Ionic liquids Heck reactions

The use of ionic liquids as reaction media for the palladium-catalyzed Heck reaction was first described by Kaufmann et ak, in 1996 [85]. Treatment of bromoben-zene with butyl acrylate to provide butyl trans-cinnamate succeeded in high yield in molten tetraallcylammonium and tetraallcylphosphonium bromide salts, without addition of phosphine ligands (Scheme 5.2-16). 

At about the same time, Seddon reported the Heck reactions of bromo-and iodoarenes in a series of /V-hexylpyridinium [C6py] + and N,N dialkylimidazolium based liquids with [PF6] and [BF4] anions.20 The effects of changing the ionic liquid and reaction conditions upon the Heck reaction of iodobenzene with ethyl acrylate were reported using 2 mol% Pd(OAc)2. 

Li S, Lin Y, Xie H, Zhang S, Xu J (2006) Bronsted guanidine acid-base ionic liquids novel reaction media for the paUadium-cateilyzed heck reaction. Oig Lett 8 391-392... 

Bohm, V.P.W. and Herrmann, W.A. (2000) Nonaqueous ionic liquids superior reaction media for the catalytic Heck-vinylation of chloroarenes. Chem. Eur. J., 6,1017-25. 

To date a number of reactions have been carried out in ionic liquids [for examples, see Dell Anna et al. J Chem Soc, Chem Commun 434 2002 Nara, Harjani and Salunkhe Tetrahedron Lett 43 1127 2002 Semeril et al. J Chem Soc Chem Commun 146 2002 Buijsman, van Vuuren and Sterrenburg Org Lett 3 3785 2007]. These include Diels-Alder reactions, transition-metal mediated catalysis, e.g. Heck and Suzuki coupling reactions, and olefin metathesis reactions. An example of ionic liquid acceleration of reactions carried out on solid phase is given by Revell and Ganesan [Org Lett 4 3071 2002]. 

In pyridinium chloride ionic liquids and in l,2-dimethyl-3-hexylimida2olium chloride ([HMMIMjCl), where the C(2) position is protected by a methyl group, only [PdClJ was observed, whereas in [HMIMjCl, the EXAFS showed the formation of a bis-carbene complex. In the presence of triphenylphosphine, Pd-P coordination was observed in all ionic liquids except where the carbene complex was formed. During the Heck reaction, the formation of palladium was found to be quicker than in the absence of reagents. Overall, the EXAFS showed the presence of small palladium clusters of approximately 1 nm diameter formed in solution. 

The first reaction pathway for the in situ formation of a metal-carbene complex in an imidazolium ionic liquid is based on the well loiown, relatively high acidity of the H atom in the 2-position of the imidazolium ion [29]. This can be removed (by basic ligands of the metal complex, for example) to form a metal-carbene complex (see Scheme 5.2-2, route a)). Xiao and co-workers demonstrated that a Pd imida-zolylidene complex was formed when Pd(OAc)2 was heated in the presence of [BMIMjBr [30]. The isolated Pd carbene complex was found to be active and stable in Heck coupling reactions (for more details see Section 5.2.4.4). Welton et al. were later able to characterize an isolated Pd-carbene complex obtained in this way by X-ray spectroscopy [31]. The reaction pathway to the complex is displayed in Scheme 5.2-3. 

The use of imidazolium-based ionic liquids in Pd-catalyzed Heck reactions always carries with it the possibility of in situ formation of Pd-carbene complexes (for more details see Section 5.2.2.3). The formation of these under the conditions of the Heck reaction was confirmed by investigations by Xiao et al. [30], who described a significantly enhanced reactivity of the Heck reaction in [BMIM]Br in relation to the same reaction in [BMIM][Bp4] and explained this difference by the fact that formation of Pd-carbene complexes was observed only in the bromide melt. 

Seddon s group described the option of carrying out Heck reactions in ionic liquids that do not completely mix with water. These authors studied different Heck reactions in the triphasic [BMIM][PFg]/water/hexane system [91]. While the [BMIM]2[PdCl4] catalyst used remains in the ionic liquid, the products dissolve in the organic layer, with the salt formed as a by-product of the reaction ([H-base]X) being extracted into the aqueous phase. 

The ease of formation of the carbene depends on the nucleophilicity of the anion associated with the imidazolium. For example, when Pd(OAc)2 is heated in the presence of [BMIM][Br], the formation of a mixture of Pd imidazolylidene complexes occurs. Palladium complexes have been shown to be active and stable catalysts for Heck and other C-C coupling reactions [34]. The highest activity and stability of palladium is observed in the ionic liquid [BMIM][Brj. Carbene complexes can be formed not only by deprotonation of the imidazolium cation but also by direct oxidative addition to metal(O) (Scheme 5.3-3). These heterocyclic carbene ligands can be functionalized with polar groups in order to increase their affinity for ionic liquids. While their donor properties can be compared to those of donor phosphines, they have the advantage over phosphines of being stable toward oxidation. 

Many organic chemical transformations have been carried out in ionic liquids hydrogenation [4, 5], oxidation [6], epoxidation [7], and hydroformylation [8] reactions, for example. In addition to these processes, numerous synthetic routes involve a carbon-carbon (C-C) bond-forming step. As a result, many C-C bondforming procedures have been studied in ambient-temperature ionic liquids. Among those reported are the Friedel-Crafts acylation [9] and allcylation [10] reactions, allylation reactions [11, 12], the Diels-Alder reaction [13], the Heck reaction [14], and the Suzuld [15] and Trost-Tsuji coupling [16] reactions. 

As mentioned in the discussion of the reaction mechanism for this transformation, the active species is a dicoordinate Pd(0) complex, and it is unclear whether an associative or a dissociative process is operative for oxidative addition. In this context, different NHC complexes containing only one carbene ligand have been tested in the Mizoroki-Heck reaction. The most successful are those prepared by Beller, which were able to perform the Mizoroki-Heck reaction of non-activated aryl chlorides with moderate to good yields in ionic liquids (Scheme 6.13). The same compounds have also been applied to the Mizoroki-Heck reaction of aryldiazonium... 

Heavy water reactors (HWR), 27 582-585 safety features in, 27 583 Heck reaction, ionic liquids in, 26 889-890 Hectoral, 25 793... 

Although the Heck reaction is synthetically very useful, it requires quite high molar quantities of palladium catalyst to be effective. As such, one of the main goals is to find a solvent that helps to increase the lifetime of the catalyst and consequently reduce the amount of catalyst required. In this respect, ionic liquids show considerable promise. Another key goal in this area is to be able to replace iodo- and bromoarenes, usually used as substrates in these reactions, with chloroarenes, which are more environmentally acceptable. Again, ionic liquids show some promise in this respect. Scheme 10.2 shows the Heck reaction between styrene and chlorobenzene that has been investigated in a number of ionic liquids. 

When Heck reactions and other C-C coupling reactions are carried out in imidazolium-based ionic liquids, the base can react with the acidic proton on the... 

Thus, room-temperature ionic liquids have the potential to provide environmentally friendly solvents for the chemical and pharmaceutical industries. The ionic liquid environment is very different from normal polar and nonpolar organic solvents both the thermodynamics and the kinetics of chemical reactions are different, and so the outcome of a reaction may also be different. Organic reactions that have been successfully studied in ionic liquids include Friedel-Crafts, Diels-Alder,Heck catalysis, chlorination, enzyme catalysis,polymeriz-... 

Ott, L. S. Cline, M. L. Deetlefs, M. et al. Nanoclusters in ionic liquids evidence for A-heterocyclic carbene formation from imidazolium-based ionic liquids detected by H-2 NMR, J. Am. Chem. Soc., 2005, 127(16), 5758-5759 Hamill, N. A., Hardacre, C. McMath, S. E. J. In situ XAES investigation of palladium species present during the Heck reaction in room temperature ionic liquids. Green Chem., 2002, 4(2), 139-142. 

Kobayashi, S. J0rgensen, K. A. (Eds.) Cycloaddition Reactions in Organic Synthesis, Wiley-VCH, Weinheim, Germany, 2002 Carmichael, A. J., Earle, M. J., Holbrey, J. D. et al. The Heck reaction in ionic liquids a multiphasic catalyst system, Org. Lett., 1999, 1, 997-1000 Forsyth, S. A., Gunaratne, H. Q. N. Hardacre, C. et al. Utilisation of ionic liquid solvents for the synthesis of Lily-of-the-Valley fragrance beta-Lilial (R), 3-(4-t-butylphenyl)- 2-methylpropanal, J. Mol. Catal. A-Chem., 2005, 231(1-2), 61-66. 

The Mizoroki-Heck reaction in liquid imidazolium salts as the solvent is a special case of an in situ system Under the reaction conditions NHC complexes of palladium are formed as the active catalyst from the solvent and the ligand-free palladium precursor. In general, ionic liquids are novel reaction media for homogeneous catalysis. They allow easy separation of product and catalyst after the reaction. ... 

Heck and C-C coupling reactions (183). The highest activity and stability of palladium was observed in the ionic liquid [BMIM]Br. 

In contrast, ionic liquids have been reported to be suitable solvents for Heck reactions because the products can be readily separated from the ionic liquids containing the homogeneous palladium catalysts. An early test with a palladium complex in ionic liquids showed remarkably improved recyclability of the catalyst (255), but palladium black still formed after several runs with recycled catalyst. 

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... 

When another palladium complex, diiodobis(l, 3-dimethylimidazolium-2-ylidene)palladium(II), was used as a catalyst (257), it resulted in a large improvement in catalyst stability in the same ionic liquid. The Heck reaction performed better in the ionic liquid than in organic solvents such as dimethylfuran (DMF). In the reaction of bromobenzene with styrene, the yield of stilbene was increased from 20% in DMF to 99% in [NBu4][Br]. The ionic liquid showed excellent solubility for all the reacting molecules. 

In experiments with a supported palladium catalyst, Pd/C, satisfactory yields were obtained without the use of phosphine ligands for the Heck reactions of aryl iodide with acrylonitrile, styrene, and methyl methacrylate in the ionic liquid [BMIM]PF6 (259). The addition of triethylamine improved the yields. The Pd/C remained in the ionic liquid only. The ionic liquid containing Pd/C can be reused as... 

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