the imine-based palladacycle developed by Milstein et al. [114] and appUed it in the Heck reaction between bromobenzene and styrene, the recycling experiment did not deliver the expected results. The catalyst was duly filtered off and reused, but the solid lost its activity after the second use [115]. On the other hand, when bromobenzene and styrene were added to the filtrate the reaction proceeded at the same rate (Scheme 10.8). 

This catalyst is exceptionally active and allows the Heck reaction to be performed on iodobenzene at 30 °C. The catalyst is inhibited by addition of a 300-fold excess of Hg. Hammett correlation of the reaction on pora-substituted bromobenzenes gave a p = 2.7, which is in accord with an oxidative addition on Pd(0).TEM showed the presence of nanoparticles in a solution of the catalyst which was pre-treated with n-butyl acrylate, NaOAc and TBAB. After addition of iodobenzene nanoparticles could no longer be detected showing that the oxidative addition of iodobenzene to the colloids is indeed a very fast reaction. Reaction with haloarenes and acrylate esters attached to a solid support gave the Heck products in excellent yields, proving that the catalyst is not heterogeneous in nature. 

Progress in Heck Reactions Catalyzed by Palladium Supported on Solids -Activation of Bromobenzene and Aryl Chlorides... 

The Suzuki-Miyaura cross-coupling reaction is a standard method for carbon-carbon bond formation between an aryl halide or triflate and a boronic acid derivative, catalyzed by a palladium-metal complex. As with the Mizoroki-Heck reaction, this cross-coupling reaction has been developed in ionic liquids in order to recycle and reuse the catalyst. In 2000, the first cross-coupling of a halide derivative with phenylboronic acid in [bmim] [BF4] was described. As expected, the reaction proceeded much faster with bromobenzene and iodobenzene, whereas almost no biphenyl 91 was obtained using the chloride derivative (Scheme 36). The ionic liquid allowed the reactivity to be increased, with a turnover number between 72 and 78. Furthermore, the catalyst could be reused repeatedly without loss of activity, even when the reaction was performed under air. Cross-coupling with chlorobenzene was later achieved - although with only a moderate yield (42%) - using ultrasound activation. 

As part of comparative studies, Iyer [47] reported the use of Vaska s complex [IrCl(CO)(PPh3)2l (92) in intermolecular Mizoroki-Heck-type reactions of methyl acrylate (1) and styrene (2). Aryl iodides could be used as electrophiles, while bromobenzene, chlorobenzene and aliphatic halides gave no desired product. The catalytic activity was found to be lower than that observed when using Wilkinson s complex [RhCl(PPh3)3] (84). Thus, a higher reaction temperature of 150 °C was mostly required. In contrast to the corresponding cobalt-catalysed reaction, however, Vaska s complex (92) proved applicable to orf/io-substituted aryl iodides (Scheme 10.33). 

Palladium acetate on silica remains in a dissolved state in the ionic liquid in the pores of silica when it is prepared by evaporation of tetrahydrofuran from a Pd(0Ac)2/Si02/[BMIm]PF6 mixture [44]. Atomic force microscopy revealed a smooth surface of the silica. Mizoroki-Heck reactions of iodo- and bromobenzene carried out with various acrylates in hydrocarbon solvents resulted in an easy separation of catalyst and product. Leaching of the catalyst into the hydrocarbon solvent occurred to less than 0.24%. The catalyst was successfully recycled and reused six times with conserved activity. 

Gedanken and coworkers [194] exploited power ultrasound to generate in situ amorphous-carbon-activated palladium metallic clusters that proved to be a catalyst for Mizoroki-Heck reactions (without phosphine ligands) of bromobenzene and styrene (yield to an appreciable extent of 30%). The catalyst is stable in most organic solvents, without showing any palladium powder segregation, even after heating them to 400 °C. 

Thus, the regioselectivity of the Heck reactions with unsymmetrical aikenes can favorably be manipulated by appropriate variations of the catalyst cocktail [123] for example, the best conditions for the couphng of bromobenzene with t-butyl acrylate in the presence of Pd[(o-Tol)3P]2Cl2 (Tol, tolyl) were found to be with potassium carbonate in ethanol at 80 °C. This is unusual for this kind of catalyst system. The active catalyst is actually believed to be nanodispersed palladium metal generated by reduction of the catalyst precursor by ethanol under basic conditions (Table 8.5). 

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