Hydroformylation and Hydrocarboxylation

Hydroformylation involves the reaction of C=C bonds with syngas (i.e., a mixture of carbon monoxide and hydrogen) and produces aldehyde functional groups. Hydroformylation of diene-based polymers is mostly performed by means of providing sites for further derivations. The most commonly explored secondary modification of aldehyde functional groups is hydrogenation to give primary alcohol functionality however, aldehyde may also be converted to nitrile, acetate, or amine functionalities.  

Since the mid-1990s, most studies of polymer-related hydroformylation have involved the use of polymer-bound rhodium catalysts for the hydroformylation of small molecule olefins. However, a few recent papers have focused on the catalytic hydroformylation of high-molecular-weight polymers [previously, formyl loading higher than 50% had not been 

In a later report, Im-Erbsin and coworkers explored hydroformylation for chemical modifications of ultrahigh-molecular-weight ( 2,000,000 g/mol) d5-l,4-PBD. The only catalyst investigated was HRh(CO)(PPh3)3. Under conditions of 70 °C and 5.5 MPa syngas pressure for 10 h, 80% of the C=C bonds in PBD were converted to formyl groups (Fig. 5C). Similar conversions were achieved by Chen and coworkers under comparable reaction conditions for the hydroformylation of SBR (Fig. 5B). However, no post-hydroformylation polymer molecular-weight information was provided for either reaction system. 

At nearly the same time, Jun and coworkers explored a versatile simultaneous hydroacylation and hydrogenation of low-molecular-weight PBD. A novel C—C bond coupling method between a primary alcohol and a 1-alkene in the presence of a rhodium catalyst afforded ketone functionality. The primary alcohol was initially oxidized to an aldehyde by the rhodium catalyst, and subsequent hydroacylation of the aldehyde with 

1- alkene produced a ketone-functionalized alkane (Fig. 7A). The authon discovered that a catalyst system composed of RhCl3-H20, PPh3, and 

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The most typical examples in oleochemistry are the hydrogenation, the carbon monoxide reactions hydroformylation and hydrocarboxylation, and the oxidation reaction. 

Asymmetric hydroformylation and hydrocarboxylation reactions have been reviewed/ From a comparison of the X-ray structures, it has been pointed out that the chiral coordination structure of diop (la) is very different from that of diphol (lb) and the results obtained in rhodium-catalyzed hydroformylations with these ligands have been rationalized/ ... 

Note that alkene insertion into an M-H bond may occur in two different ways giving two possible isomers Markovnikov (metal connected to the more branched carbon) and anti-Markovnikov (metal connected to the less branched carbon). This has important consequences on the selectivities of many homogeneous catalytic reactions such as isomerization, hydroformylation, and hydrocarboxylation. 

Ojima, I. Eguchi, M. Tzamarioudaki, M. Transition Metal Hydrides Hydrocarboxylation, Hydroformylation, and Asymmetric Hydrogenation. In Wilkinson, G. Stone, F. B. A. Abel, E. W., Eds., Comprehensive Organometallic Chemistry 2, Vol. 12, Pergamon, Oxford, 1995, Chapter 2. 

Metal-catalysed hydrocarboxylation of olefins (Equation 3) is the poor relative of the more famous hydroformylation. It generally requires forcing reaction conditions and suffers from mediocre activities and selectivities (n/i ratio). Moreover, the same products can be made via hydroformylation and oxidation of the aldehyde product.431 Consequently, there are few industrial applications of hydrocarboxylation e.g. Ni(CO)4-catalysed production of propionic acid by hydrocarboxylation of ethylene.432,433... 

In the previous chapters we discussed alkene-based homogeneous catalytic reactions such as hydrocarboxylation, hydroformylation, and polymerization. In this chapter we discuss a number of other homogeneous catalytic reactions where an alkene is one of the basic raw materials. The reactions that fall under this category are many. Some of the industrially important ones are isomerization, hydrogenation, di-, tri-, and oligomerization, metathesis, hydrocyana-tion, hydrosilylation, C-C coupling, and cyclopropanation. We have encountered most of the basic mechanistic steps involved in these reactions before. Insertions, carbenes, metallocycles, and p -allyl complexes are especially important for some of the reactions that we are about to discuss. 

Other asymmetric synthetic processes used for the manufacturing of (S)-(-l-)-naproxen can also be applied to the production of (S)-(-l-)-ibuprofen these include the Rh-phosphite catalyzed hydroformylation [33], hydrocyanation [21], and hydrocarboxylation reactions [20],... 

Traditionally carbonylation reactions are underestimated in fine chemical business. Due to an abundance of starting materials and relatively inexpensive carbon monoxide or syn gas carbonylations will be enq>loyed more often to synthesize interesting building blocks amino acids via amidocarbonylation, profenes by asymmetric hydroformylations or hydrocarboxylations, reductive and oxidative carbonylations towards urethanes and ureas, etc. 

Long-chain aliphatic olefins give only insufficient conversion to the acids due to low solubility and isomerization side reactions. In order to overcome these problems the effect of co-solvents and chemically modified /i-cyclodextrins as additives was investigated for the hydrocarboxylation of 1-decene [23], Without such a promoter, conversion and acid selectivity are low, 10% and 20% respectively. Addition of co-solvents significantly increases conversion, but does not reduce the isomerization. In contrast, the addition of dimethyl-/i-cyclodextrin increased conversion and induced 90% selectivity toward the acids. This effect is rationalized by a host/ guest complex of the cyclic carbohydrate and the olefin which prevents isomerization of the double bond. This pronounced chemoselectivity effect of cyclodextrins is also observed in the hydroformylation and the Wacker oxidation of water-insoluble olefins [24, 25]. More recent studies of the biphasic hydrocarboxylation include the reaction of vinyl aromatic compounds to the isomeric arylpropanoic acids [29, 30], and of small, sparingly water-soluble alkenes such as propene [31]. 

Transition metal catalyzed asymmetric hydrocarboration reactions are addition reactions forming one C—C and one C—H bond. Prominent examples are hydrovinylation, hydroformylation, hydroacylation, hydrocarboxylation, and hydrocyanation. Various related conversions, such as hydroalkylation, hydroarylation, conjugate addition, reductive dimerization, and metal induced ene reactions are collected in Section 1.5.8.2.6. dealing with miscellaneous methods of this type. Some of these methods are not exclusively mediated by metal catalysts and therefore are also covered in other sections of this volume. 

In the synthesis of optically active a-arylpropanoic acids21, hydrovinylation represents one of the potential methods besides hydroformylation (Section 1.5.8.2.3) and hydrocarboxylation (Section 1.5.8.2.4). These systems are regarded as an important new class of non-steroidal antiinflammatory agents21. 

Side reactions such as double-bond migration and others are observed, similar to hydroformylation. Mechanistically, hydrocarboxylation is related to hydroformylation up until the metal acyl formation stage13. The presence of an acidic compound shifts the reaction towards formation of carboxylic acid derivatives and suppresses reductive elimination which forms aldehydes. The mechanism of the final steps is unclear13. 

Recent developments in hydroformylation and the mechanisms of Co-, Rh-, and Ir-catalyzed olefin hydrocarboxylations have been reviewed. The proceedings of a symposium on Catalytic Activation of Carbon Monoxide should also prove useful to those readers who wish to familiarize themselves with current areas of interest. ... 

Ojima I, Eguchi M, Tzamarioudaki M. Transition metal hydrides hydrocarboxylation, hydroformylation, and asymmetric hydrogenation. In Ahel EW, Stone FGA, Wilkinson G, Hegedus LS, editors. Comprehensive orgarwmetallic chemistry II. Volume 12. Oxford Elsevier 1995. p 9-38. 

C-19 dicarboxyhc acid can be made from oleic acid or derivatives and carbon monoxide by hydroformylation, hydrocarboxylation, or carbonylation. In hydroformylation, ie, the Oxo reaction or Roelen reaction, the catalyst is usually cobalt carbonyl or a rhodium complex (see Oxo process). When using a cobalt catalyst a mixture of isomeric C-19 compounds results due to isomerization of the double bond prior to carbon monoxide addition (80). 

The nickel or cobalt catalyst causes isomerization of the double bond resulting in a mixture of C-19 isomers. The palladium complex catalyst produces only the 9-(10)-carboxystearic acid. The advantage of the hydrocarboxylation over the hydroformylation reaction is it produces the carboxyUc acids in a single step and obviates the oxidation of the aldehydes produced by hydroformylation. 

Most ring syntheses of this type are of modern origin. The cobalt or rhodium carbonyl catalyzed hydrocarboxylation of unsaturated alcohols, amines or amides provides access to tetrahydrofuranones, pyrrolidones or succinimides, although appreciable amounts of the corresponding six-membered heterocycle may also be formed (Scheme 55a) (73JOM(47)28l). Hydrocarboxylation of 4-pentyn-2-ol with nickel carbonyl yields 3-methylenetetrahy-drofuranone (Scheme 55b). Carbonylation of Schiff bases yields 2-arylphthalimidines (Scheme 55c). The hydroformylation of o-nitrostyrene, subsequent reduction of the nitro group and cyclization leads to the formation of skatole (Scheme 55d) (81CC82). 

Decene was hydrocarboxylated with a [PdClaj/TPPTS catalyst in acidic aqueous solutions (pH adjusted to 1.8) in the presence of various chemically modified cyclodextrins (Scheme 10.11) [18]. As in most cases, the best results were obtained with DiOMe-P-CD. In an interesting series of reactions 1-decene was hydrocarboxylated in 50 50 mixtures with other compounds. Although all additives decreased somewhat the rate of 1-decene hydroformylation, the order of this inhibitory effect was 1,3,5-trimethylbenzene < cumene < undecanoic acid, which corresponds to the order of the increasing stability of the inclusion complexes of additives with p-CD, at least for 1,3,5-trimethylbenzene (60 M ) and cumene (1200 M ). These results clearly show the possible effect of competition of the various components in the reaction mixture for the cyclodextrin. 

Since the discovery and development of highly efficient Rh catalysts with chiral diphosphites and phosphine-phosphites in the 1990s, the enantioselectivity of asymmetric hydroformylation has reached the equivalent level to that of asymmetric hydrogenation for several substrates. Nevertheless, there still exist substrates that require even further development of more efficient chiral ligands, catalyst systems, and reaction conditions. Diastereoselective hydroformylation is expected to find many applications in the total synthesis of complex natural products as well as the syntheses of biologically active compounds of medicinal and agrochemical interests in the near future. Advances in asymmetric hydrocarboxylation has been much slower than that of asymmetric hydroformylation in spite of its high potential in the syntheses of fine chemicals. 

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... 

Advance in asymmetric hydrocarboxylation has been much slower than that of asymmetric hydroformylation in spite of its high potential in the syntheses of fine chemicals. However, some very encouraging results have recently been reported, and thus much improvements in this reaction can be expected in the next decade. 

Other approaches that have been suggested include catalytic asymmetric hydroformylation of 2-methoxy-6-vinylnaphthalene (6) using a rhodium catalyst on BINAPHOS ligand followed by oxidation of the resultant aldehyde 7 to yield 5-naproxen (Scheme 6.3).22 However, the tendency of the aldehyde to racemize and the co-generation of the linear aldehyde isomer make the process less attractive. Other modifications related to this process include catalytic asymmetric hydroesterification,23 hydrocarboxylation,24 and hydrocyanation.25... 

The HCo(CO)4-catalyzed hydrocarboxylation of alkenes has also been known for a long time. The mechanism is analogous to that presented for hydroformyla-tion (Scheme 1), except that H2O is used instead of H2. Hydrocarboxylation is generally slower than hydro-formylation, and it is believed that the concentrations of the intermediate species are quite low relative to those seen for hydroformylation. Pyridine has a rateenhancing effect that is believed to be due to the facile cleavage of the (acyl)Co(CO)4 intermediate. This reaction forms [pyridine-acyl] + [Co(CO)4] , which is more rapidly hydrolyzed by water to form the product carboxylic acid and HCo(CO)4. 

The hydrocarboxylation reactions discussed above have been proposed to involve direct addition of water to the metal center prior to elimination of the product, analogous to the oxidative addition of hydrogen to a metal center at the end of a hydroformylation catalytic cycle. Another class of hydrocarboxylation reactions is more analogous to the haUde-promoted Monsanto acetic acid process, where one has a reductive elimination of an acyl halide species that is rapidly hydrolyzed with free water to generate the carboxylic acid and HX. 

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