Heck aryl halides with olefins

Nanometer size Pd colloids in block copolymer micelles of polystyrene polyvinylpyridine as catalysts have been used is a novel way by Klingelhofer for Heck reaction of C-C coupling of aryl halides with olefins. 

Palladium catalyzed reaction of aryl halides with olefins is a useful synthetic method for C-C bond formation [219, 220]. The most commonly used catalyst is palladium acetate, although other palladium complexes have also been used. Solvent-free Heck reactions with excellent yields have been performed in a household MW oven with palladium acetate as catalyst and triethylamine as base (Scheme 8.88) [221]. A comparison study revealed that the longer reaction times and deployment of high pressures, typical of the classical heating method, are avoided using this MW procedure. 

Combination of the oxidative addition of aryl halide with olefin insertion followed by -hydrogen elimination provides a useful olefin arylation process catalyzed by a palladium complex (Mizoroki-Heck reaction) [63-65]. The essential part of the catalytic cycle is shown in Scheme 1.23. 

Another method that is widely used for C-C bond formation is the Heck coupling [3]. The arylation of olefinic double bonds is mostly catalyzed by palladium complexes in homogeneous solution. Important advantages of this reaction are the broad availability of arylbromides and chlorides and the tolerance of the reaction for a wide variety of functional groups. There were also developed heterogeneous Pd/C catalysts which exhibit high activity for the Heck reaction of aryl halides with olefins. The reaction conditions are 80 200 °C, solvents (NMP, DMF, tolueneAvater), base addition is necessary (NaOAc, amines, alkali carbonates). The reaction scheme can be described as follows (Eq. 8-22). 

Scheme 6.33 PdClj catalyzed Heck reaction of aryl halides with olefins in water.

Among early reported Pd-catalyzed reactions, the Mori-Ban indole synthesis has proven to be very useful for pyrrole annulation. In 1977, based on their success with the nickel-catalyzed synthesis of indole from 2-chloro-A -allylaniline, the group led by Mori and Ban disclosed Pd-catalyzed intramolecular reactions of aryl halides with pendant olefins [111]. Compound 117, easily prepared from 2-bromo-A-acetylaniline and methyl bromocrotonate, was adopted as a cyclization precursor. Treatment of 117 with PdiOAc), (2 mol%), PhjP (4 mol%), and NaHCOj in DMF provided indole 118 via an intramolecular Heck reaction followed by olefin isomerization to afford the fully aromatic product. Although yields fr om the initial report were moderate, they have been greatly improved over the last two decades [112]. 

The Pd-catalyzed coupling reaction of an aryl halide and olefin is a very efficient and practical method for making C—C bonds. The Heck alkenylation of aryl bromides with ethylene was used by Dow Chemical to make high-purity 2- and 4-vinyltoluenes, which are of interest as co-monomers in styrene polymers [159]. The monomer, o-vinyltoluene (99), has a low toxicity and an attractive co-monomer for styrene polymers. o-Vinyltoluene improved heat distortion properties of styrene and polymerization rate. It also minimized color formation or cross-linking and it was difficult to make by other routes [159]. Catalyst turnover, rate, and lifetime were significantly improved. 

Palladacycles prepared by the addition of furancarbothioamide to a methanol solution of Li2PdCl4 at room temperature are soluble in hexane, chloroform, and moderately soluble in polar solvents DMF and DMSO [187]. These palladacycles are thermally stable, not sensitive to air or moisture, and can be applied effectively in the Heck reaction of aryl halides with terminal olefins and in the Suzuki reaction of aryl halides with arylboronic acids. These reactions were performed under aerobic conditions, leading to turnover numbers... 

The palladium-catalysed Heck reaction of aryl or vinyl halides with olefins has been widely used in synthetic chemistry. The reaction works impressively well with a wide range of electron-deficient and neutral olefins, generally affording (1-arylatcd products. In the case of electron-rich olefins, however, a mixture of regioisomers is usually obtained under standard Heck reaction conditions (Figure 5.1).[1] This... 

The final common class of coupling reactions to form C-C bonds described here is the coupling of an aryl halide with an olefin to cleave the C-H bond of the olefin and replace it with an aryl group. This reaction, which is shown generically in Equation 19.18, was first reported by Mizoroki the synthetic utility of this process and e most useful conditions for this process at the time were reported by Heck. ° This process is often called the "Heck reaction," or more appropriately the "Mizoroki-Heck reaction." " The Heck reaction is most commonly conducted with electron-deficient olefins, such as styrene or acrylate derivatives. The electronic properties of these substrates tend to favor formation of the conjugated products. The reaction can also be conducted effectively with ethylene a Heck reaction between 6-methoxy-2-bromonaphthalene and ethylene is one step of a short, catalytic commercial synthesis of naproxen. In contrast, intermolecular reactions of internal olefins typically form mixtures of regioisomeric products. Intramolecular Mizoroki-Heck reactions with intemal olefins are more common. Mizoroki-Heck reactions of aliphatic electrophiles have been reported, but remain rare. Applications of the Mizoroki-Heck reaction have been reviewed. ... 

Activated Pd-containing LDH in brucite layers or supports is an efficient catalyst for the Heck reaction, i.e the reaction between aryl halides and olefins to give C—C coupled products (625b,625c). For example, an LDH with Pd Mg Al = 4 100 40 gives 100% conversion, over 80% yield, and over 99% trans product for the reaction of iodobenzene with methyl acrylate at 140°C for 4 h (625b). 

The Mizoroki-Heck reaction is a metal catalysed transformation that involves the reaction of a non-functionalised olefin with an aryl or alkenyl group to yield a more substituted aUcene [11,12]. The reaction mechanism is described as a sequence of oxidative addition of the catalytic active species to an aryl halide, coordination of the alkene and migratory insertion, P-hydride elimination, and final reductive elimination of the hydride, facilitated by a base, to regenerate the active species and complete the catalytic cycle (Scheme 6.5). 

The Heck reactions depicted so far all involve the coupling of halopyridines and other olefins. The alternate approach, coupling of a vinylpyridine with an aryl halide is also feasible, although less commonly employed. 4-Vinylpyridine was coupled successfully with diethyl 4-bromobenzylphosphonate (7.50.) in the presence of a highly active catalyst system consisting of palladium acetate and tn-o-tolylphosphine to give the desired product in 89% yield, which was used for grafting the pyridine moiety onto metal oxides.70... 

The basic pattern of the Heck reaction in its classical form is depicted in Scheme 1. It involves, for instance, the reaction of an aryl halide (1) with an olefin in the presence of a base and a catalytic amount of a palladium complex to give a styrene derivative (2) under elimination of HX. 

The rate of reaction and regioselectivity of Heck olefination are sensitive to steric hindrance about the C=C bond of the vinylic partner. For simple aryl halides reacting with alkenes, the rate of reaction as a function of alkene substitution varies95 according to... 

The palladium-catalysed arylation of olefins with aryl halides, the Heck reaction, is usually performed in polar solvents such as acetonitrile or dimethyl sulfoxide, in combination with a base and a Pd(ii) pre-catalyst that may or may not be associated with a phosphorus ligand. Given that quaternary ammonium or phosphonium salts are known to increase reaction rates, ILs emerged as promising solvents for this reaction.In the case of imidazolium-based ionic liquids, the solvent, beside providing an unusual coulombic environment. 

In 1991 at the Central Research Laboratories of Hoechst AG we became interested in the palladium-catalyzed olefination (Heck reaction) of aryl halides and aryl diazonium compounds which is arguably one of the most powerfiil methods for the synthesis of substituted olefins. In collaboration with Herrmann and co-workers we have shown that active catalyst mixtures obtained by using in situ mixtures of Pd(II) salts and commercially available tri-o-tolylphosphine consist under the conditions of the Heck reaction primarily of cyclometaUated paUadacycles l... 

The first example of an o/t/20-alkylation/Mizoroki-IIcck coupling was reported by Catellani [4] in 1997. Using the PNP dimer as a catalyst in the presence of an aryl halide, norbomene, an alkyl iodide, a terminal olefin and a base at room temperature, 1,2,3-trisubstituted benzenes (Scheme 16), were synthesized through alkylation of a palladacycle of type 35, followed by Mizoroki-Heck coupling with an arylpalladium(II) species of type 36. Although the synthetic scope of the reaction was limited, the importance of the report reveals an unprecedented catalytic transformation where two aryl C-H bonds are converted to sp2-sp3 C-C bonds followed by a standard Mizoroki-Heck coupling. The 1,2,3-trisubstitution pattern generated in the products would be very difficult to obtain via conventional methods. 

Substitution of aryl and vinylic halides. Dieck and Heck have reported a reaction of aryl and vinylic bromides and iodides with olefins catalyzed by palladium acetate and 2 eq. of triphenylphosphine that is related to the reaction mentioned above. New olefins are formed by replacement of the vinylic hydrogen of the original olefin by the Ar or R group of the halide. 

Thus, traMi-3-alkyl-6-(phthalimido)cyclopentenes were prepared in excellent to modest yields from the corresponding tran -chloroalkene by the palladium coupling reaction [84d]. Inexpensive and efficient Pd-TMG systems, Pd(OAc)2-TMG or PdC -TMG, have been developed for the Heck reaction of an olefin with an aryl halide, in which TMG (1) acts as a ligand [84e]. In the reaction of iodobenzene with butyl acrylate the turnover numbers were up to 1000000. TMG (1) was used as a base for the palladium catalysed asymmetric Wagner-Meerwein shift of nonchiral vinylcyclopropane and cyclobutane derivatives leading to asymmetric synthesis of cyclobutanones, cyclopentenones, y-butyrolactones and 5-valerolactones [85] (Scheme 4.34). Replacement of TMG (1) with an inorganic bases such as lithium or cesium carbonate resulted in little effect. 

The Heck reaction of olefins with aryl halides proceeds successfully in the presence of palladium catalyst supported on TMG (1) modified molecular sieves without solvent. The TMG-Pd was found to be much more active and stable than the palladium catalyst without modification with TMG (1) [87]. An ionic liquid, tetramethylguanidinium lactate, was used as the TMG source. 

In the Mizoroki-Heck process, aryl and alkenyl halides are converted on reaction with olefins in the presence of a base into arylated or alkenylated olefins. The arylation case is shown in the scheme but it is applicable also to the alkenylation process. 

Xiao et al. [213] recently reported that the intermolecular Heck arylation with several electron-rich olefins can be effected with both aryl bromides and iodides in a highly regioselective manner by the use of ionic liquids. Regioselectivity towards the branched cr-olefin was up to 99/1 and there was no need for additional halide scavenger. In this case the ionic liquid seems to serves not only as a quite polar solvent but also as halide scavenger. 

Bradley et al. employed P VP-stabilized palladium colloids, which were pretreated with the base and the olefin at the reaction temperature prior to addition of the aryl halide (Table 1) [19]. The colloids were prepared by stirring [Pd(dba)2] in the presence of PVP at variable hydrogen pressures, affording particles of different average particle size (diameter 1.7 0.5 nm to 3.7 0.3 nm). The initial activities of Heck reactions catalyzed by these colloids of different average particle size were correlated with the number of low-coordinated atoms, i.e., comer and edge atoms in the palladium particles rather than all surface atoms. A general difficulty in such considerations is that the particles are not monodisperse, and also are not ideal cuboctahedra. 

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