Styrene, hydrocarboxylation

Novel heterogeneous catalysts containing a palladium complex anchored on meso-porous supports for hydrocarboxylation of aryl olefins and alcohols were found to give high regioselectivity, activity, and recyclability without leaching of palladium complex from the supports. In styrene hydrocarboxylation at 115 °C and 31 bar CO pressure, 2-phenyl-propionic acid is formed with 99% selectivity at 2600 mol styrene mol palladium h turnover frequency [137]. 

In this process, double bonds were found to be less reactive than triple bonds. Thus norbornene or styrene were hydrocarboxylated in low yields (10-40%) [121]. In unconjugated as well as conjugated ene-ynes, only the alkyne moiety was carboxylated with regio- and stereoselectivity similar to that observed for alkynes [122]. 

The hydrocarboxylation of styrene (Scheme 5.12) and styrene derivatives results in the formation of arylpropionic acids. Members of the a-arylpropionic acid family are potent non-steroidal anti-inflammatory dmgs (Ibuprofen, Naproxen etc.), therefore a direct and simple route to such compounds is of considerable industrial interest. In fact, there are several patents describing the production of a-arylpropionic acids by hydroxycarbonylation [51,53] (several more listed in [52]). The carbonylation of styrene itself serves as a useful test reaction in order to learn the properties of new catalytic systems, such as activity, selectivity to acids, regioselectivity (1/b ratio) and enantioselectivity (e.e.) in the branched product. In aqueous or in aqueous/organic biphasic systems complexes of palladium were studied exclusively, and the results are summarized in Table 5.2. 

Gonsidering that the chiral aldehydes obtained by asymmetric hydroformylation of vinylarenes are often oxidized to give the corresponding acids that exhibit biological activities, asymmetric hydrocarboxylation and its related reactions naturally attract much attention. Unfortunately, however, less successful work has not been reported on this subject than on the hydroformylation. Palladium(ii) is most commonly used for this purpose. Styrene and other vinylaromatics are most widely examined and the data for representative examples are summarized in Table 14. The products are of... 

Styrene characteristically yields the branched acid in the presence of palladium and monodentate phosphine ligands,132 142 and in the [Fe(CO)5]-promoted process.143 Palladium with certain bidentate phosphines, in turn, produces more linear acid.142 Asymmetric hydrocarboxylations with palladium complexes and chiral ligands with enantiomeric excesses up to 84% have been reported.144 145... 

The regioselectivity of the Pd(II)-catalysed hydrocarboxylation of styrene has been elucidated and two different mechanisms have been suggested to account for the differences... 

Asymmetric hydrocarboxylation of styrenes.1 Use of (S)- or (R)-l as a chiral ligand in the palladium-catalyzed hydrocarboxylation of p-isobutylstyrene (2) results in (S)- or (R)-2 (ibuprofen) in 83-84% ee. Similar enantioselectivity obtains in hydrocarboxylation of a 2-vinylnaphthalene to form naproxen. 

Table 7 Hydrocarboxylation of styrene with [PdCl2(PhCN)2] supported by monophosphines or diphosphtnes"...

Table4.Hydrocarboxylation of styrene (la) and its derivatives (Ib-c) catalyzed by chiral Pd(II) complexes... 

The hydrocarboxylation of styrene (Scheme 5.12) and styrene derivatives results in the formation of arylpropionic acids. Members of the a-arylpropionic acid family are potent non-steroidal anti-inflammatory drags (Ibuprofen, Naproxen etc.), therefore a direct and simple route to such compounds is of considerable industrial interest. In fact, there are several patents describing the production of a-arylpropionic acids by... 

The first examples of asymmetric hydrocarboxylation have been reported for various alkenes, converted in the presence of palladium(II) chloride and Diop, with a maximum ee of 14.2% 6 (for 2-phenylpropene). In this unsymmetrical addition reaction, similar to hydroformylation, both at- and -induction via C—C and C —H bond formation are observed. Styrene and 2-phenyl-l-propene (a-methylstyrene) are typical examples. 

One of the first examples of the asymmetric hydrocarboxylation of a-methylstyrene (2-phenyl-1-propene) in the presence of palladium(II) chloride and Diop was reported with a maximum enantiomeric excess of 14.2 % 6. In this case /7-induetion was achieved in the linear product via C-H bond formation. a-Induction through C.-C bond formation occurs in the branched product of styrene. Interestingly, the reaction of a-methylstyrene with different alcohols gives varying amounts of asymmetric induction. While 9.7% op is observed with ethanol, the more sterically hindered 2-propanol gives the linear product with 14.2% op6. 

The conversion of a-methylstyrene (2-phenyl- 1-propene) also serves as a model reaction in many other investigations of asymmetric hydrocarboxylation. Due to its high regioselectivity and low tendency for alkene isomerization, only the linear reaction product is formed (> 95 %) together with minor amounts of the achiral branched product. With styrene itself, and other vinyl aromatics generally lower regioselectivities are observed. The results of asymmetric hydrocarboxylation of this substrate type are compiled in Table 10. 

Table 10. Asymmetric Hydrocarboxylation of Styrene and Other Vinyl Aromatics... 

Many other chiral phosphane ligands are used in asymmetric hydrocarboxylation. In the presence of NMDPP and trifluoroacetic acid in methanol carbomethoxylation of vinyl aromatics. in particular styrene, with palladium(0)bis(dibenzylidcncacetone) takes place with marked asymmetric induction (up to 52% cc) and high selectivities towards the branched product (94%)20. With other chiral ligands and other acids only smaller inductions are observed using the same catalytic system. With an increase in carbon monoxide pressure the asymmetric induction decreases. Involvement of the complex PdH(PR3),OCOCF3 is presumed20. 

Asymmetric hydrocarboxylation of styrene and aliphatic alkenes with palladium(II) chloride in the presence of the steroidal phosphanes (+)-DICOL and (—)-DIOCOL (prepared from cholesterol) show remarkable catalytic activity and very high regioselectivity, but only poor stereoselectivities21, 22. Optical yields of up to 12.5% ee are obtained in asymmetric hydrocar-boxylations using DIOCOL. The results obtained with DICOL and DIOCOL have been compared with the inductions obtained with Diop. 

Recent progress in palladium(II) chloride catalyzed hydrocarboxylations is reported for the conversion of styrenes to give optically active free carboxylic acids24,25. The reactions are conducted in the presence of a protic acid, copper(II) chloride, oxygen, and a single enantiomer of an optically active compound selected from menthol, tartaric acid or ester, sugars, proteins, polypeptides, enzymes and chiral phosphanes. 

Thus, ibuprofen and naproxen can be synthesized in 64-89% yield and 83-91 % optical purity via palladium(Il) chloride catalyzed hydrocarboxylation of the corresponding styrenes in the presence of (-)-(/ )- or ( + )-(5)-2,2 -(l,l -binaphthyl)phosphoric acid. The hydrocarboxylation reaction is completely regiospeciftc and proceeds at room temperature under 1.01 bar carbon monoxide pressure25. 

Ibuprofen and naproxen as 2-arylpropionic acids belong to an important new class of nonsteroidal anti-inflammatory agents42. Asymmetric hydrocarboxylation of styrenes thus represents a direct access to optically active or enantiomerically pure probes. 

The results of asymmetric hydrocarboxylation of aliphatic alkenes are compiled in Table 11 and rarely exceed 20% ee. Thus, with the catalytic systems used up to now, this method is not yet conveniently applicable to the asymmetric synthesis of carboxylic acids. The new catalytic systems used for hydrocarboxylation of styrenes and heterofuuctionalized alkenes may give better results, if applied to these substrates. 

The [Pd(TPPTS)3] catalyst was applicable to the synthesis of 2-(4-isobutylphenyl)propionic acid (Ibuprofen) both by carbonylation of 1-(isobutylphenyl)ethanol and by hydrocarboxylation of 4-isobutylstyrene in the presence of p-toluenesulfonic acid under the conditions discussed above for benzyl alcohol and styrene (176). The desired branched acid was obtained with remarkable selectivity in both cases (Scheme 24). 

Recently, new mononuclear and dinuclear palladium complexes containing one neutral and one anionic sulfur donor center derived from the atropisomeiic thiol-thioether derivative (RHbinas) were used as catalysts for the hydrocarboxylation of styrene in the presence of triphenylphosphine and oxalic acid. The new complexes are active catalysts for the hydrocarboxylation of styrene, showing a high regioselectivity toward the branched product (97%) under relatively mild conditions (Eq. 2). ... 

In the last five years interesting publications have appeared on the hydrocarboxylation of olefins in aqueous-organic two-phase systemsJ ° The catalytic systems consist of water-soluble phosphine ligands and a palladium complex in an acidic medium, resulting in high yields and selectivities for the hydrocarboxylation of styrene derivatives and terminal olefins (Eq. 

Scheme 5.9 Proposed mechanism for nickel-catalyzed hydrocarboxylation of styrenes (adapted from [48])...

Scheme 5.8) was produced selectively. The suggested mechanism implies a nickel-hydride active catalyst, instead of a classic Hoberg-t5tpe oxanickelacycle (Scheme 5.9). The intermediacy of a metal-hydride species is a peculiarity also distinguishing other metal-catalyzed hydrocarboxylation reactions [48-51]. Insertion of a styrene moiety into the nickel-hydride bond provides a benzyl nickel species which undergoes carboxylation. Subsequent tmns-metalation of the reaction intermediate with Et2Zn yields the hydrocarboxylation product and releases the precatalyst. 

Representative diene-based polymers include natural rubber (NR), polyisoprene (PIP), PBD, styrene—butadiene rubber (SBR), and acrylonitrile-butadiene rubber (NBR), which together compose a key class of polymers widely used in the rubber industry. These unsaturated polyolefins are ideal polymers for chemical modifications owing to the availability of parent materials with a diverse range of molecular weights and suitable catalytic transformations of the double bonds in the polymer chain. The chemical modifications of diene-based polymers can be catalytic or noncatalytic. The C=C bonds of diene-based polymers can be transformed to saturated C—C and C—H bonds (hydrogenation), carbonyls (hydrofbrmylation and hydrocarboxylation), epoxides (epoxidation), C—Si bonds (hydrosilylation), C—Ar bonds (hydroarylation), C—B bonds (hydroboration), and C—halogen bonds (hydrohalogenation). ... 

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