Heck reaction phosphine free catalysts

Phosphine free catalysts and halogen-free reactions are known for the Heck reaction. Improvements on the palladium catalyst system are constantly being reported, including polymer-supported catalysts." °° The influence of the ligand has been examined." Efforts have been made to produce a homogeneous catalyst for the Heck reaction." The Heck reaction can be done in aq. media," ° in perfluori-nated solvents," in polyethylene glycol," ° in neat tricaprylmethylammonium... 

MT Reetz, E Westermann, R Lohmer, G Lohmer. A Highly Active Phosphine-free Catalyst System for Heck Reactions of Aryl Bromides. Tetrahedron Lett 39 8449-8452,1998. 

Consorti, C.S., Zanini, M.L., Leal, S. et al. (2003) Chloropalladated propargyl amine a highly efficient phosphine-free catalyst precursor for the Heck reaction. Org. Lett., 5, 983-6. 

Therefore, a good catalyst leads to weak fluorescence in the Heck product (15). A relatively small library of 96 known phosphines was tested in the palladium-catalyzed Heck coupling. Several sterically hindered ligands led to high catalyst activity. Fluorescence tags have also been used in the combinatorial search for metal-free catalysts in other types of reaction.42,43... 

Greater durability of the colloidal Pd/C catalysts was also observed in this case. The catalytic activity was found to have declined much less than a conventionally manufactured Pd/C catalyst after recycling both catalysts 25 times under similar conditions. Obviously, the lipophilic (Oct)4NCl surfactant layer prevents the colloid particles from coagulating and being poisoned in the alkaline aqueous reaction medium. Shape-selective hydrocarbon oxidation catalysts have been described, where active Pt colloid particles are present exclusively in the pores of ultramicroscopic tungsten heteropoly compounds [162], Phosphine-free Suzuki and Heck reactions involving iodo-, bromo-or activated chloroatoms were performed catalytically with ammonium salt- or poly(vinylpyrroli-done)-stabilized palladium or palladium nickel colloids (Equation 3.9) [162, 163],... 

Palladacycles [17] have been established as important class of catalysts, an unusual phosphine-free sulfur containing catalyst was introduced by Zim [18] et al. A phosphinite based palladacycle [19] proved to be very efficient in Suzuki coupling reactions. An N,P-Ligand type was synthesized by Kocovsky [20] et al. Tridentate pincer ligands [21] have been proved use-fill in the Heck reaction. Recent developments regarding Heck (22] and Suzuki [23] reactions have been reviewed by Fu and Littke. A new catalyst especially suitable for Heck couplings has been introduced by Beller [24] et al. 

Because aryl phosphines are not only costly but can also act as aryl sources themselves, giving rise to unwanted byproducts, there has been steady interest in extending ligand-free Heck reactions to aryl bromides and aryl chlorides. Reetz and de Vries recently found that these can be performed with high efficiency using stabilized colloidal Pd catalysts [21]. If the palladium is kept at a low concentration between 0.01 and 0.1 mol%, precipitation of the Pd(0) is avoided and the colloids serve as a reservoir for the catalytically active species (Scheme 5). This economically attractive method has been successfully applied on an industrial scale by DSM [22]. 

A different example of triphasic catalysis for the Heck, Stille and Suzuki reactions relied on a three-phase microemulsion/sol-gel transport system. Gelation of an z-octyl(triethoxy)silane, tetramethoxysilane and Pd(OAc)2 mixture in a H2O/CH2CI2 system led to a hydrophobicitized sol-gel matrix that entrapped a phosphine-free Pd(ii) precatalyst. The immobilized precatalyst was added to a preformed microemulsion obtained by mixing the hydrophobic components of a cross coupling reaction with water, sodium dodecyl sulfate and a co-surfactant, typically zz-propanol or butanol. This immobilized palladium catalyst was leach proof and easily recyclable. 

Polyurea-encapsulated palladium catalysts promote the phosphine-free Mizoroki-Heck reaction, which results in a high yield of cinnamates 46 (Scheme 86). The catalyst, which is easily recovered by filtration, is also applicable to the Suzuki-Miyaura and Stifle coupling reactions. 

Scheme 36, A and Turnover numbers up to approximately 500,000 were reported for the reaction of iodobenzene with methyl acrylate and an impressive nnmber (about 100,000) was also achieved with bromobenzene and 4-methoxy-bromobenzene. Characteristic featnres of these tridentate PCP catalysts are thermal stability and air stability. A competitive experiment, including 4-bromoiodobenzene, iodobenzene, 4-methyliodoben-zene, and 4-methoxy-iodobenzene with methyl acrylate provided a linear correlation with Hammet cr-valnes, which, however, exhibited a low p valne (1.39). It was concluded that nucleophilic aromatic substitution is not rate determining, bnt a snbsequent step with different electronic requirements, such as alkene insertion, may acconnt for this observation. Chlorobenzene could not be coupled with these catalyst. Very recently, Milstein s group reported new cyclopalladated, phosphine-free imine complexes as catalysts in the Heck arylation reaction (Scheme 36, The new dimeric imine complexes show... 

The Heck cross coupling reaction has been described with a phosphine-free PVK anchored palla-dium(II) complex as catalyst under aerobic conditions [57]. The Heck cross coupling reaction is shown in Figure 1.9. 

Gruber, A.S., Pozebon, D., Monteiro, A.L. and Dupont, J. (2001) On the use of phosphine-free PdCl2(SEt2)2 complex as catalyst precursor for the Heck reaction. Tetrahedron Lett., 42, 7345-8. 

The application of ultrasound in Mizoroki-Heck reactions is not well described. The first application of ultrasound irradiation in Mizoroki-Heck reactions performed in ionic liquids catalysed by palladium-carbene complexes and palladium nanoparticles was published in 2001 [ 190]. The Pd/C-catalysed reaction of iodobenzene and methyl methacrylate in NMP at room temperature resulted in an increased reaction rate under sonochem-ical conditions [191]. The catalyst showed high activity under phosphine-free ambient conditions and could be reused. The coupling products could be obtained in up to 70% yield. 

Scheme 7.7 Homeopathic, phosphine ligand-free palladium catalyst in Mizoroki-Heck reactions.

It was shown that palladacydes 1 [3c, 24] prepared from palladium] I) acetate and tris(o-tolyl)- or trimesitylphosphine are excellent catalysts for the Heck coupHng of triflates and halides including certain aryl chlorides. In some of these cases, a possible involvement of oxidation states +II and +IV in the catalytic cycle has been considered [25]. Similarly, other palladacydes such as 3 [26e,h] or 6 [27] have been used in the Heck reactions (Figure 8.1) [24, 26, 28]. It has been proposed that, at least for NC palladacydes, the reaction proceeds through the classical phosphine-free Pd(0)/Pd(II) catalytic cycle and that the active catalysts are actually slowly formed palladium clusters [29]. Besides classical palladacydes, complexes with pincer-type ligands such as 2 [30] have become very popular in palladium catalysis [31]. 

Apart from the catalytic systems based on Pd/phosphines typically used in Mizoroki-Heck reactions, many other types of new palladium catalysts have been developed over the last decade. Avoiding the use of the phosphine ligands is a great advantage as they usually cannot be recovered and they frequently hamper the isolation and purification of the final product. One viable alternative is the use of ligand-free palladium catalysts usually in the form of Pd(OAc)2. At the high temperatures required for Mizoroki-Heck reactions, most ligand-free palladium complexes are unstable and have a tendency to form soluble Pd(0) nanoparticles [32]. The question arises as to the role played by the Pd nanopartides formed and whether... 

The accelerating effect of water on the rate of the phosphine-free Heck reaction of Phi with methyl acrylate in A -methylpyrroIidone solvent has recently been examined to reveal that the addition of water promotes the formation of stable palladium nanoparticles serving as a source of catalyst. "... 

The Heck reaction (also called the Mizoroki-Heck reaction) is the chemical reaction of an unsaturated halide with an alkene in the presence of a base and a palladium catalyst (or palladium nanomateiial-based catalyst) to form a substituted alkene. An efficient and simple protocol for phosphine-free Heck reactions in water in the presence of a Pd(L-proline)2 complex as the catalyst under controlled micro-wave irradiation conditions is versatile and provides excellent yields of products in short reaction times (Scheme 8.17) [20], The reaction system minimizes costs, operational hazards, and envirorunental pollution. 

Allam BK, Singh KN (2011) An elEcient phosphine-free heck reaction in water using Pd(L-Proline)2 as the catalyst under microwave irradiation. Synthesis 2011(7) 1125-1131... 

The development of a Heck reaction in aqueous media, enabling a one-pot process with both reaction steps (Heck reaction and biotransformation) running in aqueous media, was also reported by Cacchi and coworkers [65]. This type of Heck reaction is based on the use of a phosphine-free perfluoro-tagged palladium nanoparticle. After detailed catalyst characterization and process development, Cacchi and coworkers also succeeded in combining this Heck reaction efficiently with the subsequent asymmetric ketone reduction toward a one-pot process. A representative example is shown in Scheme 19.25. The enzymatic process turned out to be very compatible with the Heck reaction, and the desired allylic alcohol products were obtained in yields of up to 92% and with excellent enantioselectivities of >99% ee in aU cases. This two-step one-pot process was, for example, successfully applied for the synthesis of (k)-(—)-rhododendrol ((J )-81) in 90% yield and with excellent (>99%) ee (Scheme 19.25) [65]. 

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