Asymmetric reactions hydrocarboxylation

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 asymmetric synthetic processes used for the manufacturing of (S)-(+)-naproxen can also be applied to the production of (S)-(+)-ibuprofen these include the Rh-phosphite catalyzed hydro-formylation,37 hydrocyanation,25 and hydrocarboxylation reactions.24... 

Asymmetric Hydrocarboxylation. The title reagent was used in the first example of an asymmetric hydrocarboxylation (eq 1). With the a-methylstyrene, the straight chain isomer was formed. The regiospecificity was much less pronounced, however, for other alkenic substrates. The influence of some reaction variables on the reaction shown in eq 1 was studied. For example, the presence of a solvent such as THF or benzene, the alcohol source, the effect of CO pressure, the effect of substitution on the phenyl ring, the PdC /DIOP molar ratio, or the presence of PPha along with DIOP, were varied to improve the optical yield. ... 

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. 

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. 

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. 

While early results of asymmetric hydrocarboxylation were considered as promising developments l3, for a long time only a few examples of low-to-medium asymmetric induction were reported. This failure to achieve successful asymmetric hydrocarboxylation is attributed to the fact that high carbon monoxide pressures (359.1 —452.2 bar) are necessary8. Usually palladium ) chloride is used together with Diop-type ligands. This catalyst system, prepared in situ, requires milder reaction conditions (50 °C) than cobalt (140 °C) or other metal catalysts. 

Only recently have better results for asymmetric hydrocarboxylation and interesting applications to stereoselective organic synthesis been achieved. Earlier results are extensively reviewed together with other catalytic methods7-13 39-4,1. As in asymmetric hydroformylation a simple model can be applied to predict the prevailing antipode and regioisomer in the reaction products of asymmetric hydrocarboxylation12. 

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. 

In the case of Au(I)-catalysed asymmetric hydrocarboxylation of allenes a high ee of 82% was observed when (5)-BINAP(AuCl)2 was combined with the counter ion of opposite chirality, that is /f-3.60. In the presence of the 5 -3.60 counter ion the reaction produced nearly racemic product. These examples clearly illustrate the powerful effect of the chiral counter ion on the enantioselectivity. 

An enantioselective version of this reaction to form carboxylic acids and esters would certainly be valuable. Examples of asymmetric hydrocarboxylation of norbomene have been published with significant selectivities, but asymmetric hydroesterification of vinylarenes have been less successful. No examples of these reactions that occur in high yields and with enantioselectivities over 90% have been reported. ... 

The hydroesteriflcation and hydrocarboxylation reactions catalyzed by transition metals and their complexes demonstrate the versatility of these processes. Palladium complexes are particularly useful catalysts for these reactions. Indeed, the hydrocarbonylation of a large variety of substrates has been selectively achieved by using palladium catalysts in homogeneous, heterogeneous, or biphasic systems. The results obtained for the thiocar-bonylation showed excellent regio- and stereoselectivity control for most substrates. It is anticipated that the prochiral nature of most of the reactants and products will open a new venue for the asymmetric synthesis of acids, esters, and thioesters of substantial development in the future. 

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/ ... 

---