Itaconic acid, asymmetric hydrogenation

Although the asymmetric hydrogenation of itaconic acid derivatives is a potential synthetic approach to many useful product [105], lower enantioselectivities are often reported. In contrast with other catalysts, f-Bu-BisP, Ad-BisP, t-Bu-MiniPHOS, BIPNOR 27, and Brown s ligand 25 gave high to almost perfect ees in the hydrogenation of these substrates (Scheme 23) [101]. 

Scheme 23. Rh-catalyzed asymmetric hydrogenation reactions of itaconic acid derivatives...

Bidentate chiral bis(aminophosphanes) such as 55-57 (Scheme 44) have been used for the Rh(I)-cataIyzed asymmetric hydrogenation of itaconic acid... 

In this work, various Ru-BINAP catalysts immobilized on the phosphotungstic acid(PTA) modified alumina were prepared and the effects of the reaction variables (temperature, H2 pressure, solvent and content of triethylamine) on the catalytic performance of the prepared catalysts were investigated in the asymmetric hydrogenation of dimethyl itaconate (DMIT). 

In addition, several S/S ligands were also investigated for the asymmetric hydrogenation of olefins. In 1977, James and McMillan reported the synthesis of various disulfoxide ligands, which were applied to the asymmetric ruthenium-catalysed hydrogenation of prochiral olefinic acid derivatives, such as itaconic acid. These ligands, depicted in Scheme 8.16, were active to provide... 

In 1998, Ruiz et al. reported the synthesis of new chiral dithioether ligands based on a pyrrolidine backbone from (+ )-L-tartaric acid. Their corresponding cationic iridium complexes were further evaluated as catalysts for the asymmetric hydrogenation of prochiral dehydroamino acid derivatives and itaconic acid, providing enantioselectivities of up to 68% ee, as shown in Scheme 8.18. 

Enantioselectivities of up to 47% ee were reported by Ruiz et al. in 1997 for the asymmetric hydrogenation of various prochiral dehydroamino acid derivatives and itaconic acid by using iridium cationic complexes of the novel chiral... 

On the other hand, James reported, in 1976, the use of a chiral sulfoxide as a ligand of ruthenium for the asymmetric hydrogenation of itaconic acid, providing a low enantioselectivity of 12% ee (Scheme 8.23). ... 

A 1996 work deposited four different catalytic metals on a p-cyclodextrin— epichlorohydrin copolymer to prepare Pd(Pt, Rh, Ru)-P-cyclodextrin copolymer catalysts.8 These were used to catalyze the asymmetric hydrogenations of the C=C bonds of trans-2-methyl-2-pentenoic acid, and dimethyl itaconate. 

Prochiral organic acids were hydrogenated on clay-supported Rh-chiral phosphine complexes.205,206 Hectorite-supported chiral Rh(I)-phosphine complexes were used for the asymmetric hydrogenation of a,P-unsaturated carboxylic acids.207 It was found that the interaction between the a-ester group of itaconates and phenyl groups of phosphine can play an important role in the determination of the configuration of products. 

In the early 1990s, Burk introduced a new series of efficient chiral bisphospholane ligands BPE and DuPhos.55,55a-55c The invention of these ligands has expanded the scope of substrates in Rh-catalyzed enantioselective hydrogenation. For example, with Rh-DuPhos or Rh-BPE as catalysts, extremely high efficiencies have been observed in the asymmetric hydrogenation of a-(acylamino)acrylic acids, enamides, enol acetates, /3-keto esters, unsaturated carboxylic acids, and itaconic acids. 

Table 7 Asymmetric hydrogenation of itaconic acid or dimethyl ester...

When a commercially available C2-symmetric l,4 3,6-dianhydro-D-mannite 29 is chosen as the backbone, reaction of this diol compound with chlorophos-phoric acid diaryl ester gives a series of phosphorate ligands 30. These were tested using the asymmetric hydrogenation of dimethyl itaconate as a model... 

The resulting sol-gel catalysts usually proved more stable and versatile under ambient conditions than their homogeneous analogues. For example, a remarkable asymmetric hydrogenation of prochiral itaconic acid over sol-gel entrapped (—)-Ru-BINAP in water becomes possible which simply cannot be done with non-entrapped, water-insoluble catalysts. 

Similar studies have been performed on rhodium(I) complexes of monodentate and potentially chelating sulfoxides (301, 307), again with rather mixed results. Complexes of the type [Rh(diene)(PPh3) (sulfoxide)]+ have been synthesized (302,306) for a range of chiral sulfoxides where coordination appears to be via oxygen, but attempts to asymmetrically hydrogenate itaconic acid using these precursors were... 

Breakthroughs that took place around the year 2000 have shown, in contrast to the common view, that indeed chiral monodentate phosphorus ligands can also lead to high enantioselectivities in a number of asymmetric hydrogenations. In the years following, monophosphines, monophos-phonites, monophosphoramidites, and monophosphites have been successfully used in the enantioselective hydrogenation of a-dehydroamino acids and itaconic acid derivatives [25],... 

In asymmetric hydrogenation of olefins, the overwhelming majority of the papers and patents deal with hydrogenation of enamides or other appropriately substituted prochiral olefins. The reason is very simple hydrogenation of olefins with no coordination ability other than provided by the C=C double bond, usually gives racemic products. This is a common observation both in non-aqueous and aqueous systems. The most frequently used substrates are shown in Scheme 3.6. These are the same compounds which are used for similar studies in organic solvents salts and esters of Z-a-acetamido-cinnamic, a-acetamidoacrylic and itaconic (methylenesuccinic) acids, and related prochiral substrates. The free acids and the methyl esters usually show appreciable solubility in water only at higher temperatures, while in most cases the alkali metal salts are well soluble. 

Some excellent bisphosphonite ligands have also been developed. For example, Re-etzfs binaphthol-derived ferrocene-based bisphosphonite hgand L12 has demonstrated to have excellent reactivity and enantioselectivity in the rhodium-catalyzed hydrogenation of itaconates and a-dehydroamino acid derivatives [76]. Zanotti-Gerosa s bisphosphonite ligand L13 has also been successfully apphed to the asymmetric hydrogenation of a-dehydroamino acid derivatives with up to 99% ee [77]. 

A few efficient bisphosphite ligands have been used for asymmetric hydrogenation of itaconates or a-dehydroamino acid derivatives. Reetz has developed a series of C2-symmetric bisphosphite ligands such as L14, which are based on the structure of 1,4 3,6-dianhydro-D-mannite [78]. The ligands exhibit excellent reactivity and enantioselectivity for the asymmetric hydrogenation of itaconates. 

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