Heck styrene

Heck type vinylation of 4-bromo-l-(4-methylphenylsulfonyl)-indole proceeds in good yield with such alkenes as methyl acrylate, styrene and N-vinylphthalimide using Pd(OAc)2 (5 mol%) and tri-o-tolylphosphine as the... 

Pd/P(t-Bu)., in the presence of Cy2NMe, is an unusually mild and versatile catalyst for Heck reactions of aryl chlorides (Tables 1 and 2) (as well as for room-temperature reactions of aryl bromides).21 22 23 Example A, the coupling of chlorobenzene with butyl methacrylate, illustrates the application of this method to the stereoselective synthesis of a trisubstituted olefin a-methylcinnamic acid derivatives are an important family of compounds that possess biological activity (e.g., hypolipidemic24 and antibiotic25) and serve as intermediates in the synthesis of pharmaceuticals (e.g., Sulindac, a non-steroidal anti-inflammatory drug26). Example B, the coupling of 4-chlorobenzonitrile with styrene, demonstrates that Pd/P(t-Bu). can catalyze the Heck reaction of activated aryl chlorides at room temperature. 

An interesting parallel was found while the microwave-enhanced Heck reaction was explored on the C-3 position of the pyrazinone system [29]. The additional problem here was caused by the capability of the alkene to undergo Diels-Alder reaction with the 2-azadiene system of the pyrazinone. An interesting competition between the Heck reaction and the Diels-Alder reaction has been noticed, while the outcome solely depended on the substrates and the catalyst system. Microwave irradiation of a mixture of pyrazinone (Re = H), ethyl acrylate (Y = COOEt) and Pd(dppf)Cl2 resulted in the formation of a mixture of the starting material together with the cycloaddition product in a 3 1 ratio (Scheme 15). On the contrary, when Pd(OAc)2 was used in combination with the bulky phosphine ligand 2-(di-t-butylphosphino)biphenyl [41-44], the Heck reaction product was obtained as the sole product. When a mixture of the pyrazinone (Re = Ar) with ethyl acrylate or styrene and Pd(dppf)Cl2 was irradiated at 150 °C for 15 min, both catalytic systems favored the Heck reaction product with no trace of Diels-Alder adduct. 

The much more stable MIL-lOO(Cr) lattice can also be impregnated with Pd(acac)2 via incipient wetness impregnation the loaded catalyst is active for the hydrogenation of styrene and the hydrogenation of acetylene and acetylene-ethene mixtures to ethane [58]. MIL-lOl(Cr) has been loaded with Pd using a complex multistep procedure involving an addition of ethylene diamine on the open Cr sites of the framework. The Pd-loaded MIL-lOl(Cr) is an active heterogeneous Heck catalyst for the reaction of acrylic acid with iodobenzene [73]. 

In aqueous DMF, the reaction can be applied to the formation of C-C bonds in a solid-phase synthesis with resin-bound iodobenzoates (Eq. 6.33).80 The reaction proceeds smoothly and leads to moderate to high yield of product under mild conditions. The optimal conditions involve the use of 9 1 mixture of DMF-water. Parsons investigated the viability of the aqueous Heck reactions under superheated conditions.81 A series of aromatic halides were coupled with styrenes under these conditions. The reaction proceeded to approximately the same degree at 400°C as at 260°C. Some 1,2-substituted alkanes can be used as alkene equivalents for the high-temperature Heck-type reaction in water.82... 

Although aryl halides are the substrates of choice for Heck transformations, dia-zonium salts have also gained great interest, due mainly to reasons of economy [478]. With this in mind, the group of Beller explored a domino diazotization/Heck sequence of substituted anilines 2-935 with ethylene (Scheme 2.209) [479]. The reaction proceeds best in the presence of Pd(OAc)2 and tBuONO as diazotization reagent in a mixture of acetic acid and CH2C12. Using these conditions, the desired styrenes 2-936 were isolated in yields up to 72 %. 

This protocol could be extended to a range of different ,/i-unsaturated carbonyl compounds and either activated or deactivated aryl iodides [22], An application of related Heck chemistry to the synthesis of methylated resveratrol (3,4, 5-trihydroxy-( )-stilbene) is shown in Scheme 6.4 [23]. The phytoalexin resveratrol exhibits a variety of interesting biological and therapeutic properties, among them activity against several human cancer cell lines. Botella and Najera have shown that the trimethyl ether of resveratrol (Scheme 6.4) can be rapidly prepared by microwave-assisted Heck reaction of the appropriate aryl iodide and styrene derivatives, using the same oxime-derived palladacycle as indicated in Scheme 6.3. 

A heterogeneous Pd catalyst dispersed on supports such as o-A1203, C, MgO and CaC03 was found to be an recyclable and selective catalyst for heterogeneous Heck arylation (an important method of C-C bond formation - Chapt. 11) of several olefins (styrene, a-methylstyrene, 1-decene, acrylonitrile, etc.) with iodobenzene [45], Scheme 10.5. 

In a later publication,[51] Heck reactions (between iodobenzene and styrene) were performed in the same way. In contrast to the PTC, the catalyst for the Heck reaction... 

Bis(pyrazolyl)borate copper complex 47 has been employed as a catalyst in the homogeneous and heterogeneous styrene epoxidation reactions <00JCS(CC)1653>. Pyrazole palladacycles 48 have proven to be stable and efficient catalysts for Heck vinylations of aryl iodides <00JCS(CC)2053>. An asymmetric borane reduction of ketones catalyzed by N-hydroxyalkyl-/-menthopyrazoles has been reported <00JHC983>. 

The Heck reaction, first disclosed by the Mori and Heck groups in the early 1970s [65, 66], is the Pd-catalyzed coupling reaction of organohalides (or triflates) with olefins. Nowadays, it has become an indispensable tool for organic chemists. Inevitably, many applications to heterocyclic chemistry have been pursued and successfully executed. In one case, Ohta et al. reacted 2-chloro-3,6-dimethylpyrazine (49) with styrene to furnish ( )-2,5-dimethyl-3-styrylpyrazine (50) [67]. Here, only the E isomer was observed. The outcome will become apparent during the ensuing discussions on the mechanism. 

A related Heck reaction of substituted o-bromoacetanilides with styrenes followed by selenium-induced cyclization of the resulting o-styiylacetanilides gives 2-arylindoles [378], Substituted o-bromonitrobenzenes react with ethyl vinyl ether under the influence of Pd(OAc)2 to give the corresponding o-ethoxyethenylnitrobenzenes. Zinc reduction then yields indoles [379]. The one-step Pd-catalyzed conversion of o-bromoanilines to indoles 302 with enamines (or with A/-vinyl-2-pyrrolidone) has been reported [380]. 

Without the alkoxy substituent on the olefin, steric effects prevail. The Heck adduct 164 was isolated when 2-chloro-3-pivaloylamidopyridine (163) was allowed to react with an excess of styrene [129], Steric effects can play a major role in the regioselectivity of these reactions. 

Akita and Ohta revealed one of the early Heck reactions of halopyrazines [23]. They reacted 2-chloro-3,6-dimethylpyrazine (23) with styrene in the presence of Pd(Ph3P)4 and KOAc using A(//-dimethylacetamide (DMA) as solvent to make ( )-2,5-dimethyl-3-styrylpyrazine (51). This methodology was later extended to 2-chloropyrazine IV-oxides although the yields were modest (28-38%) [37]. 

E)-stilbene was the exclusive product of the Pd colloid-catalyzed Heck arylation of styrene with chlorobenzene. Recently, a polymer-mediated self-assembly of functionalized Pd and Si02 nanoparticles have been found to be highly active catalysts for hydrogenation and Heck coupling... 

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. 

The atom economy of the cross-coupling reaction and the Heck reaction for making styrene from bromobenzene and vinyl bromide (cross), and bromobenzene and ethene (Heck) respectively are in favour of the Heck reaction, as that produces only one equivalent of salt. 

In the second series of experiments, O. Nuyken et al. investigated the Heck reaction of iodobenzene with styrene as a model for the numerous palladium-catalyzed coupling reactions (Scheme 6.6) [54]. In the literature only a few Heck coupling reactions of hydrophobic substrates in aqueous solution are known. The most detailed study has been performed by Jeffery et al. on the model reaction of iodobenzene with methylacrylate in the presence of tetrabutylammonia salts. Product yield was at least 95% after 2 h reaction time at 50 °C in pure aqueous solution [55], however more... 

Scheme 6.6 Heck coupling of iodobenzene and styrene as a model reaction for micellar catalysis using triphenylphosphine-functionalized poly(2-oxazoline)s as macroligands...

In a first test reaction, the polymer support was used for the hydroformylation of 1-octene in water in the presence of Rh(CO)2acac. Within a reaction time of 10 h at 120°C and a H2/CO (1 1) pressure of 5 MPa, conversion of up to 94% was obtained. The n iso ratio was 3 1, sometimes reaching 9 1. The quantities of 3-and 4-nonanal resulting from olefin isomerization, were below 5% [74]. The versa-tihty of the polymer support was further demonstrated with the Heck reaction of styrene and iodobenzene in the presence of Pd(OAc)2 as the metal catalyst The reaction was again performed in pure water at 50 °C and product yield of up to 80% was obtained after 20 h reaction time [75]. 

An instructive example for a positive dendritic effect was reported by Reetz et al. [71]. The authors described a poly(propylenimine) dendrimer, with diphenylphos-phine groups in the periphery (Fig. 7.20). A dendritic [PdMe2]-complex was tested as an efficient catalyst in the Heck reaction of bromobenzene and styrene to yield stilbene (85-90% conversion). The separation technique originally investigated for... 

---